Details of the Researcher

PHOTO

Naoya Fujino
Section
Tohoku University Hospital
Job title
Senior Assistant Professor
Degree

  • 博士（医学）（東北大学）

Research History 9

  • 2020/07 - Present
    東北大学病院　呼吸器内科　院内講師

  • 2017/04 - 2020/06
    Tohoku University Hospital　Department of Respiratory Medicine　Assistant Professor

  • 2016/12 - 2017/03
    Miyagi Cardiovascular and Respiratory Center　Department of Respiratory Medicine　Senior Head Physician

  • 2016/06 - 2016/11
    Tohoku University Hospital　Department of Respiratory Medicine　Assistant Professor

  • 2016/04 - 2016/05
    Tohoku University Hospital　Department of Respiratory Medicine　Clinical fellow

  • 2014/09 - 2016/03
    University of Manchester　MCCIR　Research associate

  • 2013/07 - 2014/08
    AstraZeneca AB　Postdoctoral fellow

  • 2012/04 - 2013/06
    Tohoku University Graduate School of Medicine　Postdoctoral fellow

  • 2004/04 - 2007/09
    Japanese Red Cross Ishinomaki Hospital　Resident

Show all Show first 5

Education 2

  • Tohoku University Graduate School of Medicine

    2007/10 - 2012/03

  • Tohoku University　School of Medicine

    1998/04 - 2004/03

Research Interests 5

  • Immunology

  • Allergy

  • Inflammation and repair

  • Tissue stem cells

  • Respiratory medicine

Research Areas 1

  • Life sciences / Respiratory medicine /

Awards 4

  1. The best poster prize. British Pharmacological Society James Black Meeting - Inspired Biologics 2014.

    2014

  2. International Session Award. The 52th Annual Meeting of The Japanese Respiratory Society

    2012

  3. The President’s Award. Tohoku University

    2012

  4. Distinguished Presentation Award of the 83th Obstructive Lung Disease Research Meeting

    2012

Papers 90

  1. Histological and genetic features and therapeutic responses of lung cancers explored via the global analysis of their metabolome profile. International-journal

    Daisuke Narita, Eiji Hishinuma, Risa Ebina-Shibuya, Eisaku Miyauchi, Naomi Matsukawa, Ikuko N Motoike, Kengo Kinoshita, Seizo Koshiba, Yoko Tsukita, Hirotsugu Notsuda, Nozomu Kimura, Ryota Saito, Koji Murakami, Naoya Fujino, Tomohiro Ichikawa, Mitsuhiro Yamada, Tsutomu Tamada, Hisatoshi Sugiura

    Lung cancer (Amsterdam, Netherlands)　200　108082-108082　2025/02

    DOI： 10.1016/j.lungcan.2025.108082 　

    More details Close

    BACKGROUND: Lung cancer is the deadliest disease globally, with more than 120,000 diagnosed cases and more than 75,000 deaths annually in Japan. Several treatment options for advanced lung cancer are available, and the discovery of biomarkers will be useful for personalized medicine. Using metabolome analysis, we aimed to identify biomarkers for diagnosis and treatment response by examining the changes in metabolites associated with lung cancer progression. METHODS: Plasma samples from patients with recurrent or metastatic non-small cell lung carcinomas diagnosed at Tohoku University Hospital between 2019 and 2024 were used in this study. Metabolomic analysis was performed using the Biocrates Life Sciences MxP Quant 500 kit. Multivariate, principal component, and orthogonal partial least squares discriminant analyses were performed. RESULTS: The triglyceride and phosphatidylcholine concentrations were higher in the patients with early than in those with advanced lung adenocarcinomas. However, the cholesterol ester concentrations were higher for the patients with advanced lung cancer. The concentrations of hexosylceramide were higher in patients with early lung adenocarcinoma than in those with squamous cell carcinoma. Relative to epidermal growth factor receptor (EGFR)-mutation negative cases, the EGFR-mutation positive cases showed marked differences between the ceramide and triglyceride concentrations. For the best therapeutic effect of EGFR-TKI treatment, the hexosylceramide (HexCer) (d18:1/24:0), ceramide (Cer) (d18:2/22:0), and ceramide (Cer) (d18:2/24:0) concentrations were higher for the stable and progressive disease groups. The concentrations of phosphatidylcholine (PC) ae C42:2, sphingomyelin (SM) C24:1, and lysophosphatidylcholine (lysoPC) a C18:2 were higher in the partial response group treated with immune checkpoint inhibitors and chemotherapy. CONCLUSION: Metabolomic analysis may be useful for the diagnosis and treatment of lung cancer and may provide clues for new therapeutic strategies. PC ae C42:2, SM C24:1, and lysoPC a C18:2 can serve as predictive biomarkers for monitoring the therapeutic effects of the combination of immune checkpoint inhibitors and chemotherapy.

  2. Human Lung Cell Separation Strategies for Translational Research

    Naoya Fujino, Mitsuhiro Yamada, Takuya Saito, Shuichi Konno, Hisatoshi Sugiura

    American Journal of Respiratory Cell and Molecular Biology　71　(5)　621-622　2024/11

    DOI： 10.1165/rcmb.2024-0338LE 　

    ISSN： 1044-1549

    eISSN： 1535-4989

  3. Characterization of IL-6R-expressing monocytes in the lung of patients with chronic obstructive pulmonary disease. International-journal

    Yoshinao Ono, Naoya Fujino, Takuya Saito, Shuichiro Matsumoto, Shuichi Konno, Takuto Endo, Manami Suzuki, Mitsuhiro Yamada, Yoshinori Okada, Hisatoshi Sugiura

    Respiratory investigation　62　(5)　856-866　2024/09

    DOI： 10.1016/j.resinv.2024.07.013 　

    More details Close

    BACKGROUND: Monocytes play a crucial role in innate immune responses for host defense, however, their involvement in chronic obstructive pulmonary disease (COPD) remains poorly understood. We previously identified a subset of monocytes in COPD lung tissues characterized by high interleukin-6 receptor (IL-6R) expression. This study aimed to characterize the phenotypes of IL-6Rhi monocytes in the lungs of COPD patients. METHODS: Using flow cytometry, we assessed the abundance of pulmonary CD14+IL-6Rhi cells in never smokers (CNS), control ex-smokers (CES) and COPD patients. IL-6 expression in CD14+ monocytes isolated from the peripheral blood of patients with COPD was also examined. CD45+CD206-CD14+IL-6Rhi and CD45+CD206-CD14+IL-6R-/lo cells were isolated from COPD lung tissues for transcriptome analysis. A monocyte line THP1 cell with constitutive IL-6R expression was stimulated with recombinant IL-6, followed by RNA sequencing to evaluate the IL-6 responsiveness of IL-6R+ monocytes. RESULTS: The number of pulmonary CD14+IL-6Rhi monocytes was elevated in COPD patients compared to CNS, whereas CD14+ monocytes in the peripheral blood of COPD patients did not express IL-6R. Upregulated mRNA expression in CD14+IL-6Rhi monocytes was associated with chemotaxis, monocyte differentiation, fatty acid metabolism and integrin-mediated signaling pathway. Stimulation of THP1 cells with recombinant IL-6 induced changes in the expression of genes linked to chemotaxis and organism development. CONCLUSION: In patients with COPD, CD14+IL-6Rhi monocytes are increased in lung tissues compared to those in CNS. They exhibit a transcriptome profile different from that of CD14+IL-6R-/lo monocytes.

  4. Clinical characteristics related to improved lung function with biologics in patients with severe asthma(タイトル和訳中)

    Matsumoto Shuichiro, Kamide Yosuke, Fujino Naoya, Yamada Mitsuhiro, Ono Yoshinao, Kobayashi Seiichi, Sato Teruyuki, Sekiya Kiyoshi, Endo Takuto, Tamada Tsutomu, Ichikawa Tomohiro, Aizawa Hiroyuki, Sano Hirohito, Kyogoku Yorihiko, Saito Takuya, Konno Shuichi, Suzuki Manami, Taniguchi Masami, Sugiura Hisatoshi

    アレルギー　73　(6-7)　752-752　2024/08

    Publisher: (一社)日本アレルギー学会

    ISSN： 0021-4884

    eISSN： 1347-7935

  5. Fractional exhaled nitric oxide distribution and its relevant factors in the general adult population and its healthy subpopulation. International-journal

    Mitsuhiro Yamada, Masato Takase, Kumi Nakaya, Tomohiro Nakamura, Mana Kogure, Naoki Nakaya, Naoya Fujino, Tsutomu Tamada, Chikashi Iwasaki, Manami Suzuki, Shuichiro Matsumoto, Nobuo Fuse, Akira Uruno, Kazuki Kumada, Soichi Ogishima, Shinichi Kuriyama, Masakazu Ichinose, Hisatoshi Sugiura, Atsushi Hozawa

    The journal of allergy and clinical immunology. Global　3　(3)　100253-100253　2024/08

    DOI： 10.1016/j.jacig.2024.100253 　

    More details Close

    BACKGROUND: Measurement of fractional exhaled nitric oxide (Feno) has been used in the diagnosis and management of asthma. Understanding the distribution of Feno in a larger resident population and its "healthy" subpopulation would contribute to the interpretation of Feno in clinical practice. OBJECTIVE: This study aimed to investigate the distribution and its associated factors in the adult population and its healthy subpopulations. METHODS: We conducted a cross-sectional study of 8,638 men and 17,288 women aged 20 years or older living in Miyagi prefecture, Japan. We investigated the distribution of Feno and its associated factors in all subjects, a subpopulation with no history of upper and lower airway diseases (healthy subpopulation 1), and a subpopulation with no history of upper and lower airway diseases, normal lung function, and no positivity for other biomarkers of type 2 inflammation (healthy subpopulation 2). RESULTS: The distribution of Feno in healthy subpopulations, especially in healthy subpopulation 2 (median [interquartile range], 17 [12-23] with 95th percentile of 36 ppb) was lower than in all subjects (19 [13-26] ppb with 95th percentile of 47 ppb). In healthy subpopulation 1, 10.3% had elevated Feno (≥35 ppb), and elevated Feno was positively associated with factors including obstructive ventilatory defect, blood eosinophilia, house dust mite-specific IgE positivity, and history of hypertension. Male sex was associated with elevated Feno in all subjects and healthy subpopulations. CONCLUSION: The distribution of Feno in the healthy subpopulation supports the validity of the criteria (≥35 ppb) currently used in Japan for the diagnosis of asthma.

  6. Identification of Siglec-1-negative alveolar macrophages with proinflammatory phenotypes in chronic obstructive pulmonary disease. International-journal

    Takuya Saito, Naoya Fujino, Yorihiko Kyogoku, Mitsuhiro Yamada, Koji Okutomo, Yoshinao Ono, Shuichi Konno, Takuto Endo, Koji Itakura, Shuichiro Matsumoto, Hirohito Sano, Hiroyuki Aizawa, Tadahisa Numakura, Katsuhiro Onodera, Yoshinori Okada, Tracy Hussell, Masakazu Ichinose, Hisatoshi Sugiura

    American journal of physiology. Lung cellular and molecular physiology　326　(6)　L672-L686　2024/06/01

    DOI： 10.1152/ajplung.00303.2023 　

    More details Close

    Alveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD) orchestrate persistent inflammation in the airway. However, subpopulations of AMs participating in chronic inflammation have been poorly characterized. We previously reported that Siglec-1 expression on AMs, which is important for bacteria engulfment, was decreased in COPD. Here, we show that Siglec-1-negative AMs isolated from COPD lung tissues exhibit a proinflammatory phenotype and are associated with poor clinical outcomes in patients with COPD. Using flow cytometry, we segregated three subsets of AMs based on the expression of Siglec-1 and their side scattergram (SSC) and forward scattergram (FSC) properties: Siglec-1+SSChiFSChi, Siglec-1-SSChiFSChi, and Siglec-1-SSCloFSClo subsets. The Siglec-1-SSCloFSClo subset number was increased in COPD. RNA sequencing revealed upregulation of multiple proinflammatory signaling pathways and emphysema-associated matrix metalloproteases in the Siglec-1-SSCloFSClo subset. Gene set enrichment analysis indicated that the Siglec-1-SSCloFSClo subset adopted intermediate phenotypes between monocytes and mature alveolar macrophages. Functionally, these cells produced TNF-α, IL-6, and IL-8 at baseline, and these cytokines were significantly increased in response to viral RNA. The increase in Siglec-1-negative AMs in induced sputum is associated with future exacerbation risk and lung function decline in patients with COPD. Collectively, the novel Siglec-1-SSCloFSClo subset of AMs displays proinflammatory properties, and their emergence in COPD airways may be associated with poor clinical outcomes.NEW & NOTEWORTHY Alveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD) orchestrate persistent inflammation in the airway. We find that Siglec-1-negative alveolar macrophages have a wide range of proinflammatory landscapes and a protease-expressing phenotype. Moreover, this subset is associated with the pathogenesis of COPD and responds to viral stimuli.

  7. Peripheral blood biomarkers associated with combination of immune checkpoint blockade plus chemotherapy in NSCLC. International-journal

    Nozomu Kimura, Yoko Tsukita, Risa Ebina-Shibuya, Eisaku Miyauchi, Mitsuhiro Yamada, Daisuke Narita, Ryota Saito, Chihiro Inoue, Naoya Fujino, Tomohiro Ichikawa, Tsutomu Tamada, Hisatoshi Sugiura

    Cancer biomarkers : section A of Disease markers　2024/03/20

    DOI： 10.3233/CBM-230301 　

    More details Close

    BACKGROUND: Biomarkers predicting clinical outcomes of treating non-small cell lung cancer (NSCLC) with combination of immune checkpoint inhibitors (ICIs) and chemotherapy would be valuable. OBJECTIVE: This study aims to seek predictors of combination of ICI/chemotherapy response in NSCLC patients using peripheral blood samples. METHODS: Patients diagnosed with advanced NSCLC between July 2019 and May 2021 receiving combination of ICI/chemotherapy were included and assessed for partial responses (PR), stable disease (SD) or progressive disease (PD). We measured circulating immune cells, plasma cytokines and chemokines. RESULTS: Nineteen patients were enrolled. The proportions of circulating natural killer (NK) cells within CD45 + cells, programmed death 1 (PD-1) + Tim-3 + T cells within CD4 + cells, and the amount of chemokine C-X-C ligand (CXCL10) in the plasma were significantly elevated in PR relative to SD/PD patients (median 8.1%-vs-2.1%, P= 0.0032; median 1.2%-vs-0.3%, P= 0.0050; and median 122.6 pg/ml-vs-76.0 pg/ml, P= 0.0125, respectively). Patients with 2 or 3 elevated factors had longer progression-free survival than patients with 0 or only one (not reached-vs-5.6 months, P= 0.0002). CONCLUSIONS: We conclude that NK cells, CD4 + PD-1 + Tim-3 + T cells, and CXCL10 levels in pre-treatment peripheral blood may predict the efficacy of combination of ICI/chemotherapy in NSCLC.

