Details of the Researcher

PHOTO

Yoshihide Asano
Section
Graduate School of Medicine
Job title
Professor
Degree

  • 博士（医学）（東京大学）

Profile

1998年3月         東京大学医学部医学科卒業

1998年6月         東京大学医学部附属病院　皮膚科　研修医

2000年4月         東京大学大学院医学系研究科外科学専攻皮膚科学 入学

2004年3月         東京大学大学院医学系研究科外科学専攻皮膚科学 修了、医学博士取得

2004年4月         NTT東日本関東病院　皮膚科　常勤嘱託医

2005年4月         東京大学医学部附属病院　皮膚科　助手

2006年1月         サウスカロライナ州立医科大学リウマチ免疫学教室　研究員

2009年1月         東京大学医学部附属病院　皮膚科　助教

2010年7月         東京大学大学院医学系研究科・医学部　皮膚科学　講師

2015年7月         東京大学大学院医学系研究科・医学部　皮膚科学　准教授

2017年3月         東京大学医学部附属病院　免疫疾患治療センター　副センター長兼任

2018年4月         東京大学医学部附属病院　強皮症センター　センター長兼任

2022年2月         東北大学大学院医学系研究科 神経・感覚器病態学講座 皮膚科学分野 教授

Research Areas 1

  • Life sciences / Dermatology /

Awards 9

  1. JDS Best Paper Award 2020

    2021/08　The Japanese Society for Investigative Dermatology　Regulation of skin fibrosis by RALDH1-producing dermal dendritic cells via retinoic acid-mediated regulatory T cell induction: A role in scleroderma

  2. JD Award, The Journal of Dermatology, Most Cited Paper 2020

    2021/01　The Japanese Dermatological Association

  3. JD Award, The Journal of Dermatology, Most Cited Paper 2019

    2020/01　The Japanese Dermatological Association

  4. Pola Pharma Rising Star Award 2019

    2019/11　The Japanese Society for Investigative Dermatology

  5. Rising star

    2018/05　International Investigative Dermatology 2018　Yoshihide Asano

  6. Edith-Busch Prize for Young Investigators 2018

    2018/02　Systemic Sclerosis World Congress

  7. 第１回 高木賞

    2017/04　公益財団法人 マルホ・高木皮膚科学振興財団

  8. The Japanese Society for Investigative Dermatology Award

    2016/12　The Japanese Society for Investigative Dermatology

  9. JD Award, The Journal of Dermatology, Most Cited Paper 2012

    2013/01　The Japanese Dermatological Association

Show all ︎Show 5

Papers 485

  1. Predictive factors for treatment responses to baricitinib in severe alopecia areata: A retrospective, multivariate analysis of 70 cases from a single center. International-journal

    Moyuka Wada-Irimada, Takehiro Takahashi, Mana Sekine, Toshiki Okazaki, Takuya Takahashi, Tomoko Chiba, Emi Yamazaki, Kosuke Shido, Toshiya Takahashi, Masato Mizuashi, Yoshihide Asano

    The Journal of dermatology　2025/01/27

    DOI： 10.1111/1346-8138.17641 　

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    Alopecia areata (AA) is a chronic, autoimmune skin disease characterized by non-scarring hair loss. Baricitinib, a Janus kinase inhibitor (JAKi), prevents hair loss and promotes hair regrowth by inhibiting the inflammatory Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway involved in cytotoxic T cell responses targeting hair follicles. The introduction of JAKi has transformed treatment against severe AA. However, treatment responses to JAKi are highly variable among patients, and the predictors of responsiveness remain insufficiently elucidated. This study aimed to identify independent predictive factors for the efficacy of baricitinib in patients with severe AA using multivariate analyses. A retrospective study was conducted on 70 severe AA patients who started baricitinib treatment at Tohoku University Hospital between July 2022 and August 2023. The primary outcome was the percentage of patients achieving a Severity of Alopecia Tool (SALT) score of ≤20 after 9 months of baricitinib treatment. Multivariate analysis assessed potential predictors of baricitinib treatment responses, including AA type, sex, age, disease duration, history of atopic dermatitis, intravenous methylprednisolone pulse (IVMP) therapy, and Clinician-Reported Outcome (ClinRO) measures for eyebrows and eyelashes. Achievement of a SALT score of ≤20 and SALT score improvement rates were used as objective variables in the multivariate analyses. Among the 70 patients completing 9 months of baricitinib treatment, 41% achieved a SALT score of ≤20. Multivariate analyses identified several independent predictors for positive outcomes, including shorter disease duration (≤4 years), history of IVMP, therapy SALT score of ≤95 at baricitinib initiation, and female sex. Further, we found differential response patterns based on AA type and sex. Specifically, AA type significantly influenced treatment responses, with ophiasis alopecia (OA) associated with the poorest improvement rate. In summary, the response to baricitinib in AA is significantly influenced by sex, AA type, disease duration, history of IVMP, and pre-treatment SALT score.

  2. Deep learning-based histopathological assessment of tubulo-interstitial injury in chronic kidney diseases. International-journal

    Nonoka Suzuki, Kaname Kojima, Silvia Malvica, Kenshi Yamasaki, Yoichiro Chikamatsu, Yuji Oe, Tasuku Nagasawa, Ekyu Kondo, Satoru Sanada, Setsuya Aiba, Hiroshi Sato, Mariko Miyazaki, Sadayoshi Ito, Mitsuhiro Sato, Tetsuhiro Tanaka, Kengo Kinoshita, Yoshihide Asano, Avi Z Rosenberg, Koji Okamoto, Kosuke Shido

    Communications medicine　5　(1)　3-3　2025/01/05

    DOI： 10.1038/s43856-024-00708-3 　

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    BACKGROUND: Chronic kidney disease (CKD) causes progressive and irreversible damage to the kidneys. Renal biopsies are essential for diagnosing the etiology and prognosis of CKD, while accurate quantification of tubulo-interstitial injuries from whole slide images (WSIs) of renal biopsy specimens is challenging with visual inspection alone. METHODS: We develop a deep learning-based method named DLRS to quantify interstitial fibrosis and inflammatory cell infiltration as tubulo-interstitial injury scores, from WSIs of renal biopsy specimens. DLRS segments WSIs into non-tissue areas, glomeruli, tubules, interstitium, and arteries, and detects interstitial nuclei. It then quantifies these tubulo-interstitial injury scores using the segmented tissues and detected nuclei. RESULTS: Applied to WSIs from 71 Japanese CKD patients with diabetic nephropathy or benign nephrosclerosis, DLRS-derived scores show concordance with nephrologists' evaluations. Notably, the DLRS-derived fibrosis score has a higher correlation with the estimated glomerular filtration rate (eGFR) at biopsy than scores from nephrologists' evaluations. Validated on WSIs from 28 Japanese tubulointerstitial nephritis patients and 49 European-ancestry patients with nephrosclerosis, DLRS-derived scores show a significant correlation with eGFR. In an expanded analysis of 238 Japanese CKD patients, including 167 from another hospital, deviations in eGFR from expected values based on DLRS-derived scores correlate with annual eGFR decline after biopsy. Inclusion of these deviations and DLRS-derived fibrosis scores improve predictions of the annual eGFR decline. CONCLUSIONS: DLRS-derived tubulo-interstitial injury scores are concordant with nephrologists' evaluations and correlated with eGFR across different populations and institutions. The effectiveness of DLRS-derived scores for predicting annual eGFR decline highlights the potential of DLRS as a predictor of renal prognosis.

  3. Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome associated with acute-on-chronic pancreatitis: A case report. International-journal

    Toshiki Okazaki, Takehiro Takahashi, Yoshihide Asano

    The Journal of dermatology　52　(1)　e30-e31　2025/01

    DOI： 10.1111/1346-8138.17406 　

  4. Predictors of clinical features in early-onset severe systemic sclerosis: An analysis from a multicenter prospective observational Japanese cohort. International-journal

    Saori Uesugi-Uchida, Manabu Fujimoto, Yoshihide Asano, Hirahito Endo, Daisuke Goto, Masatoshi Jinnin, Yasushi Kawaguchi, Sumiaki Tanaka, Takahiro Tokunaga, Katsunari Makino, Takashi Matsushita, Sei-Ichiro Motegi, Ayumi Yoshizaki, Shinichi Sato, Minoru Hasegawa

    The Journal of dermatology　51　(10)　1290-1297　2024/10

    DOI： 10.1111/1346-8138.17403 　

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    As the clinical course of systemic sclerosis (SSc) varies widely, prognostic indicators have been sought to predict the outcomes of individual patients. Racial differences in SSc render it necessary to validate prognostic indicators in different patient cohorts. In this study, we aimed to assess clinical and laboratory parameters in Japanese patients with early-stage SSc with diffuse cutaneous involvement and/or interstitial lung disease, and identify predictive factors for disease progression. We performed multivariate analyses of baseline clinical information to estimate symptoms 4 years later in Japanese patients with diffuse cutaneous SSc and/or SSc with interstitial lung disease. Patients were enrolled in the study within 5 years of disease onset at 10 Japanese SSc centers. Over 12 years, 115 patients followed up for 4 years were included in this study. The modified Rodnan skin score (mRSS) at 4 years correlated with the baseline mRSS and finger-to-palm distance, defined as the average length from the distal tip of the fourth finger to the distal palmar crease. The percentage predicted vital capacity (%VC) in year 4 positively and negatively correlated with initial %VC and the presence of anti-topoisomerase I antibodies, respectively. The Health Assessment Questionnaire Disability Index (HAQ-DI) at 4 years was positively and negatively associated with baseline HAQ-DI and %VC, respectively. The occurrence of digital ulcers within 4 years was associated with the initial presence of digital ulcers, finger-to-palm distance, and the presence of digital pitting scars and anti-topoisomerase I antibodies. This study identified several factors that may predict the progression of early-stage SSc in Japanese patients. Finger-to-palm distance may be a useful tool for predicting the progression of skin thickening and the development of digital ulcers in the early stages of severe SSc, but larger, long-term prospective studies are needed to confirm our findings.

  5. Eggshell membrane and its major component lysozyme and ovotransferrin enhance the secretion of decorin as an endogenous antifibrotic mediator from lung fibroblasts and ameliorate bleomycin-induced pulmonary fibrosis

    Eri Ohto-Fujita, Miho Shimizu, Aya Atomi, Hiroki Hiruta, Ryota Hosoda, Shinya Horinouchi, Shinya Miyazaki, Tomoaki Murakami, Yoshihide Asano, Yukio Hasebe, Yoriko Atomi

    Biochemistry and Biophysics Reports　39　101806-101806　2024/09

    Publisher: Elsevier BV

    DOI： 10.1016/j.bbrep.2024.101806 　

    ISSN： 2405-5808

  6. Decreased serum levels of IL-4 correlate with the efficacy of the PAI-1 inhibitor TM5614 in patients with malignant melanoma refractory to anti-PD-1 antibodies: post hoc study of TM5614-MM trial. International-journal

    Emi Yamazaki, Taku Fujimura, Manami Takahashi-Watanabe, Satsuki Tada, Chisako Kitayama, Ryo Amagai, Yumi Kambayashi, Masahiro Watanabe, Masamitsu Maekawa, Nariyasu Mano, Yoshihide Asano

    The British journal of dermatology　2024/08/31

    DOI： 10.1093/bjd/ljae343 　

  7. Three-Year Analysis of Adjuvant Therapy in Postoperative Melanoma including Acral and Mucosal Subtypes. International-journal

    Yusuke Muto, Yumi Kambayashi, Hiroshi Kato, Satoru Mizuhashi, Takamichi Ito, Takeo Maekawa, Shoichiro Ishizuki, Hiroshi Uchi, Shigeto Matsushita, Yuki Yamamoto, Koji Yoshino, Yasuhiro Fujisawa, Ryo Amagai, Kentaro Ohuchi, Akira Hashimoto, Satoshi Fukushima, Yoshihide Asano, Taku Fujimura

    Cancers　16　(15)　2024/08/02

    DOI： 10.3390/cancers16152755 　

    eISSN： 2072-6694

  8. Serum levels of AGGF1: Potential association with cutaneous and cardiopulmonary involvements in systemic sclerosis. International-journal

    Takuya Takahashi, Takehiro Takahashi, Tetsuya Ikawa, Hitoshi Terui, Toshiya Takahashi, Yuichiro Segawa, Hayakazu Sumida, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    The Journal of dermatology　51　(8)　1083-1090　2024/08

    DOI： 10.1111/1346-8138.17233 　

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    Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, aberrant immune activation, and extensive tissue fibrosis of the skin and internal organs. Because of the complicated nature of its pathogenesis, the underlying mechanisms of SSc remain incompletely understood. Angiogenic factor with a G-patch domain and a Forkhead-associated domain 1 (AGGF1) is a critical factor in angiogenesis expressed on vascular endothelial cells, associated with inflammatory and fibrotic responses. To elucidate the possible implication of AGGF1 in SSc pathogenesis, we investigated the association between serum AGGF1 levels and clinical manifestations in SSc patients. We conducted a cross-sectional analysis of AGGF1 levels in sera from 60 SSc patients and 19 healthy controls with enzyme-linked immunosorbent assay. Serum AGGF1 levels in SSc patients were significantly higher than those in healthy individuals. In particular, diffuse cutaneous SSc patients with shorter disease duration had higher levels compared to those with longer disease duration and limited cutaneous SSc patients. Patients with higher serum AGGF1 levels had a higher incidence of digital ulcers, higher modified Rodnan Skin Scores (mRSS), elevated serum Krebs von den Lungen-6 (KL-6) levels, C-reactive protein levels, and right ventricular systolic pressures (RVSP) on the echocardiogram, whereas they had reduced percentage of vital capacity (%VC) and percentage of diffusing capacity of the lungs for carbon monoxide (%DLCO) in pulmonary functional tests. In line, serum AGGF1 levels were significantly correlated with mRSS, serum KL-6 and surfactant protein D levels, RVSP, and %DLCO. These results uncovered notable correlations between serum AGGF1 levels and key cutaneous and vascular involvements in SSc, suggesting potential roles of AGGF1 in SSc pathogenesis.

  9. Eosinophilic annular erythema successfully treated with dupilumab: A case report. International-journal

    Toshiki Okazaki, Takehiro Takahashi, Yoshihide Asano

    The Journal of dermatology　51　(7)　e249-e250　2024/07

    DOI： 10.1111/1346-8138.17158 　

  10. Phase II, multicenter study of plasminogen activator inhibitor-1 inhibitor (TM5614) plus nivolumab for treating anti-PD-1 antibody-refractory malignant melanoma: TM5614-MM trial. International-journal

    Taku Fujimura, Koji Yoshino, Hiroshi Kato, Satoshi Fukushima, Shoichiro Ishizuki, Atsushi Otsuka, Shigeto Matsushita, Ryo Amagai, Yusuke Muto, Emi Yamazaki, Yumi Kambayashi, Takashi Yahata, Toshio Miyata, Yasuhiro Fujisawa, Yoshihide Asano

    The British journal of dermatology　2024/06/04

    DOI： 10.1093/bjd/ljae231 　

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    BACKGROUND: Anti-programmed cell death 1 antibodies (anti-PD-1 Abs) are widely used for advanced melanoma, but the efficacy of an anti-PD-1 Abs is limited in the Asian population. There remains an unmet need to improve the therapeutic effects of anti-PD-1 Abs treatment, particularly in melanoma patients who are refractory to anti-PD-1 Abs. The aim was to evaluate anti-PD-1 Abs treatment in combination with TM5614 (plasminogen activator inhibitor-1: PAI-1 inhibitor) in patients with unresectable melanoma. METHODS: The TM5614-MM study was a multicentre, open-label, single-arm, phase 2 clinical trial to evaluate the efficacy and safety of nivolumab in combination with TM5614 in patients with advanced, unresectable malignant melanoma recruited at 7 Japanese institutes between 13 September 2021 and 31 March 2023. Patients with metastatic or unresectable melanoma previously treated with anti-PD-1 Abs were enrolled. Nivolumab 480 mg was administered intravenously every 4 weeks for 8 weeks, while TM5614 was administered orally at a dose of 120 mg (0-4 weeks) and 180 mg once daily (5-8 weeks). The primary endpoint was the overall response rate after 8 weeks of concomitant use of TM5614. RESULTS: Thirty nine patients were enrolled, and 34 patients in the anti-PD-1 Abs-refractory cohort. The overall response rate at 8 weeks was 25.9% (95% CI: 12.9-44.9%; P = .027) in 27 anti-PD-1-Abs refractory patients by investigator assessment in the protocol per set cohort. Seven patients discontinued treatment due to progressive disease or adverse events. Treatment-related grade 3 or higher adverse events occurred in 3 of 39 patients (7.7%) in the intention-to-treat cohort. CONCLUSIONS: TM5614 in combination with nivolumab is well-tolerated and effective in anti-PD-1 Abs-refractory, unresectable melanoma. TRIAL REGISTRATION: This trial was registered with Clinical Trial gov, jRCT2021210029.

  11. Case report: Nodular scleroderma successfully treated with tocilizumab. International-journal

    Takuya Takahashi, Takehiro Takahashi, Mai Ueki, Hitoshi Terui, Yuichiro Segawa, Tetsuya Ikawa, Toshiya Takahashi, Yumi Kambayashi, Yoshihide Asano

    International journal of rheumatic diseases　27　(5)　e15200　2024/05

    DOI： 10.1111/1756-185X.15200 　

  12. 膠原病・血管炎に伴う皮膚潰瘍の治療

    浅野 善英, 浅井 純, 石井 貴之, 岩田 洋平, 小寺 雅也, 宮部 千恵, 内山 明彦, 小川 陽一, 岡村 賢, 岸部 麻里, 小池 雄太, 壽 順久, 藤本 徳毅, 宮城 拓也, 山口 由衣, 吉崎 歩, 大森 礼子

    日本皮膚科学会雑誌　134　(5)　1375-1375　2024/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  13. 創傷・褥瘡・熱傷ガイドライン(2023)-5 下腿潰瘍・下肢静脈瘤診療ガイドライン(第3版)

    前川 武雄, 伊藤 孝明, 出月 健夫, 太田 真由美, 坂井 浩志, 皿山 泰子, 田中 隆光, 新原 寛之, 伏間江 貴之, 牧野 公治, 八代 浩, 近藤 晃代, 浅野 善英, 中西 健史, 茂木 精一郎, 吉野 雄一郎, 藤原 浩, 長谷川 稔, 藤本 学, 立花 隆夫, 日本皮膚科学会, 創傷・褥瘡・熱傷ガイドライン策定委員会(下腿潰瘍・下肢静脈瘤グループ)

    日本皮膚科学会雑誌　134　(2)　225-272　2024/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  14. 日本皮膚科学会ガイドライン 創傷・褥瘡・熱傷ガイドライン(2023)-4 膠原病・血管炎にともなう皮膚潰瘍診療ガイドライン(第3版)

    浅野 善英, 浅井 純, 石井 貴之, 岩田 洋平, 小寺 雅也, 宮部 千恵, 内山 明彦, 小川 陽一, 岡村 賢, 岸部 麻里, 小池 雄太, 壽 順久, 藤本 徳毅, 宮城 拓也, 山口 由衣, 吉崎 歩, 大森 礼子, 中西 健史, 藤原 浩, 前川 武雄, 茂木 精一郎, 吉野 雄一郎, 長谷川 稔, 藤本 学, 立花 隆夫, 創傷・褥瘡・熱傷ガイドライン策定委員会(膠原病・血管炎グループ)

    日本皮膚科学会雑誌　134　(1)　1-63　2024/01

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  15. 日本皮膚科学会ガイドライン 創傷・褥瘡・熱傷ガイドライン(2023) 糖尿病性皮膚潰瘍・壊疽診療ガイドライン(第3版)

    中西 健史, 池上 隆太, 大森 俊, 加藤 裕史, 小森 敏史, 清水 知道, 杉田 和成, 谷崎 英昭, 中島 英貴, 林 周次郎, 松尾 梨沙, 三井 広, 柳澤 宏人, 山口 道也, 山崎 修, 西出 薫, 浅野 善英, 藤原 浩, 前川 武雄, 茂木 精一郎, 吉野 雄一郎, 長谷川 稔, 藤本 学, 立花 隆夫, 創傷・褥瘡・熱傷ガイドライン策定委員会(糖尿病性皮膚潰瘍・壊疽グループ)

    日本皮膚科学会雑誌　133　(13)　2969-3024　2023/12

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  16. 【膠原病-2つの強皮症を理解しよう】(Part4)限局性強皮症の注意すべき合併症(case 15) 水晶体消失と感音性難聴を伴う剣創状強皮症

    三浦 俊介, 浅野 善英

    Visual Dermatology　23　(1)　82-84　2023/12

    Publisher: (株)Gakken

    ISSN： 2186-6589

  17. 日本皮膚科学会ガイドライン 創傷・褥瘡・熱傷ガイドライン(2023) 糖尿病性皮膚潰瘍・壊疽診療ガイドライン(第3版)

    中西 健史, 池上 隆太, 大森 俊, 加藤 裕史, 小森 敏史, 清水 知道, 杉田 和成, 谷崎 英昭, 中島 英貴, 林 周次郎, 松尾 梨沙, 三井 広, 柳澤 宏人, 山口 道也, 山崎 修, 西出 薫, 浅野 善英, 藤原 浩, 前川 武雄, 茂木 精一郎, 吉野 雄一郎, 長谷川 稔, 藤本 学, 立花 隆夫, 創傷・褥瘡・熱傷ガイドライン策定委員会(糖尿病性皮膚潰瘍・壊疽グループ)

    日本皮膚科学会雑誌　133　(13)　2969-3024　2023/12

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  18. 日本皮膚科学会ガイドライン 創傷・褥瘡・熱傷ガイドライン(2023)-2 褥瘡診療ガイドライン(第3版)

    藤原 浩, 入澤 亮吉, 大塚 正樹, 加古 智子, 加持 達弥, 門野 岳史, 古賀 文二, 廣崎 邦紀, 野北 陽子, 浅野 善英, 中西 健史, 前川 武雄, 茂木 精一郎, 吉野 雄一郎, 長谷川 稔, 藤本 学, 立花 隆夫, 創傷・褥瘡・熱傷ガイドライン策定委員会(褥瘡グループ), 日本皮膚科学会

    日本皮膚科学会雑誌　133　(12)　2735-2797　2023/11

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  19. Postoperative adjuvant therapy for120 melanoma patients, including acral and mucosal subtypes: A multicenter, observational study of two-year follow-up results. International-journal

    Yusuke Muto, Yumi Kambayashi, Hiroshi Kato, Satoshi Fukushima, Takamichi Ito, Takeo Maekawa, Ishizuki Shoichiro, Hiroshi Uchi, Shigeto Matsushita, Yuki Yamamoto, Koji Yoshino, Yasuhiro Fujisawa, Ryo Amagai, Kentaro Ohuchi, Akira Hashimoto, Yoshihide Asano, Taku Fujimura

    The British journal of dermatology　2023/05/27

    DOI： 10.1093/bjd/ljad183 　

  20. GWAS for Systemic Sclerosis Identified six novel susceptibility loci including penetrating Fcγ-Receptor Region

    Yuki Ishikawa, Nao Tanaka, Yoshihide Asano, Masanari Kodera, Yuichiro Shirai, Mitsuteru Akahoshi, Minoru Hasegawa, Takashi Matsushita, Kazuyoshi Saito, Sei-ishiro Motegi, Hajime Yoshifuji, Ayumi Yoshizaki, Tomohiro Komoto, Kae Takagi, Akira Oka, Miho Kanda, Yoshihito Tanak, Yumi Ito, Kazuhisa Nakano, Hiroshi Kasamatsu, Akira Utsunomiya, Akiko Sekiguchi, Hiroaki Niro, Masatoshi Jinnin, Katsunari Makino, Takamitsu Makino, Hironobu Ihn, Motohisa Yamamoto, Chisako Suzuki, Hiroki Takahashi, Emi Nishida, Akimichi Morita, Toshiyuki Yamamoto, Manabu Fujimoto, Yuya Kondo, Daisuke Goto, Takayuki Sumida, Naho Ayuzawa, Hidetashi Yanagida, Tetsuya Horita, Tatsuya Atsumi, Hirahito Endo, Yoshihito Shima, Atsushi Kumanogoh, Jun Hirata, Nao Otomo, Hiroyuki Suetsugu, Yoshinao Koike, Kohei Tomizuka, Soichiro Yoshino, Xiaoxi Liu, Shuji Ito, Keiko Hikino, Akari Suzuki, Yukihide Momozawa, Shiro Ikegawa, Yoshiya Tanaka, Osamu Ishikawa, Kazuhiko Takehara, Takeshi Torii, Shinichi Sato, Yukinori Okada, Tsuneyo Mimori, Fumihiko Matsuda, Koichi Matsuda, Tiffany Amariuta, Issei Imoto, Keitaro Matsuo, Masataka Kuwana, Yasushi Kawaguchi, Koichiro Ohmura, Chikashi Terao

    2023/04/07

    Publisher: Research Square Platform LLC

    DOI： 10.21203/rs.3.rs-2712663/v1 　

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    Abstract We conducted a Japanese GWAS for systemic sclerosis (SSc) comprising 1,428 cases and 112,599 controls, the largest Asian GWAS for SSc ever, and identified three novel signals. The lead SNP in FCGR/FCRL region had a strong effect size (OR 2.05, P = 4.9×10−11). The complete LD SNP, rs10917688, was found in a cis-regulatory element and a part of binding motifs for IRF8. IRF8 was a significant locus in the European GWAS and rs10917688 showed an association only in the presence of the risk allele of IRF8 in Japanese. rs10917688 was marked with H3K4me1 in primary B cells, and the heritability was enriched in active histone marks of primary B cells. A meta-analysis with the latest European GWAS found additional 30 significant loci including three novel signals. PRS constructed with the effect sizes of the meta-analysis indicated potential portability of genetic associations beyond populations (AUC: 0.593). The fitting of PRS was improved by further prioritizing the top 5% SNPs of IRF8 biding sites in B cells, underscoring common genetic architecture across populations and critical roles of B cells and IRF8 for SSc development.

  21. 診断に難渋した下肢extranodal NK/T-cell lymphoma,nasal typeの1例

    水芦 政人, 山本 悠, 赤井 紗彩, 高橋 隼也, 山崎 研志, 浅野 善英, 谷田 宗男, 市川 聡, 横山 寿行

    日本皮膚科学会雑誌　133　(4)　708-709　2023/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  22. Treatment for taxane-resistant cutaneous angiosarcoma: A multicenter study of 50 Japanese cases. International-journal

    Taku Fujimura, Takeo Maekawa, Hiroshi Kato, Takamichi Ito, Shigeto Matsushita, Koji Yoshino, Yasuhiro Fujisawa, Shoichiro Ishizuki, Kojiro Segawa, Jun Yamamoto, Akira Hashimoto, Yumi Kambayashi, Yoshihide Asano

    The Journal of dermatology　2023/03/20

    DOI： 10.1111/1346-8138.16786 　

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    Cutaneous angiosarcoma (CAS) is a rare and highly aggressive type of vascular tumor. Although chemoradiotherapy with taxanes is recognized as a first-line therapy for CAS, second-line therapy for CAS remains controversial. From the above findings, the efficacy and safety profiles of taxane-switch (change paclitaxel to docetaxel or vise), eribulin methylate, and pazopanib regimens in second-line chemotherapy were evaluated retrospectively in 50 Japanese taxane-resistant CAS patients. Although there was no significant difference in progression-free survival (P = 0.3528) among the regimens, the incidence of all adverse events (AEs) (P = 0.0386), as well as severe G3 or more AEs (P = 0.0477) was significantly higher in the eribulin methylate group and pazopanib group than in the taxane-switch group. The present data suggest that switching to another taxane should be considered for the treatment of taxane-resistant CAS in second-line therapy based on the safety profiles.

  23. Native T1 mapping in early diffuse and limited systemic sclerosis, and its association with diastolic function. International-journal

    Munkhtuul Purevsuren, Masae Uehara, Masato Ishizuka, Yuichi Suzuki, Mai Shimbo, Nobutaka Kakuda, Satoshi Ishii, Hayakazu Sumida, Miki Miyazaki, Takashi Yamashita, Ayumi Yoshizaki, Yoshihide Asano, Shinichi Sato, Masaru Hatano, Issei Komuro

    Journal of cardiology　2023/03/13

    DOI： 10.1016/j.jjcc.2023.03.003 　

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    BACKGROUND: Systemic sclerosis (SSc) is divided into diffuse and limited cutaneous SSc (dcSSc and lcSSc). The dcSSc subtype has more severe internal organ damage. This study aimed to assess whether cardiovascular magnetic resonance (CMR) parametric mapping could detect early cardiac involvement and evaluate differences between these two subtypes. METHODS: Eighty SSc patients (37 dcSSc and 43 lcSSc) underwent CMR at 3.0 T (Philips Healthcare, Best, The Netherlands) in our hospital between July 2018 and July 2021. We analyzed myocardial damage by CMR parametric mapping and compared it with clinical data. RESULTS: The median duration of the disease was 10.2 months. The left ventricular ejection fraction was preserved in both groups. DcSSc had significantly higher native T1 (1333.4 ± 71.2 ms vs. 1295.0 ± 42.7 ms, p = 0.006) and extracellular volume fraction (32.6 ± 4.1 % vs. 30.3 ± 4.0 %, p = 0.018) in the mid-ventricular septum as compared to lcSSc, although there were no differences in T2 values. Native T1 values were positively correlated with the E/e' ratio and left atrial volume indices evaluated by transthoracic echocardiography in overall SSc and dcSSc, but not in lcSSc. Logistic regression analysis revealed that native T1 was an independent predictor of left ventricular diastolic dysfunction in SSc patients (odds ratio, 1.194; 95 % confidence interval, 1.021-1.396; p = 0.026). Native T1 was higher in SSc patients with progressive skin lesions. Additionally, there were positive correlations between brain natriuretic peptide, New York Heart Association functional classification, and native T1. CONCLUSIONS: CMR parametric mapping is a useful tool for detecting myocardial changes. Native T1 was the most sensitive parameter for identifying diffuse myocardial changes in the early stages of SSc and was associated with left ventricular diastolic function. DcSSc had more severe myocardial involvement than lcSSc; therefore, the use of CMR parametric mapping may aid in its prediction.

  24. Biologics for Reducing Cardiovascular Risk in Psoriasis Patients. International-journal

    Hitoshi Terui, Yoshihide Asano

    Journal of clinical medicine　12　(3)　2023/02/01

    DOI： 10.3390/jcm12031162 　

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    Psoriasis is a chronic inflammatory skin disease with a high prevalence of cardiovascular disease (CVD), obesity, dyslipidemia, hypertension, diabetes mellitus, and metabolic syndrome. Among them, CVD is the most common cause of morbidity and mortality in psoriasis patients. Since CVD is associated with considerable morbidity and mortality, primary care clinicians are increasingly committed to reducing the risk of CVD in patients with psoriasis. Biologics targeting TNF-α, IL-12/23, and IL-17 are systemic therapies that can dramatically improve the condition of psoriasis. Recent studies have reported that these inflammatory cytokine signals may promote atherosclerosis, suggesting that biologics might be effective for improving psoriasis as well as reducing the risk of CVD. Here, we reviewed cardiovascular risk in psoriasis patients, the association between psoriatic inflammation and atherosclerosis, and the efficacy of biologics for reducing the risk of cardiovascular diseases.

  25. The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors. International-journal

    Ryo Amagai, Toshiya Takahashi, Hitoshi Terui, Taku Fujimura, Kenshi Yamasaki, Setsuya Aiba, Yoshihide Asano

    International journal of molecular sciences　24　(1)　2023/01/03

    DOI： 10.3390/ijms24010875 　

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    An active form of cathelicidin antimicrobial peptide, LL-37, has immunomodulatory and stimulatory effects, though the specific pathways are not clear. The purpose of this study was to identify the cellular pathways by which LL-37 amplifies the inflammation induced by damage-associated molecular patterns (DAMPs). We performed DNA microarray, reverse transcription polymerase chain reaction, immunoblotting, and proximity ligation assays using cultured keratinocytes treated with LL-37 and/or the DAMP poly(I:C), a synthetic double-stranded RNA. In contrast to the combination of LL-37 and poly(I:C), LL-37 alone induced genes related to biological metabolic processes such as VEGFA and PTGS2 (COX-2). Inhibition of FPR2, a known receptor for cathelicidin, partially suppressed the induction of VEGFA and PTGS2. Importantly, VEGFA and PTGS2 induced by LL-37 alone were diminished by the knockdown of scavenger receptors including SCARB1 (SR-B1), OLR1 (SR-E1), and AGER (SR-J1). Moreover, LL-37 alone, as well as the combination of LL-37 and poly(I:C), showed proximity to the scavenger receptors, indicating that LL-37 acts via scavenger receptors and intermediates between them and poly(I:C). These results showed that the broad function of cathelicidin is generally dependent on scavenger receptors. Therefore, inhibitors of scavenger receptors or non-functional mock cathelicidin peptides may serve as new anti-inflammatory and immunosuppressive agents.

  26. Adverse events associated with postoperative outcomes of adjuvant anti-PD-1 antibody therapy in both acral and non-acral cutaneous melanomas: A multicenter, observational, post hoc analysis study

    Yusuke Muto, Yumi Kambayashi, Hiroshi Kato, Satoshi Fukushima, Takamichi Ito, Takeo Maekawa, Yasuhiro Fujisawa, Koji Yoshino, Hiroshi Uchi, Shigeto Matsushita, Yuki Yamamoto, Ryo Amagai, Kentaro Ohuchi, Akira Hashimoto, Yoshihide Asano, Taku Fujimura

    Journal of Dermatology　2023

    DOI： 10.1111/1346-8138.16912 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  27. Staphylococcus aureus skin colonization promotes SLE-like autoimmune inflammation via neutrophil activation and the IL-23/IL-17 axis. International-journal

    Hitoshi Terui, Kenshi Yamasaki, Moyuka Wada-Irimada, Mayuko Onodera-Amagai, Naokazu Hatchome, Masato Mizuashi, Riu Yamashita, Takeshi Kawabe, Naoto Ishii, Takaaki Abe, Yoshihide Asano, Setsuya Aiba

    Science immunology　7　(76)　eabm9811　2022/10/28

    DOI： 10.1126/sciimmunol.abm9811 　

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    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by inflammation of various organs such as skin, kidneys, bones, and brain and the presence of autoantibodies. Although the cause of SLE is not completely understood, environmental factors, genetic susceptibility, hormone factors, and environmental factors are thought to play essential roles in the pathogenesis of SLE. Among environmental factors, the microbiota are linked to the development of different autoimmune diseases. The microbiota in the nasal cavity and gut are involved in SLE development, but the influence of skin microbiota is still unclear. Here, we demonstrated that epithelial cell-specific IκBζ-deficient (NfkbizΔK5) mice showed spontaneous skin inflammation with increased abundance of Staphylococcus aureus on the skin. When S. aureus was epicutaneously applied on NfkbizΔK5 mice, NfkbizΔK5 mice developed SLE-associated autoantibodies, anti-dsDNA antibodies, anti-Sm antibodies, and glomerulonephritis with IgG deposition. Epicutaneous S. aureus application significantly increased staphylococcal colonization on the skin of NfkbizΔK5 mice with reduced expression of several antimicrobial peptides in the skin. This staphylococcal skin colonization promoted caspase-mediated keratinocyte apoptosis and neutrophil activation, inducing the interleukin-23 (IL-23)/IL-17 immune response by activating dendritic cells and T cells. Furthermore, the subcutaneous administration of anti-IL-23p19 and anti-IL-17A antibodies alleviated the systemic autoimmune response. Together, these findings underscore epithelial-immune cross-talk disturbances caused by skin dysbiosis as an essential mediator inducing autoimmune diseases.

  28. FLI1 deficiency-induced paradoxical Th2 polarization in response to IFN-γ possibly contributes to skin fibrosis in systemic sclerosis(タイトル和訳中)

    Ikawa Tetsuya, Miyagawa Takuya, Fukui Yuki, Toyama Satoshi, Omatsu Jun, Awaji Kentaro, Norimatsu Yuta, Watanabe Yusuke, Yoshizaki Ayumi, Sato Shinichi, Asano Yoshihide

    日本研究皮膚科学会年次学術大会・総会プログラム　47回　236-236　2022/10

    Publisher: (一社)日本研究皮膚科学会

  29. Successful treatment of metastatic fibrosarcomatous dermatofibrosarcoma protuberans with imatinib mesylate. International-journal

    Yumi Kambayashi, Yuki Kasahara, Kentaro Ohuchi, Ryo Amagai, Akira Hashimoto, Yoshihide Asano, Taku Fujimura

    Dermatologic therapy　35　(10)　e15736　2022/07/27

    DOI： 10.1111/dth.15736 　

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    Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor characterized by a high risk of local recurrence but a low risk of metastasis. A small subpopulation of DFSP undergoes fibrosarcomatous (FS) change, and approximately 15%-57% of cases of DFSP with FS change metastasizes, leading to a poor prognosis. In this report, a case of metastatic FS-DFSP that was successfully treated with imatinib mesylate in which the IHC staining pattern of recurrent DFSP was quantitatively analyzed in primary and metastatic DFSP areas, is described. Importantly, the recurrent area was composed of two IHC staining patterns (CD34low PD-L1high Ki67high , and CD34high PD-L1low Ki67low pattern), while the metastatic area showed a clonal pattern (CD34high PD-L1low Ki67intermediate ) in the present case. In this report, we described a case of metastatic fibrosarcomatous DFSP successfully treated with imatinib mesylate. This case suggests a subpopulation of DFSP with a favorable metastatic pattern.

  30. The Contribution of LIGHT (TNFSF14) to the Development of Systemic Sclerosis by Modulating IL-6 and T Helper Type 1 Chemokine Expression in Dermal Fibroblasts. International-journal

    Tetsuya Ikawa, Yohei Ichimura, Takuya Miyagawa, Yuki Fukui, Satoshi Toyama, Jun Omatsu, Kentaro Awaji, Yuta Norimatsu, Yusuke Watanabe, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    The Journal of investigative dermatology　142　(6)　1541-1551　2022/06

    DOI： 10.1016/j.jid.2021.10.028 　

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    Systemic sclerosis (SSc) is an autoimmune and vascular disease resulting in multiple organ fibrosis, in which IL-6 and T helper (Th)2/Th17 cytokines serve as critical disease drivers. LIGHT is a proinflammatory cytokine promoting IL-6 production in lung fibroblasts and Th1 chemokine expression in dermal fibroblasts (DFs) stimulated with IFN-γ. In this study, we investigated the potential contribution of LIGHT to SSc development using clinical samples and animal models. In SSc-involved skin, LIGHT was upregulated in inflammatory cells, whereas herpesvirus entry mediator (HVEM), a receptor of LIGHT, was downregulated in DFs. Similar expression profiles of LIGHT and HVEM were reproduced in bleomycin-treated mice. Transcription factor FLI1 bound to the HVEM promoter, and FLI1 small interfering RNA suppressed HVEM expression in normal DFs. In SSc DFs, LIGHT significantly increased IL-6 production, whereas IFN-γ/LIGHT-dependent Th1 chemokine induction was decreased compared with that in normal DFs. Importantly, LIGHT small interfering RNA significantly attenuated bleomycin-induced skin fibrosis, and serum LIGHT levels were elevated in patients with diffuse cutaneous SSc and positively correlated with clinical parameters reflecting skin and pulmonary fibrosis. Taken together, these results suggest that altered response of DFs to LIGHT, namely increased IL-6 production and decreased Th1 chemokine expression, contributes to the development of skin fibrosis in SSc.

  31. 胃前庭部毛細血管拡張症を合併した全身性強皮症の臨床的検討

    福井 夕輝, 浅野 善英, 宮嵜 美幾, 山下 尚志, 住田 隼一, 吉崎 歩, 山道 信毅, 佐藤 伸一

    日本皮膚科学会雑誌　132　(5)　1306-1306　2022/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  32. ガイドラインに基づいた膠原病・血管炎に伴う皮膚潰瘍の治療

    宮部 千恵, 浅井 純, 石井 貴之, 岩田 洋平, 内山 明彦, 小川 陽一, 岡村 賢, 岸部 麻里, 小池 雄太, 小寺 雅也, 壽 順久, 藤本 徳毅, 宮城 拓也, 山口 由衣, 吉崎 歩, 大森 礼子, 浅野 善英

    日本皮膚科学会雑誌　132　(5)　1137-1137　2022/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  33. 脊椎関節炎 乾癬性関節炎における患者自身による健康評価の検討

    立石 晶子, 大野 久美子, 吉崎 歩, 柴田 彩, 浅野 善英, 佐藤 伸一, 田中 栄, 藤尾 圭志, 神田 浩子

    日本リウマチ学会総会・学術集会プログラム・抄録集　66回　397-397　2022/03

    Publisher: (一社)日本リウマチ学会

  34. Predictors of Rituximab Effect on Modified Rodnan Skin Score in Systemic Sclerosis: a machine learning analysis of the DESIRES trial. International-journal

    Satoshi Ebata, Koji Oba, Kosuke Kashiwabara, Keiko Ueda, Yukari Uemura, Takeyuki Watadani, Takemichi Fukasawa, Shunsuke Miura, Asako Yoshizaki-Ogawa, Asano Yoshihide, Ayumi Yoshizaki, Shinichi Sato

    Rheumatology (Oxford, England)　61　(11)　4364-4373　2022/02/08

    DOI： 10.1093/rheumatology/keac023 　

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    OBJECTIVES: The DESIRES trial showed that rituximab is effective in treating skin sclerosis in systemic sclerosis. However, which patient groups are likely to benefit from rituximab is unknown. METHODS: We performed post-hoc analysis on prospective data from 54 patients who received rituximab or placebo in the DESIRES trial. Twenty-seven baseline factors were used to investigate subpopulations with different magnitudes of rituximab effect on modified Rodnan Skin Score (mRSS) change at 24 weeks. Based on a machine-learning algorithm called the causal tree, we explored the combination of predictors needed to identify subpopulations that would respond to rituximab and have good treatment outcomes. RESULTS: Three factors were identified as branches of the decision tree: "peripheral blood CD19-positive cell counts", "mRSS", and "serum surfactant protein D (SP-D) levels". Only in the subpopulation of patients with CD19-positive cell counts < 57/μl, rituximab did not show a significant improvement in mRSS vs placebo. In the subpopulation of patients with CD19-positive cell counts ≥ 57/μl and mRSS ≥ 17, mRSS was most improved with rituximab (difference -17.06 [95%CI -24.22 to -9.89]). The second greatest improvement in mRSS with rituximab was in the subpopulation with CD19-positive cell counts ≥ 57/μl, mRSS < 17, and serum SP-D levels ≥ 151 ng/ml (difference -10.35 [95% CI -14.77 to -5.93]). CONCLUSION: Systemic sclerosis patients who have high CD19-positive cell counts and high mRSS expected greater improvement in mRSS with rituximab. When the patients with high CD19-positive cell counts showed low mRSS, serum SP-D levels may modify the treatment effect. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04274257 and UMIN-CTR, https://center6.umin.ac.jp, UMIN000030139.

  35. 血清SP-D値に基づく全身性強皮症関連間質性肺炎に対するリツキシマブの治療反応性予測

    江畑 慧, 吉崎 歩, 深澤 毅倫, 浅野 善英, 佐藤 伸一, 大庭 幸治

    日本皮膚科学会雑誌　132　(2)　321-322　2022/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  36. Percentage of residual B cells after 2 weeks of rituximab treatment predicts the improvement of systemic sclerosis-associated interstitial lung disease. International-journal

    Satoshi Ebata, Ayumi Yoshizaki, Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Yoshihide Asano, Kosuke Kashiwabara, Koji Oba, Shinichi Sato

    The Journal of dermatology　49　(1)　179-183　2022/01

    DOI： 10.1111/1346-8138.16206 　

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    The benefit of rituximab (RTX) for systemic sclerosis-associated interstitial lung disease (SSc-ILD) has been shown in previous clinical trials. However, predictors of RTX efficacy have not been clarified. We investigated whether B-cell responsiveness to RTX is related to therapeutic effect. Ten SSc-ILD patients treated with RTX in an independent clinical trial (Japan Registry of Clinical Trials, jRCTs031180373) were included in this analysis. Peripheral B-cell counts were examined retrospectively before RTX administration (baseline) and at 2, 4, 12, and 24 weeks after the first RTX administration, along with percent-predicted forced vital capacity (%FVC) before and 24 weeks after RTX treatment. Relative to baseline, the percentage of residual peripheral blood B cells at 2 weeks after RTX was negatively correlated with the %FVC improvement at the 24-week assessment (r = -0.41, p = 0.04). In the subgroup with less than 5% B-cell persistence at week 2, %FVC at the 24-week assessment was significantly improved compared to baseline (p = 0.02). In another subgroup with more than 5% residual B cells, %FVC was not significantly different after 24 weeks compared to baseline (p = 0.41). In conclusion, the removal rate of B cells after 2 weeks of RTX treatment may be a useful surrogate marker of subsequent SSc-ILD improvement.

  37. Increased Red Blood Cell Distribution Width in the First Year after Diagnosis Predicts Worsening of Systemic Sclerosis-Associated Interstitial Lung Disease at 5 Years: A Pilot Study. International-journal

    Satoshi Ebata, Ayumi Yoshizaki, Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Yoshihide Asano, Kosuke Kashiwabara, Koji Oba, Shinichi Sato

    Diagnostics (Basel, Switzerland)　11　(12)　2021/12/04

    DOI： 10.3390/diagnostics11122274 　

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    The course of systemic sclerosis-associated interstitial lung disease (SSc-ILD) varies among individuals. Red blood cell distribution width (RDW) has been reported to be a predictor of idiopathic pulmonary fibrosis. However, there are no studies on the relationship between RDW and SSc-ILD. We conducted a retrospective study of 28 patients who were diagnosed with SSc-ILD on their first visit to our hospital and were followed-up for 5 years. The correlation between the changes in RDW, KL-6, and SP-D (ΔRDW, ΔKL-6, ΔSP-D) and the changes in percent-predicted forced lung volume and % carbon monoxide diffusion (Δ%FVC, Δ%DLco) was investigated. ΔRDW at 1 year after diagnosis was significantly inversely correlated with Δ%FVC at 5 years after diagnosis (r = -0.51, p < 0.001) and Δ%DLco at 5 years after diagnosis (r = -0.47, p < 0.001), whereas ΔKL-6 and ΔSP-D at 1 year were not correlated with Δ%FVC or Δ%DLco at 5 years. In the group of SSc-ILD patients with RDW increase in the first year after diagnosis, %FVC and %DLco were significantly lower than baseline at 3-, 4-, and 5-year assessments. In the group of patients without RDW increase in the first year, %FVC and %DLco did not decrease during the follow-up period. In conclusion, the changes in RDW in the first year after diagnosis may be useful surrogate markers to predict the long-term course of SSc-ILD.

  38. Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model

    Takemichi Fukasawa, Ayumi Yoshizaki, Satoshi Ebata, Asako Yoshizaki-Ogawa, Yoshihide Asano, Atsushi Enomoto, Kiyoshi Miyagawa, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Shinichi Sato

    ELIFE　10　2021/12

    DOI： 10.7554/eLife.67209.sa2 　

    ISSN： 2050-084X

  39. Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis

    Ai Kuzumi, Ayumi Yoshizaki, Kazuki M. Matsuda, Hirohito Kotani, Yuta Norimatsu, Maiko Fukayama, Satoshi Ebata, Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Yoshihide Asano, Kyojiro Morikawa, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Shinichi Sato

    Nature Communications　12　(1)　2021/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41467-021-26099-w 　

    eISSN： 2041-1723

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    <title>Abstract</title>Systemic sclerosis (SSc) is a chronic multisystem disorder characterized by fibrosis and autoimmunity. Interleukin (IL)-31 has been implicated in fibrosis and T helper (Th) 2 immune responses, both of which are characteristics of SSc. The exact role of IL-31 in SSc pathogenesis is unclear. Here we show the overexpression of IL-31 and IL-31 receptor A (IL-31RA) in dermal fibroblasts (DFs) from SSc patients. We elucidate the dual role of IL-31 in SSc, where IL-31 directly promotes collagen production in DFs and indirectly enhances Th2 immune responses by increasing pro-Th2 cytokine expression in DFs. Furthermore, blockade of IL-31 with anti-IL-31RA antibody significantly ameliorates fibrosis and Th2 polarization in a mouse model of SSc. Therefore, in addition to defining IL-31 as a mediator of fibrosis and Th2 immune responses in SSc, our study provides a rationale for targeting the IL-31/IL-31RA axis in the treatment of SSc.

  40. Endothelial CCR6 expression due to FLI1 deficiency contributes to vasculopathy associated with systemic sclerosis. International-journal

    Tetsuya Ikawa, Takuya Miyagawa, Yuki Fukui, Satoshi Toyama, Jun Omatsu, Kentaro Awaji, Yuta Norimatsu, Yusuke Watanabe, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    Arthritis research & therapy　23　(1)　283-283　2021/11/13

    DOI： 10.1186/s13075-021-02667-9 　

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    BACKGROUND: We have recently demonstrated that serum CCL20 levels positively correlate with mean pulmonary arterial pressure in patients with systemic sclerosis (SSc). Considering a proangiogenic effect of CCL20 on endothelial cells via CCR6, the CCL20/CCR6 axis may contribute to the development of SSc vasculopathy. Therefore, we explored this hypothesis using clinical samples, cultured cells, and murine SSc models. METHODS: The expression levels of CCL20 and CCR6 in the skin, mRNA levels of target genes, and the binding of transcription factor FLI1 to the target gene promoter were evaluated by immunostaining, quantitative reverse transcription PCR, and chromatin immunoprecipitation, respectively. Vascular permeability was evaluated by Evans blue dye injection in bleomycin-treated mice. Angiogenic activity of endothelial cells was assessed by in vitro angiogenesis assay. RESULTS: CCL20 expression was significantly elevated in dermal fibroblasts of patients with early diffuse cutaneous SSc, while CCR6 was significantly up-regulated in dermal small vessels of SSc patients irrespective of disease subtypes and disease duration. In human dermal microvascular endothelial cells, FLI1 siRNA induced the expression of CCR6, but not CCL20, and FLI1 bound to the CCR6 promoter. Importantly, vascular permeability, a representative SSc-like vascular feature of bleomycin-treated mice, was attenuated by Ccr6 siRNA treatment, and CCR6 siRNA suppressed the angiogenic activity of human dermal microvascular endothelial cells assayed by in vitro tube formation. CONCLUSIONS: The increased expression of endothelial CCR6 due to FLI1 deficiency may contribute to the development of SSc vasculopathy.

  41. Expert-Level Distinction of Systemic Sclerosis from Hand Photographs Using Deep Convolutional Neural Networks

    Yuta Norimatsu, Ayumi Yoshizaki, Yoshinori Kabeya, Takemichi Fukasawa, Jun Omatsu, Maiko Fukayama, Ai Kuzumi, Satoshi Ebata, Asako Yoshizaki-Ogawa, Yoshihide Asano, Haruka Ichimura, Sho Yonezawa, Hiroki Nakano, Shinichi Sato

    Journal of Investigative Dermatology　141　(10)　2536-2539　2021/10

    Publisher: Elsevier BV

    DOI： 10.1016/j.jid.2021.03.020 　

    ISSN： 0022-202X

  42. 全身性強皮症の皮膚線維化と血管障害の病態におけるCCR6の役割に関する検討

    井川 徹也, 宮川 卓也, 福井 夕輝, 遠山 聡, 尾松 淳, 淡路 健太郎, 乗松 雄大, 渡邉 裕介, 吉崎 歩, 浅野 善英, 佐藤 伸一

    日本臨床免疫学会総会プログラム・抄録集　49回　68-68　2021/10

    Publisher: (一社)日本臨床免疫学会

  43. Dermatomyositis-like eruptions and fasciitis with novel compound heterozygous MEFV mutations: Newly recognized features of a variant of familial Mediterranean fever. International-journal

    Hayakazu Sumida, Kiyoshi Migita, Hiroaki Ida, Yoshihide Asano, Jun Shimizu, Shinji Kagami, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    The Journal of dermatology　48　(9)　1453-1456　2021/09

    DOI： 10.1111/1346-8138.16031 　

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    Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent febrile attacks and serositis. The diagnosis of FMF has been based on clinical criteria, including frequent symptoms and good response to the treatment with colchicine. Some patients with FMF show skin or muscle manifestations, which may be confused with other cutaneous or muscle disorders. Here we report a female in her 40s with periodic fever, migratory myalgia, dermatomyositis-like dermatitis, arthralgia, pharyngalgia, and lymphadenopathy. The initial clinical differential diagnosis included dermatomyositis, malignant lymphoma, and adult-onset Still's disease. However, the following examinations could not explain her pathological condition with such diseases. In particular, findings from muscle and fascial biopsy demonstrated severe inflammatory cell infiltrate in the fascia, suggesting fasciitis as a possible cause of migratory myalgia. We examined the possibility of autoinflammatory diseases by genetic testing. Accordingly, she was found to have novel compound heterozygous mutations (L110P, E148Q, and P369S) in the MEFV gene. Given her genetic mutations and favorable response to colchicine, she was finally diagnosed as a variant of FMF with myalgia and previously unprecedented skin eruptions.

  44. Prognostic Relevance of Pretreatment Peripheral Neutrophil Count and Neutrophil-to-lymphocyte Ratio in Primary Cutaneous Angiosarcoma. International-journal

    Kentaro Awaji, Takuya Miyagawa, Jun Omatsu, Hiroko Numajiri, Toru Kawai, Kaoru Funamizu, Ryosuke Saigusa, Daisuke Yamada, Yoshihide Asano, Shinichi Sato

    Acta dermato-venereologica　101　(8)　adv00527　2021/08/25

    DOI： 10.2340/00015555-3898 　

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    Systemic inflammatory response markers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and monocyte-to-lymphocyte ratio, are useful prognostic factors for various malignant tumours. The aim of this study was to investigate the clinical relevance of these markers in primary cutaneous angiosarcoma. Twenty-six patients were retrospectively divided into 2 groups according to pretreatment peri-pheral blood cell counts or systemic inflammatory response marker levels; overall survival and progression-free survival were compared. Univariate analysis found that high neutrophil count (> 3.1×109/l), high neutrophil-to-lymphocyte ratio (> 2.4), high platelet-to-lymphocyte ratio (> 175) and low lymphocyte count (≤ 1.3×109/l) were related to shorter overall survival, while high neutrophil and low lymphocyte groups had shorter progression-free survival. In multivariate analysis, high neutrophil count and high neutrophil-to- lymphocyte ratio (hazard ratio 7.44 and 5.04, 95% confidence interval 1.48-37.2 and 1.26-20.1, respectiv-ely) were identified as independent prognostic factors for poor overall survival. These results indicate that systemic inflammatory response markers serve as prognostic predictors in primary cutaneous angiosarcoma, as well as in other types of soft-tissue sarcoma.

  45. Rapidly progressive interstitial lung disease associated with dermatomyositis—Longitudinal course of anti-MDA5 antibody titer in two cases

    Kentaro Awaji, Yoshihide Asano, Yuki Fukui, Tomonori Oka, Tetsuo Toyama, Shinichi Sato

    Journal of Cutaneous Immunology and Allergy　4　(4)　78-82　2021/08/01

    Publisher: John Wiley and Sons Inc

    DOI： 10.1002/cia2.12169 　

    ISSN： 2574-4593

  46. 胃前庭部毛細血管拡張症を合併した全身性強皮症の臨床的検討

    福井 夕輝, 浅野 善英, 宮嵜 美幾, 山下 尚志, 住田 隼一, 吉崎 歩, 山道 信毅, 佐藤 伸一

    日本皮膚科学会雑誌　131　(9)　2023-2032　2021/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  47. Serum levels of tissue factor pathway inhibitor: Potential association with Raynaud's phenomenon and telangiectasia in patients with systemic sclerosis. International-journal

    Yuta Norimatsu, Takuya Miyagawa, Yuki Fukui, Jun Omatsu, Satoshi Toyama, Kentaro Awaji, Tetsuya Ikawa, Yusuke Watanabe, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    The Journal of dermatology　48　(8)　1253-1256　2021/08

    DOI： 10.1111/1346-8138.15893 　

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    Vasculopathy is a critical step of systemic sclerosis (SSc) development, bridging between autoimmune inflammation and tissue fibrosis. Impaired coagulation system is a part of SSc vasculopathy, but the role of tissue factor pathway inhibitor (TFPI), a critical regulator of the extrinsic coagulation pathway, remained unknown. Therefore, we evaluated the clinical correlation of serum TFPI levels in SSc patients. Serum TFPI levels were comparable between SSc and control participants, but SSc patients with Raynaud's phenomenon and telangiectasia had significantly lower serum TFPI levels than those without. Importantly, there was a significant positive correlation between serum TFPI levels and protein S activity. These results support the critical role of impaired coagulation system in SSc.

  48. Safety and efficacy of rituximab in systemic sclerosis (DESIRES): a double-blind, investigator-initiated, randomised, placebo-controlled trial

    Satoshi Ebata, Ayumi Yoshizaki, Koji Oba, Kosuke Kashiwabara, Keiko Ueda, Yukari Uemura, Takeyuki Watadani, Takemichi Fukasawa, Shunsuke Miura, Asako Yoshizaki-Ogawa, Yoshihide Asano, Naoko Okiyama, Masanari Kodera, Minoru Hasegawa, Shinichi Sato

    The Lancet Rheumatology　3　(7)　e489-e497　2021/07

    Publisher: Elsevier BV

    DOI： 10.1016/s2665-9913(21)00107-7 　

    ISSN： 2665-9913

  49. Serum vasohibin-1 levels: A potential marker of dermal and pulmonary fibrosis in systemic sclerosis. International-journal

    Yuki Fukui, Kouki Nakamura, Megumi Hirabayashi, Takuya Miyagawa, Satoshi Toyama, Jun Omatsu, Kentaro Awaji, Tetsuya Ikawa, Yuta Norimatsu, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    Experimental dermatology　30　(7)　951-958　2021/07

    DOI： 10.1111/exd.14321 　

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    Vasohibin-1 (VASH-1) is a potent anti-angiogenic factor mainly produced by endothelial cells. In addition, VASH-1 prevents TGF-β-dependent activation of renal fibroblasts. Since systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and fibrosis of multiple organs, VASH-1 may be involved in the development of this disease. In this study, we investigated the potential role of VASH-1 in SSc by evaluating the clinical correlation between serum VASH-1 levels and the expression of VASH-1 in SSc-involved skin. Serum VASH-1 levels were higher in SSc patients, especially those with diffuse cutaneous involvement, than in healthy controls and positively correlated with skin score. Furthermore, SSc patients with interstitial lung disease had significantly elevated levels of serum VASH-1 as compared to those without. Importantly, serum VASH-1 levels correlated inversely with both the percentage of predicted vital capacity and the percentage of predicted diffusion lung capacity for carbon monoxide and positively with serum KL-6 levels, but not serum surfactant protein D levels. In SSc-involved skin, VASH1 mRNA was remarkably upregulated compared with healthy control skin, but the major source of VASH-1 was not clear. Fli1 deficiency, a predisposing factor inducing SSc-like endothelial properties, did not affect VASH-1 expression in human dermal microvascular endothelial cells. Collectively, these results suggest that VASH-1 upregulation in the skin and sera is linked to dermal and pulmonary fibrotic changes in SSc, while the contribution of VASH-1 to SSc vasculopathy seems to be limited.

  50. A potential contribution of decreased serum galectin-10 levels to systemic inflammation and pulmonary vascular involvement in systemic sclerosis. International-journal

    Kentaro Awaji, Takuya Miyagawa, Yuki Fukui, Satoshi Toyama, Jun Omatsu, Yuta Norimatsu, Tetsuya Ikawa, Yusuke Watanabe, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    Experimental dermatology　30　(7)　959-965　2021/07

    DOI： 10.1111/exd.14320 　

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    OBJECTIVE: Galectin-10 (Gal-10) is a key molecule involved in eosinophil-mediated suppression of T-cell immune response. Systemic sclerosis (SSc) is characterized by T helper (Th) 2/Th17 immune response and impaired function of regulatory T cells, but the pathological role of Gal-10 has not been studied so far. Therefore, we investigated the clinical correlation of serum Gal-10 levels in SSc patients. METHODS: Serum Gal-10 levels were determined by enzyme-linked immunosorbent assay in 38 patients with diffuse cutaneous SSc (dcSSc), 30 with limited cutaneous SSc and 20 healthy controls. Clinical correlations of serum Gal-10 levels were examined. RESULTS: Serum Gal-10 levels were significantly lower in SSc patients than in healthy controls, especially in dcSSc patients, and inversely correlated with skin score, the percentage of predicted diffusion lung capacity for carbon monoxide and estimated right ventricular systolic pressure (RVSP). Furthermore, serum Gal-10 levels had negative correlations with leucocyte counts and inflammatory parameters. Multivariate regression analysis identified C-reactive protein and RVSP as explanatory parameters for serum Gal-10 levels. CONCLUSION: Decreased serum Gal-10 levels may reflect the impairment of eosinophil-mediated regulatory system for T-cell immune response in SSc, possibly contributing to pulmonary vascular involvement leading to pulmonary arterial hypertension.

  51. Fli1 deficiency suppresses RALDH1 activity of dermal dendritic cells and related induction of regulatory T cells: a possible role in scleroderma

    Shunsuke Miura, Yusuke Watanabe, Ryosuke Saigusa, Takashi Yamashita, Kouki Nakamura, Megumi Hirabayashi, Takuya Miyagawa, Ayumi Yoshizaki, Maria Trojanowska, Shinichi Sato, Yoshihide Asano

    Arthritis Research &amp; Therapy　23　(1)　2021/05/08

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1186/s13075-021-02520-z 　

    eISSN： 1478-6362

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    Abstract Background Aldehyde dehydrogenase 1 family member A1 (RALDH1)-producing dermal dendritic cells (DCs), a conventional DC subset regulating skin fibrosis, are decreased in the involved skin of patients with systemic sclerosis (SSc). In this study, we investigated the contribution of Fli1 deficiency, a potential predisposing factor of SSc, to the phenotypical alteration of RALDH1-producing dermal DCs by using SSc model mice and SSc skin samples. Methods Bleomycin (BLM)-induced skin fibrosis was generated with Fli1+/− and wild-type mice. The proportions of DC and CD4+ T cell subsets were determined by flow cytometry in the dermis of BLM-treated mice. Fli1 expression in dermal DCs was evaluated by immunofluorescence with skin samples of SSc and healthy control subjects. Results RALDH activity of dermal DCs was significantly decreased in BLM-treated Fli1+/− mice compared with BLM-treated wild-type mice, whereas the proportion of CD103−CD11b− dermal DCs, a major DC subset producing RALDH1 in response to BLM injection, was comparable between groups. Relevant to this finding, the proportion of regulatory T cells (Tregs) in the dermis was decreased in BLM-treated Fli1+/− mice relative to BLM-treated wild-type mice, while the proportions of Th1, Th2 and Th17 cells were unaltered. In the involved skin of SSc patients, Fli1 was downregulated in CD11c+ cells, including dermal DCs. Conclusions Fli1 deficiency inhibits RALDH1 activity of CD103−CD11b− dermal DCs and related induction of Tregs in BLM-treated mice. Considering Fli1 reduction in SSc dermal DCs, Fli1deficiency may impair the dermal DC-Treg system, contributing to the development of skin fibrosis in SSc.

  52. B cell depletion inhibits fibrosis via suppressing pro‐fibrotic macrophage differentiation in a mouse model of systemic sclerosis

    Hiroko Numajiri, Ai Kuzumi, Takemichi Fukasawa, Satoshi Ebata, Asako Yoshizaki‐Ogawa, Yoshihide Asano, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Ayumi Yoshizaki, Shinichi Sato

    Arthritis & Rheumatology　73　(11)　2086-2095　2021/05/05

    Publisher: Wiley

    DOI： 10.1002/art.41798 　

    ISSN： 2326-5191

    eISSN： 2326-5205

  53. Association of serum CCL20 levels with pulmonary vascular involvement and primary biliary cholangitis in patients with systemic sclerosis. International-journal

    Tetsuya Ikawa, Takuya Miyagawa, Yuki Fukui, Shun Minatsuki, Hisataka Maki, Toshiro Inaba, Masaru Hatano, Satoshi Toyama, Jun Omatsu, Kentaro Awaji, Yuta Norimatsu, Yusuke Watanabe, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    International journal of rheumatic diseases　24　(5)　711-718　2021/05

    DOI： 10.1111/1756-185X.14103 　

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    AIM: Systemic sclerosis (SSc) is a chronic autoimmune disease resulting in vasculopathy and fibrosis of the skin and major internal organs. Especially, interstitial lung disease and pulmonary arterial hypertension are the leading causes of mortality. C-C motif ligand 20 (CCL20) is known as a homeostatic and inflammatory chemokine, which is associated with fibrosis and angiogenesis and constantly expressed in organs involved in SSc. Therefore, we investigated the potential contribution of CCL20 to the development of SSc. METHOD: We conducted cross-sectional analyses of 67 SSc patients and 20 healthy controls recruited in a single center for 9 years. Serum CCL20 levels were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed with the Mann-Whitney U test, the Kruskal-Wallis test followed by Dunn's multiple comparison test, Fisher's exact probability test and the Spearman's rank correlation coefficient. RESULTS: SSc patients had significantly higher serum CCL20 levels than healthy controls. In SSc patients, serum CCL20 levels correlated inversely with the percentage of predicated diffusion lung capacity for carbon monoxide and positively with mean pulmonary artery pressure (mPAP). In addition, SSc patients with increased serum CCL20 levels had anti-mitochondrial antibody M2 titer significantly elevated relative to those with normal levels, and SSc patients with asymptomatic primary biliary cholangitis (PBC) possessed higher serum CCL20 levels than those without. Importantly, serum CCL20 levels were associated positively with mPAP values and PBC presence by multivariate regression analysis. CONCLUSION: Serum CCL20 levels may be involved in the development of pulmonary vascular involvement leading to pulmonary arterial hypertension and asymptomatic PBC in SSc patients.

  54. Fingolimod ameliorates imiquimod-induced psoriasiform dermatitis by sequestrating interleukin-17-producing ?d T cells in secondary lymph nodes. International-journal

    Iori Okura, Masahiro Kamata, Yoshihide Asano, Aya Mitsui, Teruo Shimizu, Shinichi Sato, Yayoi Tada

    Journal of dermatological science　102　(2)　116-125　2021/05

    DOI： 10.1016/j.jdermsci.2021.04.004 　

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    BACKGROUND: Psoriasis is a chronic inflammatory skin disease. Interleukin (IL)-17A plays a key role in the pathogenesis of psoriasis. Fingolimod, which is available for the treatment of multiple sclerosis, exerts anti-inflammatory effects by sequestrating inflammatory lymphocytes in secondary lymphoid tissues and the thymus. The effect of fingolimod on psoriasis has not been reported yet. OBJECTIVE: Our objectives were to investigate the effect of fingolimod on psoriasis utilizing mice with imiquimod (IMQ)-induced psoriasiform dermatitis, and explore the possibility of fingolimod as a therapeutic agent for psoriasis. METHODS: Psoriasiform dermatitis was induced by imiquimod application on murine shaved back skin for six days. Fingolimod prepared in phosphate-buffered saline (PBS), or PBS alone as a control, was administered intraperitoneally daily from days 0 to 5. RESULTS: Fingolimod ameliorated IMQ-induced psoriasis dermatitis clinically and histologically. On day 6, the mRNA expression level of IL-17A was lower in the skin of fingolimod-treated mice than in that of PBS-treated mice, whereas it was higher in the inguinal lymph nodes of fingolimod-treated mice than in those of PBS-treated mice. Flow cytometric analyses revealed that fingolimod reduced IL-17A-producing ?d T cells infiltrating into the skin, whereas it increased these cells in the inguinal lymph nodes. Fingolimod inhibited egress of Langerhans cells from the skin to lymph nodes. CONCLUSION: Our results demonstrated that fingolimod showed effectiveness for IMQ-induced psoriasiform dermatitis by hindering the emigration of IL-17A-producing ?d T cells from the lymph nodes to the skin, and suggest that fingolimod is a promising candidate for the treatment of psoriasis.

  55. 膠原病・血管炎に伴う皮膚潰瘍 ガイドラインから学ぶ治療方針の基本と最近10年間の変遷

    石井 貴之, 浅野 善英, 浅井 純, 岩田 洋平, 内山 明彦, 小川 陽一, 岡村 賢, 岸部 麻里, 小池 雄太, 小寺 雅也, 壽 順久, 藤本 徳毅, 宮城 拓也, 宮部 千恵, 山口 由衣, 吉崎 歩

    日本皮膚科学会雑誌　131　(5)　1235-1235　2021/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  56. 脊椎関節炎:その他 乾癬性関節炎の脊椎病変の進行要因についての検討

    立石 晶子, 神田 浩子, 大野 久美子, 廣瀬 旬, 吉崎 歩, 柴田 彩, 浅野 善英, 佐藤 伸一, 田中 栄, 藤尾 圭志

    日本リウマチ学会総会・学術集会プログラム・抄録集　65回　360-360　2021/03

    Publisher: (一社)日本リウマチ学会

  57. Serum S100A12 levels: Possible association with skin sclerosis and interstitial lung disease in systemic sclerosis. International-journal

    Jun Omatsu, Ryosuke Saigusa, Takuya Miyagawa, Yuki Fukui, Satoshi Toyama, Kentaro Awaji, Tetsuya Ikawa, Yuta Norimatsu, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    Experimental dermatology　30　(3)　409-415　2021/03

    DOI： 10.1111/exd.14218 　

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    Damage-associated molecular patterns (DAMPs) have drawn much attention as a member of disease-associated molecules in systemic sclerosis (SSc). In this study, we investigated the potential contribution of S100A12, a member of DAMPs, to the development of SSc by evaluating S100A12 expression in the lesional skin and the clinical correlation of serum S100A12 levels. S100A12 expression was markedly elevated in the epidermis of SSc-involved skin at protein levels and in the bulk skin at mRNA levels. The deficiency of transcription factor Fli1, a predisposing factor of SSc, enhanced S100A12 expression and Fli1 occupied the S100A12 promoter in normal human keratinocytes. Serum S100A12 levels were higher in SSc patients, especially in those with diffuse cutaneous involvement, than in healthy controls and positively correlated with skin score. Furthermore, the presence of interstitial lung disease significantly augmented serum levels of S100A12. Importantly, serum S100A12 levels correlated inversely with both per cent forced vital capacity and per cent diffusing capacity for carbon monoxide and positively with serum levels of KL-6 and surfactant protein-D. Collectively, these results indicate a possible contribution of S100A12 to skin sclerosis and interstitial lung disease associated with SSc, further supporting the critical roles of DAMPs in the pathogenesis of this disease.

  58. Increased Regulatory T Cells and Decreased Myeloid-Derived Suppressor Cells Induced by High CCL17 Levels May Account for Normal Incidence of Cancers among Patients with Atopic Dermatitis. International-journal

    Sohshi Morimura, Makoto Sugaya, Tomonori Oka, Hiraku Suga, Tomomitsu Miyagaki, Yuichiro Tsunemi, Yoshihide Asano, Shinichi Sato

    International journal of molecular sciences　22　(4)　2021/02/18

    DOI： 10.3390/ijms22042025 　

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    The incidence of cancers in atopic dermatitis (AD) is not increased, although the Th2-dominant environment is known to downregulate tumor immunity. To gain mechanistic insights regarding tumor immunity in AD, we utilized CCL17 transgenic (TG) mice overexpressing CCL17, which is a key chemokine in AD. Tumor formation and lung metastasis were accelerated in CCL17 TG mice when melanoma cells were injected subcutaneously or intravenously. Flow cytometric analysis showed increases in regulatory T cells (Tregs) in lymph nodes in CCL17 TG mice with high mRNA levels of IL-10 and Foxp3 in tumors, suggesting that Tregs attenuated tumor immunity. The frequency of myeloid-derived suppressor cells (MDSCs), however, was significantly decreased in tumors of CCL17 TG mice, suggesting that decreased MDSCs might promote tumor immunity. Expression of CXCL17, a chemoattractant of MDSCs, was decreased in tumors of CCL17 TG mice. Depletion of Tregs by the anti-CD25 antibody markedly reduced tumor volumes in CCL17 TG mice, suggesting that tumor immunity was accelerated by the decrease in MDSCs in the absence of Tregs. Thus, CCL17 attenuates tumor immunity by increasing Tregs and Th2 cells, while it decreases MDSCs through reductions in CXCL17, which may work as a "safety-net" to reduce the risk of malignant tumors in the Th2-dominant environment.

