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Yoichi Kakuta

Section

Graduate School of Medicine

Job title

Associate Professor

Degree

researchmap

https://researchmap.jp/ykakuta

J-GLOBAL ID

201801005978287026

Research History 6

2023/04 - Present

Tohoku University　Graduate School of Medicine, Division of Gastroenterology
2013/10 - Present

Tohoku University Hospital　Department of Gastroenterology　Assistant Professor
2011/09 - 2013/09

Cedars-Sinai Medical Center　F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute　Post-Doctoral fellow
2008/04 - 2011/08

Tohoku University Hospital　Department of Gastroenterology
2003/04 - 2004/03

十和田市立中央病院　第一内科
2000/05 - 2003/03

八戸市立市民病院　消化器内科

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Education 2

Tohoku University　Graduate School of Medicine

2004/04 - 2008/03
Tohoku University

1994/04 - 2000/03

Committee Memberships 3

日本消化器病学会　炎症性腸疾患(IBD)ガイドライン作成委員

2024/11 - Present
日本炎症性腸疾患学会　機関誌編集委員

2023/04 - Present
日本炎症性腸疾患学会　学術委員

2018/09 - Present

Professional Memberships 4

JAPAN SOCIETY OF INFLAMMATORY BOWEL DISEASE
THE JAPANESE SOCIETY OF INTERNAL MEDICINE
JAPAN GASTROENTEROLOGICAL ENDOSCOPY SOCIETY
JAPANESE SOCIETY OF GASTROENTEROLOGY

Research Interests 3

Susceptibility Genes
Inflammatory Bowel Disease
Gastroenterology

Research Areas 1

Life sciences / Gastroenterology /

Awards 6

東北大学医学部奨学賞金賞

2023/01　東北大学　日本人炎症性腸疾患の遺伝的特徴の解明と臨床応用
APDWF-JGHF Emerging Leader Lectureship

2022/11　Genetics of inflammatory bowel diseases in East Asia –from population to an individual.
Tohoku Medical Society Awardd

2019/01　Tohoku Medical Society
31st JSGE Incentive Award

2018/04　Japan Society of Gastroenterology　Increased expression of IL12B mRNA transcribed from the risk haplotype for Crohn's disease is a risk factor for disease relapse in Japanese patients.
医学系研究奨励（臨床）

2010　武田科学振興財団　アリル特異的転写産物の測定を用いた炎症性腸疾患感受性遺伝子機能解析による発症メカニズムの解明
第１５回浜名湖シンポジウム審査員特別賞

2009/12　国際科学振興財団フォーラム　8. クローン病感受性遺伝子TNFSF15遺伝子多型における機能解析

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Papers 293

Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries. International-journal

Zhanju Liu, Ruize Liu, Han Gao, Seulgi Jung, Xiang Gao, Ruicong Sun, Xiaoming Liu, Yongjae Kim, Ho-Su Lee, Yosuke Kawai, Masao Nagasaki, Junji Umeno, Katsushi Tokunaga, Yoshitaka Kinouchi, Atsushi Masamune, Wenzhao Shi, Chengguo Shen, Zhenglin Guo, Kai Yuan, Shu Zhu, Dalin Li, Jianjun Liu, Tian Ge, Judy Cho, Mark J Daly, Dermot P B McGovern, Byong Duk Ye, Kyuyoung Song, Yoichi Kakuta, Mingsong Li, Hailiang Huang

Nature genetics　55　(5)　796-806　2023/05/08

DOI： 10.1038/s41588-023-01384-0 　

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Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract with the following two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). To date, most IBD genetic associations were derived from individuals of European (EUR) ancestries. Here we report the largest IBD study of individuals of East Asian (EAS) ancestries, including 14,393 cases and 15,456 controls. We found 80 IBD loci in EAS alone and 320 when meta-analyzed with ~370,000 EUR individuals (~30,000 cases), among which 81 are new. EAS-enriched coding variants implicate many new IBD genes, including ADAP1 and GIT2. Although IBD genetic effects are generally consistent across ancestries, genetics underlying CD appears more ancestry dependent than UC, driven by allele frequency (NOD2) and effect (TNFSF15). We extended the IBD polygenic risk score (PRS) by incorporating both ancestries, greatly improving its accuracy and highlighting the importance of diversity for the equitable deployment of PRS.
Response to COVID-19 vaccine is reduced in patients with inflammatory bowel disease, but improved with additional dose. International-journal