  8. 1細胞RNAシークエンスを用いたCOPD肺胞マクロファージにおける炎症性サブセットの同定

    齋藤 拓矢, 藤野 直也, 今野 周一, 小野 祥直, 遠藤 卓人, 松本 周一郎, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　13　(増刊)　165-165　2024/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  9. COPD 病因 COPD患者におけるCCR5+Siglec-1-肺胞マクロファージの増加は重症度と関連する

    今野 周一, 藤野 直也, 齋藤 拓矢, 小野 祥直, 遠藤 卓人, 松本 周一郎, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　13　(増刊)　177-177　2024/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  10. 慢性閉塞性肺疾患におけるGZMK陽性CD8+T細胞の役割解明

    松本 周一郎, 沼倉 忠久, 山田 充啓, 藤野 直也, 鈴木 眞奈美, 京極 自彦, 市川 朋宏, 玉田 勉, 杉浦 久敏

    日本呼吸器学会誌　13　(増刊)　229-229　2024/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  11. COPD肺由来IL6Rhi CD14+CD206-単核球細胞(IL6Rhi p-Mono)におけるIL6誘導性遺伝子の推定

    小野 祥直, 藤野 直也, 齋藤 拓矢, 今野 周一, 遠藤 卓人, 松本 周一郎, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　13　(増刊)　229-229　2024/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  12. 気道上皮においてAxl発現低下はアレルゲン誘導性NF-κBシグナル応答を促進する

    遠藤 卓人, 藤野 直也, 板倉 康司, 齋藤 拓矢, 小野 祥直, 今野 周一, 松本 周一郎, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　13　(増刊)　363-363　2024/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  13. 喘息 病因・病態 コントロール不良既喫煙喘息患者の末梢血CD161+制御性T細胞はTh17細胞様の表現型を有する

    京極 自彦, 藤野 直也, 松本 周一郎, 小野 祥直, 山田 充啓, 相澤 洋之, 市川 朋宏, 玉田 勉, 杉浦 久敏

    日本呼吸器学会誌　13　(増刊)　183-183　2024/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  14. Acquisition of Amikacin Resistance during Amikacin Liposome Inhalation Suspension Add-on Therapy for Mycobacterium avium Complex-Pulmonary Disease. International-journal

    Hirohito Sano, Naoya Fujino, Tadahisa Numakura, Mitsuhiro Yamada, Naoki Tode, Hisatoshi Sugiura

    Annals of the American Thoracic Society　2024/01/29

    DOI： 10.1513/AnnalsATS.202305-454RL 　

  15. [CURRENT STATUS OF SCHOOL LUNCHES RELATED TO FOOD ALLERGY AND UNMET NEEDS OF TEACHERS IN MIYAGI PREFECTURE].

    Satoshi Horino, Ayahumi Ozaki, Yuki Yamaguchi, Hiroki Miyabayashi, Haruka Aki, Hiroyuki Aizawa, Naoya Fujino, Hisatoshi Sugiura, Katsushi Miura

    Arerugi = [Allergy]　73　(5)　399-405　2024

    DOI： 10.15036/arerugi.73.399 　

    More details Close

    BACKGROUND: The number of students with food allergies is on the increase, while the problems and burdens of school teachers and staff are not yet clear. Our study was designed to identify the unmet needs of school teachers and staff dealing with food allergy in school lunches. METHODS: A written questionnaire was sent by mail to 600 elementary and junior high schools in Miyagi Prefecture. RESULTS: Responses were received from 169 schools. The prevalence of food allergy was 5.6% and the EpiPen possession rate was 0.36%. The most common problems perceived by teachers and staff were the "increase in the number of students with food allergies" and the "diversification of causative foods". Other problems included "uncertainty of foods to be removed" and "insufficient collaboration among teachers, guardians, and doctors," which could be improved by the medical providers. In the free descriptions, many respondents complained of an excessive workload and the mental burden of never making a mistake or missing anything. CONCLUSION: Our survey revealed that while there is a public demand for safe school lunches, the teachers and staff dealing with this demand are under considerable strain. It is necessary to consider reducing the burden, and a sustainable system needs to be established.

  16. 宮城県の食物アレルギーに関わる教職員の現状とアンメットニーズ

    堀野 智史, 尾崎 理史, 山口 祐樹, 宮林 広樹, 秋 はるか, 相澤 洋之, 藤野 直也, 杉浦 久敏, 三浦 克志

    日本小児アレルギー学会誌　37　(4)　359-359　2023/10

    Publisher: (一社)日本小児アレルギー学会

    ISSN： 0914-2649

    eISSN： 1882-2738

  17. CYP27A1-27-hydroxycholesterol axis in the respiratory system contributes to house dust mite-induced allergic airway inflammation. International-journal

    Tatsunori Ito, Tomohiro Ichikawa, Mitsuhiro Yamada, Yuichiro Hashimoto, Naoya Fujino, Tadahisa Numakura, Yusaku Sasaki, Ayumi Suzuki, Katsuya Takita, Hirohito Sano, Yorihiko Kyogoku, Takuya Saito, Akira Koarai, Tsutomu Tamada, Hisatoshi Sugiura

    Allergology international : official journal of the Japanese Society of Allergology　2023/08/20

    DOI： 10.1016/j.alit.2023.08.005 　

    More details Close

    BACKGROUND: 27-Hydroxycholesterol (27-HC) derived from sterol 27-hydroxylase (CYP27A1) has pro-inflammatory biological activity and is associated with oxidative stress and chronic inflammation in COPD. However, the role of regulation of CYP27A1- 27-HC axis in asthma is unclear. This study aimed to elucidate the contribution of the axis to the pathophysiology of asthma. METHODS: House dust mite (HDM) extract was intranasally administered to C57BL/6 mice and the expression of CYP27A1 in the airways was analyzed by immunostaining. The effect of pre-treatment with PBS or CYP27A1 inhibitors on the cell fraction in the bronchoalveolar lavage fluid (BALF) was analyzed in the murine model. In vitro, BEAS-2B cells were treated with HDM and the levels of CYP27A1 expression were examined. Furthermore, the effect of 27-HC on the expressions of E-cadherin and ZO-1 in the cells was analyzed. The amounts of RANTES and eotaxin from the 27-HC-treated cells were analyzed by ELISA. RESULTS: The administration of HDM increased the expression of CYP27A1 in the airways of mice as well as the number of eosinophils in the BALF. CYP27A1 inhibitors ameliorated the HDM-induced increase in the number of eosinophils in the BALF. Treatment with HDM increased the expression of CYP27A1 in BEAS-2B cells. The administration of 27-HC to BEAS-2B cells suppressed the expression of E-cadherin and ZO-1, and augmented the production of RANTES and eotaxin. CONCLUSIONS: The results of this study suggest that aeroallergen could enhance the induction of CYP27A1, leading to allergic airway inflammation and disruption of the airway epithelial tight junction through 27-HC production.

  18. A Case of IgA Vasculitis During Atezolizumab Treatment.

    Yoshinao Ono, Yoko Tsukita, Naoya Fujino, Hisatoshi Sugiura

    Internal medicine (Tokyo, Japan)　2023/08/02

    DOI： 10.2169/internalmedicine.2343-23 　

  19. 気管支喘息(成人):病態生理 喘息におけるCD161+制御性T細胞のトランスクリプトーム解析

    京極 自彦, 藤野 直也, 松本 周一郎, 小野 祥直, 佐野 寛仁, 遠藤 卓人, 今野 周一, 鈴木 眞奈美, 齋藤 拓矢, 相澤 洋之, 市川 朋宏, 山田 充啓, 玉田 勉, 杉浦 久敏

    アレルギー　72　(6-7)　866-866　2023/08

    Publisher: (一社)日本アレルギー学会

    ISSN： 0021-4884

    eISSN： 1347-7935

  20. 喘息の多様性と寛解 生物学的製剤による重症喘息のremissionに関するreal-world evidence

    松本 周一郎, 上出 庸介, 藤野 直也, 山田 充啓, 小野 祥直, 小林 誠一, 佐藤 輝幸, 関谷 潔史, 遠藤 卓人, 玉田 勉, 市川 朋宏, 小荒井 晃, 相澤 洋之, 佐野 寛仁, 京極 自彦, 齋藤 拓矢, 今野 周一, 鈴木 眞奈美, 杉浦 久敏

    アレルギー　72　(6-7)　884-884　2023/08

    Publisher: (一社)日本アレルギー学会

    ISSN： 0021-4884

    eISSN： 1347-7935

  21. Supersulphides provide airway protection in viral and chronic lung diseases. International-journal

    Tetsuro Matsunaga, Hirohito Sano, Katsuya Takita, Masanobu Morita, Shun Yamanaka, Tomohiro Ichikawa, Tadahisa Numakura, Tomoaki Ida, Minkyung Jung, Seiryo Ogata, Sunghyeon Yoon, Naoya Fujino, Yorihiko Kyogoku, Yusaku Sasaki, Akira Koarai, Tsutomu Tamada, Atsuhiko Toyama, Takakazu Nakabayashi, Lisa Kageyama, Shigeru Kyuwa, Kenji Inaba, Satoshi Watanabe, Péter Nagy, Tomohiro Sawa, Hiroyuki Oshiumi, Masakazu Ichinose, Mitsuhiro Yamada, Hisatoshi Sugiura, Fan-Yan Wei, Hozumi Motohashi, Takaaki Akaike

    Nature communications　14　(1)　4476-4476　2023/07/25

    DOI： 10.1038/s41467-023-40182-4 　

    More details Close

    Supersulphides are inorganic and organic sulphides with sulphur catenation with diverse physiological functions. Their synthesis is mainly mediated by mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulphide synthase (CPERS). Here, we identify protective functions of supersulphides in viral airway infections (influenza and COVID-19), in aged lungs and in chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF). We develop a method for breath supersulphur-omics and demonstrate that levels of exhaled supersulphides increase in people with COVID-19 infection and in a hamster model of SARS-CoV-2 infection. Lung damage and subsequent lethality that result from oxidative stress and inflammation in mouse models of COPD, IPF, and ageing were mitigated by endogenous supersulphides production by CARS2/CPERS or exogenous administration of the supersulphide donor glutathione trisulphide. We revealed a protective role of supersulphides in airways with various viral or chronic insults and demonstrated the potential of targeting supersulphides in lung disease.

  22. Associations between birth weight and lung function in a Japanese adult population: The tohoku medical megabank community-based cohort study. International-journal

    Takashi Ohe, Mitsuhiro Yamada, Atsushi Hozawa, Naoki Nakaya, Tomohiro Nakamura, Naho Tsuchiya, Akira Narita, Mana Kogure, Nobuo Fuse, Shinichi Kuriyama, Ayumi Mitsune, Ayumi Suzuki, Shuichiro Matsumoto, Tetsuya Hatakeyama, Chikashi Iwasaki, Manami Suzuki, Naoya Fujino, Tadahisa Numakura, Tomohiro Ichikawa, Akira Koarai, Tsutomu Tamada, Masayuki Yamamoto, Masakazu Ichinose, Hisatoshi Sugiura

    Respiratory investigation　61　(5)　588-600　2023/07/08

    DOI： 10.1016/j.resinv.2023.06.004 　

    More details Close

    BACKGROUND: Birth weight, as a measure of intrauterine growth, is commonly used in epidemiological studies and is reported to be associated with adult lung function. However, findings regarding this association in previous studies have been inconsistent. Furthermore, no studies have reported associations stratified by age or smoking status, or adjusted for eosinophil count or other parameters related to type 2 airway inflammation. METHODS: This cross-sectional study included 2632 men and 7237 women aged ≥20 years living in Miyagi Prefecture, Japan. Lung function was assessed based on spirometry. Birth weight data were obtained through a questionnaire survey. Analysis of covariance was used to evaluate the associations between birth weight and lung function, adjusting for potential confounders. Stratified analyses by age and smoking status were also conducted, together with a sub-analysis for low birth-weight participants. RESULTS: Birth weight was positively associated with forced expiratory volume in 1 s (FEV1) for both sexes and with vital capacity in women, after adjusting for height, age, smoking status, and parameters related to type 2 airway inflammation. The stratified analysis for smoking status revealed associations in never-smokers and ex-smokers. When stratified by age, the associations were confirmed in middle-aged participants. The effect of smoking status on the FEV1 of low birth-weight participants was not significant. CONCLUSIONS: Our analysis of a large, Japanese adult population showed that birth weight was independently and positively associated with adult lung function, even after adjustment for age, height, smoking status, and parameters related to type 2 airway inflammation.