  59. Serum TARC Levels in Patients with Systemic Sclerosis: Clinical Association with Interstitial Lung Disease. International-journal

    Ai Kuzumi, Ayumi Yoshizaki, Satoshi Ebata, Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Yoshihide Asano, Koji Oba, Shinichi Sato

    Journal of clinical medicine　10　(4)　2021/02/09

    DOI： 10.3390/jcm10040660 　

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    Systemic sclerosis (SSc) is a multisystem fibrotic disorder with autoimmune background. Accumulating evidence has highlighted the importance of T helper (Th) 2 cells in the pathogenesis of SSc and its complications. Because thymus and activation-regulated chemokine (TARC) is a potent chemoattractant for Th2 cells, we measured serum TARC levels in SSc patients and analyzed their correlation with interstitial lung disease (ILD), a major complication of SSc. Serum TARC levels were significantly elevated in patients with SSc, especially in those with the diffuse subtype, compared with healthy controls. In particular, dcSSc patients with SSc-associated ILD (SSc-ILD) showed higher TARC levels than those without SSc-ILD. However, there was no significant correlation between serum TARC levels and pulmonary function in SSc patients. Serum TARC levels did not correlate with serum levels of interleukin-13, an important Th2 cytokine, either. Furthermore, in the longitudinal study, serum TARC levels did not predict the onset or progression of SSc-ILD in patients with SSc. These results were in contrast with those of KL-6 and surfactant protein D, which correlated well with the onset, severity, and progression of SSc-ILD. Overall, these results suggest that serum TARC levels are not suitable for monitoring the disease activity of SSc-ILD.

  60. Serum heat shock protein 27 levels in patients with systemic sclerosis: a possible biomarker of skin sclerosis. International-journal

    K M Matsuda, A Yoshizaki, H Kotani, Y Norimatsu, A Kuzumi, M Fukayama, T Fukasawa, S Ebata, A Yoshizaki-Ogawa, Y Asano, K Oba, S Sato

    Journal of the European Academy of Dermatology and Venereology : JEADV　35　(2)　e157-e159　2021/02

    DOI： 10.1111/jdv.16885 　

  61. Association of serum CXCL12 levels with arthropathy in patients with systemic sclerosis. International-journal

    Tetsuya Ikawa, Takuya Miyagawa, Yuki Fukui, Satoshi Toyama, Jun Omatsu, Kentaro Awaji, Yuta Norimatsu, Yusuke Watanabe, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    International journal of rheumatic diseases　24　(2)　260-267　2021/02

    DOI： 10.1111/1756-185X.14037 　

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    AIM: Systemic sclerosis (SSc) is an autoimmune connective tissue disease, in which extensive fibrotic change and vasculopathy affect the skin and various internal organs. It also involves the joints, causing stiffness, arthralgia, and arthritis. Although arthropathy is commonly observed in SSc, its underlying mechanism remains unknown. CXCL12, also known as stromal cell derived factor 1, is associated with inflammation, mesenchymal cell recruitment, angiogenesis, and collagen production, and is implicated in the development of various joint diseases. To assess the potential contribution of CXCL12 to SSc development, we investigated the clinical association of serum CXCL12 levels in patients with SSc. METHOD: We conducted a cross-sectional analysis of 68 patients with SSc and 20 healthy controls recruited in a single center over 9 years. Serum CXCL12 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum CXCL12 levels were significantly higher in patients with SSc than in healthy controls (median 1554.0 pg/mL, 25th-75th centiles 1313.0-1914.0 pg/mL vs 967.4 pg/mL, 608.8-1271.0 pg/mL, P < 0.001). Patients with SSc with elevated CXCL12 levels had significantly more cases of arthropathy than those with normal CXCL12 levels (85.7% vs 25.0%, P = 0.01). Furthermore, patients with SSc with elevated CXCL12 levels showed an increased trend in the prevalence of limited range of motion of the finger joints compared with those with normal CXCL12 levels (60.0% vs 18.6%, P =0 .07). Moreover, serum CXCL12 levels were significantly correlated with the titers of rheumatoid factor in patients with SSc (r = .41, P = 0.001). CONCLUSION: Elevated serum CXCL12 levels may be related to the development of SSc arthropathy.

  62. Serum Calponin 3 Levels in Patients with Systemic Sclerosis: Possible Association with Skin Sclerosis and Arthralgia. International-journal

    Hirohito Kotani, Ayumi Yoshizaki, Kazuki M Matsuda, Yuta Norimatsu, Ai Kuzumi, Maiko Fukayama, Takemichi Fukasawa, Satoshi Ebata, Asako Yoshizaki-Ogawa, Yoshihide Asano, Koji Oba, Shinichi Sato

    Journal of clinical medicine　10　(2)　2021/01/14

    DOI： 10.3390/jcm10020280 　

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    Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis and vasculopathy in various organs with a background of inflammation initiated by autoimmune abnormalities. Calponin 3 plays a role in the cell motility and contractibility of fibroblasts during wound healing in the skin. We aimed to evaluate serum calponin 3 levels in SSc patients and their association with clinical manifestations of SSc. Serum samples were collected from 68 patients with SSc and 20 healthy controls. Serum calponin 3 levels were examined using enzyme-linked immunosorbent assay kits, and their association with clinical features of SSc was statistically analyzed. The upper limit of the 95% confidence interval of serum calponin 3 levels in healthy controls was utilized as the cut-off value when dividing SSc patients into the elevated and normal groups. Serum calponin 3 levels were significantly higher in SSc patients than in healthy controls (mean (95% confidence interval), 15.38 (14.66-16.11) vs. 13.56 (12.75-14.38) ng/mL, p < 0.05). The modified Rodnan total skin thickness score was significantly higher in the elevated serum calponin 3 level group than in the normal level group (median (25-75th percentiles), 10.0 (2.0-16.0) vs. 6.5 (3.25-8.75), p < 0.05). Moreover, SSc patients with increased serum calponin 3 levels also had a higher frequency of arthralgia (40% vs. 9%, p < 0.05). Elevated serum calponin 3 levels were associated with skin sclerosis and arthralgia in SSc patients. Serum calponin 3 levels might be a biomarker that reflects the severity of skin sclerosis and joint involvement in SSc.

  63. Linear childhood discoid lupus erythematosus along a Blaschko's line of the arm

    Tetsuo Toyama, Takuya Miyagawa, Shinichi Sato, Yoshihide Asano

    Journal of Cutaneous Immunology and Allergy　2021

    Publisher: John Wiley and Sons Inc

    DOI： 10.1002/cia2.12221 　

    ISSN： 2574-4593

  64. Case of aquagenic urticaria: Case report and the results of histopathological examination. International-journal

    Maiko Fukayama, Yukako Domoto, Shinichi Sato, Yoshihide Asano

    The Journal of dermatology　48　(1)　88-91　2021/01

    DOI： 10.1111/1346-8138.15615 　

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    Aquagenic urticaria (AU) is a rare skin condition in which dermal contact with water serves as a trigger of urticaria and pruritus. To make a diagnosis, a water challenge test is useful. We herein report a 16-year-old Japanese boy diagnosed with AU by water provocation test. The induced skin lesion histologically showed prominent degranulation of mast cells and lymphocytic infiltration throughout the dermis. This is the second report documenting the histopathological features of AU.

  65. Characteristics of Japanese patients with eosinophilic fasciitis: A brief multicenter study. International-journal

    Toshiyuki Yamamoto, Takashi Ito, Yoshihide Asano, Shinichi Sato, Sei-Ichiro Motegi, Osamu Ishikawa, Takashi Matsushita, Kazuhiko Takehara, Takamitsu Makino, Naoko Okiyama, Manabu Fujimoto, Masatoshi Jinnin, Hironobu Ihn

    The Journal of dermatology　47　(12)　1391-1394　2020/12

    DOI： 10.1111/1346-8138.15561 　

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    Eosinophilic fasciitis is a relatively rare cutaneous fibrotic condition affecting the deep fascia of the extremities, with or without peripheral blood eosinophilia. To examine the characteristics of Japanese patients with eosinophilic fasciitis, we conducted a brief, multicenter, retrospective survey at seven university hospitals. In total, 31 patients were identified as having eosinophilic fasciitis, among whom 30 patients fulfilled the Japanese diagnostic criteria. The male : female ratio was 2.3:1, and the mean age was 47.7 years. Three of the patients were under 20 years old. The possible triggering factors included muscle training, sports, walking or sitting for a long time, physical work, insect bite and drug. Co-occurrence of morphea was observed in nine cases (29%), and malignancies were associated in three (two hematological malignancies and one internal malignancy). Immunological abnormalities in the serum showed positive antinuclear antibody, positive rheumatoid factor, increased aldolase levels and increased immunoglobulin G levels. The patients were treated with either monotherapy or combination therapy by oral prednisolone (20-80 mg/day), methotrexate (6-10 mg/week), cyclosporin (100-150 mg/day), mizoribine, infliximab and phototherapy. Methylprednisolone pulse therapy was performed in six cases. By contrast, spontaneous improvement due to resting only was observed in two cases, and skin hardening was improved by withdrawal of the anticancer drug in one case. This study suggests several characteristics of Japanese patients with eosinophilic fasciitis, namely male predominance, rare pediatric occurrence, immunological abnormalities and coexistence with morphea. Systemic prednisolone is the first-line therapy, but pulse therapy is occasionally required for severe cases. The triggering events of physical stress are not so frequent as have previously been reported, and various factors or even unknown factors may be associated with the induction of eosinophilic fasciitis.

  66. TLR2 Deficiency Exacerbates Imiquimod-Induced Psoriasis-Like Skin Inflammation through Decrease in Regulatory T Cells and Impaired IL-10 Production. International-journal

    Momoko Nakao, Makoto Sugaya, Hideki Fujita, Tomomitsu Miyagaki, Sohshi Morimura, Sayaka Shibata, Yoshihide Asano, Shinichi Sato

    International journal of molecular sciences　21　(22)　2020/11/13

    DOI： 10.3390/ijms21228560 　

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    Emerging evidence has demonstrated that Toll-like receptors (TLRs) are associated with autoimmune diseases. In this study, we investigated the role of TLR2 in psoriasis using imiquimod-induced psoriasis-like dermatitis. Although TLR2 signaling is known to play a critical role in the induction of proinflammatory cytokines by immune cells, such as dendritic cells (DCs), macrophages, and monocytes, TLR2 deficiency unexpectedly exacerbated psoriasiform skin inflammation. Importantly, messenger RNA (mRNA) levels of Foxp-3 and IL-10 in the lesional skin were significantly decreased in TLR2 KO mice compared with wild-type mice. Furthermore, flow cytometric analysis of the lymph nodes revealed that the frequency of regulatory T cells (Tregs) among CD4-positive cells was decreased. Notably, stimulation with Pam3CSK4 (TLR2/1 ligand) or Pam2CSK4 (TLR2/6 ligand) increased IL-10 production from Tregs and DCs and the proliferation of Tregs. Finally, adoptive transfer of Tregs from wild-type mice reduced imiquimod-induced skin inflammation in TLR2 KO mice. Taken together, our results suggest that TLR2 signaling directly enhances Treg proliferation and IL-10 production by Tregs and DCs, suppressing imiquimod-induced psoriasis-like skin inflammation. Enhancement of TLR2 signaling may be a new therapeutic strategy for psoriasis.

  67. オーバーラップ症候群マウスモデルにおける全身性強皮症および全身性エリテマトーデスに関連する疾患プロセス間のクロストーク(The crosstalk between systemic sclerosis- and systemic lupus erythematosus-related disease processes in a mouse model of overlap syndrome)

    Toyama Satoshi, Miura Shunsuke, Saigusa Ryosuke, Yamashita Takashi, Nakamura Kouki, Hirabayashi Megumi, Miyagawa Takuya, Fukui Yuki, Omatsu Jun, Awaji Kentaro, Yoshizaki Ayumi, Sato Shinichi, Asano Yoshihide

    日本研究皮膚科学会年次学術大会・総会プログラム　45回　149-149　2020/11

    Publisher: (一社)日本研究皮膚科学会

  68. オーバーラップ症候群モデルマウスを用いた、全身性強皮症および全身性エリテマトーデスの病態干渉に関する検討

    遠山 聡, 三浦 俊介, 三枝 良輔, 山下 尚志, 中村 洸樹, 平林 恵, 宮川 卓也, 福井 夕輝, 尾松 淳, 淡路 健太郎, 吉崎 歩, 佐藤 伸一, 浅野 善英

    日本臨床免疫学会総会プログラム・抄録集　48回　105-105　2020/10

    Publisher: (一社)日本臨床免疫学会

  69. Decreased serum cathepsin S levels in patients with systemic sclerosis-associated interstitial lung disease. International-journal

    Satoshi Toyama, Takashi Yamashita, Ryosuke Saigusa, Shunsuke Miura, Kouki Nakamura, Megumi Hirabayashi, Takuya Miyagawa, Yuki Fukui, Jun Omatsu, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    The Journal of dermatology　47　(9)　1027-1032　2020/09

    DOI： 10.1111/1346-8138.15458 　

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    Cathepsin S (CTSS) is a lysosomal proteolytic enzyme regulating intracellular and extracellular biological activities, including immunity/inflammation and remodeling of vasculature and extracellular matrix, which are the three cardinal pathological events associated with systemic sclerosis (SSc). To elucidate the potential role of CTSS in the development of SSc, we investigated the clinical correlation of serum CTSS levels. Because serum CTSS levels were inversely correlated with estimated glomerular filtration rate (eGFR) in SSc patients with renal dysfunction (eGFR, <60 min/mL per 1.73 m2 ), SSc patients with normal renal function (eGFR, ≥60 min/mL per 1.73 m2 ) were analyzed. Serum CTSS levels were significantly decreased in diffuse cutaneous SSc patients compared with limited cutaneous SSc patients and healthy controls. Among vascular and fibrotic clinical manifestations, Raynaud's phenomenon and interstitial lung disease (ILD) were relevant to a significant decrease in serum CTSS levels. Importantly, serum CTSS levels negatively correlated with serum levels of Krebs von den Lungen-6 and surfactant protein D in total SSc patients, while not correlating with modified Rodnan total skin thickness score and the percentage of predicted diffusion lung capacity for carbon monoxide and showing a positive trend with the percentage of predicted vital capacity. These results suggest a potential contribution of decreased CTSS expression to the development of ILD in patients with SSc.

  70. Fli1 deficiency induces endothelial adipsin expression, contributing to the onset of pulmonary arterial hypertension in systemic sclerosis. International-journal

    Takuya Miyagawa, Takashi Taniguchi, Ryosuke Saigusa, Maiko Fukayama, Takehiro Takahashi, Takashi Yamashita, Megumi Hirabayashi, Shunsuke Miura, Kouki Nakamura, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    Rheumatology (Oxford, England)　59　(8)　2005-2015　2020/08/01

    DOI： 10.1093/rheumatology/kez517 　

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    OBJECTIVES: Adipsin, or complement factor D, is a serine proteinase catalysing complement factor C3 breakdown, leading to the production of opsonin (C3b), membrane attack complex (C5b-C9) and anaphylatoxins (C3a and C5a). Since adipsin is potentially associated with pulmonary arterial hypertension in SSc, we investigated adipsin expression in dermal small vessels of SSc-involved skin, the mechanism regulating adipsin expression in endothelial cells, and the correlation of serum adipsin levels with SSc clinical symptoms. METHODS: Adipsin expression was assessed by immunohistochemistry with skin sections of SSc and healthy subjects. mRNA levels of target genes and transcription factor binding to the ADIPSIN promoter were evaluated by quantitative reverse transcription PCR and chromatin immunoprecipitation, respectively. Serum adipsin levels were determined by enzyme-linked immunosorbent assay. RESULTS: Adipsin expression was remarkably increased in dermal small vessels of SSc-involved skin as compared with those of healthy control skin. Consistent with the notion that Fli1 deficiency induces SSc-like phenotypes in various types of cells, FLI1 siRNA enhanced adipsin expression at protein and mRNA levels and Fli1 bound to the ADIPSIN promoter in human dermal microvascular endothelial cells. Serum adipsin levels were significantly lower in diffuse cutaneous SSc patients than in limited cutaneous SSc patients and healthy controls, and were associated positively with elevated right ventricular systolic pressure and inversely with interstitial lung disease by multivariate regression analysis. CONCLUSION: Adipsin is up-regulated at least partially by Fli1 deficiency in endothelial cells, potentially contributing to the development of pulmonary vascular involvement in SSc.

  71. 乾癬性関節炎 実臨床下での乾癬性関節炎(PsA)に対する生物学的製剤の効果の比較検討

    立石 晶子, 神田 浩子, 井上 眞璃子, 大野 久美子, 廣瀬 旬, 吉崎 歩, 浅野 善英, 佐藤 伸一, 田中 栄, 藤尾 圭志

    日本リウマチ学会総会・学術集会プログラム・抄録集　64回　389-389　2020/08

    Publisher: (一社)日本リウマチ学会

  72. Interleukin (IL)-17F and IL-17E are related to fibrosis and vasculopathy in systemic sclerosis. International-journal

    Maiko Fukayama, Ayumi Yoshizaki, Takemichi Fukasawa, Satoshi Ebata, Ai Kuzumi, Asako Yoshizaki-Ogawa, Yoshihide Asano, Koji Oba, Shinichi Sato

    The Journal of dermatology　47　(11)　1287-1292　2020/07/19

    DOI： 10.1111/1346-8138.15508 　

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    Systemic sclerosis (SSc) is an autoimmune disease that causes fibrosis and vasculopathy of the skin and internal organs against a background of autoimmune abnormalities. In recent years, the importance of the interleukin (IL)-17 family for inflammatory diseases has received much attention, but autoimmune diseases have not yet been fully explored. As for SSc, there is also no unified perspective on the involvement of the IL-17 family in its development, and few studies have been conducted linking IL-17F and IL-17E particularly to the disease severity. In the present study, we examined the correlation between serum IL-17F and IL-17E levels and disease severity in SSc patients. Moreover, the expression of the receptors for these cytokines, IL-17RB and IL-17RC, in skin tissues obtained by skin biopsy was examined by immunohistochemistry. Both cytokines were significantly elevated in the sera of patients with diffuse cutaneous SSc patients compared with healthy controls. Serum IL-17F levels correlated with modified Rodnan total skin thickness score, a semiquantitative measure of skin sclerosis, percent predicted forced vital capacity, percent predicted carbon monoxide lung diffusion capacity and serum levels of Krebs von den Lungen-6 and surfactant protein-D, serological markers of interstitial lung disease. Serum IL-17E levels were significantly correlated with percent predicted forced vital capacity and serum Krebs von den Lungen-6 levels. Serum levels of IL-17F and IL-17E also correlated with the prevalence of digital ulcers, and serum IL-17F levels were associated with elevated right ventricle systolic pressure values. In addition, IL-17RC and IL-17RB expression was increased in the skin tissues of diffuse cutaneous SSc patients. These results suggested that IL-17F and IL-17E could be involved in fibrosis and vasculopathy in SSc through their respective receptors in the affected organ tissues.

  73. Altered properties of endothelial cells and mesenchymal stem cells underlying the development of scleroderma-like vasculopathy in Klf5+/- ;Fli1+/- mice. International-journal Peer-reviewed

    Kouki Nakamura, Takashi Taniguchi, Megumi Hirabayashi, Takashi Yamashita, Ryosuke Saigusa, Shunsuke Miura, Takehiro Takahashi, Tetsuo Toyama, Yohei Ichimura, Ayumi Yoshizaki, Maria Trojanowska, Katsuhito Fujiu, Ryozo Nagai, Shinichi Sato, Yoshihide Asano

    Arthritis & rheumatology (Hoboken, N.J.)　72　(12)　2136-2146　2020/07/06

    DOI： 10.1002/art.41423 　

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    OBJECTIVE: We previously established a new animal model (Klf5+/- ;Fli1+/- mice) broadly recapitulating fundamental pathologic features of systemic sclerosis (SSc). SSc vasculopathy is believed to occur as a result of impaired vascular remodeling, but its detailed mechanism has remained unknown. To address this issue, we investigated the properties of dermal microvascular endothelial cells (DMECs), bone marrow-derived endothelial progenitor cells (BM-EPCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs), a precursor of pericytes, in Klf5+/- ;Fli1+/- mice. METHODS: Neovascularization and angiogenesis were assessed by in vivo Matrigel plug assay and in vitro tube formation assay, respectively. The properties of BM-EPCs and BM-MSCs were assessed in in vitro studies. Dermal vasculature was visualized in vivo by FITC-dextran injection. RESULTS: Neovascularization was diminished in skin-embedded Matrigel plug in Klf5+/- ;Fli1+/- mice. Klf5+/- ;Fli1+/- DMECs showed defective tubulogenic activity, decreased expression of VE-cadherin and CD31, and imbalance of Notch1/delta-like ligand 4, suggesting that angiogenesis and anastomosis are disturbed. Klf5+/- ;Fli1+/- BM-MSCs exhibited enhanced proliferation, migration and collagen production by transforming growth factor-β1, indicating the preferential differentiation into myofibroblasts rather than pericytes. Klf5+/- ;Fli1+/- BM-EPCs displayed the transition toward mesenchymal cells, suggesting that vasculogenesis is impaired. Wound healing was delayed in Klf5+/- ;Fli1+/- mice (15.67 ± 0.82 days versus 13.50 ± 0.84 days; P = 0.0017), and vascular network was poorly developed in wound scar tissue. CONCLUSION: Klf5+/- ;Fli1+/- mice represent impaired neovascularization and vascular maturation similar to those of SSc at least partially due to the induction of SSc-like properties in DMECs, BM-EPCs and BM-MSCs, indicating the critical contribution of KLF5 and Fli1 deficiency in vascular cells and related precursors to SSc vasculopathy.

  74. Wound, pressure ulcer and burn guidelines - 1: Guidelines for wounds in general, second edition. International-journal Peer-reviewed

    Minoru Hasegawa, Yuji Inoue, Sakae Kaneko, Hiroyuki Kanoh, Yoichi Shintani, Jun Tsujita, Hideki Fujita, Sei-Ichiro Motegi, Andres Le Pavoux, Jun Asai, Yoshihide Asano, Masatoshi Abe, Masahiro Amano, Ryuta Ikegami, Takayuki Ishii, Taiki Isei, Zenzo Isogai, Takaaki Ito, Ryokichi Irisawa, Yohei Iwata, Masaki Otsuka, Yoichi Omoto, Hiroshi Kato, Takafumi Kadono, Tamihiro Kawakami, Masakazu Kawaguchi, Ryuichi Kukino, Takeshi Kono, Monji Koga, Masanari Kodera, Keisuke Sakai, Eiichi Sakurai, Yasuko Sarayama, Miki Tanioka, Hideaki Tanizaki, Naotaka Doi, Takeshi Nakanishi, Akira Hashimoto, Masahiro Hayashi, Kuninori Hirosaki, Manabu Fujimoto, Hiroshi Fujiwara, Takeo Maekawa, Koma Matsuo, Naoki Madokoro, Hiroshi Yatsushiro, Osamu Yamasaki, Yuichiro Yoshino, Takao Tachibana, Hironobu Ihn

    The Journal of dermatology　47　(8)　807-833　2020/07/02

    DOI： 10.1111/1346-8138.15401 　

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    The Japanese Dermatological Association prepared the clinical guidelines for the "Wound, pressure ulcer and burn guidelines", second edition, focusing on treatments. Among them, "Guidelines for wounds in general" is intended to provide the knowledge necessary to heal wounds, without focusing on particular disorders. It informs the basic principles of wound treatment, before explanations are provided in individual chapters of the guidelines. We updated all sections by collecting references published since the publication of the first edition. In particular, we included new wound dressings and topical medications. Additionally, we added "Question 6: How should wound-related pain be considered, and what should be done to control it?" as a new section addressing wound pain, which was not included in the first edition.

  75. Case of systemic sclerosis with multiple primary malignancies in whom anti-RNA polymerase III antibody was detected by immunoprecipitation. International-journal

    Naohiko Aozasa, Miki Miyazaki, Jun Hayakawa, Takeshi Tamaki, Yasuhito Hamaguchi, Shinichi Sato, Yoshihide Asano

    The Journal of dermatology　47　(7)　e269-e270　2020/07

    DOI： 10.1111/1346-8138.15383 　

  76. Rapid decrease of serum surfactant protein-D levels predicts the reactivity of rituximab therapy in systemic sclerosis-associated interstitial lung disease. International-journal

    Satoshi Ebata, Ayumi Yoshizaki, Takemichi Fukasawa, Yoshihide Asano, Koji Oba, Shinichi Sato

    The Journal of dermatology　47　(7)　796-800　2020/07

    DOI： 10.1111/1346-8138.15379 　

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    Systemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage and excessive fibrosis. SSc-associated interstitial lung disease (ILD) is a leading cause of death in SSc. Several studies have shown the efficacy of rituximab (RTX) in SSc-ILD, but no study has examined the relation between RTX reactivity and change of serum marker levels. In this study we examined the relation between change of serum surfactant protein-D (SP-D) levels and change of percentage forced vital capacity (FVC) in 11 SSc-ILD patients with anti-topoisomerase I antibody treated by RTX. Serum SP-D levels were significantly decreased compared with baseline at 2 weeks after first RTX infusion in good responders (P = 0.04), while not in poor responders (P = 0.77). Moreover, ΔSP-D at 2 weeks negatively correlated with Δ%FVC at 24 weeks (P = 0.001). In conclusion, we suggested that the rapid decrease of SP-D levels may be a predictive marker of RTX effect against SSc-ILD.

  77. Clinical significance of endothelial vasodilatory function evaluated by EndoPAT in patients with systemic sclerosis. International-journal

    Naohiko Aozasa, Masaru Hatano, Ryosuke Saigusa, Kouki Nakamura, Takehiro Takahashi, Tetsuo Toyama, Hayakazu Sumida, Zenshiro Tamaki, Hisataka Maki, Shun Minatsuki, Issei Komuro, Shinichi Sato, Yoshihide Asano

    The Journal of dermatology　47　(6)　609-614　2020/06

    DOI： 10.1111/1346-8138.15334 　

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    Endothelial dysfunction is a hallmark of vasculopathy associated with systemic sclerosis (SSc). Reactive hyperemia peripheral arterial tonometry is a rapid and non-invasive technique to assess peripheral microvascular endothelial function by measuring changes in digital pulse volume during reactive hyperemia. Low scores of the reactive hyperemia index (RHI) imply an impaired vasodilatory response and, accordingly, impaired endothelial and vascular health. To investigate the clinical significance of the RHI in SSc patients, RHI values were measured in 43 SSc patients and 10 healthy controls. In diffuse cutaneous SSc (dcSSc) patients, RHI values were significantly decreased compared with healthy controls, and inversely correlated with disease duration. In total SSc patients, there was a significant inverse correlation between RHI values and skin score, and interstitial lung disease was associated with the decrease in RHI values. Among vascular symptoms, the current and past history of digital ulcers was seen more frequently in patients with decreased RHI values than in those with normal RHI values. Although no SSc patients had pulmonary arterial hypertension, an inverse correlation was evident between RHI values and mean pulmonary arterial pressure measured by right heart catheterization. These results indicate that the decrease in RHI values is associated with skin fibrosis, interstitial lung disease, digital ulcers and pulmonary vascular involvement leading to pulmonary arterial hypertension, supporting the canonical idea that endothelial dysfunction is a critical event underlying the development of tissue fibrosis and vascular complications in SSc.

  78. The development of quality indicators for systemic lupus erythematosus using electronic health data: A modified RAND appropriateness method. International-journal Peer-reviewed

    Nobuyuki Yajima, Yasushi Tsujimoto, Shingo Fukuma, Ken-Ei Sada, Sayaka Shimizu, Kakuya Niihata, Ryo Takahashi, Yoshihide Asano, Teruhisa Azuma, Hideto Kameda, Masataka Kuwana, Hitoshi Kohsaka, Mayumi Sugiura-Ogasawara, Katsuya Suzuki, Tsutomu Takeuchi, Yoshiya Tanaka, Naoto Tamura, Toshihiro Matsui, Tsuneyo Mimori, Shunichi Fukuhara, Tatsuya Atsumi

    Modern rheumatology　30　(3)　525-531　2020/05

    DOI： 10.1080/14397595.2019.1621419 　

    ISSN： 1439-7595

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    Objective: Quality indicators (QIs) are tools that standardize evaluations in terms of the minimum acceptable quality of care, presumably contributing for the better management of patients with systemic lupus erythematosus (SLE). This study aimed to develop QIs for SLE using electronic health data.Methods: The modified RAND/UCLA Appropriateness Method was used to develop the QIs. First, a literature review was conducted. Second, the candidate QI items that were available to be evaluated using the electronic health data were extracted. Third, the appropriateness of the items was assessed via rating rounds and panelists' discussions.Results: We found 3621 articles in the initial search. Finally, 34 studies were reviewed, from which 17 potential indicators were extracted as candidate QIs. Twelve indicators were selected as the final QI set through the process of appropriateness. The median appropriateness of these 12 indicators was at least 7.5, and all of them were without disagreement. The QI included assessment of disease activity, treatment of SLE, drug toxicity monitoring, treatment of glucocorticoid complications, and assessment of SLE complications.Conclusion: We formulated 12 QIs for the assessment of patients with SLE based on electronic medical data. Our QI set would be a practical tool as a quality measure.

  79. Wound, Pressure Ulcer, and Burn Guidelines-6: Guidelines for the Management of Burns, second edition. International-journal Peer-reviewed

    Yoshino Y, Amano M, Omoto Y, Kawaguchi M, Sakai K, Doi N, Hashimoto A, Hayashi M, Madokoro N, Asai J, Asano Y, Abe M, Ikegami R, Ishii T, Isei T, Isogai Z, Ito T, Inoue Y, Irisawa R, Iwata Y, Ohtsuka M, Kato H, Kadono T, Kaneko S, Kanoh H, Kawakami T, Kukino R, Kono T, Koga M, Kodera M, Sakurai E, Sarayama Y, Shintani Y, Tanioka M, Tanizaki H, Tsujita J, Nakanishi T, Hasegawa M, Hirosaki K, Fujita H, Fujimoto M, Fujiwara H, Maekawa T, Matsuo K, Motegi SI, Yatsushiro H, Yamasaki O, Le Pavoux AJ, Tachibana T, Ihn H

    Journal of Dermatology　47　(11)　1207-1235　2020/04/28

    DOI： 10.1111/1346-8138.15335 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  80. Clinical course of Japanese patients with early systemic sclerosis: a multicenter, prospective, observational study. International-journal Peer-reviewed

    Akira Utsunomiya, Minoru Hasegawa, Noritaka Oyama, Yoshihide Asano, Hirahito Endo, Manabu Fujimoto, Daisuke Goto, Osamu Ishikawa, Yasushi Kawaguchi, Masataka Kuwana, Fumihide Ogawa, Hiroki Takahashi, Sumiaki Tanaka, Shinichi Sato, Kazuhiko Takehara, Hironobu Ihn

    Modern rheumatology　31　(1)　1-20　2020/04/03

    DOI： 10.1080/14397595.2020.1751408 　

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    Objectives: To investigate the clinical course of Japanese patients with early diffuse cutaneous systemic sclerosis (dcSSc) and early SSc with interstitial lung disease (ILD).Methods: We prospectively analyzed the clinical features of 207 Japanese patients with early dcSSc (n = 150) and limited cutaneous SSc (lcSSc) with ILD (n = 57) in 10 medical centers every year for 7 consecutive years.Results: Mean modified Rodnan total skin thickness score (mRSS) was 18.3 and 67.4% of the cohort had ILD. Most patients started immunosuppressive therapy and vasodilators during 7 years (83.4% and 87.9%, respectively). Mean value of mRSS of total patients was significantly reduced from the initial registration after the first year. However, other parameters for physical function associated with skin sclerosis including fist closure, hand extension, and oral aperture were not so ameliorated during the study period. Health Assessment Questionnaire-disability index and serum KL-6 levels were constant throughout the course. Percent vital capacity and the presence of ILD, clinically suspected pulmonary arterial hypertension, and digital ulcers were gradually exacerbated during the period.Conclusions: In Japanese early dcSSc patients and SSc patients with ILD, mRSS was continuously reduced during 7 years of follow-up, but there was little improvement of physical disability and organ involvement.

  81. Concurrence of polyarteritis nodosa and multiple sclerosis Peer-reviewed

    K.M. Matsuda, A. Koguchi, T. Toyama, K. Sakuishi, M. Kobayashi, S. Miura, M. Miyazaki, H. Suga, Y. Asano, T. Toda, S. Sato

    Journal of the European Academy of Dermatology and Venereology　34　(4)　2020/04

    Publisher: Wiley

    DOI： 10.1111/jdv.16107 　

    ISSN： 0926-9959

    eISSN： 1468-3083

  82. Tumoral calcinosis in systemic lupus erythematosus associated with fat necrosis. International-journal

    Moe Sakakibara, Daisuke Yamada, Satoshi Toyama, Kaoru Funamizu, Jun Omatsu, Naomi Takahashi-Shishido, Shinichi Sato, Yoshihide Asano

    The Journal of dermatology　47　(4)　e134-e135　2020/04

    DOI： 10.1111/1346-8138.15199 　

  83. Serum delta-like 4 levels: A possible association with interstitial lung disease in systemic sclerosis. International-journal

    Yuki Fukui, Takuya Miyagawa, Satoshi Toyama, Jun Omatsu, Megumi Hirabayashi, Kouki Nakamura, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano

    The Journal of dermatology　47　(4)　e136-e137　2020/04

    DOI： 10.1111/1346-8138.15245 　

  84. Increased Expression of Delta-like Ligand 4 in Mycosis Fungoides. International-journal Peer-reviewed

    Hikari Boki, Tomomitsu Miyagaki, Yuki Shono, Hiroaki Kamijo, Tomonori Oka, Hiraku Suga, Yoshihide Asano, Makoto Sugaya, Shinichi Sato

    Acta dermato-venereologica　100　(4)　adv00059　2020/02/25

    DOI： 10.2340/00015555-3402 　

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    In many malignancies, dysregulation of the Notch pathways, composed of 4 Notch receptors (Notch1-4) and 5 Notch ligands (Jagged1-2, Delta-like ligand-1, 3-4), is associated with their development. In mycosis fungoides, interaction between Notch1 and Jagged1 is known to activate the Notch pathways and promote the proliferation of tumour cells. However, the involvement of other Notch ligands has not been reported. This study investigated the roles of Delta-like ligand 4 in mycosis fungoides. Delta-like ligand 4 mRNA levels in lesional skin of patients with mycosis fungoides were significantly elevated compared with those of normal controls, and correlated with disease-specific mortality. Immunohistochemical staining demonstrated prominent expression of Delta-like ligand 4 on vascular endothelial cells and tumour cells in mycosis fungoides lesional skin. In addition, Delta-like ligand 4 augmented the proliferation of cutaneous T-cell lym-phoma cell lines. These results suggest that enhanced Delta-like ligand 4 expression may contribute directly to the progression of mycosis fungoides through proliferating tumour cells.

  85. Regulation of skin fibrosis by RALDH1-producing dermal dendritic cells via retinoic acid-mediated regulatory T cell induction: A role in scleroderma. International-journal

    Shunsuke Miura, Yoshihide Asano, Ryosuke Saigusa, Takashi Yamashita, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Ayumi Yoshizaki, Shinichi Sato, Takafumi Kadono

    Journal of dermatological science　97　(2)　125-134　2020/02

    DOI： 10.1016/j.jdermsci.2020.01.002 　

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    BACKGROUND: Skin fibrosis of systemic sclerosis (SSc) is believed to be driven by complex processes including immune abnormalities, but the underlying immune response remains enigmatic. In particular, the role of dermal dendritic cells (DCs) is totally unknown. OBJECTIVE: We investigated the impact of CD103 loss on bleomycin-induced skin fibrosis because CD103 is a critical molecule determining DC phenotypes. METHODS: Bleomycin-induced skin fibrosis was generated with Cd103-/- mice. The alterations of tissue fibrosis and related inflammation were investigated by histologic examination, hydroxyproline assay, quantitative reverse transcription PCR and flow cytometry. SSc skin samples were evaluated by immunofluorescence. RESULTS: CD103 loss decreased bleomycin-induced dermal thickness and collagen contents, along with TGF-β1 and CTGF suppression. Treg proportion was increased, while Th1/Th2/Th17 cell proportions were decreased in the skin of bleomycin-treated Cd103-/- mice. Bleomycin injection enhanced CD11b-CD103- DC proportion in wild-type mice, which was further augmented in Cd103-/- mice. Importantly, RALDH1/ALDH1A1 enzyme oxidizing retinaldehyde to retinoic acid, an inducer of Tregs, was preferentially expressed by CD11b-CD103- DCs and its expression levels were elevated in bleomycin-injected skin lesions, to a greater extent in Cd103-/- mice than in wild-type mice. Importantly, the number of RALDH1-positive DCs was decreased in the lesional skin of SSc patients and tended to inversely correlate with skin fibrosis severity. CONCLUSION: This study identified a critical role of dermal DCs as a regulator of Treg development through RALDH1 in bleomycin-treated mice and possibly in human SSc. This finding sheds new light on dermal DCs as a new therapeutic target of SSc.

  86. Wound, pressure ulcer and burn guidelines - 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers. International-journal Peer-reviewed

    Manabu Fujimoto, Jun Asai, Yoshihide Asano, Takayuki Ishii, Yohei Iwata, Tamihiro Kawakami, Masanari Kodera, Masatoshi Abe, Masahiro Amano, Ryuta Ikegami, Taiki Isei, Zenzo Isogai, Takaaki Ito, Yuji Inoue, Ryokichi Irisawa, Masaki Ohtsuka, Yoichi Omoto, Hiroshi Kato, Takafumi Kadono, Sakae Kaneko, Hiroyuki Kanoh, Masakazu Kawaguchi, Ryuichi Kukino, Takeshi Kono, Monji Koga, Keisuke Sakai, Eiichi Sakurai, Yasuko Sarayama, Yoichi Shintani, Miki Tanioka, Hideaki Tanizaki, Jun Tsujita, Naotaka Doi, Takeshi Nakanishi, Akira Hashimoto, Minoru Hasegawa, Masahiro Hayashi, Kuninori Hirosaki, Hideki Fujita, Hiroshi Fujiwara, Takeo Maekawa, Koma Matsuo, Naoki Madokoro, Sei-Ichiro Motegi, Hiroshi Yatsushiro, Osamu Yamasaki, Yuichiro Yoshino, Andres James LE Pavoux, Takao Tachibana, Hironobu Ihn

    The Journal of dermatology　47　(10)　1071-1109　2020/01/21

    DOI： 10.1111/1346-8138.15186 　

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    The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.

  87. Unusual type of scleromyxedema with multiple subcutaneous nodules, IgM-λ paraproteinemia, and scleroderma-like microangiopathy

    Kentaro Awaji, Yoshihide Asano, Mariko Takaoka, Tomonori Oka, Tomomi Miyake, Hiraku Suga, Shinichi Sato

    Journal of Scleroderma and Related Disorders　2020

    Publisher: SAGE Publications Ltd

    DOI： 10.1177/2397198320974190 　

    ISSN： 2397-1991 2397-1983

  88. Generalized pustular psoriasis occurring after the discontinuation of brodalumab because of cellulitis in a patient with psoriasis vulgaris Peer-reviewed

    Yoshio Hayashi, Shunsuke Miura, Kenta Oka, Kaori Yoshida, Ryosuke Saigusa, Asako Yoshizaki, Hiraku Suga, Ayumi Yoshizaki, Yoshihide Asano, Shinichi Sato

    Rinsho derma (Tokyo)　62　(1)　27-31　2020/01/01

    DOI： 10.18888/hi.0000001751 　

    ISSN： 0018-1404

  89. Characteristics of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis and Anticentriole Autoantibodies.

    Hisataka Maki, Kana Kubota, Masaru Hatano, Shun Minatsuki, Eisuke Amiya, Ayumi Yoshizaki, Yoshihide Asano, Hiroyuki Morita, Shinichi Sato, Issei Komuro

    International heart journal　61　(2)　413-418　2020

    DOI： 10.1536/ihj.19-659 　

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    Anticentriole autoantibodies-positive systemic sclerosis (SSc) has been reported to develop pulmonary arterial hypertension (PAH) at a high rate. In this report, we describe two patients with anticentriole antibodies-positive SSc-PAH who were treated with pulmonary vasodilators. Both cases were elderly women with poor physical conditions and clinical findings of SSc. Case 1 was resistant to combination therapy with pulmonary vasodilators; in Case 2, hemodynamic improvement was obtained by upfront combination therapy at an early stage. Because anticentriole antibodies-positive SSc-PAH rapidly deteriorates, careful hemodynamic observation and timely aggressive use of pulmonary vasodilators should be considered.

  90. Erratum: Characteristics of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis and Anticentriole Autoantibodies.

    Hisataka Maki, Kana Kubota, Masaru Hatano, Shun Minatsuki, Eisuke Amiya, Ayumi Yoshizaki, Yoshihide Asano, Hiroyuki Morita, Shinichi Sato, Issei Komuro

    International heart journal　61　(3)　629-629　2020

    DOI： 10.1536/ihj.61-3_Errata 　

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    The errors in the following list appeared in the article titled "Characteristics of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis and Anticentriole Autoantibodies" by Hisataka Maki, Kana Kubota, Masaru Hatano, Shun Minatsuki, Eisuke Amiya, Ayumi Yoshizaki, Yoshihide Asano, Hiroyuki Morita, Shinichi Sato, Issei Komuro (Vol 61, No.2, 413-418, 2020).

  91. A case of concurrent psoriasis and ulcerative colitis with development of arthritis during adalimumab treatment. International-journal

    Satoshi Toyama, Hiroko Kanda, Shoko Tateishi, Atsuo Yamada, Shinichi Sato, Yoshihide Asano

    European journal of dermatology : EJD　29　(6)　651-653　2019/12/01

    DOI： 10.1684/ejd.2019.3657 　

  92. Cutaneous phaeohyphomycosis caused by Alternaria alternata in an immunosuppressed patient. International-journal Peer-reviewed

    Kumiko Suda, Takashi Yamashita, Yuriko Kawase, Kyoko Yarita, Asako Yoshizaki, Kaname Akamata, Yoshihide Asano, Katsuhiko Kamei, Shinichi Sato

    The Journal of dermatology　46　(12)　e448-e449　2019/12

    DOI： 10.1111/1346-8138.15041 　

  93. Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti‐topoisomerase I‐positive systemic sclerosis‐associated interstitial lung disease

    Satoshi Ebata, Ayumi Yoshizaki, Takemichi Fukasawa, Shunsuke Miura, Takehiro Takahashi, Hayakazu Sumida, Yoshihide Asano, Shinichi Sato

    The Journal of Dermatology　46　(11)　1006-1013　2019/11

    Publisher: Wiley

    DOI： 10.1111/1346-8138.15079 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  94. 尋常性乾癬へのブロダルマブ投与を蜂窩織炎のため中断後、膿疱性乾癬を生じた1例

    林 剛生, 三浦 俊介, 岡 謙太, 吉田 香織, 三枝 良輔, 吉崎 麻子, 管 析, 浅野 善英, 佐藤 伸一

    日本皮膚科学会雑誌　129　(9)　1926-1926　2019/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  95. A case of scleroderma en coup de sabre with ipsilateral hearing loss and aphakia

    Shunsuke Miura, Masashi Someya, Satoshi Toyama, Toru Kawai, Takashi Yamashita, Naomi Shishido, Shinichi Sato, Yoshihide Asano

    European Journal of Dermatology　29　(4)　423-425　2019/08

    Publisher: John Libbey Eurotext

    DOI： 10.1684/ejd.2019.3572 　

    ISSN： 1167-1122

    eISSN： 1952-4013

  96. Serum levels of human β‐defensin 2: possible association with fibrosis and vasculopathy in patients with systemic sclerosis International-journal Peer-reviewed

    A. Kuzumi, A. Yoshizaki, T. Fukasawa, S. Ebata, S. Miura, A. Yoshizaki, H. Sumida, Y. Asano, S. Sato

    Journal of the European Academy of Dermatology and Venereology　33　(7)　2019/07

    Publisher: Wiley

    DOI： 10.1111/jdv.15546 　

    ISSN： 0926-9959 1468-3083

    eISSN： 1468-3083

  97. Facile fabrication of PEG-coated PLGA microspheres via SPG membrane emulsification for the treatment of scleroderma by ECM degrading enzymes. Peer-reviewed

    Ohta S, Matsuura M, Kawashima Y, Cai X, Taniguchi M, Okochi H, Asano Y, Sato S, Ito T

    Colloids and surfaces. B, Biointerfaces　179　453-461　2019/07

    DOI： 10.1016/j.colsurfb.2019.04.028 　

    ISSN： 0927-7765

    eISSN： 1873-4367

  98. Unique correlation profile of adiponectin and retinol-binding protein 4 in patients with systemic sclerosis. Peer-reviewed

    Asano Y, Masui Y, Toyama T, Sato S

    The Journal of dermatology　2019/06

    DOI： 10.1111/1346-8138.14994 　

    ISSN： 0385-2407

  99. Secukinumab decreased circulating anti-BP180-NC16a autoantibodies in a patient with coexisting psoriasis vulgaris and bullous pemphigoid. International-journal Peer-reviewed

    Kamata M, Asano Y, Shida R, Maeda N, Yoshizaki A, Miyagaki T, Kawashima T, Tada Y, Sato S

    The Journal of dermatology　46　(6)　e216-e217　2019/06

    DOI： 10.1111/1346-8138.14760 　

    ISSN： 0385-2407

  100. Skin thickness score as a surrogate marker of organ involvements in systemic sclerosis: a retrospective observational study. International-journal Peer-reviewed

    Kazuki M Matsuda, Ayumi Yoshizaki, Ai Kuzumi, Takemichi Fukasawa, Satoshi Ebata, Shunsuke Miura, Tetsuo Toyama, Asako Yoshizaki, Hayakazu Sumida, Yoshihide Asano, Koji Oba, Shinichi Sato

    Arthritis research & therapy　21　(1)　129-129　2019/05/28

    DOI： 10.1186/s13075-019-1919-6 　

    ISSN： 1478-6354

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    BACKGROUND: Previous studies have shown the relationship between higher skin thickness score and the existence of organ involvements in systemic sclerosis (SSc). Here, we firstly investigated the correlation between skin thickness score and quantitative measurements of each organ involvement in Japanese patients with SSc. METHODS: All Japanese SSc patients hospitalized to our clinic for initial evaluation of SSc were selected. Skin thickness was evaluated by modified Rodnan total skin thickness score (mRSS). Relationship between mRSS and prevalence or incidence of organ involvements was examined by logistic analyses. Correlation between mRSS and quantitative measurements of organ involvements was examined by correlation analyses and regression analyses. RESULTS: We recruited 198 patients into our study. The mean disease duration was 7.3 years with the mean follow-up duration of 3.2 years. Multivariate logistic regression analyses revealed that higher mRSS is related to higher prevalence of interstitial lung disease (P < 0.05), restrictive impairment (P < 0.01), and diffusion impairment (P < 0.05) of the lung. Correlation analyses revealed mRSS negatively correlates with forced vital capacity (P < 0.001) and diffusing capacity (P < 0.001) of the lung. Correlation between longitudinal change of mRSS and that of forced vital capacity (P < 0.05) or diffusing capacity (P < 0.001) of the lung was also demonstrated. CONCLUSIONS: Skin thickness score significantly correlates with quantitative measurements of lung involvement in Japanese patients with SSc.

  101. 先天性限局性強皮症の1例

    水野 結花, 三浦 俊介, 遠山 聡, 赤股 要, 浅野 善英, 佐藤 伸一

    日本皮膚科学会雑誌　129　(5)　1202-1202　2019/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  102. 多発性硬化症を合併した結節性多発動脈炎の1例

    松田 和樹, 遠山 哲夫, 小林 真麻, 三浦 俊介, 管 析, 浅野 善英, 小口 絢子, 作石 かおり, 佐藤 伸一

    日本皮膚科学会雑誌　129　(5)　1195-1195　2019/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  103. 膠原病・血管炎に伴う皮膚潰瘍の病態と治療

    浅野 善英, 川上 民裕, 小寺 雅也, 石井 貴之, 浅井 純, 岩田 洋平, 小川 陽一, 岸部 麻里, 内山 明彦, 吉崎 歩, 山口 由衣, 壽 順久, 藤本 徳毅, 小池 雄太, 岡村 賢, 宮城 拓也

    日本皮膚科学会雑誌　129　(5)　991-991　2019/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  104. Cyclophosphamide Pulse Therapy Normalizes Vascular Abnormalities in a Mouse Model of Systemic Sclerosis Vasculopathy. Peer-reviewed

    Yamashita T, Asano Y, Saigusa R, Taniguchi T, Hirabayashi M, Miyagawa T, Nakamura K, Miura S, Yoshizaki A, Trojanowska M, Sato S

    The Journal of investigative dermatology　139　(5)　1150-1160　2019/05

    Publisher: Elsevier BV

    DOI： 10.1016/j.jid.2018.11.016 　

    ISSN： 0022-202X

  105. A potential contribution of decreased galectin-7 expression in stratified epithelia to the development of cutaneous and oesophageal manifestations in systemic sclerosis. Peer-reviewed

    Saigusa R, Yamashita T, Miura S, Hirabayashi M, Nakamura K, Miyagawa T, Fukui Y, Yoshizaki A, Sato S, Asano Y

    Experimental dermatology　28　(5)　536-542　2019/05

    Publisher: Wiley

    DOI： 10.1111/exd.13900 　

    ISSN： 0906-6705

    eISSN： 1600-0625

  106. Systemic sclerosis: Is the epithelium a missing piece of the pathogenic puzzle? International-journal Peer-reviewed

    Asano Y, Takahashi T, Saigusa R

    Journal of dermatological science　94　(2)　259-265　2019/05

    DOI： 10.1016/j.jdermsci.2019.04.007 　

    ISSN： 0923-1811

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    Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by three cardinal pathological features, such as autoimmunity/inflammation, vasculopathy and extensive organ fibrosis. Therefore, numerous interests have been put on the roles of immune cells, vascular cells (endothelial cells and pericytes/vascular smooth muscle cells) and interstitial fibroblasts as well as their precursors in the field of SSc research. However, recent studies with clinical samples and animal models have drawn much attention to the potential role of epithelial cells as a member of critical drivers and/or modifiers in the pathogenesis of SSc. Indeed, phenotypically altered epithelial cells possibly explain the selective organ fibrosis in the skin, esophagus and lung, the origin of autoimmunity and Köbner phenomenon-associated localized scleroderma-like lesions, the mechanisms of which had remained unknown in the canonical idea of SSc pathogenesis. This article overviews the recent progress in understanding the contribution of epithelial cells to the pathogenesis of SSc. Although further studies are required to confirm the potential role of epithelial cells in SSc development, this notion may provide us with a missing piece of the puzzle to solve the unanswered questions in the pathogenesis of SSc.

  107. Possible association of decreased serum CXCL14 levels with digital ulcers in patients with systemic sclerosis. Peer-reviewed

    Fukui Y, Miyagawa T, Hirabayashi M, Yamashita T, Saigusa R, Miura S, Nakamura K, Yoshizaki A, Sato S, Asano Y

    The Journal of dermatology　46　(7)　584-589　2019/05

    Publisher: Wiley

    DOI： 10.1111/1346-8138.14914 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  108. A potential contribution of trappin-2 to the development of vasculopathy in systemic sclerosis. Peer-reviewed

    Miyagawa T, Asano Y, Saigusa R, Hirabayashi M, Yamashita T, Taniguchi T, Takahashi T, Nakamura K, Miura S, Yoshizaki A, Miyagaki T, Sato S

    Journal of the European Academy of Dermatology and Venereology : JEADV　33　(4)　753-760　2019/04

    Publisher: Wiley

    DOI： 10.1111/jdv.15387 　

    ISSN： 0926-9959

    eISSN： 1468-3083

  109. Long-term efficacy and safety results from an open-label phase III study (UNCOVER-J) in Japanese plaque psoriasis patients: impact of treatment withdrawal and retreatment of ixekizumab

    Y. Umezawa, H. Torisu-Itakura, Y. Morisaki, H. ElMaraghy, K. Nakajo, N. Akashi, H. Saeki, Toshihide Akasaka, Yoshihide Asano, Takafumi Etoh, Yasuyuki Fujita, Takashi Hashimoto, Mari Higashiyama, Atsuyuki Igarashi, Hironobu Ihn, Keiji Iwatsuki, Kenji Kabashima, Akira Kawada, Makoto Kawashima, Koichiro Nakamura, Yukari Okubo, Ryuhei Okuyama, Akira Ozawa, Koji Sayama, Mariko Seishima, Tetsuo Shiohara, Masakazu Takahara, Hidetoshi Takahashi, Kazuhiko Takehara, Keiji Tanese, Mamori Tani, Hideaki Watanabe, Keiichi Yamanaka, the Japanese Ixekizumab Study Group

    Journal of the European Academy of Dermatology and Venereology　33　(3)　568-576　2019/03/01

    Publisher: Blackwell Publishing Ltd

    DOI： 10.1111/jdv.15292 　

    ISSN： 1468-3083 0926-9959

  110. リウマチ性疾患の超音波検査 乾癬性関節炎の関節エコー所見と臨床指標との身体部位ごとの関連の検討

    住友 秀次, 立石 晶子, 白井 晴己, 大野 久美子, 廣瀬 旬, 吉崎 歩, 浅野 善英, 佐藤 伸一, 田中 栄, 藤尾 圭志, 山本 一彦, 神田 浩子

    日本リウマチ学会総会・学術集会プログラム・抄録集　63回　429-429　2019/03

    Publisher: (一社)日本リウマチ学会

  111. 実臨床における乾癬性関節炎(PsA)の機能評価についての検討

    立石 晶子, 神田 浩子, 井上 眞璃子, 大野 久美子, 廣瀬 旬, 吉崎 歩, 浅野 善英, 佐藤 伸一, 田中 栄, 藤尾 圭志

    日本リウマチ学会総会・学術集会プログラム・抄録集　63回　744-744　2019/03

    Publisher: (一社)日本リウマチ学会

  112. 乾癬性関節炎に対してTNFα阻害薬開始後に生じた有棘細胞癌の1例

    尾松 淳, 山田 大資, 中村 洸樹, 前田 成美, 船水 薫, 管 析, 浅野 善英, 佐藤 伸一

    日本皮膚科学会雑誌　129　(3)　392-392　2019/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  113. Estrogen dermatitis: Case report and examination of estrogen receptor-β in the skin. International-journal Peer-reviewed

    Fukayama M, Asano Y, Shinozaki-Ushiku A, Sato S

    The Journal of dermatology　46　(3)　263-266　2019/03

    DOI： 10.1111/1346-8138.14750 　

    ISSN： 0385-2407

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    Many women experience some skin reaction or trouble in their monthly menstrual cycle, including the exacerbation of pre-existing diseases and skin eruptions directly associated with sex hormones. We herein report a Japanese woman who experienced repeated systemic urticaria in her premenstrual period, and was diagnosed as having estrogen dermatitis based on a positive result of intradermal estrogen skin test. Of note, the expression of estrogen receptor-β was increased in small dermal vessels of this case as well as in those of patients with other inflammatory skin diseases. These results suggest that inflammation may induce estrogen receptor-β expression in small dermal vessels, which potentially modifies the pathological skin inflammation during the menstrual period, leading to the development of estrogen dermatitis.

  114. Coexistence of anti-topoisomerase I and anti-RNA polymerase III antibody in a patient with overlap syndrome. Peer-reviewed

    Shimizu T, Ogawa Y, Tomita O, Asano Y, Shimada S, Kawamura T

    European journal of dermatology : EJD　29　(1)　93-94　2019/02

    DOI： 10.1684/ejd.2018.3475 　

    ISSN： 1167-1122

  115. Assessment of endothelial function during the loading phase of infliximab in psoriasis: a potential predictor of its drug survival. International-journal Peer-reviewed

    Nakao M, Nakamura K, Fukasawa T, Shida R, Ito A, Ichimura Y, Takahashi T, Mitsui A, Yoshizaki A, Shibata S, Kamata M, Araki M, Watanabe R, Sato S, Asano Y

    International journal of dermatology　58　(1)　54-59　2019/01

    DOI： 10.1111/ijd.14200 　

    ISSN： 0011-9059

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    BACKGROUND: Tumor necrosis factor inhibitors decrease the risk of cardiovascular events in moderate to severe psoriasis, but the association between their effects on endothelial function and those on skin lesions has not been well studied. We investigated the association between infliximab effects on endothelial function during the loading phase and those on skin lesions in patients with psoriasis. METHODS: We evaluated endothelial function with reactive hyperemia-peripheral arterial tonometry index (RHI) in 15 patients with psoriasis before the first and third infusions of infliximab. Patients were stratified into two groups; those who maintained Psoriasis Area and Severity Index (PASI) 75 response for more than 6 months (defined as responders) and the others (defined as nonresponders). RESULTS: Six weeks after the initiation of infliximab (before the third infusion), PASI scores were significantly improved compared with baseline, while RHI values were not altered in the whole patient group. However, when the responders and the nonresponders were analyzed separately, RHI values tended to be decreased before the third infusion compared with baseline in the nonresponders, while being unchanged in the responders. Importantly, the difference in ∆RHI reached a statistical significance between the two groups, and the cutoff value (mean - 2 standard deviation of RHI values in the responders) identified the nonresponders with 67% of sensitivity and 100% of specificity. CONCLUSIONS: The decrease in RHI values before the third infusion may serve as a predictor for the long-term unfavorable effect of infliximab on psoriatic skin lesions.

  116. Increased expression of aquaporin-1 in dermal fibroblasts and dermal microvascular endothelial cells possibly contributes to skin fibrosis and edema in patients with systemic sclerosis. International-journal Peer-reviewed

    Takashi Yamashita, Yoshihide Asano, Ryosuke Saigusa, Takashi Taniguchi, Kouki Nakamura, Shunsuke Miura, Tetsuo Toyama, Takehiro Takahashi, Yohei Ichimura, Megumi Hirabayashi, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato

    Journal of dermatological science　93　(1)　24-32　2019/01

    DOI： 10.1016/j.jdermsci.2018.09.007 　

    ISSN： 0923-1811

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    BACKGROUND: Aquaporin-1 (AQP1), a water channel protein controlling the water contents of cells and tissues, exerts pleiotropic effects on various biological activities, including inflammation, angiogenesis, and extracellular matrix remodeling, by regulating cell behaviors and tissue water balance. OBJECTIVE: To investigate AQP1 roles in systemic sclerosis (SSc) which is characterized by autoimmune inflammation, vasculopathy, and tissue fibrosis. METHODS: AQP1 expression was evaluated by immunohistochemistry and quantitative reverse transcription PCR in skin samples from human and animal models and by immunoblotting in cultured cells. Fli1 binding to the AQP1 promoter was evaluated by chromatin immunoprecipitation. Cell migration was assessed by scratch assay. RESULTS: Dermal fibroblasts and endothelial cells highly expressed AQP1 in SSc lesional skin, and AQP1 expression in dermal fibroblasts and endothelial cells positively correlated with the degrees of tissue fibrosis and edema, respectively. Consistently, SSc dermal fibroblasts up-regulated AQP1 compared with normal dermal fibroblasts in vitro. Furthermore, TGF-β stimulation induced AQP1 expression in normal dermal fibroblasts, while TGF-β1 antisense oligonucleotide suppressed AQP1 expression in SSc dermal fibroblasts. In endothelial cells, Fli1 deficiency resulted in AQP1 up-regulation in vivo and in vitro and Fli1 bound to the AQP1 promoter. Importantly, SSc dermal fibroblasts and FLI1 siRNA-treated endothelial cells had a pro-migratory property, which was remarkably diminished by gene silencing of AQP1. CONCLUSION: AQP1 is up-regulated in SSc dermal fibroblasts and SSc endothelial cells at least partially due to autocrine TGF-β stimulation and Fli1 deficiency, respectively, possibly contributing to inflammation, vasculopathy, and tissue fibrosis by regulating tissue edema and cell migration.

  117. Sézary syndrome without erythroderma: A case report and review of published work. International-journal Peer-reviewed

    Kamijo H, Miyagaki T, Norimatsu Y, Shishido-Takahashi N, Kuzumi A, Asano Y, Sato S

    The Journal of dermatology　46　(1)　61-64　2019/01

    DOI： 10.1111/1346-8138.14692 　

    ISSN： 0385-2407

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    Sézary syndrome (SS) is defined by erythroderma and circulating atypical T cells, with or without lymphadenopathy. Recently, Thompson et al. identified a distinct population of SS patients with an atypical presentation: a high blood tumor burden of Sézary cells fulfilling criteria for SS but without fulfilling the criteria for erythroderma at the diagnosis. Here, we report a case of a 49-year-old Japanese man with SS who did not present with erythroderma initially, but exhibited erythematous itchy papules symmetrically located on the legs and arms. We also reviewed reported cases of SS without initial erythroderma. The skin manifestations at diagnosis varied from patches to tumors often seen in mycosis fungoides, and other rarer findings such as excoriation, palmoplantar keratoderma and alopecia. Pruritus was reported in most patients (86%), unlike early mycosis fungoides, and could be the main clue to the diagnosis of SS. Notably, three patients were reported to have presented with papular lesions, similar to our case. Little is known about why skin lesions in SS without erythroderma vary and why these cases did not exhibit erythroderma initially. Attenuated stimulation by colonized Staphylococcus aureus, impairment in recruitment of malignant T cells and suppression of inflammatory response induced by malignant T cells with regulatory phenotype may be associated with skin manifestations. Further studies are necessary to elucidate the etiology of this entity.

  118. Coexistence of anti-topoisomerase I and anti-RNA polymerase III antibody in a patient with overlap syndrome. Peer-reviewed

    Shimizu T, Ogawa Y, Tomita O, Asano Y, Shimada S, Kawamura T

    European journal of dermatology : EJD　2018/12

    DOI： 10.1684/ejd.2018.3461 　

    ISSN： 1167-1122

  119. Prediction of therapeutic response before and during i.v. cyclophosphamide pulse therapy for interstitial lung disease in systemic sclerosis: A longitudinal observational study. International-journal Peer-reviewed

    Sumida H, Asano Y, Tamaki Z, Aozasa N, Taniguchi T, Toyama T, Takahashi T, Ichimura Y, Noda S, Akamata K, Saigusa R, Miyazaki M, Kuwano Y, Yanaba K, Yoshizaki A, Sato S

    The Journal of dermatology　45　(12)　1425-1433　2018/12

    DOI： 10.1111/1346-8138.14669 　

    ISSN： 0385-2407

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    There have been no established parameters to predict responsiveness to i.v. cyclophosphamide (IVCY) pulse therapy in combination with corticosteroids in patients with interstitial lung disease (ILD) related to systemic sclerosis (SSc). This retrospective study was conducted to determine predictive factors for efficacy of IVCY at the time of before and during the treatment. Thirty-two Japanese SSc patients, ever treated for ILD with IVCY in combination with prednisolone, were analyzed retrospectively. We performed detailed time-course analyses of parameters derived from blood samples and pulmonary function tests. With the exclusion of eight unclassified patients, 24 patients were classified into 14 good responders (GR) or 10 poor responders (PR) on the basis of changes in percent predicted diffusing capacity for carbon monoxide (DLco). Pretreatment percent predicted DLco was significantly reduced in PR compared with GR. In addition, serum parameters such as Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D) and C-reactive protein were significantly higher in PR than in GR. Furthermore, our time-course analyses revealed a transient increase in serum KL-6 levels with a peak at 3 months after the first infusion of cyclophosphamide, which showed no relation to therapeutic efficacy. Moreover, continuously high serum KL-6 levels (>2000 U/mL) and rapid decrease in SP-D levels (<200 ng/mL) during IVCY were remarkably characteristic of PR and GR, respectively. ILD severity/activity before treatment and variability of serum KL-6 and SP-D levels during treatment may be useful to predict therapeutic effects of IVCY on SSc-ILD.

  120. Serum amyloid A levels in the blood of patients with atopic dermatitis and cutaneous T-cell lymphoma. International-journal Peer-reviewed

    Hideko Suzuki, Makoto Sugaya, Rina Nakajima, Tomonori Oka, Naomi Takahashi, Momoko Nakao, Tomomitsu Miyagaki, Yoshihide Asano, Shinichi Sato

    The Journal of dermatology　45　(12)　1440-1443　2018/12

    DOI： 10.1111/1346-8138.14665 　

    ISSN： 0385-2407

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    Serum amyloid A (SAA) is an acute phase protein, which activates immune cells and induces cytokines and chemokine. SAA levels in blood have been reported to be elevated in case of inflammation, infections, neoplasia and tissue injury. In this study, we examined SAA levels in the blood of patients with atopic dermatitis (AD) and cutaneous T-cell lymphoma (CTCL). SAA levels in sera of AD patients, those of CTCL patients and those of healthy controls were not significantly different. When AD or CTCL patients were classified by disease severity, there was still no difference in SAA levels. In AD patients, however, SAA levels positively correlated with the number of eosinophils in peripheral blood and serum soluble interleukin-2 receptor (sIL-2R) levels. There were significant correlations between SAA levels in blood and the number of white blood cells in peripheral blood and serum sIL-2R levels in CTCL patients. AD patients without topical steroid treatment and CTCL patients without narrowband ultraviolet B therapy showed increased levels of SAA, which suggested that SAA levels may easily fluctuate with treatment. These results imply a possible contribution of SAA in development of AD and CTCL.

  121. 全身性強皮症患者における血清IL-34値の検討

    久住 藍, 吉崎 歩, 遠山 聡, 深澤 毅倫, 江畑 慧, 中村 洸樹, 三枝 良輔, 三浦 俊介, 吉崎 麻子, 浅野 善英, 佐藤 伸一

    日本臨床免疫学会総会プログラム・抄録集　46回　126-126　2018/11

    Publisher: (一社)日本臨床免疫学会

  122. The vitamin D3 analog, maxacalcitol, reduces psoriasiform skin inflammation by inducing regulatory T cells and downregulating IL-23 and IL-17 production. International-journal Peer-reviewed

    Carren Sy Hau, Teruo Shimizu, Yayoi Tada, Masahiro Kamata, Shintaro Takeoka, Sayaka Shibata, Aya Mitsui, Yoshihide Asano, Makoto Sugaya, Takafumi Kadono, Shinichi Sato, Shinichi Watanabe

    Journal of dermatological science　92　(2)　117-126　2018/11

    DOI： 10.1016/j.jdermsci.2018.08.007 　

    ISSN： 0923-1811

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    BACKGROUND: Psoriasis is a Th1/Th17-mediated inflammatory dermatosis treated with topical corticosteroids and vitamin D3 analogs (VD3 As). OBJECTIVE: To compare the effects of a VD3 A maxacalcitol and betamethasone valerate (BV) steroid lotion on topical imiquimod (IMQ)-induced psoriasiform skin inflammation. METHODS: Female BALB/c mice were treated with vehicle, maxacalcitol or BV lotion on the skin for 3 days, and IMQ cream for 6 days. q-PCR, H&E, immunohistochemistry and immunofluorescence studies were performed on skin samples. Additionally, mice were treated with vehicle, maxacalcitol or BV lotion for 3 days and CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25- cells from each group were isolated from lymph nodes. Adoptive transfer of the cells was performed on recipient mice which were treated with IMQ cream for 6 days, and skin samples were obtained for q-PCR and H&E staining. RESULTS: Maxacalcitol and BV were comparable in regards clinical improvement, although maxacalcitol reduced the MHC Class II+ inflammatory cell infiltration more than BV in IMQ skin. While both treatments downregulated IL-17 A, IL-17 F, IL-22, IL-12p40, TNF-α and IL-6 mRNA expression levels, only maxacalcitol downregulated IL-23p19 expression. Significantly increased Foxp3+ cell infiltrations and IL-10 expression were noted in maxacalcitol-treated IMQ skin. Adoptive transfer of Treg cells from maxacalcitol-treated donor mice improved IMQ-induced inflammation clinically and histopathologically more than the recipients of Treg cells from BV-treated donor groups, showing reduced levels of inflammatory cytokines and increased IL-10 expression. CONCLUSION: These results indicate that maxacalcitol reduces psoriasiform skin inflammation by inducing Treg cells as well as downregulating IL-23 and IL-17 production.

  123. Progranulin overproduction due to constitutively activated c-Abl/PKC-δ/Fli1 pathway contributes to the resistance of dermal fibroblasts to the anti-fibrotic effect of tumor necrosis factor-α in localized scleroderma. International-journal Peer-reviewed

    Miyagawa T, Ichimura Y, Nakamura K, Hirabayashi M, Yamashita T, Saigusa R, Miura S, Takahashi T, Toyama T, Taniguchi T, Akamata K, Yoshizaki A, Sato S, Asano Y

    Journal of dermatological science　92　(2)　207-214　2018/11

    DOI： 10.1016/j.jdermsci.2018.09.005 　

    ISSN： 0923-1811

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    BACKGROUND: Dermal fibroblasts derived from patients with systemic sclerosis (SSc) overproduce progranulin (PGRN), an endogenous antagonist of tumor necrosis factor (TNF) receptors, due to the deficiency of transcription factor Fli1. Fli1 expression is also decreased in dermal fibroblasts derived from patients with localized scleroderma (LSc). OBJECTIVE: To investigate the expression levels of PGRN and its contribution to the induction of pro-fibrotic phenotype in LSc dermal fibroblasts. METHODS: PGRN expression levels were determined by immunohistochemistry and quantitative reverse transcription PCR in the skin of human subjects. The role of PGRN in fibroblast activation was examined with gene silencing technique. The involvement of c-Abl/protein kinase C (PKC)-δ/Fli1 pathway in the regulation of PGRN expression was investigated by immunoblotting. RESULTS: The expression levels of PGRN and TNF-α were elevated in LSc skin lesions compared with healthy control skin. LSc dermal fibroblasts were less responsive to the anti-fibrotic effect of TNF-α than normal dermal fibroblasts. Importantly, gene silencing of PGRN reversed the response to TNF-α in LSc dermal fibroblasts. Similar to SSc dermal fibroblasts, the inhibition of c-Abl/PKC-δ/Fli1 pathway by gene silencing of ABL1 or PRKCD significantly suppressed PGRN expression in LSc dermal fibroblasts. CONCLUSION: PGRN overproduction due to constitutively activated c-Abl/PKC-δ/Fli1 pathway may contribute to the resistance of LSc dermal fibroblasts to the anti-fibrotic effect of TNF-α, which may be involved in maintaining their pro-fibrotic phenotype under the pro-inflammatory condition, as is the case with SSc.

  124. Serum Soluble CD48 Levels as a Prognostic Marker in Mycosis Fungoides and Sézary Syndrome. International-journal Peer-reviewed

    Tomonori Oka, Tomomitsu Miyagaki, Naomi Takahashi, Rina Nakajima, Hiroaki Kamijo, Hiraku Suga, Yoshihide Asano, Makoto Sugaya, Shinichi Sato

    The Journal of investigative dermatology　138　(10)　2286-2288　2018/10

    DOI： 10.1016/j.jid.2018.03.1519 　

    ISSN： 0022-202X

  125. Serum interleukin-34 levels in patients with systemic sclerosis: Clinical association with interstitial lung disease. International-journal Peer-reviewed

    Kuzumi A, Yoshizaki A, Toyama S, Fukasawa T, Ebata S, Nakamura K, Yamashita T, Saigusa R, Miura S, Hirabayashi M, Yoshizaki A, Asano Y, Sato S

    The Journal of dermatology　45　(10)　1216-1220　2018/10

    DOI： 10.1111/1346-8138.14538 　

    ISSN： 0385-2407

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    Interleukin (IL)-34 is a hematopoietic cytokine promoting proliferation and differentiation of macrophages. Because abnormal activation of macrophages is involved in the development of systemic sclerosis (SSc), we investigated serum IL-34 levels in patients with SSc. Serum IL-34 levels were significantly increased in diffuse cutaneous SSc compared with limited cutaneous SSc and healthy controls, while there were no significant differences between limited cutaneous SSc and healthy controls. In addition, SSc patients with increased serum IL-34 levels more often had interstitial lung disease (ILD) than those with normal levels. Moreover, in SSc patients, serum IL-34 levels negatively correlated with the percentage of predicted vital capacity, while they positively correlated with ground-glass opacity score and fibrotic score on chest computed tomography. Collectively, increased serum IL-34 levels were associated with greater frequency and severity of ILD in SSc patients. Serum IL-34 levels may be a useful serological marker for SSc-associated ILD.