Hisashi Shiga, Yoichi Kakuta, Kumiko An, Yuko Abe, Shinichi Fujimaki, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Seik-Soon Khor, Yosuke Kawai, Katsushi Tokunaga, Yoshitaka Kinouchi, Atsushi Masamune

Journal of gastroenterology and hepatology　38　(1)　44-51　2022/09/06

DOI： 10.1111/jgh.16001 　

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BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination is recommended for patients with inflammatory bowel disease (IBD); however, suppressed immune responses have been reported for fully vaccinated patients under immunosuppressive therapy, mainly from Western countries. We prospectively analyzed antibody titers of IBD patients in Asia induced by two-dose and additional dose of messengerRNA COVID-19 vaccine. METHODS: After measuring high-affinity antibody titers, factors associated with antibody titers were identified by multiple regression analyses using the following covariates: sex, age (≥60 or <60 years), disease type (Crohn's disease or ulcerative colitis), vaccine type (BNT162b2 or mRNA-1273), time from second/third vaccination, molecular-targeted agent (anti-tumor necrosis factor [TNF] agents, ustekinumab, vedolizumab, tofacitinib, or no molecular-targeted agents), thiopurine, steroid, and 5-aminosalicylic acid. RESULTS: Among 409 patients analyzed, mean titer was 1316.7 U/mL (SD, 1799.3); 403 (98.5%) were judged to be seropositive (≥0.8 U/mL), and 389 (95.1%) had neutralizing antibodies (≥15 U/mL). After the third vaccination, mean titer raised up to 21 123.8 U/mL (SD, 23 474.5); all 179 were seropositive, and 178 (99.4%) had neutralizing antibodies. In 248 patients with genetic data, there was no difference in mean titer after two/third doses between carriers and non-carriers of HLA-A24 associated with severe disease during COVID-19 infection. A multiple regression analyses using covariates revealed that older age, vaccine type (BNT162b2), time from second/third dose, anti-TNF agent, tofacitinib, and thiopurine were independently associated with lower antibody titers. CONCLUSIONS: Our findings further support the recommendation for COVID-19 vaccination in patients under immunosuppressive therapy, especially additional third dose for patients receiving anti-TNF agents and/or thiopurine or tofacitinib.
Novel Diagnostic Autoantibodies Against Endothelial Protein C Receptor in Patients With Ulcerative Colitis. International-journal

Yoichi Kakuta, Tsuyoshi Shirai, Dermot P B McGovern, Jonathan Braun, Hiroshi Fujii, Atsushi Masamune

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association　21　(3)　844-846　2021/12/28

DOI： 10.1016/j.cgh.2021.12.035 　

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There have been many reports on serologic autoantibodies in inflammatory bowel diseases (IBD),1 consisting of ulcerative colitis (UC) and Crohn's disease (CD), and recently Kuwada et al2 reported a new autoantibody against integrin αvβ6 with high sensitivity and specificity for UC. Concurrently, we had discovered autoantibodies against endothelial protein C receptor (EPCR) in Takayasu arteritis (TAK), which is sometimes complicated by UC.3 Interestingly, this autoantibody was found in most patients with TAK associated with UC, and we found that the positivity rate in patients with UC without TAK was also high, suggesting that anti-EPCR antibody is a candidate autoantibody useful for the diagnosis of UC.4 To clarify the diagnostic usefulness of anti-EPCR antibodies in patients with IBD and their relationship to several disease subphenotypes and their disease activities, we analyzed the serum samples from patients with IBD and non-IBD control subjects in Japan and the United States.
Crohn's disease and early exposure to thiopurines are independent risk factors for mosaic chromosomal alterations in patients with inflammatory bowel diseases. International-journal