  23. COPD 基礎 慢性閉塞性肺疾患における末梢血GZMK陽性免疫細胞の役割解明

    松本 周一郎, 沼倉 忠久, 山田 充啓, 藤野 直也, 市川 朋宏, 小荒井 晃, 玉田 勉, 杉浦 久敏

    日本呼吸器学会誌　12　(増刊)　158-158　2023/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  24. COPD 基礎 COPDの臨床病態におけるSiglec-1-肺胞マクロファージの機能解明

    藤野 直也, 齋藤 拓矢, 小野 祥直, 京極 自彦, 今野 周一, 遠藤 卓人, 松本 周一郎, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　12　(増刊)　158-158　2023/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  25. COPD 基礎 COPD肺組織におけるIL-6受容体高発現単球の同定

    小野 祥直, 藤野 直也, 齋藤 拓矢, 遠藤 卓人, 今野 周一, 松本 周一郎, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　12　(増刊)　158-158　2023/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  26. 宮城県内におけるアレルギー疾患医療実態調査

    相澤 洋之, 藤野 直也, 松本 周一郎, 佐野 寛仁, 齋藤 拓矢, 畠山 哲八, 京極 自彦, 市川 朋宏, 小荒井 晃, 堀野 智史, 三浦 克志, 杉浦 久敏

    アレルギー　72　(1)　26-36　2023/02

    Publisher: (一社)日本アレルギー学会

    ISSN： 0021-4884

    eISSN： 1347-7935

  27. 宮城県内におけるアレルギー疾患医療実態調査

    相澤 洋之, 藤野 直也, 松本 周一郎, 佐野 寛仁, 齋藤 拓矢, 畠山 哲八, 京極 自彦, 市川 朋宏, 小荒井 晃, 堀野 智史, 三浦 克志, 杉浦 久敏

    アレルギー　72　(1)　26-36　2023/02

    Publisher: (一社)日本アレルギー学会

    ISSN： 0021-4884

    eISSN： 1347-7935

  28. [A SURVEY ON MEDICAL CARE FOR ALLERGIC DISEASES IN MIYAGI].

    Hiroyuki Aizawa, Naoya Fujino, Shuichiro Matsumoto, Hirohito Sano, Takuya Saito, Tetsuya Hatakeyama, Yorihiko Kyogoku, Tomohiro Ichikawa, Akira Koarai, Satoshi Horino, Katsushi Miura, Hisatoshi Sugiura

    Arerugi = [Allergy]　72　(1)　26-36　2023

    DOI： 10.15036/arerugi.72.26 　

    More details Close

    OBJECTIVE: In Miyagi, the number of allergy specialists per population is higher at Sendai city compared to the other areas (non-Sendai areas). Therefore, the healthcare delivery for allergic diseases are unevenly distributed. In the current study, we investigated differences of medical care for allergic diseases between Sendai city and non-Sendai areas. METHODS: We conducted a web-based questionnaire survey to all of hospitals and clinics in the prefecture. The questionnaire responses were analyzed and compared between the Sendai city and non-Sendai areas. RESULTS: Responses to the questionnaire were obtained from 175 hospitals and clinics, including 72 internal physicians, 34 pediatricians, 17 dermatologists, 15 otorhinolaryngologists, 12 ophthalmologists and 25 others. More clinicians in non-Sendai areas felt the difficulty in treating asthma and chronic urticaria than those in Sendai city. Fewer institutions prescribed biologics for severe allergic diseases in non-Sendai areas than in Sendai city, which might be due to the lack of knowledge on the biologic agents. On the other hand, referring patients with anaphylaxis to specialized hospitals tended to be more difficult in Sendai city compared to in non-Sendai areas. Additionally, the regional medical liaison system is needed to refer patients with severe allergic diseases to advanced medical institutions. CONCLUSION: There are unique problems about allergy care in Miyagi.

  29. 今月の症例 肉芽腫を越えて肺胞腔への進展を示したコクシジオイデス症の1例

    佐野 寛仁, 藤野 直也, 齊藤 涼子, 山田 充啓, 玉田 勉, 齋藤 拓矢, 伊藤 辰徳, 亀井 克彦, 杉浦 久敏

    日本内科学会雑誌　111　(7)　1422-1427　2022/07

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

    eISSN： 1883-2083

  30. 今月の症例 肉芽腫を越えて肺胞腔への進展を示したコクシジオイデス症の1例

    佐野 寛仁, 藤野 直也, 齊藤 涼子, 山田 充啓, 玉田 勉, 齋藤 拓矢, 伊藤 辰徳, 亀井 克彦, 杉浦 久敏

    日本内科学会雑誌　111　(7)　1422-1427　2022/07

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

    eISSN： 1883-2083

  31. Decreased expression of airway epithelial Axl is associated with eosinophilic inflammation in severe asthma. International-journal

    Koji Itakura, Naoya Fujino, Yosuke Kamide, Ikuo Saito, Mitsuhiro Yamada, Koji Okutomo, Yoko Tsukita, Takuya Saito, Tomohiro Ichikawa, Tadahisa Numakura, Yorihiko Kyogoku, Hiroyuki Aizawa, Yoshinao Ono, Shuichiro Matsumoto, Tracy Hussell, Masami Taniguchi, Masakazu Ichinose, Hisatoshi Sugiura

    Allergology international : official journal of the Japanese Society of Allergology　71　(3)　383-394　2022/07

    DOI： 10.1016/j.alit.2022.02.010 　

    More details Close

    BACKGROUND: Airway epithelium-derived cytokines are critical to provoke and perpetuate type 2 inflammation in asthma. Yet it is poorly understood how this epithelial cell-driven inflammatory response is negatively regulated. We previously reported that Axl receptor tyrosine kinase was expressed by basal cells in the airway epithelium and had a role in defining their stem cell identity. However, whether and how Axl regulates airway type 2 inflammation remains unknown. METHODS: We performed immunofluorescence staining to compare Axl expression in airway epithelium between non-asthmatic subjects, mild-moderate asthma and severe asthma. We confirmed this result by interrogating public databases of global gene expression in endobronchial biopsies. We then quantified eosinophil numbers infiltrating into the trachea of wild-type or Axl-knockout mice that were intranasally treated with house dust mite extracts (HDM). Cell-based assays using siRNA targeting Axl were further performed to identify molecules involved in Axl-mediated regulation of inflammation. RESULTS: Histological assessments and transcriptome analyses revealed decreases in protein and mRNA of Axl in airway basal cells of severe asthmatics. This reduction of Axl expression was correlated with infiltration of eosinophils and mast cells in severe asthmatics. Eosinophil infiltration was more evident in the trachea of Axl-knockout mice in response to repetitive HDM administration. siRNA-mediated knockdown of Axl increased mRNA and protein expression of granulocyte macrophage-colony stimulating factor (GM-CSF) in human bronchial epithelial cells. CONCLUSIONS: Axl kinase expressed by basal cells may suppress excessive eosinophilic inflammation via inhibition of GM-CSF in the airway. Axl reduction has clinical implications for the pathogenesis of severe asthma.

  32. 【COPDと気管支喘息、その周辺疾患-病態・診断・治療の最新動向-】COPD診断へのアプローチ COPDにおける併存症総論

    藤野 直也, 杉浦 久敏

    日本臨床　80　(増刊6 COPDと気管支喘息,その周辺疾患)　246-251　2022/06

    Publisher: (株)日本臨床社

    ISSN： 0047-1852

  33. dsDNA刺激誘導性インターフェロン産生に与えるタバコ煙の影響の検討

    相澤 洋之, 小荒井 晃, 沼倉 忠久, 市川 朋宏, 藤野 直也, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　11　(増刊)　129-129　2022/04

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  34. 【喘息の発症メカニズムと治療・管理】診断と治療・管理 成人喘息の診断・管理のためのバイオマーカー

    藤野 直也, 杉浦 久敏

    医学のあゆみ　281　(1)　75-78　2022/04

    Publisher: 医歯薬出版(株)

    ISSN： 0039-2359

  35. dsDNA刺激誘導性インターフェロン産生に与えるタバコ煙の影響の検討

    相澤 洋之, 小荒井 晃, 沼倉 忠久, 市川 朋宏, 藤野 直也, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　11　(増刊)　129-129　2022/04

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  36. Genetic loci for lung function in Japanese adults with adjustment for exhaled nitric oxide levels as airway inflammation indicator. International-journal

    Mitsuhiro Yamada, Ikuko N Motoike, Kaname Kojima, Nobuo Fuse, Atsushi Hozawa, Shinichi Kuriyama, Fumiki Katsuoka, Shu Tadaka, Matsuyuki Shirota, Miyuki Sakurai, Tomohiro Nakamura, Yohei Hamanaka, Kichiya Suzuki, Junichi Sugawara, Soichi Ogishima, Akira Uruno, Eiichi N Kodama, Naoya Fujino, Tadahisa Numakura, Tomohiro Ichikawa, Ayumi Mitsune, Takashi Ohe, Kengo Kinoshita, Masakazu Ichinose, Hisatoshi Sugiura, Masayuki Yamamoto

    Communications biology　4　(1)　1288-1288　2021/11/15

    DOI： 10.1038/s42003-021-02813-8 　

    More details Close

    Lung function reflects the ability of the respiratory system and is utilized for the assessment of respiratory diseases. Because type 2 airway inflammation influences lung function, genome wide association studies (GWAS) for lung function would be improved by adjustment with an indicator of the inflammation. Here, we performed a GWAS for lung function with adjustment for exhaled nitric oxide (FeNO) levels in two independent Japanese populations. Our GWAS with genotype imputations revealed that the RNF5/AGER locus including AGER rs2070600 SNP, which introduces a G82S substitution of AGER, was the most significantly associated with FEV1/FVC. Three other rare missense variants of AGER were further identified. We also found genetic loci with three candidate genes (NOS2, SPSB2 and RIPOR2) associated with FeNO levels. Analyses with the BioBank-Japan GWAS resource revealed genetic links of FeNO and asthma-related traits, and existence of common genetic background for allergic diseases and their biomarkers. Our study identified the genetic locus most strongly associated with airway obstruction in the Japanese population and three genetic loci associated with FeNO, an indicator of type 2 airway inflammation in adults.

  37. Increased LHX9 expression in alveolar epithelial type 2 cells of patients with chronic obstructive pulmonary disease. International-journal

    Koji Okutomo, Naoya Fujino, Mitsuhiro Yamada, Takuya Saito, Yoshinao Ono, Yoshinori Okada, Masakazu Ichinose, Hisatoshi Sugiura

    Respiratory investigation　60　(1)　119-128　2021/09/18

    DOI： 10.1016/j.resinv.2021.08.007 　

    More details Close

    BACKGROUND: Alveolar epithelial type 2 (AT2) cells serve as stem cells in alveolar epithelium and are assumed to lose their stem cell function in the lungs of chronic obstructive pulmonary disease (COPD). Although we previously reported that LHX9 mRNA expression was up-regulated in AT2 cells of COPD lung tissues, it is yet to be elucidated how LHX9 is associated with the vulnerability of AT2 cells in COPD. METHODS: AT2 cells were isolated from lung tissues of 10 non-COPD subjects and 11 COPD patients. LHX9 mRNA expression was determined by quantitative RT-PCR. To identify up-stream molecules, an alveolar epithelial cell line A549 was exposed to pro-inflammatory cytokines in vitro. siRNA-mediated Lhx9 knockdown was performed to determine how Lhx9 affected the cellular viability and the cell-division cycle. RESULTS: LHX9 mRNA expression was increased in AT2 cells from COPD lung tissues, compared to those from non-COPD tissues. The airflow obstruction was independently correlated with the increase in LHX9 expression. Among several pro-inflammatory cytokines, interferon-γ was a strong inducer of LHX9 expression in A549 cells. Lhx9 was involved in the increased susceptibility to serum starvation-induced death of A549 cells. CONCLUSIONS: Our data suggest that IFN-γ predominantly increases the LHX9 expression which enhances the susceptibility to cell death. Considering the independent association of the increased LHX9 expression in AT2 cells with airflow obstruction, the IFN-γ-Lhx9 axis might contribute to the vulnerability of AT2 cells in the lungs of COPD patients.

  38. Upregulation of leukocyte immunoglobulin-like receptor B4 on interstitial macrophages in COPD; their possible protective role against emphysema formation. International-journal

    Ayumi Mitsune, Mitsuhiro Yamada, Naoya Fujino, Tadahisa Numakura, Tomohiro Ichikawa, Ayumi Suzuki, Shuichiro Matsumoto, Yoshiya Mitsuhashi, Koji Itakura, Tomonori Makiguchi, Akira Koarai, Tsutomu Tamada, Shota Endo, Toshiyuki Takai, Yoshinori Okada, Satoshi Suzuki, Masakazu Ichinose, Hisatoshi Sugiura

    Respiratory research　22　(1)　232-232　2021/08/23

    DOI： 10.1186/s12931-021-01828-3 　

    More details Close

    BACKGROUND: Leukocyte immunoglobulin-like receptor B4 (LILRB4) is one of the inhibitory receptors in various types of immune cells including macrophages. Previous reports suggested that LILRB4 could be involved in a negative feedback system to prevent excessive inflammatory responses. However, its role has been unclear in chronic obstructive pulmonary disease (COPD), in which macrophages play a crucial role in the pathogenesis. In this study, we aimed to examine the changes of LILRB4 on macrophages both in the lung specimens of COPD patients and the lungs of a mouse emphysema model. We then tried to compare the differences in both inflammation and emphysematous changes of the model between wild-type and LILRB4-deficient mice in order to elucidate the role of LILRB4 in the pathogenesis of COPD. METHODS: We prepared single-cell suspensions of resected lung specimens of never-smokers (n = 21), non-COPD smokers (n = 16), and COPD patients (n = 14). The identification of LILRB4-expressing cells and the level of LILRB4 expression were evaluated by flow cytometry. We analyzed the relationships between the LILRB4 expression and clinical characteristics including respiratory function. In the experiments using an elastase-induced mouse model of emphysema, we also analyzed the LILRB4 expression on lung macrophages. We compared inflammatory cell accumulation and emphysematous changes induced by elastase instillation between wild-type and LILRB4-deficient mice. RESULTS: The levels of surface expression of LILRB4 are relatively high on monocyte linage cells including macrophages in the human lungs. The percentage of LILRB4+ cells in lung interstitial macrophages was increased in COPD patients compared to non-COPD smokers (p = 0.018) and correlated with the severity of emphysematous lesions detected by CT scan (rs = 0.559, p < 0.001), whereas the amount of smoking showed no correlation with LILRB4 expression. Increased LILRB4 on interstitial macrophages was also observed in elastase-treated mice (p = 0.008). LILRB4-deficient mice showed severer emphysematous lesions with increased MMP-12 expression in the model. CONCLUSIONS: LILRB4 on interstitial macrophages was upregulated both in human COPD lungs and in a mouse model of emphysema. This upregulated LILRB4 may have a protective effect against emphysema formation, possibly through decreasing MMP-12 expression in the lungs.