  126. Rapid alteration of serum interleukin-6 levels may predict the reactivity of i.v. cyclophosphamide pulse therapy in systemic sclerosis-associated interstitial lung disease. Peer-reviewed

    Numajiri H, Yoshizaki A, Fukasawa T, Ebata S, Nakamura K, Yamashita T, Saigusa R, Miura S, Hirabayashi M, Yoshizaki A, Sumida H, Asano Y, Kazoe Y, Mawatari K, Kitamori T, Sato S

    The Journal of dermatology　45　(10)　1221-1224　2018/10

    Publisher: Wiley

    DOI： 10.1111/1346-8138.14580 　

    ISSN： 0385-2407

  127. Increased HMGB1 levels in lesional skin and sera in patients with cutaneous T-cell lymphoma. International-journal Peer-reviewed

    Naoyuki Senda, Tomomitsu Miyagaki, Hiroaki Kamijo, Rina Nakajima, Tomonori Oka, Naomi Takahashi, Hiraku Suga, Ayumi Yoshizaki, Yoshihide Asano, Makoto Sugaya, Shinichi Sato

    European journal of dermatology : EJD　28　(5)　621-627　2018/10/01

    DOI： 10.1684/ejd.2018.3400 　

    ISSN： 1167-1122

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    BACKGROUND: High mobility group box-1 (HMGB1) is a ubiquitously expressed non-histone nuclear protein which acts as a danger signal when released from cells. HMGB1, which is associated with inflammation, angiogenesis, and T helper (Th)2 polarization, contributes to the development of various inflammatory diseases and malignancies. However, it remains to be determined whether HMGB1 is involved in cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To investigate the role of HMGB1 in CTCL. MATERIALS & METHODS: Serum HMGB1 levels were measured in patients with CTCL and healthy controls using an enzyme-linked immunosorbent assay. HMGB1 messenger RNA (mRNA) expression in CTCL and normal skin was examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. Moreover, we analysed correlations between the levels of HMGB1 and other cytokines and chemokines, laboratory data, disease activity, and prognosis. RESULTS: HMGB1 levels were significantly higher in sera of CTCL patients than those of normal controls and correlated with serum levels of soluble interleukin-2 receptor, lactate dehydrogenase, thymus and activation-regulated chemokine, and the number of eosinophils in peripheral blood. Serum HMGB1 levels also reflected disease activity and prognosis for each patient with CTCL. HMGB1 mRNA levels in CTCL lesional skin were significantly elevated and correlated with IL-4, IL-10, IL-19, and angiogenin mRNA levels. Immunohistochemical staining revealed that HMGB1 was expressed not only in the nucleus but also in the cytoplasm of various cells in CTCL lesional skin. CONCLUSION: These results suggest that enhanced HMGB1 expression may contribute to the progression of CTCL through Th2 polarization and promotion of angiogenesis.

  128. Wound, pressure ulcer and burn guidelines - 2: Guidelines for the diagnosis and treatment of pressure ulcers, second edition. International-journal Peer-reviewed

    Hiroshi Fujiwara, Zenzo Isogai, Ryokichi Irisawa, Masaki Otsuka, Takafumi Kadono, Monji Koga, Kuninori Hirosaki, Jun Asai, Yoshihide Asano, Masatoshi Abe, Masahiro Amano, Ryuta Ikegami, Takayuki Ishii, Taiki Isei, Takaaki Ito, Yuji Inoue, Yohei Iwata, Yoichi Omoto, Hiroshi Kato, Sakae Kaneko, Hiroyuki Kanoh, Tamihiro Kawakami, Masakazu Kawaguchi, Ryuichi Kukino, Takeshi Kono, Masanari Kodera, Keisuke Sakai, Eiichi Sakurai, Yasuko Sarayama, Yoichi Shintani, Miki Tanioka, Hideaki Tanizaki, Jun Tsujita, Naotaka Doi, Takeshi Nakanishi, Akira Hashimoto, Minoru Hasegawa, Masahiro Hayashi, Hideki Fujita, Manabu Fujimoto, Takeo Maekawa, Koma Matsuo, Naoki Madokoro, Sei-Ichiro Motegi, Hiroshi Yatsushiro, Osamu Yamasaki, Yuichiro Yoshino, Andres Le Pavoux, Takao Tachibana, Hironobu Ihn

    The Journal of dermatology　47　(9)　929-978　2018/09/08

    DOI： 10.1111/1346-8138.14587 　

    ISSN： 0385-2407

  129. Direct Interaction between Autoreactive B Cells and Endothelial Colony Forming Cells Induces Cytokine Production from B Cells through B Cell Receptor and IL-6-JAK2-STAT3 Signaling Pathway, Suppressing Proliferation of Endothelial Colony Forming Cells in S Peer-reviewed

    Fukasawa Takemichi, Yoshizaki Ayumi, Ebata Satoshi, Nakamura Kouki, Asano Yoshihide, Kazoe Yutaka, Mawatari Kazuma, Kitamori Takehiko, Sato Shinichi

    ARTHRITIS & RHEUMATOLOGY　70　2018/09

    ISSN： 2326-5191

  130. CXCL13 produced by macrophages due to Fli1 deficiency may contribute to the development of tissue fibrosis, vasculopathy and immune activation in systemic sclerosis. International-journal Peer-reviewed

    Taniguchi T, Miyagawa T, Toyama S, Yamashita T, Nakamura K, Saigusa R, Ichimura Y, Takahashi T, Toyama T, Yoshizaki A, Sato S, Asano Y

    Experimental dermatology　27　(9)　1030-1037　2018/09

    DOI： 10.1111/exd.13724 　

    ISSN： 0906-6705

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    CXCL13, a chemokine for B cells, follicular T cells, T helper 17 cells, and regulatory T cells, is reported to contribute to the development of systemic sclerosis (SSc), reflecting aberrant activation of immune system. To better understand the role of CXCL13 in SSc, we investigated the influence of Fli1 deficiency, a potential predisposing factor of this disease, on CXCL13 expression and assessed the clinical correlation of serum CXCL13 levels by multivariate regression analysis. Haploinsufficient loss of Fli1 remarkably induced CXCL13 expression in murine peritoneal macrophages, while gene silencing of FLI1 did not affect the expression of CXCL13 in human dermal fibroblasts and human dermal microvascular endothelial cells. Serum CXCL13 levels were elevated in SSc patients compared with healthy controls and correlated positively with skin score and negatively with pulmonary function test results. SSc patients with elevated serum CXCL13 levels had longer disease duration, diffuse cutaneous involvement, interstitial lung disease (ILD), heart involvement, pulmonary arterial hypertension, Raynaud's phenomenon, pitting scars, digital ulcers, telangiectasia, and high serum IgG levels more frequently than the other patients. In particular, serum CXCL13 levels were associated with ILD and digital ulcers by multivariate regression analysis. Taken together, these results indicate that CXCL13 expression is upregulated by Fli1 deficiency in macrophages, potentially contributing to the development of tissue fibrosis, vasculopathy and immune activation in SSc, especially ILD and digital ulcers.

  131. Diagnostic criteria, severity classification and guidelines of eosinophilic fasciitis. International-journal Peer-reviewed

    Masatoshi Jinnin, Toshiyuki Yamamoto, Yoshihide Asano, Osamu Ishikawa, Shinichi Sato, Kazuhiko Takehara, Minoru Hasegawa, Manabu Fujimoto, Hironobu Ihn

    The Journal of dermatology　45　(8)　881-890　2018/08

    DOI： 10.1111/1346-8138.14160 　

    ISSN： 0385-2407

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    We established diagnostic criteria and severity classification of eosinophilic fasciitis because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for eosinophilic fasciitis, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of eosinophilic fasciitis.

  132. Diagnostic criteria, severity classification and guidelines of lichen sclerosus et atrophicus. International-journal Peer-reviewed

    Minoru Hasegawa, Osamu Ishikawa, Yoshihide Asano, Shinichi Sato, Masatoshi Jinnin, Kazuhiko Takehara, Manabu Fujimoto, Toshiyuki Yamamoto, Hironobu Ihn

    The Journal of dermatology　45　(8)　891-897　2018/08

    DOI： 10.1111/1346-8138.14171 　

    ISSN： 0385-2407

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    We established diagnostic criteria and severity classification of lichen sclerosus et atrophicus, because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there is no clinical guideline for lichen sclerosus et atrophicus in Japan, so we proposed its clinical guideline. The clinical guidelines were formulated by clinical questions and recommendations on the basis of evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guidelines easy to use and reliable including the newest evidence, and to present guidance for various clinical problems in treatment of lichen sclerosus et atrophicus.

  133. An orally-active adiponectin receptor agonist mitigates cutaneous fibrosis, inflammation and microvascular pathology in a murine model of systemic sclerosis. Peer-reviewed

    Yamashita T, Lakota K, Taniguchi T, Yoshizaki A, Sato S, Hong W, Zhou X, Sodin-Semrl S, Fang F, Asano Y, Varga J

    Scientific reports　8　(1)　11843　2018/08

    DOI： 10.1038/s41598-018-29901-w 　

  134. Successful treatment of palmoplantar pustular psoriasis with brodalumab. International-journal Peer-reviewed

    Nakao M, Asano Y, Kamata M, Yoshizaki A, Sato S

    European journal of dermatology : EJD　28　(4)　538-539　2018/08

    DOI： 10.1684/ejd.2018.3325 　

    ISSN： 1167-1122

  135. 足趾骨髄炎の治療中に生じたメトロニダゾール脳症の1例

    尾松 淳, 赤股 要, 永井 幸司郎, 遠山 聡, 高橋 岳浩, 吉崎 歩, 浅野 善英, 佐藤 伸一

    皮膚科の臨床　60　(8)　1244-1248　2018/07

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  136. 両大腿に高度な皮膚石灰沈着症を伴った全身性エリテマトーデスの1例

    榊原 萌, 遠山 聡, 船水 薫, 尾松 淳, 宍戸 菜穂美, 赤股 要, 浅野 善英, 山田 大資

    日本皮膚科学会雑誌　128　(8)　1666-1667　2018/07

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  137. Diagnostic criteria, severity classification and guidelines of localized scleroderma. International-journal Peer-reviewed

    Yoshihide Asano, Manabu Fujimoto, Osamu Ishikawa, Shinichi Sato, Masatoshi Jinnin, Kazuhiko Takehara, Minoru Hasegawa, Toshiyuki Yamamoto, Hironobu Ihn

    The Journal of dermatology　45　(7)　755-780　2018/07

    DOI： 10.1111/1346-8138.14161 　

    ISSN： 0385-2407

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    We established diagnostic criteria and severity classification of localized scleroderma because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for localized scleroderma, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of localized scleroderma.

  138. 初診時紅皮症を呈さなかったセザリー症候群の1例

    上條 広章, 宮垣 朝光, 乗松 雄大, 久住 藍, 宍戸 菜穂美, 管 析, 赤股 要, 浅野 善英, 佐藤 伸一

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集　34回　129-129　2018/06

    Publisher: (一社)日本皮膚悪性腫瘍学会

  139. Interleukin-25 is involved in cutaneous T-cell lymphoma progression by establishing a T helper 2-dominant microenvironment. Peer-reviewed

    Nakajima R, Miyagaki T, Hirakawa M, Oka T, Takahashi N, Suga H, Yoshizaki A, Fujita H, Asano Y, Sugaya M, Sato S

    The British journal of dermatology　178　(6)　1373-1382　2018/06

    DOI： 10.1111/bjd.16237 　

    ISSN： 0007-0963

  140. Successful treatment with rituximab in a Japanese patient with systemic sclerosis-associated interstitial lung disease resistant to oral steroid and cyclophosphamide Peer-reviewed

    Hiroko Numajiri, Ayumi Yoshizaki, Satoshi Ebata, Takemichi Fukasawa, Takashi Yamashita, Takehiro Takahashi, Takashi Taniguchi, Yoshihide Asano, Shinichi Sato

    Journal of Dermatology　45　(6)　e140-e141　2018/06/01

    Publisher: Blackwell Publishing Ltd

    DOI： 10.1111/1346-8138.14189 　

    ISSN： 1346-8138 0385-2407

  141. Diagnostic criteria, severity classification and guidelines of systemic sclerosis. International-journal Peer-reviewed

    Yoshihide Asano, Masatoshi Jinnin, Yasushi Kawaguchi, Masataka Kuwana, Daisuke Goto, Shinichi Sato, Kazuhiko Takehara, Masaru Hatano, Manabu Fujimoto, Naoki Mugii, Hironobu Ihn

    The Journal of dermatology　45　(6)　633-691　2018/06

    DOI： 10.1111/1346-8138.14162 　

    ISSN： 0385-2407

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    Several effective drugs have been identified for the treatment of systemic sclerosis (SSc). However, in advanced cases, not only their effectiveness is reduced but they may be also harmful due to their side-effects. Therefore, early diagnosis and early treatment is most important for the treatment of SSc. We established diagnostic criteria for SSc in 2003 and early diagnostic criteria for SSc in 2011, for the purpose of developing evaluation of each organ in SSc. Moreover, in November 2013, the American College of Rheumatology and the European Rheumatology Association jointly developed new diagnostic criteria for increasing their sensitivity and specificity, so we revised our diagnostic criteria and severity classification of SSc. Furthermore, we have revised the clinical guideline based on the newest evidence. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of SSc.

  142. Decreased IL-10-producing regulatory B cells in patients with advanced mycosis fungoides. International-journal Peer-reviewed

    Taro Akatsuka, Tomomitsu Miyagaki, Rina Nakajima, Hiroaki Kamijo, Tomonori Oka, Naomi Takahashi, Hiraku Suga, Ayumi Yoshizaki, Yoshihide Asano, Makoto Sugaya, Shinichi Sato

    European journal of dermatology : EJD　28　(3)　314-319　2018/06/01

    DOI： 10.1684/ejd.2018.3319 　

    ISSN： 1167-1122

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    BACKGROUND: Historically, B cells have been considered as positive regulators of humoral immune responses. Specific B-cell subsets, however, negatively regulate immune responses and are termed "regulatory B cells" (Bregs). Recently, Bregs have been linked to not only inflammatory and autoimmune diseases, but also malignancies via suppressing anti-tumour immunity. OBJECTIVES: To investigate the involvement of Bregs in advanced mycosis fungoides (MF). MATERIALS & METHODS: The frequency of CD19+CD24hiCD27+ memory B cells and CD19+CD24hiCD38hi transitional B cells (which enrich IL-10-producing Bregs) was examined in peripheral blood from patients with advanced MF (n = 11) and healthy controls (n = 9) by flow cytometry. The frequency of IL-10-producing Bregs was also measured by flow cytometry. The correlation between frequency or number of B-cell subsets and disease severity markers was also analysed. RESULTS: The frequency of CD19+CD24hiCD27+ B cells, CD19+CD24hiCD38hi B cells, and IL-10-producing B cells was decreased in peripheral blood of advanced MF patients. The frequency and number of these B-cell subsets inversely correlated with serum soluble IL-2 receptor and serum lactate dehydrogenase levels. CONCLUSIONS: The development of IL-10-producing Bregs is impaired in patients with advanced MF and a decrease in IL-10-producing Bregs may play an important role in the progression of advanced MF.

  143. 余剰分層植皮片を用いた,採皮創への戻しチップ植皮の有効性と当科における手法の工夫について

    尾松 淳, 山田 大資, 沼尻 宏子, 河合 徹, 大垣 淳, 船水 薫, 三枝 良輔, 宮川 卓也, 浅野 善英, 佐藤 伸一

    日本皮膚科学会雑誌　128　(5)　1181-1181　2018/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  144. ガイドラインに基づいた膠原病・血管炎に伴う皮膚潰瘍の診療

    吉崎 歩, 浅井 純, 石井 貴之, 岩田 洋平, 内山 明彦, 岡村 賢, 小川 陽一, 川上 民裕, 岸部 麻理, 小池 雄太, 小寺 雅也, 壽 順久, 藤本 徳毅, 宮城 拓也, 山口 由衣, 浅野 善英

    日本皮膚科学会雑誌　128　(5)　1061-1061　2018/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  145. Increased interleukin-36γ expression in skin and sera of patients with atopic dermatitis and mycosis fungoides/Sézary syndrome. International-journal Peer-reviewed

    Sayaka Otobe, Makoto Sugaya, Rina Nakajima, Tomonori Oka, Naomi Takahashi, Miyoko Kabasawa, Tomomitsu Miyagaki, Yoshihide Asano, Shinichi Sato

    The Journal of dermatology　45　(4)　468-471　2018/04

    DOI： 10.1111/1346-8138.14198 　

    ISSN： 0385-2407

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    Interleukin (IL)-36γ is expressed by keratinocytes and functions as a key initiator of inflammation in the skin. IL-36γ expression is enhanced by tumor necrosis factor-α and IL-17A, having a strong association with psoriasis. In this study, we examined the role of IL-36γ in atopic dermatitis (AD) and mycosis fungoides (MF)/Sézary syndrome (SS). Serum levels of IL-36γ in AD patients and MF/SS patients were elevated compared with those of healthy controls. Importantly, serum IL-36γ levels in AD patients positively correlated with Eczema Area and Severity Index and those of MF/SS patients positively correlated with serum soluble IL-2 receptor levels. IL-36γ mRNA levels in AD skin and MF/SS skin were significantly higher than those of normal skin. IL-36γ mRNA levels in MF/SS skin positively correlated with IL-17A mRNA levels. Immunohistochemical staining revealed that IL-36γ was highly expressed in keratinocytes in lesional skin of AD and MF/SS. Taken together, our study demonstrated that IL-36γ expression was increased in sera and skin of patients with AD and MF/SS as was reported in psoriatic patients.

  146. Impact of a new simplified disability scoring system for adult patients with localized scleroderma. International-journal Peer-reviewed

    Naoko Okiyama, Yoshihide Asano, Yasuhito Hamaguchi, Masatoshi Jinnin, Sei-Ichiro Motegi, Haruka Koizumi, Minoru Hasegawa, Osamu Ishikawa, Shinichi Sato, Kazuhiko Takehara, Toshiyuki Yamamoto, Manabu Fujimoto, Hironobu Ihn

    The Journal of dermatology　45　(4)　431-435　2018/04

    DOI： 10.1111/1346-8138.14214 　

    ISSN： 0385-2407

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    Localized scleroderma (LoS) involves dermal but not internal inflammation and fibrosis. Cosmetic changes often impact quality of life (QOL), however, impairment of activities of daily living (ADL) in LoS patients has not been investigated. To determine what factor(s) are associated with ADL in adult patients with LoS, we performed a retrospective observational study in 177 Japanese adult LoS patients using a novel LoS disability score based on Barthel's indices of ADL: feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfers, mobility and stairs. LoS disability scores increased in proportion to the number of affected body parts but were not correlated to age and duration of illness. The presence of leg lesions significantly impaired ADL of LoS patients compared with lesions on other body parts. Patients treated with systemic medications, who tended to have multiple lesions, presented higher LoS disability scores than those without systemic treatments. Our study proposes that physicians evaluate ADL, not only QOL, in LoS patients. Our findings using LoS disability scoring indicate that multiple affected body parts and leg lesions are risk factors for ADL impairment.

  147. 脊椎関節炎1 実臨床におけるASDASの乾癬性関節炎(PsA)の関節評価についての検討

    立石 晶子, 神田 浩子, 大野 久美子, 内藤 昌志, 廣瀬 旬, 吉崎 歩, 浅野 善英, 佐藤 伸一, 田中 栄, 藤尾 圭志

    日本リウマチ学会総会・学術集会プログラム・抄録集　62回　434-434　2018/03

    Publisher: (一社)日本リウマチ学会

  148. 脊椎関節炎2 乾癬性関節炎(PsA)の仙腸関節炎とその他の体軸病変についての検討

    立石 晶子, 神田 浩子, 大野 久美子, 内藤 昌志, 廣瀬 旬, 吉崎 歩, 浅野 善英, 佐藤 伸一, 田中 栄, 藤尾 圭志

    日本リウマチ学会総会・学術集会プログラム・抄録集　62回　585-585　2018/03

    Publisher: (一社)日本リウマチ学会

  149. 臨床所見より著しく広範囲に病変がみられたA群レンサ球菌による壊死性筋膜炎の1例

    水野 結花, 遠山 聡, 江畑 慧, 尾松 淳, 三枝 良輔, 赤股 要, 山田 大資, 浅野 善英, 谷口 隆志, 三浦 俊介

    日本皮膚科学会雑誌　128　(3)　439-439　2018/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  150. SLE・抗リン脂質抗体症候群1 全身性エリテマトーデス患者の診療の質指標の開発

    矢嶋 宣幸, 佐田 憲映, 高橋 良, 浅野 善英, 東 光久, 亀田 秀人, 桑名 正隆, 上阪 等, 鈴木 勝也, 竹内 勤, 田中 良哉, 田村 直人, 松井 利浩, 三森 経世, 渥美 達也

    日本リウマチ学会総会・学術集会プログラム・抄録集　62回　445-445　2018/03

    Publisher: (一社)日本リウマチ学会

  151. Systemic sclerosis complicated with localized scleroderma-like lesions induced by Köbner phenomenon. International-journal Peer-reviewed

    Saigusa R, Asano Y, Yamashita T, Takahashi T, Nakamura K, Miura S, Ichimura Y, Toyama T, Taniguchi T, Sumida H, Tamaki Z, Miyazaki M, Yoshizaki A, Sato S

    Journal of dermatological science　89　(3)　282-289　2018/03

    DOI： 10.1016/j.jdermsci.2017.12.005 　

    ISSN： 0923-1811

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    BACKGROUND: Scleroderma is a chronic disease of unknown etiology characterized by skin fibrosis and is divided into two clinical entities: systemic sclerosis (SSc) and localized scleroderma (LSc). In general, LSc is rarely complicated with SSc, but a certain portion of SSc patients manifests bilateral symmetric LSc-like lesions on the trunk and extremities. OBJECTIVE: We investigated SSc patients with LSc-like lesions to clarify the underlying pathophysiology. METHODS: Nine SSc cases complicated with LSc-like lesions were clinically and histologically characterized. RESULTS: SSc patients with LSc-like lesions exhibited multiple progressive hyper- and/or hypo-pigmented plaques with mild sclerosis symmetrically distributed on the trunk and extremities, especially abdominal region. In histological assessment, epidermal IL-1α expression was elevated in both forearms and LSc-like lesions of these patients to a greater extent than in forearms of control patients (SSc patients without LSc-like lesions). Of note, the infiltration and degranulation of mast cells were evident throughout the dermis of LSc-like lesions, while detectable to a lesser extent in forearms of SSc patients with LSc-like lesions and control patients. CONCLUSION: The epidermis of SSc patients with LSc-like lesions seems to possess an inflammatory phenotype, leading to the activation of mast cells in the dermis of mechanically stressed skin. Köbner phenomenon may be involved in the induction of LSc-like lesions in a certain subset of SSc.

  152. Fli1-haploinsufficient dermal fibroblasts promote skin-localized transdifferentiation of Th2-like regulatory T cells Peer-reviewed

    Ryosuke Saigusa, Yoshihide Asano, Takashi Taniguchi, Megumi Hirabayashi, Kouki Nakamura, Shunsuke Miura, Takashi Yamashita, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Ayumi Yoshizaki, Maria Trojanowska, Shinichi Sato

    Arthritis Research and Therapy　20　(1)　23　2018/02/07

    Publisher: BioMed Central Ltd.

    DOI： 10.1186/s13075-018-1521-3 　

    ISSN： 1478-6362 1478-6354

  153. 頭部に生じた表在性皮膚脂肪腫性母斑

    沼尻 宏子, 宮川 卓也, 尾松 淳, 船水 薫, 三枝 良輔, 平川 麻衣子, 山田 大資, 増井 友里, 浅野 善英, 佐藤 伸一

    日本皮膚科学会雑誌　128　(2)　229-230　2018/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  154. 頭部に生じたらせん腺癌の1例

    尾松 淳, 三枝 良輔, 遠山 聡, 沼尻 宏子, 船水 薫, 平川 麻衣子, 宮川 卓也, 赤股 要, 山田 大資, 浅野 善英, 佐藤 伸一

    日本皮膚科学会雑誌　128　(2)　232-232　2018/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  155. Primary dermal melanomaと考えた無色素性悪性黒色腫の1例

    南原 優希奈, 宮川 卓也, 山田 大資, 沼尻 宏子, 尾松 淳, 三枝 良輔, 赤股 要, 増井 友里, 浅野 善英, 佐藤 伸一, 三井 浩

    Skin Cancer　32　(3)　290-294　2018/02

    Publisher: (一社)日本皮膚悪性腫瘍学会

    ISSN： 0915-3535

    eISSN： 1884-3549

  156. A potential contribution of psoriasin to vascular and epithelial abnormalities and inflammation in systemic sclerosis Peer-reviewed

    T. Takahashi, Y. Asano, T. Yamashita, K. Nakamura, R. Saigusa, S. Miura, Y. Ichimura, T. Toyama, M. Hirabayashi, T. Taniguchi, A. Yoshizaki, S. Sato

    Journal of the European Academy of Dermatology and Venereology　32　(2)　291-297　2018/02/01

    Publisher: Blackwell Publishing Ltd

    DOI： 10.1111/jdv.14459 　

    ISSN： 1468-3083 0926-9959

  157. Possible pro-inflammatory role of heparin-binding epidermal growth factor-like growth factor in the active phase of systemic sclerosis. International-journal Peer-reviewed

    Megumi Hirabayashi, Yoshihide Asano, Takashi Yamashita, Shunsuke Miura, Kouki Nakamura, Takashi Taniguchi, Ryosuke Saigusa, Takehiro Takahashi, Yohei Ichimura, Takuya Miyagawa, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato

    The Journal of dermatology　45　(2)　182-188　2018/02

    DOI： 10.1111/1346-8138.14088 　

    ISSN： 0385-2407

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    Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family growth factors, which affects multiple aspects of the wound healing process such as epithelialization, wound contraction and angiogenesis. In our study, we measured the serum HB-EGF levels of 51 systemic sclerosis (SSc) patients, which showed a significant increase compared with those of 20 normal subjects. Further analysis revealed a positive correlation between the HB-EGF level and pulmonary ground-glass score but no correlation between the former and pulmonary fibrosis score. Other findings include: a significant increase of serum sialylated carbohydrate antigen KL-6 levels and significant shortness of disease duration in the diffuse cutaneous SSc patients with elevated HB-EGF levels; and significantly higher HB-EGF levels in the presence of Raynaud's phenomenon, in that of telangiectasia, and in the absence of contracture of phalanges in all SSc patients. We then evaluated HB-EGF mRNA levels of fibroblasts harvested from skin samples of the SSc patients and those of foreskin-derived fibroblasts treated with transforming growth factor-β, both of which were significantly higher than each control. In conclusion, we speculate that HB-EGF plays a pro-inflammatory role in the active skin and lung lesions of SSc.

  158. Systemic sclerosis Peer-reviewed

    Yoshihide Asano

    Journal of Dermatology　45　(2)　128-138　2018/02/01

    Publisher: Blackwell Publishing Ltd

    DOI： 10.1111/1346-8138.14153 　

    ISSN： 1346-8138 0385-2407

  159. 体軸病変を有する乾癬性関節炎の機能障害についての検討

    立石 晶子, 神田 浩子, 大野 久美子, 廣瀬 旬, 吉崎 歩, 浅野 善英, 佐藤 伸一, 田中 栄, 藤尾 圭志

    日本脊椎関節炎学会誌　(Suppl.)　50-50　2018

    Publisher: 日本脊椎関節炎学会

    eISSN： 2435-6778

  160. Serum vascular endothelial growth factor A levels reflect itch severity in mycosis fungoides and Sézary syndrome. International-journal Peer-reviewed

    Minami Sakamoto, Tomomitsu Miyagaki, Hiroaki Kamijo, Tomonori Oka, Naomi Takahashi, Hiraku Suga, Ayumi Yoshizaki, Yoshihide Asano, Makoto Sugaya, Shinichi Sato

    The Journal of dermatology　45　(1)　95-99　2018/01

    DOI： 10.1111/1346-8138.14033 　

    ISSN： 0385-2407

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    Angiogenesis is an important step to support progression of malignancies, including mycosis fungoides (MF) and Sézary syndrome (SS). Vascular endothelial growth factor (VEGF)-A, a key player in angiogenesis, is secreted by tumor cells of MF/SS and its expression levels in lesional skin correlated with disease severity. In this study, we examined serum VEGF-A levels in MF/SS patients. Serum VEGF-A levels were elevated in patients with erythrodermic MF/SS and the levels decreased after treatment. Importantly, serum VEGF-A levels positively correlated with markers for pruritus. We also found that VEGF-A upregulated mRNA expression of thymic stromal lymphopoietin by keratinocytes. Taken together, our study suggests that VEGF-A can promote progression and pruritus in MF/SS. Inhibition of VEGF-A signaling can be a therapeutic strategy for patients with erythrodermic MF/SS.

  161. TBX4 is involved in the super-enhancer-driven transcriptional programs underlying features specific to lung fibroblasts. International-journal Peer-reviewed

    Masafumi Horie, Naoya Miyashita, Yu Mikami, Satoshi Noguchi, Yasuhiro Yamauchi, Maho Suzukawa, Takeshi Fukami, Ken Ohta, Yoshihide Asano, Shinichi Sato, Yoko Yamaguchi, Mitsuhiro Ohshima, Hiroshi I Suzuki, Akira Saito, Takahide Nagase

    American journal of physiology. Lung cellular and molecular physiology　314　(1)　L177-L191-L191　2018/01/01

    DOI： 10.1152/ajplung.00193.2017 　

    ISSN： 1040-0605

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    Lung fibroblasts participate in the pathogenesis of respiratory diseases, including lung cancer and pulmonary fibrosis. Although fibroblasts are ubiquitous constituents of various organs, their cellular diversity among different organs has been poorly characterized. Here, we aimed to investigate the distinct gene signature of lung fibroblasts that represents its pulmonary origin and the underlying gene regulatory networks. Promoter-level differential expression analysis by cap analysis of gene expression (CAGE) sequencing revealed distinct gene expression patterns of fibroblasts derived from different anatomical sites and identified 88 coding genes with higher expression in lung fibroblasts relative to other fibroblasts. Multiple key transcription factors important for lung mesenchyme development, including the T-box transcription factors TBX2, TBX4, and TBX5 were enriched in this lung-specific signature and were associated with super-enhancers. TBX4 showed highly specific expression in lung fibroblasts and was required for cell proliferation and collagen gel contraction capacity. Transcriptome analysis revealed that TBX4 could broadly regulate fibroblast-related pathways and partly contribute to super-enhancer-mediated transcriptional programs. Of pathological importance, lung fibroblast-specific genes were globally downregulated in lung cancer-associated fibroblasts (CAFs). Notably, TBX2, TBX4, and TBX5 were downregulated and hypermethylated in lung CAFs, suggesting an association between epigenetic silencing of these factors and phenotypic alteration of lung fibroblasts in cancer. Our study highlights the importance of T-box transcription factors, especially TBX4, and super-enhancers in the roles of lung fibroblasts in pulmonary physiology and pathogenesis.

  162. Gastroesophageal Reflux Disease-Related Disorders of Systemic Sclerosis Based on the Analysis of 66 Patients. International-journal Peer-reviewed

    Rie Matsuda, Nobutake Yamamichi, Takeshi Shimamoto, Hayakazu Sumida, Yu Takahashi, Chihiro Minatsuki, Shinya Kodashima, Satoshi Ono, Keiko Niimi, Yosuke Tsuji, Yoshiki Sakaguchi, Itaru Saito, Yosuke Kataoka, Itsuko Asada-Hirayama, Hikaru Kakimoto, Seiichi Yakabi, Chihiro Takeuchi, Yuta Matsumoto, Zenshiro Tamaki, Mitsuhiro Fujishiro, Yoshihide Asano, Shinichi Sato, Kazuhiko Koike

    Digestion　98　(4)　201-208　2018

    DOI： 10.1159/000489848 　

    ISSN： 0012-2823

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    BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD)-related disorders of systemic sclerosis (SSc) patients have not been adequately investigated. METHODS: Sixty-six SSc patients (5 males and 61 females; 56.6 ± 14.6 years old) who underwent esophagogastroduodenoscopy were analyzed on the basis of 16 background factors. They were additionally compared with 116 matched non-SSc subjects controlling age, sex, and use of proton pump inhibitors (PPIs). RESULTS: The mean disease duration of 66 patients was 5.1 ± 8.1 years, and their breakdown was as follows: 53 (80.3%) with GERD, 38 (57.6%) with GERD-related symptoms, and 20 (30.3%) with reflux esophagitis (RE; LA-A: 10, LA-B: 5, LA-C: 4, LA-D: 1). Use of PPI (p = 0.0455), complication of interstitial lung disease (p = 0.0242), and history of cyclophosphamide therapy (p = 0.0184) denoted significant association with GERD-related symptoms. Older age (p = 0.0211) was significantly associated with RE. None of GERD-related disorders showed any difference between 37 diffuse cutaneous SSc and 29 limited cutaneous SSc patients. The matched analysis indicated that SSc patients had higher prevalence of GERD (p < 0.0001), GERD-related symptoms (p = 0.0034), and RE (p = 0.0002). CONCLUSION: SSc patients tend to have worse GERD symptoms and severer RE. However, most SSc-associated factors did not show significant association with GERD-related disorders, indicating the difficulty in predicting GERD-related disorders among SSc patients.

  163. Increased endocan expression in lesional skin and decreased endocan expression in sera in atopic dermatitis Peer-reviewed

    Hideko Suzuki, Tomomitsu Miyagaki, Sayaka Otobe, Rina Nakajima, Tomonori Oka, Naomi Takahashi, Miyoko Kabasawa, Hiraku Suga, Ayumi Yoshizaki, Yoshihide Asano, Shinichi Sato, Makoto Sugaya

    JOURNAL OF DERMATOLOGY　44　(12)　1392-1395　2017/12

    DOI： 10.1111/1346-8138.13974 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  164. A possible implication of reduced levels of LIF, LIFR, and gp130 in vasculopathy related to systemic sclerosis Peer-reviewed

    Takashi Taniguchi, Takuya Miyagawa, Zenshiro Tamaki, Kouki Nakamura, Takashi Yamashita, Ryosuke Saigusa, Takehiro Takahashi, Tetsuo Toyama, Yohei Ichimura, Ayumi Yoshizaki, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato, Yoshihide Asano

    ARCHIVES OF DERMATOLOGICAL RESEARCH　309　(10)　833-842　2017/12

    DOI： 10.1007/s00403-017-1786-4 　

    ISSN： 0340-3696

    eISSN： 1432-069X

  165. Lymphangiosarcoma of the hip arising in a congenital non-irradiated lymphangioma Peer-reviewed

    Takuya Miyagawa, Takafumi Kadono, Ryosuke Saigusa, Daisuke Yamada, Yuri Masui, Hideki Fujita, Yoshihide Asano, Shinichi Sato

    JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT　15　(12)　1235-1237　2017/12

    DOI： 10.1111/ddg.13356 　

    ISSN： 1610-0379

    eISSN： 1610-0387

  166. Lymphangiosarkom der Hüfte in einem nicht bestrahlten kongenitalen Lymphangiom Peer-reviewed

    Takuya Miyagawa, Takafumi Kadono, Ryosuke Saigusa, Daisuke Yamada, Yuri Masui, Hideki Fujita, Yoshihide Asano, Shinichi Sato

    JDDG - Journal of the German Society of Dermatology　15　(12)　1235-1237　2017/12/01

    Publisher: Wiley-VCH Verlag

    DOI： 10.1111/ddg.13356_g 　

    ISSN： 1610-0387 1610-0379

  167. Increased Interleukin-19 Expression in Cutaneous T-cell Lymphoma and Atopic Dermatitis. International-journal Peer-reviewed

    Tomonori Oka, Makoto Sugaya, Naomi Takahashi, Rina Nakajima, Sayaka Otobe, Miyoko Kabasawa, Hiraku Suga, Tomomitsu Miyagaki, Yoshihide Asano, Shinichi Sato

    Acta dermato-venereologica　97　(10)　1172-1177　2017/11/15

    DOI： 10.2340/00015555-2723 　

    ISSN： 0001-5555

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    Interleukin-19 (IL-19), a pro-inflammatory cytokine known to stimulate the production of T helper type 2 (Th2) cytokines, is induced by IL-17A and highly expressed in the lesional skin of psoriasis and atopic dermatitis (AD). This aim of this study was to investigate whether IL-19 is involved in cutaneous T-cell lym-phoma (CTCL) and AD. IL-19 levels were significantly higher in the sera of patients with AD and those with advanced-stage CTCL than in normal controls, correlating significantly with clinical disease markers. IL-19 mRNA levels in lesional skin of both diseases were significantly elevated. Immunohistochemical staining revealed that IL-19 was expressed in the epidermis of AD skin and CTCL skin. In vitro, IL-17A and IL-4 increased IL-19 mRNA expression in human keratinocytes. Thus, IL-19 was increased in the sera and skin of AD and CTCL. These results suggest that IL-19 is important for bridging Th17 to Th2 in these diseases.

  168. 血小板特異的Fli1ノックアウトマウスでは創傷閉鎖が促進され、血管新生が増強される(Platelet-specific Fli1-knockout mice show accelerated wound closure and enhanced angiogenesis)

    Hirabayashi Megumi, Asano Yoshihide, Yamashita Takashi, Saigusa Ryosuke, Miura Shunsuke, Nakamura Kouki, Miyagawa Takuya, Taniguchi Takashi, Yoshizaki Ayumi, Sato Shinichi

    日本研究皮膚科学会年次学術大会・総会プログラム　42回　184-184　2017/11

    Publisher: (一社)日本研究皮膚科学会

  169. Treg特異的Fli1コンディショナルノックアウトマウスにおいてTh17/Tregバランスの脱制御は全身性硬化症様表現型の基礎的原因である(Dysregulated Th17/Treg balance underlies the systemic sclerosis-like phenotypes of Treg-specific Fli1 conditional knock out mice)

    Nakamura Kouki, Asano Yoshihide, Miyagawa Takuya, Hirabayashi Megumi, Yamashita Takashi, Saigusa Ryosuke, Miura Shunsuke, Toyama Tetsuo, Takahashi Takehiro, Ichimura Yohei, Taniguchi Takashi, Yoshizaki Ayumi, Trojanowska Maria, Sato Shinichi

    日本研究皮膚科学会年次学術大会・総会プログラム　42回　186-186　2017/11

    Publisher: (一社)日本研究皮膚科学会

  170. 真皮樹状細胞におけるFli1欠損はRALDH1産生を阻害しTreg抑制および組織線維症に至る(The deficiency of Fli1 suppresses RALDH1 production in dermal dendritic cells, leading to Treg suppression and tissue fibrosis)

    Miura Shunsuke, Asano Yoshihide, Saigusa Ryosuke, Yamashita Takashi, Nakamura Kouki, Hirabayashi Megumi, Miyagawa Takuya, Yoshizaki Ayumi, Trojanowska Maria, Sato Shinichi

    日本研究皮膚科学会年次学術大会・総会プログラム　42回　193-193　2017/11

    Publisher: (一社)日本研究皮膚科学会

  171. 全身性硬化症の発症における上皮増殖因子受容体リガンドamphiregulinの役割(The role of amphiregulin, an epidermal growth factor receptor ligand, in the development of systemic sclerosis)

    Saigusa Ryosuke, Asano Yoshihide, Fukui Yuki, Miyagawa Takuya, Hirabayashi Megumi, Nakamura Kouki, Miura Shunsuke, Yamashita Takashi, Taniguchi Takashi, Yoshizaki Ayumi, Sato Shinichi

    日本研究皮膚科学会年次学術大会・総会プログラム　42回　198-198　2017/11

    Publisher: (一社)日本研究皮膚科学会

  172. Fli1欠損脂肪細胞により誘発された特発性皮膚線維症と脈管障害 全身性硬化症における脂肪細胞の潜在的役割(Spontaneous dermal fibrosis and vasculopathy induced by Fli1-deficient adipocytes: a potential role of adipocytes in systemic sclerosis)

    Miyagawa Takuya, Asano Yoshihide, Saigusa Ryosuke, Yamashita Takashi, Hirabayashi Megumi, Nakamura Kouki, Miura Shunsuke, Taniguchi Takashi, Yoshizaki Ayumi, Trojanowska Maria, Sato Shinichi

    日本研究皮膚科学会年次学術大会・総会プログラム　42回　205-205　2017/11

    Publisher: (一社)日本研究皮膚科学会

  173. トシリズマブ投与により皮膚硬化の改善および爪上皮毛細血管の新生がみられた全身性強皮症の1例

    遠山 聡, 赤股 要, 江畑 慧, 深澤 毅倫, 三浦 俊介, 山下 尚志, 谷口 隆志, 吉崎 歩, 浅野 善英, 佐藤 伸一

    Journal of Environmental Dermatology and Cutaneous Allergology　11　(5)　446-446　2017/11

    Publisher: (一社)日本皮膚アレルギー・接触皮膚炎学会

    ISSN： 1882-0123

  174. 紅斑局面を呈した左大腿隆起性皮膚線維肉腫の1例

    深澤 桂子, 尾松 淳, 久住 藍, 三枝 良輔, 宮川 卓也, 赤股 要, 山田 大資, 宮嵜 美幾, 浅野 善英, 宍戸 菜穂美

    日本皮膚科学会雑誌　127　(12)　2649-2650　2017/11

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  175. Transforming growth factor β-inhibitor Repsox downregulates collagen expression of scleroderma dermal fibroblasts and prevents bleomycin-induced mice skin fibrosis. International-journal Peer-reviewed

    Maho Ide, Masatoshi Jinnin, Yukiko Tomizawa, Zhongzhi Wang, Ikko Kajihara, Satoshi Fukushima, Yoshinobu Hashizume, Yoshihide Asano, Hironobu Ihn

    Experimental dermatology　26　(11)　1139-1143　2017/11

    DOI： 10.1111/exd.13366 　

    ISSN： 0906-6705

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    Inhibition of transforming growth factor (TGF)-β1 signalling may be one of the most reliable approaches to treat skin fibrosis of scleroderma. Although there have been many basic researches of TGF-β blockade reagents, few of them were proved to have inhibitory effects on fibrosis both in vitro and in vivo. In this study, we randomly chose four commercially available low molecular weight compounds (Repsox, LY2109761, LY364947 and K02288) from TGF-β1 inhibitor library, and compared their antifibrotic effects in vitro and in vivo. We demonstrated that Repsox has the most potent inhibitory effects on TGF-β-induced expression of CTGF and collagen of cultured normal dermal fibroblasts in vitro and their constitutive overexpression of scleroderma fibroblast in vitro. In addition, Repsox could attenuate skin fibrosis by bleomycin in vivo, via the downregulation of CTGF or collagen. Our results may facilitate clinical trial of Repsox against fibrotic diseases in future.

  176. Multiple-opposing rotation flaps for the scalp defect including hair whorl Peer-reviewed

    Takuya Miyagawa, Takafumi Kadono, Ryosuke Saigusa, Hiroko Numajiri, Jun Omatsu, Kaoru Funamizu, Daisuke Yamada, Yuri Masui, Yoshihide Asano, Shinichi Sato

    JOURNAL OF DERMATOLOGY　44　(11)　E302-E303　2017/11

    DOI： 10.1111/1346-8138.13952 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  177. Nivolumab-induced vitiligo successfully treated with narrowband UVB phototherapy Peer-reviewed

    Takuya Miyagawa, Takafumi Kadono, Yuri Masui, Daisuke Yamada, Ryosuke Saigusa, Hiroko Numajiri, Jun Omatsu, Yoshihide Asano, Shinichi Sato

    European Journal of Dermatology　27　(6)　656-658　2017/11/01

    Publisher: John Libbey Eurotext

    DOI： 10.1684/ejd.2017.3096 　

    ISSN： 1952-4013 1167-1122

  178. 298 Fli1-deficient adipocytes promote the spontaneous development of dermal fibrosis and vasculopathy mimicking systemic sclerosis through adipocytes-to-myofibroblast transdifferentiation and defective vasculogenesis

    T. Miyagawa, Y. Asano, R. Saigusa, K. Nakamura, M. Hirabayashi, T. Yamashita, S. Miura, T. Taniguchi, A. Yoshizaki, M. Trojanowska, S. Sato

    Journal of Investigative Dermatology　137　(10)　S244-S244　2017/10

    Publisher: Elsevier BV

    DOI： 10.1016/j.jid.2017.07.493 　

    ISSN： 0022-202X

  179. 305 Fli1 deficiency alters the phenotype of dermal dendritic cells, promoting the development of dermal fibrosis in bleomycin-treated mice

    S. Miura, Y. Asano, R. Saigusa, T. Yamashita, K. Nakamura, M. Hirabayashi, T. Miyagawa, A. Yoshizaki, M. Trojanowska, S. Sato

    Journal of Investigative Dermatology　137　(10)　S245-S245　2017/10

    Publisher: Elsevier BV

    DOI： 10.1016/j.jid.2017.07.500 　

    ISSN： 0022-202X

  180. Single Cell Analysis Revealed That the Response to Cyclophosphamide Therapy Is Regulated By B Cells in Systemic Sclerosis-Associated Interstitial Lung Disease Peer-reviewed

    Satoshi Ebata, Ayumi Yoshizaki, Takemichi Fukasawa, Kouki Nakamura, Maiko Hirakawa, Takashi Yamashita, Shunsuke Miura, Ryosuke Saigusa, Megumi Hirabayashi, Asako Yoshizaki, Kaname Akamata, Yoshihide Asano, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　69　2017/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  181. Single B Cell Analysis Revealed the Relationship Among the Cytokine Profile, Antibody Affinity, and Pathogenic Roles of Autoantigen-Reactive B Cells in Systemic Sclerosis Peer-reviewed

    Takemichi Fukasawa, Ayumi Yoshizaki, Satoshi Ebata, Kouki Nakamura, Ryosuke Saigusa, Takashi Yamashita, Yoshihide Asano, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　69　2017/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  182. The impact of transcription factor Fli1 deficiency on the regulation of angiogenesis Peer-reviewed

    Tetsuo Toyama, Yoshihide Asano, Takuya Miyagawa, Kouki Nakamura, Megumi Hirabayashi, Takashi Yamashita, Ryosuke Saigusa, Shunsuke Miura, Yohei Ichimura, Takehiro Takahashi, Takashi Taniguchi, Ayumi Yoshizaki, Shinichi Sato

    EXPERIMENTAL DERMATOLOGY　26　(10)　912-918　2017/10

    DOI： 10.1111/exd.13341 　

    ISSN： 0906-6705

    eISSN： 1600-0625

  183. Serum H-ficolin levels: Clinical association with interstitial lung disease in patients with systemic sclerosis Peer-reviewed

    Takuya Miyagawa, Yoshihide Asano, Yuka de Mestier, Ryosuke Saigusa, Takashi Taniguchi, Takashi Yamashita, Kouki Nakamura, Megumi Hirabayashi, Shunsuke Miura, Yohei Ichimura, Takehiro Takahashi, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato

    JOURNAL OF DERMATOLOGY　44　(10)　1168-1171　2017/10

    DOI： 10.1111/1346-8138.13877 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  184. RXRB Is an MHC-Encoded Susceptibility Gene Associated with Anti-Topoisomerase I Antibody-Positive Systemic Sclerosis. International-journal Peer-reviewed

    Akira Oka, Yoshihide Asano, Minoru Hasegawa, Manabu Fujimoto, Osamu Ishikawa, Masataka Kuwana, Yasushi Kawaguchi, Toshiyuki Yamamoto, Hiroki Takahashi, Daisuke Goto, Hirahito Endo, Masatoshi Jinnin, Shuhei Mano, Kazuyoshi Hosomichi, Tomotaka Mabuchi, Mahoko Takahashi Ueda, So Nakagawa, Stephan Beck, Seiamak Bahram, Kazuhiko Takehara, Shinichi Sato, Hironobu Ihn

    The Journal of investigative dermatology　137　(9)　1878-1886　2017/09

    DOI： 10.1016/j.jid.2017.04.028 　

    ISSN： 0022-202X

    More details Close

    Systemic sclerosis is a systemic autoimmune and connective tissue disorder associated with the human leukocyte antigen locus. However, the functional relationship between human leukocyte antigen gene(s) and disease development remains unknown. To elucidate major histocompatibility complex-linked systemic sclerosis genetics, we performed genotyping of major histocompatibility complex-borne microsatellites and HLA-DPB1 alleles using DNA obtained from 318 anti-topoisomerase I antibody-positive patients and 561 healthy controls, all of Japanese descent. Those results revealed two major histocompatibility complex haplotypes associated with systemic sclerosis. Exome sequencing and targeted analysis of these risk haplotypes identified rs17847931 in RXRB as a susceptibility variant (P = 1.3 × 10-15; odds ratio [OR] = 9.4) with amino acid substitution p.V95A on the risk haplotype harboring HLA-DPB1∗13:01. No identical variant in the other haplotype including DPB1*09:01 was observed, though that haplotype also showed a significant association (P = 8.5 × 10-22; OR = 4.3) with systemic sclerosis. Furthermore, the number of risk factors was shown to be a predominant factor, as individuals with two factors had elevated risk (P = 6.7 × 10-13; OR = 30.2). We concluded that RXRB may be involved in antifibrotic activity in skin and chromatin remodeling.

  185. Systemic Sclerosis Dermal Fibroblasts Suppress Th1 Cytokine Production via Galectin-9 Overproduction due to Fli1 Deficiency Peer-reviewed

    Ryosuke Saigusa, Yoshihide Asano, Kouki Nakamura, Megumi Hirabayashi, Shunsuke Miura, Takashi Yamashita, Takashi Taniguchi, Yohei Ichimura, Takehiro Takahashi, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　137　(9)　1850-1859　2017/09

    DOI： 10.1016/j.jid.2017.04.035 　

    ISSN： 0022-202X

    eISSN： 1523-1747

  186. Contribution of Soluble Forms of Programmed Death 1 and Programmed Death Ligand 2 to Disease Severity and Progression in Systemic Sclerosis Peer-reviewed

    Takemichi Fukasawa, Ayumi Yoshizaki, Satoshi Ebata, Kouki Nakamura, Ryosuke Saigusa, Syunsuke Miura, Takashi Yamashita, Megumi Hirabayashi, Yohei Ichimura, Takashi Taniguchi, Yoshihide Asano, Hisashi Shimizu, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　69　(9)　1879-1890　2017/09

    DOI： 10.1002/art.40164 　

    ISSN： 2326-5191

    eISSN： 2326-5205

  187. 胃癌手術後に軽快したBazex症候群の1例

    西牧 美幸, 上田 朋子, 尾松 淳, 浅野 善英, 山田 大資, 野田 真史

    日本皮膚科学会雑誌　127　(9)　2123-2123　2017/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  188. Critical contribution of the interleukin-6/signal transducer and activator of transcription 3 axis to vasculopathy associated with systemic sclerosis Peer-reviewed

    Takashi Taniguchi, Yoshihide Asano, Takemichi Fukasawa, Ayumi Yoshizaki, Shinichi Sato

    JOURNAL OF DERMATOLOGY　44　(8)　967-971　2017/08

    DOI： 10.1111/1346-8138.13827 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  189. Fli1 Deficiency Induces CXCL6 Expression in Dermal Fibroblasts and Endothelial Cells, Contributing to the Development of Fibrosis and Vasculopathy in Systemic Sclerosis Peer-reviewed

    Takashi Taniguchi, Yoshihide Asano, Kouki Nakamura, Takashi Yamashita, Ryosuke Saigusa, Yohei Ichimura, Takehiro Takahashi, Tetsuo Toyama, Ayumi Yoshizaki, Shinichi Sato

    JOURNAL OF RHEUMATOLOGY　44　(8)　1198-1205　2017/08

    DOI： 10.3899/jrheum.161092 　

    ISSN： 0315-162X

    eISSN： 1499-2752

  190. BET bromodomain inhibitor JQ1 decreases CD30 and CCR4 expression and proliferation of cutaneous T-cell lymphoma cell lines Peer-reviewed

    Hiroaki Kamijo, Makoto Sugaya, Naomi Takahashi, Tomonori Oka, Tomomitsu Miyagaki, Yoshihide Asano, Shinichi Sato

    ARCHIVES OF DERMATOLOGICAL RESEARCH　309　(6)　491-497　2017/08

    DOI： 10.1007/s00403-017-1749-9 　

    ISSN： 0340-3696

    eISSN： 1432-069X

  191. OP0087 Platelet-specific fli1-knockout mice show accelerated wound closure associated with increased myofibroblast formation in the inflammatory phase

    M Hirabayashi, Y Asano, T Yamashita, R Saigusa, S Miura, K Nakamura, T Miyagawa, Y Ichimura, T Taniguchi, A Yoshizaki, S Sato

    Oral Presentations　2017/06/15

    Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism

    DOI： 10.1136/annrheumdis-2017-eular.1350 　

  192. Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis. International-journal Peer-reviewed

    Chikashi Terao, Takahisa Kawaguchi, Philippe Dieude, John Varga, Masataka Kuwana, Marie Hudson, Yasushi Kawaguchi, Marco Matucci-Cerinic, Koichiro Ohmura, Gabriela Riemekasten, Aya Kawasaki, Paolo Airo, Tetsuya Horita, Akira Oka, Eric Hachulla, Hajime Yoshifuji, Paola Caramaschi, Nicolas Hunzelmann, Murray Baron, Tatsuya Atsumi, Paul Hassoun, Takeshi Torii, Meiko Takahashi, Yasuharu Tabara, Masakazu Shimizu, Akiko Tochimoto, Naho Ayuzawa, Hidetoshi Yanagida, Hiroshi Furukawa, Shigeto Tohma, Minoru Hasegawa, Manabu Fujimoto, Osamu Ishikawa, Toshiyuki Yamamoto, Daisuke Goto, Yoshihide Asano, Masatoshi Jinnin, Hirahito Endo, Hiroki Takahashi, Kazuhiko Takehara, Shinichi Sato, Hironobu Ihn, Soumya Raychaudhuri, Katherine Liao, Peter Gregersen, Naoyuki Tsuchiya, Valeria Riccieri, Inga Melchers, Gabriele Valentini, Anne Cauvet, Maria Martinez, Tsuneyo Mimori, Fumihiko Matsuda, Yannick Allanore

    Annals of the rheumatic diseases　76　(6)　1150-1158　2017/06

    DOI： 10.1136/annrheumdis-2016-210645 　

    ISSN： 0003-4967

    More details Close

    OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease characterised by skin and systemic fibrosis culminating in organ damage. Previous genetic studies including genome-wide association studies (GWAS) have identified 12 susceptibility loci satisfying genome-wide significance. Transethnic meta-analyses have successfully expanded the list of susceptibility genes and deepened biological insights for other autoimmune diseases. METHODS: We performed transethnic meta-analysis of GWAS in the Japanese and European populations, followed by a two-staged replication study comprising a total of 4436 cases and 14 751 controls. Associations between significant single nuclear polymorphisms (SNPs) and neighbouring genes were evaluated. Enrichment analysis of H3K4Me3, a representative histone mark for active promoter was conducted with an expanded list of SSc susceptibility genes. RESULTS: We identified two significant SNP in two loci, GSDMA and PRDM1, both of which are related to immune functions and associated with other autoimmune diseases (p=1.4×10-10 and 6.6×10-10, respectively). GSDMA also showed a significant association with limited cutaneous SSc. We also replicated the associations of previously reported loci including a non-GWAS locus, TNFAIP3. PRDM1 encodes BLIMP1, a transcription factor regulating T-cell proliferation and plasma cell differentiation. The top SNP in GSDMA was a missense variant and correlated with gene expression of neighbouring genes, and this could explain the association in this locus. We found different human leukocyte antigen (HLA) association patterns between the two populations. Enrichment analysis suggested the importance of CD4-naïve primary T cell. CONCLUSIONS: GSDMA and PRDM1 are associated with SSc. These findings provide enhanced insight into the genetic and biological basis of SSc.

  193. Adiponectin is an endogenous anti-fibrotic mediator and therapeutic target Peer-reviewed

    Roberta G. Marangoni, Yuri Masui, Feng Fang, Benjamin Korman, Gabriel Lord, Junghwa Lee, Katja Lakota, Jun Wei, Philipp E. Scherer, Laszlo Otvos, Toshimasa Yamauchi, Naoto Kubota, Takashi Kadowaki, Yoshihide Asano, Shinichi Sato, Warren G. Tourtellotte, John Varga

    SCIENTIFIC REPORTS　7　(1)　4397　2017/06

    DOI： 10.1038/s41598-017-04162-1 　

    ISSN： 2045-2322

  194. 897 Abnormally activated angiogenesis and impaired vasculogenesis underlie the vasculopathy in Fli1/Klf5 double-heterozygote knockout mice, a new animal model of systemic sclerosis

    K. Nakamura, Y. Asano, T. Miyagawa, M. Hirabayashi, T. Yamashita, R. Saigusa, S. Miura, T. Toyama, T. Takahashi, Y. Ichimura, T. Taniguchi, A. Yoshizaki, M. Trojanowska, S. Sato

    Journal of Investigative Dermatology　137　(5)　S155-S155　2017/05

    Publisher: Elsevier BV

    DOI： 10.1016/j.jid.2017.02.924 　

    ISSN： 0022-202X

  195. クリオピリン関連周期熱症候群を合併した抗セントロメア抗体陽性全身性強皮症の1例

    遠山 聡, 高橋 岳浩, 赤股 要, 尾松 淳, 深澤 毅倫, 平林 恵, 浅野 善英, 佐藤 伸一, 小野 真太郎, 小原 収, 今井 耕輔

    日本皮膚科学会雑誌　127　(6)　1359-1359　2017/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  196. primary dermal melanomaと考えた無色素性悪性黒色腫の1例

    南原 優希奈, 宮川 卓也, 山田 大資, 沼尻 宏子, 尾松 淳, 三枝 良輔, 増井 友里, 浅野 善英, 佐藤 伸一, 三井 浩

    日本皮膚悪性腫瘍学会学術大会プログラム・抄録集　33回　180-180　2017/05

    Publisher: (一社)日本皮膚悪性腫瘍学会

  197. 汗腺の段階的な変性・破壊像を認めた特発性後天性全身性無汗症の1例

    尾松 淳, 赤股 要, 永井 幸司郎, 遠山 聡, 角田 麻衣子, 高橋 岳浩, 浅野 善英, 佐藤 伸一

    日本皮膚科学会雑誌　127　(5)　1151-1151　2017/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  198. 創傷・褥瘡・熱傷ガイドライン(第2版)について 講演を聴けば分かる第1版(2011年)からの改正点ならびに変更点 膠原病・血管炎に伴う皮膚潰瘍診療ガイドライン改訂と診療のポイント

    岩田 洋平, 浅井 純, 石井 貴之, 川上 民裕, 小寺 雅也, 浅野 善英

    日本皮膚科学会雑誌　127　(5)　983-983　2017/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  199. RXRB is a MHC-encoded susceptibility gene associated with anti-topoisomerase I antibody-positive systemic sclerosis

    Oka, Akira, Asano, Yoshihide, Hasegawa, Minoru, Fujimoto, Manabu, Ishikawa, Osamu, Kuwana, Masataka, Kawaguchi, Yasushi, Yamamoto, Toshiyuki, Takahashi, Hiroki, Goto, Daisuke, Endo, Hirahito, Jinnin, Masatoshi, Mano, Shuhei, Hosomichi, Kazuyoshi, Mabuchi, Tomotaka, Ueda, Mahoko Takahashi, Nakagawa, So, Beck, Stephan, Bahram, Seiamak, Takehara, Kazuhiko, Sato, Shinichi, Ihn, Hironobu

    The Journal of investigative dermatology　137　(9)　1878-1886　2017/05

    Publisher: ELSEVIER SCIENCE INC

    DOI： 10.1016/j.jid.2017.04.028 　

    ISSN： 1523-1747

    More details Close

    Systemic sclerosis (SSc) is a systemic autoimmune and connective tissue disorder associated with the human leukocyte antigen (HLA) locus. However, the functional relationship between HLA gene(s) and disease development remains unknown. To elucidate major histocompatibility complex (MHC)-linked SSc genetics, we performed genotyping of MHC-borne microsatellites and HLA-DPB1 alleles using DNA obtained from 318 anti-topoisomerase I antibody-positive patients and 561 healthy controls, all of Japanese descent. Those results revealed 2 MHC haplotypes associated with SSc. Exome sequencing and targeted analysis of these risk haplotypes identified rs17847931 in retinoid X receptor beta (RXRB) as a susceptibility variant (P=1.3×10(-15); odds ratio (OR)=9.4) with amino acid substitution p.V95A on the risk haplotype harboring HLA-DPB1*13:01. No identical variant in the other haplotype including DPB1*09:01 was observed, though that haplotype also showed a significant association (P=8.5×10(-22); OR =4.3) with SSc. Furthermore, the number of risk factors was shown to be a predominant factor, as individuals with 2 factors had elevated risk (P=6.7 × 10(-13); OR=30.2). We concluded that RXRB may b

  200. Placental Growth Factor and Vascular Endothelial Growth Factor Together Regulate Tumour Progression via Increased Vasculature in Cutaneous T-cell Lymphoma Peer-reviewed

    Tomomitsu Miyagaki, Makoto Sugaya, Tomonori Oka, Naomi Takahashi, Makiko Kawaguchi, Hiraku Suga, Hideki Fujita, Ayumi Yoshizaki, Yoshihide Asano, Shinichi Sato

    ACTA DERMATO-VENEREOLOGICA　97　(5)　586-592　2017/05

    DOI： 10.2340/00015555-2623 　

    ISSN： 0001-5555

    eISSN： 1651-2057

  201. CXCL17 Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation by Recruiting Myeloid-Derived Suppressor Cells and Regulatory T Cells Peer-reviewed

    Tomonori Oka, Makoto Sugaya, Naomi Takahashi, Takehiro Takahashi, Sayaka Shibata, Tomomitsu Miyagaki, Yoshihide Asano, Shinichi Sato

    JOURNAL OF IMMUNOLOGY　198　(10)　3897-3908　2017/05

    DOI： 10.4049/jimmunol.1601607 　

    ISSN： 0022-1767

    eISSN： 1550-6606

  202. 足趾骨髄炎の治療中に生じたメトロニダゾール脳症の一例

    尾松 淳, 赤股 要, 遠山 聡, 高橋 岳浩, 吉崎 歩, 浅野 善英, 佐藤 伸一

    日本臨床皮膚科医会雑誌　34　(2)　302-302　2017/04

    Publisher: 日本臨床皮膚科医会

    ISSN： 1349-7758

    eISSN： 1882-272X

  203. Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52-week, open-label, phase 3 study (UNCOVER-J) Peer-reviewed

    Hidehisa Saeki, Hidemi Nakagawa, Ko Nakajo, Taeko Ishii, Yoji Morisaki, Takehiro Aoki, Gregory S. Cameron, Olawale O. Osuntokun, the Japanese Ixekizumab Study Group, Toshihide Akasaka, Yoshihide Asano, Takafumi Etoh, Yasuyuki Fujita, Takashi Hashimoto, Mari Higashiyama, Atsuyuki Igarashi, Hironobu Ihn, Keiji Iwatsuki, Kenji Kabashima, Akira Kawada, Makoto Kawashima, Koichiro Nakamura, Yukari Okubo, Ryuhei Okuyama, Akira Ozawa, Koji Sayama, Mariko Seishima, Tetsuo Shiohara, Masakazu Takahara, Hidetoshi Takahashi, Kazuhiko Takehara, Keiji Tanese, Mamori Tani, Yoshinori Umezawa, Hideaki Watanabe, Keiichi Yamanaka

    Journal of Dermatology　44　(4)　355-362　2017/04/01

    Publisher: Blackwell Publishing Ltd

    DOI： 10.1111/1346-8138.13622 　

    ISSN： 1346-8138 0385-2407

  204. Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma Peer-reviewed

    Takehiro Takahashi, Yoshihide Asano, Koji Sugawara, Takashi Yamashita, Kouki Nakamura, Ryosuke Saigusa, Yohei Ichimura, Tetsuo Toyama, Takashi Taniguchi, Kaname Akamata, Shinji Noda, Ayumi Yoshizaki, Daisuke Tsuruta, Maria Trojanowska, Shinichi Sato

    JOURNAL OF EXPERIMENTAL MEDICINE　214　(4)　1129-1151　2017/04

    DOI： 10.1084/jem.20160247 　

    ISSN： 0022-1007

    eISSN： 1540-9538

  205. Serum LL-37 levels correlate with the efficacy of i.v. cyclophosphamide pulse for skin sclerosis and interstitial lung disease in systemic sclerosis Peer-reviewed

    Takehiro Takahashi, Yoshihide Asano, Takashi Taniguchi, Ayumi Yoshizaki, Shinichi Sato

    JOURNAL OF DERMATOLOGY　44　(4)　468-469　2017/04

    DOI： 10.1111/1346-8138.13553 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  206. 脊椎関節炎 生物学的製剤投与中乾癬性関節炎の末梢関節評価におけるDAPSAの有用性の検討

    神田 浩子, 立石 晶子, 大野 久美子, 伊沢 直広, 廣瀬 旬, 吉崎 歩, 浅野 善英, 佐藤 伸一, 田中 栄, 山本 一彦

    日本リウマチ学会総会・学術集会プログラム・抄録集　61回　458-458　2017/03

    Publisher: (一社)日本リウマチ学会

  207. 脊椎関節炎 乾癬性関節炎における仙腸関節炎の重要性の検討

    立石 晶子, 神田 浩子, 大野 久美子, 伊沢 直広, 廣瀬 旬, 吉崎 歩, 浅野 善英, 佐藤 伸一, 田中 栄, 山本 一彦

    日本リウマチ学会総会・学術集会プログラム・抄録集　61回　459-459　2017/03

    Publisher: (一社)日本リウマチ学会

  208. Glycyrrhizin Ameliorates Fibrosis, Vasculopathy, and Inflammation in Animal Models of Systemic Sclerosis Peer-reviewed

    Takashi Yamashita, Yoshihide Asano, Takashi Taniguchi, Kouki Nakamura, Ryosuke Saigusa, Shunsuke Miura, Tetsuo Toyama, Takehiro Takahashi, Yohei Ichimura, Ayumi Yoshizaki, Maria Trojanowska, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　137　(3)　631-640　2017/03

    DOI： 10.1016/j.jid.2016.08.037 　

    ISSN： 0022-202X

    eISSN： 1523-1747

  209. Ethosuximide-induced lupus-scleroderma syndrome with disease-specific autoanti-bodies Peer-reviewed

    Tetsuo Toyama, Yoshihide Asano, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Zenshiro Tamaki, Shinji Kagami, Hiroshi Mitsui, Shinichi Sato

    EUROPEAN JOURNAL OF DERMATOLOGY　27　(2)　196-197　2017/03

    DOI： 10.1684/ejd.2016.2942 　

    ISSN： 1167-1122

    eISSN： 1952-4013

  210. A case of systemic sclerosis with linear scleroderma developing after fracture surgery Peer-reviewed

    Ryosuke Saigusa, Yoshihide Asano, Takashi Yamashita, Hayakazu Sumida, Miki Miyazaki, Shinichi Sato

    EUROPEAN JOURNAL OF DERMATOLOGY　27　(2)　200-201　2017/03

    DOI： 10.1684/ejd.2016.2956 　

    ISSN： 1167-1122

    eISSN： 1952-4013

  211. Frontiers of Antifibrotic Therapy in Systemic Sclerosis Peer-reviewed

    Joerg H. W. Distler, Carol Feghali-Bostwick, Alina Soare, Yoshihide Asano, Oliver Distler, David J. Abraham

    ARTHRITIS & RHEUMATOLOGY　69　(2)　257-267　2017/02

    DOI： 10.1002/art.39865 　

    ISSN： 2326-5191

    eISSN： 2326-5205

  212. Serum angiopoietin-2 level as a potential biomarker in psoriasis vulgaris Peer-reviewed

    Takehiro Takahashi, Yoshihide Asano, Sayaka Shibata, Yayoi Tada, Shinichi Sato

    JOURNAL OF DERMATOLOGY　44　(2)　205-206　2017/02

    DOI： 10.1111/1346-8138.13529 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  213. Safety and tolerability of bosentan for digital ulcers in Japanese patients with systemic sclerosis: Prospective, multicenter, open-label study. International-journal Peer-reviewed

    Yasuhito Hamaguchi, Takayuki Sumida, Yasushi Kawaguchi, Hironobu Ihn, Sumiaki Tanaka, Yoshihide Asano, Sei-Ichiro Motegi, Masataka Kuwana, Hirahito Endo, Kazuhiko Takehara

    The Journal of dermatology　44　(1)　13-17　2017/01

    DOI： 10.1111/1346-8138.13497 　

    ISSN： 0385-2407

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    A multicenter, open-label study was performed to investigate the safety and tolerability of bosentan in Japanese patients with systemic sclerosis (SSc) and secondary digital ulcers. Twenty-eight patients were enrolled. The safety and tolerability of bosentan was monitored over 52 weeks of study treatment (primary end-point), while incidence and healing of digital ulcers were also assessed up to week 16. The following adverse events occurred in 5% or more of patients during the 52-week treatment period: upper respiratory tract infection (50.0%), abnormal liver function tests (42.9%), digital ulcers (25.0%), anemia (17.9%), peripheral edema (14.3%), diarrhea (10.7%), urinary tract infection (7.1%), arthralgia (7.1%), constipation (7.1%) and herpes zoster (7.1%). Eight patients experienced at least one serious adverse event, including drug-related serious adverse events in two patients, which were abnormal liver function tests and fluid retention (pericardial effusion) in one patient each. During the 16-week observation period, seven out of 28 patients (25%) developed new digital ulcers. In this study, adverse events were comparable with those previously reported with bosentan. Approximately half of the patients had adverse events associated with abnormal liver function tests, thus we conclude that liver function should be monitored regularly during treatment with bosentan.

  214. Plasma plasmin-alpha 2-plasmin inhibitor complex levels may predict the effect of cyclophosphamide for systemic sclerosis-related interstitial lung disease Peer-reviewed

    Ryosuke Saigusa, Yoshihide Asano, Kouki Nakamura, Takashi Yamashita, Yohei Ichimura, Takehiro Takahashi, Tetsuo Toyama, Takashi Taniguchi, Ayumi Yoshizaki, Miki Miyazaki, Zenshiro Tamaki, Shinichi Sato

    MODERN RHEUMATOLOGY　27　(4)　618-622　2017

    DOI： 10.1080/14397595.2016.1226472 　

    ISSN： 1439-7595

    eISSN： 1439-7609

  215. Recent advances in the treatment of skin involvement in systemic sclerosis. Peer-reviewed

    Asano Y

    Inflammation and regeneration　37　12　2017

    DOI： 10.1186/s41232-017-0047-4 　

    ISSN： 1880-9693

  216. 全身性硬化症のモデルマウスにおいてFli1欠損γδT細胞はIL-17Aの産生増加を介して組織線維症と脈管障害を増悪化する(Fli1-deficient γδT cells augment tissue fibrosis and vasculopathy in a murine model of systemic sclerosis via increased IL-17A production)

    Saigusa Ryosuke, Asano Yoshihide, Miyagawa Takuya, Hirabayashi Megumi, Nakamura Kouki, Miura Shunsuke, Yamashita Takashi, Ichimura Yohei, Takahashi Takehiro, Toyama Tetsuo, Taniguchi Takashi, Yoshizaki Ayumi, Trojanowska Maria, Sato Shinichi

    日本研究皮膚科学会年次学術大会・総会プログラム　41回　157-157　2016/12

    Publisher: (一社)日本研究皮膚科学会

  217. 新規の全身性硬化症のモデル動物は血管新生の促進と脈管形成障害に起因した創傷治癒の遅延を呈する(A new animal model of systemic sclerosis exhibits delayed wound healing due to accelerated angiogenesis and defective vasculogenesis)

    Nakamura Kouki, Asano Yoshihide, Miyagawa Takuya, Hirabayashi Megumi, Yamashita Takashi, Saigusa Ryosuke, Miura Shunsuke, Toyama Tetsuo, Takahashi Takehiro, Ichimura Yohei, Taniguchi Takashi, Yoshizaki Ayumi, Trojanowska Maria, Sato Shinichi

    日本研究皮膚科学会年次学術大会・総会プログラム　41回　194-194　2016/12

    Publisher: (一社)日本研究皮膚科学会

  218. A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis Peer-reviewed

    T. Takahashi, Y. Asano, K. Nakamura, T. Yamashita, R. Saigusa, Y. Ichimura, T. Toyama, T. Taniguchi, A. Yoshizaki, Z. Tamaki, Y. Tada, M. Sugaya, T. Kadono, S. Sato

    BRITISH JOURNAL OF DERMATOLOGY　175　(6)　1195-1203　2016/12

    DOI： 10.1111/bjd.14699 　

    ISSN： 0007-0963

    eISSN： 1365-2133

  219. Case of disseminated granuloma annulare with giant plaques Peer-reviewed

    Ryosuke Saigusa, Yoshihide Asano, Shinichi Sato

    JOURNAL OF DERMATOLOGY　43　(12)　1443-1444　2016/12

    DOI： 10.1111/1346-8138.13432 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  220. Increased syndecan-4 expression in sera and skin of patients with atopic dermatitis Peer-reviewed

    Momoko Nakao, Makoto Sugaya, Naomi Takahashi, Sayaka Otobe, Rina Nakajima, Tomonori Oka, Miyoko Kabasawa, Hiraku Suga, Sohshi Morimura, Tomomitsu Miyagaki, Hideki Fujita, Yoshihide Asano, Shinichi Sato

    ARCHIVES OF DERMATOLOGICAL RESEARCH　308　(9)　655-660　2016/11

    DOI： 10.1007/s00403-016-1683-2 　

    ISSN： 0340-3696

    eISSN： 1432-069X

  221. Glycyrrhizin ameliorates fibrosis, vasculopathy, and immune abnormalities in animal models of systemic sclerosis

    Takashi Yamashita, Yoshihide Asano, Takashi Taniguchi, Ryosuke Saigusa, Kouki Nakamura, Shunsuke Miura, Tetsuo Toyama, Takehiro Takahashi, Yohei Ichimura, Ayumi Yoshizaki, Maria Trojanowska, Shinichi Sato

    Journal of Dermatological Science　84　(1)　e102-e102　2016/10

    Publisher: Elsevier BV

    DOI： 10.1016/j.jdermsci.2016.08.308 　

    ISSN： 0923-1811

  222. Nucleosome in patients with systemic sclerosis: possible association with immunological abnormalities via abnormal activation of T and B cells Peer-reviewed

    Ayumi Yoshizaki, Takashi Taniguchi, Ryosuke Saigusa, Takemichi Fukasawa, Satoshi Ebata, Hiroko Numajiri, Kouki Nakamura, Takashi Yamashita, Takehiro Takahashi, Tetsuo Toyama, Yoshihide Asano, Thomas F. Tedder, Shinichi Sato

    ANNALS OF THE RHEUMATIC DISEASES　75　(10)　1858-1865　2016/10

    DOI： 10.1136/annrheumdis-2015-207405 　

    ISSN： 0003-4967

    eISSN： 1468-2060

  223. Linear scleroderma with prominent multiple lymphadenopathy followed by the development of polymyositis: A case report and review of published work Peer-reviewed

    Takehiro Takahashi, Yoshihide Asano, Maiko Hirakawa, Kouki Nakamura, Ryosuke Saigusa, Naohiko Aozasa, Hayakazu Sumida, Hideki Fujita, Makoto Sugaya, Aki Ohmori, Jun Shimizu, Shinichi Sato

    JOURNAL OF DERMATOLOGY　43　(10)　1224-1227　2016/10

    DOI： 10.1111/1346-8138.13424 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  224. Is macitentan not a treatment option for digital ulcers in systemic sclerosis? Peer-reviewed

    Yoshihide Asano

    Annals of Translational Medicine　4　(Suppl 1)　S6　2016/10/01

    Publisher: AME Publishing Company

    DOI： 10.21037/atm.2016.08.67 　

    ISSN： 2305-5847 2305-5839

  225. The wound/burn guidelines - 6: Guidelines for the management of burns. International-journal Peer-reviewed

    Yuichiro Yoshino, Mikio Ohtsuka, Masakazu Kawaguchi, Keisuke Sakai, Akira Hashimoto, Masahiro Hayashi, Naoki Madokoro, Yoshihide Asano, Masatoshi Abe, Takayuki Ishii, Taiki Isei, Takaaki Ito, Yuji Inoue, Shinichi Imafuku, Ryokichi Irisawa, Masaki Ohtsuka, Fumihide Ogawa, Takafumi Kadono, Tamihiro Kawakami, Ryuichi Kukino, Takeshi Kono, Masanari Kodera, Masakazu Takahara, Miki Tanioka, Takeshi Nakanishi, Yasuhiro Nakamura, Minoru Hasegawa, Manabu Fujimoto, Hiroshi Fujiwara, Takeo Maekawa, Koma Matsuo, Osamu Yamasaki, Andres Le Pavoux, Takao Tachibana, Hironobu Ihn

    The Journal of dermatology　43　(9)　989-1010　2016/09

    DOI： 10.1111/1346-8138.13288 　

    ISSN： 0385-2407

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    Burns are a common type of skin injury encountered at all levels of medical facilities from private clinics to core hospitals. Minor burns heal by topical treatment alone, but moderate to severe burns require systemic management, and skin grafting is often necessary also for topical treatment. Inappropriate initial treatment or delay of initial treatment may exert adverse effects on the subsequent treatment and course. Therefore, accurate evaluation of the severity and initiation of appropriate treatment are necessary. The Guidelines for the Management of Burn Injuries were issued in March 2009 from the Japanese Society for Burn Injuries as guidelines concerning burns, but they were focused on the treatment for extensive and severe burns in the acute period. Therefore, we prepared guidelines intended to support the appropriate diagnosis and initial treatment for patients with burns that are commonly encountered including minor as well as moderate and severe cases. Because of this intention of the present guidelines, there is no recommendation of individual surgical procedures.