Yoichi Kakuta, Hideya Iwaki, Junji Umeno, Yosuke Kawai, Masahiro Kawahara, Tetsuya Takagawa, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Hisashi Shiga, Kenji Watanabe, Shiro Nakamura, Hiroshi Nakase, Makoto Sasaki, Hiroyuki Hanai, Yuta Fuyuno, Atsushi Hirano, Takayuki Matsumoto, Hisaaki Kudo, Naoko Minegishi, Minoru Nakamura, Tadakazu Hisamatsu, Akira Andoh, Masao Nagasaki, Katsushi Tokunaga, Yoshitaka Kinouchi, Atsushi Masamune

Journal of Crohn's & colitis　16　(4)　643-655　2021/11/09

DOI： 10.1093/ecco-jcc/jjab199 　

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BACKGROUND AND AIMS: Mosaic chromosomal alterations (mCAs) increase the risk for hematopoietic malignancies and may be risk factors for several other diseases. Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are associated with mCAs, and patients may be at risk for hematopoietic malignancy development and/or modification of IBD phenotypes. In the present study, we screened patients with IBD for the presence of mCAs and explored the possible pathophysiological and genetic risk factors for mCAs. METHODS: We analyzed mCAs in peripheral blood from 3,339 patients with IBD and investigated the clinical and genetic risk factors for mCAs. RESULTS: CD and exposure to thiopurines before the age of 20 years were identified as novel independent risk factors for mCAs (odds ratio = 2.15 and 5.68, P = 1.17e-2 and 1.60e-3, respectively). In contrast, there were no significant associations of disease duration, anti-tumor necrosis factor alpha antibodies, or other clinical factors with mCAs. Gene ontology enrichment analysis revealed that genes specifically located in the mCAs in patients with CD were significantly associated with factors related to mucosal immune responses. A genome-wide association study revealed that ERBIN, CD96, and AC068672.2 were significantly associated with mCAs in patients with CD (P = 1.56e-8, 1.65e-8, and 4.92e-8, respectively). CONCLUSION: The difference in mCAs between patients with CD and UC supports the higher incidence of hematopoietic malignancies in CD. Caution should be exercised when using thiopurines in young patients with IBD, particularly CD, in light of possible chromosomal alterations.
Thiopurine pharmacogenomics and pregnancy in inflammatory bowel disease.

Akira Andoh, Masahiro Kawahara, Takayuki Imai, Goichi Tatsumi, Osamu Inatomi, Yoichi Kakuta

Journal of gastroenterology　56　(10)　881-890　2021/07/21

DOI： 10.1007/s00535-021-01805-z 　

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The thiopurine drugs azathioprine and 6-mercaptopurine are widely used for the maintenance of clinical remission in steroid-dependent inflammatory bowel disease (IBD). Thiopurines are recommended to be continued throughout pregnancy in IBD patients, but conclusive safety data in pregnant patients remain still insufficient. On the other hand, a strong association between a genetic variant of nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15 p.Arg139Cys) and thiopurine-induced myelotoxicity has been identified. Pharmacokinetic studies have revealed that thiopurine metabolism is altered in pregnant IBD patients and suggested that the fetus may be exposed to the active-thiopurine metabolite, 6-thioguaninetriphosphate, in the uterus. A recent study using knock-in mice harboring the p.Arg138Cys mutation which corresponds to human p.Arg139Cys showed that oral administration of 6-MP at clinical dose induces a severe toxic effect on the fetus harboring the homozygous or heterozygous risk allele. This suggests that NUDT15 genotyping may be required in both women with IBD who are planning pregnancy (or pregnant) and their partner to avoid adverse outcomes for their infant. The risk to the fetus due to maternal thiopurine use is minimal but there are some concerns that are yet to be clarified. In particular, a pharmacogenomic approach to the fetus is considered necessary.
Distinct autoantibodies against endothelial protein C receptor in ulcerative colitis. International-journal

Tsuyoshi Shirai, Yoichi Kakuta, Hiroshi Fujii

Gastroenterology　161　(5)　1724-1725　2021/03/24

DOI： 10.1053/j.gastro.2021.03.037 　
HLA-DQB1*03:01 and HLA-DQA1*05:05 as key genetic determinants of infliximab response and immunogenicity in Japanese patients with inflammatory bowel disease.