  39. Triple versus LAMA/LABA combination therapy for Japanese patients with COPD: A systematic review and meta-analysis

    Akira Koarai, Mitsuhiro Yamada, Tomohiro Ichikawa, Naoya Fujino, Tomotaka Kawayama, Hisatoshi Sugiura

    Respiratory Investigation　2021/06

    Publisher: Elsevier BV

    DOI： 10.1016/j.resinv.2021.04.007 　

    ISSN： 2212-5345

  40. ACO (Asthma–COPD Overlap) Is Independent from COPD, a Case in Favor: A Systematic Review

    Naoya Fujino, Hisatoshi Sugiura

    Diagnostics　11　(5)　859-859　2021/05/11

    Publisher: MDPI AG

    DOI： 10.3390/diagnostics11050859 　

    eISSN： 2075-4418

    More details Close

    Asthma and chronic obstructive pulmonary disease (COPD) are now recognized to be able to co-exist as asthma–COPD overlap (ACO). It is clinically relevant to evaluate whether patients with COPD concurrently have components of asthma in primary care. This is because: (i) ACO is a relatively common condition among asthma (over 40 years of age) or COPD irrespective of its diagnosis criteria; (ii) patients with ACO can have higher frequency of exacerbation and more rapid decline in lung function than those with asthma or COPD; and (iii) asthmatic features such as eosinophilic airway inflammation are promising indicators for prediction of inhaled corticosteroid-responsiveness in COPD. The aim of this review to evaluate diagnostic markers for ACO. We searched PubMed for articles related to ACO published until 2020. Articles associated with diagnostic biomarkers were included. We identified a total of 25 studies, some of which have revealed that a combination of biomarkers such as fractional exhaled nitric oxide and serum immunoglobulin E is useful to discern type 2 inflammation in the airways of COPD. Here, we review the current understanding of the clinical characteristics, biomarkers and molecular pathophysiology of ACO in the context of how ACO can be differentiated from COPD.

  41. 酸化ストレスのdsDNA刺激誘導性インターフェロン産生に与える影響の検討

    小荒井 晃, 宍倉 裕, 相澤 洋之, 沼倉 忠久, 市川 朋宏, 藤野 直也, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　10　(増刊)　167-167　2021/04

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  42. COPD増悪病態とレチノイン酸経路の関与の検討

    相澤 洋之, 小荒井 晃, 宍倉 裕, 沼倉 忠久, 藤野 直也, 市川 朋宏, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　10　(増刊)　250-250　2021/04

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  43. PGC-1α regulates airway epithelial barrier dysfunction induced by house dust mite. International-journal

    Tsutomu Saito, Tomohiro Ichikawa, Tadahisa Numakura, Mitsuhiro Yamada, Akira Koarai, Naoya Fujino, Koji Murakami, Shun Yamanaka, Yusaku Sasaki, Yorihiko Kyogoku, Koji Itakura, Hirohito Sano, Katsuya Takita, Rie Tanaka, Tsutomu Tamada, Masakazu Ichinose, Hisatoshi Sugiura

    Respiratory research　22　(1)　63-63　2021/02/19

    DOI： 10.1186/s12931-021-01663-6 　

    More details Close

    BACKGROUND: The airway epithelial barrier function is disrupted in the airways of asthmatic patients. Abnormal mitochondrial biogenesis is reportedly involved in the pathogenesis of asthma. However, the role of mitochondrial biogenesis in the airway barrier dysfunction has not been elucidated yet. This study aimed to clarify whether the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a central regulator of mitochondrial biogenesis, is involved in the disruption of the airway barrier function induced by aeroallergens. METHODS: BEAS-2B cells were exposed to house dust mite (HDM) and the expressions of PGC-1α and E-cadherin, a junctional protein, were examined by immunoblotting. The effect of SRT1720, a PGC-1α activator, was investigated by immunoblotting, immunocytochemistry, and measuring the transepithelial electrical resistance (TEER) on the HDM-induced reduction in mitochondrial biogenesis markers and junctional proteins in airway bronchial epithelial cells. Furthermore,the effects of protease activated receptor 2 (PAR2) inhibitor, GB83, Toll-like receptor 4 (TLR4) inhibitor, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), protease inhibitors including E64 and 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) on the HDM-induced barrier dysfunction were investigated. RESULTS: The amounts of PGC-1α and E-cadherin in the HDM-treated cells were significantly decreased compared to the vehicle-treated cells. SRT1720 restored the expressions of PGC-1α and E-cadherin reduced by HDM in BEAS-2B cells. Treatment with SRT1720 also significantly ameliorated the HDM-induced reduction in TEER. In addition, GB83, LPS-RS, E64 and AEBSF prevented the HDM-induced reduction in the expression of PGC1α and E-cadherin. CONCLUSIONS: The current study demonstrated that HDM disrupted the airway barrier function through the PAR2/TLR4/PGC-1α-dependent pathway. The modulation of this pathway could be a new approach for the treatment of asthma.

  44. Longitudinal Relationship Between Growth Differentiation Factor 11 and Physical Activity in Chronic Obstructive Pulmonary Disease. International-journal

    Rie Tanaka, Akira Koarai, Mitsuhiro Yamada, Naoya Fujino, Tomohiro Ichikawa, Tadahisa Numakura, Katsuhiro Onodera, Yorihiko Kyogoku, Tsutomu Tamada, Motohiko Miura, Yoshiaki Minakata, Masakazu Ichinose, Hisatoshi Sugiura

    International journal of chronic obstructive pulmonary disease　16　999-1006　2021

    DOI： 10.2147/COPD.S301690 　

    More details Close

    Background: Daily physical activity is reduced in patients with chronic obstructive pulmonary disease (COPD) and a reduced level of physical activity has been shown to be an important predictor for the prognosis, such as increased risk of exacerbation and mortality. However, there has not yet been a useful biomarker of the physical activity. In our previous cross-sectional study, we showed that the level of one of the possible myokines, which is an anti-aging factor, growth differentiation factor 11 (GDF11), was decreased in the plasma from patients with COPD and correlated with the physical activity. To clarify this relationship, we conducted a longitudinal evaluation of such factors. Patients and Methods: Twenty-four COPD patients were enrolled and prospectively followed. We measured the levels of plasma GDF11 and systemic inflammatory markers with immunoblotting or ELISA, respectively. We also evaluated lung function and daily physical activity using a triaxial accelerometer and the incidence of exacerbation. Results: The change in the plasma level of GDF11, but not systemic inflammatory markers, was positively correlated with the change in the physical activity in an intensity-dependent manner (between the change in the number of steps and GDF11; r = 0.41, p = 0.047). In the multiple regression analysis, the relationship was confirmed (β = 0.93, p < 0.001). In addition, patients who maintained their plasma level of GDF11 showed a significantly lower incidence in exacerbations of COPD than those with decreased levels of GDF11 (p = 0.041). Conclusion: The longitudinal change in the plasma level of GDF11 was positively correlated with the change in the daily physical activity in COPD. GDF11 could be a useful humoral factor that reflects the physical activity in COPD.

  45. Negative heart signを呈した肺サルコイドーシスの1例

    鈴木 歩, 藤野 直也, 平野 泰三, 村上 康司, 玉田 勉, 杉浦 久敏

    日本呼吸器学会誌　10　(1)　78-82　2021/01

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  46. 【長期処方時代の薬物療法を支える薬剤師になるための慢性疾患治療薬の使い分けと患者モニタリング】COPD Doctor's Eye

    藤野 直也, 杉浦 久敏

    調剤と情報　26　(15)　2664-2669　2020/11

    Publisher: (株)じほう

    ISSN： 1341-5212

  47. Treatment with LABA versus LAMA for stable COPD: A systematic review and meta-analysis

    Akira Koarai, Hisatoshi Sugiura, Mitsuhiro Yamada, Tomohiro Ichikawa, Naoya Fujino, Tomotaka Kawayama, Masakazu Ichinose

    BMC Pulmonary Medicine　20　(1)　2020/04

    DOI： 10.1186/s12890-020-1152-8 　

    eISSN： 1471-2466

  48. 注目の新薬 ビレーズトリエアロスフィア(ブデソニド/グリコピロニウム臭化物/ホルモテロールフマル酸塩水和物製剤)

    藤野 直也, 杉浦 久敏

    診断と治療　108　(2)　263-266　2020/02

    Publisher: (株)診断と治療社

    ISSN： 0370-999X

  49. Decreased expression of a phagocytic receptor Siglec-1 on alveolar macrophages in chronic obstructive pulmonary disease Peer-reviewed

    Atsushi Tanno, Naoya Fujino, Mitsuhiro Yamada, Hisatoshi Sugiura, Taizou Hirano, Rie Tanaka, Hirohito Sano, Satoshi Suzuki, Yoshinori Okada, Masakazu Ichinose

    Respiratory Research　21　(1)　2020/01/28

    DOI： 10.1186/s12931-020-1297-2 　

    ISSN： 1465-9921

    eISSN： 1465-993X

  50. Improving the viability of tissue-resident stem cells using an organ-preservation solution Peer-reviewed

    Takaya Suzuki, Chiharu Ota, Naoya Fujino, Yukiko Tando, Satoshi Suzuki, Mitsuhiro Yamada, Takashi Kondo, Yoshinori Okada, Hiroshi Kubo

    FEBS Open Bio　9　(12)　2093-2104　2019/12/01

    DOI： 10.1002/2211-5463.12748 　

    eISSN： 2211-5463

  51. Nitrosative stress in patients with asthma–chronic obstructive pulmonary disease overlap Peer-reviewed

    Yorihiko Kyogoku, Hisatoshi Sugiura, Tomohiro Ichikawa, Tadahisa Numakura, Akira Koarai, Mitsuhiro Yamada, Naoya Fujino, Yutaka Tojo, Katsuhiro Onodera, Rie Tanaka, Kei Sato, Hirohito Sano, Shun Yamanaka, Koji Itakura, Ayumi Mitsune, Tsutomu Tamada, Takaaki Akaike, Masakazu Ichinose

    Journal of Allergy and Clinical Immunology　144　(4)　972-983.e14　2019/10

    DOI： 10.1016/j.jaci.2019.04.023 　

    ISSN： 0091-6749

    eISSN： 1097-6825

  52. Increase in circulating ACE-positive endothelial microparticles during acute lung injury Peer-reviewed

    Yusuke Takei, Mitsuhiro Yamada, Koji Saito, Yoshinobu Kameyama, Hisatoshi Sugiura, Tomonori Makiguchi, Naoya Fujino, Akira Koarai, Hiroaki Toyama, Kazutomo Saito, Yutaka Ejima, Yu Kawazoe, Daisuke Kudo, Shigeki Kushimoto, Masanori Yamauchi, Masakazu Ichinose

    The European respiratory journal　54　(4)　2019/10/01

    DOI： 10.1183/13993003.01188-2018 　

    ISSN： 0903-1936

    eISSN： 1399-3003

  53. Sensing of apoptotic cells through Axl causes lung basal cell proliferation in inflammatory diseases Peer-reviewed

    Naoya Fujino, Oliver J. Brand, David J. Morgan, Toshifumi Fujimori, Aleksander M. Grabiec, Christopher P. Jagger, Rose A. Maciewicz, Mitsuhiro Yamada, Koji Itakura, Hisatoshi Sugiura, Masakazu Ichinose, Tracy Hussell

    Journal of Experimental Medicine　216　(9)　2184-2201　2019/09/01

    DOI： 10.1084/jem.20171978 　

    ISSN： 0022-1007

    eISSN： 1540-9538

  54. Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas Peer-reviewed

    Yoko Tsukita, Naoya Fujino, Eisaku Miyauchi, Ryoko Saito, Fumiyoshi Fujishima, Koji Itakura, Yorihiko Kyogoku, Koji Okutomo, Mitsuhiro Yamada, Tatsuma Okazaki, Hisatoshi Sugiura, Akira Inoue, Yoshinori Okada, Masakazu Ichinose

    Molecular Cancer　18　(1)　24　2019/02/11

    DOI： 10.1186/s12943-019-0953-y 　

    eISSN： 1476-4598

  55. Pulmonary Lymphatic Perfusion Syndrome. International-journal Peer-reviewed

    Hirano T, Fujino N, Takase K, Ota H, Tanaka R, Saito R, Suzuki A, Okutomo K, Sato T, Kageyama S, Tamada T, Sugiura H, Ichinose M

    American journal of respiratory and critical care medicine　199　(4)　529-530　2018/09

    DOI： 10.1164/rccm.201806-1125IM 　

    ISSN： 1073-449X

  56. Correction: Oxidative stress enhances the expression of IL-33 in human airway epithelial cells. [Respir Res., 19, (2018) (52)] DOI: 10.1186/s12931-018-0752-9 Peer-reviewed

    Hiroyuki Aizawa, Akira Koarai, Yutaka Shishikura, Satoru Yanagisawa, Mutsuo Yamaya, Hisatoshi Sugiura, Tadahisa Numakura, Mitsuhiro Yamada, Tomohiro Ichikawa, Naoya Fujino, Masafumi Noda, Yoshinori Okada, Masakazu Ichinose

    Respiratory Research　19　(1)　2018/06/12

    DOI： 10.1186/s12931-018-0817-9 　

    ISSN： 1465-9921

    eISSN： 1465-993X

  57. Expression of cytochrome P450 mRNAs in Type II alveolar cells from subjects with chronic obstructive pulmonary disease Peer-reviewed

    Satoshi Kamata, Naoya Fujino, Mitsuhiro Yamada, Ken Grime, Satoshi Suzuki, Chiharu Ota, Yukiko Tando, Yoshinori Okada, Akira Sakurada, Masafumi Noda, Yasushi Matsuda, Hisatoshi Sugiura, Masakazu Ichinose