  226. Serum levels of interleukin-18-binding protein isoform a: Clinical association with inflammation and pulmonary hypertension in systemic sclerosis Peer-reviewed

    Kouki Nakamura, Yoshihide Asano, Takashi Taniguchi, Shun Minatsuki, Toshiro Inaba, Hisataka Maki, Masaru Hatano, Takashi Yamashita, Ryosuke Saigusa, Yohei Ichimura, Takehiro Takahashi, Tetsuo Toyama, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato

    JOURNAL OF DERMATOLOGY　43　(8)　912-918　2016/08

    DOI： 10.1111/1346-8138.13252 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  227. The wound/burn guidelines - 5: Guidelines for the management of lower leg ulcers/varicose veins. International-journal Peer-reviewed

    Takaaki Ito, Ryuichi Kukino, Masakazu Takahara, Miki Tanioka, Yasuhiro Nakamura, Yoshihide Asano, Masatoshi Abe, Takayuki Ishii, Taiki Isei, Yuji Inoue, Shinichi Imafuku, Ryokichi Irisawa, Masaki Ohtsuka, Mikio Ohtsuka, Fumihide Ogawa, Takafumi Kadono, Tamihiro Kawakami, Masakazu Kawaguchi, Takeshi Kono, Masanari Kodera, Keisuke Sakai, Takeshi Nakanishi, Akira Hashimoto, Minoru Hasegawa, Masahiro Hayashi, Manabu Fujimoto, Hiroshi Fujiwara, Takeo Maekawa, Koma Matsuo, Naoki Madokoro, Osamu Yamasaki, Yuichiro Yoshino, Andres Le Pavoux, Takao Tachibana, Hironobu Ihn

    The Journal of dermatology　43　(8)　853-68　2016/08

    DOI： 10.1111/1346-8138.13286 　

    ISSN： 0385-2407

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    Varicose veins are treated at multiple clinical departments, but as patients often visit the dermatology clinic first due to leg ulcers, the present Guidelines for the Management of Lower Leg Ulcers/Varicose Veins were prepared in consideration of the importance of the dermatologist's role. Also, the disease concept of chronic venous insufficiency or chronic venous disorders and the CEAP classification of these disorders are presented. The objective of the present guidelines is to properly guide the diagnosis and treatment of lower leg ulcers/varicose veins by systematically presenting evidence-based recommendations that support clinical decisions.

  228. Decreased interleukin-21 expression in skin and blood in advanced mycosis fungoides Peer-reviewed

    Miyoko Kabasawa, Makoto Sugaya, Tomonori Oka, Naomi Takahashi, Makiko Kawaguchi, Hiraku Suga, Tomomitsu Miyagaki, Takehiro Takahashi, Sayaka Shibata, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Hitoshi Okochi, Shinichi Sato

    JOURNAL OF DERMATOLOGY　43　(7)　819-822　2016/07

    DOI： 10.1111/1346-8138.13278 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  229. Association of anti-RNA polymerase III antibody and silicone breast implants in patients with systemic sclerosis Peer-reviewed

    Ryosuke Saigusa, Yoshihide Asano, Kouki Nakamura, Takashi Yamashita, Yohei Ichimura, Takehiro Takahashi, Tetsuo Toyama, Takashi Taniguchi, Ayumi Yoshizaki, Miki Miyazaki, Zenshiro Tamaki, Shinichi Sato

    JOURNAL OF DERMATOLOGY　43　(7)　808-810　2016/07

    DOI： 10.1111/1346-8138.13292 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  230. The wound/burn guidelines - 4: Guidelines for the management of skin ulcers associated with connective tissue disease/vasculitis. International-journal Peer-reviewed

    Manabu Fujimoto, Yoshihide Asano, Takayuki Ishii, Fumihide Ogawa, Tamihiro Kawakami, Masanari Kodera, Masatoshi Abe, Taiki Isei, Takaaki Ito, Yuji Inoue, Shinichi Imafuku, Ryokichi Irisawa, Masaki Ohtsuka, Mikio Ohtsuka, Takafumi Kadono, Masakazu Kawaguchi, Ryuichi Kukino, Takeshi Kono, Keisuke Sakai, Masakazu Takahara, Miki Tanioka, Takeshi Nakanishi, Yasuhiro Nakamura, Akira Hashimoto, Minoru Hasegawa, Masahiro Hayashi, Hiroshi Fujiwara, Takeo Maekawa, Koma Matsuo, Naoki Madokoro, Osamu Yamasaki, Yuichiro Yoshino, Andres Le Pavoux, Takao Tachibana, Hironobu Ihn

    The Journal of dermatology　43　(7)　729-57　2016/07

    DOI： 10.1111/1346-8138.13275 　

    ISSN： 0385-2407

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    The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.

  231. The development of chronic inflammatory demyelinating polyneuropathy during adalimumab treatment in a patient with psoriasis vulgaris Peer-reviewed

    Momoko Nakao, Yoshihide Asano, Kouki Nakamura, Rino Shida, Takehiro Takahashi, Ayumi Yoshizaki, Aya Mitsui, Sayaka Shibata, Mayuko Araki, Rei Watanabe, Yuko Ikawa, Chizuko Toyoda, Hisayoshi Oka, Shinichi Sato

    European Journal of Dermatology　26　(4)　404-405　2016/07/01

    Publisher: John Libbey Eurotext

    DOI： 10.1684/ejd.2016.2781 　

    ISSN： 1952-4013 1167-1122

  232. Circulating galectin-1 concentrations in systemic sclerosis: potential contribution to digital vasculopathy Peer-reviewed

    Koichi Yanaba, Yoshihide Asano, Kaname Akamata, Shinji Noda, Naohiko Aozasa, Takashi Taniguchi, Takehiro Takahashi, Tetsuo Toyama, Yohei Ichimura, Hayakazu Sumida, Yoshihiro Kuwano, Miki Miyazaki, Shinichi Sato

    INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES　19　(6)　622-627　2016/06

    DOI： 10.1111/1756-185X.12288 　

    ISSN： 1756-1841

    eISSN： 1756-185X

  233. Monosodium Urate Crystals Induce Functional Expression of P2Y(14) Receptor in Human Keratinocytes Peer-reviewed

    Hideya Uratsuji, Yayoi Tada, Carren Sy Hau, Sayaka Shibata, Masahiro Kamata, Tomohiko Kawashima, Yoshihide Asano, Makoto Sugaya, Takafumi Kadono, Akihiko Asahina, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　136　(6)　1293-1296　2016/06

    DOI： 10.1016/j.jid.2016.01.026 　

    ISSN： 0022-202X

    eISSN： 1523-1747

  234. The wound/burn guidelines - 3: Guidelines for the diagnosis and treatment for diabetic ulcer/gangrene. International-journal Peer-reviewed

    Taiki Isei, Masatoshi Abe, Takeshi Nakanishi, Koma Matsuo, Osamu Yamasaki, Yoshihide Asano, Takayuki Ishii, Takaaki Ito, Yuji Inoue, Shinichi Imafuku, Ryokichi Irisawa, Masaki Ohtsuka, Mikio Ohtsuka, Fumihide Ogawa, Takafumi Kadono, Masanari Kodera, Tamihiro Kawakami, Masakazu Kawaguchi, Ryuichi Kukino, Takeshi Kono, Keisuke Sakai, Masakazu Takahara, Miki Tanioka, Yasuhiro Nakamura, Akira Hashimoto, Minoru Hasegawa, Masahiro Hayashi, Manabu Fujimoto, Hiroshi Fujiwara, Takeo Maekawa, Naoki Madokoro, Yuichiro Yoshino, Andres Le Pavoux, Takao Tachibana, Hironobu Ihn

    The Journal of dermatology　43　(6)　591-619　2016/06

    DOI： 10.1111/1346-8138.13285 　

    ISSN： 0385-2407

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    We aimed to prepare guidelines for the management of diabetic ulcer/gangrene with emphasis on the diagnosis and treatment of skin symptoms. They serve as a tool to improve the quality of the diagnosis and treatment in each patient and, further, to improve the level of the care for diabetic ulcer in Japan by systematically presenting evidence-based recommendations for clinical judgments by incorporating various viewpoints.

  235. 437 αE integrin contributes to the pathological dermal fibrosis in a bleomycin-treated murine model of systemic sclerosis via the activation of retinoic acid pathway

    S. Miura, Y. Asano, R. Saigusa, T. Yamashita, T. Taniguchi, T. Takahashi, Y. Ichimura, T. Toyama, A. Yoshizaki, T. Kadono, S. Sato

    Journal of Investigative Dermatology　136　(5)　S77-S77　2016/05

    Publisher: Elsevier BV

    DOI： 10.1016/j.jid.2016.02.472 　

    ISSN： 0022-202X

  236. 皮膚科医が行うべき膠原病・血管炎による皮膚潰瘍のケアについて学ぼう

    浅井 純, 浅野 善英, 石井 貴之, 岩田 洋平, 川上 民裕, 小寺 雅也, 藤本 学

    日本皮膚科学会雑誌　126　(5)　769-769　2016/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  237. The first case report of fatal acute pulmonary dysfunction in a systemic sclerosis patient treated with rituximab. Peer-reviewed

    Nakamura K, Yoshizaki A, Takahashi T, Saigusa R, Taniguchi T, Asano Y, Gonoi W, Hinata M, Shinozaki-Ushiku A, Sato S, Scandinavian journal of rheumatology

    Scand J Rheumatol　45　(3)　249-250　2016/05

    DOI： 10.3109/03009742.2015.1102963 　

    More details Close

    Nakamura K, Yoshizaki A, Takahashi T, Saigusa R, Taniguchi T, Asano Y, Gonoi W, Hinata M, Shinozaki-Ushiku A, Sato S, Scandinavian journal of rheumatology, 2016, vol. 45, no. 3, pp. 249-250

  238. The wound/burn guidelines - 2: Guidelines for the diagnosis and treatment for pressure ulcers. International-journal Peer-reviewed

    Takao Tachibana, Shinichi Imafuku, Ryokichi Irisawa, Masaki Ohtsuka, Takafumi Kadono, Hiroshi Fujiwara, Yoshihide Asano, Masatoshi Abe, Takayuki Ishii, Taiki Isei, Takaaki Ito, Yuji Inoue, Mikio Ohtsuka, Fumihide Ogawa, Masanari Kodera, Tamihiro Kawakami, Masakazu Kawaguchi, Ryuichi Kukino, Takeshi Kono, Keisuke Sakai, Masakazu Takahara, Miki Tanioka, Takeshi Nakanishi, Yasuhiro Nakamura, Akira Hashimoto, Minoru Hasegawa, Masahiro Hayashi, Manabu Fujimoto, Takeo Maekawa, Koma Matsuo, Naoki Madokoro, Osamu Yamasaki, Yuichiro Yoshino, Andres Le Pavoux, Hironobu Ihn

    The Journal of dermatology　43　(5)　469-506　2016/05

    DOI： 10.1111/1346-8138.13274 　

    ISSN： 0385-2407

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    The Wound/Burn Guidelines Committee consists of members commissioned by the Board of Directors of the Japanese Dermatological Association (JDA). It held several meetings and evaluations in writing since October 2008, and drafted five guidelines for the diagnosis and treatment including commentaries on wounds in general and the Guidelines for the Diagnosis and Treatment for Pressure Ulcers by taking opinions of the Scientific Committee and Board of Directors of JDA into consideration.

  239. A potential contribution of altered cathepsin L expression to the development of dermal fibrosis and vasculopathy in systemic sclerosis Peer-reviewed

    Takashi Yamashita, Yoshihide Asano, Takashi Taniguchi, Kouki Nakamura, Ryosuke Saigusa, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato

    EXPERIMENTAL DERMATOLOGY　25　(4)　287-292　2016/04

    DOI： 10.1111/exd.12920 　

    ISSN： 0906-6705

    eISSN： 1600-0625

  240. The wound/burn guidelines - 1: Wounds in general. International-journal Peer-reviewed

    Yuji Inoue, Minoru Hasegawa, Takeo Maekawa, Andres Le Pavoux, Yoshihide Asano, Masatoshi Abe, Takayuki Ishii, Takaaki Ito, Taiki Isei, Shinichi Imafuku, Ryokichi Irisawa, Masaki Ohtsuka, Mikio Ohtsuka, Fumihide Ogawa, Takafumi Kadono, Masanari Kodera, Tamihiro Kawakami, Masakazu Kawaguchi, Ryuichi Kukino, Takeshi Kono, Keisuke Sakai, Masakazu Takahara, Miki Tanioka, Takeshi Nakanishi, Yasuhiro Nakamura, Akira Hashimoto, Masahiro Hayashi, Manabu Fujimoto, Hiroshi Fujiwara, Koma Matsuo, Naoki Madokoro, Osamu Yamasaki, Yuichiro Yoshino, Takao Tachibana, Hironobu Ihn

    The Journal of dermatology　43　(4)　357-75　2016/04

    DOI： 10.1111/1346-8138.13276 　

    ISSN： 0385-2407

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    The Japanese Dermatological Association determined to prepare the Wound/Burn Guidelines focusing on treatments, catering to needs for the clinical practice of dermatology. Among these guidelines, "Wounds in General" was intended to explain knowledge necessary "to heal wounds" without specifying particular disorders.

  241. その他の膠原病 乾癬性関節炎患者の体軸病変についての評価

    立石 晶子, 神田 浩子, 大野 久美子, 吉崎 歩, 浅野 善英, 門野 夕峰, 佐藤 伸一, 田中 栄, 山本 一彦

    日本リウマチ学会総会・学術集会プログラム・抄録集　60回　406-406　2016/03

    Publisher: (一社)日本リウマチ学会

  242. Serum IL-33 levels are increased in patients with psoriasis. International-journal Peer-reviewed

    Mitsui A, Tada Y, Takahashi T, Shibata S, Kamata M, Miyagaki T, Fujita H, Sugaya M, Kadono T, Sato S, Asano Y

    Clinical and experimental dermatology　41　(2)　183-189　2016/03

    DOI： 10.1111/ced.12670 　

    ISSN： 0307-6938

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    BACKGROUND: Interleukin (IL)-33 is a recently identified cytokine, which is a member of the IL-1 family and binds to a heterodimeric receptor comprising ST2 (suppression of tumorigenicity 2) and IL-1 receptor accessory protein. Serum levels of IL-33 have been reported to be upregulated in various T helper (Th)1/Th17-mediated diseases, such as rheumatoid arthritis and inflammatory bowel disease. IL-33 expression is increased in lesional skin in patients with psoriasis, but serum levels in patients with psoriasis have not yet been studied. AIM: To study serum IL-33 levels in patients with psoriasis, a Th1/Th17-mediated skin disease, before and after anti-tumour necrosis factor (TNF)-α therapy. METHODS: Serum IL-33 levels were measured in patients with psoriasis vulgaris (PV), psoriatic arthritis (PsA) or pustular psoriasis (PP), and compared with those of healthy controls. Associations between serum IL-33 levels and serum TNF-α, IL-6, vascular endothelial growth factor and C-reactive protein levels were also studied. In addition, the effect of IL-33 stimulation on IL-6, IL-8, TNF-α and VEGF secretion by human keratinocyte was analysed. RESULTS: Serum IL-33 levels in patients with PV, PsA and PP were significantly higher than those in healthy controls. Serum IL-33 levels correlated with serum TNF-α levels in patients with psoriasis, and decreased after anti-TNF-α therapy. IL-33 stimulated IL-6 and IL-8 secretion by human keratinocytes. CONCLUSIONS: These results suggest that serum IL-33 levels generally reflect increased inflammation in patients with psoriasis.

  243. Fli1 deficiency contributes to the downregulation of endothelial protein C receptor in systemic sclerosis: a possible role in prothrombotic conditions Peer-reviewed

    R. Saigusa, Y. Asano, T. Yamashita, T. Taniguchi, T. Takahashi, Y. Ichimura, T. Toyama, A. Yoshizaki, T. Miyagaki, M. Sugaya, S. Sato

    BRITISH JOURNAL OF DERMATOLOGY　174　(2)　338-347　2016/02

    DOI： 10.1111/bjd.14183 　

    ISSN： 0007-0963

    eISSN： 1365-2133

  244. Scleroderma en coup de sabre with recurrent episodes of brain hemorrhage Peer-reviewed

    Takehiro Takahashi, Yoshihide Asano, Tomonori Oka, Tomomitsu Miyagaki, Zenshiro Tamaki, Senshu Nonaka, Shinichi Sato

    JOURNAL OF DERMATOLOGY　43　(2)　203-206　2016/02

    DOI： 10.1111/1346-8138.13023 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  245. Tamibarotene Ameliorates Bleomycin-Induced Dermal Fibrosis by Modulating Phenotypes of Fibroblasts, Endothelial Cells, and Immune Cells Peer-reviewed

    Tetsuo Toyama, Yoshihide Asano, Kaname Akamata, Shinji Noda, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Koichi Shudo, Shinichi Sato, Takafumi Kadono

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　136　(2)　387-398　2016/02

    DOI： 10.1016/j.jid.2015.10.058 　

    ISSN： 0022-202X

    eISSN： 1523-1747

  246. P1-14 強皮症血管障害モデルマウスの創傷治癒異常に対してボセンタンとbFGFが及ぼす影響についての検討

    山下 尚志, 浅野 善英, 赤股 要, 宮川 卓也, 平林 恵, 中村 洸樹, 三浦 俊介, 三枝 良輔, 市村 洋平, 高橋 岳浩, 遠山 哲夫, 谷口 隆志, 吉崎 歩, Trojanowska Maria, 佐藤 伸一

    日本臨床免疫学会会誌　39　(4)　381b-381b　2016

    Publisher: 日本臨床免疫学会

    DOI： 10.2177/jsci.39.381b 　

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    <p>  全身性強皮症は免疫異常，血管障害，線維化を主要3病態とする原因不明の膠原病である．本症の病態理解・治療開発が遅れている理由の一つとして，その病態を忠実に再現した動物モデルが存在しなかったことが挙げられるが，最近我々は転写因子Fli1の恒常的発現低下により線維芽細胞，血管内皮細胞，マクロファージにおいて強皮症特有の形質が誘導できることを示し，さらに血管内皮細胞特異的Fli1欠失（Fli1 ECKO）マウスでは強皮症の血管障害に特徴的な血管の構造異常と機能異常が再現できることを明らかにした．強皮症の血管障害に対しては肺動脈性肺高血圧症治療薬が有用であり，特にボセンタン（エンドセリン受容体拮抗薬）は皮膚潰瘍の新規発症を予防する効果が2つの良質な臨床試験により証明されている．また，明確なエビデンスはないが，bFGF製剤は強皮症に伴う難治性皮膚潰瘍の治療に有用であり，実臨床において広く使用されている．しかしながら，これらの薬剤が強皮症の血管障害に及ぼす影響とその分子メカニズムは未だ不明な点が多い．そこで今回我々は，Fli1 ECKOマウスの創傷治癒異常の分子メカニズム，およびボセンタンとbFGFがその異常に及ぼす影響について検討した．一連の研究結果により，Fli1 ECKOマウスにおける創傷治癒異常の分子メカニズム，およびボセンタンとbFGFがFli1欠失血管内皮細胞の動態に及ぼす影響が明らかとなったので，その詳細を報告する．</p>

  247. P2-15 ブレオマイシン誘発皮膚線維化モデルにおけるCD103陰性真皮樹状細胞の役割

    三浦 俊介, 浅野 善英, 三枝 良輔, 山下 尚志, 谷口 隆志, 高橋 岳浩, 市村 洋平, 遠山 哲夫, 吉崎 歩, 門野 岳史, 佐藤 伸一

    日本臨床免疫学会会誌　39　(4)　411a-411a　2016

    Publisher: 日本臨床免疫学会

    DOI： 10.2177/jsci.39.411a 　

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    <p>  皮膚線維化は，全身性強皮症やGVHDなどの様々な全身性疾患に生じる重要な病態である．現在有効な治療法はないが，ステロイドや免疫抑制薬が一定の治療効果を示すことから免疫異常の関与が示唆されている．過去に皮膚線維化の病態におけるT細胞，B細胞，マクロファージの役割に関する検討は行われているが，樹状細胞の役割についてはいまだ不明な点が多い．そこで，樹状細胞の機能を制御する鍵分子であるCD103に注目し，CD103−/−マウスを用いてブレオマイシン（BLM）誘発皮膚線維化モデルを作成し，皮膚線維化の病態における樹状細胞の役割について検討した．BLM投与4週間後において，CD103−/−マウスでは野生型マウスに比較して皮膚の線維化が有意に抑制された．また，CD103−/−マウスの病変部皮膚におけるI型コラーゲン，TGF-β1，CTGFの発現量は有意に低下し，MMP-13の発現量は有意に亢進していた．一方，BLM投与1週間後では，CD103−/−マウスの病変部皮膚の真皮において制御性T細胞の割合が増加し，Th1細胞，Th2細胞，Th17細胞の割合が減少していた．さらに，CD103−/−マウスではCD103−CD11b−真皮樹状細胞の割合が増加し，同細胞におけるALDH1A1（レチノイン酸産生を制御する酵素）産生とALDH活性が亢進していた．以上より，皮膚線維化の過程においてCD103−CD11b−真皮樹状細胞はレチノイン酸を介して制御性T細胞を誘導し，線維化を抑制している可能性が示唆された．</p>

  248. Collagen vascular disease Peer-reviewed

    Yoshihide Asano

    Immunology of the Skin: Basic and Clinical Sciences in Skin Immune Responses　489-501　2016/01/01

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-55855-2_31 　

  249. Overview of animal models Peer-reviewed

    Yoshihide Asano, Jörg H.W. Distler

    Scleroderma: From Pathogenesis to Comprehensive Management　281-293　2016/01/01

    Publisher: Springer International Publishing

    DOI： 10.1007/978-3-319-31407-5_19 　

  250. Fli1 Peer-reviewed

    Yoshihide Asano

    Systemic Sclerosis　187-209　2016/01/01

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-55708-1_12 　

  251. 全身性強皮症 診断基準・重症度分類・診療ガイドライン

    全身性強皮症, 診断基準, 重症度分類, 診療ガイドライン委員会, 浅野, 善英, 神人, 正寿, 川口, 鎮司, 桑名, 正隆, 後藤, 大輔, 佐藤, 伸一, 竹原, 和彦, 波多野, 将, 藤本, 学, 麦井, 直樹, 尹, 浩信

    The Japanese Journal of Dermatology　126　(10)　1831-1896　2016

    Publisher: Japanese Dermatological Association

    ISSN： 1346-8146

  252. A case of scleredema adultorum successfully treated with narrow-band ultraviolet B phototherapy Peer-reviewed

    Junko Yoshimura, Yoshihide Asano, Takehiro Takahashi, Yuta Uwajima, Shinji Kagami, Hiromi Honda, Takeo Idezuki, Atsuyuki Igarashi, Shinichi Sato

    MODERN RHEUMATOLOGY　26　(2)　302-306　2016

    DOI： 10.3109/14397595.2013.875640 　

    ISSN： 1439-7595

    eISSN： 1439-7609

  253. Effect of ambrisentan on peripheral circulation in patients with systemic sclerosis Peer-reviewed

    Hayakazu Sumida, Yoshihide Asano, Masaru Hatano, Naohiko Aozasa, Tetsuo Toyama, Kaname Akamata, Miki Miyazaki, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Shinji Noda, Yoshihiro Kuwano, Koichi Yanaba, Shinichi Sato

    MODERN RHEUMATOLOGY　26　(3)　454-457　2016

    DOI： 10.3109/14397595.2014.885377 　

    ISSN： 1439-7595

    eISSN： 1439-7609

  254. Serum level of circulating syndecan-1: A possible association with proliferative vasculopathy in systemic sclerosis Peer-reviewed

    Ching-Ying Wu, Yoshihide Asano, Takashi Taniguchi, Shinichi Sato, Hsin-Su Yu

    JOURNAL OF DERMATOLOGY　43　(1)　63-66　2016/01

    DOI： 10.1111/1346-8138.12986 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  255. Recent advances in animal models of systemic sclerosis Peer-reviewed

    Yoshihide Asano

    JOURNAL OF DERMATOLOGY　43　(1)　19-28　2016/01

    DOI： 10.1111/1346-8138.13185 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  256. Progranulin Overproduction Due to Fli-1 Deficiency Contributes to the Resistance of Dermal Fibroblasts to Tumor Necrosis Factor in Systemic Sclerosis Peer-reviewed

    Yohei Ichimura, Yoshihide Asano, Kaname Akamata, Shinji Noda, Takashi Taniguchi, Takehiro Takahashi, Tetsuo Toyama, Yayoi Tada, Makoto Sugaya, Shinichi Sato, Takafumi Kadono

    ARTHRITIS & RHEUMATOLOGY　67　(12)　3245-3255　2015/12

    DOI： 10.1002/art.39312 　

    ISSN： 2326-5191

    eISSN： 2326-5205

  257. Multifaceted contribution of the TLR4-activated IRF5 transcription factor in systemic sclerosis Peer-reviewed

    Ryosuke Saigusa, Yoshihide Asano, Takashi Taniguchi, Takashi Yamashita, Yohei Ichimura, Takehiro Takahashi, Tetsuo Toyama, Ayumi Yoshizaki, Koji Sugawara, Daisuke Tsuruta, Tadatsugu Taniguchi, Shinichi Sato

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　112　(49)　15136-15141　2015/12

    DOI： 10.1073/pnas.1520997112 　

    ISSN： 0027-8424

  258. 全身性硬化症の発症に対するB細胞におけるFli1の欠損の影響(The impact of Fli1 deficiency in B cells on the development of systemic sclerosis)

    Saigusa Ryosuke, Asano Yoshihide, Nakamura Kouki, Miura Shunsuke, Yamashita Takashi, Ichimura Yohei, Takahashi Takehiro, Toyama Tetsuo, Taniguchi Takashi, Yoshizaki Ayumi, Trojanowska Maria, Sato Shinichi

    日本研究皮膚科学会年次学術大会・総会プログラム　40回　139-139　2015/11

    Publisher: (一社)日本研究皮膚科学会

  259. Epigenetic suppression of Fli1, a potential predisposing factor in the pathogenesis of systemic sclerosis Peer-reviewed

    Yoshihide Asano

    INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY　67　86-91　2015/10

    DOI： 10.1016/j.biocel.2015.06.004 　

    ISSN： 1357-2725

    eISSN： 1878-5875

  260. Case of psoriasis vulgaris developing ulcerative colitis during adalimumab treatment Peer-reviewed

    Kouki Nakamura, Yoshihide Asano, Sayaka Shibata, Momoko Nakao, Rino Shida, Takehiro Takahashi, Aya Mitsui, Mayuko Araki, Atsuo Yamada, Shinichi Sato

    JOURNAL OF DERMATOLOGY　42　(10)　1029-1030　2015/10

    DOI： 10.1111/1346-8138.12996 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  261. A possible contribution of lipocalin-2 to the development of dermal fibrosis, pulmonary vascular involvement and renal dysfunction in systemic sclerosis Peer-reviewed

    T. Takahashi, Y. Asano, S. Noda, N. Aozasa, K. Akamata, T. Taniguchi, Y. Ichimura, T. Toyama, H. Sumida, Y. Kuwano, Y. Tada, M. Sugaya, T. Kadono, S. Sato

    BRITISH JOURNAL OF DERMATOLOGY　173　(3)　681-689　2015/09

    DOI： 10.1111/bjd.13779 　

    ISSN： 0007-0963

    eISSN： 1365-2133

  262. Double heterozygous mice for Klf5 and Fli1 genes: a new animal model of systemic sclerosis recapitulating its three cardinal pathological features Peer-reviewed

    Yoshihide Asano

    MEDICAL MOLECULAR MORPHOLOGY　48　(3)　123-128　2015/09

    DOI： 10.1007/s00795-015-0107-2 　

    ISSN： 1860-1480

    eISSN： 1860-1499

  263. Vasculopathy in scleroderma Peer-reviewed

    Yoshihide Asano, Shinichi Sato

    SEMINARS IN IMMUNOPATHOLOGY　37　(5)　489-500　2015/09

    DOI： 10.1007/s00281-015-0505-5 　

    ISSN： 1863-2297

    eISSN： 1863-2300

  264. Increased expression of chemerin in endothelial cells due to Fli1 deficiency may contribute to the development of digital ulcers in systemic sclerosis Peer-reviewed

    Kaname Akamata, Yoshihide Asano, Takashi Taniguchi, Takashi Yamashita, Ryosuke Saigusa, Kouki Nakamura, Shinji Noda, Naohiko Aozasa, Tetsuo Toyama, Takehiro Takahashi, Yohei Ichimura, Hayakazu Sumida, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    RHEUMATOLOGY　54　(7)　1308-1316　2015/07

    DOI： 10.1093/rheumatology/keu479 　

    ISSN： 1462-0324

    eISSN： 1462-0332

  265. Elevated serum galectin-9 levels in patients with atopic dermatitis Peer-reviewed

    Rina Nakajima, Tomomitsu Miyagaki, Tomonori Oka, Momoko Nakao, Makiko Kawaguchi, Hiraku Suga, Sohshi Morimura, Hiromichi Kai, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato, Makoto Sugaya

    JOURNAL OF DERMATOLOGY　42　(7)　723-726　2015/07

    DOI： 10.1111/1346-8138.12884 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  266. Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from gamma delta-T cells Peer-reviewed

    Sayaka Shibata, Yayoi Tada, Carren Sy Hau, Aya Mitsui, Masahiro Kamata, Yoshihide Asano, Makoto Sugaya, Takafumi Kadono, Yosuke Masamoto, Mineo Kurokawa, Toshimasa Yamauchi, Naoto Kubota, Takashi Kadowaki, Shinichi Sato

    NATURE COMMUNICATIONS　6　7687　2015/07

    DOI： 10.1038/ncomms8687 　

    ISSN： 2041-1723

  267. Serum heparanase levels: A protective marker against digital ulcers in patients with systemic sclerosis Peer-reviewed

    Ching-Ying Wu, Yoshihide Asano, Takashi Taniguchi, Shinichi Sato, Hsin-Su Yu

    JOURNAL OF DERMATOLOGY　42　(6)　625-628　2015/06

    DOI： 10.1111/1346-8138.12842 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  268. Endothelin Receptor Blockade Ameliorates Vascular Fragility in Endothelial Cell-Specific Fli-1-Knockout Mice by Increasing Fli-1 DNA Binding Ability Peer-reviewed

    Kaname Akamata, Yoshihide Asano, Takashi Yamashita, Shinji Noda, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Maria Trojanowska, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　67　(5)　1335-1344　2015/05

    DOI： 10.1002/art.39062 　

    ISSN： 2326-5191

    eISSN： 2326-5205

  269. Serum vaspin levels: A possible correlation with digital ulcers in patients with systemic sclerosis Peer-reviewed

    Shunsuke Miura, Yoshihide Asano, Ryosuke Saigusa, Takashi Yamashita, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Zenshiro Tamaki, Yayoi Tada, Makoto Sugaya, Shinichi Sato, Takafumi Kadono

    JOURNAL OF DERMATOLOGY　42　(5)　528-531　2015/05

    DOI： 10.1111/1346-8138.12810 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  270. Association of anti-RNA polymerase III antibody and malignancy in Japanese patients with systemic sclerosis Peer-reviewed

    Ryosuke Saigusa, Yoshihide Asano, Kouki Nakamura, Shunsuke Miura, Yohei Ichimura, Takehiro Takahashi, Tetsuo Toyama, Takashi Taniguchi, Shinji Noda, Naohiko Aozasa, Kaname Akamata, Hayakazu Sumida, Miki Miyazaki, Zenshiro Tamaki, Koichi Yanaba, Yoshihiro Kuwano, Shinichi Sato

    JOURNAL OF DERMATOLOGY　42　(5)　524-527　2015/05

    DOI： 10.1111/1346-8138.12827 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  271. Serum omentin levels: A possible contribution to vascular involvement in patients with systemic sclerosis Peer-reviewed

    Shunsuke Miura, Yoshihide Asano, Ryosuke Saigusa, Takashi Yamashita, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Zenshiro Tamaki, Yayoi Tada, Makoto Sugaya, Shinichi Sato, Takafumi Kadono

    JOURNAL OF DERMATOLOGY　42　(5)　461-466　2015/05

    DOI： 10.1111/1346-8138.12824 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  272. 膠原病・血管炎に伴う皮膚潰瘍診療ガイドライン

    小寺 雅也, 浅井 純, 浅野 善英, 石井 貴之, 岩田 洋平, 川上 民裕, 藤本 学

    日本皮膚科学会雑誌　125　(4)　763-763　2015/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  273. Fibrosis, Vascular Activation, and Immune Abnormalities Resembling Systemic Sclerosis in Bleomycin-Treated Fli-1-Haploinsufficient Mice Peer-reviewed

    Takashi Taniguchi, Yoshihide Asano, Kaname Akamata, Shinji Noda, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Maria Trojanowska, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　67　(2)　517-526　2015/02

    DOI： 10.1002/art.38948 　

    ISSN： 2326-5191

    eISSN： 2326-5205

  274. A possible contribution of endothelial CCN1 downregulation due to Fli1 deficiency to the development of digital ulcers in systemic sclerosis Peer-reviewed

    Ryosuke Saigusa, Yoshihide Asano, Takashi Taniguchi, Takashi Yamashita, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Zenshiro Tamaki, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    EXPERIMENTAL DERMATOLOGY　24　(2)　127-132　2015/02

    DOI： 10.1111/exd.12602 　

    ISSN： 0906-6705

    eISSN： 1600-0625

  275. P4-007 骨髄系細胞におけるFli1の恒常的発現低下が血管の恒常性に及ぼす影響についての検討

    谷口 隆志, 浅野 善英, 赤股 要, 野田 真史, 高橋 岳浩, 市村 洋平, 遠山 哲夫, 三枝 良輔, 吉崎 歩, Trojanowska Maria, 佐藤 伸一

    日本臨床免疫学会会誌　38　(4)　332a-332a　2015

    Publisher: The Japan Society for Clinical Immunology

    DOI： 10.2177/jsci.38.332a 　

    ISSN： 0911-4300

    More details Close

    全身性強皮症（SSc）は血管障害と線維化を特徴とする原因不明の自己免疫疾患である．SScにおける血管障害には血管の恒常性の破綻が深く関与しており，血管内皮細胞の恒常的活性化による血管新生の異常活性化とともに，骨髄系細胞の異常による脈管形成の障害がみられることがその病態として知られている．SScでは病変部皮膚における様々な細胞において転写因子Fli1の発現が恒常的に低下しており，Fli1の恒常的発現低下は疾病素因として本症の病態に深く関与している．我々はこれまでに血管内皮細胞におけるFli1の恒常的発現低下が血管新生の異常活性化を引き起こし，SScにおける血管の恒常性の破綻や血管障害を再現することを明らかにしてきたが，骨髄系細胞におけるFli1の発現低下が血管の恒常性に及ぼす影響については未だ明らかではない．そこで今回我々は，骨髄系細胞におけるFli1の恒常的発現低下が血管の恒常性に及ぼす影響を明らかにするため，骨髄系細胞特異的Fli1欠失マウス（LysM-Cre+/−Fli1flox/flox）を作成しその表現型を検討した．その結果，骨髄系細胞におけるFli1の恒常的発現低下は脈管形成の異常や血管の恒常性の破綻をもたらし，増殖性血管障害・破壊性血管障害といったSScに類似した血管障害を引き起こすことが明らかになった．以上より，SScにおける血管の恒常性の破綻，血管障害の病態に骨髄系細胞におけるFli1の恒常的発現低下が関与している可能性が示唆された．

  276. P3-002 全身性強皮症患者における抗Fcγ受容体抗体価についての検討

    門野 岳史, 冨田 学, 浅野 善英, 佐藤 伸一

    日本臨床免疫学会会誌　38　(4)　324b-324b　2015

    Publisher: The Japan Society for Clinical Immunology

    DOI： 10.2177/jsci.38.324b 　

    ISSN： 0911-4300

    More details Close

    全身性強皮症は血管障害と皮膚や内臓の線維化を特徴とする自己免疫疾患である．Fcγ受容体は様々な免疫反応を制御し，人ではFcγRI，FcγRIIA，FcγRIIB，FcγRIIIA，FcγRIIIBなど複数存在する．Fcγ受容体を介するシグナルは免疫を正に制御する場合と負に制御する場合とがあり，一般にFcγRIIBを介するシグナルは免疫反応を抑制し，その他の受容体を介するものは免疫反応を亢進させると考えられている．全身性強皮症では様々な自己抗体が出現するが，今回これらFcγ受容体に対する自己抗体抗体価をELISAにて測定し，臨床症状との相関について検討した．全身性強皮症患者において血清抗FcγRIIB抗体値は健常人や限局性強皮症患者より有意に高値を示した．また，限局皮膚硬化型とびまん皮膚硬化型との間に差はみられなかった．また，爪上皮出血点が見られる例では血清抗FcγRIIB抗体は高値を示し，逆にびまん性色素沈着や石灰化が見られる例では低値を示した．更に，血清抗FcγRI抗体値，血清抗FcγRIIA抗体値，血清抗FcγRIIIB抗体値について検討したところ，何れも全身性強皮症患者において健常人より有意に高値を示した．以上より，全身性強皮症においてはFcγ受容体に対する血清抗体値が全般に高く，これが全身性強皮症におけるimmune dysregulationに関与する可能性が考えられた．

  277. 【潰瘍の病態と治療】膠原病・血管炎に伴う皮膚潰瘍の治療アルゴリズム

    藤本 学, 浅野 善英, 石井 貴之, 小川 文秀, 川上 民裕, 小寺 雅也, 浅井 純, 岩田 洋平

    Derma.　(226)　71-77　2015/01

    Publisher: (株)全日本病院出版会

    ISSN： 1343-0831

  278. Amelioration of Tissue Fibrosis by Toll-like Receptor 4 Knockout in Murine Models of Systemic Sclerosis Peer-reviewed

    Takehiro Takahashi, Yoshihide Asano, Yohei Ichimura, Tetsuo Toyama, Takashi Taniguchi, Shinji Noda, Kaname Akamata, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　67　(1)　254-265　2015/01

    DOI： 10.1002/art.38901 　

    ISSN： 2326-5191

    eISSN： 2326-5205

  279. New criteria improve recognition of early systemic sclerosis Peer-reviewed

    Yoshihide Asano, Shinichi Sato

    NATURE REVIEWS RHEUMATOLOGY　11　(1)　3-4　2015/01

    DOI： 10.1038/nrrheum.2014.191 　

    ISSN： 1759-4790

    eISSN： 1759-4804

  280. 皮膚科医が行うべき難治性皮膚潰瘍の対処法とは? 創傷・熱傷ガイドラインの改訂版の変更点についても言及 皮膚科医が行うべき膠原病・血管炎の皮膚潰瘍の対処法とは?

    川上 民裕, 浅井 純, 浅野 善英, 石井 貴之, 岩田 洋平, 小川 文秀, 小寺 雅也, 藤本 学

    日本皮膚科学会雑誌　124　(13)　2907-2911　2014/12

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  281. Histological features of localized scleroderma 'en coup de sabre': A study of 16 cases Peer-reviewed

    T. Taniguchi, Y. Asano, Z. Tamaki, K. Akamata, N. Aozasa, S. Noda, T. Takahashi, Y. Ichimura, T. Toyama, M. Sugita, H. Sumida, Y. Kuwano, M. Miyazaki, K. Yanaba, S. Sato

    Journal of the European Academy of Dermatology and Venereology　28　(12)　1805-1810　2014/12/01

    Publisher: Blackwell Publishing Ltd

    DOI： 10.1111/jdv.12280 　

    ISSN： 1468-3083 0926-9959

  282. Development of systemic sclerosis in patients with Behcet's disease: Remission of Behcet's disease in parallel with the progression of skin sclerosis Peer-reviewed

    Yohei Ichimura, Yoshihide Asano, Takehiro Takahashi, Tetsuo Toyama, Takashi Taniguchi, Zenshiro Tamaki, Sayako Isomura, Tomomitsu Miyagaki, Hiroshi Mitsui, Shinichi Sato

    JOURNAL OF DERMATOLOGY　41　(12)　1113-1114　2014/12

    DOI： 10.1111/1346-8138.12688 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  283. Simultaneous downregulation of KLF5 and Fli1 is a key feature underlying systemic sclerosis Peer-reviewed

    Shinji Noda, Yoshihide Asano, Satoshi Nishimura, Takashi Taniguchi, Katsuhito Fujiu, Ichiro Manabe, Kouki Nakamura, Takashi Yamashita, Ryosuke Saigusa, Kaname Akamata, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Daisuke Tsuruta, Maria Trojanowska, Ryozo Nagai, Shinichi Sato

    NATURE COMMUNICATIONS　5　5797　2014/12

    DOI： 10.1038/ncomms6797 　

    ISSN： 2041-1723

  284. TOX expression in different subtypes of cutaneous lymphoma Peer-reviewed

    Sohshi Morimura, Makoto Sugaya, Hiraku Suga, Tomomitsu Miyagaki, Hanako Ohmatsu, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    ARCHIVES OF DERMATOLOGICAL RESEARCH　306　(9)　843-849　2014/11

    DOI： 10.1007/s00403-014-1501-7 　

    ISSN： 0340-3696

    eISSN： 1432-069X

  285. Serum levels of anti-Fc gamma receptor IIB/C antibodies are increased in patients with systemic sclerosis Peer-reviewed

    Takafumi Kadono, Manabu Tomita, Zenshiro Tamaki, Shinichi Sato, Yoshihide Asano

    JOURNAL OF DERMATOLOGY　41　(11)　1009-1012　2014/11

    DOI： 10.1111/1346-8138.12651 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  286. Late-onset anaphylactic reactions following i.v. cyclophosphamide pulse in a patient with systemic sclerosis and systemic lupus erythematosus overlap syndrome Peer-reviewed

    Takashi Taniguchi, Yoshihide Asano, Zenshiro Tamaki, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Shinji Kagami, Hiroshi Mitsui, Shinichi Sato

    JOURNAL OF DERMATOLOGY　41　(10)　912-914　2014/10

    DOI： 10.1111/1346-8138.12619 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  287. 【角化症・炎症性角化症】アダリムマブ投与中にHBV-DNAが陽転化した尋常性乾癬の1例

    長田 麻友美, 柴田 彩, 鎌田 昌洋, 中尾 桃子, 吉村 英子, 高橋 岳浩, 三井 彩, 荒木 麻由子, 藤田 英樹, 浅野 善英, 多田 弥生, 四柳 宏, 佐藤 伸一

    皮膚科の臨床　56　(8)　1111-1114　2014/08

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  288. Serum resistin levels: a possible correlation with pulmonary vascular involvement in patients with systemic sclerosis Peer-reviewed

    Yuri Masui, Yoshihide Asano, Kaname Akamata, Naohiko Aozasa, Shinji Noda, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Yoshihiro Kuwano, Koichi Yanaba, Yayoi Tada, Makoto Sugaya, Shinichi Sato, Takafumi Kadono

    RHEUMATOLOGY INTERNATIONAL　34　(8)　1165-1170　2014/08

    DOI： 10.1007/s00296-013-2880-3 　

    ISSN： 0172-8172

    eISSN： 1437-160X

  289. Skin Barrier Dysfunction and Low Antimicrobial Peptide Expression in Cutaneous T-cell Lymphoma Peer-reviewed

    Hiraku Suga, Makoto Sugaya, Tomomitsu Miyagaki, Hanako Ohmatsu, Makiko Kawaguchi, Naomi Takahashi, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    CLINICAL CANCER RESEARCH　20　(16)　4339-4348　2014/08

    DOI： 10.1158/1078-0432.CCR-14-0077 　

    ISSN： 1078-0432

    eISSN： 1557-3265

  290. Serum levels of matrix metalloproteinase-13 in patients with eosinophilic fasciitis. International-journal Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Masatoshi Jinnin, Zenshiro Tamaki, Kunihiko Tamaki, Shinichi Sato

    The Journal of dermatology　41　(8)　746-8　2014/08

    DOI： 10.1111/1346-8138.12563 　

    ISSN： 0385-2407

    More details Close

    Matrix metalloproteinase-13 (MMP-13), a member of the collagenase family, has been implicated in the pathogenesis of connective tissue diseases characterized by extracellular matrix remodeling. Since serum MMP-13 levels reflect disease severity of systemic sclerosis and localized scleroderma, we evaluated the clinical significance of serum MMP-13 levels in eosinophilic fasciitis (EF). All the EF patients had serum MMP-13 levels lower than the mean - 2SD of healthy controls. Serum MMP-13 levels were also significantly decreased in EF patients compared with diffuse cutaneous systemic sclerosis, limited cutaneous systemic sclerosis, and generalized morphea patients. Although serum MMP-13 levels did not reflect any clinical and serological features of EF, these results indicate that MMP-13 may be involved in the development of this disease.

  291. Serum Autotaxin Levels Correlate with Pruritus in Patients with Atopic Dermatitis Peer-reviewed

    Aomoko Nakao, Makoto Sugaya, Hiraku Suga, Makiko Kawaguchi, Sohshi Morimura, Hiromichi Kai, Hanako Ohmatsu, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　134　(6)　1745-1747　2014/06

    DOI： 10.1038/jid.2014.24 　

    ISSN： 0022-202X

    eISSN： 1523-1747

  292. Decreased interleukin-20 expression in scleroderma skin contributes to cutaneous fibrosis. International-journal Peer-reviewed

    Hideo Kudo, Masatoshi Jinnin, Yoshihide Asano, Maria Trojanowska, Wakana Nakayama, Kuniko Inoue, Noritoshi Honda, Ikko Kajihara, Katsunari Makino, Satoshi Fukushima, Hironobu Ihn

    Arthritis & rheumatology (Hoboken, N.J.)　66　(6)　1636-47　2014/06

    DOI： 10.1002/art.38380 　

    ISSN： 2326-5191

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    OBJECTIVE: To clarify the role of interleukin-20 (IL-20) in the regulatory mechanism of extracellular matrix expression and to determine the contribution of IL-20 to the phenotype of systemic sclerosis (SSc). METHODS: Protein and messenger RNA (mRNA) levels of collagen, Fli-1, IL-20, and IL-20 receptor (IL-20R) were analyzed using polymerase chain reaction (PCR) array, immunoblotting, immunohistochemical staining, enzyme-linked immunosorbent assay, and real-time PCR. RESULTS: PCR array revealed that IL-20 decreased gene expression of α2(I) collagen (0.03-fold), Smad3 (0.02-fold), and endoglin (0.05-fold) in cultured normal dermal fibroblasts. Fli-1 protein expression was induced by IL-20 (~2-fold). The inhibition of collagen by IL-20, the induction of Fli-1 by IL-20, and the reduction of Smad3 and endoglin by IL-20 were also observed in SSc fibroblasts. Serum IL-20 levels were reduced only slightly in SSc patients but were significantly decreased in patients with scleroderma spectrum disorders (the prodromal stage of SSc) compared with those in normal subjects (111.3 pg/ml versus 180.4 pg/ml; P < 0.05). On the other hand, IL-20 mRNA expression in SSc skin was decreased compared with that in normal skin (P < 0.05), which may result in the induction of collagen synthesis in SSc dermal fibroblasts. IL-20R was expressed in normal and SSc fibroblasts. Moreover, IL-20 supplementation by injection into the skin reversed skin fibrosis induced by bleomycin in mice (~0.5-fold). CONCLUSION: IL-20 reduces basal collagen transcription via Fli-1 induction, while down-regulation of Smad3 and endoglin may cancel the effect of transforming growth factor β in SSc fibroblasts. To confirm the therapeutic value of IL-20 and IL-20R, their function and expression in vivo should be further studied.

  293. Effects of the immunosuppressant rapamycin on the expression of human α2(I) collagen and matrix metalloproteinase 1 genes in scleroderma dermal fibroblasts. International-journal Peer-reviewed

    Zenshiro Tamaki, Yoshihide Asano, Masahide Kubo, Hironobu Ihn, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    Journal of dermatological science　74　(3)　251-9　2014/06

    DOI： 10.1016/j.jdermsci.2014.02.002 　

    ISSN： 0923-1811

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    BACKGROUND: Rapamycin has been shown to exert an anti-fibrotic effect on skin fibrosis in a certain subset of patients with systemic sclerosis (SSc) and in bleomycin-treated animal models. OBJECTIVES: To investigate the mechanism responsible for the anti-fibrotic effect of rapamycin especially by focusing on human α2(I) collagen (COL1A2) and matrix metalloproteinase 1 (MMP1) genes in normal and systemic sclerosis (SSc) dermal fibroblasts. METHODS: The expression levels of type I procollagen and MMP1 proteins were analyzed by immunoblotting and the mRNA levels of COL1A2 and MMP1 genes were evaluated by quantitative real-time RT-PCR. The activities of COL1A2 and MMP1 promoters were determined by reporter analysis. RESULTS: Rapamycin significantly decreased the levels of type I procollagen protein and COL1A2 mRNA, while significantly increasing the levels of MMP1 protein and mRNA in normal dermal fibroblasts. Similar effects of rapamycin were also observed in SSc dermal fibroblasts. Importantly, the inhibitory and stimulatory effects of rapamycin on the mRNA levels of COL1A2 and MMP1 genes, respectively, were significantly greater in SSc dermal fibroblasts than in normal dermal fibroblasts. In SSc dermal fibroblasts, rapamycin affected the expression of COL1A2 gene at the post-transcriptional level. In contrast, rapamycin altered the expression of MMP1 gene at the transcriptional level through the JNK/c-Jun signaling pathway in those cells. CONCLUSION: Rapamycin has a potential to directly regulate the deposition of type I collagen in extracellular matrix through inhibiting type I collagen synthesis and promoting its degradation by MMP1, suggesting that this drug is useful for the treatment of SSc.

  294. Successful use of intravenous cyclophosphamide pulse therapy for interstitial lung disease in a patient with systemic sclerosis on hemodialysis Peer-reviewed

    Takehiro Takahashi, Yoshihide Asano, Ryo Sunaga, Yohei Ichimura, Takashi Taniguchi, Mizuho Yamamoto, Zenshiro Tamaki, Tomonori Takekoshi, Hiroshi Mitsui, Makoto Sugaya, Takamoto Ohse, Shinichi Sato

    JOURNAL OF DERMATOLOGY　41　(6)　533-535　2014/06

    DOI： 10.1111/1346-8138.12495 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  295. The Role of IL-32 in Cutaneous T-Cell Lymphoma Peer-reviewed

    Hiraku Suga, Makoto Sugaya, Tomomitsu Miyagaki, Makiko Kawaguchi, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　134　(5)　1428-1435　2014/05

    DOI： 10.1038/jid.2013.488 　

    ISSN： 0022-202X

    eISSN： 1523-1747

  296. Fli1 deficiency contributes to the suppression of endothelial CXCL5 expression in systemic sclerosis Peer-reviewed

    Yohei Ichimura, Yoshihide Asano, Kaname Akamata, Takehiro Takahashi, Shinji Noda, Takashi Taniguchi, Tetsuo Toyama, Naohiko Aozasa, Hayakazu Sumida, Yoshihiro Kuwano, Koichi Yanaba, Yayoi Tada, Makoto Sugaya, Shinichi Sato, Takafumi Kadono

    ARCHIVES OF DERMATOLOGICAL RESEARCH　306　(4)　331-338　2014/05

    DOI： 10.1007/s00403-013-1431-9 　

    ISSN： 0340-3696

    eISSN： 1432-069X

  297. Successful experience of rituximab therapy for systemic sclerosis-associated interstitial lung disease with concomitant systemic lupus erythematosus Peer-reviewed

    Hayakazu Sumida, Yoshihide Asano, Zenshiro Tamaki, Naohiko Aozasa, Takashi Taniguchi, Takehiro Takahashi, Tetsuo Toyama, Yohei Ichimura, Shinji Noda, Kaname Akamata, Miki Miyazaki, Yoshihiro Kuwano, Koichi Yanaba, Shinichi Sato

    JOURNAL OF DERMATOLOGY　41　(5)　418-420　2014/05

    DOI： 10.1111/1346-8138.12461 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  298. 皮膚科医が行うべき膠原病・血管炎の皮膚潰瘍の対処法とは?

    川上 民裕, 浅井 純, 浅野 善英, 石井 貴之, 岩田 洋平, 小寺 雅也, 藤本 学

    日本皮膚科学会雑誌　124　(4)　647-647　2014/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  299. 右下肢の皮下脂肪萎縮と脚長差を生じた小児線状強皮症

    中村 洸樹, 浅野 善英, 住田 隼一, 中尾 桃子, 蒲澤 美代子, 高橋 岳浩, 大場 温子, 田中 学, 佐藤 伸一

    日本皮膚科学会雑誌　124　(4)　803-803　2014/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  300. TLR4, rather than TLR2, regulates wound healing through TGF-beta and CCL5 expression Peer-reviewed

    Hiraku Suga, Makoto Sugaya, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    JOURNAL OF DERMATOLOGICAL SCIENCE　73　(2)　117-124　2014/02

    DOI： 10.1016/j.jdermsci.2013.10.009 　

    ISSN： 0923-1811

    eISSN： 1873-569X

  301. The Impact of Endothelin Receptor Blockade on a Murine Model of Systemic Sclerosis-associated Vasculopathy

    ASANO Yoshihide

    Hifu no kagaku　13　(22)　S1-6　2014

    Publisher: Meeting of Osaka Dermatological Association/Meeting of Keiji Dermatological Association

    DOI： 10.11340/skinresearch.13.S1 　

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    Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by immune abnormalities, vasculopathy, and fibrosis of the skin and certain internal organs with unknown etiology. Although the established treatment for SSc does not exist, recent studies have demonstrated that bosentan, a dual endothelin receptor antagonist, prevents the development of new digital ulcers in patients with SSc. Furthermore, there are a couple of clinical reports suggesting the potential disease modifying effect of bosentan on SSc vasculopathy. Therefore, in this study, to elucidate the molecular mechanism underlying the effect of bosentan on SSc vasculopathy, we investigated the impact of bosentan on Fli1+/- mice, which reproduce the histological and functional abnormalities of SSc vasculopathy. A series of experiments demonstrated the following findings: (i) endothelin-1 (ET-1) induces the phosphorylation of Fli1, which results in the decrease of Fli1 DNA binding ability and the promotion of Fli1 degradation through proteasome pathway, via &ldquo;c-Abl-PKC-&delta;&rdquo; pathway in human dermal microvascular endothelial cells (HDMECs), (ii) bosentan suppresses Fli1 phosphorylation, while increasing Fli1 DNA binding ability and Fli1 expression levels, in HDMECs by inhibiting the autocrine ET-1 stimulation, (iii) bosentan improves vasculopathy of Fli1+/- mice at least partially by increasing the expression levels of Fli1 in dermal microvascular endothelial cells. Given that Fli1 deficiency due to epigenetic suppression is deeply associated with the developmental process of SSc, these results suggest that bosentan may exert a disease modifying effect on SSc vasculopathy at least partially by reversing the expression levels of Fli1 in dermal microvascular endothelial cells.Skin Research, Suppl. 22: 1-6, 2015

  302. Serum Levels of Angiopoietin-2, but not Angiopoietin-1, are Elevated in Patients with Erythrodermic Cutaneous T-cell Lymphoma Peer-reviewed

    Makiko Kawaguchi, Makoto Sugaya, Hiraku Suga, Tomomitsu Miyagaki, Hanako Ohmatsu, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    ACTA DERMATO-VENEREOLOGICA　94　(1)　9-13　2014

    DOI： 10.2340/00015555-1633 　

    ISSN： 0001-5555

    eISSN： 1651-2057

  303. Serum Angiopoietin-like Protein 3 Levels: Possible Correlation with Progressive Skin Sclerosis, Digital Ulcers and Pulmonary Vascular Involvement in Patients with Systemic Sclerosis Peer-reviewed

    Yohei Ichimura, Yoshihide Asano, Kaname Akamata, Naohiko Aozasa, Shinji Noda, Takashi Taniguchi, Takehiro Takahashi, Tetsuo Toyama, Hayakazu Sumida, Yoshihiro Kuwano, Koichi Yanaba, Yayoi Tada, Makoto Sugaya, Shinichi Sato, Takafumi Kadono

    ACTA DERMATO-VENEREOLOGICA　94　(2)　157-162　2014

    DOI： 10.2340/00015555-1680 　

    ISSN： 0001-5555

    eISSN： 1651-2057

  304. Variations in Serum TARC and I-TAC Levels Reflect Minor Changes in Disease Activity and Pruritus in Atopic Dermatitis Peer-reviewed

    Takayuki Kimura, Makoto Sugaya, Hiraku Suga, Sohshi Morimura, Aide Miyamoto, Hiromichi Kai, Shinji Kagami, Koichi Yanaba, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    ACTA DERMATO-VENEREOLOGICA　94　(3)　331-332　2014

    DOI： 10.2340/00015555-1709 　

    ISSN： 0001-5555

    eISSN： 1651-2057

  305. Clinical correlation of brachial artery flow-mediated dilation in patients with systemic sclerosis Peer-reviewed

    Takehiro Takahashi, Yoshihide Asano, Eisuke Amiya, Masaru Hatano, Zenshiro Tamaki, Munenori Takata, Atsuko Ozeki, Aya Watanabe, Shuichi Kawarasaki, Takashi Taniguchi, Yohei Ichimura, Tetsuo Toyama, Masafumi Watanabe, Yasunobu Hirata, Ryozo Nagai, Issei Komuro, Shinichi Sato

    MODERN RHEUMATOLOGY　24　(1)　106-111　2014/01

    DOI： 10.3109/14397595.2013.854064 　

    ISSN： 1439-7595

    eISSN： 1439-7609

  306. A unifying hypothesis for the pathogenesis of systemic sclerosis based on the deficiency of transcription factor Fli1: The development of a new animal model of systemic sclerosis Peer-reviewed

    Yoshihide Asano

    Japanese Journal of Clinical Immunology　37　(6)　475-487　2014

    Publisher: Japan Society for Clinical Immunology

    DOI： 10.2177/jsci.37.475 　

    ISSN： 1349-7413 0911-4300

  307. Depsipeptide and roxithromycin induce apoptosis of lymphoma cells by blocking extracellular signal-regulated kinase activation Peer-reviewed

    Sohshi Morimura, Makoto Sugaya, Hiromichi Kai, Tomomitsu Miyagaki, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Takashi Murakami, Sinichi Sato

    JOURNAL OF DERMATOLOGY　41　(1)　57-62　2014/01

    DOI： 10.1111/1346-8138.12351 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  308. Serum adhesion molecule levels as prognostic markers in patients with early systemic sclerosis: a multicentre, prospective, observational study. International-journal Peer-reviewed

    Minoru Hasegawa, Yoshihide Asano, Hirahito Endo, Manabu Fujimoto, Daisuke Goto, Hironobu Ihn, Katsumi Inoue, Osamu Ishikawa, Yasushi Kawaguchi, Masataka Kuwana, Fumihide Ogawa, Hiroki Takahashi, Sumiaki Tanaka, Shinichi Sato, Kazuhiko Takehara

    PloS one　9　(2)　e88150　2014

    DOI： 10.1371/journal.pone.0088150 　

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    OBJECTIVE: To assess the utility of circulating adhesion molecule levels as a prognostic indicator of disease progression in systemic sclerosis (SSc) patients with early onset disease. METHODS: Ninety-two Japanese patients with early onset SSc presenting with diffuse skin sclerosis and/or interstitial lung disease were registered in a multicentre, observational study. Concentrations of intercellular adhesion molecule (ICAM) -1, E-selectin, L-selectin, and P-selectin in serum samples from all patients were measured by enzyme-linked immunosorbent asssay (ELISA). In 39 patients, adhesion molecule levels were measured each year for four years. The ability of baseline adhesion molecule levels to predict subsequent progression and severity in clinical and laboratory features were evaluated statistically. RESULTS: At their first visit, serum levels of ICAM-1, E-selection, P-selectin were significantly elevated and serum L-selectin levels were significantly reduced in patients with SSc compared with healthy controls. Overall, serum ICAM-1 levels at each time point were significantly inversely associated with the %vital capacity (VC) of the same time and subsequent years by univariate analysis. The initial serum ICAM-1 levels were significantly inversely associated with the %VC at the fourth year by multiple regression analysis. The initial serum P-selectin levels were significantly associated with the health assessment questionnaire disability index (HAQ-DI) at the fourth year by multiple regression analysis. Initial adhesion molecule levels were not significantly associated with other clinical features including skin thickness score. Baseline adhesion molecule levels were not significantly associated with subsequent rate of change of clinical parameters. CONCLUSION: In patients with SSc, serum levels of ICAM-1 and P-selectin may serve as prognostic indicators of respiratory dysfunction and physical disability, respectively. Further longitudinal studies of larger populations are needed to confirm these findings.

  309. Serum levels of mannose-binding lectin in systemic sclerosis: a possible contribution to the initiation of skin sclerosis in the diffuse cutaneous subtype Peer-reviewed

    Kaname Akamata, Yoshihide Asano, Naohiko Aozasa, Shinji Noda, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Yoshihiro Kuwano, Koichi Yanaba, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    EUROPEAN JOURNAL OF DERMATOLOGY　24　(1)　123-125　2014/01

    DOI： 10.1684/ejd.2013.2245 　

    ISSN： 1167-1122

    eISSN： 1952-4013

  310. Neutrophil-rich Anaplastic Large Cell Lymphoma Expressing Interleukin-8 Peer-reviewed

    Takuya Miyagawa, Makoto Sugaya, Asako Okada, Yoshihide Asano, Takafumi Kadono, Shinichi Sato

    ACTA DERMATO-VENEREOLOGICA　94　(6)　741-742　2014

    DOI： 10.2340/00015555-1849 　

    ISSN： 0001-5555

    eISSN： 1651-2057

  311. Bosentan reverses the pro-fibrotic phenotype of systemic sclerosis dermal fibroblasts via increasing DNA binding ability of transcription factor Fli1 Peer-reviewed

    Kaname Akamata, Yoshihide Asano, Naohiko Aozasa, Shinji Noda, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Shinichi Sato

    ARTHRITIS RESEARCH & THERAPY　16　(2)　R86　2014

    DOI： 10.1186/ar4529 　

    ISSN： 1478-6354

    eISSN： 1478-6362

  312. ICAM-1 deficiency exacerbates sarcoid-like granulomatosis induced by Propionibacterium acnes through impaired IL-10 production by regulatory T cells. International-journal Peer-reviewed

    Masahiro Kamata, Yayoi Tada, Aya Mitsui, Sayaka Shibata, Tomomitsu Miyagaki, Yoshihide Asano, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    The American journal of pathology　183　(6)　1731-1739　2013/12

    DOI： 10.1016/j.ajpath.2013.08.021 　

    ISSN： 0002-9440

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    Propionibacterium acnes has been implicated as one of the suggested causative antigens for sarcoidosis, a systemic granulomatous disease. By injecting heat-killed P. acnes into the dorsal skin of C57BL/6J mice on days 1, 3, 5, and 14, sarcoid-like granulomatosis was induced in skin and lungs of these mice on day 28. To clarify the role of cell adhesion molecules in cutaneous sarcoidosis, we induced sarcoid-like granulomatosis in mice deficient of intercellular adhesion molecule (ICAM)-1, L-selectin, P-selectin, or E-selectin via repeated P. acnes injection. Histopathologic analysis revealed that granuloma formation was aggravated in the skin and lungs of ICAM-1-deficient mice compared with wild-type mice. Within skin granulomas of ICAM-1-deficient mice, P. acnes immunization up-regulated mRNA expression of tumor necrosis factor-α, although it failed to induce IL-10 mRNA expression in contrast to wild-type mice. Infiltration of regulatory T cells into skin granuloma was similar between wild-type mice and ICAM-1-deficient mice. P. acnes immunization induced IL-10 production by CD4(+)CD25(+)Foxp3(+) regulatory T cells in lymph nodes of wild-type mice in vivo, which was absent in regulatory T cells of ICAM-1-deficient mice. Our results indicate that ICAM-1 is imperative for inducing regulatory T cells to produce IL-10 in vivo, which would prevent granuloma formation.

  313. Animal Models of Scleroderma: Current State and Recent Development Peer-reviewed

    Yoshihide Asano, Shinichi Sato

    CURRENT RHEUMATOLOGY REPORTS　15　(12)　382　2013/12

    DOI： 10.1007/s11926-013-0382-7 　

    ISSN： 1523-3774

    eISSN： 1534-6307

  314. Serum chemokine levels as prognostic markers in patients with early systemic sclerosis: a multicenter, prospective, observational study. International-journal Peer-reviewed

    Minoru Hasegawa, Yoshihide Asano, Hirahito Endo, Manabu Fujimoto, Daisuke Goto, Hironobu Ihn, Katsumi Inoue, Osamu Ishikawa, Yasushi Kawaguchi, Masataka Kuwana, Fumihide Ogawa, Hiroki Takahashi, Sumiaki Tanaka, Shinichi Sato, Kazuhiko Takehara

    Modern rheumatology　23　(6)　1076-84　2013/11

    DOI： 10.1007/s10165-012-0795-6 　

    ISSN： 1439-7595

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    OBJECTIVE: To assess the utility of serum chemokine levels as a prognostic indicator of disease progression in systemic sclerosis (SSc) patients with early onset disease. METHODS: Seventy Japanese patients with early onset SSc presenting with diffuse skin sclerosis and/or interstitial lung disease were registered in a multicenter, observational study. Concentrations of CCL2, CCL5, CXCL8, CXCL9, and CXCL10 in serum samples from all patients were measured using cytometric beads array. In 33 patients, chemokine levels were measured each year for 4 years. The ability of baseline chemokine levels to predict changes in clinical features were evaluated statistically by multiple regression analysis. RESULTS: At their first visit, serum levels of CCL2, CCL5, CXCL8, CXCL9, and CXCL10 were significantly elevated in patients with SSc compared with healthy controls. There were significant associations between CCL2 and CXCL8 levels and between CXCL9 and CXCL10 levels in patients. The initial serum CXCL8 levels were significantly associated with the HAQ-DI at the fourth year while the %VC of baseline tended to be negatively associated with HAQ-DI at the fourth year. Initial chemokine levels were not associated with other clinical features including skin thickness score and the respiratory function. CONCLUSION: Serum CXCL8 level may serve as a prognostic indicator of the physical dysfunction in SSc. Further longitudinal studies of larger populations are needed to confirm these findings.

  315. Presence of desaturated hemoglobin enhances the contribution of blood cells to flow-mediated dilation in subjects with systemic sclerosis Peer-reviewed

    Eisuke Amiya, Munenori Takata, Masafumi Watanabe, Takehiro Takahashi, Yoshihide Asano, Masaru Hatano, Atsuko Ozeki, Aya Watanabe, Shuichi Kawarasaki, Zenshiro Tamaki, Takashi Taniguchi, Yohei Ichimura, Tetsuo Toyama, Ryozo Nagai, Shinichi Sato, Issei Komuro

    International Journal of Cardiology　168　(3)　3125-3127　2013/10/03

    DOI： 10.1016/j.ijcard.2013.04.046 　

    ISSN： 0167-5273 1874-1754

  316. Regulatory B cells suppress imiquimod-induced, psoriasis-like skin inflammation. International-journal Peer-reviewed

    Koichi Yanaba, Masahiro Kamata, Nobuko Ishiura, Sayaka Shibata, Yoshihide Asano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Thomas F Tedder, Shinichi Sato

    Journal of leukocyte biology　94　(4)　563-73　2013/10

    DOI： 10.1189/jlb.1112562 　

    ISSN： 0741-5400

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    Psoriasis is an inflammatory cutaneous disorder characterized by marked epidermal thickening and Th1 and Th17 cell infiltration. At present, the contribution of B cells to the pathogenesis of psoriasis is unclear. In mice, topical application of imiquimod induces inflamed skin lesions and serves as an experimental animal model for human psoriasis. In this study, we showed that imiquimod-induced skin inflammation was more severe in CD19(-/-) than WT mice. These inflammatory responses were negatively regulated by a unique IL-10-producing CD1d(hi)CD5(+) regulatory B cell subset (B10 cells) that was absent in CD19(-/-) mice and represented only 1-2% of splenic B220(+) cells in WT mice. Splenic B10 cells entered the circulation and migrated to draining LNs during imiquimod-induced skin inflammation, thereby suppressing IFN-γ and IL-17 production. Furthermore, adoptive transfer of these B10 cells from WT mice reduced inflammation in CD19(-/-) mice. The present findings provide direct evidence that B10 cells regulate imiquimod-induced skin inflammation and offer insights into regulatory B cell-based therapies for the treatment of psoriasis.