Ryuya Osaka, Takeo Naito, Seik-Soon Khor, Yoichi Kakuta, Yosuke Kawai, Masao Nagasaki, Hiroshi Meguro, Hideya Iwaki, Daisuke Okamoto, Hiroshi Nagai, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Yoshitaka Kinouchi, Atsushi Masamune

Journal of gastroenterology　2026/02/06

DOI： 10.1007/s00535-026-02354-z 　

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BACKGROUND: Specific human leukocyte antigen (HLA) genotypes, particularly HLA-DQA1*05, have been proposed as predictors for infliximab (IFX) treatment response and immunogenicity in Western populations. However, the evidence regarding the effect of HLA-DQA1*05 remains limited in East Asian populations, including in Japan. Moreover, HLA-DQA1*05 frequency differs substantially from those in Western populations. Comprehensive analyses of the association between HLA alleles and IFX treatment outcomes may contribute to the identification of novel prognostic markers for IFX therapies. METHODS: We retrospectively analyzed 301 biologic-naïve Japanese patients with inflammatory bowel disease (IBD). IFX persistence was assessed at both 2-digit and 4-digit HLA allele resolutions, and associations with anti-drug antibody levels at 1 year after the initiation of IFX therapy were evaluated. RESULTS: At the 2-digit resolution analysis, HLA-DQB1*03 (hazard ratio [HR] = 2.39, p = 1.89E-06) and HLA-DQA1*05 (HR = 1.99, p = 3.91E-04) were significantly associated with early IFX discontinuation. At the 4-digit resolution analysis, HLA-DQB1*03:01 (HR = 2.03, p = 9.42E-05) and HLA-DQA1*05:05 (HR = 2.18, p = 4.42E-05) showed similar associations. All HLA-DQA1*05:05 alleles formed haplotypes with HLA-DQB1*03:01. Importantly, HLA-DQB1*03:01 was also associated with early discontinuation of IFX even when it formed haplotypes with alleles other than HLA-DQA1*05:05. Both HLA-DQB1*03:01 and HLA-DQA1*05:05 were significantly associated with elevated anti-drug antibody levels (p = 3.23E-03 and 3.54E-03, respectively). CONCLUSIONS: HLA-DQB1*03:01 encompasses the information of HLA-DQA1*05:05 and serves as a strong genetic predictor of IFX treatment persistence and immunogenicity in Japanese patients with IBD, offering a potential biomarker for personalized therapy.
Orofacial granulomatosis in pediatric Crohn's disease: clinical outcomes and genetic background in the era of biologics: a retrospective study in Japan. International-journal

Ryusuke Nambu, Takeo Naito, Mei Haruyama, Junichi Hosokawa, Hirotaka Shimizu, Ichiro Takeuchi, Shin-Ichiro Hagiwara, Tatsuki Mizuochi, Yugo Takaki, Takashi Ishige, Takuya Nishizawa, Takahiro Kudo, Natsuki Ito, Yosuke Kawai, Yoichi Kakuta, Masao Nagasaki, Toshiaki Shimizu, Itaru Iwama, Katsuhiro Arai

Intestinal research　2026/01/02

DOI： 10.5217/ir.2025.00109 　

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BACKGROUND/AIMS: Occasionally, pediatric Crohn's disease (CD) may develop after diagnosis of orofacial granulomatosis (OFG), which is characterized by chronic granulomatous lesions of the oral mucosa, lips, and perioral area. This study aimed to clarify clinical characteristics, treatment responses, and potential genetic contributors in pediatric patients with CD complicating OFG. METHODS: We studied pediatric patients with CD complicating OFG who were treated from 2013 to 2022 at 7 Japanese institutions specializing in pediatric inflammatory bowel disease. Their clinical courses were analyzed retrospectively, and analyses of 71 genes associated with monogenic inflammatory bowel disease were performed. RESULTS: Among 13 patients, 8 were girls. Median ages at diagnosis of OFG and CD were 9.2 (3.8-15.3) and 10.3 (6.4-15.3) years old, respectively. Upper gastrointestinal lesions were frequent in 8 cases (62%), while perianal lesions were present in 7 (54%). OFG failed to improve or relapsed despite remission of intestinal lesions in about half of the patients (n = 7, 54%). During follow-up, OFG went into remission in 7 patients, including 6 of the 9 who were treated with biologics (66%) and 1 of the 4 who were not (25%). In 8 patients, the NCF1 p.Arg90His allele was detected by genetic analysis; 7 were heterozygous and 1 homozygous, a higher prevalence than in the general Japanese population. CONCLUSIONS: Clinical features of OFG associated with pediatric CD are diverse, and biologic agents were beneficial for OFG patients. NCF1 p.Arg90His mutation may contribute to the pathogenesis of pediatric CD complicating OFG.
Differences in Anti-αvβ6 Integrin Antibody Expression between U.S. and Japanese Cohorts in Inflammatory Bowel Disease. International-journal