    Pharmacology Research and Perspectives　6　(3)　e00405　2018/06

    DOI： 10.1002/prp2.405 　

    eISSN： 2052-1707

  58. Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease Peer-reviewed

    Rie Tanaka, Hisatoshi Sugiura, Mitsuhiro Yamada, Tomohiro Ichikawa, Akira Koarai, Naoya Fujino, Satoru Yanagisawa, Katsuhiro Onodera, Tadahisa Numakura, Kei Sato, Yorihiko Kyogoku, Hirohito Sano, Shun Yamanaka, Tatsuma Okazaki, Tsutomu Tamada, Motohiko Miura, Tsuneyuki Takahashi, Masakazu Ichinose

    International Journal of COPD　13　1333-1342　2018/04

    DOI： 10.2147/COPD.S157035 　

    ISSN： 1176-9106

    eISSN： 1178-2005

  59. Oxidative stress enhances the expression of IL-33 in human airway epithelial cells Peer-reviewed

    Hiroyuki Aizawa, Akira Koarai, Yutaka Shishikura, Satoru Yanagisawa, Mutsuo Yamaya, Hisatoshi Sugiura, Tadahisa Numakura, Mitsuhiro Yamada, Tomohiro Ichikawa, Naoya Fujino, Masafumi Noda, Yoshinori Okada, Masakazu Ichinose

    Respiratory Research　19　(1)　52　2018/03/27

    DOI： 10.1186/s12931-018-0752-9 　

    ISSN： 1465-9921

    eISSN： 1465-993X

  60. Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease Peer-reviewed

    Rie Tanaka, Hisatoshi Sugiura, Mitsuhiro Yamada, Tomohiro Ichikawa, Akira Koarai, Naoya Fujino, Satoru Yanagisawa, Katsuhiro Onodera, Tadahisa Numakura, Kei Sato, Yorihiko Kyogoku, Hirohito Sano, Shun Yamanaka, Tatsuma Okazaki, Tsutomu Tamada, Motohiko Miura, Tsuneyuki Takahashi, Masakazu Ichinose

    INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE　13　1333-1342　2018

    DOI： 10.2147/COPD.S157035 　

    ISSN： 1178-2005

  61. Production of reactive persulfide species in chronic obstructive pulmonary disease Peer-reviewed

    Tadahisa Numakura, Hisatoshi Sugiura, Takaaki Akaike, Tomoaki Ida, Shigemoto Fujii, Akira Koarai, Mitsuhiro Yamada, Katsuhiro Onodera, Yuichiro Hashimoto, Rie Tanaka, Kei Sato, Yutaka Shishikura, Taizou Hirano, Satoru Yanagisawa, Naoya Fujino, Tatsuma Okazaki, Tsutomu Tamada, Yasushi Hoshikawa, Yoshinori Okada, Masakazu Ichinose

    THORAX　72　(12)　1074-1083　2017/12

    DOI： 10.1136/thoraxjnl-2016-209359 　

    ISSN： 0040-6376

    eISSN： 1468-3296

  62. Diminished airway macrophage expression of the Axl receptor tyrosine kinase is associated with defective efferocytosis in asthma Peer-reviewed

    Aleksander M. Grabiec, Nicholas Denny, John A. Doherty, Kaisa E. Happonen, Jenny Hankinson, Emma Connolly, Mark E. Fife, Toshifumi Fujimori, Naoya Fujino, Anu Goenka, Susan Holden, Gael Tavernier, Rajesh Shah, Peter C. Cook, Andrew S. MacDonald, Robert M. Niven, Bjorn Dahlback, Stephen J. Fowler, Angela Simpson, Tracy Hussell

    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY　140　(4)　1144-+　2017/10

    DOI： 10.1016/j.jaci.2017.03.024 　

    ISSN： 0091-6749

    eISSN： 1097-6825

  63. Decrease in an anti-ageing factor, growth differentiation factor 11, in chronic obstructive pulmonary disease Peer-reviewed

    Katsuhiro Onodera, Hisatoshi Sugiura, Mitsuhiro Yamada, Akira Koarai, Naoya Fujino, Satoru Yanagisawa, Rie Tanaka, Tadahisa Numakura, Shinsaku Togo, Kei Sato, Yorihiko Kyogoku, Yuichiro Hashimoto, Tatsuma Okazaki, Tsutomu Tamada, Seiichi Kobayashi, Masaru Yanai, Motohiko Miura, Yasushi Hoshikawa, Yoshinori Okada, Satoshi Suzuki, Masakazu Ichinose

    THORAX　72　(10)　893-904　2017/10

    DOI： 10.1136/thoraxjnl-2016-209352 　

    ISSN： 0040-6376

    eISSN： 1468-3296

  64. Phenotypic screening identifies Axl kinase as a negative regulator of an alveolar epithelial cell phenotype Peer-reviewed

    Naoya Fujino, Hiroshi Kubo, Rose A. Maciewicz

    LABORATORY INVESTIGATION　97　(9)　1047-1062　2017/09

    DOI： 10.1038/labinvest.2017.52 　

    ISSN： 0023-6837

    eISSN： 1530-0307

  65. Serum extracellular vesicular miR-21-5p is a predictor of the prognosis in idiopathic pulmonary fibrosis Peer-reviewed

    Tomonori Makiguchi, Mitsuhiro Yamada, Yusuke Yoshioka, Hisatoshi Sugiura, Akira Koarai, Shigeki Chiba, Naoya Fujino, Yutaka Tojo, Chiharu Ota, Hiroshi Kubo, Seiichi Kobayashi, Masaru Yanai, Sanae Shimura, Takahiro Ochiya, Masakazu Ichinose

    Respiratory Research　17　(1)　110　2016/09/05

    DOI： 10.1186/s12931-016-0427-3 　

    ISSN： 1465-9921

    eISSN： 1465-993X

  66. Serum extracellular vesicular miR-21-5p is a predictor of the prognosis in idiopathic pulmonary fibrosis Peer-reviewed

    Tomonori Makiguchi, Mitsuhiro Yamada, Yusuke Yoshioka, Hisatoshi Sugiura, Akira Koarai, Shigeki Chiba, Naoya Fujino, Yutaka Tojo, Chiharu Ota, Hiroshi Kubo, Seiichi Kobayashi, Masaru Yanai, Sanae Shimura, Takahiro Ochiya, Masakazu Ichinose

    RESPIRATORY RESEARCH　17　2016/09

    DOI： 10.1186/s12931-016-0427-3 　

    ISSN： 1465-993X

    eISSN： 1465-9921

  67. Isolation of individual cellular components from lung tissues of patients with lymphangioleiomyomatosis Peer-reviewed

    Katsutoshi Ando, Naoya Fujino, Keiko Mitani, Chiharu Ota, Yoshinori Okada, Takashi Kondo, Teruaki Mizobuchi, Masatoshi Kurihara, Kenji Suzuki, Yoshito Hoshika, Hiroki Ebana, Etsuko Kobayashi, Kazuhisa Takahashi, Hiroshi Kubo, Kuniaki Seyama

    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY　310　(10)　L899-L908　2016/05

    DOI： 10.1152/ajplung.00365.2015 　

    ISSN： 1040-0605

    eISSN： 1522-1504

  68. Inflammatory responses in the initiation of lung repair and regeneration: Their role in stimulating lung resident stem cells Peer-reviewed

    Mitsuhiro Yamada, Naoya Fujino, Masakazu Ichinose

    Inflammation and Regeneration　36　(1)　15　2016

    DOI： 10.1186/s41232-016-0020-7 　

    ISSN： 1880-9693

    eISSN： 1880-8190

  69. The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung Peer-reviewed

    T. Fujimori, A. M. Grabiec, M. Kaur, T. J. Bell, N. Fujino, P. C. Cook, F. R. Svedberg, A. S. MacDonald, R. A. Maciewicz, D. Singh, T. Hussell

    MUCOSAL IMMUNOLOGY　8　(5)　1021-1030　2015/09

    DOI： 10.1038/mi.2014.129 　

    ISSN： 1933-0219

    eISSN： 1935-3456

  70. Histone deacetylase inhibitor restores surfactant protein-C expression in alveolar-epithelial type II cells and attenuates bleomycin-induced pulmonary fibrosis in vivo Peer-reviewed

    Chiharu Ota, Mitsuhiro Yamada, Naoya Fujino, Hozumi Motohashi, Yukiko Tando, Yusuke Takei, Takaya Suzuki, Toru Takahashi, Satoshi Kamata, Tomonori Makiguchi, Mutsuo Yamaya, Hiroshi Kubo

    EXPERIMENTAL LUNG RESEARCH　41　(8)　422-434　2015/09

    DOI： 10.3109/01902148.2015.1060275 　

    ISSN： 0190-2148

    eISSN： 1521-0499

  71. c-Kit immunoexpression delineates a putative endothelial progenitor cell population in developing human lungs Peer-reviewed

    Takaya Suzuki, Satoshi Suzuki, Naoya Fujino, Chiharu Ota, Mitsuhiro Yamada, Takashi Suzuki, Mutsuo Yamaya, Takashi Kondo, Hiroshi Kubo

    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY　306　(9)　L855-L865　2014/05

    DOI： 10.1152/ajplung.00211.2013 　

    ISSN： 1040-0605

    eISSN： 1522-1504

  72. Annual FEV1 changes and numbers of circulating endothelial microparticles in patients with COPD: a prospective study Peer-reviewed

    Toru Takahashi, Seiichi Kobayashi, Naoya Fujino, Takaya Suzuki, Chiharu Ota, Yukiko Tando, Mitsuhiro Yamada, Masaru Yanai, Mutsuo Yamaya, Shin Kurosawa, Masanori Yamauchi, Hiroshi Kubo

    BMJ OPEN　4　(3)　e004571　2014

    DOI： 10.1136/bmjopen-2013-004571 　

    ISSN： 2044-6055

  73. The increase of microRNA-21 during lung fibrosis and its contribution to epithelial-mesenchymal transition in pulmonary epithelial cells Peer-reviewed

    Mitsuhiro Yamada, Hiroshi Kubo, Chiharu Ota, Toru Takahashi, Yukiko Tando, Takaya Suzuki, Naoya Fujino, Tomonori Makiguchi, Kiyoshi Takagi, Takashi Suzuki, Masakazu Ichinose

    Respiratory Research　14　(1)　95　2013/09/24

    DOI： 10.1186/1465-9921-14-95 　

    ISSN： 1465-9921

    eISSN： 1465-993X

  74. The increase of microRNA-21 during lung fibrosis and its contribution to epithelial-mesenchymal transition in pulmonary epithelial cells Peer-reviewed

    Mitsuhiro Yamada, Hiroshi Kubo, Chiharu Ota, Toru Takahashi, Yukiko Tando, Takaya Suzuki, Naoya Fujino, Tomonori Makiguchi, Kiyoshi Takagi, Takashi Suzuki, Masakazu Ichinose

    RESPIRATORY RESEARCH　14　2013/09

    DOI： 10.1186/1465-9921-14-95 　

    ISSN： 1465-993X

    eISSN： 1465-9921

  75. Differences in the released endothelial microparticle subtypes between human pulmonary microvascular endothelial cells and aortic endothelial cells in vitro Peer-reviewed

    Toru Takahashi, Seiichi Kobayashi, Naoya Fujino, Takaya Suzuki, Chiharu Ota, Yukiko Tando, Mei He, Mitsuhiro Yamada, Shin Kurosawa, Mutsuo Yamaya, Hiroshi Kubo

    EXPERIMENTAL LUNG RESEARCH　39　(4-5)　155-161　2013/05

    DOI： 10.3109/01902148.2013.784932 　

    ISSN： 0190-2148

    eISSN： 1521-0499

  76. Increased Severity of 2009 Pandemic Influenza A Virus Subtype H1N1 Infection in Alveolar Type II Cells From Patients With Pulmonary Fibrosis Peer-reviewed

    Naoya Fujino, Hiroshi Kubo, Chiharu Ota, Takaya Suzuki, Toru Takahashi, Mitsuhiro Yamada, Satoshi Suzuki, Takashi Kondo, Ryouichi Nagatomi, Yukiko Tando, Mutsuo Yamaya

    JOURNAL OF INFECTIOUS DISEASES　207　(4)　692-693　2013/02

    DOI： 10.1093/infdis/jis739 　

    ISSN： 0022-1899

  77. Increased circulating endothelial microparticles in COPD patients: a potential biomarker for COPD exacerbation susceptibility Peer-reviewed

    Toru Takahashi, Seiichi Kobayashi, Naoya Fujino, Takaya Suzuki, Chiharu Ota, Mei He, Mitsuhiro Yamada, Satoshi Suzuki, Masaru Yanai, Shin Kurosawa, Mutsuo Yamaya, Hiroshi Kubo

    THORAX　67　(12)　1067-1074　2012/12

    DOI： 10.1136/thoraxjnl-2011-201395 　

    ISSN： 0040-6376

  78. Surgical stress increases circulating endothelial microparticles in the elderly Peer-reviewed

    T. Takahashi, H. Kim, N. Fujino, T. Suzuki, C. Ota, M. Yamada, M. Yamaya, S. Suzuki, S. Kurosawa

    ANAESTHESIA AND INTENSIVE CARE　40　(5)　899-902　2012/09

    ISSN： 0310-057X

  79. Analysis of gene expression profiles in alveolar epithelial type II-like cells differentiated from human alveolar epithelial progenitor cells Peer-reviewed

    Naoya Fujino, Chiharu Ota, Takaya Suzuki, Satoshi Suzuki, Ahmed E. Hegab, Mitsuhiro Yamada, Toru Takahashi, Mei He, Takashi Kondo, Hidemasa Kato, Mutsuo Yamaya, Hiroshi Kubo