  317. Fli1 Represses Transcription of the Human α2(I) Collagen Gene by Recruitment of the HDAC1/p300 Complex Peer-reviewed

    Yoshihide Asano, Maria Trojanowska

    PLoS ONE　8　(9)　e74930　2013/09/13

    DOI： 10.1371/journal.pone.0074930 　

    ISSN： 1932-6203

  318. Dynamics of serum angiopoietin-2 levels correlate with efficacy of intravenous pulse cyclophosphamide therapy for interstitial lung disease associated with systemic sclerosis Peer-reviewed

    Takehiro Takahashi, Yoshihide Asano, Kaname Akamata, Naohiko Aozasa, Takashi Taniguchi, Shinji Noda, Yuri Masui, Yohei Ichimura, Tetsuo Toyama, Zenshiro Tamaki, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    MODERN RHEUMATOLOGY　23　(5)　884-890　2013/09

    DOI： 10.1007/s10165-012-0755-1 　

    ISSN： 1439-7595

    eISSN： 1439-7609

  319. Serum visfatin levels in patients with atopic dermatitis and cutaneous T-cell lymphoma Peer-reviewed

    Hiraku Suga, Makoto Sugaya, Tomomitsu Miyagaki, Makiko Kawaguchi, Sohshi Morimura, Hiromichi Kai, Shinji Kagami, Hanako Ohmatsu, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    EUROPEAN JOURNAL OF DERMATOLOGY　23　(5)　629-635　2013/09

    DOI： 10.1684/ejd.2013.2107 　

    ISSN： 1167-1122

    eISSN： 1952-4013

  320. Cutaneous polyarteritis nodosa localized to the arm receiving an infusion of abatacept Peer-reviewed

    Sayaka Shibata, Yoshihide Asano, Shinichi Sato

    European Journal of Dermatology　23　(5)　738-739　2013/09

    DOI： 10.1684/ejd.2013.2160 　

    ISSN： 1167-1122 1952-4013

  321. Serum-soluble herpes virus entry mediator levels reflect disease severity and Th2 environment in cutaneous T-cell lymphoma. International-journal Peer-reviewed

    Tomomitsu Miyagaki, Makoto Sugaya, Hiraku Suga, Hanako Ohmatsu, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    Acta dermato-venereologica　93　(4)　465-7　2013/07/06

    DOI： 10.2340/00015555-1523 　

    ISSN： 0001-5555

  322. Ciclosporin A inhibits production of interleukin-12/23p40 and interleukin-23 by the human monocyte cell line, THP-1. International-journal Peer-reviewed

    Kamata M, Tada Y, Tatsuta A, Kawashima T, Shibata S, Mitsui H, Asano Y, Sugaya M, Kadono T, Kanda N, Watanabe S, Sato S

    Clinical and experimental dermatology　38　(5)　545-548　2013/07

    DOI： 10.1111/ced.12110 　

    ISSN： 0307-6938

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    Ciclosporin (Cs)A is an effective treatment for psoriasis. However, to date, the effect of CsA on the production of interleukins (ILs) is unknown. We investigated how CsA affects production of IL-12/23p40 and IL-23 production by the human monocyte cell line, THP-1, which is able to differentiate into macrophage-like cells or normal human keratinocytes (NHKs). THP-1 cells were preincubated with CsA, then stimulated with lipopolysaccharide (LPS), polyinosinic:polycytidylic acid or adenosine triphosphate. The levels of IL-12/23p40 and IL-23 released into the supernatant were assayed by ELISA. CsA significantly reduced both IL-12/23p40 and IL-23 production by LPS-stimulated THP-1 cells, but not in LPS-stimulated macrophage-like differentiated THP-1 cells. None of the stimuli used significantly induced either IL-12/23p40 or IL-23 production in NHKs. CsA inhibits not only IL-12/23p40 and IL-12p70, but also heterodimeric IL-23 production by human monocytes, which may be one possible mechanism for the therapeutic efficacy of CsA in psoriasis.

  323. A possible contribution of visfatin to the resolution of skin sclerosis in patients with diffuse cutaneous systemic sclerosis via a direct anti-fibrotic effect on dermal fibroblasts and Th1 polarization of the immune response. International-journal Peer-reviewed

    Yuri Masui, Yoshihide Asano, Sayaka Shibata, Shinji Noda, Kaname Akamata, Naohiko Aozasa, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Koichi Yanaba, Yayoi Tada, Makoto Sugaya, Shinichi Sato, Takafumi Kadono

    Rheumatology (Oxford, England)　52　(7)　1239-44　2013/07

    DOI： 10.1093/rheumatology/ket010 　

    ISSN： 1462-0324

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    OBJECTIVE: Visfatin is a member of the adipocytokines with pro-fibrotic, pro-inflammatory and immunomodulating properties potentially implicated in the pathogenesis of certain fibrotic and inflammatory autoimmune diseases. In this study, we investigated THE CLINICAL SIGNIFICANCE OF SERUM VISFATIN LEVELS AND ITS CONTRIBUTION TO THE DEVELOPMENTAL PROCESS IN SSC. METHODS: Serum visfatin levels were determined by a specific ELISA in 57 SSc patients and 19 healthy controls. The mRNA levels of target genes were determined in normal and SSc fibroblasts by real-time RT-PCR. The levels of IL-12p70 produced by THP-1 cells were measured by a specific ELISA. RESULTS: Serum visfatin levels were comparable among total SSc, diffuse cutaneous SSc (dcSSc), limited cutaneous SSc and healthy controls. The only finding in a series of analyses regarding the correlation of serum visfatin levels with clinical symptoms and laboratory data was the significantly longer disease duration in dcSSc with elevated serum visfatin levels than in those with normal levels. Consistently, serum visfatin levels were significantly elevated in late-stage dcSSc (disease duration >6 years), but not in early and mid-stage dcSSc compared with healthy controls. In in vitro experiments, visfatin reversed the pro-fibrotic phenotype of SSc dermal fibroblasts and induced the expression of IL-12p70 in THP-1 cells treated with IFN-γ plus lipopolysaccharide. CONCLUSION: Visfatin may contribute to the resolution of skin sclerosis in late-stage dcSSc via a direct anti-fibrotic effect on dermal fibroblasts and Th1 polarization of the immune response.

  324. Serum levels of ADAM12-S: possible association with the initiation and progression of dermal fibrosis and interstitial lung disease in patients with systemic sclerosis Peer-reviewed

    T. Taniguchi, Y. Asano, K. Akamata, N. Aozasa, S. Noda, T. Takahashi, Y. Ichimura, T. Toyama, H. Sumida, Y. Kuwano, K. Yanaba, Y. Tada, M. Sugaya, T. Kadono, S. Sato

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY　27　(6)　747-753　2013/06

    DOI： 10.1111/j.1468-3083.2012.04558.x 　

    ISSN： 0926-9959

  325. CD19 Expression in B Cells Regulates Atopic Dermatitis in a Mouse Model Peer-reviewed

    Koichi Yanaba, Masahiro Kamata, Yoshihide Asano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Thomas F. Tedder, Shinichi Sato

    AMERICAN JOURNAL OF PATHOLOGY　182　(6)　2214-2222　2013/06

    DOI： 10.1016/j.ajpath.2013.02.042 　

    ISSN： 0002-9440

    eISSN： 1525-2191

  326. Endothelial GATA-6 Deficiency Promotes Pulmonary Arterial Hypertension Peer-reviewed

    Angela Ghatnekar, Izabela Chrobak, Charlie Reese, Lukasz Stawski, Francesca Seta, Elaine Wirrig, Jesus Paez-Cortez, Margaret Markiewicz, Yoshihide Asano, Russell Harley, Richard Silver, Carol Feghali-Bostwick, Maria Trojanowska

    AMERICAN JOURNAL OF PATHOLOGY　182　(6)　2391-2406　2013/06

    DOI： 10.1016/j.ajpath.2013.02.039 　

    ISSN： 0002-9440

  327. Clinical significance of serum soluble Tie1 levels in patients with systemic sclerosis. International-journal Peer-reviewed

    Shinji Noda, Yoshihide Asano, Naohiko Aozasa, Kaname Akamata, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Yoshihiro Kuwano, Koichi Yanaba, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    Archives of dermatological research　305　(4)　325-31　2013/05

    DOI： 10.1007/s00403-012-1307-4 　

    ISSN： 0340-3696

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    Tie1 is an endothelial cell-specific tyrosine kinase receptor, which maintains vascular integrity and regulates angiogenesis via modulating angiopoietin/Tie2 signaling. Since the altered angiogenesis is closely related to the developmental process of systemic sclerosis (SSc), we herein investigated the clinical significance of serum soluble Tie1 (sTie1) levels and the expression levels of Tie1 in dermal microvascular endothelial cells (DMECs) in patients with SSc. Although serum sTie1 levels were comparable among total SSc, diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and healthy controls, SSc patients with decreased serum sTie1 levels had significantly shorter disease duration than those with serum sTie1 levels not decreased. In SSc patients with disease duration of >6 years, the prevalence of clinical symptoms associated with proliferative vasculopathy, such as digital ulcers, scleroderma renal crisis, and elevated right ventricular systolic pressure, was significantly higher in patients with decreased serum sTie1 levels than in those with serum sTie1 levels not decreased. In immunohistochemistry, Tie1 expression was reduced in DMECs of SSc patients with disease duration of <3 years compared with those of healthy controls. Collectively, in SSc patients with short disease duration, decreased serum sTie1 levels may reflect the down-regulation of Tie1 in DMECs. The decrease in serum sTie1 levels may serve as a marker of proliferative vasculopathy in SSc with disease duration of >6 years.

  328. Decreased cathepsin V expression due to Fli1 deficiency contributes to the development of dermal fibrosis and proliferative vasculopathy in systemic sclerosis. International-journal Peer-reviewed

    Shinji Noda, Yoshihide Asano, Takehiro Takahashi, Kaname Akamata, Naohiko Aozasa, Takashi Taniguchi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Yoshihiro Kuwano, Koichi Yanaba, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    Rheumatology (Oxford, England)　52　(5)　790-9　2013/05

    DOI： 10.1093/rheumatology/kes379 　

    ISSN： 1462-0324

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    OBJECTIVES: Cathepsin V (CTSV) is a proteolytic enzyme potentially modulating angiogenic processes, collagen degradation and keratinocyte differentiation. We aimed to investigate the clinical association of serum CTSV levels and the mechanism by which CTSV expression is altered in SSc. METHODS: Serum CTSV levels were determined by ELISA in 51 SSc and 18 healthy subjects. CTSV expression was evaluated by immunostaining in SSc and normal skin and by RT-real-time PCR in normal and SSc dermal fibroblasts, normal dermal fibroblasts treated with TGF-β1 or Fli1 siRNA and human dermal microvascular endothelial cells (ECs) treated with Fli1 siRNA. RESULTS: Serum CTSV levels were significantly lower in dcSSc and lcSSc patients than in healthy controls. In early-stage dcSSc, serum CTSV levels were remarkably and uniformly decreased compared with healthy controls. The decrease in serum CTSV levels in mid- and late-stage dcSSc and in lcSSc was linked to the development of proliferative vasculopathy. CTSV expression was decreased in microvascular ECs, pericytes/vascular smooth muscle cells and keratinocytes of dcSSc and lcSSc skin and in dermal fibroblasts of dcSSc skin compared with control skin. Consistently, CTSV expression was decreased in cultured dermal fibroblasts from early-stage dcSSc. Furthermore, mRNA levels of the CTSV gene were significantly decreased in normal fibroblasts treated with TGF-β1 or Fli1 siRNA and in human dermal microvascular ECs treated with Fli1 siRNA. CONCLUSION: Loss of CTSV expression may contribute to the development of fibrosis, vasculopathy and the altered phenotype of keratinocytes in SSc.

  329. Visfatin Enhances the Production of Cathelicidin Antimicrobial Peptide, Human beta-Defensin-2, Human beta-Defensin-3, and S100A7 in Human Keratinocytes and Their Orthologs in Murine Imiquimod-Induced Psoriatic Skin Peer-reviewed

    Carren S. Hau, Naoko Kanda, Shinji Noda, Aya Tatsuta, Masahiro Kamata, Sayaka Shibata, Yoshihide Asano, Shinichi Sato, Shinichi Watanabe, Yayoi Tada

    AMERICAN JOURNAL OF PATHOLOGY　182　(5)　1705-1717　2013/05

    DOI： 10.1016/j.ajpath.2013.01.044 　

    ISSN： 0002-9440

    eISSN： 1525-2191

  330. 全身性強皮症における%FMD値と臨床症状および各種検査値との相関に関する検討

    高橋 岳浩, 浅野 善英, 市村 洋平, 遠山 哲夫, 谷口 隆志, 玉城 善史郎, 佐藤 伸一, 高田 宗典, 網谷 英介, 渡辺 昌文

    日本皮膚科学会雑誌　123　(5)　966-966　2013/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  331. Association of nerve growth factor, chemokine (C-C motif) ligands and immunoglobulin E with pruritus in cutaneous T-cell lymphoma. International-journal Peer-reviewed

    Hiraku Suga, Makoto Sugaya, Tomomitsu Miyagaki, Hanako Ohmatsu, Hideki Fujita, Shinji Kagami, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    Acta dermato-venereologica　93　(2)　144-9　2013/03/27

    DOI： 10.2340/00015555-1428 　

    ISSN： 0001-5555

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    Many patients with cutaneous T-cell lymphoma (CTCL) experience severe pruritus. This study evaluated serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in patients with CTCL. Although serum NGF and BDNF levels in patients with CTCL were not significantly higher than in healthy controls, serum NGF levels in patients with Sézary syndrome were higher than in those with mycosis fungoides and in healthy controls. Enhanced NGF expression by keratinocytes and increased dermal nerve fibres were detected in lesional skin of subjects with Sézary syndrome. Correlations between pruritus in CTCL and serum levels of NGF, BDNF, chemokine (C-C motif) ligand 1 (CCL1), CCL17, CCL26, CCL27, lactate dehydrogenase (LDH), IgE, and soluble interleukin-2 receptor were analysed. Serum CCL1, CCL26, LDH, and IgE levels correlated with pruritus in patients with CTCL. NGF may be associated with increased dermal nerve fibres and pruritus in Sézary syndrome, and CCL1, CCL26, and IgE may be associated with pruritus in CTCL.

  332. Clinical significance of serum retinol binding protein-4 levels in patients with systemic sclerosis. International-journal Peer-reviewed

    T Toyama, Y Asano, T Takahashi, N Aozasa, K Akamata, S Noda, T Taniguchi, Y Ichimura, H Sumida, Z Tamaki, Y Masui, Y Tada, M Sugaya, S Sato, T Kadono

    Journal of the European Academy of Dermatology and Venereology : JEADV　27　(3)　337-44　2013/03

    DOI： 10.1111/j.1468-3083.2011.04413.x 　

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    BACKGROUND: Retinol binding protein-4 (RBP-4) is a member of adipocytokines, which is potentially associated with fibrosis, vasodilation, and angiogenesis in addition to insulin resistance. OBJECTIVE: To investigate the clinical significance of serum RBP4 levels in patients with systemic sclerosis (SSc), which is a systemic autoimmune disease characterized by fibrosis and vasculopathy. METHODS: Serum RBP4 levels were determined by enzyme-linked immunosorbent assay in 62 SSc patients and 19 healthy controls. RESULTS: Similar to patients with chronic kidney disease, serum RBP4 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction. Therefore, analyses were carried out by excluding SSc patients with estimated glomerular filtration rate <60 mL/min/1.73 m(2) . Serum RBP4 levels were significantly lower in diffuse cutaneous SSc (dcSSc) than in control subjects [median (25-75 percentile); 25.8 μg/mL (19.6-47.0) vs. 43.1 μg/mL (31.7-53.4), P < 0.05], while there was no significant difference between limited cutaneous SSc (lcSSc) [28.0 μg/mL (25.4-43.3)] and control subjects. In both of dcSSc and lcSSc, patients with Raynaud's phenomenon had RBP4 levels significantly lower than those without. Furthermore, serum RBP4 levels inversely correlated with pulmonary function test results in dcSSc and with right ventricular systolic pressure in lcSSc. CONCLUSION  Decreased RBP4 levels are associated with the prevalence of Raynaud's phenomenon in dcSSc and lcSSc, with the severity of interstitial lung disease in dcSSc, and with the degree of pulmonary vascular involvement in lcSSc, suggesting the possible contribution of RBP4 to the pathological events in this disorder.

  333. Clinical significance of monitoring serum adiponectin levels during intravenous pulse cyclophosphamide therapy in interstitial lung disease associated with systemic sclerosis Peer-reviewed

    Yuri Masui, Yoshihide Asano, Takehiro Takahashi, Sayaka Shibata, Kaname Akamata, Naohiko Aozasa, Shinji Noda, Takashi Taniguchi, Yohei Ichimura, Tetsuo Toyama, Zenshiro Tamaki, Hayakazu Sumida, Koichi Yanaba, Yayoi Tada, Makoto Sugaya, Shinichi Sato, Takafumi Kadono

    MODERN RHEUMATOLOGY　23　(2)　323-329　2013/03

    DOI： 10.1007/s10165-012-0660-7 　

    ISSN： 1439-7595

  334. Clinical correlation of brachial artery flow-mediated dilation in patients with systemic sclerosis. International-journal Peer-reviewed

    Takahashi T, Asano Y, Amiya E, Hatano M, Tamaki Z, Takata M, Ozeki A, Watanabe A, Kawarasaki S, Taniguchi T, Ichimura Y, Toyama T, Watanabe M, Hirata Y, Nagai R, Komuro I, Sato S

    Modern rheumatology　2013/03

    DOI： 10.1007/s10165-013-0867-2 　

    ISSN： 1439-7595

    eISSN： 1439-7609

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    OBJECTIVE: To investigate the clinical significance of flow-mediated dilation (FMD) in systemic sclerosis (SSc). METHODS: Thirty-three SSc patients and 12 healthy controls were studied. Ultrasound assessment of the brachial artery FMD was performed on all subjects. The results were expressed as the percentage of increase in brachial artery diameter following hyperemia. RESULTS: Limited cutaneous SSc (lcSSc) patients had significantly lower FMD values than healthy controls (5.3 ± 2.7 versus 7.7 ± 2.0 %, p < 0.05), while the values in diffuse cutaneous SSc (dcSSc) patients (6.7 ± 4.0 %) were comparable to those in lcSSc patients and healthy controls. Although FMD values did not correlate with any clinical features in dcSSc patients, there was an inverse correlation between FMD values and disease duration in lcSSc patients (r = -0.64, p < 0.05). Furthermore, lcSSc patients with decreased FMD values showed significantly higher prevalence of digital ulcers and elevated right ventricular systolic pressure than those with normal values (for each; 75 versus 10 %, p < 0.05). CONCLUSION: The FMD values represent the severity of vascular damages, which progress along with disease duration and lead to digital ulcers and pulmonary arterial hypertension, in lcSSc patients.

  335. An inverse correlation of serum angiogenin levels with estimated glomerular filtration rate in systemic sclerosis patients with renal dysfunction Peer-reviewed

    Kaname Akamata, Yoshihide Asano, Shinji Noda, Takashi Taniguchi, Takehiro Takahashi, Yohei Icihmura, Tetsuo Toyama, Hayakazu Sumida, Yoshihiro Kuwano, Koichi Yanaba, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    EUROPEAN JOURNAL OF DERMATOLOGY　23　(2)　269-270　2013/03

    DOI： 10.1684/ejd.2013.1924 　

    ISSN： 1167-1122

  336. IL-27 Activates Th1-Mediated Responses in Imiquimod-Induced Psoriasis-Like Skin Lesions Peer-reviewed

    Sayaka Shibata, Yayoi Tada, Yoshihide Asano, Koichi Yanaba, Makoto Sugaya, Takafumi Kadono, Naoko Kanda, Shinichi Watanabe, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　133　(2)　479-488　2013/02

    DOI： 10.1038/jid.2012.313 　

    ISSN： 0022-202X

    eISSN： 1523-1747

  337. P6-08  ブレオマイシン誘発強皮症モデルマウスの線維化と免疫異常の病態に対してレチノイドAm80が及ぼす影響についての検討

    遠山 哲夫, 浅野 善英, 高橋 岳浩, 市村 洋平, 谷口 隆志, 野田 真史, 赤股 要, 門野 岳史, 佐藤 伸一

    日本臨床免疫学会会誌　36　(5)　401b-401b　2013

    Publisher: The Japan Society for Clinical Immunology

    DOI： 10.2177/jsci.36.401b 　

    ISSN： 0911-4300

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    全身性強皮症は血管障害と皮膚および内臓諸臓器の線維化を特徴とする原因不明の膠原病で，その発症には免疫異常の関与が示唆されている．Am80は急性前骨髄球性白血病治療薬として承認されている合成レチノイドで，近年ループス腎炎や血管炎など各種膠原病に対する有用性が臨床試験や動物実験により示唆されている．今回我々はAm80が全身性強皮症の病態に及ぼす影響について，ブレオマイシン（BLM）誘発強皮症モデルマウスを用いて検討した．Am80はBLM刺激により誘導される真皮の肥厚およびI型コラーゲン蛋白の発現を有意に抑制した．また，病変部皮膚におけるI型コラーゲン遺伝子のmRNAの発現量を有意に抑制し，MMP1遺伝子のmRNAの発現量を有意に亢進させた．更に，Am80は病変部皮膚においてCTGF，TGF-β，ICAM-1，IL-17A，TNFα，IFNg，MCP-1遺伝子のmRNAの発現量を有意に抑制した．一方，培養強皮症皮膚線維芽細胞およびTGF-β刺激で活性化された培養正常ヒト皮膚線維芽細胞において，Am80はI型コラーゲン遺伝子の発現を有意に抑制し，MMP1遺伝子の発現を有意に亢進させた．以上の結果より，Am80は皮膚線維芽細胞に対する直接的作用と，各種成長因子，細胞接着因子，サイトカイン，ケモカインの発現調節を介した間接的作用により，皮膚において抗線維化作用を示すことが明らかとなった．<br>

  338. P3-10  ブレオマイシン誘発強皮症モデルマウスの線維化と免疫異常の病態における転写因子Fli1の役割についての検討

    谷口 隆志, 浅野 善英, 市村 洋平, 高橋 岳浩, 遠山 哲夫, 野田 真史, 赤股 要, 佐藤 伸一

    日本臨床免疫学会会誌　36　(5)　384a-384a　2013

    Publisher: The Japan Society for Clinical Immunology

    DOI： 10.2177/jsci.36.384a 　

    ISSN： 0911-4300

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    全身性強皮症は血管障害と線維化を特徴とする原因不明の自己免疫疾患である．本症では転写因子Fli1の発現が恒常的に低下しており，皮膚線維芽細胞と血管内皮細胞の恒常的活性化に深く関与している．一方，Fli1+/−マウスでは強皮症を発症する上での基盤となる皮膚線維芽細胞の恒常的な活性化および皮膚小血管の機能異常と構造異常を再現できるが，強皮症の臨床症状は再現できない．今回我々は，Fli1の恒常的発現低下が強皮症を発症する上での疾病素因となっている可能性について検討するため，Fli1+/−マウスを用いブレオマイシン（BLM）誘発強皮症モデルマウスを作成し，その形質変化について検討した．Fli1+/−マウスでは野生型マウスと比較して，BLM刺激による真皮の肥厚が有意に亢進し，I型コラーゲン蛋白の発現量も有意に亢進した．Fli1+/−マウスの病変部皮膚では，BLM投与1週間の炎症期では，血管内皮細胞においてTh2/Th17に偏倚した炎症を誘導する細胞接着分子の発現変化が認められた．また，BLM投与4週間の硬化期では，皮膚線維芽細胞においてCTGFや潜在型TGF-βの活性化に重要なインテグリンαVβ3，αVβ5の発現が亢進しており，浸潤しているマクロファージではarginase-1陽性細胞の割合が有意に亢進していた．以上の結果より，Fli1の恒常的発現低下はBLM刺激に対して，様々な細胞において強皮症に特徴的な形質変化を促し，皮膚の強力な線維化を誘導することが明らかとなった．<br>

  339. P3-09  ブレオマイシン誘発強皮症モデルマウスの線維化および免疫異常におけるToll様受容体4の役割についての検討

    高橋 岳浩, 浅野 善英, 赤股 要, 谷口 隆志, 野田 真史, 市村 洋平, 遠山 哲夫, 佐藤 伸一

    日本臨床免疫学会会誌　36　(5)　383b-383b　2013

    Publisher: The Japan Society for Clinical Immunology

    DOI： 10.2177/jsci.36.383b 　

    ISSN： 0911-4300

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    Toll様受容体（TLR）はパターン認識受容体ファミリーに属し自然免疫系において病原体の認識と炎症性シグナル応答に重要とされる．TLR4は細菌感染の免疫応答に中心的な役割を果たす一方，非感染性の慢性炎症にも深く関与する．今回我々は野生型およびTLR4ノックアウトマウスを用いてブレオマイシン誘発強皮症モデルマウスを作成し，その線維化と免疫異常の病態においてTLR4が果たす役割について検討を行った．野生型マウスを用いた検討ではブレオマイシン投与により局所皮膚および肺においてTLR4は有意に発現が上昇していた．さらに，TLR4ノックアウトマウスでは野生型マウスに比較してブレオマイシン投与で誘導される線維化が有意に減弱し，線維化促進的に作用する各種サイトカイン，ケモカイン，細胞接着分子もTLR4ノックアウトマウスでは発現が有意に抑制されていた．さらに，野生型マウスではブレオマイシン投与局所皮膚の所属リンパ節中のリンパ球のフローサイトメトリーを用いた解析ではTh2/Th17系への顕著な偏倚が認められた一方，TLR4ノックアウトマウスではその偏倚は減弱されていた．ブレオマイシン投与による線維化の誘導にはヒアルロン酸などのTLR4の内因性リガンド発現によるTLR4シグナリングの活性化，線維化促進的サイトカインの発現上昇，さらにそれによる免疫異常の誘導が関与している可能性が考えられた．<br>

  340. Serum apelin levels: clinical association with vascular involvements in patients with systemic sclerosis Peer-reviewed

    N. Aozasa, Y. Asano, K. Akamata, S. Noda, Y. Masui, D. Yamada, Z. Tamaki, Y. Tada, M. Sugaya, T. Kadono, S. Sato

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY　27　(1)　37-42　2013/01

    DOI： 10.1111/j.1468-3083.2011.04354.x 　

    ISSN： 0926-9959

  341. Increased CCL18 expression in patients with cutaneous T-cell lymphoma: association with disease severity and prognosis. Peer-reviewed

    Miyagaki T, Sugaya M, Suga H, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S

    Journal of the European Academy of Dermatology and Venereology : JEADV　27　(1)　e60-7　2013/01

    DOI： 10.1111/j.1468-3083.2012.04495.x 　

    ISSN： 0926-9959

  342. Serum soluble CD26 levels: diagnostic efficiency for atopic dermatitis, cutaneous T-cell lymphoma and psoriasis in combination with serum thymus and activation-regulated chemokine levels. International-journal Peer-reviewed

    Miyagaki T, Sugaya M, Suga H, Morimura S, Kamata M, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S

    Journal of the European Academy of Dermatology and Venereology : JEADV　27　(1)　19-24　2013/01

    DOI： 10.1111/j.1468-3083.2011.04340.x 　

    ISSN： 0926-9959

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    BACKGROUND: CD26 is a multifunctional type II transmembrane glycoprotein, which also exists as a secreted isoform, soluble CD26 (sCD26). The CD26 expression on circulating T cells is decreased in some skin diseases such as cutaneous T-cell lymphoma (CTCL) and psoriasis. It remains to be determined whether sCD26 can be used as a marker of skin diseases or not. OBJECTIVE: To investigate utility of sCD26 as a diagnostic marker of skin diseases in combination with thymus and activation-regulated chemokine (TARC). METHODS: Serum sCD26 levels were measured using enzyme-linked immunosorbent assay in 130 participants including 32 patients with atopic dermatitis (AD); 45 patients with CTCL; 26 patients with psoriasis; and 27 healthy controls. RESULTS: Serum sCD26 levels in patients with CTCL and psoriasis (162.1 ± 80.2 ng/mL and 125.4 ± 82.1 ng/mL respectively) were significantly lower than those of healthy controls (392.6 ± 198.7 ng/mL; P < 0.01 and 0.01 respectively). In patients with CTCL, serum sCD26 levels of patients with advanced stage were 135.0 ± 51.5 ng/mL and they were significantly lower than those with early stage (193.1 ± 96.0 ng/mL; P < 0.05). When we used serum sCD26 and TARC levels for diagnostic criteria, sensitivity, specificity, positive predictive value and negative predictive value for AD, CTCL and psoriasis were 65.2-73.7%, 81.4-97.6%, 65.2-94.4%, and 81.4-88.9% respectively. CONCLUSION: Serum sCD26 levels, combined with serum TARC levels, are helpful in diagnosis of AD, CTCL and psoriasis.

  343. Decrease in circulating autotaxin by oral administration of prednisolone. Peer-reviewed

    Hayakazu Sumida, Kazuhiro Nakamura, Keisuke Yanagida, Ryunosuke Ohkawa, Yoshihide Asano, Takafumi Kadono, Kunihiko Tamaki, Koji Igarashi, Junken Aoki, Shinichi Sato, Satoshi Ishii, Takao Shimizu, Yutaka Yatomi

    Clin. Chim. Acta　415　74-80　2013/01

    DOI： 10.1016/j.cca.2012.10.003 　

    ISSN： 1873-3492

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    Autotaxin (ATX), secreted mainly from adipose tissue, functions as a lysophospholipase D (lysoPLD) to hydrolyze lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). ATX-LPA signaling is implicated in a wide range of physiological and pathophysiological processes including immune response.<br /> The present study measured serum ATX antigen levels in patients with various autoimmune diseases using a recently developed automated enzyme immunoassay. In addition, serum lysoPLD activity was assessed by measuring choline liberation from the substrate LPC. Moreover, the effect of prednisolone (PSL) on mRNA expression of ATX was evaluated using cultured adipose tissue from mice.<br /> Decreased serum ATX antigen levels were observed after the initiation of treatment with PSL. The decreased levels recovered during tapering of PSL dose in a dose-dependent manner without exacerbation of disease activity. Moreover, decreased ATX mRNA expression in PSL-treated cultured murine adipose tissue suggested that the effect of PSL on serum ATX may have resulted from changes in adipose tissue ATX expression.<br /> Our results suggest that measurement of serum ATX antigen level may be clinically useful for the a

  344. Autoantibodies to small ubiquitin-like modifier activating enzymes in Japanese patients with dermatomyositis: Comparison with a UK Caucasian cohort Peer-reviewed

    Manabu Fujimoto, Takashi Matsushita, Yasuhito Hamaguchi, Kenzo Kaji, Yoshihide Asano, Fumihide Ogawa, Toshifumi Yamaoka, Keita Fujikawa, Toshiaki Tsukada, Keita Sato, Takeshi Echigo, Minoru Hasegawa, Kazuhiko Takehara

    Annals of the Rheumatic Diseases　72　(1)　151-153　2013/01

    DOI： 10.1136/annrheumdis-2012-201736 　

    ISSN： 0003-4967

    eISSN： 1468-2060

  345. Increased circulating fibrinogen-like protein 2 in patients with systemic sclerosis. International-journal Peer-reviewed

    Koichi Yanaba, Yoshihide Asano, Shinji Noda, Kaname Akamata, Naohiko Aozasa, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Yoshihiro Kuwano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    Clinical rheumatology　32　(1)　43-7　2013/01

    DOI： 10.1007/s10067-012-2089-y 　

    ISSN： 0770-3198

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    Fibrinogen-like protein 2 (FGL2), a member of the fibrinogen-related superfamily of proteins, is expressed on the surface of macrophages, T cells, and endothelial cells and directly cleaves prothrombin to thrombin. The aim of this study is to determine the serum FGL2 level and its association with clinical parameters in patients with systemic sclerosis (SSc). Serum FGL2 level was examined by enzyme-linked immunosorbent assay in 61 patients with SSc, 24 patients with systemic lupus erythematosus, and 24 healthy individuals. In a retrospective longitudinal study, sera from 13 patients with SSc were analyzed. The serum FGL2 level was increased in patients with SSc compared with healthy individuals (P < 0.001) and patients with systemic lupus erythematosus (P < 0.01). Among patients with SSc, there were no differences in serum FGL2 level between limited cutaneous SSc and diffuse cutaneous SSc. In the longitudinal study, the FGL2 level was generally unchanged at follow-up. The results show that the serum FGL2 level was increased in patients with SSc but not in patients with systemic lupus erythematosus or healthy individuals. Therefore, FGL2 possibly contribute to the development of SSc.

  346. Increased production of soluble inducible costimulator in patients with diffuse cutaneous systemic sclerosis Peer-reviewed

    Koichi Yanaba, Yoshihide Asano, Shinji Noda, Kaname Akamata, Naohiko Aozasa, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Yoshihiro Kuwano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    ARCHIVES OF DERMATOLOGICAL RESEARCH　305　(1)　17-23　2013/01

    DOI： 10.1007/s00403-012-1292-7 　

    ISSN： 0340-3696

  347. Decrease in circulating autotaxin by oral administration of prednisolone Peer-reviewed

    Hayakazu Sumida, Kazuhiro Nakamura, Keisuke Yanagida, Ryunosuke Ohkawa, Yoshihide Asano, Takafumi Kadono, Kunihiko Tamaki, Koji Igarashi, Junken Aoki, Shinichi Sato, Satoshi Ishii, Takao Shimizu, Yutaka Yatomi

    CLINICA CHIMICA ACTA　415　74-80　2013/01

    DOI： 10.1016/j.cca.2012.10.003 　

    ISSN： 0009-8981

  348. Constitutive activation of c-Abl/protein kinase C-delta/Fli1 pathway in dermal fibroblasts derived from patients with localized scleroderma Peer-reviewed

    S. Noda, Y. Asano, K. Akamata, N. Aozasa, T. Taniguchi, T. Takahashi, Y. Ichimura, T. Toyama, H. Sumida, K. Yanaba, Y. Tada, M. Sugaya, T. Kadono, S. Sato

    BRITISH JOURNAL OF DERMATOLOGY　167　(5)　1098-1105　2012/11

    DOI： 10.1111/j.1365-2133.2012.11055.x 　

    ISSN： 0007-0963

    eISSN： 1365-2133

  349. Serum angiogenin levels are decreased in patients with psoriasis. International-journal Peer-reviewed

    Miyagaki T, Sugaya M, Kamata M, Suga H, Morimura S, Tatsuta A, Uwajima Y, Yamamoto M, Shibata S, Fujita H, Asano Y, Kadono T, Sato S, Tada Y

    Clinical and experimental dermatology　37　(7)　792-793　2012/10

    DOI： 10.1111/j.1365-2230.2012.04345.x 　

    ISSN： 0307-6938

  350. Association of the numbers of CD163(+) cells in lesional skin and serum levels of soluble CD163 with disease progression of cutaneous T cell lymphoma Peer-reviewed

    Makoto Sugaya, Tomomitsu Miyagaki, Hanako Ohmatsu, Hiraku Suga, Hiromichi Kai, Masahiro Kamata, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Hitoshi Okochi, Shinichi Sato

    JOURNAL OF DERMATOLOGICAL SCIENCE　68　(1)　45-51　2012/10

    DOI： 10.1016/j.jdermsci.2012.07.007 　

    ISSN： 0923-1811

  351. Augmented production of soluble CD93 in patients with systemic sclerosis and clinical association with severity of skin sclerosis Peer-reviewed

    K. Yanaba, Y. Asano, S. Noda, K. Akamata, N. Aozasa, T. Taniguchi, T. Takahashi, Y. Ichimura, T. Toyama, H. Sumida, Y. Kuwano, Y. Tada, M. Sugaya, T. Kadono, S. Sato

    BRITISH JOURNAL OF DERMATOLOGY　167　(3)　542-547　2012/09

    DOI： 10.1111/j.1365-2133.2012.11020.x 　

    ISSN： 0007-0963

  352. Clinical significance of serum growth differentiation factor-15 levels in systemic sclerosis: association with disease severity Peer-reviewed

    Koichi Yanaba, Yoshihide Asano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    MODERN RHEUMATOLOGY　22　(5)　668-675　2012/09

    DOI： 10.1007/s10165-011-0568-7 　

    ISSN： 1439-7595

  353. Adiponectin Regulates Cutaneous Wound Healing by Promoting Keratinocyte Proliferation and Migration via the ERK Signaling Pathway Peer-reviewed

    Sayaka Shibata, Yayoi Tada, Yoshihide Asano, Carren S. Hau, Toyoaki Kato, Hidehisa Saeki, Toshimasa Yamauchi, Naoto Kubota, Takashi Kadowaki, Shinichi Sato

    JOURNAL OF IMMUNOLOGY　189　(6)　3231-3241　2012/09

    DOI： 10.4049/jimmunol.1101739 　

    ISSN： 0022-1767

  354. BAFF levels are increased in lesional skin and sera in patients with cutaneous T-cell lymphoma. Peer-reviewed

    Ohmatsu H, Sugaya M, Miyagaki T, Suga H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S

    The British journal of dermatology　167　(2)　359-367　2012/08

    DOI： 10.1111/j.1365-2133.2012.10998.x 　

    ISSN： 0007-0963

  355. Improvement of endothelial function in parallel with the amelioration of dry cough and dyspnea due to interstitial pneumonia by intravenous cyclophosphamide pulse therapy in patients with systemic sclerosis: a preliminary report of two cases Peer-reviewed

    Takehiro Takahashi, Yoshihide Asano, Eisuke Amiya, Masaru Hatano, Zenshiro Tamaki, Atsuko Ozeki, Aya Watanabe, Shuichi Kawarasaki, Tomoko Nakao, Takashi Taniguchi, Yohei Ichimura, Tetsuo Toyama, Masafumi Watanabe, Yasunobu Hirata, Ryozo Nagai, Shinichi Sato

    MODERN RHEUMATOLOGY　22　(4)　598-601　2012/08

    DOI： 10.1007/s10165-011-0545-1 　

    ISSN： 1439-7595

    eISSN： 1439-7609

  356. Clinical significance of serum levels of secretory leukocyte protease inhibitor in patients with systemic sclerosis Peer-reviewed

    Naohiko Aozasa, Yoshihide Asano, Kaname Akamata, Shinji Noda, Yuri Masui, Zenshiro Tamaki, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    MODERN RHEUMATOLOGY　22　(4)　576-583　2012/08

    DOI： 10.1007/s10165-011-0553-1 　

    ISSN： 1439-7595

    eISSN： 1439-7609

  357. A possible contribution of elevated serum clusterin levels to the inhibition of digital ulcers and pulmonary arterial hypertension in systemic sclerosis Peer-reviewed

    Koichi Yanaba, Yoshihide Asano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    ARCHIVES OF DERMATOLOGICAL RESEARCH　304　(6)　459-463　2012/08

    DOI： 10.1007/s00403-012-1219-3 　

    ISSN： 0340-3696

  358. Angiogenin levels are increased in lesional skin and sera in patients with erythrodermic cutaneous T cell lymphoma Peer-reviewed

    Tomomitsu Miyagaki, Makoto Sugaya, Hiraku Suga, Kaname Akamata, Hanako Ohmatsu, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    ARCHIVES OF DERMATOLOGICAL RESEARCH　304　(5)　401-406　2012/07

    DOI： 10.1007/s00403-012-1238-0 　

    ISSN： 0340-3696

  359. Leukaemic variant of cutaneous T-cell lymphoma with CD3- CD4+ phenotype. Peer-reviewed

    Taniguchi T, Sugaya M, Miyagaki T, Kogure A, Takekoshi T, Asano Y, Mitsui H, Sato S

    Clinical and experimental dermatology　37　(4)　443-445　2012/06

    DOI： 10.1111/j.1365-2230.2011.04247.x 　

    ISSN： 0307-6938

  360. Long-term complete resolution of severe chronic idiopathic urticaria after dapsone treatment Peer-reviewed

    Shinji Noda, Yoshihide Asano, Shinichi Sato

    JOURNAL OF DERMATOLOGY　39　(5)　496-497　2012/05

    DOI： 10.1111/j.1346-8138.2011.01310.x 　

    ISSN： 0385-2407

  361. Increased serum soluble CD147 levels in patients with systemic sclerosis: association with scleroderma renal crisis Peer-reviewed

    Koichi Yanaba, Yoshihide Asano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Yasuhito Hamaguchi, Shinichi Sato

    CLINICAL RHEUMATOLOGY　31　(5)　835-839　2012/05

    DOI： 10.1007/s10067-012-1949-9 　

    ISSN： 0770-3198

    eISSN： 1434-9949

  362. Clinical significance of serum decoy receptor 3 levels in patients with systemic sclerosis Peer-reviewed

    Daisuke Yamada, Yoshihide Asano, Takehiro Takahashi, Yuri Masui, Naohiko Aozasa, Kaname Akamata, Shinji Noda, Zenshiro Tamaki, Yayoi Tada, Makoto Sugaya, Shinichi Sato, Takafumi Kadono

    EUROPEAN JOURNAL OF DERMATOLOGY　22　(3)　351-357　2012/05

    DOI： 10.1684/ejd.2012.1702 　

    ISSN： 1167-1122

    eISSN： 1952-4013

  363. Serum lipocalin-2 levels are increased in patients with psoriasis. International-journal Peer-reviewed

    Kamata M, Tada Y, Tatsuta A, Kawashima T, Shibata S, Mitsui H, Asano Y, Sugaya M, Kadono T, Kanda N, Watanabe S, Sato S

    Clinical and experimental dermatology　37　(3)　296-299　2012/04

    DOI： 10.1111/j.1365-2230.2011.04265.x 　

    ISSN： 0307-6938

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    The protein lipocalin (LCN)-2 is known to be related to insulin resistance, obesity and atherosclerotic diseases. Psoriasis is an inflammatory skin disease related to metabolic syndrome. The aim of this study was to examine the relationship between serum LCN2 levels and indicators for metabolic syndrome and inflammatory cytokine levels in patients with psoriasis. Serum LCN2 levels were measured in patients with psoriasis, atopic dermatitis (AD) or bullous pemphigoid (BP), and compared with those of healthy controls. Serum LCN2 levels were also compared with several indicators for metabolic syndrome, and with serum levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α, two markers of inflammation. Serum LCN2 levels in patients with psoriasis were significantly higher than those of healthy controls, but there was no significant correlation between serum LCN2 and body mass index. Serum LCN2 levels also correlated with serum IL-6 and TNF-α levels in patients with psoriasis. Serum LCN2 levels are a general indicator for increased inflammation in the patients with psoriasis.

  364. Clinical significance of circulating platelet-activating factor acetylhydrolase levels in systemic sclerosis Peer-reviewed

    Koichi Yanaba, Yoshihide Asano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    ARCHIVES OF DERMATOLOGICAL RESEARCH　304　(3)　203-208　2012/04

    DOI： 10.1007/s00403-011-1196-y 　

    ISSN： 0340-3696

  365. Low Herpesvirus Entry Mediator (HVEM) Expression on Dermal Fibroblasts Contributes to a Th2-Dominant Microenvironment in Advanced Cutaneous T-Cell Lymphoma Peer-reviewed

    Tomomitsu Miyagaki, Makoto Sugaya, Hiraku Suga, Sohshi Morimura, Hanako Ohmatsu, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　132　(4)　1280-1289　2012/04

    DOI： 10.1038/jid.2011.470 　

    ISSN： 0022-202X

  366. Delayed wound healing by treatment of rapamycin and the effect of growth factors

    Ayumi Yoshizaki, Yoshihide Asano, Koichi Yanaba, Shinichi Sato

    Skin Research　11　(17)　39-44　2012/03

    ISSN： 1347-1813

  367. Serum adiponectin levels inversely correlate with the activity of progressive skin sclerosis in patients with diffuse cutaneous systemic sclerosis Peer-reviewed

    Y. Masui, Y. Asano, S. Shibata, S. Noda, N. Aozasa, K. Akamata, D. Yamada, Z. Tamaki, Y. Tada, M. Sugaya, S. Sato, T. Kadono

    JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY　26　(3)　354-360　2012/03

    DOI： 10.1111/j.1468-3083.2011.04077.x 　

    ISSN： 0926-9959

  368. High levels of LIGHT and low levels of soluble herpesvirus entry mediator in sera of patients with atopic dermatitis. Peer-reviewed

    Morimura S, Sugaya M, Kai H, Kato T, Miyagaki T, Ohmatsu H, Kagami S, Asano Y, Mitsui H, Tada Y, Kadono T, Sato S

    Clinical and experimental dermatology　37　(2)　181-182　2012/03

    DOI： 10.1111/j.1365-2230.2011.04079.x 　

    ISSN： 0307-6938

  369. Serum Levels of Galectin-3: Possible Association with Fibrosis, Aberrant Angiogenesis, and Immune Activation in Patients with Systemic Sclerosis Peer-reviewed

    Takashi Taniguchi, Yoshihide Asano, Kaname Akamata, Shinji Noda, Yuri Masui, Daisuke Yamada, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Zenshiro Tamaki, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    JOURNAL OF RHEUMATOLOGY　39　(3)　539-544　2012/03

    DOI： 10.3899/jrheum.110755 　

    ISSN： 0315-162X

    eISSN： 1499-2752

  370. Proteasome Inhibitor Bortezomib Ameliorates Intestinal Injury in Mice Peer-reviewed

    Koichi Yanaba, Yoshihide Asano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    PLOS ONE　7　(3)　e34587　2012/03

    DOI： 10.1371/journal.pone.0034587 　

    ISSN： 1932-6203

  371. Myositis-specific anti-155/140 autoantibodies target transcription intermediaryfactor 1 family proteins. Peer-reviewed

    Fujimoto Manabu, Hamaguchi Yasuhito, Kaji Kenzo, Matsushita Takashi, Ichimura Yuki, Kodera Masanari, Ishiguro Naoko, Ueda-Hayakawa Ikuko, Asano Yoshihide, Ogawa Fumihide, Fujikawa Keita, Miyagi Takuya, Mabuchi Eriko, Hirose Kenji, Akimoto Narihiro, Hatta Naohito, Tsutsui Kiyohiro, Higashi Akira, Igarashi Atsuyuki, Seishima Mariko, Hasegawa Minoru, Takehara Kazuhiko

    Arthritis and rheumatism　64　(2)　513-522　2012/02

    DOI： 10.1002/art.33403 　

    ISSN： 1529-0131

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    To identify the 140-kd autoantigen recognized by anti-155/140 autoantibodies that are associated with adult cancer-associated dermatomyositis (DM) and juvenile DM and to determine the clinical relevance of anti-155/140 antibodies in a large cohort.Sera from 456 DM patients were assessed for the presence of anti-155/140 antibodies by immunoprecipitation using K562 cell extracts as substrate. Using immunoprecipitation and Western blotting, we then examined whether anti-155/140-positive sera recognized transcription intermediary factor 1α (TIF-1α), TIF-1β, and TIF-1γ. The clinical associations of antigen reactivity were also evaluated.Anti-155/140-positive sera reacted with 140-kd TIF-1α in addition to 155-kd TIF-1γ. Among sera from 456 DM patients, 52 were reactive with both TIF-1α and TIF-1γ, while another 25 were reactive with TIF-1γ alone. Additionally, 7 were reactive with TIF-1β. Malignancy was more frequently found in adult patients with both anti-TIF-1α and anti-TIF-1γ antibodies than in those with anti-TIF-1γ antibodies alone (73% versus 50%; P&lt;0.05). In addition to juvenile DM patients and middle-aged and older DM patients with high percentages of malignancy, 8

  372. Serum levels of soluble CD21 in patients with systemic sclerosis. International-journal Peer-reviewed

    Manabu Tomita, Takafumi Kadono, Norihito Yazawa, Tomohiko Kawashima, Zenshiro Tamaki, Ryuichi Ashida, Hanako Ohmatsu, Yoshihide Asano, Makoto Sugaya, Masahide Kubo, Hironobu Ihn, Kunihiko Tamaki, Shinichi Sato

    Rheumatology international　32　(2)　317-21　2012/02

    DOI： 10.1007/s00296-010-1610-3 　

    ISSN： 0172-8172

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    Systemic sclerosis (SSc) is a systemic disorder that typically results in fibrosis of the skin and multiple internal organ systems. Although the precise mechanism is unknown, overproduction of extracellular matrix proteins, including collagens and fibronectins, and aberrant immune activation might be involved in the pathogenesis. The soluble cluster of differentiation 21 (sCD21) represents the extracellular portion of the CD21 glycoprotein that is released by shedding from the cell surfaces into plasma. sCD21 binds complement fragments and activates monocytes through binding to membrane CD23. The present study was undertaken to investigate the serum levels of sCD21 in patients with SSc. Serum sCD21 levels were reduced with age both in patients with SSc and normal controls. Serum sCD21 levels in patients with SSc were significantly decreased compared to those in control subjects. When we divided patients with SSc into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), patients with lcSSc had lower levels of serum sCD21 than those with dcSSc. Moreover, the prevalence of pulmonary fibrosis in the patients with dcSSc inversely correlated with serum sCD21 levels. Our finding may support the notion that B-cell activation is involved in the mechanism for pulmonary fibrosis and skin sclerosis.

  373. Efficacy of low-dose imatinib mesylate for cutaneous involvement in systemic sclerosis: a preliminary report of three cases Peer-reviewed

    Zenshiro Tamaki, Yoshihide Asano, Masaru Hatano, Atsushi Yao, Tomohiko Kawashima, Manabu Tomita, Koichiro Kinugawa, Ryozo Nagai, Shinichi Sato

    MODERN RHEUMATOLOGY　22　(1)　94-99　2012/02

    DOI： 10.1007/s10165-011-0472-1 　

    ISSN： 1439-7595

    eISSN： 1439-7609

  374. Severe generalized pustular psoriasis accompanied by bullae formation with increased serum vascular endothelial growth factor level Peer-reviewed

    Mizuho Yamamoto, Yayoi Tada, Akihiko Asahina, Hidehisa Saeki, Yoshihide Asano, Takayuki Kimura, Makoto Sugaya, Kanako Kikuchi, Kunihiko Tamaki, Shinichi Sato

    JOURNAL OF DERMATOLOGY　39　(2)　183-185　2012/02

    DOI： 10.1111/j.1346-8138.2011.01235.x 　

    ISSN： 0385-2407

  375. Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins Peer-reviewed

    Manabu Fujimoto, Yasuhito Hamaguchi, Kenzo Kaji, Takashi Matsushita, Yuki Ichimura, Masanari Kodera, Naoko Ishiguro, Ikuko Ueda-Hayakawa, Yoshihide Asano, Fumihide Ogawa, Keita Fujikawa, Takuya Miyagi, Eriko Mabuchi, Kenji Hirose, Narihiro Akimoto, Naohito Hatta, Kiyohiro Tsutsui, Akira Higashi, Atsuyuki Igarashi, Mariko Seishima, Minoru Hasegawa, Kazuhiko Takehara

    Arthritis and Rheumatism　64　(2)　513-522　2012/02

    DOI： 10.1002/art.33403 　

    ISSN： 0004-3591

    eISSN： 1529-0131

  376. A Possible Contribution of Altered Cathepsin B Expression to the Development of Skin Sclerosis and Vasculopathy in Systemic Sclerosis Peer-reviewed

    Shinji Noda, Yoshihide Asano, Kaname Akamata, Naohiko Aozasa, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Koichi Yanaba, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    PLOS ONE　7　(2)　e32272　2012/02

    DOI： 10.1371/journal.pone.0032272 　

    ISSN： 1932-6203

  377. Effects of bosentan on nondigital ulcers in patients with systemic sclerosis

    T. Taniguchi, Y. Asano, M. Hatano, Z. Tamaki, M. Tomita, T. Kawashima, M. Miyazaki, H. Sumida, K. Akamata, T. Takahashi, Y. Ichimura, T. Toyama, M. Sugita, S. Noda, A. Yao, K. Kinugawa, S. Sato

    British Journal of Dermatology　166　(2)　417-421　2012

    DOI： 10.1111/j.1365-2133.2011.10581.x 　

    ISSN： 0007-0963 1365-2133

  378. P1-015  限局性強皮症皮膚線維芽細胞におけるc-Abl/PKCδ/Fli1経路の恒常的活性化の意義

    野田 真史, 浅野 善英, 佐藤 伸一

    日本臨床免疫学会会誌　35　(4)　334a-334a　2012

    Publisher: The Japan Society for Clinical Immunology

    DOI： 10.2177/jsci.35.334a 　

    ISSN： 0911-4300

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    TGFβシグナルのSmad非依存性経路の一つであるc-Abl/PKCδ/Fli1経路は全身性強皮症皮膚線維芽細胞の恒常的活性化に強く関与している．今回我々はc-Abl/PKCδ/Fli1経路が限局性強皮症皮膚線維芽細胞の恒常的活性化に関与している可能性について検討した．全細胞溶解液を用いた免疫ブロットでは，c-AblとPKCδの発現量，およびc-AblとFli1のリン酸化は限局性強皮症皮膚線維芽細胞において正常皮膚線維芽細胞よりも亢進していた．一方，核抽出液におけるFli1の発現量とクロマチン免疫沈降法で評価したCOL1A2遺伝子プロモーター領域に結合するFli1はいずれも減少していた．また，PKC-dの細胞内局在について蛍光抗体法で検討したところ，限局性強皮症皮膚線維芽細胞ではPKCδはより核内に局在していた．以上の細胞実験の結果は皮膚組織を用いた免疫染色によりin vivoにおいても再現性を確認できた．さらに，RNA干渉によるc-Ablの遺伝子サイレンシングにより，限局性強皮症皮膚線維芽細胞では・型コラーゲン蛋白の発現量，COL1A2遺伝子のmRNAの発現量がいずれも減少したが，PDGFR阻害薬では同様の効果は見られなかった．以上より，c-Abl/PKCδ/Fli1経路の恒常的な活性化が限局性強皮症皮膚線維芽細胞の恒常的な活性化に寄与していることが示された．また，過去に報告されたメシル酸イマチニブの限局性強皮症の皮膚硬化に対する有効性はc-Abl/PKCδ/Fli1経路の抑制により発揮されている可能性が示唆された．<br>

  379. P1-027  全身性強皮症の病態におけるビスファチンの役割

    増井 友里, 浅野 善英, 柴田 彩, 門野 岳史, 佐藤 伸一

    日本臨床免疫学会会誌　35　(4)　340a-340a　2012

    Publisher: The Japan Society for Clinical Immunology

    DOI： 10.2177/jsci.35.340a 　

    ISSN： 0911-4300

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    全身性強皮症は皮膚および内臓諸臓器の線維化と血管障害を特徴とする全身性の自己免疫疾患である．その発症機序はいまだ不明であるが，炎症・自己免疫・血管障害など様々な要因により線維芽細胞が恒常的に活性化され，結果的に細胞外基質の過剰な沈着が生じると考えられている．その過程にはTGF-βをはじめとし，多くの炎症性サイトカインや成長因子が関与していることが明らかにされている．<br>   ビスファチンは主に脂肪細胞から分泌されるアディポサイトカインの一つで，内臓脂肪蓄積量と高度に相関し，内臓脂肪蓄積を基盤とした病態や脂肪細胞の分化・誘導に関与していると言われている．また，炎症・線維化・免疫調節への関与も報告されており，関節リウマチやベーチェット病，炎症性腸疾患などの炎症性自己免疫疾患での病態に関わることが示唆されている．<br>   今回我々は全身性強皮症患者において血清ビスファチン濃度を測定し，臨床症状や検査データとの関連について検討を行った．さらにTHP-1細胞およびヒト皮膚線維芽細胞を用いてビスファチンが線維化の過程に及ぼす影響を検討し，全身性強皮症の線維化の病態におけるビスファチンの役割について考察した．<br>

  380. Investigation of prognostic factors for skin sclerosis and lung function in Japanese patients with early systemic sclerosis: a multicentre prospective observational study. International-journal Peer-reviewed

    Minoru Hasegawa, Yoshihide Asano, Hirahito Endo, Manabu Fujimoto, Daisuke Goto, Hironobu Ihn, Katsumi Inoue, Osamu Ishikawa, Yasushi Kawaguchi, Masataka Kuwana, Yoshinao Muro, Fumihide Ogawa, Tetsuo Sasaki, Hiroki Takahashi, Sumiaki Tanaka, Kazuhiko Takehara, Shinichi Sato

    Rheumatology (Oxford, England)　51　(1)　129-33　2012/01

    DOI： 10.1093/rheumatology/ker333 　

    ISSN： 1462-0324

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    OBJECTIVE: To clarify the clinical course of SSc in Japanese patients with early-onset disease. It is well known that ethnic variations exist in the clinical features and severity of SSc. However, neither the clinical course nor prognostic factors have been thoroughly investigated in the Japanese population. METHODS: Ninety-three Japanese patients of early-onset SSc (disease duration: <3 years) with diffuse skin sclerosis and/or interstitial lung disease were registered in a multi-centre observational study. All patients had a physical examination with laboratory tests at their first visit and at each of the three subsequent years. Factors that could predict the severity of skin sclerosis and lung involvement were examined statistically by multiple regression analysis. RESULTS: Two patients died from SSc-related myocardial involvement and four patients died from other complications during the 3-year study. Among various clinical data assessed, the initial modified Rodnan total skin thickness score (MRSS) and maximal oral aperture were associated positively and negatively with MRSS at Year 3, respectively. Additionally, initial ESR tended to be associated with final MRSS. Pulmonary vital capacity (VC) in the third year was significantly associated with initial %VC. Furthermore, patients with anti-topo I antibody tended to show reduced %VC at Year 3. CONCLUSIONS: Several possible prognostic factors for skin sclerosis and lung function were detected in Japanese patients with early SSc. Further longitudinal studies of larger populations will be needed to confirm these findings.

  381. P2Y(6) Receptor Signaling Pathway Mediates Inflammatory Responses Induced by Monosodium Urate Crystals Peer-reviewed

    Hideya Uratsuji, Yayoi Tada, Tomohiko Kawashima, Masahiro Kamata, Carren Sy Hau, Yoshihide Asano, Makoto Sugaya, Takafumi Kadono, Akihiko Asahina, Shinichi Sato, Kunihiko Tamaki

    JOURNAL OF IMMUNOLOGY　188　(1)　436-444　2012/01

    DOI： 10.4049/jimmunol.1003746 　

    ISSN： 0022-1767

    eISSN： 1550-6606

  382. Serum IL-31 Levels are Increased in Patients with Cutaneous T-cell Lymphoma Peer-reviewed

    Hanako Ohmatsu, Makoto Sugaya, Hiraku Suga, Sohshi Morimura, Tomomitsu Miyagaki, Hiromichi Kai, Shinji Kagami, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    ACTA DERMATO-VENEREOLOGICA　92　(3)　282-283　2012

    DOI： 10.2340/00015555-1345 　

    ISSN： 0001-5555

  383. Dermatomyositis with anti-OJ antibody Peer-reviewed

    Shinji Noda, Yoshihide Asano, Zenshiro Tamaki, Megumi Hirabayashi, Mizuho Yamamoto, Tomonori Takekoshi, Toshihiko Hoashi, Makoto Sugaya, Rieko Morimoto, Takafumi Etoh, Kenzo Kaji, Manabu Fujimoto, Masataka Kuwana, Shinichi Sato

    RHEUMATOLOGY INTERNATIONAL　31　(12)　1673-1675　2011/12

    DOI： 10.1007/s00296-010-1695-8 　

    ISSN： 0172-8172

  384. IL-22, but Not IL-17, Dominant Environment in Cutaneous T-cell Lymphoma Peer-reviewed

    Tomomitsu Miyagaki, Makoto Sugaya, Hiraku Suga, Masahiro Kamata, Hanako Ohmatsu, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    CLINICAL CANCER RESEARCH　17　(24)　7529-7538　2011/12

    DOI： 10.1158/1078-0432.CCR-11-1192 　

    ISSN： 1078-0432

    eISSN： 1557-3265

  385. Immunization With DNA Topoisomerase I and Freund's Complete Adjuvant Induces Skin and Lung Fibrosis and Autoimmunity via Interleukin-6 Signaling Peer-reviewed

    Ayumi Yoshizaki, Koichi Yanaba, Asako Ogawa, Yoshihide Asano, Takafumi Kadono, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　63　(11)　3575-3585　2011/11

    DOI： 10.1002/art.30539 　

    ISSN： 0004-3591

  386. High Calcium, ATP, and Poly(I:C) Augment the Immune Response to beta-Glucan in Normal Human Epidermal Keratinocytes Peer-reviewed

    Carren Sy Hau, Yayoi Tada, Sayaka Shibata, Hideya Uratsuji, Yoshihide Asano, Makoto Sugaya, Takafumi Kadono, Naoko Kanda, Shinichi Watanabe, Kunihiko Tamaki, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　131　(11)　2255-2262　2011/11

    DOI： 10.1038/jid.2011.201 　

    ISSN： 0022-202X

  387. Differential patterns of CXCR3, CCR3, and CCR10 expression in mycosis fungoides, Sezary syndrome and CD30(+) lymphoproliferative disorders: Immunohistochemical study of 43 samples Peer-reviewed

    Hiraku Suga, Makoto Sugaya, Tomomitsu Miyagaki, Hanako Ohmatsu, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    JOURNAL OF DERMATOLOGICAL SCIENCE　64　(2)　142-144　2011/11

    DOI： 10.1016/j.jdermsci.2011.07.004 　

    ISSN： 0923-1811

  388. Significant attenuation of macrovascular involvement by bosentan in a patient with diffuse cutaneous systemic sclerosis with multiple digital ulcers and gangrene Peer-reviewed

    Yohei Ichimura, Yoshihide Asano, Masaru Hatano, Zenshiro Tamaki, Tomonori Takekoshi, Asako Kogure, Manabu Tomita, Tomohiko Kawashima, Miki Miyazaki, Takashi Taniguchi, Takehiro Takahashi, Hiroshi Mitsui, Makoto Sugaya, Atsushi Yao, Koichiro Kinugawa, Shinichi Sato

    MODERN RHEUMATOLOGY　21　(5)　548-552　2011/10

    DOI： 10.1007/s10165-011-0436-5 　

    ISSN： 1439-7595

    eISSN： 1439-7609

  389. The Specific Free Radical Scavenger Edaravone Suppresses Fibrosis in the Bleomycin-Induced and Tight Skin Mouse Models of Systemic Sclerosis Peer-reviewed

    Ayumi Yoshizaki, Koichi Yanaba, Asako Ogawa, Yohei Iwata, Fumihide Ogawa, Motoi Takenaka, Kazuhiro Shimizu, Yoshihide Asano, Takafumi Kadono, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　63　(10)　3086-3097　2011/10

    DOI： 10.1002/art.30470 　

    ISSN： 0004-3591

  390. Serum Interleukin 9 Levels Are Increased in Patients with Systemic Sclerosis: Association with Lower Frequency and Severity of Pulmonary Fibrosis Peer-reviewed

    Koichi Yanaba, Ayumi Yoshizaki, Yoshihide Asano, Takafumi Kadono, Shinichi Sato

    JOURNAL OF RHEUMATOLOGY　38　(10)　2193-2197　2011/10

    DOI： 10.3899/jrheum.110268 　

    ISSN： 0315-162X

  391. Blocking MAPK Signaling Downregulates CCL21 in Lymphatic Endothelial Cells and Impairs Contact Hypersensitivity Responses Peer-reviewed

    Tomomitsu Miyagaki, Makoto Sugaya, Hitoshi Okochi, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Andrew Blauvelt, Kunihiko Tamaki, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　131　(9)　1927-1935　2011/09

    DOI： 10.1038/jid.2011.135 　

    ISSN： 0022-202X

  392. The development of Th1-mediated sarcoidosis improves the clinical course of Th2-mediated atopic dermatitis Peer-reviewed

    Tomomitsu Miyagaki, Yoshihide Asano, Sayaka Shibata, Yuki Ohno, Yuichiro Tsunemi, Hidehisa Saeki, Kunihiko Tamaki, Shinichi Sato

    MODERN RHEUMATOLOGY　21　(4)　406-409　2011/08

    DOI： 10.1007/s10165-010-0404-5 　

    ISSN： 1439-7595

  393. Systemic sclerosis with an unusual rapid development of huge calcinosis (tumoral calcinosis) Peer-reviewed

    Naohiko Aozasa, Yoshihide Asano, Ryuichi Ashida, Zenshiro Tamaki, Mizuho Yamamoto, Manabu Tomita, Tomohiko Kawashima, Makoto Sugaya, Kunihiko Tamaki, Shinichi Sato

    JOURNAL OF DERMATOLOGY　38　(8)　836-838　2011/08

    DOI： 10.1111/j.1346-8138.2010.01078.x 　

    ISSN： 0385-2407

  394. Bosentan: a novel therapy for leg ulcers in Werner syndrome. International-journal Peer-reviewed

    Shinji Noda, Yoshihide Asano, Sho Masuda, Takuya Miyagawa, Miki Sugita, Mizuho Yamamoto, Asako Kogure, Zenshiro Tamaki, Hiroshi Mitsui, Toshihiko Hoashi, Makoto Sugaya, Shinichi Sato

    Journal of the American Academy of Dermatology　65　(2)　e54-e55-e55　2011/08

    DOI： 10.1016/j.jaad.2011.03.013 　

    ISSN： 0190-9622

  395. Pityriasis lichenoides et varioliformis acuta exacerbated after tonsillectomy Peer-reviewed

    Shinji Noda, Yoshihide Asano, Shinichi Sato

    EUROPEAN JOURNAL OF DERMATOLOGY　21　(4)　648-649　2011/07

    DOI： 10.1684/ejd.2011.1341 　

    ISSN： 1167-1122

  396. Disseminated cutaneous and visceral Kaposi&apos;s sarcoma in a patient with rheumatoid arthritis receiving corticosteroids and tacrolimus Peer-reviewed

    Takashi Taniguchi, Yoshihide Asano, Makiko Kawaguchi, Asako Kogure, Hiroshi Mitsui, Makoto Sugaya, Shinichi Sato

    MODERN RHEUMATOLOGY　21　(3)　309-312　2011/06

    DOI： 10.1007/s10165-010-0389-0 　

    ISSN： 1439-7595

  397. Serum IL-33 levels are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis Peer-reviewed

    Koichi Yanaba, Ayumi Yoshizaki, Yoshihide Asano, Takafumi Kadono, Shinichi Sato

    CLINICAL RHEUMATOLOGY　30　(6)　825-830　2011/06

    DOI： 10.1007/s10067-011-1686-5 　

    ISSN： 0770-3198

    eISSN： 1434-9949

  398. The c-Abl Tyrosine Kinase Controls Protein Kinase C delta-Induced Fli-1 Phosphorylation in Human Dermal Fibroblasts Peer-reviewed

    Andreea M. Bujor, Yoshihide Asano, Paul Haines, Robert Lafyatis, Maria Trojanowska

    ARTHRITIS AND RHEUMATISM　63　(6)　1729-1737　2011/06

    DOI： 10.1002/art.30284 　

    ISSN： 0004-3591

  399. Semaphorin 7A on keratinocytes induces interleukin-8 production by monocytes Peer-reviewed

    Masahiro Kamata, Yayoi Tada, Hideya Uratsuji, Tomohiko Kawashima, Yoshihide Asano, Makoto Sugaya, Takafumi Kadono, Kunihiko Tamaki, Shinichi Sato

    JOURNAL OF DERMATOLOGICAL SCIENCE　62　(3)　176-182　2011/06

    DOI： 10.1016/j.jdermsci.2011.02.004 　

    ISSN： 0923-1811

    eISSN： 1873-569X

  400. Development of Behcet&apos;s disease in a Caucasian with human leukocyte antigen B51 after immigration to Japan Peer-reviewed

    Takayuki Kimura, Yoshihide Asano, Mizuho Yamamoto, Makoto Sugaya, Shinichi Sato

    JOURNAL OF DERMATOLOGY　38　(6)　581-584　2011/06

    DOI： 10.1111/j.1346-8138.2010.01125.x 　

    ISSN： 0385-2407

  401. Localized scleroderma en coup de sabre exacerbated during pregnancy followed by postpartum development of rheumatoid arthritis Peer-reviewed

    Shinji Noda, Yoshihide Asano, Ryuichi Ashida, Zenshiro Tamaki, Manabu Tomita, Tomohiko Kawashima, Shinichi Sato

    EUROPEAN JOURNAL OF DERMATOLOGY　21　(3)　441-442　2011/05

    DOI： 10.1684/ejd.2011.1342 　

    ISSN： 1167-1122

  402. Lichen planus in a patient with long-term exposure to chrome Peer-reviewed

    Shinji Noda, Yoshihide Asano, Shinichi Sato

    EUROPEAN JOURNAL OF DERMATOLOGY　21　(3)　417-418　2011/05

    DOI： 10.1684/ejd.2011.1291 　

    ISSN： 1167-1122

  403. Severe Livedoid Vasculopathy Associated With Antiphosphatidylserine-Prothrombin Complex Antibody Successfully Treated With Warfarin Peer-reviewed

    Shinji Noda, Yoshihide Asano, Masahide Yamazaki, Yohei Ichimura, Zenshiro Tamaki, Tomonori Takekoshi, Makoto Sugaya, Shinichi Sato

    ARCHIVES OF DERMATOLOGY　147　(5)　621-623　2011/05

    DOI： 10.1001/archdermatol.2011.106 　

    ISSN： 0003-987X

  404. Hyperviscosity syndrome associated with systemic plasmacytosis Peer-reviewed

    S. Noda, Y. Tsunemi, Y. Ichimura, A. Miyamoto, Z. Tamaki, T. Takekoshi, Y. Asano, T. Hoashi, M. Sugaya, T. Inoue, S. Sato

    Clinical and Experimental Dermatology　36　(3)　273-276　2011/04

    DOI： 10.1111/j.1365-2230.2010.03928.x 　

    ISSN： 0307-6938 1365-2230

  405. Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: A multicenter cross-sectional study Peer-reviewed

    Yasuhito Hamaguchi, Masataka Kuwana, Kana Hoshino, Minoru Hasegawa, Kenzo Kaji, Takashi Matsushita, Kazuhiro Komura, Motonobu Nakamura, Masanari Kodera, Norihiro Suga, Akira Higashi, Koji Ogusu, Kiyohiro Tsutsui, Akira Furusaki, Hiroshi Tanabe, Shunsuke Sasaoka, Yoshinao Muro, Mika Yoshikawa, Naoko Ishiguro, Masahiro Ayano, Eiji Muroi, Keita Fujikawa, Yukihiro Umeda, Masaaki Kawase, Eriko Mabuchi, Yoshihide Asano, Kinuyo Sodemoto, Mariko Seishima, Hidehiro Yamada, Shinichi Sato, Kazuhiko Takehara, Manabu Fujimoto

    Archives of Dermatology　147　(4)　391-398　2011/04

    DOI： 10.1001/archdermatol.2011.52 　

    ISSN： 0003-987X

    eISSN： 1538-3652

  406. Adiponectin as an anti-inflammatory factor in the pathogenesis of psoriasis: induction of elevated serum adiponectin levels following therapy. Peer-reviewed

    Shibata S, Tada Y, Hau C, Tatsuta A, Yamamoto M, Kamata M, Karakawa M, Asano Y, Mitsui H, Sugaya M, Kadono T, Saeki H, Kanda N, Sato S

    The British journal of dermatology　164　(3)　667-670　2011/03

    DOI： 10.1111/j.1365-2133.2010.10123.x 　

    ISSN： 0007-0963

  407. CCL11-CCR3 Interactions Promote Survival of Anaplastic Large Cell Lymphoma Cells via ERK1/2 Activation Peer-reviewed

    Tomomitsu Miyagaki, Makoto Sugaya, Takashi Murakami, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Hitoshi Okochi, Kunihiko Tamaki, Shinichi Sato

    CANCER RESEARCH　71　(6)　2056-2065　2011/03

    DOI： 10.1158/0008-5472.CAN-10-3764 　

    ISSN： 0008-5472

    eISSN： 1538-7445

  408. Altered dynamics of transforming growth factor β(TGF-β) receptors in scleroderma fibroblasts. International-journal Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Masatoshi Jinnin, Kunihiko Tamaki, Shinichi Sato

    Annals of the rheumatic diseases　70　(2)　384-7　2011/02

    DOI： 10.1136/ard.2009.127811 　

    ISSN： 0003-4967

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    OBJECTIVES: To investigate the difference in the dynamics of transforming growth factor β (TGF-β) receptors between normal and scleroderma fibroblasts. METHODS: The cell surface expression levels of TGF-β receptors were determined by biotinylation and immunoprecipitation assay. The dynamics of TGF-β receptors on the cell surface was determined by the reversible biotinylation assay. The subcellular localisation of TGF-β receptors was determined by immunoprecipitation using antibodies against clathrin and caveolin. RESULTS: Although the total expression levels of TGF-β receptors were elevated in scleroderma fibroblasts compared with normal fibroblasts, there was no significant difference in the cell surface expression levels of TGF-β receptors between these two groups. However, the internalisation rate of TGF-β receptors was higher in scleroderma fibroblasts compared with normal fibroblasts. Furthermore, caveolin constitutively made a complex with TGF-β receptors, while the interaction of clathrin with TGF-β receptors was marginal in scleroderma fibroblasts. CONCLUSIONS: The dynamics of TGF-β receptors on the cell surface is accelerated in scleroderma fibroblasts. Considering that the activation state of TGF-β signalling is regulated by a balance between the clathrin-dependent internalisation and the lipid raft-caveolar internalisation, the accumulation of TGF-β receptors in caveolin-positive vesicles may result in the deceleration of caveolin-dependent internalisation and subsequently lead to the relative acceleration of clathrin-dependent internalisation.