Yoichi Kakuta, Dalin Li, Philip Debbas, Soshi Okazaki, Motoi Sawahashi, Shaohong Yang, Hideya Iwaki, Daisuke Okamoto, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Hisashi Shiga, Yoshitaka Kinouchi, Tsuyoshi Shirai, Hiroshi Fujii, Dermot P B McGovern, Atsushi Masamune

Inflammatory bowel diseases　32　(1)　130-140　2026/01/01

DOI： 10.1093/ibd/izaf246 　

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BACKGROUND: Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), have complex pathologies requiring precise diagnostic tools. We evaluated the clinical utility of anti-integrin αvβ6 antibodies in diagnosing UC, focusing on differences between a U.S. cohort (self-reported White) and a Japanese cohort, and additionally assessed whether combining anti-αvβ6 with anti-EPCR improved diagnostic performance. METHODS: Serum anti-αvβ6 antibody levels were measured in 1138 participants (514 in the U.S. cohort, 624 in the Japanese cohort), including 1093 IBD cases and 45 healthy control subjects. Positivity rates and titers were compared between cohorts, and associations with clinical subphenotypes and anti-EPCR were examined. RESULTS: Anti-αvβ6 positivity was significantly higher in UC patients (85.4%) than in CD patients (16.4%) or control subjects (0%). Within UC, high positivity was observed across all disease extents, with only minor cohort differences. Longer disease duration was associated with lower positivity in both cohorts. In CD, the U.S. cohort showed higher positivity (23.4%) than the Japanese cohort (10.1%), particularly in colonic CD. Absence of ileal involvement, strictures, or perianal disease was associated with higher positivity. Anti-αvβ6 and anti-EPCR levels were strongly correlated, but their expression patterns differed in primary sclerosing cholangitis-associated IBD. Combining anti-αvβ6 and anti-EPCR improved UC diagnostic accuracy (area under the curve, 0.98; 95% confidence interval, 0.95-1.00) over either antibody alone (P = .00264). CONCLUSIONS: Anti-αvβ6 is a valuable biomarker for UC diagnosis. However, this study demonstrated differences in its behavior between U.S. and Japanese cohorts, particularly in CD. Cohort-informed interpretation and combined antibody testing may improve diagnostic precision and disease stratification in IBD.
【便通異常症の最新知識】下痢をきたす疾患偽膜性腸炎

諸井林太郎, 岩城英也, 岡本大祐, 永井博, 下山雄丞, 内藤健夫, 志賀永嗣, 角田洋一, 正宗淳

臨牀と研究　102　(10)　1048-1052　2025/10
Publisher: 大道学館出版部
ISSN： 0021-4965
Autoantibodies against endothelial protein C receptor and integrin αvβ6 predict the development of ulcerative colitis.

Motoi Sawahashi, Yoichi Kakuta, Takeo Naito, Soshi Okazaki, Kinuko Ohneda, Masatsugu Orui, Taku Obara, Soichi Ogishima, Kazuki Kumada, Hisaaki Kudo, Fuji Nagami, Atsushi Hozawa, Hideya Iwaki, Hiroshi Nagai, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Yoshitaka Kinouchi, Tsuyoshi Shirai, Hiroshi Fujii, Atsushi Masamune