    Respiratory Investigation　50　(3)　110-116　2012/09

    DOI： 10.1016/j.resinv.2012.07.002 　

    ISSN： 2212-5345

  80. A Novel Method for Isolating Individual Cellular Components from the Adult Human Distal Lung Peer-reviewed

    Naoya Fujino, Hiroshi Kubo, Chiharu Ota, Takaya Suzuki, Satoshi Suzuki, Mitsuhiro Yamada, Toru Takahashi, Mei He, Takashi Suzuki, Takashi Kondo, Mutsuo Yamaya

    AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY　46　(4)　422-430　2012/04

    DOI： 10.1165/rcmb.2011-0172OC 　

    ISSN： 1044-1549

  81. Administration of a specific inhibitor of neutrophil elastase attenuates pulmonary fibrosis after acute lung injury in mice Peer-reviewed

    Naoya Fujino, Hiroshi Kubo, Tomoko Suzuki, Mei He, Takaya Suzuki, Mitsuhiro Yamada, Toru Takahashi, Chiharu Ota, Mutsuo Yamaya

    EXPERIMENTAL LUNG RESEARCH　38　(1)　28-36　2012/02

    DOI： 10.3109/01902148.2011.633306 　

    ISSN： 0190-2148

  82. Gene expression profiles of alveolar type II cells of chronic obstructive pulmonary disease: a case-control study Peer-reviewed

    Naoya Fujino, Chiharu Ota, Toru Takahashi, Takaya Suzuki, Satoshi Suzuki, Mitsuhiro Yamada, Ryouichi Nagatomi, Takashi Kondo, Mutsuo Yamaya, Hiroshi Kubo

    BMJ OPEN　2　(6)　2012

    DOI： 10.1136/bmjopen-2012-001553 　

    ISSN： 2044-6055

  83. The increase in surface CXCR4 expression on lung extravascular neutrophils and its effects on neutrophils during endotoxin-induced lung injury Peer-reviewed

    Mitsuhiro Yamada, Hiroshi Kubo, Seiichi Kobayashi, Kota Ishizawa, Mei He, Takaya Suzuki, Naoya Fujino, Hiroyuki Kunishima, Masamitsu Hatta, Katsushi Nishimaki, Tetsuji Aoyagi, Kouichi Tokuda, Miho Kitagawa, Hisakazu Yano, Hirokazu Tamamura, Nobutaka Fujii, Mitsuo Kaku

    CELLULAR & MOLECULAR IMMUNOLOGY　8　(4)　305-314　2011/07

    DOI： 10.1038/cmi.2011.8 　

    ISSN： 1672-7681

  84. Receptor for advanced glycation end products binds to phosphatidylserine and assists in the clearance of apoptotic cells Peer-reviewed

    Mei He, Hiroshi Kubo, Konosuke Morimoto, Naoya Fujino, Takaya Suzuki, Toru Takahasi, Mitsuhiro Yamada, Mutsuo Yamaya, Tomoyuki Maekawa, Yasuhiko Yamamoto, Hiroshi Yamamoto

    EMBO REPORTS　12　(4)　358-364　2011/04

    DOI： 10.1038/embor.2011.28 　

    ISSN： 1469-221X

  85. Isolation of alveolar epithelial type II progenitor cells from adult human lungs Peer-reviewed

    Naoya Fujino, Hiroshi Kubo, Takaya Suzuki, Chiharu Ota, Ahmed E. Hegab, Mei He, Satoshi Suzuki, Takashi Suzuki, Mitsuhiro Yamada, Takashi Kondo, Hidemasa Kato, Mutsuo Yamaya

    LABORATORY INVESTIGATION　91　(3)　363-378　2011/03

    DOI： 10.1038/labinvest.2010.187 　

    ISSN： 0023-6837

  86. Inhibitory effects of carbocisteine on type A seasonal influenza virus infection in human airway epithelial cells Peer-reviewed

    Mutsuo Yamaya, Hidekazu Nishimura, Kyoko Shinya, Yukimasa Hatachi, Takahiko Sasaki, Hiroyasu Yasuda, Motoki Yoshida, Masanori Asada, Naoya Fujino, Takaya Suzuki, Xue Deng, Hiroshi Kubo, Ryoichi Nagatomi

    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY　299　(2)　L160-L168　2010/08

    DOI： 10.1152/ajplung.00376.2009 　

    ISSN： 1040-0605

    eISSN： 1522-1504

  87. Isolation and Characterization of Murine Multipotent Lung Stem Cells Peer-reviewed

    Ahmed E. Hegab, Hiroshi Kubo, Naoya Fujino, Takaya Suzuki, Mei He, Hidemasa Kato, Mutsuo Yamaya

    STEM CELLS AND DEVELOPMENT　19　(4)　523-535　2010/04

    DOI： 10.1089/scd.2009.0287 　

    ISSN： 1547-3287

  88. Successful treatment of refractory bronchioloalveolar carcinoma with S-1 (oral fluoropyrimidine) Peer-reviewed

    Seiichi Kobayashi, Naoya Fujino, Satoshi Suzuki, Masaru Yanai

    RESPIROLOGY　14　(5)　771-772　2009/07

    DOI： 10.1111/j.1440-1843.2009.01546.x 　

    ISSN： 1323-7799

  89. Effects of pneumococcal vaccination on hospitalization and exacerbations in elderly Japanese chronic obstructive pulmonary disease patients Peer-reviewed

    Mutsuo Yamaya, Naoya Fujino, Hiroshi Kubo, Hiroyuki Arai

    GERIATRICS & GERONTOLOGY INTERNATIONAL　9　(2)　206-209　2009/06

    DOI： 10.1111/j.1447-0594.2008.00496.x 　

    ISSN： 1444-1586

  90. Intranasal HGF administration ameliorates the physiologic and morphologic changes in lung emphysema Peer-reviewed

    Ahmed E. Hegab, Hiroshi Kubo, Mutsuo Yamaya, Masanori Asada, Mei He, Naoya Fujino, Shinya Mizuno, Toshikazu Nakamura

    MOLECULAR THERAPY　16　(8)　1417-1426　2008/08

    DOI： 10.1038/mt.2008.137 　

    ISSN： 1525-0016

Show all ︎Show first 5

Misc. 91

  1. 重症喘息患者を対象とした全血網羅的遺伝子発現解析;好中球活性化の関与

    鈴木眞奈美, 山田充啓, 藤野直也, 吉良聡, 笠澄望, 元池育子, 元池育子, 上出庸介, 関谷潔史, 小林誠一, 佐藤輝幸, 松本周一郎, 小野祥直, 今野周一, 遠藤卓人, 玉田勉, 谷口正実, 勝岡史城, 木下賢吾, 杉浦久敏

    アレルギー　73　(6/7)　2024

    ISSN： 0021-4884

  2. 食物アレルギー・疫学 宮城県の小・中学校における食物アレルギー対応の実態調査

    尾崎 理史, 堀野 智史, 宇根岡 慧, 山口 祐樹, 秋 はるか, 相澤 洋之, 藤野 直也, 杉浦 久敏, 三浦 克志

    アレルギー　70　(6-7)　797-797　2021/08

    Publisher: (一社)日本アレルギー学会

    ISSN： 0021-4884

    eISSN： 1347-7935

  3. 酸化ストレスのdsDNA刺激誘導性インターフェロン産生に与える影響の検討

    小荒井 晃, 宍倉 裕, 相澤 洋之, 沼倉 忠久, 市川 朋宏, 藤野 直也, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　10　(増刊)　167-167　2021/04

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  4. COPD増悪頻回患者における血清細胞外小胞microRNAの発現プロファイル

    山田 充啓, 牧口 友紀, 藤野 直也, 光根 歩, 小林 誠一, 矢内 勝, 一ノ瀬 正和, 杉浦 久敏

    日本呼吸器学会誌　10　(増刊)　211-211　2021/04

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  5. 慢性閉塞性肺疾患の増悪における肺胞マクロファージのSiglec-1発現低下

    齋藤 拓矢, 藤野 直也, 京極 自彦, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　10　(増刊)　211-211　2021/04

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  6. COPD増悪病態とレチノイン酸経路の関与の検討

    相澤 洋之, 小荒井 晃, 宍倉 裕, 沼倉 忠久, 藤野 直也, 市川 朋宏, 山田 充啓, 杉浦 久敏

    日本呼吸器学会誌　10　(増刊)　250-250　2021/04

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  7. 組織幹細胞保存液の開発とヒト組織への応用

    鈴木隆哉, 大田千晴, 藤野直也, 丹藤由紀子, 山田充啓, 鈴木聡, 岡田克典, 久保裕司

    日本再生医療学会総会(Web)　19th　2020

  8. Reactive sulfur species are involved in cigarette smoke-induced cellular senescence

    Shun Yamanaka, Tomohiro Ichikawa, Hisatoshi Sugiura, Tadahisa Numakura, Hirohito Sano, Mitsuhiro Yamada, Naoya Fujino, Rie Tanaka, Yorihiko Kyogoku, Takaaki Akaike, Masakazu Ichinose

    EUROPEAN RESPIRATORY JOURNAL　54　2019/09

    DOI： 10.1183/13993003.congress-2019.PA4055 　

    ISSN： 0903-1936

    eISSN： 1399-3003

  9. 当院におけるEGFR遺伝子変異陽性非小細胞肺癌に対する再生検の現状 Peer-reviewed

    板倉 康司, 齋藤 良太, 鈴木 歩, 大江 崇, 佐々木 優作, 奥友 洸二, 滝田 克也, 佐野 寛仁, 安藤 正勝, 東條 裕, 牧口 友紀, 藤野 直也, 山田 充啓, 一ノ瀬 正和

    気管支学　41　(Suppl.)　S337-S337　2019/06

    Publisher: (NPO)日本呼吸器内視鏡学会

    ISSN： 0287-2137

    eISSN： 2186-0149

  10. リンパ管造影が有効であったPulmonary lymphatic perfusion syndromeによる難治性乳び胸の一例

    影山 咲子, 大田 英輝, 外山 由貴, 高浪 健太郎, 平野 泰三, 藤野 直也, 一ノ瀬 正和, 高瀬 圭

    日本インターベンショナルラジオロジー学会雑誌　34　(Suppl.)　396-396　2019/05

    Publisher: (一社)日本インターベンショナルラジオロジー学会

    ISSN： 1340-4520

    eISSN： 2185-6451

  11. 敗血症患者血中ACE陽性EMPのARDS発症に対する予測的価値 Peer-reviewed

    山田 充啓, 武井 裕介, 牧口 友紀, 藤野 直也, 杉浦 久敏, 山内 正憲, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　141-141　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  12. 気管支喘息 病態生理 Axl受容体チロシンキナーゼによる重症喘息の好酸球性気道炎症制御機構 Peer-reviewed

    板倉 康司, 藤野 直也, 山田 充啓, 上出 庸介, 齋藤 生朗, 杉浦 久敏, 谷口 正実, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　152-152　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  13. COPD 病態 COPD病態における活性イオウ分子種の役割の検討 Peer-reviewed

    山中 駿, 市川 朋宏, 杉浦 久敏, 沼倉 忠久, 山田 充啓, 藤野 直也, 京極 自彦, 光根 歩, 板倉 康司, 佐野 寛仁, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　163-163　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  14. COPD患者肺間質マクロファージにおける抑制性受容体LILRB4の発現上昇 Peer-reviewed

    光根 歩, 山田 充啓, 藤野 直也, 三橋 善哉, 板倉 康司, 杉浦 久敏, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　192-192　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  15. COPDにおける新規活性イオウ分子種産生酵素の役割に関する新知見 Peer-reviewed

    佐野 寛仁, 杉浦 久敏, 山田 充啓, 藤野 直也, 沼倉 忠久, 赤池 孝章, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　192-192　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  16. 気管支喘息における気道上皮細胞の機能障害とミトコンドリア新生の役割に関する検討 Peer-reviewed

    齋藤 勉, 市川 朋宏, 藤野 直也, 沼倉 忠久, 佐々木 優作, 板倉 康司, 山田 充啓, 杉浦 久敏, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　213-213　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  17. 気管支喘息 病態生理 Axl受容体チロシンキナーゼによる重症喘息の好酸球性気道炎症制御機構

    板倉 康司, 藤野 直也, 山田 充啓, 上出 庸介, 齋藤 生朗, 杉浦 久敏, 谷口 正実, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　152-152　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

  18. COPD 病態 COPD病態における活性イオウ分子種の役割の検討

    山中 駿, 市川 朋宏, 杉浦 久敏, 沼倉 忠久, 山田 充啓, 藤野 直也, 京極 自彦, 光根 歩, 板倉 康司, 佐野 寛仁, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　163-163　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

  19. COPD患者肺間質マクロファージにおける抑制性受容体LILRB4の発現上昇

    光根 歩, 山田 充啓, 藤野 直也, 三橋 善哉, 板倉 康司, 杉浦 久敏, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　192-192　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

  20. COPDにおける新規活性イオウ分子種産生酵素の役割に関する新知見

    佐野 寛仁, 杉浦 久敏, 山田 充啓, 藤野 直也, 沼倉 忠久, 赤池 孝章, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　192-192　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

  21. 気管支喘息における気道上皮細胞の機能障害とミトコンドリア新生の役割に関する検討

    齋藤 勉, 市川 朋宏, 藤野 直也, 沼倉 忠久, 佐々木 優作, 板倉 康司, 山田 充啓, 杉浦 久敏, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　213-213　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

  22. 敗血症患者血中ACE陽性EMPのARDS発症に対する予測的価値

    山田 充啓, 武井 裕介, 牧口 友紀, 藤野 直也, 杉浦 久敏, 山内 正憲, 一ノ瀬 正和

    日本呼吸器学会誌　8　(増刊)　141-141　2019/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