  409. IL-10-Producing Regulatory B10 Cells Inhibit Intestinal Injury in a Mouse Model Peer-reviewed

    Koichi Yanaba, Ayumi Yoshizaki, Yoshihide Asano, Takafumi Kadono, Thomas F. Tedder, Shinichi Sato

    AMERICAN JOURNAL OF PATHOLOGY　178　(2)　735-743　2011/02

    DOI： 10.1016/j.ajpath.2010.10.022 　

    ISSN： 0002-9440

  410. P-057(O2-1-2) High calcium, ATP and poly (I:C) augment the immune response to &beta;-glucan in human keratinocytes

    Program and Abstracts of Annual Meeting of the Japanese Society for Medical Mycology　52　100-100　2011

    Publisher: The Japanese Society for Medical Mycology

    DOI： 10.11534/jsmm.52y.0_100_1 　

  411. Serum CCL23 levels are increased in patients with systemic sclerosis Peer-reviewed

    Koichi Yanaba, Ayumi Yoshizaki, Eiji Muroi, Fumihide Ogawa, Yoshihide Asano, Takafumi Kadono, Shinichi Sato

    ARCHIVES OF DERMATOLOGICAL RESEARCH　303　(1)　29-34　2011/01

    DOI： 10.1007/s00403-010-1078-8 　

    ISSN： 0340-3696

  412. CCR10 and CCL27 are overexpressed in cutaneous squamous cell carcinoma Peer-reviewed

    Hiromichi Kai, Takafumi Kadono, Takashi Kakinuma, Manabu Tomita, Hanako Ohmatsu, Yoshihide Asano, Yayoi Tada, Makoto Sugaya, Shinichi Sato

    PATHOLOGY RESEARCH AND PRACTICE　207　(1)　43-48　2011

    DOI： 10.1016/j.prp.2010.10.007 　

    ISSN： 0344-0338

  413. Ultraviolet Light-induced Kobner Phenomenon Contributes to the Development of Skin Eruptions in Multicentric Reticulohistiocytosis Peer-reviewed

    Takashi Taniguchi, Yoshihide Asano, Asako Okada, Makoto Sugaya, Shinichi Sato

    ACTA DERMATO-VENEREOLOGICA　91　(2)　160-163　2011

    DOI： 10.2340/00015555-0961 　

    ISSN： 0001-5555

  414. Zosteriform Venous Malformations with an Atypical Presentation Peer-reviewed

    Shinji Noda, Yoshihide Asano, Rumi Sugie, Kyoko Mizuno, Makoto Adachi

    ACTA DERMATO-VENEREOLOGICA　91　(3)　369-371　2011

    DOI： 10.2340/00015555-1043 　

    ISSN： 0001-5555

  415. A Case of Systemic Sclerosis with Sarcoidosis Peer-reviewed

    Hiraku Suga, Yoshihide Asano, Zenshiro Tamaki, Mizuho Yamamoto, Makoto Sugaya, Jun Shimizu, Shinichi Sato

    ACTA DERMATO-VENEREOLOGICA　91　(6)　718-720　2011

    DOI： 10.2340/00015555-1155 　

    ISSN： 0001-5555

  416. Serum TARC/CCL17 levels are increased in dermatomyositis associated with interstitial lung disease. International-journal Peer-reviewed

    Tomohiko Kawashima, Yayoi Tada, Yoshihide Asano, Norihito Yazawa, Manabu Tomita, Zenshiro Tamaki, Masahide Kubo, Hironobu Ihn, Makoto Sugaya, Takafumi Kadono, Kunihiko Tamaki, Shinichi Sato

    Journal of dermatological science　60　(1)　52-4　2010/10

    DOI： 10.1016/j.jdermsci.2010.07.012 　

    ISSN： 0923-1811

  417. Close association of anti-U1 ribonucleoprotein antibody with drug allergy in patients with connective tissue diseases Peer-reviewed

    Ryuichi Ashida, Yoshihide Asano, Zenshiro Tamaki, Manabu Tomita, Tomohiko Kawashima, Kaname Aakamata, Shinichi Sato

    JOURNAL OF DERMATOLOGICAL SCIENCE　60　(1)　56-57　2010/10

    DOI： 10.1016/j.jdermsci.2010.08.005 　

    ISSN： 0923-1811

  418. The impact of Fli1 deficiency on the pathogenesis of systemic sclerosis Peer-reviewed

    Yoshihide Asano, Andreea M. Bujor, Maria Trojanowska

    JOURNAL OF DERMATOLOGICAL SCIENCE　59　(3)　153-162　2010/09

    DOI： 10.1016/j.jdermsci.2010.06.008 　

    ISSN： 0923-1811

  419. A case of dermatomyositis with "liver disease associated with rheumatoid diseases" positive for anti-liver-kidney microsome-1 antibody Peer-reviewed

    Shinji Noda, Yoshihide Asano, Zenshiro Tamaki, Tomonori Takekoshi, Makoto Sugaya, Shinichi Sato

    CLINICAL RHEUMATOLOGY　29　(8)　941-943　2010/08

    DOI： 10.1007/s10067-010-1397-3 　

    ISSN： 0770-3198

  420. Treatment With Rapamycin Prevents Fibrosis in Tight-Skin and Bleomycin-Induced Mouse Models of Systemic Sclerosis Peer-reviewed

    Ayumi Yoshizaki, Koichi Yanaba, Asako Yoshizaki, Yohei Iwata, Kazuhiro Komura, Fumihide Ogawa, Motoi Takenaka, Kazuhiro Shimizu, Yoshihide Asano, Minoru Hasegawa, Manabu Fujimoto, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　62　(8)　2476-2487　2010/08

    DOI： 10.1002/art.27498 　

    ISSN： 0004-3591

  421. Dihydrosphingosine 1-Phosphate Has a Potent Antifibrotic Effect in Scleroderma Fibroblasts via Normalization of Phosphatase and Tensin Homolog Levels Peer-reviewed

    Shizhong Bu, Yoshihide Asano, Andreea Bujor, Kristin Highland, Faye Hant, Maria Trojanowska

    ARTHRITIS AND RHEUMATISM　62　(7)　2117-2126　2010/07

    DOI： 10.1002/art.27463 　

    ISSN： 0004-3591

  422. Endothelial Fli1 Deficiency Impairs Vascular Homeostasis A Role in Scleroderma Vasculopathy Peer-reviewed

    Yoshihide Asano, Lukasz Stawski, Faye Hant, Kristin Highland, Richard Silver, Gabor Szalai, Dennis K. Watson, Maria Trojanowska

    AMERICAN JOURNAL OF PATHOLOGY　176　(4)　1983-1998　2010/04

    DOI： 10.2353/ajpath.2010.090593 　

    ISSN： 0002-9440

  423. P-076 Histamine, ATP and Poly (I:C) augment the immune response to &beta;-glucan in human keratinocytes

    Carren Hau

    Program and Abstracts of Annual Meeting of the Japanese Society for Medical Mycology　52　80-80　2010

    Publisher: The Japanese Society for Medical Mycology

    DOI： 10.11534/jsmm.52x.0_80_4 　

  424. Future treatments in systemic sclerosis Peer-reviewed

    Yoshihide Asano

    JOURNAL OF DERMATOLOGY　37　(1)　54-70　2010/01

    DOI： 10.1111/j.1346-8138.2009.00758.x 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  425. A Case of Primary Idiopathic Cutaneous Pustular Vasculitis Peer-reviewed

    Yoshihide Asano, Kenzo Kaji, Takeo Idezuki, Atsuyuki Igarashi

    ACTA DERMATO-VENEREOLOGICA　90　(4)　420-421　2010

    DOI： 10.2340/00015555-0857 　

    ISSN： 0001-5555

  426. Clinical and laboratory features of Japanese patients with scleroderma and telangiectasia Peer-reviewed

    R. Ashida, H. Ihn, Y. Mimura, M. Jinnin, Y. Asano, M. Kubo, K. Tamaki

    CLINICAL AND EXPERIMENTAL DERMATOLOGY　34　(7)　781-783　2009/10

    DOI： 10.1111/j.1365-2230.2008.03148.x 　

    ISSN： 0307-6938

  427. Retrospective study of clinical and laboratory features in Japanese scleroderma patients with cardiac involvement. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Yoshihide Asano, Kenichi Yamane, Norihito Yazawa, Kunihiko Tamaki

    Journal of dermatological science　55　(1)　70-2　2009/07

    DOI： 10.1016/j.jdermsci.2009.03.004 　

    ISSN： 0923-1811

  428. Phosphorylation of Fli1 at Threonine 312 by Protein Kinase C delta Promotes Its Interaction with p300/CREB-Binding Protein-Associated Factor and Subsequent Acetylation in Response to Transforming Growth Factor beta Peer-reviewed

    Yoshihide Asano, Maria Trojanowska

    MOLECULAR AND CELLULAR BIOLOGY　29　(7)　1882-1894　2009/04

    DOI： 10.1128/MCB.01320-08 　

    ISSN： 0270-7306

  429. Transcription Factor Fli1 Regulates Collagen Fibrillogenesis in Mouse Skin Peer-reviewed

    Yoshihide Asano, Margaret Markiewicz, Masahide Kubo, Gabor Szalai, Dennis K. Watson, Maria Trojanowska

    MOLECULAR AND CELLULAR BIOLOGY　29　(2)　425-434　2009/01

    DOI： 10.1128/MCB.01278-08 　

    ISSN： 0270-7306

  430. Smad1 pathway is activated in systemic sclerosis fibroblasts and is targeted by imatinib mesylate Peer-reviewed

    Jaspreet Pannu, Yoshihide Asano, Sashidhar Nakerakanti, Edwin Smith, Stefania Jablonska, Maria Blaszczyk, Peter ten Dijke, Maria Trojanowska

    ARTHRITIS AND RHEUMATISM　58　(8)　2528-2537　2008/08

    DOI： 10.1002/art.23698 　

    ISSN： 0004-3591

  431. Transforming growth factor-beta regulates DNA binding activity of transcription factor fli1 by p300/CREB-binding protein-associated factor-dependent acetylation Peer-reviewed

    Yoshihide Asano, Joanna Czuwara, Maria Trojanowska

    JOURNAL OF BIOLOGICAL CHEMISTRY　282　(48)　34672-34683　2007/11

    DOI： 10.1074/jbc.M703907200 　

    ISSN： 0021-9258

  432. Necrobiotic xanthogranuloma with paraproteinemia successfully treated with melphalan, prednisolone and skin graft Peer-reviewed

    Hidehisa Saeki, Manabu Tomita, Hiromichi Kai, Yuki Ohno, Andre Le Pavoux, Takafumi Kadono, Yuichiro Tsunemi, Naoki Sakurai, Yoshihide Asano, Kunihiko Tamaki

    JOURNAL OF DERMATOLOGY　34　(11)　795-797　2007/11

    DOI： 10.1111/j.1346-8138.2007.00387.x 　

    ISSN： 0385-2407

  433. Distinct effects of gonadectomy in mate and female mice on collagen fibrillogenesis in the skin Peer-reviewed

    Margaret Markiewicz, Yoshihide Asano, Sergey Znoyko, Yong Gong, Dennis K. Watson, Maria Trojanowska

    JOURNAL OF DERMATOLOGICAL SCIENCE　47　(3)　217-226　2007/09

    DOI： 10.1016/j.jdermsci.2007.05.008 　

    ISSN： 0923-1811

  434. Anti-p53 antibodies in patients with dermatomyositis/polymyositis. International-journal Peer-reviewed

    Yoshihiro Mimura, Norihito Yazawa, Zenshirou Tamaki, Ryuichi Ashida, Masatoshi Jinnin, Yoshihide Asano, Yayoi Tada, Masahide Kubo, Hironobu Ihn, Kunihiko Tamaki

    Clinical rheumatology　26　(8)　1328-31　2007/08

    DOI： 10.1007/s10067-006-0473-1 　

    ISSN： 0770-3198

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    Dermatomyositis/polymyositis (DM/PM), which is often accompanied by various immunological abnormalities, was reported to be associated with an increased incidence of malignancies. In this study, we analyzed serum levels of anti-p53 antibody (anti-p53 Ab) in DM/PM patients and in normal controls. Serum levels of anti-p53 Abs were significantly higher in DM/PM patients than those in healthy controls. However, there was no significant difference between serum levels in patients with malignancies and those in patients without malignancies. Anti-p53 Abs were positive in 13% (4 out of 31) of the DM/PM patients. Of these four patients, only one had an internal malignancy. Immunoglobulin G levels were significantly higher in patients positive for anti-p53 Ab than those who were not. These results seemed to suggest that the presence of anti-p53 Abs in DM/PM patients is due to immunological abnormalities in this disease.

  435. Clinical features of scleroderma patients with contracture of phalanges. International-journal Peer-reviewed

    Ryuichi Ashida, Hironobu Ihn, Yoshihiro Mimura, Masatoshi Jinnin, Yoshihide Asano, Masahide Kubo, Kunihiko Tamaki

    Clinical rheumatology　26　(8)　1275-7　2007/08

    DOI： 10.1007/s10067-006-0490-0 　

    ISSN： 0770-3198

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    Contracture of phalanges (CP) is a frequent complication of patients with systemic sclerosis (SSc). The objective of this study was to examine the prevalance of CP in patients with SSc and investigate the clinical and laboratory features of SSc patients with CP. Three hundred and fifty patients with SSc were examined. CP was found in 164 of the 350 patients (47%) with SSc. The prevalence of oesophageal involvement, pulmonary fibrosis or heart involvement was significantly greater in the patients with CP than that in those without CP. Our study suggested that the presence of CP may be a marker of oesophageal involvement, pulmonary fibrosis and heart involvement.

  436. Linear connective tissue nevus Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Kunihiko Tamaki

    PEDIATRIC DERMATOLOGY　24　(4)　439-441　2007/07

    DOI： 10.1111/j.1525-1470.2007.00477.x 　

    ISSN： 0736-8046

  437. Involvement of the constitutive complex formation of c-Ski/SnoN with Smads in the impaired negative feedback regulation of transforming growth factor beta signaling in scleroderma fibroblasts. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Yoshihiro Mimura, Yoshihide Asano, Kunihiko Tamaki

    Arthritis and rheumatism　56　(5)　1694-705　2007/05

    DOI： 10.1002/art.22588 　

    ISSN： 0004-3591

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    OBJECTIVE: The principal effect of transforming growth factor beta1 (TGFbeta1) on mesenchymal cells is its stimulation of extracellular matrix synthesis. Previous reports indicated the significance of the autocrine TGFbeta loop in the pathogenesis of scleroderma. The aim of this study was to examine c-Ski and SnoN, principal molecules in the negative regulation of TGFbeta signaling, to further understand the autocrine TGFbeta loop in scleroderma. METHODS: Levels of expression of c-Ski/SnoN on cultured normal and scleroderma fibroblasts were determined by Western blotting, Northern blotting, and immunohistochemical staining. To determine the protein-protein interaction between c-Ski/SnoN, Smads, and p300, immunoprecipitation was performed. A transient transfection assay was performed to measure promoter activity of the alpha2(I) collagen gene and the 3TP-Lux plasmid construct. RESULTS: Scleroderma fibroblasts exhibited increased c-Ski/SnoN levels compared with normal fibroblasts, both in vivo and in vitro. Although c-Ski/SnoN constitutively formed a complex with Smads by immunoprecipitation, the inhibitory effect of c-Ski/SnoN on the promoter activity of human alpha2(I) collagen and 3TP-Lux was impaired in scleroderma fibroblasts. Immunoprecipitation analyses also revealed that overexpressed c-Ski/SnoN could not compete with p300 in these cells. CONCLUSION: These results indicate that impaired competition with p300 is the possible cause of dysfunction of c-Ski/SnoN in scleroderma fibroblasts and that this might contribute to maintenance of the autocrine TGFbeta loop in this disease.

  438. Epidermal growth factor up-regulates transforming growth factor-beta receptor type II in human dermal fibroblasts via p38 mitogen-activated protein kinase pathway. International-journal Peer-reviewed

    Kenichi Yamane, Yoshihide Asano, Kunihiko Tamaki, Hironobu Ihn

    Biochemical and biophysical research communications　352　(1)　69-77　2007/01/05

    DOI： 10.1016/j.bbrc.2006.10.148 　

    ISSN： 0006-291X

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    TGF-beta receptors (TbetaRs) are serine/threonine kinase receptors that bind to TGF-beta and propagate intracellular signaling through Smad proteins. TbetaRs are repressed in some human cancers and expressed at high levels in several fibrotic diseases. We demonstrated that epidermal growth factor (EGF) up-regulates type II TGF-beta receptor (TbetaRII) expression in human dermal fibroblasts. EGF-mediated induction of TbetaRII expression was inhibited by the treatment of fibroblasts with a specific p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, whereas MEK inhibitor PD98059 did not block the up-regulation of TbetaRII by EGF. EGF induced the TbetaRII promoter activity, and this induction was significantly blocked by SB203580, but not by PD98059. The overexpression of the dominant negative form of p38alpha or p38beta significantly reduced the induction of TbetaRII promoter activity by EGF. These results indicate that the EGF-mediated induction of TbetaRII expression involves the p38 MAPK signaling pathway. The EGF-mediated induction of TbetaRII expression may participate in a synergistic interplay between EGF and TGF-beta signaling pathway.

  439. Involvement of alphavbeta5 integrin in the establishment of autocrine TGF-beta signaling in dermal fibroblasts derived from localized scleroderma. International-journal Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Masatoshi Jinnin, Yoshihiro Mimura, Kunihiko Tamaki

    The Journal of investigative dermatology　126　(8)　1761-9　2006/08

    DOI： 10.1038/sj.jid.5700331 　

    ISSN： 0022-202X

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    Localized scleroderma (LSc) is a connective tissue disorder limited to skin and subcutaneous tissue, which may share pathogenic processes with systemic sclerosis (SSc). We previously demonstrated that upregulated expression of integrin alphavbeta5 might contribute to autocrine TGF-beta signaling in SSc fibroblasts. Based on these data, we presently focused on alphavbeta5 and assessed its involvement in pathogenesis of LSc. We initially demonstrated that LSc fibroblasts might be activated by the stimulation of autocrine TGF-beta. Consistent with SSc fibroblasts, expression levels of alphavbeta5 were elevated in LSc fibroblasts in vitro and in vivo. Anti-alphavbeta5 antibody partially reversed expression levels of type I procollagen and MMP-1 and constitutive DNA-Smad3 binding in LSc fibroblasts. In LSc fibroblasts pretreated with antisense TGF-beta1, exogenous latent TGF-beta1 stimulation increased expression of type I procollagen in an alphavbeta5-dependent manner. The luciferase activities of TMLC cells, Mv1Lu cells stably expressing a portion of the plasminogen activator inhibitor 1 promoter, co-cultured with LSc fibroblasts were significantly elevated compared with those co-cultured with normal fibroblasts and were significantly reduced in the presence of anti-alphavbeta5 antibody. Anti-alphavbeta5 antibody reversed the myofibroblastic features of LSc fibroblasts. These results indicate that upregulated expression of alphavbeta5 contributes to autocrine TGF-beta signaling in LSc fibroblasts.

  440. Rheumatoid factor isotypes in mixed connective tissue disease. International-journal Peer-reviewed

    Yoshihiro Mimura, Hironobu Ihn, Masatoshi Jinnin, Yoshihide Asano, Kenichi Yamane, Kunihiko Tamaki

    Clinical rheumatology　25　(4)　572-4　2006/07

    DOI： 10.1007/s10067-005-0185-y 　

    ISSN： 0770-3198

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    Mixed connective tissue disease (MCTD) is a connective tissue disorder that is often accompanied by various immunological abnormalities. In this study, we analyzed serum levels of rheumatoid factor (RF) isotypes in patients with MCTD and in normal controls to determine if any of these isotypes reflects the severity of the disease. IgM-RF, IgG-RF, and IgA-RF were positive in 48, 38, and 33% of the patients, respectively. The frequency of positive anti-SS-A antibody and decrease in white blood cell counts were significantly greater in patients with elevated IgA-RF levels than that in those with normal levels. These results suggest that the presence of RF isotypes can be regarded as one of the various immunological abnormalities of MCTD.

  441. Multiple small pulmonary emboli associated with transient anti phospholipid syndrome in human Parvovirus B19 infection Peer-reviewed

    Yoshihide Asano, Maiko Sarukawa, Takeo Idezuki, Syoichiro Harada, Kenzo Kaji, Ichiro Nakasu, Atsuyuki Igarashi

    CLINICAL RHEUMATOLOGY　25　(4)　585-587　2006/07

    DOI： 10.1007/s10067-005-0032-1 　

    ISSN： 0770-3198

  442. Potential regulatory elements of the constitutive up-regulated alpha2(I) collagen gene in scleroderma dermal fibroblasts. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Yoshihiro Mimura, Yoshihide Asano, Kunihiko Tamaki

    Biochemical and biophysical research communications　343　(3)　904-9　2006/05/12

    DOI： 10.1016/j.bbrc.2006.03.037 　

    ISSN： 0006-291X

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    The promoter activity of the full-length alpha2(I) collagen gene is higher in scleroderma fibroblasts, when compared to normal fibroblasts. In this study, to investigate the molecular mechanisms up-regulating the expression of the alpha2(I) collagen gene in scleroderma dermal fibroblasts more clearly, we compared promoter activities of serial 5'-deletion mutants and the substitution mutants of the alpha2(I) collagen promoter constructs between normal and scleroderma fibroblasts. The transient transfection assays using a series of 5'-deletions of the promoter revealed that the up-regulated fold-increase in scleroderma fibroblasts relative to that in normal fibroblasts was significantly decreased by the removal of bp -353 to -264 fragment or bp -264 to -186 fragment. The substitution mutations introduced into binding sites of Sp1 (bp -303 and -271), Ets1 (bp -285 and -282), as well as Smad (bp -263 and -258) also abrogated the fold-increase in promoter activity in scleroderma fibroblasts synergistically. A DNA affinity precipitation assay showed that the binding activity of Ets1 as well as Smad3 to their binding sites was increased in scleroderma fibroblasts compared with normal cells. Taken together, our promoter analysis emphasized that Ets1 form a transcriptionally active complex with Smad and Sp1 by autocrine transforming growth factor (TGF)-beta signaling, leading to the intrinsic up-regulation of alpha2(I) collagen promoter activity in scleroderma fibroblasts. The blockade of autocrine TGF-beta signaling is thought to be one of the most reliable approaches in the treatment of scleroderma, and further study targeting Ets1, Smad or Sp1 may contribute to this blockade.

  443. A case of Rothmann-Makai panniculitis successfully treated with tetracycline Peer-reviewed

    Y. Asano, T. Idezuki, A. Igarashi

    Clinical and Experimental Dermatology　31　(3)　365-367　2006/05

    DOI： 10.1111/j.1365-2230.2005.02055.x 　

    ISSN： 0307-6938 1365-2230

  444. High-dose intravenous immunoglobulin infusion in polyarteritis nodosa: report on one case and review of the literature. International-journal Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Takeo Maekawa, Takafumi Kadono, Kunihiko Tamaki

    Clinical rheumatology　25　(3)　396-8　2006/05

    DOI： 10.1007/s10067-005-0015-2 　

    ISSN： 0770-3198

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    We describe a 58-year-old Japanese female who developed polyarteritis nodosa (PN). Her skin disease and systemic symptoms were resistant to dapsone (1.5 mg kg(-1) day(-1)), high-dose oral prednisone (1 mg kg(-1) day(-1)) and azathioprine (2 mg kg(-1) day(-1)), and intravenous cyclophosphamide pulse therapy (10 mg kg(-1) day(-1)). She was ultimately treated with infusion of high-dose intravenous immunoglobulin (IVIG) at a dose of 0.1 g kg(-1) daily for five consecutive days weekly for a period of 12 weeks, resulting in remission of his cutaneous and systemic symptoms and successful tapering of his prednisone and azathioprine dose. However, 12 months later, relapsing fever and polyarthritis recurred, and eventually, 24 months later, indurated erythema and punched-out ulcers appeared on the lower legs. These symptoms were reduced after increasing the dose of oral prednisone (1 mg kg(-1) day(-1)). Our case indicates that the high-dose IVIG infusion therapy may be useful for controlling PN in certain periods since the long-term observation revealed deterioration of symptoms. We review related articles and discuss its effectiveness in PN.

  445. Epidermal growth factor affects the synthesis and degradation of type I collagen in cultured human dermal fibroblasts. International-journal Peer-reviewed

    Yoshihiro Mimura, Hironobu Ihn, Masatoshi Jinnin, Yoshihide Asano, Kenichi Yamane, Kunihiko Tamaki

    Matrix biology : journal of the International Society for Matrix Biology　25　(4)　202-12　2006/05

    DOI： 10.1016/j.matbio.2005.12.002 　

    ISSN： 0945-053X

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    EGF and type I collagen are known to play important roles in wound healing. In the present study, we demonstrated that EGF down-regulates the expression of type I procollagen protein as well as alpha2(I) collagen mRNA in cultured human dermal fibroblasts. EGF induced the degradation of type I procollagen protein in conditioned medium through the up-regulation of MMP-1 expression. EGF down-regulated alpha2(I) mRNA expression partially at the post-transcriptional level by reducing the mRNA stability. In contrast, EGF up-regulated MMP-1 mRNA expression mostly at the transcriptional level, in that it had a stimulatory effect on MMP-1 promoter activity, but no effect on MMP-1 mRNA stability. The MEK/ERK signaling pathway was shown to be involved in EGF-mediated type I collagen and MMP-1 expression.

  446. Generalized granuloma annulare treated with short-term administration of etretinate Peer-reviewed

    Yoshihide Asano, Atsushi Saito, Takeo Idezuki, Atsuyuki Igarashi

    Journal of the American Academy of Dermatology　54　(5)　S245-S247　2006/05

    DOI： 10.1016/j.jaad.2006.01.028 　

    ISSN： 0190-9622

  447. Platelet derived growth factor induced tenascin-C transcription is phosphoinositide 3-kinase/Akt-dependent and mediated by Ets family transcription factors. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Yoshihide Asano, Kenichi Yamane, Maria Trojanowska, Kunihiko Tamaki

    Journal of cellular physiology　206　(3)　718-27　2006/03

    DOI： 10.1002/jcp.20527 　

    ISSN： 0021-9541

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    Previous studies have identified several cytokines as inducers of tenascin-C (TN-C) expression in various tissue culture systems. However, the signaling pathways of the regulation of TN-C expression are almost unknown. In this study, we clarified the molecular mechanism(s) underlying the regulation of the TN-C gene by platelet derived growth factor (PDGF) in cultured human dermal fibroblasts. PDGF induced the expression of TN-C protein as well as mRNA in a dose-dependent manner. Actinomycin D, an RNA synthesis inhibitor, significantly blocked the PDGF-mediated upregulation of TN-C mRNA expression, whereas cycloheximide, a protein synthesis inhibitor, did not. The PDGF-mediated induction of TN-C expression was inhibited by the treatment of fibroblasts with a selective phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, or LY294002. These results suggest that PDGF induced the expression of TN-C at a transcriptional level via phosphoinositide3-kinase/Akt signaling pathways. We performed serial 5' deletions and a transient transfection analysis to define the region in the TN-C promoter mediating the responsiveness to PDGF. Overexpression of Sp1, Ets1, or Ets2 activated the TN-C promoter and superinduced TN-C promoter activity stimulated by PDGF, whereas overexpression of Fli1 inhibited the effects of PDGF on TN-C expression. Mutation of the Sp1/3 binding sites or Ets binding sites in the TN-C promoter region responsible to PDGF abrogated the PDGF-inducible promoter activity. Immunoprecipitation analysis revealed that Sp1, Ets1, and Ets2 form a transcriptionally active complex. On the other hand, the interaction of Fli1 with Sp1 decreased after PDGF treatment. These results suggest that the upregulation of TN-C expression by PDGF involves Ets family transcription factors, co-operating with Sp1.

  448. Upregulation of tenascin-C expression by IL-13 in human dermal fibroblasts via the phosphoinositide 3-kinase/Akt and the protein kinase C signaling pathways. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Yoshihide Asano, Kenichi Yamane, Maria Trojanowska, Kunihiko Tamaki

    The Journal of investigative dermatology　126　(3)　551-60　2006/03

    DOI： 10.1038/sj.jid.5700090 　

    ISSN： 0022-202X

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    In this study, we examined the genes targeted by IL-13 in human dermal fibroblasts using a cDNA microarray. We focused on the tenascin-C (TN-C) gene, which was identified as one of the genes induced by IL-13. IL-13 induced transcriptional activity of TN-C. IL-13-mediated TN-C expression was inhibited by treatment with wortmannin or LY294002, or Calphostin C. IL-13 induced the phosphorylation of the phosphoinositide 3-kinase (PI3K) regulatory subunit p85, induced tyrosine phosphorylation of Akt, upregulated Akt kinase activity, and activated protein kinase C (PKC)-delta and -epsilon. The IL-13-induced increase in TN-C protein expression was abrogated by the transfection of a dominant-negative mutant of Akt, PKC-delta, or PKC-epsilon. In conclusion, we showed that the PI3K/Akt and/or PKC signaling pathways are essential for the IL-13-mediated increase in TN-C. Both serum levels of IL-13 and the expression levels of TN-C in the dermis are increased in patients with systemic sclerosis. Our findings suggest that the expression of TN-C is upregulated in this disease due to IL-13 signaling, and that a blockade of the PI3K or PKC signaling pathway may also have therapeutic value by reducing the amount of TN-C produced during fibrosis.

  449. Increased expression of integrin alphavbeta5 induces the myofibroblastic differentiation of dermal fibroblasts. International-journal Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Kenichi Yamane, Masatoshi Jinnin, Kunihiko Tamaki

    The American journal of pathology　168　(2)　499-510　2006/02

    DOI： 10.2353/ajpath.2006.041306 　

    ISSN： 0002-9440

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    The biological effect of cytokines is mainly determined by the cytokine-receptor interaction, which is modulated by the concentration and the activity of cytokines and/or their receptors. Because alphav-containing integrins can bind to and/or activate latent TGF-beta, these integrins have been thought to be involved in the pathogenesis of fibrotic disorders. Our recent observations that alphavbeta5 is up-regulated in scleroderma fibroblasts and that the transient overexpression of alphavbeta5 increases the human alpha2(I) collagen gene expression in normal fibroblasts suggest the involvement of alphavbeta5 in the self-activation system in scleroderma fibroblasts. In this study, we established stable transfectants with alphavbeta5 using normal dermal fibroblasts and demonstrated that such cells differentiated into myofibroblasts by the stimulation of autocrine TGF-beta. This observation is explained by 1) alphavbeta5 recruiting latent TGF-beta1 on the cell surface, 2) endogenous active TGF-beta localizing on the cell surface, and 3) alphavbeta5 interacting with TGF-beta receptors. Furthermore, blockade of alphavbeta5 reversed the myofibroblastic phenotype in scleroderma fibroblasts. These data identify a novel mechanism for the establishment of autocrine TGF-beta signaling in dermal fibroblasts by the up-regulation of alphavbeta5 and suggest the possibility of regulating fibrotic disorders, especially scleroderma, by targeting this integrin.

  450. Increased expression of integrin alpha(v)beta3 contributes to the establishment of autocrine TGF-beta signaling in scleroderma fibroblasts. International-journal Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Kenichi Yamane, Masatoshi Jinnin, Yoshihiro Mimura, Kunihiko Tamaki

    Journal of immunology (Baltimore, Md. : 1950)　175　(11)　7708-18　2005/12/01

    DOI： 10.4049/jimmunol.175.11.7708 　

    ISSN： 0022-1767

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    The constitutive secretion of latent TGF-beta by many cell types in culture suggests that extracellular mechanisms to control the activity of this potent cytokine are important in the pathogenesis of the diseases in which this cytokine may be involved, including fibrotic disorders. In this study, we focused on the alpha(v)beta3 integrin, which is recently demonstrated to function as an active receptor for latent TGF-beta1 through its interaction with latency-associated peptide-beta1, and investigated the involvement of this integrin in the pathogenesis of scleroderma. Scleroderma fibroblasts exhibited increased alpha(v)beta3 expression compared with normal fibroblasts in vivo and in vitro. In scleroderma fibroblasts, ERK pathway was constitutively activated and such abnormality induced the up-regulation of alpha(v)beta3. Transient overexpression of alpha(v)beta3 in normal fibroblasts induced the increase in the promoter activity of human alpha2(I) collagen gene and the decrease in that of human MMP-1 gene. These effects of alpha(v)beta3 were almost completely abolished by the treatment with anti-TGF-beta Ab or TGF-beta1 antisense oligonucleotide. Furthermore, the addition of anti-alpha(v)beta3) Ab reversed the expression of type I procollagen protein and MMP-1 protein, the promoter activity of human alpha2(I) collagen gene, and the myofibroblastic phenotype in scleroderma fibroblasts. These results suggest that the up-regulated expression of alpha(v)beta3 contributes to the establishment of autocrine TGF-beta loop in scleroderma fibroblasts, and this integrin is a potent target for the treatment of scleroderma.

  451. Anti-agalactosyl immunoglobulin G antibodies in localized scleroderma Peer-reviewed

    Y Mimura, H Ihn, M Jinnin, Y Asano, K Yamane, N Yazawa, K Tamaki

    INTERNATIONAL JOURNAL OF DERMATOLOGY　44　(10)　817-820　2005/10

    DOI： 10.1111/j.1365-4632.2005.02584.x 　

    ISSN： 0011-9059

  452. Involvement of alphavbeta5 integrin-mediated activation of latent transforming growth factor beta1 in autocrine transforming growth factor beta signaling in systemic sclerosis fibroblasts. International-journal Peer-reviewed

    Yoshihde Asano, Hironobu Ihn, Kenichi Yamane, Masatoshi Jinnin, Yoshihiro Mimura, Kunihiko Tamaki

    Arthritis and rheumatism　52　(9)　2897-905　2005/09

    DOI： 10.1002/art.21246 　

    ISSN： 0004-3591

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    OBJECTIVE: To confirm the involvement of alphavbeta5 in the self-activation system in systemic sclerosis (SSc) fibroblasts. METHODS: Levels of alphavbeta5 expression were analyzed by immunoprecipitation. The promoter activity of the human alpha2(I) collagen gene was determined by transient transfection assay. Phosphorylation levels and DNA binding ability of Smad3 were investigated by immunoprecipitation and DNA affinity precipitation, respectively. The localization of active transforming growth factor beta (TGFbeta) was determined by coculture assay using TMLC cells (mink lung epithelial reporter cells that stably express a portion of the plasminogen activator inhibitor 1 promoter). The morphologic features of cells were determined by immunofluorescence analysis. RESULTS: Levels of alphavbeta5 expression were significantly elevated in SSc fibroblasts compared with normal fibroblasts. Treatment with anti-alphavbeta5 antibody or beta5 antisense oligonucleotide significantly reduced human alpha2(I) collagen gene promoter activity in SSc fibroblasts. In SSc fibroblasts pretreated with TGFbeta1 antisense oligonucleotide, the exogenous latent TGFbeta1 stimulation significantly increased human alpha2(I) collagen gene promoter activity; this effect was significantly reduced in the presence of anti-alphavbeta5 antibody. Phosphorylation levels and DNA binding ability of Smad3 in SSc fibroblasts were significantly reduced by treatment with beta5 antisense oligonucleotide. The luciferase activity of TMLC cells cocultured with SSc fibroblasts was significantly elevated compared with that of TMLC cells cocultured with normal fibroblasts and was significantly reduced in the presence of anti-alphavbeta5 antibody. Anti-alphavbeta5 antibody reversed the myofibroblastic features of SSc fibroblasts. CONCLUSION: Up-regulated expression of alphavbeta5 contributes to the establishment of autocrine TGFbeta signaling in SSc fibroblasts through activation of endogenous latent TGFbeta1.

  453. Constitutive phosphorylation of focal adhesion kinase is involved in the myofibroblast differentiation of scleroderma fibroblasts. International-journal Peer-reviewed

    Yoshihiro Mimura, Hironobu Ihn, Masatoshi Jinnin, Yoshihide Asano, Kenichi Yamane, Kunihiko Tamaki

    The Journal of investigative dermatology　124　(5)　886-92　2005/05

    DOI： 10.1111/j.0022-202X.2005.23701.x 　

    ISSN： 0022-202X

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    Most of the cultured scleroderma fibroblasts have been reported to be myofibroblasts that have the ability to express alpha smooth muscle actin (alphaSMA). It is reported that, in human lung fibroblasts, alphaSMA is induced by transforming growth factor-beta (TGF-beta), which requires focal adhesion kinase (FAK) phosphorylation on its Tyr-397 site. In this study, we investigated how alphaSMA expression is upregulated in cultured scleroderma fibroblasts. 4-amino-5-(4-chlorophenyl)-7-(butyl)pyrazolo[3,4-d]pyrimidine, which is a pharmacologic inhibitor of FAK/Src, markedly diminished upregulated alphaSMA expression in scleroderma fibroblasts as well as in normal fibroblasts stimulated with TGF-beta. Likewise, alphaSMA expression was significantly reduced in sclerderma fibroblasts transfected with kinase-deficient FAK mutant. FAK phosphorylation levels on Tyr-397 in scleroderma fibroblasts were significantly higher than those in normal fibroblasts. Both alphaSMA expression and FAK phosphorylation levels in scleroderma fibroblasts were markedly diminished by the treatment with TGF-beta antisense oligonucleotide. These results indicate that the constitutive phosphorylation of FAK, which is possibly because of the autocrine TGF-beta signaling, may play an important role in alphaSMA expression in scleroderma fibroblasts.

  454. Constitutive thrombospondin-1 overexpression contributes to autocrine transforming growth factor-beta signaling in cultured scleroderma fibroblasts. International-journal Peer-reviewed

    Yoshihiro Mimura, Hironobu Ihn, Masatoshi Jinnin, Yoshihide Asano, Kenichi Yamane, Kunihiko Tamaki

    The American journal of pathology　166　(5)　1451-63　2005/05

    DOI： 10.1016/s0002-9440(10)62362-0 　

    ISSN： 0002-9440

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    The extracellular matrix (ECM) glycoprotein thrombospondin-1 (TSP-1) has been reported to activate the latent complex of transforming growth factor-beta (TGF-beta), the major effects of which in mesenchymal cells is stimulation of the synthesis of ECM. Previous reports suggested the involvement of an autocrine TGF-beta loop in the pathogenesis of scleroderma. In this study, we examined whether TSP-1 plays a role in maintaining the autocrine TGF-beta loop in scleroderma. TSP-1 expression was increased in scleroderma patients compared with in healthy controls in vivo and in vitro. TGF-beta blocking antibody or TGF-beta1 antisense oligonucleotide markedly reduced the up-regulated TSP-1 expression in scleroderma fibroblasts but had little effect on normal fibroblasts. The expression of TSP-1 is up-regulated in scleroderma fibroblasts, possibly at the post-transcriptional level just like in normal fibroblasts stimulated with exogenous TGF-beta1. TSP-1 blocking peptide or antisense oligonucleotide had an inhibitory effect on the up-regulated alpha2I collagen and phosopho-Smad3 levels in scleroderma fibroblasts but had little effects on normal fibroblasts. The transient overexpression of TSP-1 up-regulated alpha2I collagen and phospho-Smad3 levels in normal fibroblasts but had no major effect on scleroderma fibroblasts. Furthermore, these effects of transiently overexpressed TSP-1, which possibly occurred via the activation of latent TGF-beta1, were abolished by the TGF-beta1 antisense oligonucleotide. These results indicate that the constitutive overexpression of TSP-1 may play an important role in autocrine TGF-beta signaling and accumulation of ECM in scleroderma fibroblasts.

  455. Clinical and laboratory features of scleroderma patients developing skeletal myopathy. International-journal Peer-reviewed

    Yoshihiro Mimura, Hironobu Ihn, Masatoshi Jinnin, Yoshihide Asano, Kenichi Yamane, Kunihiko Tamaki

    Clinical rheumatology　24　(2)　99-102　2005/04

    DOI： 10.1007/s10067-004-0975-7 　

    ISSN： 0770-3198

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    Skeletal muscle involvement, or myopathy, has been a recognized feature of systemic sclerosis (SSc). We studied retrospectively 302 Japanese patients with SSc to elucidate the clinical and laboratory features in scleroderma patients developing skeletal myopathy during their clinical course. Forty-three patients (14%) developed skeletal myopathy during their course of the disease. The mean age of the patients who developed skeletal myopathy was significantly lower than that of those who did not. The ratio of male to female was significantly higher in the myopathic patients. The patients with diffuse cutaneous SSc were more likely to develop myopathy than those with limited cutaneous SSc. The prevalences of heart involvement, pulmonary fibrosis, diffuse pigmentation of the skin, and contracture of phalanges were significantly greater in those with skeletal myopathy than in those without. None of the patients with skeletal myopathy had anticentromere antibody. These findings suggested that the SSc patients with severe internal organ involvement, such as pulmonary fibrosis and heart disease, and some other complications were prone to develop skeletal myopathy during their clinical course of the disease.

  456. Differential effects of the immunosuppressant FK-506 on human alpha2(I) collagen gene expression and transforming growth factor beta signaling in normal and scleroderma fibroblasts. International-journal Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Kenichi Yamane, Masatoshi Jinnin, Yoshihiro Mimura, Kunihiko Tamaki

    Arthritis and rheumatism　52　(4)　1237-47　2005/04

    DOI： 10.1002/art.20934 　

    ISSN： 0004-3591

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    OBJECTIVE: To investigate the effects of FK-506 on the expression of the human alpha2(I) collagen gene and transforming growth factor beta (TGFbeta) signaling in normal and scleroderma fibroblasts. METHODS: The expression levels of type I procollagen protein and alpha2(I) collagen messenger RNA (mRNA) were analyzed by immunoblotting and Northern blotting, respectively. The promoter activities of alpha2(I) collagen gene and 3TP-Lux were determined by transient transfection assay. Interaction between TGFbeta receptor type I and FK-506 binding protein 12 (FKBP12) was evaluated by immunoprecipitation. RESULTS: FK-506 did not affect the basal expression of type I procollagen protein or alpha2(I) collagen mRNA, but it significantly reduced the TGFbeta1-induced expression of type I procollagen protein and alpha2(I) collagen mRNA in normal fibroblasts. The effect of FK-506 was regulated posttranscriptionally, but not transcriptionally. In scleroderma fibroblasts, FK-506 significantly reduced the expression of type I procollagen protein and alpha2(I) collagen mRNA through posttranscriptional regulation, but not transcriptional regulation. FK-506 increased the basal activity of the 3TP-Lux promoter, but it did not affect the TGFbeta1-induced promoter activity in normal fibroblasts. In contrast, FK-506 did not affect the basal or the TGFbeta1-induced 3TP-Lux promoter activity in scleroderma fibroblasts. Furthermore, FKBP12, which protects TGFbeta receptor type I from ligand-independent activation by TGFbeta receptor type II, constitutively dissociated from TGFbeta receptor type I in scleroderma fibroblasts. CONCLUSION: FK-506 inhibits alpha2(I) collagen gene expression by reducing the stability of mRNA without exhibiting its activation effect on TGFbeta signaling in scleroderma fibroblasts.

  457. Regulation of fibrogenic/fibrolytic genes by platelet-derived growth factor C, a novel growth factor, in human dermal fibroblasts. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Yoshihiro Mimura, Yoshihide Asano, Kenichi Yamane, Kunihiko Tamaki

    Journal of cellular physiology　202　(2)　510-7　2005/02

    DOI： 10.1002/jcp.20154 　

    ISSN： 0021-9541

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    Platelet-derived growth factor (PDGF) is a potent mitogenic and chemotactic cytokine, and PDGF-C is a novel growth factor belonging to the PDGF family. In this study, to determine whether this growth factor can contribute to fibrosis and tissue remodeling, we examined the effect of PDGF-CC on the expression of fibrogenic/fibrolytic genes such as type I collagen, fibronectin (FN), matrix metalloproteinases (MMPs), and their inhibitors (TIMPs) in normal human dermal fibroblasts in vitro. PDGF elevated the levels of MMP-1 or TIMP-1 protein as well as mRNA, whereas this cytokine had no influence on the expression of type I collagen, FN, or TIMP-2. PDGF-CC also increased the levels of MMP-1 catalytic activity in the cultured media and mRNA expression, which was paralleled that on the levels of promoter activation. Additionally, PDGF-CC induced the mitogenic and migratory activity of human dermal fibroblasts in a dose-dependent manner. On the other hand, we also determined the specificity of the inhibitory effect of monoclonal antibodies against PDGF-CC generated by immunizing balb/c mice with recombinant human PDGF-CC. This antibody could inhibit the regulatory effects of MMP-1 or TIMP-1 synthesis as well as the mitogenic effects on human dermal fibroblasts induced by PDGF-CC, whereas this antibody did not affect those induced by other PDGF forms such as PDGF-AA, -AB, or -BB. These results suggest that this cytokine plays a role in the tissue remodeling.

  458. Effects of hepatocyte growth factor on the expression of type I collagen and matrix metalloproteinase-1 in normal and scleroderma dermal fibroblasts. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Yoshihiro Mimura, Yoshihide Asano, Kenichi Yamane, Kunihiko Tamaki

    The Journal of investigative dermatology　124　(2)　324-30　2005/02

    DOI： 10.1111/j.0022-202X.2004.23601.x 　

    ISSN： 0022-202X

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    We investigated the direct effect of hepatocyte growth factor (HGF) on the expression of type I collagen in normal and scleroderma dermal fibroblasts, and analyzed the mechanisms underlying the effect in vitro. HGF did not change the protein expression of type I procollagen in the medium of normal human fibroblasts, whereas it reduced the expression in scleroderma fibroblasts. But mRNA levels and the promoter activity of alpha2(I) collagen gene were not significantly affected by HGF in either of the cells. On the other hand, matrix metalloproteinase-1 expression or activity was increased by HGF in both cells, but HGF had stronger effects in scleroderma fibroblasts than normal fibroblasts. Scleroderma fibroblasts overexpressed c-met protein, the receptor for HGF. The overexpression in scleroderma fibroblasts was abolished by the addition of antisense transforming growth factor (TGF)-beta1 oligonucleotide. Our study indicated that HGF may reduce type I collagen accumulation only in scleroderma fibroblasts by enhancing collagenolysis activity, probably because of the overexpression of c-met because of autocrine TGF-beta signaling. Thus, further investigation of the effects of HGF on collagen metabolism may contribute to the treatment of fibrosis in scleroderma.

  459. Alpha2(I) collagen gene regulation by protein kinase C signaling in human dermal fibroblasts. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Kenichi Yamane, Yoshihiro Mimura, Yoshihide Asano, Kunihiko Tamaki

    Nucleic acids research　33　(4)　1337-51　2005

    DOI： 10.1093/nar/gki275 　

    ISSN： 0305-1048

    eISSN： 1362-4962

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    We investigated the mechanisms by which protein kinase C (PKC) regulates the expression of the alpha2(I) collagen gene in normal dermal fibroblasts. Reduction of PKC-alpha activity by treatment with Gö697-6 or by overexpression of a dominant negative (DN) mutant form decreased alpha2(I) collagen gene expression. This decrease required a sequence element in the collagen promoter that contains Sp1/Sp3 binding sites. Reduction of PKC-delta activity by rottlerin or overexpression of DN PKC-delta also decreased alpha2(I) collagen gene expression. This effect required a separate sequence element containing Sp1/Sp3-binding sites and an Ets-binding site. In both cases, point mutations within the response elements abrogated the response to PKC inhibition. Forced overexpression of Sp1 rescued the PKC inhibitor-mediated reduction in collagen protein expression. A DNA affinity precipitation assay revealed that inhibition of PKC-delta by rottlerin increased the binding activity of endogenous Fli1 and decreased that of Ets1. On the other hand, TGF-beta1, which increased the expression of PKC-delta, had the opposite effect, increasing the binding activity of Ets1 and decreasing that of Fli1. Our results suggest that PKC-delta is involved in the regulation of the alpha2(I) collagen gene in the presence or absence of TGF-beta. Alteration of the balance of Ets1 and Fli1 may be a novel mechanism regulating alpha2(I) collagen expression.

  460. Matrix metalloproteinase-1 up-regulation by hepatocyte growth factor in human dermal fibroblasts via ERK signaling pathway involves Ets1 and Fli1. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Yoshihiro Mimura, Yoshihide Asano, Kenichi Yamane, Kunihiko Tamaki

    Nucleic acids research　33　(11)　3540-9　2005

    DOI： 10.1093/nar/gki648 　

    ISSN： 0305-1048

    eISSN： 1362-4962

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    In this study, we clarified the molecular mechanism(s) underlying the regulation of matrix metalloproteinase (MMP)-1 gene by hepatocyte growth factor (HGF) in cultured human dermal fibroblasts. HGF induced MMP-1 protein as well as mRNA at a transcriptional level via extracellular signal-regulated kinase (ERK) signaling pathway. The region in the MMP-1 promoter mediating the inducible responsiveness to HGF, defined by the transient transfection analysis of the serial 5' deletion constructs, contained an Ets binding site. Mutation of this Ets binding site abrogated the HGF-inducible promoter activity. Ets1 up-regulated the expression of MMP-1 promoter activity, whereas Fli1 had antagonistic effects on them. After HGF treatment, the protein level and the binding activity of Ets1 was increased and those of Fli1 was decreased, which were canceled by PD98059. These results suggest that HGF up-regulates MMP-1 expression via ERK signaling pathway through the balance of Ets1 and Fli1, which may be a novel mechanism of regulating MMP-1 gene expression.

  461. Rheumatoid factor isotypes and anti-agalactosyl IgG antibodies in systemic sclerosis Peer-reviewed

    Y Mimura, H Ihn, M Jinnin, Y Asano, K Yamane, N Yazawa, K Tamaki

    BRITISH JOURNAL OF DERMATOLOGY　151　(4)　803-808　2004/10

    DOI： 10.1111/j.1365-2133.2004.06195.x 　

    ISSN： 0007-0963

  462. Serum levels of tissue inhibitor of metalloproteinase-1 and 2 in patients with eosinophilic fasciitis Peer-reviewed

    M Jinnin, H Ihn, K Yamane, Y Asano, N Yazawa, K Tamaki

    BRITISH JOURNAL OF DERMATOLOGY　151　(2)　407-412　2004/08

    DOI： 10.1111/j.1365-2133.2004.06062.x 　

    ISSN： 0007-0963

  463. Serum matrix metalloproteinase-3 in systemic sclerosis. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Yoshihide Asano, Kenichi Yamane, Norihito Yazawa, Kunihiko Tamaki

    Archives of dermatological research　296　(1)　25-9　2004/06

    DOI： 10.1007/s00403-004-0468-1 　

    ISSN： 0340-3696

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    To determine the serum levels of matrix metalloproteinase-3 (MMP-3) in patients with systemic sclerosis (SSc) and investigate their clinical significance in this disease, serum samples from 83 patients with SSc and 30 healthy volunteers were examined by a specific enzyme-linked immunosorbent assay (ELISA). There was no significant difference in serum levels of MMP-3 between SSc patients and healthy controls. However, in female patients, there was a significant difference in serum MMP-3 levels between patients subsequently developing accompanying rheumatoid arthritis (RA) and those not developing RA, and patients with increased levels of MMP-3 were more likely to develop RA than those with normal MMP-3 levels. Additionally, arthralgia, elevated CRP, and elevated rheumatoid factor were seen significantly more frequently in patients with increased MMP-3 levels than in those with normal MMP-3 levels. These results suggest that increased serum MMP-3 is a marker for developing RA in SSc patients. SSc patients with increased serum MMP-3 levels need to be followed up carefully because of the risk of developing overlapping RA.

  464. Phosphatidylinositol 3-kinase is involved in alpha2(I) collagen gene expression in normal and scleroderma fibroblasts. International-journal Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Kenichi Yamane, Masatoshi Jinnin, Yoshihiro Mimura, Kunihiko Tamaki

    Journal of immunology (Baltimore, Md. : 1950)　172　(11)　7123-35　2004/06/01

    DOI： 10.4049/jimmunol.172.11.7123 　

    ISSN： 0022-1767

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    TGF-beta is implicated in the pathogenesis of fibrotic disorders. It has been shown that Smad3 promotes the human alpha2(I) collagen (COL1A2) gene expression by TGF-beta1 in human dermal fibroblasts. Here, we investigated the role of phosphatidylinositol 3-kinase (PI3K) in the COL1A2 gene expression in normal and scleroderma fibroblasts. In normal fibroblasts, the PI3K inhibitor, LY294002, significantly decreased the basal and the TGF-beta1-induced increased stability of COL1A2 mRNA. The TGF-beta1-induced COL1A2 promoter activity, but not the basal activity, was significantly attenuated by LY294002 or the dominant negative mutant of p85 subunit of PI3K, while the constitutive active mutant of p110 subunit of PI3K did not affect the basal or the TGF-beta1-induced COL1A2 promoter activity. LY294002 significantly decreased the phosphorylation of Smad3 induced by TGF-beta1. Furthermore, the transient overexpression of 2xFYVE, which induces the mislocalization of FYVE domain proteins, decreased the TGF-beta1-induced Smad3 phosphorylation to a similar extent to LY294002. In scleroderma fibroblasts, the blockade of PI3K significantly decreased the mRNA stability and the promoter activity of the COL1A2 gene. Furthermore, LY294002 and the transient overexpression of 2xFYVE completely diminished the constitutive phosphorylation of Smad3. These results indicate that 1) the basal activity of PI3K is necessary for the COL1A2 mRNA stabilization in normal and scleroderma fibroblasts, 2) there is an unidentified FYVE domain protein specifically interacting with Smad3, and 3) the basal activity of PI3K and the FYVE domain protein are indispensable for the efficient TGF-beta/Smad3 signaling in normal fibroblasts and for the establishment of the constitutive activation of TGF-beta/Smad3 signaling in scleroderma fibroblasts.

  465. Epidermal growth factor induces fibronectin expression in human dermal fibroblasts via protein kinase C delta signaling pathway. International-journal Peer-reviewed

    Yoshihiro Mimura, Hironobu Ihn, Masatoshi Jinnin, Yoshihide Asano, Kenichi Yamane, Kunihiko Tamaki

    The Journal of investigative dermatology　122　(6)　1390-8　2004/06

    DOI： 10.1111/j.0022-202X.2004.22618.x 　

    ISSN： 0022-202X

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    Epidermal growth factor (EGF) and fibronectin are known to play an important role in wound healing. In this study, we demonstrated that EGF upregulates the expression of fibronectin mRNA and protein in human dermal fibroblasts. Actinomycin D, an RNA synthesis inhibitor, significantly blocked basal mRNA expression, but the addition of EGF compensated the blockage. Cycloheximide, a protein synthesis inhibitor, did not block this upregulation by EGF. In addition, the treatment with EGF significantly reduced the degradation rate of fibronectin mRNA. But EGF did not increase fibronectin promoter activity. EGF-mediated induction of fibronectin expression was inhibited by the treatment of fibroblasts with protein kinase C (PKC) inhibitor, Calphostin C and Rottlerin. The transfection of a dominant-negative mutant of PKCdelta into fibroblasts significantly reduced the induction of fibronectin protein expression by EGF. EGF enhanced PKCdelta protein expression and also translocated PKCdelta to the membrane. Rottlerin blocked the EGF-mediated reduction of mRNA degradation rate. These results indicate that EGF-mediated induction of fibronectin expression occurs at the post-transcriptional level and involves PKCdelta signaling pathway.

  466. Serum levels of manganese superoxide dismutase in patients with localized scleroderma. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Norihito Yazawa, Yoshihide Asano, Kenichi Yamane, Kunihiko Tamaki

    Experimental dermatology　13　(6)　357-60　2004/06

    DOI： 10.1111/j.0906-6705.2004.00160.x 　

    ISSN： 0906-6705

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    The objective was to determine the serum levels of manganese superoxide dismutase (Mn SOD) in patients with localized scleroderma and investigate their clinical significance in this disease. Serum samples from 15 patients with localized scleroderma and 20 healthy volunteers were examined by a specific enzyme-linked immunosorbent assay. Serum levels of Mn SOD were significantly higher in patients with generalized morphea than those in healthy individuals. And the patients with elevated serum Mn SOD levels had significantly larger number of sclerotic lesions and significantly higher serum levels of soluble interleukin-2 receptor than those without it. These results suggested that the serum levels of this enzyme may be a serological marker for the disease activity and the extent of skin involvement in this disease.

  467. Increased expression levels of integrin alphavbeta5 on scleroderma fibroblasts. International-journal Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Kenichi Yamane, Masahide Kubo, Kunihiko Tamaki

    The American journal of pathology　164　(4)　1275-92　2004/04

    DOI： 10.1016/s0002-9440(10)63215-4 　

    ISSN： 0002-9440

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    Integrin alphavbeta5 is a receptor for vitronectin, a plasma glycoprotein that is also distributed in extracellular matrix of various tissues. Matrix-bound vitronectin has the potential to stabilize the active form of plasminogen activator inhibitor-1, resulting in the inhibition of the plasmin-mediated pericellular proteolytic cascade. In this study, we compared the levels of alphavbeta5 and matrix-bound vitronectin between normal and scleroderma fibroblasts and investigated the association with fibrosis. We demonstrated that alphavbeta5 was up-regulated on scleroderma fibroblasts. The up-regulated alphavbeta5 contributed to the increase in vitronectin-binding ability in scleroderma fibroblasts, which led to the vitronectin-dependent activation of plasminogen activator inhibitor-1. In immunohistochemistry, the alphav and beta5 subunits were stained strongly on scleroderma fibroblasts and the amount of vitronectin was increased in the pericellular matrix of those cells. The transient overexpression of alphavbeta5 on normal fibroblasts enhanced the human alpha2(I) collagen promoter activity through Sp-1 and Smad3 as well as the vitronectin-dependent plasminogen activator inhibitor-1 activity. This effect on the promoter activity was also observed in the absence of vitronectin and completely disappeared in the presence of anti-alphavbeta5 antibody. These results indicate that the up-regulated alphavbeta5 may contribute to the phenotypical alteration of scleroderma fibroblasts, while at the same time suppressing the plasmin-mediated pericellular proteolytic cascade.

  468. Tenascin-C upregulation by transforming growth factor-beta in human dermal fibroblasts involves Smad3, Sp1, and Ets1. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Yoshihide Asano, Kenichi Yamane, Maria Trojanowska, Kunihiko Tamaki

    Oncogene　23　(9)　1656-67　2004/03/04

    DOI： 10.1038/sj.onc.1207064 　

    ISSN： 0950-9232

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    In cultured human dermal fibroblasts, transforming growth factor (TGF)-beta induced the mRNA expression of tenascin-C (TN-C). The molecular mechanism(s) underlying this process is not presently understood. In this study, we performed serial 5' deletion and a transient transfection analysis to define a region in the TN-C promoter mediating the inducible responsiveness to TGF-beta. This region contains an atypical nucleotide recognition element for the Smad family of transcriptional regulators. A DNA affinity precipitation assay revealed that Smad2/Smad3 bound to this site in a transient and specific manner. Overexpression of Smad3 or Smad4 activated the TN-C promoter activity and superinduced the TN-C promoter activity stimulated by TGF-beta. Moreover, simultaneous cotransfection of Smad3 and Smad4 activated the TN-C promoter activity in a synergistic manner. Mutation of the Smad-binding sites, the Ets-binding sites, or Sp1/3-binding sites in the TN-C promoter abrogated the TGF-beta/Smad-inducible promoter activity. Immunoprecipitation analysis revealed that Smad3, Sp1, and Ets1 form a transcriptionally active complex. Furthermore, the interaction between Smads and CBP/p300 in TGF-beta signaling was confirmed. These findings demonstrate the existence of a novel, functional binding element in the proximal region of the TN-C promoter mediating responsiveness to TGF-beta involving Smad3/4, Sp1, Ets1, and CBP/p300.

  469. Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in scleroderma fibroblasts. International-journal Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Kenichi Yamane, Masahide Kubo, Kunihiko Tamaki

    The Journal of clinical investigation　113　(2)　253-64　2004/01

    DOI： 10.1172/JCI16269 　

    ISSN： 0021-9738

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    The principal effect of TGF-beta1 on mesenchymal cells is its stimulation of ECM synthesis. Previous reports indicated the significance of the autocrine TGF-beta loop in the pathogenesis of scleroderma. In this study, we focused on Smad7 and Smurfs, principal molecules in the negative regulation of TGF-beta signaling, to further understand the autocrine TGF-beta loop in scleroderma. Scleroderma fibroblasts exhibited increased Smad7 levels compared with normal fibroblasts in vivo and in vitro. Smad7 constitutively formed a complex with the TGF-beta receptors, and the inhibitory effect of Smad7 on the promoter activity of human alpha2(I) collagen and 3TP-lux was completely impaired in scleroderma fibroblasts. Furthermore, the protein stability of TGF-beta receptor type I was significantly increased in scleroderma fibroblasts compared with normal fibroblasts. There was no significant difference in Smurf1 and Smurf2 levels between normal and scleroderma fibroblasts, and the transiently overexpressed Smurf1 and/or Smurf2 did not affect TGF-beta receptor type I protein levels in scleroderma fibroblasts. These results indicate that the impaired Smad7-Smurf-mediated inhibitory effect on TGF-beta signaling might contribute to maintaining the autocrine TGF-beta loop in scleroderma fibroblasts. To our knowledge, this is the first report of a disturbed negative regulation of TGF-beta signaling in fibrotic disorders.

  470. Elevated serum levels of manganese superoxide dismutase in patients with eosinophilic fasciitis. International-journal Peer-reviewed

    Masatoshi Jinnin, Hironobu Ihn, Norihito Yazawa, Yoshihide Asano, Kenichi Yamane, Kunihiko Tamaki

    Clinical rheumatology　22　(6)　505-505　2003/12

    DOI： 10.1007/s10067-003-0781-7 　

    ISSN： 0770-3198

  471. Effect of D-penicillamine on pulmonary fibrosis in patients with systemic sclerosis Peer-reviewed

    M Jinnin, H Ihn, Y Asano, K Yamane, N Yazawa, K Tamaki

    ANNALS OF THE RHEUMATIC DISEASES　62　(10)　1019-1020　2003/10

    ISSN： 0003-4967

  472. Antagonistic effects of TNF-alpha on TGF-beta signaling through down-regulation of TGF-beta receptor type II in human dermal fibroblasts. International-journal Peer-reviewed

    Kenichi Yamane, Hironobu Ihn, Yoshihide Asano, Masatoshi Jinnin, Kunihiko Tamaki

    Journal of immunology (Baltimore, Md. : 1950)　171　(7)　3855-62　2003/10/01

    DOI： 10.4049/jimmunol.171.7.3855 　

    ISSN： 0022-1767

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    Transforming growth factor-beta stimulates the production of the extracellular matrix, whereas TNF-alpha has antifibrotic activity. Understanding the molecular mechanism underlying the antagonistic activities of TNF-alpha against TGF-beta is critical in the context of tissue repair and maintenance of tissue homeostasis. In the present study, we demonstrated a novel mechanism by which TNF-alpha blocks TGF-beta-induced gene and signaling pathways in human dermal fibroblasts. We showed that TNF-alpha prevents TGF-beta-induced gene trans activation, such as alpha2(I) collagen or tissue inhibitor of metalloproteinases 1, and TGF-beta signaling pathways, such as Smad3, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases, without inducing levels of inhibitory Smad7 in human dermal fibroblasts. TNF-alpha down-regulates the expression of type II TGF-beta receptor (TbetaRII) proteins, but not type I TGF-beta receptor (TbetaRI), in human dermal fibroblasts. However, neither TbetaRII mRNA nor TbetaRII promoter activity was decreased by TNF-alpha. TNF-alpha-mediated decrease of TbetaRII protein expression was not inhibited by the treatment of fibroblasts with either a selective inhibitor of I-kappaB-alpha phosphorylation, BAY 11-7082, or a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, PD98059. Calpain inhibitor I (ALLN), a protease inhibitor, inhibits TNF-alpha-mediated down-regulation of TbetaRII. We found that TNF-alpha triggered down-regulation of TbetaRII, leading to desensitization of human dermal fibroblasts toward TGF-beta. Furthermore, these events seemed to cause a dramatic down-regulation of alpha2(I) collagen and tissue inhibitor of metalloproteinases 1 in systemic sclerosis fibroblasts. These results indicated that TNF-alpha impaired the response of the cells to TGF-beta by regulating the turnover of TbetaRII.

  473. Elevated circulating soluble CD40 ligand in patients with mixed connective tissue disease Peer-reviewed

    M Jinnin, H Ihn, N Yazawa, Y Asano, K Yamane, K Tamaki

    CLINICAL RHEUMATOLOGY　22　(1)　37-39　2003/02

    DOI： 10.1007/s10067-002-0669-y 　

    ISSN： 0770-3198

  474. Plasma plasmin-alpha(2)-plasmin inhibitor complex levels are increased in systemic sclerosis patients with pulmonary hypertension Peer-reviewed

    M Jinnin, H Ihn, K Yamane, Y Asano, N Yazawa, K Tamaki

    RHEUMATOLOGY　42　(2)　240-243　2003/02

    DOI： 10.1093/rheumatology/keg071 　

    ISSN： 1462-0324

  475. The prevalence and clinical significance of anti-U1 RNA antibodies in patients with systemic sclerosis. International-journal Peer-reviewed

    Yoshihide Asano, Hironobu Ihn, Kenichi Yamane, Masahide Kubo, Kunihiko Tamaki

    The Journal of investigative dermatology　120　(2)　204-10　2003/02

    DOI： 10.1046/j.1523-1747.2003.12028.x 　

    ISSN： 0022-202X

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    We studied the prevalence and clinical significance of anti-U1 RNA antibodies in patients with systemic sclerosis. The presence of anti-U1 RNA antibodies was determined using immunoprecipitation in systemic sclerosis patients with anti-U1 RNP antibodies (n=36), antitopoisomerase I antibodies (n=20), or anticentromere antibodies (n=20), mixed connective tissue disease patients (n=23), systemic lupus erythematosus patients with anti-U1 RNP antibodies (n=26), and normal controls (n=20). Moreover, antigen specificities for anti-U1 RNP antibodies were examined in patients with systemic sclerosis by immunoblotting and enzyme-linked immunosorbent assay. Anti-U1 RNA antibodies was detected in 22 of 36 systemic sclerosis patients (61%) with anti-U1 RNP antibodies, 14 of 23 patients (61%) with mixed connective tissue disease, and eight of 26 systemic lupus erythematosus patients (31%) with anti-U1 RNP antibodies. Anti-U1 RNA antibodies were not detected in other groups. As for systemic sclerosis patients, the frequencies of pulmonary fibrosis and reduced percentage diffusion capacity for carbon monoxide were significantly greater in patients with anti-U1 RNA antibodies than in those without (76%vs 18%, p<0.005; 82%vs 27%, p<0.005, respectively). Moreover, patients with anti-U1 RNA antibodies had significantly lower percentage diffusion capacity for carbon monoxide and percentage vital capacity values than those without (51.9+/-16.8 vs 79.4+/-16.4, p<0.01; 83.8+/-21.4 vs 101.4+/-12.9, p<0.05, respectively). Regarding the antigen specificities of anti-U1 RNP antibodies in systemic sclerosis patients, the frequency of anti-70 kDa antibodies determined by immunoblotting was significantly higher in patients with anti-U1 RNA antibodies than in those without (77%vs 43%, p<0.05). This finding was also confirmed by enzyme-linked immunosorbent assay for anti-70 kDa antibodies (86%vs 43%, p<0.05). These results indicate that anti-U1 RNA antibodies may be a serologic indicator for pulmonary fibrosis in systemic sclerosis patients with anti-U1 RNP antibodies.

  476. Clinical features of patients with systemic sclerosis accompanied by rheumatoid arthritis Peer-reviewed

    A Jinnin, H Ihn, K Yamane, Y Asano, N Yazawa, K Tamaki

    CLINICAL AND EXPERIMENTAL RHEUMATOLOGY　21　(1)　91-94　2003/01

    ISSN： 0392-856X

  477. Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis: correlation with interstitial lung disease Peer-reviewed

    H Ihn, Y Asano, M Kubo, K Yamane, M Jinnin, N Yazawa, M Fujimoto, K Tamaki

    RHEUMATOLOGY　41　(11)　1268-1272　2002/11

    ISSN： 1462-0324

  478. Serum levels of tissue inhibitor of metalloproteinases in patients with mixed connective tissue disease Peer-reviewed

    M Jinnin, H Ihn, K Yamane, Y Asano, N Yazawa, K Tamaki

    CLINICAL AND EXPERIMENTAL RHEUMATOLOGY　20　(4)　539-542　2002/07

    ISSN： 0392-856X

  479. Prevalence of 52-kd and 60-kd Ro/SS-A autoantibodies in Japanese patients with polymyositis/dermatomyositis. International-journal Peer-reviewed

    Masahide Kubo, Hironobu Ihn, Yoshihide Asano, Kenichi Yamane, Norihito Yazawa, Kunihiko Tamaki

    Journal of the American Academy of Dermatology　47　(1)　148-51　2002/07

    ISSN： 0190-9622

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    To determine the prevalence of 52-kd and 60-kd Ro/SS-A antibodies in Japanese patients with polymyositis/dermatomyositis, we examined serum samples from 61 patients with PM/DM, 10 patients with primary Sjögren's syndrome, and 25 healthy control subjects. Six serum samples possessed anti-Ro/SS-A antibodies and were positive for anti-Ro52, anti-Ro60, or both. Two reacted with both Ro52 and Ro60, and 4 reacted with Ro52 alone. The results suggest that Ro52 is the main antigen of anti-Ro/SS-A antibodies in patients with polymyositis/dermatomyositis and that its coexistence with other defined antibodies suggests the existence of a subgroup of patients with various serologic abnormalities.

  480. A case of linear scleroderma with muscle calcification Peer-reviewed

    M Jinnin, H Ihn, Y Asano, K Yamane, N Yazawa, K Tamaki

    BRITISH JOURNAL OF DERMATOLOGY　146　(6)　1084-1086　2002/06

    ISSN： 0007-0963

  481. 背部に遊走性紅斑を生じたライム病 最近報告された国内72症例の臨床的特徴 Peer-reviewed

    金子 健彦, 浅野 善英, 服部 尚子, 小宮根 真弓, 川端 康浩, 相馬 良直, 薦田 房子

    臨床皮膚科　56　(4)　291-294　2002/04

    Publisher: (株)医学書院

    ISSN： 0021-4973

    eISSN： 1882-1324

  482. IL-4 up-regulates the expression of tissue inhibitor of metalloproteinase-2 in dermal fibroblasts via the p38 mitogen-activated protein kinase dependent pathway. International-journal Peer-reviewed

    Hironobu Ihn, Kenichi Yamane, Yoshihide Asano, Masahide Kubo, Kunihiko Tamaki

    Journal of immunology (Baltimore, Md. : 1950)　168　(4)　1895-902　2002/02/15

    DOI： 10.4049/jimmunol.168.4.1895 　

    ISSN： 0022-1767

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    Tissue inhibitor of metalloproteinase-2 (TIMP-2) is a potent inhibitor of activated matrix metalloproteinases such as gelatinase and collagenase, and thus helps to control extracellular matrix metabolism and deposition by connective tissue cells. We examined the responsiveness of the expression of TIMP-2 to various cytokines in dermal fibroblasts and studied the regulatory and signaling mechanisms of the response. TIMP-2 protein and mRNA expression was induced by IL-4 in a dose- and time-dependent manner, but not by TGF-beta, oncostatin M, or IL-6. IL-4 induction of TIMP-2 expression was dependent upon transcription. The p38 mitogen-activated protein kinase (MAPK) inhibitors SB202190 and SB203580 suppressed IL-4-induced TIMP-2 expression, suggesting the involvement of p38 MAP kinase in the signaling of IL-4 leading to TIMP-2 expression. Immunoblotting analysis using a specific Ab against phosphorylated p38 MAP kinase (Thr(180)/Tyr(182)) showed that IL-4 induced phosphorylation of p38 MAP kinase in human dermal fibroblasts. Furthermore, the p38 MAP kinase assay showed that IL-4 induces p38 MAPK activation in human dermal fibroblasts. The expression of the dominant-negative mutant p38 MAPK represses the IL-4-induced TIMP-2 expression in human dermal fibroblasts. Thus, IL-4 can potentially alter the dermal matrix metabolism by regulating TIMP-2.