  23. COPDにおける新規活性イオウ分子種産生酵素の役割に関する新知見

    佐野寛仁, 杉浦久敏, 山田充啓, 藤野直也, 沼倉忠久, 赤池孝章, 一ノ瀬正和

    日本呼吸器学会誌(Web)　8　2019

    ISSN： 2186-5884

  24. 気管支喘息における気道上皮細胞の機能障害とミトコンドリア新生の役割に関する検討

    齋藤勉, 市川朋宏, 藤野直也, 沼倉忠久, 佐々木優作, 板倉康司, 山田充啓, 杉浦久敏, 一ノ瀬正和

    日本呼吸器学会誌(Web)　8　2019

    ISSN： 2186-5884

  25. COPD病態における活性イオン分子種の役割の検討

    山中駿, 市川朋宏, 杉浦久敏, 沼倉忠久, 山田充啓, 藤野直也, 京極自彦, 光根歩, 板倉康司, 佐野寛仁, 一ノ瀬正和

    日本呼吸器学会誌(Web)　8　2019

    ISSN： 2186-5884

  26. PRODUCTION OF REACTIVE PERSULFIDE SPECIES IN LUNGS OF PATIENTS WITH COPD AND THEIR EFFECTS ON LUNG-RESIDENT CELLS

    Tadahisa Numakura, Hisatoshi Sugiura, Takaaki Akaike, Mitsuhiro Yamada, Tomohiro Ichikawa, Naoya Fujino, Akira Koarai, Masakazu Ichinose

    RESPIROLOGY　23　125-126　2018/11

    ISSN： 1323-7799

    eISSN： 1440-1843

  27. 抗TNFα抗体抵抗性のペムブロリズマブによる難治性大腸炎の1例

    佐野 寛仁, 小林 誠, 佐々木 優作, 藤野 直也, 山田 充啓, 一ノ瀬 正和

    日本呼吸器学会誌　7　(6)　409-414　2018/11

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  28. Oxidative stress enhances the expression of IL-33 in human airway epithelial cells (vol 19, 52, 2018)

    Hiroyuki Aizawa, Akira Koarai, Yutaka Shishikura, Satoru Yanagisawa, Mutsuo Yamaya, Hisatoshi Sugiura, Tadahisa Numakura, Mitsuhiro Yamada, Tomohiro Ichikawa, Naoya Fujino, Masafumi Noda, Yoshinori Okada, Masakazu Ichinose

    RESPIRATORY RESEARCH　19　2018/06

    DOI： 10.1186/s12931-018-0817-9 　

    ISSN： 1465-993X

    eISSN： 1465-9921

  29. ヒト気道上皮細胞のIL-33発現に対する酸化ストレスの影響の検討 Peer-reviewed

    相澤 洋之, 小荒井 晃, 宍倉 裕, 柳澤 悟, 山谷 睦雄, 杉浦 久敏, 沼倉 忠久, 山田 充啓, 市川 朋宏, 藤野 直也, 一ノ瀬 正和

    アレルギー　67　(4-5)　564-564　2018/05

    Publisher: (一社)日本アレルギー学会

    ISSN： 0021-4884

    eISSN： 1347-7935

  30. ニトロ化ストレス,活性硫黄種に着目したCOPD合併喘息(ACO)の病態解明に関する検討 Peer-reviewed

    京極 自彦, 杉浦 久敏, 沼倉 忠久, 市川 朋宏, 田中 里江, 小荒井 晃, 山田 充啓, 藤野 直也, 一ノ瀬 正和

    アレルギー　67　(4-5)　576-576　2018/05

    Publisher: (一社)日本アレルギー学会

    ISSN： 0021-4884

    eISSN： 1347-7935

  31. 【アンチテーゼとしての難治性呼吸器疾患の個別化医療】 COPDに対するPrecision Medicineの展望

    藤野 直也, 杉浦 久敏

    THE LUNG-perspectives　26　(2)　138-141　2018/05

    Publisher: (株)メディカルレビュー社

    ISSN： 0919-5742

  32. ヒト気道上皮細胞のIL-33発現に対する酸化ストレスの影響の検討

    相澤 洋之, 小荒井 晃, 宍倉 裕, 柳澤 悟, 山谷 睦雄, 杉浦 久敏, 沼倉 忠久, 山田 充啓, 市川 朋宏, 藤野 直也, 一ノ瀬 正和

    アレルギー　67　(4-5)　564-564　2018/05

    Publisher: (一社)日本アレルギー学会

    ISSN： 0021-4884

  33. ニトロ化ストレス,活性硫黄種に着目したCOPD合併喘息(ACO)の病態解明に関する検討

    京極 自彦, 杉浦 久敏, 沼倉 忠久, 市川 朋宏, 田中 里江, 小荒井 晃, 山田 充啓, 藤野 直也, 一ノ瀬 正和

    アレルギー　67　(4-5)　576-576　2018/05

    Publisher: (一社)日本アレルギー学会

    ISSN： 0021-4884

  34. EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を制御する

    突田容子, 藤野直也, 宮内栄作, 井上彰, 板倉康司, 山田充啓, 岡崎達馬, 桜田晃, 杉浦久敏, 岡田克典, 一ノ瀬正和

    日本呼吸器学会誌(Web)　7　(増刊)　267-267　2018/03/10

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5884

  35. COPDの肺胞マクロファージにおける細菌貪食受容体Siglec-1の発現低下 Peer-reviewed

    丹野 篤, 藤野 直也, 山田 充啓, 杉浦 久敏, 平野 泰三, 田中 里江, 一ノ瀬 正和

    日本呼吸器学会誌　7　(増刊)　143-143　2018/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  36. EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を制御する

    突田 容子, 藤野 直也, 宮内 栄作, 井上 彰, 板倉 康司, 山田 充啓, 岡崎 達馬, 桜田 晃, 杉浦 久敏, 岡田 克典, 一ノ瀬 正和

    日本呼吸器学会誌　7　(増刊)　267-267　2018/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  37. ヒト気道上皮のIL-33発現に対する酸化ストレスの影響

    相澤 洋之, 小荒井 晃, 宍倉 裕, 柳澤 悟, 山谷 睦雄, 杉浦 久敏, 沼倉 忠久, 山田 充啓, 市川 朋宏, 藤野 直也, 一ノ瀬 正和

    日本呼吸器学会誌　7　(増刊)　143-143　2018/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  38. COPDの肺胞マクロファージにおける細菌貪食受容体Siglec-1の発現低下

    丹野 篤, 藤野 直也, 山田 充啓, 杉浦 久敏, 平野 泰三, 田中 里江, 一ノ瀬 正和

    日本呼吸器学会誌　7　(増刊)　143-143　2018/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

  39. ヒト気道上皮のIL-33発現に対する酸化ストレスの影響

    相澤 洋之, 小荒井 晃, 宍倉 裕, 柳澤 悟, 山谷 睦雄, 杉浦 久敏, 沼倉 忠久, 山田 充啓, 市川 朋宏, 藤野 直也, 一ノ瀬 正和

    日本呼吸器学会誌　7　(増刊)　143-143　2018/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

  40. EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を制御する

    突田 容子, 藤野 直也, 宮内 栄作, 井上 彰, 板倉 康司, 山田 充啓, 岡崎 達馬, 桜田 晃, 杉浦 久敏, 岡田 克典, 一ノ瀬 正和

    日本呼吸器学会誌　7　(増刊)　267-267　2018/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

  41. ヒト気道上皮のIL-33発現に対する酸化ストレスの影響

    相澤洋之, 小荒井晃, 宍倉裕, 柳澤悟, 山谷睦雄, 杉浦久敏, 沼倉忠久, 山田充啓, 市川朋宏, 藤野直也, 一ノ瀬正和

    日本呼吸器学会誌(Web)　7　2018

    ISSN： 2186-5884

  42. 肺循環・肺損傷 ACE陽性EMPに着目した新規ARDSバイオマーカーの開発

    武井 祐介, 山田 充啓, 藤野 直也, 斎藤 浩二, 山内 正憲, 杉浦 久敏, 一ノ瀬 正和

    日本呼吸器学会誌　6　(増刊)　124-124　2017/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  43. COPD 病因・病態 COPD患者由来肺血管内皮細胞の単離と網羅的遺伝子発現解析

    東條 裕, 山田 充啓, 藤野 直也, 千葉 茂樹, 渋谷 里紗, 杉浦 久敏, 小川 浩正, 一ノ瀬 正和

    日本呼吸器学会誌　6　(増刊)　125-125　2017/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  44. Gene Expression Profiles In Isolated Lung Endothelial Cells In Chronic Obstructive Pulmonary Disease

    Y. Tojo, M. Yamada, N. Fujino, S. Chiba, R. Shibuya, A. Koarai, H. Sugiura, H. Ogawa, M. Ichinose

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　195　2017

    ISSN： 1073-449X

    eISSN： 1535-4970

  45. Sensing Of Apoptotic Cells Via Axl Kinase Triggers Cell Cycle Re-Entry Of Airway Basal Cells In Mice

    N. Fujino, T. Fujimori, A. Grabiec, R. A. Maciewicz, T. Hussell

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　195　2017

    ISSN： 1073-449X

    eISSN： 1535-4970

  46. トシリズマブ(抗IL-6R抗体)による加療中に発症した肺結核の1例

    山田 充啓, 三橋 善哉, 京極 自彦, 三浦 絵美里, 東條 裕, 藤野 直也, 岡崎 達馬, 玉田 勉, 杉浦 久敏, 一ノ瀬 正和

    結核　92　(1)　51-51　2017/01

    Publisher: (一社)日本結核病学会

    ISSN： 0022-9776

    eISSN： 1884-2410

  47. FACSによるLAM細胞分離法の確立

    安藤 克利, 藤野 直也, 大田 千晴, 岡田 克典, 栗原 正利, 江花 弘基, 高橋 和久, 久保 裕司, 瀬山 邦明

    日本呼吸器学会誌　5　(増刊)　275-275　2016/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  48. A NOVEL METHOD OF ISOLATING INDIVIDUAL CELLS FROM LUNG LESIONS OF LYMPHANGIOLEIOMYOMATOSIS

    Katsutoshi Ando, Naoya Fujino, Keiko Mitani, Chiharu Ota, Yoshinori Okada, Takashi Kondo, Teruaki Mizobuchi, Masatoshi Kurihara, Kenji Suzuki, Yoshito Hoshika, Hiroki Ebana, Etsuko Kobayashi, Hiroshi Kubo, Kuniaki Seyama, Kazuhisa Takahashi

    RESPIROLOGY　20　108-108　2015/12

    ISSN： 1323-7799

    eISSN： 1440-1843

  49. FACSによるLAM細胞分離法の確立

    安藤 克利, 藤野 直也, 三谷 恵子, 大田 千晴, 丹藤 由希子, 岡田 克典, 近藤 丘, 溝渕 輝明, 栗原 正利, 鈴木 健司, 星加 義人, 江花 弘基, 高橋 和久, 久保 裕司, 瀬山 邦明

    日本気胸・嚢胞性肺疾患学会雑誌　15　(1)　85-85　2015/07

    Publisher: 日本気胸・嚢胞性肺疾患学会

    ISSN： 1883-0412

  50. Disease-Specific Cellular Proportion Pattern Of Combined Pulmonary Fibrosis And Emphysema (cpfe)

    C. Ota, Y. Tando, S. Kamata, M. Yamada, K. Ichikado, S. Suzuki, N. Fujino, M. Yamaya, H. Kubo

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　191　2015

    ISSN： 1073-449X

    eISSN： 1535-4970

  51. THE ROLE OF THE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS IN LPS-INDUCED LUNG INJURY IN MICE

    M. He, K. Morimoto, N. Fujino, T. Suzuki, T. Takahasi, Mitsuhiro Yamada, M. Yamaya, Y. Yamamoto, H. Yamamoto, Z. Qiu, Hiroshi Kubo

    RESPIROLOGY　19　10-10　2014/11

    DOI： 10.1111/resp.12417_11 　

    ISSN： 1323-7799

    eISSN： 1440-1843

  52. 地域基幹病院呼吸器内科病棟における急性期NPPV療法

    小林 誠一, 花釜 正和, 矢満田 慎介, 石田 雅嗣, 佐藤 ひかり, 藤野 直也, 田代 祐介, 矢内 勝

    石巻赤十字病院誌　(17)　3-7　2014/03

    Publisher: 石巻赤十字病院

    ISSN： 1346-0730

  53. AXL receptor tyrosine kinase controls epithelial differentiation of human lung progenitor cells

    Naoya Fujino, Hiroshi Kubo, Rose Maciewicz

    EUROPEAN RESPIRATORY JOURNAL　42　2013/09

    ISSN： 0903-1936

    eISSN： 1399-3003

  54. 【呼吸器病学TOPICS 2012-13】 細胞・分子生物学 ヒトII型肺胞上皮前駆細胞の分離と難治性肺疾患治療への応用

    藤野 直也

    分子呼吸器病　17　(1)　18-20　2013/03

    Publisher: (株)先端医学社

    ISSN： 1342-436X

  55. ヒトⅡ型肺胞上皮前駆細胞の分離と難治性肺疾患治療への応用 (特集 呼吸器病学TOPICS 2012-13) -- (細胞・分子生物学)

    藤野 直也

    分子呼吸器病　17　(1)　18-20,4　2013/03

    Publisher: 先端医学社

    ISSN： 1342-436X

  56. Identification And Characteristics Of Lung Alveolar Epithelial Label-Retaining Cells

    M. Yamada, H. Kubo, N. Fujino, T. Takahashi, C. Ota, T. Suzuki, Y. Tando, M. Ichinose

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　187　2013

    ISSN： 1073-449X

    eISSN： 1535-4970

  57. Relationships Between Annual Changes In Fev1 And Numbers Of Circulating Endothelial Microparticles In COPD Patients

    T. Takahashi, S. Kobayashi, N. Fujino, T. Suzuki, Y. Tando, C. Ota, M. Yamada, S. Kurosawa, M. Yanai, M. Yamaya, H. Kubo

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　187　2013

    ISSN： 1073-449X

    eISSN： 1535-4970

  58. Both Mir-21 And Mir-155c Increase In Serum Exosomes During Bleomycin- Induced Lung Injury In Mice

    M. Yamada, H. Kubo, S. Kobayashi, C. Ota, T. Takahashi, N. Fujino, T. Suzuki, Y. Tando, M. Yanai, M. Ichinose

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　187　2013

    ISSN： 1073-449X

    eISSN： 1535-4970

  59. miR-200/miR-21は肺胞上皮細胞のEMTを制御する

    山田 充啓, 久保 裕司, 鈴木 隆哉, 藤野 直也, 大田 千春, 高橋 徹, 國島 広之, 青柳 哲史, 賀来 満夫

    日本呼吸器学会誌　1　(増刊)　242-242　2012/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 2186-5876

    eISSN： 2186-5884

  60. RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS BINDS TO PHOSPHATIDYLSERINE AND MEDIATES CLEARANCE OF APOPTOTIC CELLS IN LPS-INDUCED LUNG INJURY IN MICE

    M. He, H. Kubo, K. Morimoto, N. Fujino, T. Suzuki, T. Takahasi, M. Yamada, M. Yamaya, Y. Yamamoto, H. Yamamoto

    RESPIROLOGY　16　24-24　2011/11

    ISSN： 1323-7799

  61. 組織幹細胞保存液StemSurviveの開発

    鈴木 隆哉, 久保 裕司, 藤野 直也, 大田 千晴, 高橋 徹, 岡田 克典, 山谷 睦雄, 近藤 丘

    Organ Biology　18　(2)　249-249　2011/10

    Publisher: (一社)日本臓器保存生物医学会

    DOI： 10.11378/organbio.18.249 　

    ISSN： 1340-5152

  62. 急性肺損傷における肺好中球上CXCR4発現上昇の機序とその役割

    山田 充啓, 久保 裕司, 何 梅, 鈴木 隆哉, 藤野 直也, 國島 広之, 西巻 雄司, 青柳 哲史, 平潟 洋一, 賀来 満夫

    日本呼吸器学会雑誌　49　(増刊)　149-149　2011/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 1343-3490

  63. Expression Patterns Of Two Important Regulatory Micrornas In Epithelial-Mesenchymal Transition During Experimental Bleomycin-Induced Lung Fibrosis

    M. Yamada, H. Kubo, N. Fujino, M. He, T. Suzuki, T. Takahashi, C. Ota, T. Aoyagi, H. Kunishima, M. Yamaya, M. Kaku

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　183　2011

    ISSN： 1073-449X

    eISSN： 1535-4970

  64. A Novel Differentiation Assay System For Human Alveolar Epithelial Type II Cells From Alveolar Epithelial Stem/Progenitor Cells In Vitro

    C. Ota, N. Fujino, T. Suzuki, M. He, S. Suzuki, M. Yamada, T. Kondo, H. Kato, M. Yamaya, H. Kubo

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　183　2011

    ISSN： 1073-449X

    eISSN： 1535-4970

  65. ENDOGENOUS STEM CELL POPULATION IN ADULT HUMAN LUNGS

    Hiroshi Kubo, Fujino Naoya, Takaya Suzuki, Chiharu Ota, Toru Takahasi, Mei He, Mitsuhiro Yamada, Mutsuo Yamaya

    RESPIROLOGY　15　42-42　2010/11

    ISSN： 1323-7799

  66. 肺の幹細胞生物学

    藤野 直也

    東北医学雑誌　122　(1)　111-112　2010/06

    Publisher: 東北医学会

    ISSN： 0040-8700

  67. 胎児肺におけるc-kitのダイナミックで多系列な発現(Dynamic and multilineage expression of c-kit in developing human lungs)

    鈴木 隆哉, 久保 裕司, 藤野 直也, 何 梅, 山谷 睦雄, 近藤 丘

    日本呼吸器外科学会雑誌　24　(3)　427-427　2010/04

    Publisher: (NPO)日本呼吸器外科学会

    ISSN： 0919-0945

  68. 胎児肺におけるc-kit発現の解析

    鈴木 隆哉, 久保 裕司, 藤野 直也, 山谷 睦雄, 近藤 丘

    日本呼吸器学会雑誌　48　(増刊)　252-252　2010/03

    Publisher: (一社)日本呼吸器学会

    ISSN： 1343-3490

  69. Autotaxin Is Involved In Pulmonary Edema During Acid-induced Acute Lung Injury

    M. Yamada, H. Kubo, S. Okudaira, T. Suzuki, N. Fujino, M. He, N. Yamamoto, T. Aoyagi, H. Kunishima, J. Aoki, M. Yamaya, M. Kaku

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　181　2010

    ISSN： 1073-449X

  70. 呼吸器系の生物学 高齢者肺炎と肺防御機構

    山谷 睦雄, 久保 裕司, 藤野 直也

    Annual Review呼吸器　2010　1-6　2010/01

    Publisher: (株)中外医学社

  71. ワクチン・去痰薬などの役割 (治療学)

    山谷睦雄, 吉田元樹, 中山勝敏, 安田浩康, 藤野直也, 久保裕司

    治療学　43　(9)　70-74　2009/09/10

  72. 【COPD 新ガイドラインで期待される予防と治療】 慢性安定期の診療 ワクチン・去痰薬などの役割

    山谷 睦雄, 吉田 元樹, 中山 勝敏, 安田 浩康, 藤野 直也, 久保 裕司

    治療学　43　(9)　982-986　2009/09

    Publisher: ライフサイエンス出版(株)

    ISSN： 0386-8109

  73. 高齢者重症肺炎に対するNPPVの有用性についての検討

    小林 誠一, 花釜 正和, 藤野 直也, 矢内 勝

    日本呼吸器学会雑誌　47　(増刊)　180-180　2009/05

    Publisher: (一社)日本呼吸器学会

    ISSN： 1343-3490

  74. アルカリ誤飲による腐食性食道炎の一例

    山本 康央, 石田 雅嗣, 藤野 直也, 長田 元伸, 石塚 圭一

    Gastroenterological Endoscopy　51　(Suppl.1)　906-906　2009/04

    Publisher: (一社)日本消化器内視鏡学会

    ISSN： 0387-1207

  75. マクロライド薬のインフルエンザへの有用性は？ (インフルエンザの最新知識Q&A 2009)

    山谷睦雄, 藤野直也, 久保裕司

    インフルエンザの最新知識Q&A 2009　83-84　2009/02

  76. New Preservation Solution for Endogenous Tissue Stem Cells

    T. Suzuki, H. Kubo, N. Fujino, A. E. Hegab, M. He, Y. Okada, M. Yamaya, T. Kondo

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　179　2009

    ISSN： 1073-449X

  77. CD117 Positive Cells without Mast Cell Lineage Are Localized in the Lung Parenchyma and Alveolar Wall in Adult Human Lungs.

    T. Suzuki, H. Kubo, N. Fujino, A. E. Hegab, M. He, M. Yamaya, T. Kondo

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　179　2009

    ISSN： 1073-449X

  78. Mesenchymal Stem Cells with Alveolar Epithelial Phenotype Were Isolated from Adult Human Lungs.

    N. Fujino, T. Suzuki, A. E. Hegab, M. He, M. Yamaya, H. Kubo

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE　179　2009

    ISSN： 1073-449X

  79. 【喫煙関連間質性肺疾患(smoking-related interstitial lung diseases:SRILD)をめぐって】 喫煙に伴う肺気腫と周縁疾患の病態

    山谷 睦雄, 藤野 直也, 久保 裕司

    日本胸部臨床　67　(9)　733-743　2008/09

    Publisher: 克誠堂出版(株)

    ISSN： 0385-3667

  80. 【ウイルス感染とアレルギー】 ライノウイルス感染と気管支喘息

    山谷 睦雄, 久保 裕司, 藤野 直也, 吉田 元樹, 西村 秀一

    臨床免疫・アレルギー科　50　(3)　295-301　2008/09

    Publisher: (有)科学評論社

    ISSN： 1881-1930

  81. Pathogenesis of smoking-induced emphysema and related lung disease

    山谷 睦雄, 藤野 直也, 久保 裕司

    The Japanese journal of chest diseases　67　(9)　733-743　2008/09

    Publisher: 克誠堂出版

    ISSN： 0385-3667

  82. Rhinovirus infection and bronchial asthma

    山谷 睦雄, 久保 裕司, 藤野 直也

    Clinical immunology & allergology　50　(3)　295-301　2008/09

    Publisher: 科学評論社

    ISSN： 1881-1930

  83. FOLFOXによる薬剤性肺障害2例の検討

    藤野 直也, 宮坂 康宣, 小林 誠一, 高橋 徹, 矢内 勝

    日本呼吸器学会雑誌　46　(増刊)　176-176　2008/05

    Publisher: (一社)日本呼吸器学会

    ISSN： 1343-3490

  84. 急性肺損傷後の修復過程における好中球エラスターゼ(NE)の役割の検討

    藤野 直也, 久保 裕司, Hegab Ahmed E, 何 梅, 山谷 睦雄, 鈴木 朋子, Downey Gregory P

    日本呼吸器学会雑誌　46　(増刊)　257-257　2008/05

    Publisher: (一社)日本呼吸器学会

    ISSN： 1343-3490

  85. 術前のtiotropium吸入が効果的だった重度COPD合併肺癌の手術例

    鈴木 聡, 藤野 直也, 小林 誠一, 松本 香好美, 矢内 勝

    内科　101　(1)　189-191　2008/01

    Publisher: (株)南江堂

    ISSN： 0022-1961

  86. A case of successful lung resection in a lung cancer patient with severe COPD following preoperative treatment with tiotropium bromide

    鈴木 聡, 藤野 直也, 小林 誠一

    内科　101　(1)　189-191　2008/01

    Publisher: 南江堂

    ISSN： 0022-1961

  87. 心タンポナーデで発症し、化学療法が奏効した心臓原発悪性リンパ腫

    高川 真徳, 土屋 洋之, 藤野 直也

    石巻赤十字病院誌　(11)　39-42　2007/11

    Publisher: 石巻赤十字病院

    ISSN： 1346-0730

  88. 結腸・直腸癌に対する腹腔鏡下手術導入による効果(第105回日本外科学会定期学術集会)

    石橋 悟, 金田 巖, 藤野 直也, 田代 祐介, 横山 元昭, 阿部 薫夫, 大原 勝人, 井上 宰, 初貝 和明, 石井 正, 古田 昭彦

    日本外科学会雑誌　106　(0)　428-428　2005/04/05

    Publisher: 一般社団法人日本外科学会

    ISSN： 0301-4894

  89. 結腸・直腸癌に対する腹腔鏡下手術導入による効果

    石橋 悟, 金田 巖, 藤野 直也, 田代 祐介, 横山 元昭, 阿部 薫夫, 大原 勝人, 井上 宰, 初貝 和明, 石井 正, 古田 昭彦

    日本外科学会雑誌　106　(臨増)　428-428　2005/04

    Publisher: (一社)日本外科学会

    ISSN： 0301-4894

  90. 胆嚢捻転症の2例

    藤野 直也, 金田 巌, 古田 昭彦, 石井 正, 石橋 悟, 初貝 和明, 大原 勝人, 阿部 薫夫, 井上 宰, 横山 元昭, 力丸 裕也

    東北医学雑誌　116　(2)　183-183　2004/12

    Publisher: 東北医学会

    ISSN： 0040-8700

  91. CTで診断しえた術後内ヘルニアの4例

    横山 元昭, 金田 巌, 古田 昭彦, 石井 正, 石橋 悟, 初貝 和明, 大原 勝人, 阿部 薫夫, 井上 宰, 藤野 直也, 力丸 裕也

    東北医学雑誌　116　(2)　192-192　2004/12

    Publisher: 東北医学会

    ISSN： 0040-8700

Show all ︎Show first 5

Research Projects 5

  1. Molecular mechanisms on how alveolar epithelial cells respond to exogenous stress in COPD

    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: Tohoku University

    2020/04/01 - 2023/03/31

  2. Why is prognosis of lung transplant recipient from elderly donors poor? &#8211;Elucidation of mechanisms and establishment of therapeutic intervention strategy-

    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

    2019/04/01 - 2023/03/31

  3. Apototic cell-induced supression of inflammation in the airway

    Fujino Naoya

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Early-Career Scientists

    Institution: Tohoku University

    2018/04/01 - 2020/03/31

    More details Close

    Ten percent of the population are suffering from bronchial asthma in Japan. But more importantly, 10% of asthmatics have severe phenotypes which are resistant to regular medication such as inhaled corticosteroids. In this research we have uncovered a novel molecule, Axl receptor tyrosine kinase, which is a strong suppressor of inflammation of asthma. We have observe a decrease in Axl expression in airways of severe asthma patients, which could explain why more inflammation occur in severe asthmatics.

  4. Investigation of Axl receptor tyrosine kinase in COPD airways

    Fujino Naoya

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Research Activity Start-up

    Institution: Tohoku University

    2016/08/26 - 2018/03/31

    More details Close

    Axl receptor tyrosine kinase is known to be expressed by macrophages and dendritic cells. The applicant previously found that Axl was also expressed by airway basal cells. However the role of Axl in airway basal cells of chronic obstructive pulmonary disease (COPD) has not been determined. We found that the number of Axl+/P63+ basal cells increased in COPD ex-smokers bronchioles compared to control never-smokers and control ex-smokers. In vitro experiments using human bronchial epithelial cell line Beas2B cells indicated that Axl did not regulate epithelial-to-mesenchymal transition, which was reported to be associated with cancer progression. However we found that Axl kinase regulated chemokine and cytokine expression in Beas2B cells, which promote neutrophil inflammation. These data suggested that Axl kinase in the airway has roles in cellular proliferation and regulation of inflammation.

  5. Identification of microRNAs that regulate differentiation of human lung progenitor cells

    FUJINO Naoya

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Research Activity Start-up

    Institution: Tohoku University

    2012/08/31 - 2014/03/31

    More details Close

    Tissue-specific stem/progenitor cells have the ability to self-renew and the potential to differentiate into multiple cell-types and have a role in homeostasis and repair. The aim of this study was to identify microRNA (miRNA) that regulate function of human lung progenitor cells. We found that expression of miR-200c was inhibited in human lung progenitor cells compared with human mature alveolar epithelial cells. Transfection of a synthetic RNA, which mimics miR-200c, suppressed proliferation in human lung progenitor cells. This suggests that the genes targeted by miR-200c regulate growth of human lung progenitor cells.