  483. Clinical significance of surfactant protein D as a serum marker for evaluating pulmonary fibrosis in patients with systemic sclerosis Peer-reviewed

    Y Asano, H Ihn, K Yamane, N Yazawa, M Kubo, M Fujimoto, K Tamaki

    ARTHRITIS AND RHEUMATISM　44　(6)　1363-1369　2001/06

    ISSN： 0004-3591

  484. 病理組織型と耐糖能障害の関連を示唆した脂肪類壊死の2例 Peer-reviewed

    浅野 善英, 藤田 悦子, 服部 尚子, 湧川 基史, 金子 健彦, 鳥居 秀嗣, 小宮根 真弓, 朝比奈 昭彦, 川端 康浩, 相馬 良直

    皮膚科の臨床　43　(4)　562-563　2001/04

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  485. Clinical and laboratory features of scleroderma patients with pulmonary hypertension Peer-reviewed

    K Yamane, H Ihn, Y Asano, N Yazawa, M Kubo, K Kikuchi, Y Soma, K Tamaki

    RHEUMATOLOGY　39　(11)　1269-1271　2000/11

    ISSN： 1462-0324

Show all ︎Show first 5

Misc. 325

  1. 頭部の瘢痕性脱毛から診断に至った,溶骨性腫瘤を伴うExtranodal marginal zone B-cell lymphomaの1例

    小林 愛里, 水芦 政人, 浅野 善英, 相場 節也, 横山 寿行

    西日本皮膚科　85　(3)　238-239　2023/06

    Publisher: 日本皮膚科学会-西部支部

    ISSN： 0386-9784

    eISSN： 1880-4047

  2. Development of HGF Aptamer Sustained-release Dissolved Microneedles and Application in Scleroderma Model

    CHEN M., LIN C., CAI X., TSAI C., DAI Y., 大川将志, 稲垣奈都子, 太田誠一, 植木亮介, 山東信介, 朴鍾こう, 金範しゅん, 浅野善英, 佐藤伸一, 伊藤大知

    化学工学会秋季大会研究発表講演要旨集(CD-ROM)　53rd　2022

  3. 膠原病・血管炎に伴う皮膚潰瘍-ガイドラインから学ぶ治療方針の基本と最近10年間の変遷-

    石井貴之, 浅野善英, 浅井純, 岩田洋平, 内山明彦, 小川陽一, 岡村賢, 岸部麻里, 小池雄太, 小寺雅也, 壽順久, 藤本徳毅, 宮城拓也, 宮部千恵, 山口由衣, 吉崎歩

    日本皮膚科学会雑誌　131　(5)　2021

    ISSN： 0021-499X

  4. Localized scleroderma-like lesions induced by the Köbner phenomenon in a patient with systemic sclerosis positive for anticentromere antibody

    Yoshihide Asano, Shinichi Sato

    European Journal of Dermatology　30　(4)　431-432　2020/07/01

    Publisher: John Libbey

    DOI： 10.1684/ejd.2020.3808 　

    ISSN： 1952-4013 1167-1122

  5. Localized scleroderma histologically characterized by liquefaction degeneration and upper dermis fibrosis: a possible association with chemotherapy

    S. Toyama, S. Sato, Y. Asano

    Clinical and Experimental Dermatology　45　(5)　632-634　2020/07/01

    Publisher: Blackwell Publishing Ltd

    DOI： 10.1111/ced.14216 　

    ISSN： 1365-2230 0307-6938

  6. Case of systemic sclerosis with multiple primary malignancies in whom anti-RNA polymerase III antibody was detected by immunoprecipitation

    Naohiko Aozasa, Miki Miyazaki, Jun Hayakawa, Takeshi Tamaki, Yasuhito Hamaguchi, Shinichi Sato, Yoshihide Asano

    Journal of Dermatology　47　(7)　e269-e270　2020/07/01

    DOI： 10.1111/1346-8138.15383 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  7. Rationally-based therapeutic disease modification in systemic sclerosis: Novel strategies

    Yoshihide Asano, John Varga

    Seminars in Cell and Developmental Biology　101　146-160　2020/05/01

    Publisher: Elsevier Ltd

    DOI： 10.1016/j.semcdb.2019.12.007 　

    ISSN： 1096-3634 1084-9521

  8. Subacute thyroiditis in psoriasis patients treated with biologics targeting tumor necrosis factor-alpha and interleukin-17A, a report of two cases

    Kouki Nakamura, Masahiro Kamata, Shinichi Sato, Yoshihide Asano

    JOURNAL OF CUTANEOUS IMMUNOLOGY AND ALLERGY　3　(2)　33-34　2020/04

    DOI： 10.1002/cia2.12093 　

    eISSN： 2574-4593

  9. Overlapping systemic sclerosis and sarcoidosis with mutually exclusive disease activities: a case report and analysis of previous studies

    Kouki Nakamura, Shinichi Sato, Yoshihide Asano

    European Journal of Dermatology　30　(1)　50-52　2020/01/01

    Publisher: John Libbey Eurotext

    DOI： 10.1684/ejd.2019.3683 　

    ISSN： 1952-4013 1167-1122

  10. 強皮症・皮膚線維化疾患の診断基準・重症度分類・診療ガイドラインに関する研究 2016年厚生労働省研究班作成の全身性強皮症診断基準の感度と特異度の評価

    川口鎮司, 浅野善英, 石川治, 桑名正隆, 後藤大輔, 神人正寿, 竹原和彦, 長谷川稔, 波多野将, 藤本学, 牧野貴充, 山本俊幸, 佐藤伸一, 高木香恵, 栃本明子, 樋口智明, 尹浩信

    強皮症・皮膚線維化疾患の診断基準・重症度分類・診療ガイドラインに関する研究 令和元年度 総括・分担研究報告書(Web)　2020

  11. Localized scleroderma manifesting with skin lesions associated with mechanical stress

    Satoshi Toyama, Shinichi Sato, Yoshihide Asano

    European Journal of Dermatology　29　(4)　439-440　2019/07/01

    Publisher: John Libbey Eurotext

    DOI： 10.1684/ejd.2019.3601 　

    ISSN： 1952-4013 1167-1122

  12. リウマチ性疾患の超音波検査 乾癬性関節炎の関節エコー所見と臨床指標との身体部位ごとの関連の検討

    住友 秀次, 立石 晶子, 白井 晴己, 大野 久美子, 廣瀬 旬, 吉崎 歩, 浅野 善英, 佐藤 伸一, 田中 栄, 藤尾 圭志, 山本 一彦, 神田 浩子

    日本リウマチ学会総会・学術集会プログラム・抄録集　63回　429-429　2019/03

    Publisher: (一社)日本リウマチ学会

  13. 強皮症-1 本邦における全身性強皮症早期重症例の臨床症状の多施設前向き研究

    宇都宮 慧, 長谷川 稔, 浅野 善英, 石川 治, 遠藤 平仁, 川口 鎮司, 桑名 正隆, 後藤 大輔, 佐藤 伸一, 高橋 裕樹, 竹原 和彦, 田中 住明, 藤本 学, 尹 浩信

    日本リウマチ学会総会・学術集会プログラム・抄録集　63回　530-530　2019/03

    Publisher: (一社)日本リウマチ学会

  14. 強皮症・皮膚線維化疾患の診断基準・重症度分類・診療ガイドラインに関する研究 強皮症の早期分類基準の検証

    桑名正隆, 浅野善英, 川口鎮司, 後藤大輔, 神人正寿, 竹原和彦, 波多野将, 藤本学, 牧野貴充, 佐藤伸一, 白井悠一郎, 尹浩信

    強皮症・皮膚線維化疾患の診断基準・重症度分類・診療ガイドラインに関する研究 平成30年度 総括・分担研究報告書(Web)　2019

  15. 関節拘縮を伴ったSezary症候群の1例

    久住 藍, 宍戸 菜穂美, 管 析, 赤股 要, 宮垣 朝光, 浅野 善英, 佐藤 伸一, 田中 麻理子

    日本皮膚科学会雑誌　128　(6)　1364-1364　2018/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  16. 強皮症治療のためのSPG膜乳化法による細胞外マトリクス分解酵素封入マイクロビーズの開発

    川島佑太, 太田誠一, 大河内仁志, 浅野善英, 佐藤伸一, 伊藤大知, 伊藤大知

    化学工学会年会研究発表講演要旨集(CD-ROM)　83rd　2018

  17. SPG膜乳化法を用いた細胞外マトリクス分解酵素徐放性マイクロビーズの開発とその強皮症治療効果の検証

    太田誠一, 川島佑太, 松浦麻衣, 大河内仁志, 浅野善英, 佐藤伸一, 伊藤大知

    化学工学会秋季大会研究発表講演要旨集(CD-ROM)　50th　2018

  18. 生物学的製剤複数使用経験を有するSAPHO症候群の2症例

    山田 紗依子, 永渕 泰雄, 住友 秀次, 久保 かなえ, 庄田 宏文, 神田 浩子, 浅野 善英, 藤尾 圭志

    日本リウマチ学会関東支部学術集会プログラム・抄録集　28回　92-92　2017/12

    Publisher: 日本リウマチ学会-関東支部

  19. Accelerated Wound Healing in Megakaryocyte/Platelet-Specific Fli1 Knockout Mice Due to the up-Regulated Expression of Interferon-gamma

    Megumi Hirabayashi, Yoshihide Asano, Takashi Yamashita, Ryosuke Saigusa, Shunsuke Miura, Kouki Nakamura, Takuya Miyagawa, Takashi Taniguchi, Ayumi Yoshizaki, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　69　2017/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  20. 日本皮膚科学会ガイドライン 創傷・褥瘡・熱傷ガイドライン 褥瘡診療ガイドライン

    藤原 浩, 磯貝 善蔵, 入澤 亮吉, 大塚 正樹, 門野 岳史, 古賀 文二, 廣崎 邦紀, 浅井 純, 浅野 善英, 安部 正敏, 天野 正宏, 池上 隆太, 石井 貴之, 爲政 大幾, 伊藤 孝明, 井上 雄二, 岩田 洋平, 尾本 陽一, 加藤 裕史, 金子 栄, 加納 宏行, 川上 民裕, 川口 雅一, 久木野 竜一, 幸野 健, 小寺 雅也, 境 恵祐, 櫻井 英一, 皿山 泰子, 新谷 洋一, 谷岡 未樹, 谷崎 英昭, 辻田 淳, 土井 直孝, 中西 健史, 橋本 彰, 長谷川 稔, 林 昌浩, 藤田 英樹, 藤本 学, 前川 武雄, 松尾 光馬, 間所 直樹, 茂木 精一郎, 八代 浩, 山崎 修, 吉野 雄一郎, レパヴー アンドレ, 立花 隆夫, 尹 浩信

    日本皮膚科学会雑誌 = The Japanese journal of dermatology　127　(8)　1689-1744　2017/08

    Publisher: 日本皮膚科学会

    ISSN： 0021-499X

  21. イミキモド誘発乾癬様皮膚炎におけるCXCL17の役割

    岡 知徳, 菅谷 誠, 高橋 菜穂美, 高橋 岳浩, 柴田 彩, 浅野 善英, 宮垣 朝光, 佐藤 伸一

    日本臨床免疫学会会誌　40　(4)　317-317　2017/08

    Publisher: 日本臨床免疫学会

    ISSN： 0911-4300

    eISSN： 1349-7413

  22. Pansclerotic morpheaの1例

    谷口 隆志, 浅野 善英, 吉崎 歩, 江畑 慧, 乙部 さやか, 赤股 要, 宮垣 朝光, 佐藤 伸一, 馬場 淳徳

    日本皮膚科学会雑誌　127　(7)　1563-1563　2017/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  23. 金属ヘラ絞り加工業従事による粉塵暴露が発症に関連したと考えた全身性強皮症

    中村 理沙絵, 谷口 隆志, 遠山 聡, 柏山 薫, 遠山 哲夫, 高橋 岳浩, 赤股 要, 宮垣 朝光, 浅野 善英, 佐藤 伸一

    西日本皮膚科　79　(3)　309-310　2017/06

    Publisher: 日本皮膚科学会-西部支部

    ISSN： 0386-9784

  24. Unprecedented success of rituximab therapy for prednisolone- and immunosuppressant-resistant systemic sclerosis-associated interstitial lung disease

    S. Ebata, A. Yoshizaki, T. Fukasawa, K. Nakamura, T. Yamashita, S. Miura, R. Saigusa, Y. Ichimura, T. Takahashi, M. Hirabayashi, T. Taniguchi, K. Akamata, Y. Asano, S. Sato

    Scandinavian Journal of Rheumatology　46　(3)　247-252　2017/05/04

    Publisher: Taylor and Francis Ltd

    DOI： 10.1080/03009742.2016.1231341 　

    ISSN： 1502-7732 0300-9742

  25. Increased interleukin-36 gamma expression in skin and sera of patients with atopic dermatitis and cutaneous T-cell lymphoma

    S. Otobe, M. Sugaya, R. Nakajima, T. Oka, N. Takahashi, M. Kabasawa, T. Miyagaki, Y. Asano, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　137　(5)　S45-S45　2017/05

    ISSN： 0022-202X

    eISSN： 1523-1747

  26. The vitamin D3 analog, maxacalcitol, ameliorates imiquimod induced murine psoriasiform skin inflammation by inducing regulatory T cells and downregulating Th17 responses

    C. Sy Hau, T. Shimizu, Y. Tada, S. Takeoka, S. Shibata, A. Mitsui, M. Kamata, Y. Asano, M. Sugaya, T. Kadono, S. Sato, S. Watanabe

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　137　(5)　S4-S4　2017/05

    ISSN： 0022-202X

    eISSN： 1523-1747

  27. BET bromodomain inhibitor JQ1 decreases CD30 and CCR4 expression as well as proliferation of cutaneous T-cell lymphoma

    M. Sugaya, H. Kamijo, N. Takahshi, T. Oka, T. Miyagaki, Y. Asano, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　137　(5)　S116-S116　2017/05

    ISSN： 0022-202X

    eISSN： 1523-1747

  28. Increased Interleukin-19 expression in cutaneous T-cell lymphoma as well as atopic dermatitis

    T. Oka, M. Sugaya, N. Takahashi, R. Nakajima, S. Otobe, M. Kabasawa, H. Suga, T. Miyagaki, Y. Asano, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　137　(5)　S44-S44　2017/05

    ISSN： 0022-202X

    eISSN： 1523-1747

  29. TLR2 deficiency exacerbates imiquimod-induced psoriasis-like skin inflammation through downregulation of regulatory T cells and impaired IL-10 production by regulatory T cells and dendritic cells

    M. Nakao, M. Sugaya, H. Fujita, T. Miyagaki, S. Morimura, S. Shibata, Y. Asano, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　137　(5)　S2-S2　2017/05

    ISSN： 0022-202X

    eISSN： 1523-1747

  30. The combination of bosentan with bFGF accelerates wound healing in endothelial cell-specific Fli1 knockout mice mimicking scleroderma vasculopathy

    T. Yamashita, Y. Asano, A. Yoshizaki, M. Trojanowska, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　137　(5)　S154-S154　2017/05

    ISSN： 0022-202X

    eISSN： 1523-1747

  31. Fli1-deficient B cells induce scleroderma-like vascular disorganization via activating pro-angiogenic gene program in dermal microvascular endothelial cells - A possible role in scleroderma vasculopathy

    R. Saigusa, Y. Asano, A. Yoshizaki, M. Trojanowska, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　137　(5)　S1-S1　2017/05

    ISSN： 0022-202X

    eISSN： 1523-1747

  32. Efficacy and safety of dose escalation of infliximab therapy in Japanese patients with psoriasis: Results of the SPREAD study Peer-reviewed

    Hideshi Torii, Masayuki Nakano, Toshiro Yano, Kazuoki Kondo, Hidemi Nakagawa, Yasuyuki Fujita, Keita Horie, Miki Ito, Mari Iitani, Kei Ito, Takahide Kaneko, Toshihide Akasaka, Mamitaro Ohtuki, Masato Yasuda, Masatoshi Abe, Yurika Tanida, Tadashi Terui, Satoru Arai, Toshiaki Nakano, Takafumi Etoh, Yoshihide Asano, Yoshinori Umezawa, Hidehisa Saeki, Makoto Adachi, Mariko Seishima, Yoshiki Tokura, Akimichi Morita, Keiichi Yamanaka, Mamoru Tani, Hirotsugu Tanimura, Fumikazu Yamazaki, Chikako Nishigori, Sakae Kaneko, Masahiko Muto, Motonobu Nakamura, Ryosuke Hino, Juichiro Nakayama, Teruaki Nakano, Atsushi Utani, Toshihiro Sato, Hironobu Ihn

    Journal of Dermatology　44　(5)　552-559　2017/05

    DOI： 10.1111/1346-8138.13698 　

    ISSN： 0385-2407

    eISSN： 1346-8138

  33. A case of scleroderma en coup de sabre progressing gradually over 60 years

    R. Saigusa, Y. Asano, H. Sumida, S. Sato

    Scandinavian Journal of Rheumatology　46　(1)　83-84　2017/01/02

    Publisher: Taylor and Francis Ltd

    DOI： 10.3109/03009742.2016.1158315 　

    ISSN： 1502-7732 0300-9742

  34. 強皮症・皮膚線維化疾患の診断基準・重症度分類・診療ガイドライン作成 全身性強皮症の腎障害の重症度分類と診療ガイドライン

    川口鎮司, 浅野善英, 桑名正隆, 後藤大輔, 神人正寿, 竹原和彦, 波多野将, 藤本学, 佐藤伸一, 高木香恵, 栃本明子, 樋口智昭, 市村裕輝, 尹浩信

    強皮症・皮膚線維化疾患の診断基準・重症度分類・診療ガイドライン作成事業 平成28年度 総括・分担研究報告書(Web)　2017

  35. 創傷・褥瘡・熱傷ガイドライン―4：膠原病・血管炎にともなう皮膚潰瘍診療ガイドライン

    藤本 学, 浅井 純, 浅野 善英, 石井 貴之, 岩田 洋平, 川上 民裕, 小寺 雅也, 安部 正敏, 天野 正宏, 池上 隆太, 爲政 大幾, 磯貝 善蔵, 伊藤 孝明, 井上 雄二, 入澤 亮吉, 大塚 正樹, 尾本 陽一, 加藤 裕史, 門野 岳史, 金子 栄, 加納 宏行, 川口 雅一, 久木野 竜一, 幸野 健, 古賀 文二, 境 恵祐, 櫻井 英一, 皿山 泰子, 新谷 洋一, 谷岡 未樹, 谷崎 英昭, 辻田 淳, 土井 直孝, 中西 健史, 橋本 彰, 長谷川 稔, 林 昌浩, 廣崎 邦紀, 藤田 英樹, 藤原 浩, 前川 武雄, 松尾 光馬, 間所 直樹, 茂木 精一郎, 八代 浩, 山崎 修, 吉野 雄一郎, レパヴー アンドレ, 立花 隆夫, 尹 浩信

    日本皮膚科学会雑誌　127　(9)　2033-2075　2017

    Publisher: 公益社団法人 日本皮膚科学会

    DOI： 10.14924/dermatol.127.2033 　

    ISSN： 0021-499X

  36. 創傷・褥瘡・熱傷ガイドライン―1：創傷一般ガイドライン

    井上 雄二, 金子 栄, 加納 宏行, 新谷 洋一, 辻田 淳, 長谷川 稔, 藤田 英樹, 茂木 精一郎, レパヴー アンドレ, 浅井 純, 浅野 善英, 安部 正敏, 天野 正宏, 池上 隆太, 石井 貴之, 爲政 大幾, 磯貝 善蔵, 伊藤 孝明, 入澤 亮吉, 岩田 洋平, 大塚 正樹, 尾本 陽一, 加藤 裕史, 門野 岳史, 川上 民裕, 川口 雅一, 久木野 竜一, 幸野 健, 古賀 文二, 小寺 雅也, 境 恵祐, 櫻井 英一, 皿山 泰子, 谷岡 未樹, 谷崎 英昭, 土井 直孝, 中西 健史, 橋本 彰, 林 昌浩, 廣崎 邦紀, 藤本 学, 藤原 浩, 前川 武雄, 松尾 光馬, 間所 直樹, 八代 浩, 山崎 修, 吉野 雄一郎, 立花 隆夫, 尹 浩信

    日本皮膚科学会雑誌　127　(8)　1659-1687　2017

    Publisher: 公益社団法人 日本皮膚科学会

    DOI： 10.14924/dermatol.127.1659 　

    ISSN： 0021-499X

  37. 創傷・褥瘡・熱傷ガイドライン―3：糖尿病性潰瘍・壊疽ガイドライン

    爲政 大幾, 安部 正敏, 池上 隆太, 加藤 裕史, 櫻井 英一, 谷崎 英昭, 中西 健史, 松尾 光馬, 山崎 修, 浅井 純, 浅野 善英, 天野 正宏, 石井 貴之, 磯貝 善蔵, 伊藤 孝明, 井上 雄二, 入澤 亮吉, 岩田 洋平, 大塚 正樹, 尾本 陽一, 門野 岳史, 金子 栄, 加納 宏行, 川上 民裕, 川口 雅一, 久木野 竜一, 幸野 健, 古賀 文二, 小寺 雅也, 境 恵祐, 皿山 泰子, 新谷 洋一, 谷岡 未樹, 辻田 淳, 土井 直孝, 橋本 彰, 長谷川 稔, 林 昌浩, 廣崎 邦紀, 藤田 英樹, 藤本 学, 藤原 浩, 前川 武雄, 間所 直樹, 茂木 精一郎, 八代 浩, 吉野 雄一郎, レパヴー アンドレ, 立花 隆夫, 尹 浩信

    日本皮膚科学会雑誌　127　(9)　1989-2031　2017

    Publisher: 公益社団法人 日本皮膚科学会

    DOI： 10.14924/dermatol.127.1989 　

    ISSN： 0021-499X

  38. 創傷・褥瘡・熱傷ガイドライン―2：褥瘡診療ガイドライン

    藤原 浩, 磯貝 善蔵, 入澤 亮吉, 大塚 正樹, 門野 岳史, 古賀 文二, 廣崎 邦紀, 浅井 純, 浅野 善英, 安部 正敏, 天野 正宏, 池上 隆太, 石井 貴之, 爲政 大幾, 伊藤 孝明, 井上 雄二, 岩田 洋平, 尾本 陽一, 加藤 裕史, 金子 栄, 加納 宏行, 川上 民裕, 川口 雅一, 久木野 竜一, 幸野 健, 小寺 雅也, 境 恵祐, 櫻井 英一, 皿山 泰子, 新谷 洋一, 谷岡 未樹, 谷崎 英昭, 辻田 淳, 土井 直孝, 中西 健史, 橋本 彰, 長谷川 稔, 林 昌浩, 藤田 英樹, 藤本 学, 前川 武雄, 松尾 光馬, 間所 直樹, 茂木 精一郎, 八代 浩, 山崎 修, 吉野 雄一郎, レパヴー アンドレ, 立花 隆夫, 尹 浩信

    日本皮膚科学会雑誌　127　(9)　1933-1988　2017

    Publisher: 公益社団法人 日本皮膚科学会

    DOI： 10.14924/dermatol.127.1933 　

    ISSN： 0021-499X

  39. 創傷・褥瘡・熱傷ガイドライン―5：下腿潰瘍・下肢静脈瘤診療ガイドライン

    伊藤 孝明, 久木野 竜一, 皿山 泰子, 谷岡 未樹, 前川 武雄, 八代 浩, 浅井 純, 浅野 善英, 安部 正敏, 天野 正宏, 池上 隆太, 石井 貴之, 爲政 大幾, 磯貝 善蔵, 井上 雄二, 入澤 亮吉, 岩田 洋平, 大塚 正樹, 尾本 陽一, 加藤 裕史, 谷崎 英昭, 門野 岳史, 金子 栄, 加納 宏行, 川上 民裕, 川口 雅一, 幸野 健, 古賀 文二, 小寺 雅也, 境 恵祐, 櫻井 英一, 新谷 洋一, 辻田 淳, 土井 直孝, 中西 健史, 橋本 彰, 長谷川 稔, 林 昌浩, 廣崎 邦紀, 藤田 英樹, 藤本 学, 藤原 浩, 松尾 光馬, 間所 直樹, 茂木 精一郎, 山崎 修, 吉野 雄一郎, レパヴー アンドレ, 立花 隆夫, 尹 浩信

    日本皮膚科学会雑誌　127　(10)　2239-2259　2017

    Publisher: 公益社団法人 日本皮膚科学会

    DOI： 10.14924/dermatol.127.2239 　

    ISSN： 0021-499X

  40. 創傷・褥瘡・熱傷ガイドライン―6：熱傷診療ガイドライン

    吉野 雄一郎, 天野 正宏, 尾本 陽一, 川口 雅一, 境 恵祐, 土井 直孝, 橋本 彰, 林 昌浩, 間所 直樹, 浅井 純, 浅野 善英, 安部 正敏, 池上 隆太, 石井 貴之, 爲政 大幾, 磯貝 善蔵, 伊藤 孝明, 井上 雄二, 入澤 亮吉, 岩田 洋平, 大塚 正樹, 加藤 裕史, 門野 岳史, 金子 栄, 加納 宏行, 川上 民裕, 久木野 竜一, 幸野 健, 古賀 文二, 小寺 雅也, 櫻井 英一, 皿山 泰子, 新谷 洋一, 谷岡 未樹, 谷崎 英昭, 辻田 淳, 中西 健史, 長谷川 稔, 廣崎 邦紀, 藤田 英樹, 藤本 学, 藤原 浩, 前川 武雄, 松尾 光馬, 茂木 精一郎, 八代 浩, 山崎 修, レパヴー アンドレ, 立花 隆夫, 尹 浩信

    日本皮膚科学会雑誌　127　(10)　2261-2292　2017

    Publisher: 公益社団法人 日本皮膚科学会

    DOI： 10.14924/dermatol.127.2261 　

    ISSN： 0021-499X

  41. The efficacy of dantrolene sodium for muscle cramps in patients with localized scleroderma

    K. Nakamura, A. Yoshizaki, R. Saigusa, T. Taniguchi, Y. Asano, S. Sato

    Journal of the European Academy of Dermatology and Venereology　30　(12)　e188-e189　2016/12/01

    Publisher: Blackwell Publishing Ltd

    DOI： 10.1111/jdv.13497 　

    ISSN： 1468-3083 0926-9959

  42. Anaplastic large cell lymphoma involving skin and muscle associated with polymyositis

    T. Miyagaki, M. Sugaya, Y. Hayashi, K. Nakamura, N. Takahashi, Y. Asano, S. Sato, A. Koguchi, N. Yamaguchi, J. Ueda, J. Shimizu, S. Tsuji, K. Taoko, M. Kurokawa

    AUSTRALASIAN JOURNAL OF DERMATOLOGY　57　32-32　2016/11

    ISSN： 0004-8380

    eISSN： 1440-0960

  43. Regulatory B cells ameliorate the symptoms of systemic sclerosis via an antigen-specific manner: the novel therapeutic strategy for autoimmune diseases

    A. Yoshizaki, T. Fukasawa, S. Ebata, T. Taniguchi, Y. Asano, Y. Kazoe, K. Mawatari, T. Kitamori, S. Sato

    AUSTRALASIAN JOURNAL OF DERMATOLOGY　57　9-9　2016/11

    ISSN： 0004-8380

    eISSN： 1440-0960

  44. 日本皮膚科学会ガイドライン 好酸球性筋膜炎 診断基準・重症度分類・診療ガイドライン

    神人 正寿, 山本 俊幸, 浅野 善英, 石川 治, 佐藤 伸一, 竹原 和彦, 長谷川 稔, 藤本 学, 尹 浩信, 好酸球性筋膜炎診断基準, 重症度分類, 診療ガイドライン委員会

    日本皮膚科学会雑誌　126　(12)　2241-2250　2016/11

    Publisher: (公社)日本皮膚科学会

    DOI： 10.14924/dermatol.126.2241 　

    ISSN： 0021-499X

    eISSN： 1346-8146

  45. 日本皮膚科学会ガイドライン 硬化性萎縮性苔癬 診断基準・重症度分類・診療ガイドライン

    長谷川 稔, 石川 治, 浅野 善英, 佐藤 伸一, 神人 正寿, 竹原 和彦, 藤本 学, 山本 俊幸, 尹 浩信, 硬化性萎縮性苔癬診断基準, 重症度分類, 診療ガイドライン委員会

    日本皮膚科学会雑誌　126　(12)　2251-2257　2016/11

    Publisher: (公社)日本皮膚科学会

    DOI： 10.14924/dermatol.126.2251 　

    ISSN： 0021-499X

    eISSN： 1346-8146

  46. Klf5+/-;Fli1+/- Mice Recapitulate Protracted Wound Healing and Cardiac and Intestinal Involvement Associated with Systemic Sclerosis

    Kouki Nakamura, Yoshihide Asano, Takuya Miyagawa, Megumi Hirabayashi, Takashi Yamashita, Ryosuke Saigusa, Shunsuke Miura, Tetsuo Toyama, Takehiro Takahashi, Yohei Ichimura, Takashi Taniguchi, Ayumi Yoshizaki, Maria Trojanowska, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　68　2016/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  47. The Regulatory B Cells Ameliorate Skin Sclerosis, Lung Fibrosis, and Autoimmunity Via an Anti-Oxidative Effect in Systemic Sclerosis Model Mice

    Ayumi Yoshizaki, Takemichi Fukasawa, Satoshi Ebata, Kouki Nakamura, Takashi Yamashita, Ryosuke Saigusa, Yohei Ichimura, Takehiro Takahashi, Takashi Taniguchi, Asano Yoshihide, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　68　2016/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  48. Fli1-Haploinsufficient Dermal Fibroblasts Promote Skin-Localized Transdifferentiation of Th2-and Th17-like Regulatory T Cells

    Ryosuke Saigusa, Yoshihide Asano, Takuya Miyagawa, Megumi Hirabayashi, Kouki Nakamura, Shunsuke Miura, Takashi Yamashita, Yohei Ichimura, Takehiro Takahashi, Tetsuo Toyama, Takashi Taniguchi, Ayumi Yoshizaki, Maria Trojanowska, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　68　2016/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  49. 全身性エリテマトーデスの初発症状として発症した蛋白漏出性胃腸症

    乙部 さやか, 谷口 隆志, 江畑 慧, 山下 尚志, 赤股 要, 宮垣 朝光, 浅野 善英, 佐藤 伸一

    Journal of Environmental Dermatology and Cutaneous Allergology　10　(4)　461-461　2016/10

    Publisher: (一社)日本皮膚アレルギー・接触皮膚炎学会

    ISSN： 1882-0123

  50. 日本皮膚科学会ガイドライン 全身性強皮症 診断基準・重症度分類・診療ガイドライン

    全身性強皮症診断基準・重症度分類・診療ガイドライン委員会, 浅野 善英, 神人 正寿, 川口 鎮司, 桑名 正隆, 後藤 大輔, 佐藤 伸一, 竹原 和彦, 波多野 将, 藤本 学, 麦井 直樹, 尹 浩信

    日本皮膚科学会雑誌 = The Japanese journal of dermatology　126　(10)　1831-1896　2016/10

    Publisher: 日本皮膚科学会

    ISSN： 0021-499X

  51. CXCL17 Attenuates imiquimod-induced Psoriasis-like skin inflammation by recruiting myeloid-derived suppressor cells and regulatory T cells

    T. Oka, M. Sugaya, N. Takahashi, T. Takahashi, S. Shibata, T. Miyagaki, Y. Asano, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　136　(9)　S202-S202　2016/09

    ISSN： 0022-202X

    eISSN： 1523-1747

  52. Serum Autotaxin Levels Correlate with Pruritus in Patients with Atopic Dermatitis (vol 134, pg 1745, 2014)

    Momoko Nakao, Makoto Sugaya, Hiraku Suga, Makiko Kawaguchi, Sohshi Morimura, Hiromichi Kai, Hanako Ohmatsu, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　136　(9)　1925-1925　2016/09

    DOI： 10.1016/j.jid.2016.07.001 　

    ISSN： 0022-202X

    eISSN： 1523-1747

  53. 稀な組織型の膵癌を合併した皮膚筋炎

    遠山 聡, 渡辺 理沙絵, 柏山 薫, 谷口 隆志, 宮垣 朝光, 浅野 善英, 遠山 哲夫

    日本皮膚科学会雑誌　126　(9)　1732-1732　2016/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  54. Vascular endothelial growth factor-A and placental growth factor regulate tumor progression via increased vasculature in cutaneous T cell lymphoma

    T. Miyagaki, M. Sugaya, T. Oka, N. Takahashi, M. Kawaguchi, H. Suga, H. Fujita, A. Yoshizaki, Y. Asano, S. Sato

    EUROPEAN JOURNAL OF IMMUNOLOGY　46　238-238　2016/08

    ISSN： 0014-2980

    eISSN： 1521-4141

  55. 抗MDA5抗体陽性皮膚筋炎に合併した急速進行性間質性肺炎の病勢をコントロールし得た1例

    山口 慶, 高橋 岳浩, 深澤 毅倫, 沼尻 宏子, 宮垣 朝光, 浅野 善英, 佐藤 伸一, 大塚 十里, 清水 潤

    日本皮膚科学会雑誌　126　(7)　1317-1317　2016/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  56. その他の膠原病 乾癬性関節炎の末梢関節病変の活動性評価の検討

    神田 浩子, 立石 晶子, 住友 秀次, 白井 晴己, 大野 久美子, 吉崎 歩, 浅野 善英, 門野 夕峰, 佐藤 伸一, 田中 栄, 山本 一彦

    日本リウマチ学会総会・学術集会プログラム・抄録集　60回　407-407　2016/03

    Publisher: (一社)日本リウマチ学会

  57. 強皮症・皮膚線維化疾患の診断基準・重症度分類・診療ガイドライン作成事業 全身性強皮症の腎障害の重症度分類と診療ガイドライン

    川口鎮司, 浅野善英, 桑名正隆, 後藤大輔, 神人正寿, 竹原和彦, 波多野将, 藤本学, 佐藤伸一, 高木香恵, 栃本明子, 樋口智昭, 尹浩信

    強皮症・皮膚線維化疾患の診断基準・重症度分類・診療ガイドライン作成事業 平成27年度 総括・分担研究報告書　2016

  58. 日本皮膚科学会ガイドライン 好酸球性筋膜炎 診断基準・重症度分類・診療ガイドライン

    神人 正寿, 山本 俊幸, 浅野 善英, 石川 治, 佐藤 伸一, 竹原 和彦, 長谷川 稔, 藤本 学, 尹 浩信, 好酸球性筋膜炎診断基準, 重症度分類, 診療ガイドライン委員会

    日本皮膚科学会雑誌　126　(12)　2241-2250　2016

    Publisher: (公社)日本皮膚科学会

    DOI： 10.14924/dermatol.126.2241 　

    ISSN： 0021-499X

  59. 限局性強皮症 診断基準・重症度分類・診療ガイドライン

    限局性強皮症 診断基準・重症度分類・診療ガイドライン委員会, 尹 浩信, 浅野 善英, 藤本 学, 石川 治, 佐藤 伸一, 神人 正寿, 竹原 和彦, 長谷川 稔, 山本 俊幸

    日本皮膚科学会雑誌　126　(11)　2039-2067　2016

    Publisher: 公益社団法人 日本皮膚科学会

    DOI： 10.14924/dermatol.126.2039 　

    ISSN： 0021-499X

  60. 日本皮膚科学会ガイドライン 硬化性萎縮性苔癬 診断基準・重症度分類・診療ガイドライン

    長谷川 稔, 石川 治, 浅野 善英, 佐藤 伸一, 神人 正寿, 竹原 和彦, 藤本 学, 山本 俊幸, 尹 浩信, 硬化性萎縮性苔癬診断基準, 重症度分類, 診療ガイドライン委員会

    日本皮膚科学会雑誌　126　(12)　2251-2257　2016

    Publisher: (公社)日本皮膚科学会

    DOI： 10.14924/dermatol.126.2251 　

    ISSN： 0021-499X

  61. CRP上昇から感染性心内膜炎が明らかとなった全身性エリテマトーデス(SLE)の1例

    渡邉 理沙絵, 柏山 薫, 宮垣 朝光, 浅野 善英, 吉崎 歩, 武田 悦寛, 明城 正博, 山内 治雄, 木下 修, 星野 康弘, 小野 稔

    日本皮膚科学会雑誌　125　(12)　2308-2308　2015/11

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  62. ST合剤によるさまざまなアレルギー症状を呈した全身性エリテマトーデスの1例

    林 剛生, 市村 洋平, 遠山 哲夫, 河合 徹, 宮垣 朝光, 浅野 善英, 菅谷 誠, 佐藤 伸一

    Journal of Environmental Dermatology and Cutaneous Allergology　9　(5)　454-454　2015/11

    Publisher: (一社)日本皮膚アレルギー・接触皮膚炎学会

    ISSN： 1882-0123

  63. Fli1 Deficiency Contributes to the Downregulation of Endothelial Protein C Receptor in Systemic Sclerosis: A Possible Role in Pro-Thrombotic Condition

    Ryosuke Saigusa, Yoshihide Asano, Takashi Taniguchi, Takashi Yamashita, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　67　2015/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  64. Regulatory B Cells Regulate Skin and Lung Fibrosis and Immunological Abnormalities in a Topoisomerase I and Complete Freund's Adjuvant-Induced Scleroderma Model Via an Antigen-Specific Manner

    Ayumi Yoshizaki, Takashi Taniguchi, Kouki Nakamura, Ryosuke Saigusa, Takashi Yamashita, Takehiro Takahashi, Tetsuo Toyama, Yohei Ichimura, Yoshihide Asano, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　67　2015/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  65. Glycyrrhizin Ameliorates Fibrosis, Vasculopathy, and Immune Abnormalities in Animal Models of Systemic Sclerosis

    Takashi Yamashita, Yoshihide Asano, Takashi Taniguchi, Ryosuke Saigusa, Kouki Nakamura, Syunnsuke Miura, Tetsuo Toyama, Takehiro Takahashi, Yohei Ichimura, Ayumi Yoshizaki, Maria Trojanowska, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　67　2015/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  66. Successful Treatment of Pityriasis Rubra Pilaris with the Combination Therapy of Etretinate and Cyclosporine

    57　(10)　1526-1530　2015/09

    Publisher: 金原出版

    ISSN： 0018-1404

  67. 左鼠径部に生じたtufted angiomaの1例

    井上 里佳, 森村 壮志, 浅野 善英, 宮川 卓也

    日本皮膚科学会雑誌　125　(7)　1454-1454　2015/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  68. Decreased IL-21 expression in skin and blood contributes to progression of mycosis fungoides

    M. Kabasawa, M. Sugaya, T. Oka, N. Takahashi, M. Kawaguchi, H. Suga, T. Miyagaki, H. Fujita, Y. Asano, Y. Tada, T. Kadono, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　135　S31-S31　2015/05

    ISSN： 0022-202X

    eISSN： 1523-1747

  69. Arthritis possibly induced and exacerbated by a tumour necrosis factor antagonist in a patient with psoriasis vulgaris

    T. Takahashi, Y. Asano, S. Shibata, K. Nakamura, M. Nakao, R. Shida, A. Mitsui, M. Araki, R. Watanabe, H. Fujita, Y. Tada, S. Sato

    British Journal of Dermatology　172　(5)　1458-1460　2015/05/01

    Publisher: Blackwell Publishing Ltd

    DOI： 10.1111/bjd.13587 　

    ISSN： 1365-2133 0007-0963

  70. CCL17 attenuates tumor immunity by increasing regulatory T cells and Th2 cells while decreasing myeloid-derived suppressor cells in tumor microenvironment

    S. Morimura, M. Sugaya, T. Oka, H. Suga, T. Miyagaki, Y. Tsunemi, Y. Asano, Y. Tada, T. Kadono, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　135　S2-S2　2015/05

    ISSN： 0022-202X

    eISSN： 1523-1747

  71. シリコン注入による豊胸術後、多彩な膠原病様症状を呈しヒト・アジュバント病が疑われた一例

    嵩 夕輝, 玉城 善史郎, 沼尻 宏子, 丸 陽美, 中村 洸樹, 増井 友里, 宮垣 朝光, 浅野 善英, 佐藤 伸一

    日本皮膚科学会雑誌　125　(4)　923-923　2015/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  72. Acquired Immune Deficiency Syndrome Associated with Kaposi's Sarcoma with Marked Facial Edema

    57　(4)　409-413　2015/04

    Publisher: 金原出版

    ISSN： 0018-1404

  73. 好酸球性多発血管炎性肉芽腫症の1例

    河合 徹, 玉城 善史郎, 岡 知徳, 宮垣 朝光, 浅野 善英

    日本皮膚科学会雑誌　125　(3)　463-463　2015/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  74. 強皮症・皮膚線維化疾患の診断基準・重症度分類・診療ガイドライン作成事業 全身性強皮症の腎障害の重症度分類と診療ガイドライン

    川口鎮司, 浅野善英, 桑名正隆, 後藤大輔, 神人正寿, 竹原和彦, 波多野将, 藤本学, 佐藤伸一, 高木香恵, 栃本明子, 樋口智昭, 尹浩信

    強皮症・皮膚線維化疾患の診断基準・重症度分類・診療ガイドライン作成事業 平成26年度 総括・分担研究報告書　2015

  75. 抗体医薬の現況と展望 (第113回日本皮膚科学会総会 皮膚科の職人魂) -- (膠原病update)

    浅野 善英

    日本皮膚科学会雑誌 = The Japanese journal of dermatology　124　(13)　2615-2617　2014/12

    Publisher: 日本皮膚科学会

    ISSN： 0021-499X

  76. A new animal model of systemic sclerosis

    251　(8)　595-598　2014/11/22

    Publisher: 医歯薬出版

    ISSN： 0039-2359

  77. Am80 Ameliorates Bleomycin-Induced Dermal Fibrosis By Suppressing the Pro-Fibrotic Phenotype of Fibroblasts, Endothelial Cells, and Immune Cells.

    Tetsuo Toyama, Yoshihide Asano, Takehiro Takahashi, Ryosuke Saigusa, Yohei Ichimura, Takashi Taniguchi, Shinji Noda, Kaname Akamata, Shinichi Sato, Takafumi Kadono, Koichi Shudo

    ARTHRITIS & RHEUMATOLOGY　66　S1313-S1313　2014/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  78. Loss of IRF5 Ameliorates Tissue Fibrosis in a Murine Model of Systemic Sclerosis

    Ryosuke Saigusa, Yoshihide Asano, Takashi Taniguchi, Yohei Ichimura, Takehiro Takahashi, Tetsuo Toyama, Ayumi Yoshizaki, Tadatsugu Taniguchi, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　66　S758-S759　2014/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  79. Progranulin Overproduction Due to Fli1 Deficiency Contributes to the Resistance of Dermal Fibroblasts to Tumor Necrosis Factor a in Systemic Sclerosis.

    Yohei Ichimura, Yoshihide Asano, Kaname Akamata, Shinji Noda, Takashi Taniguchi, Takehiro Takahashi, Tetsuo Toyama, Yayoi Tada, Makoto Sugaya, Shinichi Sato, Takafumi Kadono

    ARTHRITIS & RHEUMATOLOGY　66　S329-S329　2014/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  80. Increased Expression of Chemerin in Endothelial Cells Due to Fli1 Deficiency May Contribute to the Development of Digital Ulcers in Systemic Sclerosis.

    Kaname Akamata, Yoshihide Asano, Takashi Taniguchi, Haya. Kazu Stnnida, Naoltiko Aozasa, Shinji Noda, Tetsuo Toyama, Takehiro Takahashi, Yohei Ichimura, Ayutni Yoshizaki, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　66　S328-S329　2014/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  81. Potential Roles of Toll-like Receptor 4 in the Murine Models of Systemic Sclerosis.

    Takehiro Takahashi, Yoshihide Asano, Yohei Ichimura, Tetsuo Toyama, Takashi Taniguchi, Shinji Noda, Kaname Akamata, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　66　S330-S331　2014/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  82. Nucleosome, a Basic Repeating Unit of Chromatin, in Patients with Systemic Sclerosis: Possible Association with Immunological Abnormalities Via Abnormal Activation of T and B Cells.

    Ayurni Yoshizaki, Yoshihide Asano, Takashi Taniguchi, Ryosuke Saigusa, Kotiki Nakamura, Takashi Yamashita, Takehiro Takahashi, Tetsuo Toyama, Yohei Ichimura, Zenshiro Tamaki, Miki Miyazaki, Shinichi Sato

    ARTHRITIS & RHEUMATOLOGY　66　S332-S332　2014/10

    ISSN： 2326-5191

    eISSN： 2326-5205

  83. 胸腺癌を合併した皮膚筋炎の1例

    三枝 良輔, 住田 隼一, 藤田 英樹, 浅野 善英, 菅谷 誠, 佐藤 伸一, 肥田 あゆみ, 清水 潤, 安樂 真樹

    日本皮膚科学会雑誌　124　(9)　1767-1767　2014/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  84. CASE REPORTS : Acquired Reactive Perforating Collagenosis Successfully Treated with Allopurinol

    56　(7)　1031-1034　2014/07

    Publisher: 金原出版

    ISSN： 0018-1404

  85. 経過中に多発性筋炎を発症した限局性強皮症

    高橋 岳浩, 浅野 善英, 平川 麻衣子, 中村 洸樹, 三枝 良輔, 青笹 尚彦, 住田 隼一, 宮垣 朝光, 藤田 英樹, 佐藤 伸一

    西日本皮膚科　76　(3)　281-281　2014/06

    Publisher: 日本皮膚科学会-西部支部

    ISSN： 0386-9784

  86. Skin barrier dysfunction and relatively low antimicrobial peptide expression in cutaneous T-cell lymphoma

    H. Suga, M. Sugaya, T. Miyagaki, H. Ohmatsu, M. Kawaguchi, N. Takahashi, H. Fujita, Y. Asano, Y. Tada, T. Kadono, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　134　S62-S62　2014/05

    ISSN： 0022-202X

    eISSN： 1523-1747

  87. Periostin contributes to a Th2-dominant environment of cutaneous T-cell lymphoma via thymic stromal lymphopoietin expression

    N. Takahashi, M. Sugaya, H. Suga, T. Miyagaki, H. Ohmatsu, M. Kawaguchi, H. Fujita, Y. Asano, Y. Tada, T. Kadono, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　134　S6-S6　2014/05

    ISSN： 0022-202X

    eISSN： 1523-1747

  88. 【膠原病】乳癌を合併した抗155/140kDa蛋白抗体陽性の皮膚筋炎

    長田 麻友美, 高橋 岳浩, 市村 洋平, 上嶋 祐太, 宮垣 朝光, 鑑 慎司, 三井 浩, 浅野 善英, 多田 敬一郎, 濱口 儒人, 藤本 学, 佐藤 伸一

    皮膚科の臨床　56　(2)　167-170　2014/02

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  89. 尋常性乾癬患者に対する活性型ビタミンD3外用薬ローテーション療法におけるカルシポトリオール軟膏とマキサカルシトール軟膏の比較検討

    藤田 英樹, 三井 彩, 上嶋 祐太, 鎌田 昌洋, 柴田 彩, 山本 瑞穂, 三井 浩, 荒木 麻由子, 竹腰 知紀, 浅野 善英, 多田 弥生, 佐藤 伸一

    臨牀と研究　91　(2)　299-303　2014/02

    Publisher: 大道学館出版部

    ISSN： 0021-4965

  90. 強皮症 : 線維化から考える (第112回日本皮膚科学会総会 いま望まれる皮膚科心療) -- (教育講演 全身性強皮症,シェーグレン症候群 : 最近の動向)

    浅野 善英

    日本皮膚科学会雑誌 = The Japanese journal of dermatology　123　(13)　2579-2581　2013/12

    Publisher: 日本皮膚科学会

    ISSN： 0021-499X

  91. 膠原病・血管炎に伴う皮膚潰瘍診療ガイドラインについて (第112回日本皮膚科学会総会 いま望まれる皮膚科心療) -- (教育講演 創傷・熱傷ガイドライン : 第1版の課題と改訂に向けた取り組み)

    小川 文秀, 浅野 善英, 石井 貴之

    日本皮膚科学会雑誌 = The Japanese journal of dermatology　123　(13)　2888-2891　2013/12

    Publisher: 日本皮膚科学会

    ISSN： 0021-499X

  92. 一過性の経過をたどり、免疫抑制療法を中止し得た抗CADM-140/MDA5抗体陽性皮膚筋炎

    谷口 隆志, 浅野 善英, 小暮 麻子, 竹腰 知紀, 菅谷 誠, 佐藤 伸一

    Journal of Environmental Dermatology and Cutaneous Allergology　7　(5)　473-473　2013/11

    Publisher: (一社)日本皮膚アレルギー・接触皮膚炎学会

    ISSN： 1882-0123

  93. Fli1 Haploinsufficiency Exacerbates Dermal Fibrosis Via Activation Of Fibroblasts, Endothelial Cells and Macrophages In Bleomycin-Treated Mice

    Takashi Taniguchi, Yoshihide Asano, Kaname Akamata, Shinji Noda, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Maria Trojanowska, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　65　S1156-S1156　2013/10

    ISSN： 0004-3591

    eISSN： 1529-0131

  94. Downregulation Of KLF5 and Fli1 Cooperatively Contribute To Distinct Manifestations Of Systemic Sclerosis In Vitro and In Vivo

    Shinji Noda, Yoshihide Asano, Katsuhito Fujiu, Ichiro Manabe, Ryozo Nagai, Kaname Akamata, Takashi Taniguchi, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Daisuke Tsuruta, Maria Trojanowska, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　65　S1156-S1157　2013/10

    ISSN： 0004-3591

    eISSN： 1529-0131

  95. Clinical Significance Of Endothelial Vasodilator Function Evaluated By Endopat In Patients With Systemic Sclerosis

    Naohiko Aozasa, Yoshihide Asano, Masaru Hatano, Ryosuke Saigusa, Kouta Takakuwa, Takehiro Takahashi, Tetsuo Toyama, Hayakazu Sumida, Atsushi Yao, Koichiro Kinugawa, Hisataka Maki, Toshiro Inaba, Hironori Muraoka, Shun Minatsuki, Issei Komuro, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　65　S1106-S1106　2013/10

    ISSN： 0004-3591

    eISSN： 1529-0131

  96. Primary Cutaneous Cryptococcosis

    55　(8)　966-969　2013/08

    Publisher: 金原出版

    ISSN： 0018-1404

  97. 臨牀研究 全身性強皮症に伴う肺高血圧症およびレイノー現象に対するベラプロストナトリウム徐放錠の有用性の検討

    浅野 善英, 玉城 善史郎, 住田 隼一

    臨牀と研究　90　(5)　698-702　2013/05

    Publisher: 大道学館出版部

    ISSN： 0021-4965

  98. Adiponectin deficiency exacerbates psoriasiform skin inflammation by promoting IL-17 production from gamma delta T cells

    S. Shibata, Y. Tada, Y. Asano, M. Sugaya, T. Kadono, T. Yamauchi, N. Kubota, T. Kadowaki, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　133　S34-S34　2013/05

    ISSN： 0022-202X

  99. The role of transcription factors in the pathogenesis of systemic sclerosis

    243　(10)　879-882　2012/12/08

    Publisher: 医歯薬出版

    ISSN： 0039-2359

  100. 膠原病および類縁疾患における自己抗体の検査法と読み方 (第111回 日本皮膚科学会総会 : 進化する皮膚科 : 知と技を磨く) -- (教育講演 皮膚診断学 : 知っておくべき検査法とその考え方)

    浅野 善英

    日本皮膚科学会雑誌 = The Japanese journal of dermatology　122　(13)　3399-3401　2012/12

    Publisher: 日本皮膚科学会

    ISSN： 0021-499X

  101. 膠原病・血管炎 (第111回 日本皮膚科学会総会 : 進化する皮膚科 : 知と技を磨く) -- (教育講演 創傷・熱傷ガイドライン : その完成と今後の課題)

    石井 貴之, 藤本 学, 浅野 善英

    日本皮膚科学会雑誌 = The Japanese journal of dermatology　122　(13)　3631-3633　2012/12

    Publisher: 日本皮膚科学会

    ISSN： 0021-499X

  102. 強皮症の血管障害 (第111回 日本皮膚科学会総会 : 進化する皮膚科 : 知と技を磨く) -- (教育講演 進化する皮膚科学 : 研究の進展)

    浅野 善英

    日本皮膚科学会雑誌 = The Japanese journal of dermatology　122　(13)　3261-3264　2012/12

    Publisher: 日本皮膚科学会

    ISSN： 0021-499X

  103. 乳癌を合併した抗p155/140抗体陽性の皮膚筋炎

    長田 麻友美, 高橋 岳浩, 市村 洋平, 上嶋 祐太, 宮垣 朝光, 鑑 慎司, 三井 浩, 浅野 善英

    日本皮膚科学会雑誌　122　(11)　2697-2697　2012/10

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  104. Clinical Correlation of Flow-Mediated Endothelium-Dependent Vasodilatation in Systemic Sclerosis.

    Takehiro Takahashi, Yoshihide Asano, Eisuke Amiya, Masaru Hatano, Atsuko Ozeki, Aya Watanabe, Shuichi Kawarasaki, Tomoko Nakao, Zenshiro Tamaki, Takashi Taniguchi, Yohei Ichimura, Tetsuo Toyama, Masafumi Watanabe, Yasunobu Hirata, Ryozo Nagai, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　64　(10)　S300-S300　2012/10

    ISSN： 0004-3591

  105. Possible Contribution of Decreased Cathepsin V Expression to the Development of Dermal Fibrosis, Proliferative Vasculopathy, and Altered Keratinocyte Phenotype in Systemic Sclerosis.

    Yoshihide Asano, Shinji Noda, Takehiro Takahashi, Sayaka Shibata, Kaname Akamata, Naohiko Aozasa, Takashi Taniguchi, Yohei Ichimura, Tetsuo Toyama, Hayakazu Sumida, Yoshihiro Kuwano, Koichi Yanaba, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　64　(10)　S651-S651　2012/10

    ISSN： 0004-3591

  106. Histological Features of Localized Scleroderma'en Coup De Sabre': A Study of 16 Cases

    Takashi Taniguchi, Yoshihide Asano, Zenshiro Tamaki, Kaname Akamata, Naohiko Aozasa, Shinji Noda, Takehiro Takahashi, Yohei Ichimura, Tetsuo Toyama, Miki Sugita, Hayakazu Sumida, Yoshihiro Kuwano, Miki Miyazaki, Koichi Yanaba, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　64　(10)　S303-S304　2012/10

    ISSN： 0004-3591

  107. A Possible Contribution of Visfatin to the Resolution of Skin Sclerosis in Patients with Diffuse Cutaneous Systemic Sclerosis Via a Direct Anti-Fibrotic Effect On Dermal Fibroblasts and Th1 Polarization of the Immune Response

    Tetsuo Toyama, Yoshihide Asano, Yuri Masui, Sayaka Shibata, Kaname Akamata, Shinji Noda, Naohiko Aozasa, Takashi Tanigu-Chi, Takehiro Takahashi, Yohei Ichimura, Hayakazu Sumida, Koichi Yanaba, Takafumi Kadono, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　64　(10)　S644-S645　2012/10

    ISSN： 0004-3591

  108. 【乾癬】 アダリムマブの中断後、再開時に効果減弱をみるも増量にて回復した関節症性乾癬の1例

    山本 瑞穂, 多田 弥生, 谷口 隆志, 小暮 麻子, 唐川 大, 竹腰 知紀, 浅野 善英, 菅谷 誠, 佐藤 伸一

    皮膚科の臨床　54　(10)　1325-1328　2012/10

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  109. NMO/筋炎 抗MDA5(CADM-140)抗体陽性筋炎3例の筋病理像の検討

    肥田 あゆみ, 清水 潤, 辻 省次, 浅野 善英, 前田 明子

    日本神経免疫学会学術集会抄録集　24回　77-77　2012/09

    Publisher: 日本神経免疫学会

  110. Arthus reaction and chemokine

    58　(3)　322-326　2012/09

    Publisher: 科学評論社

    ISSN： 1881-1930

  111. beta 7 integrin deficiency attenuates immune complex-mediated tissue injury

    D. Yamada, T. Kadono, Y. Masui, Y. Asano, Y. Tada, M. Sugaya, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　132　S24-S24　2012/09

    ISSN： 0022-202X

  112. Interleukin-10-producing regulatory B cells (B10 cells) ameliorate psoriasis in mice

    K. Yanaba, Y. Asano, Y. Tada, M. Sugaya, T. Kadono, T. F. Tedder, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　132　S15-S15　2012/09

    ISSN： 0022-202X

  113. Mechanism of delayed wound healing in endothelial cell-specific Fli1 knockout mice

    Yoshihide Asano, Shinichi Sato

    JOURNAL OF DERMATOLOGY　39　142-142　2012/06

    ISSN： 0385-2407

  114. 筋層内転移により広範な皮下出血を生じた頭部血管肉腫の1例

    高橋 岳浩, 門野 岳史, 中川 誠太郎, 平林 恵, 管 析, 山本 瑞穂, 山田 大資, 増井 友里, 浅野 善英, 三井 浩, 菅谷 誠, 佐藤 伸一, 住友 賢哉, 高澤 豊, 深山 正久

    日本皮膚科学会雑誌　122　(7)　1809-1810　2012/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  115. IL-22, but not IL-17, dominant environment in cutaneous T-cell lymphoma

    T. Miyagaki, M. Sugaya, H. Suga, M. Kamata, H. Ohmatsu, H. Fujita, Y. Asano, Y. Tada, T. Kadono, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　132　S97-S97　2012/05

    ISSN： 0022-202X

  116. 日本皮膚科学会ガイドライン 全身性強皮症診療ガイドライン

    佐藤 伸一, 藤本 学, 桑名 正隆, 川口 鎮司, 後藤 大輔, 遠藤 平仁, 尹 浩信, 小川 文秀, 浅野 善英, 石川 治, 高橋 裕樹, 山本 俊幸, 竹原 和彦, 全身性強皮症診療ガイドライン作成委員会

    日本皮膚科学会雑誌　122　(5)　1293-1345　2012/04

    Publisher: (公社)日本皮膚科学会

    DOI： 10.14924/dermatol.122.1293 　

    ISSN： 0021-499X

    eISSN： 1346-8146

  117. 皮膚筋炎が疑われ、経過中多彩な臨床像を呈した1例

    住田 隼一, 浅野 善英, 柴田 彩, 上嶋 祐太, 磯村 清子, 高橋 岳浩, 樽見 さおり, 鑑 慎司, 菅谷 誠, 佐藤 伸一

    日本皮膚科学会雑誌　122　(4)　1212-1212　2012/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  118. UVA1照射によって皮膚硬化の改善がみられた斑状強皮症の1例

    古橋 卓也, 加藤 裕史, 齋藤 稚代, 森田 明理, 浅野 善英, 佐藤 伸一

    日本皮膚科学会雑誌　122　(3)　740-740　2012/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  119. ボセンタンが著効した汎発性強皮症に伴う難治性皮膚潰瘍

    谷口 隆志, 小暮 麻子, 冨田 学, 菅谷 誠, 浅野 善英, 波多野 将

    日本皮膚科学会雑誌　122　(3)　711-711　2012/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  120. ウェルナー症候群に伴う難治性下腿潰瘍に対するボセンタンの使用経験

    野田 真史, 宮川 卓也, 杉田 美樹, 山本 瑞穂, 小暮 麻子, 玉城 善史郎, 菅谷 誠, 浅野 善英, 三井 浩, 帆足 俊彦

    日本皮膚科学会雑誌　122　(3)　723-723　2012/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  121. Systemic Sclerosis

    140　(11)　2315-2318　2012/02

    Publisher: 日本医師会

    ISSN： 0021-4493

  122. 嗄声の改善が見られた皮膚筋炎の1例

    市村 洋平, 玉城 善史郎, 小暮 麻子, 竹腰 知紀, 宮垣 朝光, 菅谷 誠, 浅野 善英

    日本皮膚科学会雑誌　122　(2)　454-454　2012/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  123. 創傷・熱傷ガイドライン委員会報告-3：糖尿病性潰瘍・壊疽ガイドライン

    為政大幾, 安部正敏, 中西健史, 松尾光馬, 山﨑 修, 浅野善英, 石井貴之, 伊藤孝明, 井上雄二, 今福信一, 入澤亮吉, 大塚正樹, 大塚幹夫, 小川文秀, 門野岳史, 小寺雅也, 川上民裕, 川口雅一, 久木野竜一, 幸野 健, 境 恵祐, 高原正和, 谷岡未樹, 中村泰大, 橋本 彰, 長谷川稔, 林 昌浩, 藤本 学, 藤原 浩, 前川武雄, 間所直樹, 吉野雄一郎, レパブー・アンドレ, 立花隆夫, 尹 浩信

    日皮会誌　122　281-319　2012

    DOI： 10.14924/dermatol.122.281 　

  124. Sweet病様症状を伴って発症したBehcet病の1例

    記村 貴之, 山本 瑞穂, 浅野 善英, 菅谷 誠, 菊池 かな子, 玉置 邦彦

    日本皮膚科学会雑誌　122　(1)　123-123　2012/01

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  125. 甲状腺乳頭癌を合併した皮膚筋炎の1例

    平林 恵, 玉城 善史郎, 帆足 俊彦, 山本 瑞穂, 浅野 善英, 菅谷 誠, 菊池 かな子, 佐藤 伸一, 多田 久里守, 金子 俊之, 高崎 芳成

    日本皮膚科学会雑誌　122　(1)　151-151　2012/01

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  126. 乳頭部に生じた基底細胞癌の1例

    青笹 尚彦, 岡田 麻子, 門野 岳史, 山本 瑞穂, 浅野 善英, 常深 祐一郎, 菅谷 誠, 玉置 邦彦, 佐藤 伸一

    日本皮膚科学会雑誌　122　(1)　153-153　2012/01

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  127. ベゲタミンによるdrug-induced hypersensitivity syndrome

    記村 貴之, 浅野 善英, 山本 瑞穂, 中島 広子, 菅谷 誠, 菊池 かな子, 玉置 邦彦

    日本皮膚科学会雑誌　122　(1)　164-164　2012/01

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  128. 第13因子補充療法が消化管症状に著効したアナフィラクトイド紫斑

    宮川 卓也, 張本 明子, 管 析, 岡田 麻子, 蘆田 龍一, 大松 華子, 菅谷 誠, 浅野 善英

    日本皮膚科学会雑誌　122　(1)　164-165　2012/01

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  129. 自己抗体の読み方

    浅野 善英

    日本皮膚科学会雑誌　121　(13)　2927-2929　2011/12/15

    Publisher: 日本皮膚科学会

    ISSN： 0021-499X

  130. 膠原病・血管炎にともなう皮膚潰瘍

    藤本 学, 浅野 善英, 石井 貴之, 小川 文秀, 川上 民裕, 小寺 雅也

    日本皮膚科学会雑誌　121　(13)　2878-2879　2011/12/15

    ISSN： 0021-499X

  131. 全身性強皮症の診療ガイドライン

    浅野 善英

    日本皮膚科学会雑誌　121　(13)　3117-3119　2011/12/15

    Publisher: 日本皮膚科学会

    ISSN： 0021-499X

  132. 全身に結節型皮膚サルコイドが多発したサルコイドーシスの1例

    宮垣 朝光, 佐伯 秀久, 柴田 彩, 大野 祐樹, 常深 祐一郎, 浅野 善英, 小宮根 真弓, 菊池 かな子, 玉置 邦彦

    日本皮膚科学会雑誌　121　(14)　3425-3425　2011/12

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  133. 日本皮膚科学会ガイドライン 創傷・熱傷ガイドライン委員会報告 熱傷診療ガイドライン

    吉野 雄一郎, 大塚 幹夫, 川口 雅一, 境 恵祐, 橋本 彰, 林 昌浩, 間所 直樹, 浅野 善英, 安部 正敏, 石井 貴之, 爲政 大幾, 伊藤 孝明, 井上 雄二, 今福 信一, 入澤 亮吉, 大塚 正樹, 小川 文秀, 門野 岳史, 川上 民裕, 久木野 竜一, 幸野 健, 小寺 雅也, 高原 正和, 谷岡 未樹, 中西 健史, 中村 泰大, 長谷川 稔, 藤本 学, 藤原 浩, 前川 武雄, 松尾 光馬, 山崎 修, レパヴー・アンドレ, 立花 隆夫, 尹 浩信, 創傷, 熱傷ガイドライン委員会

    日本皮膚科学会雑誌　121　(14)　3279-3306　2011/12

    Publisher: (公社)日本皮膚科学会

    DOI： 10.14924/dermatol.121.3279 　

    ISSN： 0021-499X

    eISSN： 1346-8146

  134. The Role of Adiponectin in the Pathogenesis of Dermal Fibrosis in Systemic Sclerosis

    Yoshihide Asano, Yuri Masui, Takafumi Kadono, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　63　(10)　S906-S906　2011/10

    ISSN： 0004-3591

  135. Bosentan Reverses the Profibrotic Phenotype of Systemic Sclerosis Dermal Fibroblasts Through Increasing the DNA Binding Ability of Transcription Factor Fli1

    Kaname Akamata, Yoshihide Asano, Shinichi Sato

    ARTHRITIS AND RHEUMATISM　63　(10)　S579-S579　2011/10

    ISSN： 0004-3591

  136. 日本皮膚科学会ガイドライン 創傷・熱傷ガイドライン委員会報告 膠原病・血管炎にともなう皮膚潰瘍診療ガイドライン

    藤本 学, 浅野 善英, 石井 貴之, 小川 文秀, 川上 民裕, 小寺 雅也, 安部 正敏, 爲政 大幾, 伊藤 孝明, 井上 雄二, 今福 信一, 入澤 亮吉, 大塚 正樹, 大塚 幹夫, 門野 岳史, 川口 雅一, 久木野 竜一, 幸野 健, 境 恵祐, 高原 正和, 谷岡 未樹, 中西 健史, 中村 泰大, 橋本 彰, 長谷川 稔, 林 昌浩, 藤原 浩, 前川 武雄, 松尾 光馬, 間所 直樹, 山崎 修, 吉野 雄一郎, レパヴー・アンドレ, 立花 隆夫, 尹 浩信, 創傷, 熱傷ガイドライン委員会

    日本皮膚科学会雑誌　121　(11)　2187-2223　2011/10

    Publisher: (公社)日本皮膚科学会

    DOI： 10.14924/dermatol.121.2187 　

    ISSN： 0021-499X

    eISSN： 1346-8146

  137. Sarcoid-like skin granulomatosis induced by Propionibacterium acnes in mice; role of cell adhesion molecules in the formation of granuloma

    Masahiro Kamata, Yayoi Tada, Yoshihide Asano, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　131　S30-S30　2011/09

    ISSN： 0022-202X

  138. Monosodium urate crystals induce functional expression of P2Y(14) receptor coupling to IL-8/CXCL8 production in human keratinocytes

    Hideya Uratsuji, Yayoi Tada, Masahiro Kamata, Tomohiko Kawashima, Carren Hau, Yoshihide Asano, Makoto Sugaya, Takafumi Kadono, Shinichi Sato, Kunihiko Tamaki

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　131　S56-S56　2011/09

    ISSN： 0022-202X

  139. Decreased cathepsin V levels in the sera and skin of patients with systemic sclerosis

    Shinji Noda, Yoshihide Asano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　131　S29-S29　2011/09

    ISSN： 0022-202X

  140. 日本皮膚科学会ガイドライン 創傷・熱傷ガイドライン委員会報告 糖尿病性潰瘍・壊疽ガイドライン

    爲政 大幾, 安部 正敏, 中西 健史, 松尾 光馬, 山崎 修, 浅野 善英, 石井 貴之, 伊藤 孝明, 井上 雄二, 今福 信一, 入澤 亮吉, 大塚 正樹, 大塚 幹夫, 小川 文秀, 門野 岳史, 小寺 雅也, 川上 民裕, 川口 雅一, 久木野 竜一, 幸野 健, 境 恵祐, 高原 正和, 谷岡 未樹, 中村 泰大, 橋本 彰, 長谷川 稔, 林 昌浩, 藤本 学, 藤原 浩, 前川 武雄, 間所 直樹, 吉野 雄一郎, レパヴー・アンドレ, 立花 隆夫, 尹 浩信, 創傷, 熱傷ガイドライン委員会

    日本皮膚科学会雑誌　121　(10)　1997-2035　2011/09

    Publisher: (公社)日本皮膚科学会

    DOI： 10.14924/dermatol.121.1997 　

    ISSN： 0021-499X

    eISSN： 1346-8146

  141. 高カルシウム、ATP、poly(I:C)はヒトケラチノサイトにおける免疫応答を増強する(High calcium, ATP and poly(I:C) augment the immune response to β-glucan in human keratinocytes)

    ハウ・カレン, 多田 弥生, 柴田 彩, 浦辻 秀弥, 浅野 善英, 菅谷 誠, 門野 岳史, 神田 奈緒子, 渡辺 晋一, 玉置 邦彦, 佐藤 伸一

    Medical Mycology Journal　52　(Suppl.1)　100-100　2011/09

    Publisher: (一社)日本医真菌学会

    ISSN： 2185-6486

    eISSN： 2186-165X

  142. 日本皮膚科学会ガイドライン 創傷・熱傷ガイドライン委員会報告 褥瘡診療ガイドライン

    立花 隆夫, 今福 信一, 入澤 亮吉, 大塚 正樹, 門野 岳史, 藤原 浩, 浅野 善英, 安部 正敏, 石井 貴之, 爲政 大幾, 伊藤 孝明, 井上 雄二, 大塚 幹夫, 小川 文秀, 小寺 雅也, 川上 民裕, 川口 雅一, 久木野 竜一, 幸野 健, 境 恵祐, 高原 正和, 谷岡 未樹, 中西 健史, 中村 泰大, 橋本 彰, 長谷川 稔, 林 昌浩, 藤本 学, 前川 武雄, 松尾 光馬, 間所 直樹, 山崎 修, 吉野 雄一郎, レパヴー・アンドレ, 尹 浩信, 創傷, 熱傷ガイドライン委員会

    日本皮膚科学会雑誌　121　(9)　1791-1839　2011/08

    Publisher: (公社)日本皮膚科学会

    DOI： 10.14924/dermatol.121.1791 　

    ISSN： 0021-499X

    eISSN： 1346-8146

  143. Rapamycinが強皮症皮膚線維芽細胞に対して抗線維化作用を示すメカニズム

    浅野 善英, 玉城 善史郎, 久保 正英, 尹 浩信, 佐藤 伸一

    日本臨床免疫学会会誌　34　(4)　289-289　2011/08

    Publisher: 日本臨床免疫学会

    DOI： 10.14906/jscisho.39.0.101.0 　

    ISSN： 0911-4300

    eISSN： 1349-7413

  144. 全身性強皮症の病態におけるアディポネクチンの役割

    増井 友里, 浅野 善英, 柴田 彩, 野田 真史, 青笹 尚彦, 赤股 要, 山田 大資, 玉城 善史郎, 多田 弥生, 菅谷 誠, 門野 岳史, 佐藤 伸一

    日本臨床免疫学会会誌　34　(4)　290-290　2011/08

    Publisher: 日本臨床免疫学会

    DOI： 10.14906/jscisho.39.0.103.0 　

    ISSN： 0911-4300

  145. CXCL10、CXCR3ノックアウトマウスにおける逆アルサス反応

    野田 真史, 浅野 善英, 多田 弥生, 菅谷 誠, 門野 岳史, 佐藤 伸一

    日本臨床免疫学会会誌　34　(4)　294-294　2011/08

    Publisher: 日本臨床免疫学会

    DOI： 10.14906/jscisho.39.0.111.0 　

    ISSN： 0911-4300

  146. 膠原病とアレルギー

    尹 浩信, 浅野 善英

    皮膚アレルギーフロンティア　9　(2)　116-123　2011/07

    Publisher: (株)メディカルレビュー社

    ISSN： 1348-7280

  147. CXCL10、CXCR3ノックアウトマウスにおける逆アルサス反応

    野田 真史, 浅野 善英, 多田 弥生, 菅谷 誠, 門野 岳史, 佐藤 伸一

    Journal of Environmental Dermatology and Cutaneous Allergology　5　(3)　285-285　2011/07

    Publisher: (一社)日本皮膚アレルギー・接触皮膚炎学会

    ISSN： 1882-0123

  148. A case of taxane-induced scleroderma: a different expression profile of Fli1 proteins in dermal fibroblasts and microvascular endothelial cells compared with systemic sclerosis

    T. Takahashi, Y. Asano, Y. Ichimura, T. Taniguchi, A. Kogure, Z. Tamaki, T. Takekoshi, M. Sugaya, S. Sato

    BRITISH JOURNAL OF DERMATOLOGY　164　(6)　1393-1395　2011/06

    DOI： 10.1111/j.1365-2133.2011.10243.x 　

    ISSN： 0007-0963

  149. 光ケブネル現象を伴った多中心性細網組織球症

    谷口 隆志, 浅野 善英, 小暮 麻子, 菅谷 誠, 佐藤 伸一

    西日本皮膚科　73　(3)　334-334　2011/06

    Publisher: 日本皮膚科学会-西部支部

    ISSN： 0386-9784

  150. ステロイド、タクロリムス内服中の関節リウマチ患者に生じたHIV陰性カポジ肉腫の1例

    谷口 隆志, 浅野 善英, 川口 真喜子, 三井 浩, 菅谷 誠, 佐藤 伸一

    日本皮膚科学会雑誌　121　(6)　1117-1117　2011/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  151. パクリタキセル投与後に発症した強皮症様皮膚硬化

    高橋 岳浩, 玉城 善史郎, 竹腰 知紀, 浅野 善英, 菅谷 誠, 佐藤 伸一, 小暮 麻子

    日本皮膚科学会雑誌　121　(6)　1123-1123　2011/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  152. 胃癌を合併した皮膚筋炎の1例

    管 析, 玉城 善史郎, 山本 瑞穂, 帆足 俊彦, 浅野 善英, 菅谷 誠, 佐藤 伸一, 永瀬 将史, 布部 創也, 瀬戸 泰之

    日本皮膚科学会雑誌　121　(6)　1123-1124　2011/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  153. Unusual skin involvement in eosinophilic fasciitis

    S. Noda, Y. Asano, Z. Tamaki, T. Takekoshi, Y. Ichimura, T. Takahashi, K. Sonoda, M. Sugaya, S. Sato

    Clinical and Experimental Dermatology　36　(3)　310-311　2011/04

    DOI： 10.1111/j.1365-2230.2010.03942.x 　

    ISSN： 0307-6938 1365-2230

  154. Urticarial vasculitis presenting as erythema gyratum repens-like eruption

    S. Noda, T. Takekoshi, Z. Tamaki, Y. Asano, M. Sugaya, S. Sato

    Journal of the European Academy of Dermatology and Venereology　25　(4)　493-495　2011/04

    DOI： 10.1111/j.1468-3083.2010.03747.x 　

    ISSN： 0926-9959 1468-3083

  155. Involvement of the CXCL10/CXCR3 axis in the mechanism responsible for cutaneous reverse passive Arthus reaction

    S. Noda, Y. Asano, Y. Tada, M. Sugaya, T. Kadono, S. Sato

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　131　S2-S2　2011/04

    ISSN： 0022-202X

  156. 強皮症の皮膚病変 (内科医がおさえておくべき皮膚科の基本) -- (膠原病の皮疹のみかた)

    浅野 善英

    診断と治療　99　146-154　2011/03

    Publisher: 診断と治療社

    ISSN： 0370-999X

  157. 増殖性天疱瘡の1例

    宮川 卓也, 浅野 善英, 平林 恵, 山本 瑞穂, 小暮 麻子, 鎌田 昌洋, 帆足 俊彦, 菅谷 誠, 佐藤 伸一

    日本皮膚科学会雑誌　121　(3)　587-587　2011/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  158. サルコイドーシスを合併した全身性強皮症の1例

    管 析, 玉城 善史郎, 山本 瑞穂, 浅野 善英, 菅谷 誠, 佐藤 伸一, 清水 潤

    日本皮膚科学会雑誌　121　(3)　590-590　2011/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  159. 結節性痒疹と鑑別を要したperipheral T cell lymphoma,not otherwise specifiedの1例

    谷口 隆志, 菅谷 誠, 益田 将, 宮垣 朝光, 小暮 麻子, 竹腰 知紀, 鑑 慎司, 浅野 善英, 三井 浩, 佐藤 伸一

    日本皮膚科学会雑誌　121　(3)　612-612　2011/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  160. Rapamycinが強皮症皮膚線維芽細胞に対して抗線維化作用を示すメカニズム

    浅野 善英, 玉城 善史郎, 久保 正英, 尹 浩信, 佐藤 伸一

    日本臨床免疫学会総会抄録集　39　(0)　101-101　2011

    Publisher: 日本臨床免疫学会

    DOI： 10.14906/jscisho.39.0.101.0 　

    More details Close

    全身性強皮症は皮膚および内臓諸臓器の線維化と血管障害を特徴とする全身性の自己免疫疾患である。その原因はいまだ不明であるが、恒常的に活性化された線維芽細胞によって細胞外基質が過剰に産生され、かつ分解が抑制されることにより、線維化が生じると考えられている。rapamycinはcalcineulin inhibitorの一つであるが、ブレオマイシンによる強皮症モデルマウスにおいて強力な抗線維化作用を示し、また全身性強皮症患者の皮膚硬化を改善させる作用がある可能性も報告されている。今回われわれは、正常および強皮症皮膚線維芽細胞においてalpha2(I) collagen (COL1A2)遺伝子とmatrix metalloproteinase 1 (MMP1)遺伝子に注目し、rapamycinが抗線維化作用を示す機序について検討を行った。rapamycinは、強皮症皮膚線維芽細胞においてCOL1A2遺伝子のmRNAの発現を著明に抑制し、一方でMMP1遺伝子の発現を著明に亢進させた。rapamycinはCOL1A2遺伝子のmRNAの発現を転写後レベルで抑制し、一方でMMP1遺伝子のmRNAの発現を転写レベルでc-Jun/JNK pathway依存性に亢進させた。また、rapamycinは正常皮膚線維芽細胞と比較して、強皮症皮膚線維芽細胞においてより強力にこれらの作用を示した。以上の結果から、rapamycinはI型コラーゲンの産生を抑制すると同時に分解を亢進させることにより、強力な抗線維化作用を示すことが明らかとなった。

  161. 創傷・熱傷ガイドライン委員会報告-5：下腿潰瘍・下肢静脈瘤診療ガイドライン

    伊藤孝明, 九木野竜一, 高原正和, 谷岡未樹, 中村泰大, 浅野善英, 安部正敏, 石井貴之, 為政大幾, 井上雄二, 今福信一, 入澤亮吉, 大塚正樹, 大塚幹夫, 小川文秀, 門野岳史, 川上民裕, 川口雅一, 幸野 健, 小寺雅也, 境 恵祐, 中西健史, 橋本 彰, 長谷川稔, 林 昌浩, 藤本 学, 藤原 浩, 前川武雄, 松尾光馬, 間所直樹, 山﨑 修, 吉野雄一郎, レパブー・アンドレ, 立花隆夫, 尹 浩信

    日皮会誌　121　2431-2448　2011

    DOI： 10.14924/dermatol.121.2431 　

  162. 創傷・熱傷ガイドライン委員会報告-1：創傷一般。

    井上雄二, 長谷川稔, 前川武雄, レパブー・アンドレ, 浅野善英, 安部正敏, 石井貴之, 伊藤孝明, 為政大幾, 今福信一, 入澤亮吉, 大塚正樹, 大塚幹夫, 小川文秀, 門野岳史, 小寺雅也, 川上民裕, 川口雅一, 九木野竜一, 幸野 健, 境 恵祐, 高原正和, 谷岡未樹, 中西健史, 中村泰大, 橋本 彰, 林 昌浩, 藤本 学, 藤原 浩, 松尾光馬, 間所直樹, 山﨑 修, 吉野雄一郎, 立花隆夫, 尹 浩信

    日皮会誌　121　(8)　1539-1559　2011

    Publisher: Japanese Dermatological Association

    DOI： 10.14924/dermatol.121.1539 　

    ISSN： 0021-499X

  163. 膠原病・血管炎

    浅野 善英

    日本皮膚科学会雑誌　120　(13)　2879-2880　2010/12/15

    ISSN： 0021-499X

  164. 乳頭部に生じた基底細胞癌の1例

    青笹 尚彦, 門野 岳史, 山本 瑞穂, 岡田 麻子, 常深 祐一郎, 浅野 善英, 菅谷 誠, 玉置 邦彦, 佐藤 伸一

    皮膚科の臨床　52　(12)　1913-1915　2010/11

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  165. Neonatal lupus erythematosus

    52　(9)　1205-1208　2010/09

    Publisher: 金原出版

    ISSN： 0018-1404

  166. A prominent effect of low dose imatinib mesylate for cutaneous involvements in systemic sclerosis

    Zenshiro Tamaki, Yoshihide Asano, Masaru Hatano, Atsushi Yao, Tomohiko Kawashima, Manabu Tomita, Koichiro Kinugawa, Ryozo Nagai, Shinichi Sato

    JOURNAL OF DERMATOLOGY　37　67-67　2010/09

    ISSN： 0385-2407

  167. The Role of GATA-6 in the pathogenesis of pulmonary arterial hypertension in scleroderma

    Angela Ghatnekar, Lukasz Stawski, Elaine Wirrig, Margaret Markiewicz, Yoshihide Asano, Russell Harley, Richard Silver, Maria Trojanowska

    CLINICAL AND EXPERIMENTAL RHEUMATOLOGY　28　(5)　S65-S65　2010/09

    ISSN： 0392-856X

  168. Beta7 integrin deficiency suppress cutaneous tumor formation

    Hiromichi Kai, Takafumi Kadono, Hanako Ohmatsu, Manabu Tomita, Yoshihide Asano, Makoto Sugaya, Shinichi Sato

    JOURNAL OF IMMUNOLOGY　184　2010/04

    ISSN： 0022-1767

    eISSN： 1550-6606

  169. L-selectin expression on CD4+T cells is critical for antibody production, whereas L-selectin expression on both CD4+and CD8+T cells is important for dermatitis in a mouse model of atopic dermatitis

    Takafumi Kadono, Manabu Tomota, Hanako Ohmatsu, Hiromichi Kai, Yoshihide Asano, Makoto Sugaya, Shinichi Sato

    JOURNAL OF IMMUNOLOGY　184　2010/04

    ISSN： 0022-1767

    eISSN： 1550-6606

  170. コリン性蕁麻疹を伴った特発性後天性全身性無汗症の1例

    宮川 卓也, 浅野 善英, 張本 明子, 岡田 麻子, 菅谷 誠, 門野 岳史, 菊池 かな子, 佐藤 伸一

    日本皮膚科学会雑誌　120　(5)　1056-1056　2010/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  171. Erythema gyratum repens様の皮疹を呈した蕁麻疹様血管炎の1例

    野田 真史, 竹腰 知紀, 玉城 善史郎, 浅野 善英, 菅谷 誠, 門野 岳史, 佐藤 伸一

    日本皮膚科学会雑誌　120　(5)　1067-1067　2010/04

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  172. アトピー性皮膚炎 (初診外来における初期診療)

    浅野 善英, 佐藤 伸一

    診断と治療　98　333-338　2010/03

    Publisher: 診断と治療社

    ISSN： 0370-999X

  173. ALTERED DYNAMICS OFTGF-BETA RECEPTORS IN SCLERODERMA FIBROBLASTS

    Y. Asano, H. Ihn, M. Jinnin, Y. Mimura, K. Tamaki, S. Sato

    CLINICAL AND EXPERIMENTAL RHEUMATOLOGY　28　(2)　S73-S73　2010/03

    ISSN： 0392-856X

  174. EFFECTS OF THE IMMUNOSUPPRESSANT RAPAMYCIN ON HUMAN ALPHA2 (I) COLLAGEN IN SCLERODERMA FIBROBLASTS

    Z. Tamaki, Y. Asano, M. Kubo, H. Ihn, N. Yazaya, R. Ashida, M. Tommita, T. Kawashima, K. Tamaki, S. Sato

    CLINICAL AND EXPERIMENTAL RHEUMATOLOGY　28　(2)　S98-S98　2010/03

    ISSN： 0392-856X

  175. 抗OJ抗体が陽性であった皮膚筋炎の1例

    野田 真史, 玉城 善史郎, 平林 恵, 浅野 善英, 竹腰 知紀, 帆足 俊彦, 菅谷 誠, 佐藤 伸一, 森本 里江子, 江藤 隆史

    日本皮膚科学会雑誌　120　(3)　701-701　2010/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  176. 診断、治療に苦慮したneutrophil-rich anaplastic large cell lymphomaの1例

    宮川 卓也, 菅谷 誠, 岡田 麻子, 浅野 善英, 門野 岳史, 佐藤 伸一

    日本皮膚科学会雑誌　120　(3)　743-743　2010/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  177. Nodular Sclerodermaを伴った汎発性強皮症の1例

    宮垣朝光, 浅野善英, 和泉理江子, 尹 浩信, 佐伯秀久, 玉置邦彦

    皮膚臨床　52　1231-1234　2010

  178. 菌状息肉症(MF)の紅斑内に生じたリンパ腫様丘疹症(LyP)の1例

    山本 瑞穂, 菅谷 誠, 青笹 尚彦, 大松 華子, 浅野 善英, 玉置 邦彦

    日本皮膚科学会雑誌　120　(1)　85-86　2010/01

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  179. 【皮膚筋炎-2009】 臨床例 脂肪織炎を呈し急速進行性間質性肺炎を合併した皮膚筋炎

    糸魚川 彩, 浅野 善英, 荒木 麻由子, 門野 岳史, 玉置 邦彦, 尹 浩信

    皮膚病診療　31　(9)　1039-1042　2009/09

    Publisher: (株)協和企画

    ISSN： 0387-7531

  180. 特異な臨床像を示した限局性強皮症の1例

    神人 正寿, 尹 浩信, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    日本皮膚科学会雑誌　118　(7)　1283-1283　2008/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  181. ループス腎炎を伴い皮疹の治療に難渋した全身性エリテマトーデス(SLE)の1例

    大松 華子, 桑野 嘉弘, 神人 正寿, 浅野 善英, 矢澤 徳仁, 佐伯 秀久, 尹 浩信, 朝比奈 昭彦, 菊池 かな子, 玉置 邦彦

    日本皮膚科学会雑誌　118　(6)　1111-1111　2008/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  182. プレドニゾロン内服が奏効した小児generalized morpheaの1例

    三村 佳弘, 冨田 学, 玉城 善史郎, 神人 正寿, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦, 蘆田 龍一, 久保 正英, 尹 浩信

    西日本皮膚科　69　(4)　451-451　2007/08

    Publisher: 日本皮膚科学会-西部支部

    ISSN： 0386-9784

    eISSN： 1880-4047

  183. 成人Still病の3例

    冨田 学, 玉城 善史郎, 永尾 麻由子, 増井 友里, 渡邉 彩, 蘆田 龍一, 佐々木 苗胤, 浅野 善英, 白井 明, 三井 浩, 山根 謙一, 菅谷 誠, 矢澤 徳仁, 門野 岳史, 佐伯 秀久, 渡邊 孝宏, 小宮根 真弓, 菊池 かな子, 玉置 邦彦, 前川 武雄, 久保 正英, 尹 浩信

    西日本皮膚科　69　(3)　334-335　2007/06

    Publisher: 日本皮膚科学会-西部支部

    ISSN： 0386-9784

    eISSN： 1880-4047

  184. 頭蓋骨病変および脳波異常を伴った限局性強皮症の1例

    冨田 学, 玉城 善史郎, 蘆田 龍一, 三村 佳宏, 神人 正寿, 浅野 善英, 矢澤 徳仁, 久保 正英, 玉置 邦彦, 尹 浩信

    日本皮膚科学会雑誌　117　(2)　180-180　2007/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  185. An usual manifestation of linear scleroderma ‘en coup de sabre' on the vertex and frontparietal regions

    Asano Y, Ihn H, Tamaki K

    Clin Exp Dermatol　32　758-759　2007

    DOI： 10.1111/j.1365-2230.2007.02521.x 　

  186. 腸管嚢腫様気腫症を合併した汎発性強皮症の1例

    和泉里江子, 浅野善英, 佐伯秀久, 尹 浩信, 玉置邦彦

    皮膚臨床　49　447-450　2007

  187. High-dose intravenous immune globulin infusion as treatment for diffuse scleroderma

    IHN H

    Br J Dermatol　156　1058-1060　2007

    DOI： 10.1111/j.1365-2133.2007.07777.x 　

  188. 汎発性強皮症患者における毛細血管拡張と臨床症状の相関について

    蘆田 龍一, 尹 浩信, 玉城 善史郎, 三村 佳弘, 神人 正寿, 浅野 善英, 矢澤 徳仁, 久保 正英, 玉置 邦彦

    日本皮膚科学会雑誌　116　(9)　1343-1343　2006/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  189. 限局性強皮症における血清中MMP-13濃度の臨床的意義

    浅野 善英, 久保 正英, 神人 正寿, 三村 佳弘, 蘆田 龍一, 玉置 邦彦, 尹 浩信

    日本皮膚科学会雑誌　116　(9)　1343-1343　2006/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  190. 限局性強皮症皮膚組織におけるTIMP-1の発現について

    玉城 善史郎, 三村 佳弘, 神人 正寿, 浅野 善英, 玉置 邦彦, 尹 浩信, 蘆田 龍一, 久保 正英

    日本皮膚科学会雑誌　116　(9)　1343-1343　2006/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  191. Integrin αvβ5の恒常的な強発現が正常皮膚線維芽細胞に及ぼす影響

    浅野 善英, 山根 謙一, 神人 正寿, 玉置 邦彦, 尹 浩信

    日本皮膚科学会雑誌　116　(9)　1347-1347　2006/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  192. 強皮症皮膚線維芽細胞におけるTGF-β受容体の動態

    浅野 善英, 神人 正寿, 三村 佳弘, 玉置 邦彦, 尹 浩信

    日本皮膚科学会雑誌　116　(9)　1347-1347　2006/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  193. ヒト皮膚線維芽細胞におけるEGFによるI型collagen発現抑制の機序について

    三村 佳弘, 神人 正寿, 山根 謙一, 浅野 善英, 玉置 邦彦, 尹 浩信

    日本皮膚科学会雑誌　116　(9)　1347-1347　2006/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  194. 汎発性強皮症患者由来皮膚線維芽細胞におけるc-SkiおよびSnoNの発現

    神人 正寿, 三村 佳弘, 浅野 善英, 山根 謙一, 玉置 邦彦, 尹 浩信

    日本皮膚科学会雑誌　116　(9)　1347-1347　2006/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  195. Hepatocyte Growth FactorのMatrix Metalloproteinase-1発現誘導作用の機序の検討

    神人 正寿, 三村 佳弘, 浅野 善英, 山根 謙一, 玉置 邦彦, 尹 浩信

    日本皮膚科学会雑誌　116　(9)　1347-1347　2006/08

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  196. 腸管嚢腫様気腫症を合併した汎発性強皮症の1例

    和泉 里江子, 浅野 善英, 久保 正英, 佐伯 秀久, 尹 浩信, 菊池 かな子, 玉置 邦彦

    日本皮膚科学会雑誌　116　(6)　960-961　2006/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  197. 免疫グロブリン大量静注療法が強皮症皮膚線維芽細胞に及ぼす影響

    浅野 善英, 尹 浩信, 浅島 信子, 矢澤 徳仁, 三村 佳弘, 神人 正寿, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　116　(2)　227-227　2006/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  198. 汎発性強皮症における血清中MMP-13濃度の臨床的意義

    浅野 善英, 尹 浩信, 久保 正英, 神人 正寿, 三村 佳弘, 蘆田 龍一, 玉置 邦彦

    日本皮膚科学会雑誌　116　(2)　227-228　2006/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  199. 強皮症線維芽細胞におけるα smooth muscle actin(SMA)発現亢進の機序について

    三村 佳弘, 尹 浩信, 神人 正寿, 山根 謙一, 浅野 善英, 玉置 邦彦

    日本皮膚科学会雑誌　116　(2)　228-228　2006/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  200. 強皮症皮膚線維芽細胞の恒常的活性化におけるインテグリンαvβ5の役割

    浅野 善英, 尹 浩信, 山根 謙一, 神人 正寿, 三村 佳弘, 玉置 邦彦

    日本皮膚科学会雑誌　116　(2)　228-228　2006/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  201. PDGF-Cの皮膚線維芽細胞に対する作用の検討

    神人 正寿, 尹 浩信, 三村 佳弘, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　116　(2)　228-228　2006/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  202. 強皮症線維芽細胞におけるトロンボスポンジンIの発現について。

    尹 浩信, 三村佳弘, 浅野善英, 神人正寿, 山根謙一, 玉置邦彦

    厚生労働科学研究費補助金特定疾患対策研究事業「強皮症における病因解明と根治的治療法の開発」平成17年度総括・分担研究報告書　155-164　2006

  203. ヒト皮膚線維芽細胞におけるEGFによるI型コラーゲン発現抑制の機序について。

    尹 浩信, 三村佳弘, 浅野善英, 神人正寿, 山根謙一, 玉置邦彦

    厚生労働科学研究費補助金特定疾患対策研究事業「強皮症における病因解明と根治的治療法の開発」平成17年度総括・分担研究報告書　141-148　2006

  204. Clinical significance of serum matrix metalloproteinase-13 levels in patients with localized scleroderma.

    Asano Y, Ihn H, Kubo M, Jinnin M, Mimura Y, Ashida R, Tamaki K

    Clin Exp Rheumatol　24　394-399　2006

  205. Clinical significance of serum levels of matrix metalloproteinase-13 in patients with systemic sclerosis

    ASANO Y

    Rheumatology　45　303-307　2006

    DOI： 10.1093/rheumatology/kei143 　

  206. Constitutive phosphorylated Smad3 interactes with Sp1 and p300/CBP in scleroderma fibroblasts

    IHN H

    Rheumatology　45　157-165　2006

    DOI： 10.1093/rheumatology/kei124 　

  207. 汎発性強皮症における免疫グロブリン大量療法について

    尹 浩信, 三村 佳弘, 矢澤 徳仁, 神人 正寿, 浅野 善英, 山根 謙一, 玉置 邦彦

    西日本皮膚科　67　(6)　663-663　2005/12

    Publisher: 日本皮膚科学会-西部支部

    ISSN： 0386-9784

    eISSN： 1880-4047

  208. 診療の実際から 蕁麻疹,皮膚疾患に伴う掻痒に対するベシル酸ベポタスチン(タリオン錠)の使用経験

    尹 浩信, 三村 佳弘, 神人 正寿, 浅野 善英, 山根 謙一, 玉置 邦彦

    新薬と臨牀　54　(7)　825-830　2005/07

    Publisher: (株)医薬情報研究所

    ISSN： 0559-8672

  209. 汎発性強皮症患者における手指屈曲拘縮と臨床症状との相関

    蘆田 龍一, 尹 浩信, 玉城 善史郎, 三村 佳弘, 神人 正寿, 浅野 善英, 久保 正英, 藤本 学, 玉置 邦彦

    日本皮膚科学会雑誌　115　(7)　1061-1062　2005/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  210. 混合性結合組織病における血清中クラス別リウマトイド因子の検討

    三村 佳弘, 尹 浩信, 神人 正寿, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　115　(7)　1062-1062　2005/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  211. 強皮症皮膚線維芽細胞に対するFK506の作用

    浅野 善英, 尹 浩信, 山根 謙一, 神人 正寿, 三村 佳弘, 玉置 邦彦

    日本皮膚科学会雑誌　115　(7)　1064-1064　2005/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  212. 有棘細胞癌におけるTGFβ受容体発現量について

    久保 正英, 尹 浩信, 山根 謙一, 神人 正寿, 浅野 善英, 玉置 邦彦

    日本皮膚科学会雑誌　115　(7)　1064-1064　2005/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  213. hepatocyte growth factorのI型コラーゲン代謝に対する作用

    神人 正寿, 尹 浩信, 三村 佳弘, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　115　(7)　1065-1065　2005/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  214. alpha 2(1) collagen gene regulation by protein kinase C signaling in human dermal fibroblasts

    M Jinnin, H Ihn, K Yamane, Y Mimura, Y Asano, K Tamaki

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　124　(4)　A89-A89　2005/04

    ISSN： 0022-202X

  215. 強皮症線維芽細胞におけるαsmooth muscle actin(SMA)発現亢進の機序について

    三村 佳弘, 尹 浩信, 神人 正寿, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本研究皮膚科学会年次学術大会・総会プログラム　30回　149-149　2005/04

    Publisher: (一社)日本研究皮膚科学会

  216. 正常および強皮症皮膚線維芽細胞におけるヒトα2(I)collagen遺伝子の発現およびTGF-β signalingの活性化に対するFK506の作用

    浅野 善英, 尹 浩信, 山根 謙一, 神人 正寿, 三村 佳弘, 玉置 邦彦

    日本研究皮膚科学会年次学術大会・総会プログラム　30回　121-121　2005/04

    Publisher: (一社)日本研究皮膚科学会

  217. 皮膚線維芽細胞におけるProtein kinase Cによるalpha2(I)コラーゲン遺伝子の転写制御

    神人 正寿, 尹 浩信, 三村 佳弘, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本研究皮膚科学会年次学術大会・総会プログラム　30回　158-158　2005/04

    Publisher: (一社)日本研究皮膚科学会

  218. 限局性強皮症皮膚線維芽細胞におけるintegrinαvβ3およびαvβ5の発現亢進の意義

    浅野 善英, 尹 浩信, 山根 謙一, 神人 正寿, 三村 佳弘, 玉置 邦彦

    日本皮膚科学会雑誌　115　(2)　164-164　2005/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  219. 汎発性強皮症線維芽細胞におけるSmad3のリン酸化とSmad3,Sp1,p300/CBPの相互作用

    尹 浩信, 山根 謙一, 浅野 善英, 神人 正寿, 玉置 邦彦

    日本皮膚科学会雑誌　115　(2)　164-164　2005/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  220. 混合性結合組織病における血清抗ガラクトース欠損IgG抗体値の検討

    三村 佳弘, 尹 浩信, 神人 正寿, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　115　(2)　164-164　2005/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  221. 皮膚線維芽細胞におけるTGF-βのtenascin-C産生促進作用について

    神人 正寿, 尹 浩信, 三村 佳弘, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　115　(2)　165-165　2005/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  222. 強皮症皮膚線維芽細胞におけるSmad7の発現量とその意義。

    尹 浩信, 浅野善英, 山根謙一, 玉置邦彦

    厚生労働科学研究費補助金特定疾患対策研究事業「強皮症における病因解明と根治的治療法の開発」平成14年度~平成16年度総合研究報告書　80-87　2005

  223. Sclerosing paniculitis is associated with pulmonary hypertension in systemic sclerosis.

    Jinnin M, Ihn H, Asano Y, Yamane K, Yazawa N, Tamaki K

    Br J Dermatol　153　579-583　2005

    DOI： 10.1111/j.1365-2133.2005.06680.x 　

  224. A case of diffuse scleroderma successfully treated with high-dose intravenous immune globulin infusion

    ASANO Y

    Rheumatology　44　824-826　2005

    DOI： 10.1093/rheumatology/keh600 　

  225. Involvement of αVβ5 intgrin-mediated activation of latent transforming growth factor β1 in autocrine transforming growth factor β signaling in systemic sclerosis fibroblasts.

    Asano Y, Ihn H, Yamane K, Jinnin M, Mimura Y, Tamaki K

    Arthritis Rheum　52　2897-2905　2005

  226. Serum levels of anti-agalactosyl IgG antibodies in mixed connective tissue disease.

    Mimura Y, Ihn H, Jinnin M, Asano Y, Yamane K, Yazawa N, Tamaki K

    Br J Dermatol　152　806-808　2005

    DOI： 10.1111/j.1365-2133.2005.06478.x 　

  227. Rheumatoid factor isotypes in localized scleroderma.

    Mimura Y, Ihn H, Jinnin M, Asano Y, Yamane K, Tamaki K

    Clin Exp Dermatol　30　405-408　2005

    DOI： 10.1111/j.1365-2230.2005.01776.x 　

  228. 心臓粘液腫を伴った汎発性強皮症の1例。

    三村佳弘, 神人正寿, 浅野善英, 山根謙一, 矢澤徳仁, 藤本 学, 尹 浩信, 玉置邦彦

    皮膚臨床　47　189-191　2005

  229. Protein kinase Cによる皮膚線維芽細胞におけるI型コラーゲン遺伝子転写制御。

    神人正寿, 尹 浩信, 山根謙一, 三村佳弘, 浅野善英, 玉置邦彦

    医薬の門　45　8-11　2005

  230. 蕁麻疹、皮膚疾患に伴う掻痒に対するベシル酸ベポタスチン(タリオン錠)の使用経験。

    尹 浩信, 三村佳弘, 神人正寿, 浅野善英, 山根謙一, 玉置邦彦

    新薬と臨床　54　59-64　2005

  231. 強皮症皮膚線維芽細胞におけるヒトα2(I)collagen遺伝子の発現およびTGF-β signalingの活性化に対するFK506の作用。

    尹 浩信, 浅野善英, 山根謙一, 神人正寿, 三村佳弘, 玉置邦彦

    厚生労働科学研究費補助金特定疾患対策研究事業「強皮症における病因解明と根治的治療法の開発」平成16年度総括・分担研究報告書　176-184　2005

  232. 汎発性強皮症皮膚線維化におけるインテグリンαvβ5の意義--latent TGF-β1受容体としてのインテグリンの機能 (線維化のメカニズムと疾患)

    浅野 善英

    医学のあゆみ　211　(11)　1051-1056　2004/12/11

    Publisher: 医歯薬出版

    ISSN： 0039-2359

  233. 筋症状を合併した汎発性強皮症患者の臨床学的及び血清学的特徴

    三村 佳弘, 尹 浩信, 神人 正寿, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　114　(10)　1683-1683　2004/09

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  234. 限局性強皮症における血清中クラス別リウマトイド因子の検討

    三村 佳弘, 尹 浩信, 神人 正寿, 山根 謙一, 浅野 善英, 玉置 邦彦

    日本皮膚科学会雑誌　114　(10)　1683-1683　2004/09

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  235. 好酸球性筋膜炎における血清manganese superoxide dismutase値の検討

    神人 正寿, 尹 浩信, 三村 佳弘, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　114　(10)　1683-1683　2004/09

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  236. 皮膚線維芽細胞におけるepidermal growth factorによるII型TGF-β受容体発現亢進の機序について

    山根 謙一, 尹 浩信, 浅野 善英, 玉置 邦彦

    日本皮膚科学会雑誌　114　(10)　1684-1684　2004/09

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  237. 強皮症線維芽細胞におけるintegrin αvβ3発現亢進の意義

    浅野 善英, 尹 浩信, 山根 謙一, 神人 正寿, 三村 佳弘, 玉置 邦彦

    日本皮膚科学会雑誌　114　(10)　1684-1684　2004/09

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  238. protein kinase Cによる皮膚線維芽細胞におけるI型コラーゲン遺伝子の転写制御

    神人 正寿, 尹 浩信, 三村 佳弘, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　114　(10)　1684-1684　2004/09

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

    eISSN： 1346-8146

  239. 【タクロリムス軟膏 これからの外用療法】 アトピー性皮膚炎以外での奏効例 エリテマトーデス(LE)

    三村 佳弘, 神人 正寿, 浅野 善英, 山根 謙一, 矢澤 徳仁, 久保 正英, 藤本 学, 尹 浩信, 玉置 邦彦

    Visual Dermatology　3　(8)　824-825　2004/07

    Publisher: (株)学研メディカル秀潤社

    ISSN： 2186-6589

  240. 【タクロリムス軟膏 これからの外用療法】 アトピー性皮膚炎以外での奏効例 限局性強皮症

    浅野 善英, 尹 浩信, 三村 佳弘, 神人 正寿, 山根 謙一, 久保 正英, 藤本 学, 玉置 邦彦

    Visual Dermatology　3　(8)　826-827　2004/07

    Publisher: (株)学研メディカル秀潤社

    ISSN： 2186-6589

  241. A case of peplomycin-induced scleroderma

    Y Asano, H Ihn, J Shikada, T Kadono, K Kikuchi, K Tamaki

    BRITISH JOURNAL OF DERMATOLOGY　150　(6)　1213-1214　2004/06

    DOI： 10.1111/j.1365-2133.2004.05969.x 　

    ISSN： 0007-0963

  242. 汎発性強皮症線維芽細胞におけるSmad3のリン酸化とSmad3,Sp1,p300/CBPの相互作用

    尹 浩信, 山根 謙一, 浅野 善英, 神人 正寿, 玉置 邦彦

    Connective Tissue　36　(2)　107-107　2004/06

    Publisher: 日本結合組織学会

    ISSN： 0916-572X

  243. 皮膚線維芽細胞におけるTGF-βによるTenascin-C遺伝子発現促進作用の機序

    神人 正寿, 尹 浩信, 三村 佳弘, 浅野 善英, 山根 謙一, 玉置 邦彦

    Connective Tissue　36　(2)　111-111　2004/06

    Publisher: 日本結合組織学会

    ISSN： 0916-572X

  244. 【膠原病】 プレドニゾロン内服が奏効した小児Generalized Morpheaの1例

    三村 佳弘, 中村 謙介, 山根 謙一, 神人 正寿, 浅野 善英, 尹 浩信, 玉置 邦彦

    皮膚科の臨床　46　(5)　727-729　2004/05

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  245. 汎発性強皮症皮膚線維芽細胞のコラーゲン遺伝子発現亢進におけるSmad3のリン酸化とSmad3,Sp1,p300/CBPの相互作用の関与

    尹 浩信, 山根 謙一, 浅野 善英, 神人 正寿, 玉置 邦彦

    日本研究皮膚科学会年次学術大会・総会プログラム　29回　99-99　2004/04

    Publisher: (一社)日本研究皮膚科学会

  246. 皮膚線維芽細胞におけるTGF-βによるTenascin-C産生促進作用の機序

    神人 正寿, 尹 浩信, 三村 佳弘, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本研究皮膚科学会年次学術大会・総会プログラム　29回　174-174　2004/04

    Publisher: (一社)日本研究皮膚科学会

  247. ヒト皮膚線維芽細胞におけるEGFによるfibronectin発現亢進の機序について

    三村 佳弘, 尹 浩信, 神人 正寿, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本研究皮膚科学会年次学術大会・総会プログラム　29回　175-175　2004/04

    Publisher: (一社)日本研究皮膚科学会

  248. TGF-beta刺激によるhuman alpha2(I)collagen遺伝子発現亢進におけるPI3-kinaseの意義

    浅野 善英, 尹 浩信, 山根 謙一, 神人 正寿, 三村 佳弘, 玉置 邦彦

    日本研究皮膚科学会年次学術大会・総会プログラム　29回　175-175　2004/04

    Publisher: (一社)日本研究皮膚科学会

  249. Fibronectin expression is post-trancriptionally up-regulated by epidermal growth factor in human dermal fibroblasts via protein kinase C-delta signaling pathway

    Y Mimura, H Ihn, M Jinnin, Y Asano, K Yamane, K Tamaki

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　122　(3)　A30-A30　2004/03

    ISSN： 0022-202X

  250. Tenascin-C up-regulation by transforming growth factor-beta in human dermal fibroblasts involves Smad3, Sp1, and Ets1

    M Jinnin, H Ihn, Y Asano, K Yamane, K Tamaki

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　122　(3)　A94-A94　2004/03

    ISSN： 0022-202X

  251. 心臓粘液腫を合併した汎発性強皮症の1例

    三村 佳弘, 中村 謙介, 蘆田 龍一, 神人 正寿, 浅野 善英, 山根 謙一, 矢澤 徳仁, 藤本 学, 尹 浩信, 鳥居 秀嗣, 菊池 かな子, 玉置 邦彦, 本村 昇

    日本皮膚科学会雑誌　114　(3)　649-649　2004/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  252. 大腸癌を合併し顔面の著明な色素沈着を伴った皮膚筋炎の1例

    浅野 善英, 久保 正英, 尹 浩信, 前川 武雄, 鹿田 純一郎, 門野 岳史, 菊池 かな子, 玉置 邦彦

    皮膚科の臨床　46　(3)　485-488　2004/03

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  253. 限局性強皮症における血清抗ガラクトース欠損IgG抗体値の検討

    三村 佳弘, 尹 浩信, 神人 正寿, 山根 謙一, 浅野 善英, 玉置 邦彦

    日本皮膚科学会雑誌　114　(2)　194-195　2004/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  254. 限局性強皮症における血清manganese superoxide dismutase値の検討

    神人 正寿, 尹 浩信, 矢澤 徳仁, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　114　(2)　195-195　2004/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  255. 混合性結合織病における血清tissue inhibitor of metalloproteinase-1,2の検討

    神人 正寿, 尹 浩信, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    日本皮膚科学会雑誌　114　(2)　195-195　2004/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  256. 皮膚筋炎/多発性筋炎患者における血清SP-D値の臨床的意義について

    尹 浩信, 浅野 善英, 久保 正英, 山根 謙一, 神人 正寿, 矢澤 徳仁, 藤本 学, 玉置 邦彦

    日本皮膚科学会雑誌　114　(2)　195-195　2004/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  257. 基底細胞癌におけるIL-13のTenascin-C産生促進作用について

    神人 正寿, 尹 浩信, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　114　(2)　196-196　2004/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  258. TGF-β刺激によるヒトα2(I)collagen遺伝子発現亢進におけるPI3-kinaseの意義

    浅野 善英, 尹 浩信, 山根 謙一, 神人 正寿, 三村 佳弘, 玉置 邦彦

    日本皮膚科学会雑誌　114　(2)　196-196　2004/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  259. 角層下膿疱症を伴った汎発性強皮症の1例

    三村 佳弘, 神人 正寿, 浅野 善英, 山根 謙一, 矢澤 徳仁, 尹 浩信, 玉置 邦彦

    皮膚科の臨床　46　(1)　105-107　2004/01

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  260. Tenascin-C up-regulation by transforming growth factor-beta in human dermal fibroblasts involves Smad3, Sp1, and Ets1

    M Jinnin, H Ihn, Y Asano, K Yamane, M Trojanowska, K Tamaki

    ARTHRITIS AND RHEUMATISM　48　(9)　S416-S416　2003/09

    ISSN： 0004-3591

  261. Constitutive complex formation of smad7 with transforming growth factor (TGF) - beta receptors in scleroderma fibroblasts.

    Y Asano, H Ihn, K Yamane, M Kubo, K Tamaki

    ARTHRITIS AND RHEUMATISM　48　(9)　S155-S155　2003/09

    ISSN： 0004-3591

  262. 強皮症皮膚線維芽細胞におけるSmad 7の発現量とその意義

    浅野 善英, 尹 浩信, 山根 謙一, 久保 正英, 玉置 邦彦

    日本皮膚科学会雑誌　113　(7)　87-94　2003/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  263. Upregulated Tenascin-C Expression in Stroma around Basal Cell Carcinoma;Induction by Interleukin-13 in Human Dermal Fibroblasts via PI3-K/Akt and PKC pathway

    Jinnin Masatoshi, Ihn Hironobu, Asano Yoshihide, Yamane Kenichi, Tamaki Kunihiko

    Connective tissue　35　(2)　93-93　2003/06

    Publisher: The Japanese Society for Connective Tissue

    ISSN： 0916-572X

  264. 汎発性強皮症患者のIgG,IgM,IgA型リウマトイド因子・抗ガラクトース欠損IgG抗体

    三村 佳弘, 尹 浩信, 神人 正寿, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    日本皮膚科学会雑誌　113　(7)　1156-1156　2003/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  265. sclerosing panniculitisを合併した汎発性強皮症患者の臨床的特徴

    神人 正寿, 尹 浩信, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    日本皮膚科学会雑誌　113　(7)　204-206　2003/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  266. 混合性結合織病における可溶性CD40 ligand値の検討

    神人 正寿, 尹 浩信, 矢澤 徳仁, 浅野 善英, 山根 謙一, 玉置 邦彦

    日本皮膚科学会雑誌　113　(7)　1156-1156　2003/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  267. transforming growth factor β情報伝達系に対するtumor necrosis factor αの拮抗作用とその機序

    山根 謙一, 尹 浩信, 浅野 善英, 神人 正寿, 玉置 邦彦

    日本皮膚科学会雑誌　113　(7)　1158-1158　2003/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  268. 慢性関節リウマチを合併した汎発性強皮症患者の臨床的特徴

    神人 正寿, 尹 浩信, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    日本皮膚科学会雑誌　113　(7)　201-203　2003/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  269. 乳児期に発症した汎発性扁平黄色腫の1例

    浅野 善英, 尹 浩信, 朝比奈 昭彦, 玉置 邦彦

    日本皮膚科学会雑誌　113　(6)　1024-1024　2003/05

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  270. Upregulated tenascin-C expression in stroma around basal cell carcinoma: Induction by interleukin-13 in human dermal fibroblasts via phosphoinositide 3-kinase/Akt and protein C kinase signaling pathway

    M Jinnin, H Ihn, Y Asano, K Yamane, M Trojanowska, K Tamaki

    FASEB JOURNAL　17　(5)　A1013-A1013　2003/03

    ISSN： 0892-6638

  271. Antagonistic effects of TNFalpha on TGFbeta signaling through downregulation of TGFbeta receptor type II in human dermal fibroblasts

    K Yamane, H Ihn, Y Asano, M Jinnin, K Tamaki

    FASEB JOURNAL　17　(5)　A1017-A1018　2003/03

    ISSN： 0892-6638

  272. Increased expression of integrin alpha v beta 5 in scleroderma fibroblasts

    Y Asano, H Ihn, K Yamane, M Kubo, K Tamaki

    FASEB JOURNAL　17　(5)　A1351-A1351　2003/03

    ISSN： 0892-6638

  273. 【小児の皮膚病 臨床例】 乳児期に発症した汎発性正脂血性扁平黄色腫

    浅野 善英, 尹 浩信, 玉置 邦彦

    皮膚病診療　25　(3)　315-318　2003/03

    Publisher: (株)協和企画

    ISSN： 0387-7531

  274. 抗U3-RNP抗体陽性男性汎発性強皮症の1例

    神人 正寿, 浅野 善英, 久保 正英, 尹 浩信, 大河内 仁志, 玉置 邦彦

    皮膚科の臨床　45　(3)　313-316　2003/03

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  275. Circulating soluble CD40 ligand in patients with eosinophilic fasciitis

    M Jinnin, H Ihn, N Yazawa, Y Asano, K Yamane, K Tamaki

    ANNALS OF THE RHEUMATIC DISEASES　62　(2)　190-191　2003/02

    ISSN： 0003-4967

  276. SLEに伴ったReticular Erythematous Mucinosisの1例

    神人 正寿, 山根 謙一, 尹 浩信, 浅野 善英, 矢澤 徳仁, 玉置 邦彦

    皮膚科の臨床　45　(1)　55-57　2003/01

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  277. 脂肪織炎を伴った皮膚筋炎の1例

    神人 正寿, 河野 志保美, 尹 浩信, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    皮膚科の臨床　45　(1)　59-62　2003/01

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  278. 【膠原病 その多様な病態と多彩な皮疹】 知っておくべき膠原病の特徴的皮疹 レイノー現象と爪上皮内出血点

    尹 浩信, 神人 正寿, 三村 佳弘, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    Visual Dermatology　2　(1)　24-25　2002/12

    Publisher: (株)学研メディカル秀潤社

    ISSN： 2186-6589

  279. Autoimmune response to 52-kDa and 60-kDa Ro/SS-A antigens in mixed connective tissue disease

    M Jinnin, H Ihn, Y Asano, K Yamane, N Yazawa, K Tamaki

    BRITISH JOURNAL OF DERMATOLOGY　147　(4)　827-829　2002/10

    ISSN： 0007-0963

  280. 汎発性強皮症に伴う胃食道逆流症に対するエカベトナトリウム(ガストローム顆粒)の効果 既存消化器症状治療薬への上乗せ効果の確認

    尹 浩信, 山根 謙一, 神人 正寿, 浅野 善英, 矢澤 徳仁, 久保 正英, 藤本 学, 玉置 邦彦

    Pharma Medica　20　(10)　191-201　2002/10

    Publisher: (株)メディカルレビュー社

    ISSN： 0289-5803

  281. 全身性強皮症に合併する逆流性食道炎に対するプロトンポンプ阻害剤rabeprazoleの臨床効果の検討

    尹 浩信, 三村 佳弘, 神人 正寿, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    新薬と臨牀　51　(9)　872-876　2002/09

    Publisher: (株)医薬情報研究所

    ISSN： 0559-8672

  282. 混合性結合織病における抗SS-A抗体の抗原特異性

    神人 正寿, 尹 浩信, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    日本皮膚科学会雑誌　112　(10)　1395-1395　2002/09

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  283. 汎発性強皮症における甲状腺抗体と甲状腺機能異常

    矢澤 徳仁, 尹 浩信, 神人 正寿, 浅野 善英, 山根 謙一, 藤本 学, 菊池 かな子, 玉置 邦彦

    日本皮膚科学会雑誌　112　(10)　1398-1398　2002/09

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  284. 汎発性強皮症患者の肺線維症に対するD-ペニシラミンの有効性の検討

    神人 正寿, 尹 浩信, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    日本皮膚科学会雑誌　112　(10)　1398-1398　2002/09

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  285. 汎発性強皮症における血清matrix metalloproteinase-3値の検討

    神人 正寿, 尹 浩信, 山根 謙一, 浅野 善英, 矢澤 徳仁, 玉置 邦彦

    日本皮膚科学会雑誌　112　(10)　1398-1398　2002/09

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  286. 汎発性強皮症皮膚線維芽細胞におけるintegrinαvβ5の発現量とその意義

    浅野 善英, 尹 浩信, 山根 謙一, 久保 正英, 玉置 邦彦

    日本皮膚科学会雑誌　112　(10)　1398-1398　2002/09

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  287. 汎発性強皮症皮膚線維芽細胞におけるインテグリンalpha v beta5の発現量について

    浅野 善英, 尹 浩信, 山根 謙一, 久保 正英, 玉置 邦彦

    日本研究皮膚科学会年次学術大会・総会プログラム　27回　153-153　2002/08

    Publisher: (一社)日本研究皮膚科学会

  288. 皮膚線維芽細胞におけるIL-13のTenascin-C産生促進作用について

    神人 正寿, 尹 浩信, 山根 謙一, 浅野 善英, 玉置 邦彦

    日本研究皮膚科学会年次学術大会・総会プログラム　27回　163-163　2002/08

    Publisher: (一社)日本研究皮膚科学会

  289. Increased expression of integrin EovE5 in scleroderma fibroblasts

    Y Asano, H Ihn, K Yamane, M Kubo, K Tamaki

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　119　(1)　225-225　2002/07

    ISSN： 0022-202X

  290. 【乾癬 その多様な臨床】 他疾患との合併 強皮症を合併した乾癬

    神人 正寿, 尹 浩信, 浅野 善英, 山根 謙一, 矢澤 徳仁, 朝比奈 昭彦, 玉置 邦彦

    Visual Dermatology　1　(5)　518-519　2002/07

    Publisher: (株)学研メディカル秀潤社

    ISSN： 2186-6589

  291. 汎発性強皮症患者の心病変の検討

    神人 正寿, 尹 浩信, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    日本皮膚科学会雑誌　112　(8)　1135-1135　2002/07

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  292. 汎発性強皮症における血漿plasmin-α2 plasmin inhibitor complex(PIC)値の検討

    神人 正寿, 尹 浩信, 山根 謙一, 浅野 善英, 矢澤 徳仁, 玉置 邦彦

    日本皮膚科学会雑誌　112　(8)　1135-1136　2002/07

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  293. 抗ゴルジ抗体陽性の汎発性強皮症の2例

    矢澤 徳仁, 尹 浩信, 神人 正寿, 浅野 善英, 山根 謙一, 藤本 学, 菊池 かな子, 玉置 邦彦, 佐藤 伸一, 相馬 良直

    日本皮膚科学会雑誌　112　(8)　1136-1136　2002/07

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  294. 汎発性強皮症患者における抗U1 RNA抗体の出現頻度と臨床的意義

    浅野 善英, 尹 浩信, 山根 謙一, 久保 正英, 玉置 邦彦

    日本皮膚科学会雑誌　112　(8)　1136-1136　2002/07

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  295. 好酸球性筋膜炎における血清tissue inhibitor of metalloproteinase-1,2値の検討

    神人 正寿, 尹 浩信, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    日本皮膚科学会雑誌　112　(8)　1138-1138　2002/07

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  296. INCREASED EXPRESSION OF INTEGRIN αvβ5 IN SCLERODERMA FIBROBLASTS.

    Asano Yoshihide, Ihn Hironobu, Yamane Kenichi, Kubo Masahide, Tamaki Kunihiko

    Connective tissue　34　(1)　58-58　2002/04

    Publisher: The Japanese Society for Connective Tissue

    ISSN： 0916-572X

    More details Close

    Extracellular matrix (ECM) metabolism of fibroblasts is tightly regulated by multiple environmental influences, including adhesion to the ECM and soluble factors (i.e. polypeptide growth factors and inflammatoty cytokines). Cell-ECM interaction is mediated through distinct receptors on the cell surface, mainly belonging to the integrins. Metabolism of collagen, the major structural component of ECM, is partially mediated through its receptors, including integrin α1β1 and α2β1. Integrin α1β1 provides negative feedback on collagen synthesis, whereas integrin α2β1 stimulates the synthesis of matrix metalloproteases. Reduced expression of both integrins in scleroderma fibroblasts correlate with upregulated collagen synthesis and downregulated metalloproteases of these cells. Thus, to date, much of the focus in scleroderma fibroblasts has been on the expression of the collagen receptors. In this study, we focused on another integrin, αvβ5, and its ligand, vitronectin. Vitronectin is a plasma protein that is also found distributed in ECM of various tissues in vivo, including dermal fibers in the skin. Matrix vitronectin binds various kinds of protease inhibitor, including plasnimogen activator inhibitor type-i, and controls their activities. The conformation of vitronectin regualtes its removal from ECM by human skin fibroblasts through integrin αvβ5. Increasing evidence supports the notion that integrin αvβ5 might regulate matrix turnover and remodeling through vitronectin related pericellular proteolysis. In the present study, we compared expression levels of integrin αvβ5 on dermal fibroblasts and the deposition levels of vitronectin in dermal tissue between scleroderma and healthy controls. Immunoblotting and Northern blot analysis showed that β5 subunit is upregulated in scleroderma fibroblasts. Increased expression of integrin αvβ5 on cell surface of scleroderma fibroblasts was also demonstrated by immunoprecipitation In immunohistochemical analysis, expression levels of integrin αvβ5 on dermal fibroblasts as well as vitronectin in dermal tissue was elevated in scleroderma skin sections. These results indicate that vitronectin dependent inhibition of pericellular proteolytic cascade may contribute to excessive extracellular matrix deposition in scleroderma and suggest the possibility that integrin αvβ5 serves to transduce a signal related to activation of lesional fibroblasts. Our data strengthen the concept that an important pathogenetic mechanism in scleroderma may be the abberant expression of ECM receptors.

  297. 特異な臨床像を示した限局性強皮症の1例

    神人 正寿, 尹 浩信, 浅野 善英, 山根 謙一, 矢澤 徳仁, 玉置 邦彦

    皮膚科の臨床　44　(3)　297-299　2002/03

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  298. 限局性強皮症における抗U3-RNP抗体について

    山根 謙一, 尹 浩信, 久保 正英, 浅野 善英, 矢澤 徳仁, 玉置 邦彦, 桑名 正隆

    日本皮膚科学会雑誌　112　(2)　146-146　2002/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  299. total skin scoreとポイント制診断基準案の比較検討

    浅野 善英, 尹 浩信, 山根 謙一, 矢澤 徳仁, 久保 正英, 菊池 かな子, 玉置 邦彦, 相馬 良直

    日本皮膚科学会雑誌　112　(2)　146-146　2002/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  300. 女性化乳房を伴った男性汎発性強皮症の1例

    アンドレ・レパヴー, 浅野 善英, 出月 健夫, 矢澤 徳仁, 佐伯 秀久, 尹 浩信, 大河内 仁志, 玉置 邦彦

    日本皮膚科学会雑誌　112　(2)　150-150　2002/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  301. 血清surfactant protein D(SP-D)による汎発性強皮症患者の肺線維症の評価について

    浅野 善英, 尹 浩信, 山根 謙一, 矢澤 徳仁, 久保 正英, 藤本 学, 玉置 邦彦

    日本皮膚科学会雑誌　112　(2)　163-163　2002/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  302. Anti-U5 snRNP antibody as a possible serological marker for scleroderma-polymyositis overlap

    Kubo Masahide, Ihn Hironobu, Kuwana Masataka, Asano Yoshihide, Tamaki Takeshi, Yamane Kenichi, Tamaki Kunihiko

    Rheumatology　41　(5)　531-534　2002

  303. Differential expression of transforming growth factor-beta receptors in squamous cell carcinoma

    M Kubo, H Ihn, K Yamane, Y Asano, M Jinnin, K Tamaki

    BRITISH JOURNAL OF DERMATOLOGY　145　(5)　840-842　2001/11

    ISSN： 0007-0963

  304. 汎発性強皮症に伴う消化器症状に対するクエン酸モサプリドの効果

    尹 浩信, 山根 謙一, 神人 正寿, 浅野 善英, 矢澤 徳仁, 久保 正英, 藤本 学, 玉置 邦彦

    臨床医薬　17　(10)　1439-1445　2001/10

    Publisher: (株)臨床医薬研究協会

    ISSN： 0910-8211

  305. The prevalence and clinical significance of anti-U1 RNA antibodies in patients with systemic sclerosis

    Y Asano, H Ihn, K Yamane, M Kubo, N Yazawe, M Fujimoto, K Tamaki

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　117　(2)　551-551　2001/08

    ISSN： 0022-202X

  306. chilblain lupusの1例

    浅野 善英, 尹 浩信, 朝比奈 昭彦, 玉置 邦彦

    日本皮膚科学会雑誌　111　(8)　1275-1275　2001/07

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  307. 免疫抑制剤及びγ-globulin投与により改善した結節性多発動脈炎の1例

    前川 武雄, 尹 浩信, 浅野 善英, 大河内 仁志, 玉置 邦彦

    西日本皮膚科　63　(3)　341-341　2001/06

    Publisher: 日本皮膚科学会-西部支部

    ISSN： 0386-9784

  308. 【膠原病】 Morpheaを伴った好酸球性筋膜炎の1例

    浅野 善英, 久保 正英, 尹 浩信, 神人 正寿, 出月 健夫, 大河内 仁志, 菊池 かな子, 玉置 邦彦

    皮膚科の臨床　43　(5)　591-594　2001/05

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  309. Rapid loss of insulin secretion in a patient with fulminant type 1 diabetes mellitus and carbamazepine hypersensitivity syndrome

    Nobuo Sekine, Toru Motokura, Toshihiko Oki, Yumi Umeda, Nobukazu Sasaki, Michio Hayashi, Hiroyuki Sato, Toshiro Fujita, Takehiko Kaneko, Yoshihide Asano, Kanako Kikuchi

    Journal of the American Medical Association　285　(9)　1153-1154　2001/03/07

    DOI： 10.1001/jama.285.9.1153 　

    ISSN： 0098-7484

  310. 皮膚筋炎を合併した汎発性強皮症の1例

    浅野 善英, 尹 浩信, 神人 正寿, 久保 正英, 門野 岳史, 湧川 基史, 大河内 仁志, 菊池 かな子, 玉置 邦彦

    日本皮膚科学会雑誌　111　(3)　409-409　2001/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  311. 抗Th/To抗体陽性汎発性強皮症の男性例

    浅野 善英, 久保 正英, 尹 浩信, 鹿田 純一郎, 門野 岳史, 菊池 かな子, 玉置 邦彦

    日本皮膚科学会雑誌　111　(2)　165-170　2001/02

    Publisher: (公社)日本皮膚科学会

    DOI： 10.14924/dermatol.111.165 　

    ISSN： 1346-8146 0021-499X

  312. Antibodies to Th/To ribonucleoprotein in patients with localized scleroderma

    Yamane Kenichi, Ihn Hironobu, Kubo Masahide, Kuwana Masataka, Asano Yoshihide, Yazawa Norihito, Tamaki Kunihiko

    Rheumatology　40　(6)　683-686　2001

  313. Anti-U1RNP antibodies in patients with localized scleroderma

    Yamane Kenichi, Ihn Hironobu, Kubo Masahide, Kuwana Masataka, Asano Yoshihide, Yazawa Norihito, Tamaki Kunihiko

    Archives of Dermatological Research　293　(9)　455-459　2001

    DOI： 10.1007/s004030100254 　

  314. Anti-U3 snRNP antibodies in localised scleroderma

    Yamane Kenichi, Ihn Hironobu, Kubo Masahide, Asano Yoshihide, Yazawa Norihito, Tamaki Kunihiko, Kuwana Masataka

    Annals of the Rheumatic Diseases　60　(12)　1157-1158　2001

    DOI： 10.1136/ard.60.12.1157 　

  315. 【膠原病】 肺癌を伴ったOverlap症候群の1例

    浅野 善英, 久保 正英, 尹 浩信, 鹿田 純一郎, 門野 岳史, 菊池 かな子, 玉木 毅, 相馬 良直, 玉木 邦彦

    皮膚科の臨床　42　(9)　1321-1325　2000/09

    Publisher: 金原出版(株)

    ISSN： 0018-1404

  316. 限局性強皮症患者における抗U1RNP抗体の頻度及び抗原特異性について

    山根 謙一, 尹 浩信, 久保 正英, 桑名 正隆, 浅野 善英, 矢澤 徳仁, 菊池 かな子, 玉置 邦彦

    日本臨床免疫学会会誌　23　(4)　392-392　2000/08

    Publisher: 日本臨床免疫学会

    ISSN： 0911-4300

  317. 肺癌を伴い難治性筋炎を合併した汎発性強皮症の1例

    浅野 善英, 鹿田 純一郎, 久保 正英, 門野 岳史, 尹 浩信, 菊池 かな子, 玉置 邦彦, 玉木 毅, 相馬 良直

    西日本皮膚科　62　(3)　425-425　2000/06

    Publisher: 日本皮膚科学会-西部支部

    ISSN： 0386-9784

  318. 限局性強皮症患者における抗U1RNP抗体の頻度及び抗原特異性について

    山根 謙一, 尹 浩信, 久保 正英, 浅野 善英, 矢澤 徳仁, 菊池 かな子, 玉置 邦彦, 相馬 良直

    日本皮膚科学会雑誌　110　(7)　1163-1163　2000/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  319. 限局性強皮症患者における抗Th/To抗体について

    山根 謙一, 尹 浩信, 久保 正英, 浅野 善英, 矢澤 徳仁, 玉置 邦彦, 菊池 かな子, 桑名 正隆

    日本皮膚科学会雑誌　110　(7)　1177-1178　2000/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  320. 肺高血圧症を合併した汎発性強皮症患者の臨床症状,検査所見の検討

    山根 謙一, 尹 浩信, 浅野 善英, 矢澤 徳仁, 久保 正英, 菊池 かな子, 玉置 邦彦, 相馬 良直

    日本皮膚科学会雑誌　110　(7)　1163-1163　2000/06

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  321. morpheaを伴った好酸球性筋膜炎の1例

    浅野 善英, 神人 正寿, 出月 健夫, 久保 正英, 尹 浩信, 大河内 仁志, 菊池 かな子, 玉置 邦彦

    日本皮膚科学会雑誌　110　(3)　321-321　2000/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  322. 抗Th/To抗体陽性汎発性強皮症の男性例

    浅野 善英, 鹿田 純一郎, 久保 正英, 門野 岳史, 尹 浩信, 菊池 かな子, 玉置 邦彦

    日本皮膚科学会雑誌　110　(2)　191-191　2000/02

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  323. Comparisison of the Clinical Significance of a Points System and Modified Rodnan Total Skin Thickness Score in Patients with Systemic Sclerosis

    ASANO Yoshihide, IHN Hironobu, YAMANE Kenichi, YAZAWA Norihito, KUBO Masahide, KIKUCHI Kanako, SOMA Yoshinao, TAMAKI Kunihiko

    日本皮膚科学会雑誌　110　(13)　2107-2107　2000

    Publisher: (公社)日本皮膚科学会

    DOI： 10.14924/dermatol.110.2107 　

    ISSN： 0021-499X

  324. 当科外来を受診した汎発性強皮症における抗U5 snRNP抗体単独陽性例

    久保 正英, 尹 浩信, 浅野 善英, 菊池 かな子, 玉置 邦彦, 玉木 毅, 相馬 良直, 桑名 正隆

    日本皮膚科学会雑誌　109　(3)　494-494　1999/03

    Publisher: (公社)日本皮膚科学会

    ISSN： 0021-499X

  325. Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: An association with malignancy

    K. Kaji, M. Fujimoto, M. Hasegawa, M. Kondo, Y. Saito, K. Komura, T. Matsushita, H. Orito, Y. Hamaguchi, K. Yanaba, M. Itoh, Y. Asano, M. Seishima, F. Ogawa, S. Sato, K. Takehara

    Rheumatology　46　25-28

    DOI： 10.1093/rheumatology/kel161 　

    ISSN： 1462-0324

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    Objective. Myositis-specific autoantibodies (MSAs) are a useful tool in diagnosis, defining clinical subsets and predicting prognosis of dermatomyositis (DM) and polymyositis (PM). In this study, we identified a novel MSA reactive with 155 and 140 kDa nuclear proteins [anti-155/140 antibody (Ab)] and determined the clinical feature of DM patients positive for this autoantibody (autoAb). Methods. Sera from 52 Japanesepatients with DM, 9 with PM, 48 with systemic lupus erythematosus (SLE), 126 with systemic sclerosis and 18 with idiopathic interstitial pneumonia were examined by immunoprecipitation assays. Positive sera were further characterized by immunodepletion and immunofluorescence staining. Results. Seven of the 52 (13%) Japanese patients with DM immunoprecipitated 155 and 140 kDa proteins from 35S-labelled K562 leukaemia cell extract. No patients with SLE, systemic sclerosis or idiopathic interstitial pneumonia as well as healthy controls were positive for this autoAb. Patients with anti-155/140 Ab developed heliotrope rash, Gottron&#039;s papules or sign and flagellate erythema significantly more frequently than those negative. Notably, internal malignancy was found at significa

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Presentations 13

  1. 全⾝性強⽪症に伴う難治性⽪膚潰瘍の病態と治療戦略 Invited

    浅野善英

    第52回 日本臨床免疫学会総会　2024/10/10

  2. 皮膚細菌叢を介した自己免疫疾患発症機序 Invited

    浅野善英

    第52回 日本臨床免疫学会総会　2024/10/10

  3. 尋常性白斑の病態形成におけるエピジェネティクスの役割：最近の研究の進歩 Invited

    浅野善英

    第6回 日本白斑学会学術大会　2024/09/22

  4. 皮膚免疫疾患の病態理解と治療の進歩 Invited

    浅野善英

    日本臨床免疫学会 免疫疾患横断セミナーシリーズ 第5回　2024/07/13

  5. Commensal Bacteria: Orchestrators of Autoimmune Skin Inflammation and Beyond in SLE Invited

    Yoshihide Asano

    FOCIS 2024　2024/06/18

  6. 強皮症診療におけるセンチネルポジション としての皮膚科医の果たすべき役割 Invited

    浅野善英

    第123回 日本皮膚科学会総会　2024/06/08

  7. 膠原病・血管炎に伴う皮膚潰瘍の治療 Invited

    浅野善英

    第123回 日本皮膚科学会総会　2024/06/09

  8. 乾癬性関節炎の最新のTopics （基礎＆病態の観点より） Invited

    浅野善英

    日本皮膚科学会東北六県合同地方会第406回例会　2024/05/18

  9. 昔からある検査と最近の検査の進歩 Invited

    浅野善英

    第40回 日本臨床皮膚科医会総会・臨床学術大会　2024/04/21

  10. How to treat skin fibrosis and digital ulcerations in SSc? A practical approach Invited

    Yoshihide Asano

    8th Systemic Sclerosis World Congress　2024/03/14

  11. What can we learn from Fli1-deficient mice, new animal models of systemic sclerosis? Invited

    Yoshihide Asano

    The 49th Annual Meeting of Taiwanese Dermatological Association　2023/12/10

  12. The Pathogenesis of Systemic Sclerosis: An Understanding Based on a Common Pathologic Cascade across Multiple Organs and Additional Organ-Specific Pathologies Invited

    Yoshihide Asano

    The 49th Annual Meeting of Taiwanese Dermatological Association　2023/12/09

  13. 強皮症診療の進歩 ～最近の知見と新しい治療戦略～ Invited

    浅野善英

    第5回 日本アレルギー学会東北地方会　2023/11/25

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Research Projects 13

  1. Development of novel assist tool for the diagnosis of skin cancer by the active measurement of effective thermal conductivity

    Taku Fujimura, Yoshihide Asano, Yumi Kambayashi, Ryo Amagai

    Offer Organization: Japan Agency for Medical Research and Development

    Category: DermatoOncology

    Institution: Tohoku University Graduate School of Medicine

    2023/10 - 2026/03

  2. The identification of systemic sclerosis-related transcription factor network induced by FLI1 deficiency for the development of a new therapeutic agent

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2022/04/01 - 2025/03/31

  3. A new therapeutic strategy against systemic sclerosis targeting skin immunity

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Research (Exploratory)

    Institution: Tohoku University

    2021/07/09 - 2023/03/31

  4. Functional analysis of RXRB genetically identified as a susceptibility gene for systemic sclerosis

    Oka Akira

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tokai University

    2019/04/01 - 2022/03/31

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    We have already identified a susceptibility mutation on the RXRB gene (retinoic acid receptor) that carries a strong genetic risk for systemic sclerosis (SSc). Therefore, they investigated the function of the mutation using fibroblasts isolated from patient-affected areas. Our studies showed that in the presence of retinoic acid, the expression of a gene group involved in the cell cycle was significantly increased only in cells with the mutation. This group containds cyclin-dependent kinase 1 (CDK1), and molecules targeting CDK1 have already shown promise as a treatment for SSc, it is strongly suggested that this mutation may be biologically involved in the pathogenesis of SSc.

  5. The analysis of SSc pathogenesis utilizing 9 strains of new murine models

    Asano Yoshihide

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    2019/04/01 - 2022/03/31

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    This study was undertaken to investigate the gene program which is driven in the early stage of systemic sclerosis by using animal models with deficiency of Fli1 in various cell types. Major findings were as follows: (i) activated Fli1 +/- B cells produce excessive amount of IL-6 in the presence of macrophages through TLR9 stimulation, (ii) Fli1 deficiency increases the proportion of newly formed B cells, especially B-1a-like B cells, (iii) age-associated B cells are detected in splenic newly formed B cells. These results suggest that Fli1 deficiency is associated with the induction of B cell subset which likely plays a key role in early disease process of systemic sclerosis.

  6. The development of oligonucleotide therapeutics targeting epithelial cells in systemic sclerosis

    Asano Yoshihide, Trojanowska Maria

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: The University of Tokyo

    2016/04/01 - 2019/03/31

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    Based on the clinical observation that a part of patients with systemic sclerosis (SSc) develops skin sclerosis due to Koebner phenomenon, we investigated molecules invovled in this phenomenon and sought to develop a new treatment targeting such molecules against skin sclerosis of SSc. We identified IL-1 alpha and CTGF that are invovled in the epithelial cell-dependent induction of skin fibrosis in epithelial cell-specific Fli1 knockout mice (Fli1 flox/flox; K14-Cre) which spontaneously develop skin fibrosis. We also found the potential of epithelial cell-producing psoriasin and LL-37 to promote the development of skin fibrosis in the clinical studies with sera and skin sections of SSc patients. We are currently going to generate oligonucleotide therapeutics targeting these molecules produced by epithelial cells by using drug delivery system such as ointment, cream and microneedle.

  7. The analysis of systemic sclerosis pathogenesis with mice lacking the Fli1 gene in various cell types

    Asano Yoshihide, Trojanowska Maria, Zhuang Yuan

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: The University of Tokyo

    2016/04/01 - 2019/03/31

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    Fli1 deficiency is a potential predisposing factor in the development of systemic sclerosis (SSc). To investigate the role of various cell types in the pathogenesis of SSc, we generated mice lacking the Fli1 gene in endothelial cells, epithelial cells, B cells, gamma delta T cells, regulatory T cells, adipocytes, megakaryocytes or myeloid cells by using loxp-Cre system. Of note, all the 8 strains of mice reproduced all or a part of the three cardinal pathological features of SSc, such as autoimmunity/inflammation, vasculopathy and tissue fibrosis. Since B cell- and myeloid cell-specific Fli1 knockout mice strictly recapitulated the three pathological features, these results suggest that B cells and myeloid cells play a central role in the development of SSc and the other cell types contribute to the induction of SSc clinical phenotype.

  8. The generation of a new animal model of systemic sclerosis by focusing on environmental factors

    Sato Shinichi, Asano Yoshihide

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: The University of Tokyo

    2014/04/01 - 2016/03/31

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    Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by three cardinal pathological features, including immune abnormalities/inflammation, vasculopathy, and fibrosis. Although the pathogenesis of SSc still remains unknown, it is generally accepted that environmental factors play a critical role in the development of this disease in genetically predisposed individuals. In SSc dermal fibroblasts, two transcription factors, Fli1 and KLF5, are epigenetically suppressed, suggesting that the downregulation of these molecules is likely to be predisposing factors of SSc. Of note, mice with heterozygous deletion of Fli1 and Klf5 spontaneously developed the three cardinal pathological features of SSc, strictly recapitulating the sequential pathological process (initiating with immune abnormalities, followed by vasculopathy, and eventually resulting in tissue fibrosis). Further studies with this murine model would provide a useful clue to understand SSc pathogenesis.

  9. The role of transcription factor Fli1 in macrophage polarization in patients with systemic sclerosis

    Asano Yoshihide

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: The University of Tokyo

    2013/04/01 - 2016/03/31

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    Systemic sclerosis (SSc) is characterized by three pathological features, including immune abnormalities/inflammation, vasculopathy, and fibrosis. A series of our studies demonstrated that Fli1 deficiency contributes to the development of vasculopathy and fibrosis of SSc, but the role of Fli1 deficiency in immune abnormalities/inflammation still remains unknown. Therefore, to address this issue, we here investigated the impact of Fli1 deficiency on myeloid cells. Our results demonstrated the following findings: (i) Fli1 deficiency promotes the differentiation of macrophages into M2 subtype, (ii) myeloid cell-specific Fli1 knockout (Fli1 MyeKO) mice spontaneously develop dermal fibrosis due to endothelial-to-mesenchyaml transition following initial vascular changes, (iii) Fli1 MyeKO mice exhibit Th2/Th17-skewed immune polarization. Taken together, these results indicate that myeloid Fli1 deficiency is involved in the development of the three cardinal pathological features of SSc.

  10. The establishment of animal models of systemic sclerosis based on Fli1 deficiency

    Sato Shinichi, ASANO Yoshihide, KADONO Takafumi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: The University of Tokyo

    2013/04/01 - 2016/03/31

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    Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by initial vascular injury and resultant tissue fibrosis with autoimmune background. In addition to autoantibody production, B cells have been shown to be directly involved in the development of SSc. Since our studies have proved a critical role of Fli1 deficiency in the induction of SSc-like phenotypes in dermal fibroblasts, endothelial cells, and macrophages, we here investigated the role of Fli1-deficeint B cells in SSc pathogenesis. When we generated B cell-specific Fli1 knockout mice (Fli1flox/flox;Cd19-Cre+/-), B cells were abnormally activated and these mice spontaneously developed vascular changes resembling SSc vasculopathy, subsequently exhibiting tissue fibrosis of the skin and lung. These results indicate that Fli1 deficiency induces SSc-like phenotypes in B cells as well as other cell types, integrating the expression of fibrosis-related gene programs into the development of SSc.

  11. A new animal model of systemic sclerosis

    SATO Shinichi, ASANO Yoshihide

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: The University of Tokyo

    2012/04/01 - 2014/03/31

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    To assess the contribution of anti-DNA topoisomerase I(anti-topo I)antibody, tissue fibrosis and cytokine production were examined in mice treated with topo I and either Freund's complete adjuvant (CFA) or Freund's incomplete adjuvant(IFA). Treatment with topo I and CFA,in contrast to treatment with topo I and IFA,induced skin and lung fibrosis with increased interleukin (IL)-6 and IL-17 production. Anti-topo I antibody levels were greater in mice treated with topo I and CFA than with topo I and IFA.Furthermore,treatment with topo I and CFA increased Th2 and Th17 cell frequencies in bronchoalveolar lavage fluid,whereas treatment with topo I and IFA increased Th1 and Treg cell frequencies.Moreover,loss of IL-6 expression ameliorated skin and lung fibrosis and decreased Th2 and Th17 cell frequencies. This study shows that treatment with topo I and CFA induces SSc-like tissue fibrosis and autoimmunity.

  12. The role of endothelin in the pathogenesis of vasculopathy associated with systemic sclerosis

    ASANO Yoshihide

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: The University of Tokyo

    2011 - 2012

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    Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by initial vascular injuries and resultant fibrosis of skin and certain internal organs. Although the pathogenesis of SSc still remains unknown, recent studies have demonstrated that endothelins play a crucial role in the development of vasculopathy and fibrosis associated with SSc. Consistently, we recently showed that Fli1 deficiency is closely linked to the activation of fibroblasts and endothelial cells in SSc and a dual endothelin receptor antagonist, bosentan, reverses the pro-fibrotic phenotype of SSc dermal fibroblasts by increasing the transcriptional activity of Fli1. Based on these findings, we herein investigated the impact of bosentan on SSc vasculopathy using endothelia cell-specific Fli1 knockout mice, which mimic the morphological and functional abnormalities of SSc vasculopathy. A series of studies revealed that bosentan reverses Fli1 deficiency-dependent vasculopathy in these mice by increasing transcriptional activity of Fli1, suggesting that a similar mechanism potentially underpins the clinical efficacy of bosentan for SSc vasculopathy.

  13. The significance of constitutive downregulation of Fli1 gene expression in the pathogenesis of dermal fibrosis and vasculopathy in systemic sclerosis

    ASANO Yoshihide

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: The University of Tokyo

    2009 - 2010

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    Previous reports demonstrated that constitutive downregulation of Fli1 gene largely contributes to the activation of dermal fibroblasts and dermal microvascular endothelial cells in systemic sclerosis, leading to the development of dermal fibrosis and vasculopathy in this disease. Our current study revealed that one of the possible targets by which endothelin receptor actagonist prevents the development of new digital ulcers in SSc is transcription factor Fli1 and that constitutive downregulation of this transcription factor is associated with the delayed wound healing in this disease.

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