Journal of gastroenterology　60　(9)　1108-1117　2025/09

DOI： 10.1007/s00535-025-02263-7 　

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BACKGROUND: A method for predicting ulcerative colitis (UC) onset has not been established. Serum autoantibodies have been suggested as potential predictive biomarkers for UC onset. We aimed to validate the risks associated with serological and environmental factors and construct a model for predicting UC development. METHODS: Using the population-based cohort studies (n > 83,000), we identified 42 individuals who were diagnosed with UC later in life and compared them with matched healthy controls. We analyzed serum anti-integrin αvβ6 antibody (anti-αvβ6) and anti-endothelial protein C receptor antibody (anti-EPCR) titers, and lifestyle and dietary habits to explore UC onset predictors. The predictive performance of the models was evaluated based on these predictors. RESULTS: The sensitivity and specificity of anti-EPCR for predicting UC onset were 51.4% and 97.8%, respectively, comparable to those of anti-αvβ6 (52.5% and 97.6%, respectively). The proportion of individuals with insomnia was significantly higher in the preclinical UC group (adjusted odds ratio = 2.14, 95% confidence interval [CI] 1.11-4.04, p = 0.019). The predictive performance of anti-EPCR alone was high with an area under the curve (AUC) of 0.89 (95%CI 0.83-0.96), and that of anti-EPCR combined with anti-αvβ6 was even better with an AUC of 0.92 (95%CI 0.87-0.97); the lifestyle model had lower predictive accuracy (AUC = 0.65, 95%CI 0.55-0.74). CONCLUSIONS: Anti-EPCR and anti-αvβ6 each strongly predict UC onset. The combined anti-EPCR and anti-αvβ6 model had stronger predictive performance than the single models.
免疫チェックポイント阻害薬により長期奏効を得た未分化肉腫の小腸転移再発例

今村健人, 内藤健夫, 岩城英也, 岡本大祐, 下山雄丞, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　219回　48-48　2025/07
Publisher: 日本消化器病学会-東北支部
約6年間にわたり消化管内に滞留したチュッパチャップスのスティック部分を下部消化管内視鏡で回収し得た一例

西村早織, 下山雄丞, 小笠原かな子, 木曽康平, 松下良, 保田悠乃介, 大坂龍也, 矢野翔太, 岩城英也, 岡本大祐, 永井博, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 斉藤将大, 大沼忍, 正宗淳

日本消化器内視鏡学会東北支部例会　174回　88-88　2025/07
Publisher: 日本消化器内視鏡学会-東北支部
Evaluation of Organoid-Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross-Sectional Study. International-journal

Atsuhiro Sasaki, Masatake Kuroha, Masaki Tosa, Seiichi Takahashi, Shinya Oomori, Eiki Nomura, Tatsuya Kikuchi, Motoyuki Onodera, Yuichiro Sato, Teruko Miyazawa, Hirofumi Chiba, Naonobu Yokoyama, Jun Kusaka, Daisuke Okamoto, Tomoyuki Handa, Mikako Sugimura, Masahiro Iwabuchi, Keiichiro Hiramoto, Hidekazu Shirota, Hideya Iwaki, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Hisashi Shiga, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Clinical and translational science　18　(6)　e70270　2025/06

DOI： 10.1111/cts.70270 　

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Exosomal microRNAs (miRNAs) are candidates for liquid biopsies. Organoid culture systems enable long-term expansion of the colon epithelium. This study evaluated exosomal miRNAs from colorectal cancer organoids for liquid biopsy. Organoids were established from normal colon and colorectal cancer tissues. Exosomes were isolated from conditioned media. miRNAs were extracted from exosomes and compared using microarray analysis. Exosomal miRNAs expression levels in the sera of healthy patients and patients with colorectal cancer were compared at a single institution. The multicenter study was validated using miRNAs upregulated in the serum of colorectal cancer patients, along with exosomal miRNAs reported to be upregulated in colorectal adenoma organoids and sera. A total of 44 exosomal miRNAs were commonly expressed in both normal colorectal epithelial cells and colorectal cancer organoids, whereas 59 were exclusively expressed in colorectal cancer organoids. In a single-center cohort study, two exosomal miRNAs (miR-4284 and miR-5100) were upregulated in the serum of colorectal cancer patients. In a multicenter study, four exosomal miRNAs (miR-4284, miR-5100, miR-1246, and miR-1290) were upregulated in the serum of patients with colorectal cancer. The combination of these four exosomal miRNAs had comparable diagnostic performance to carcinoembryonic antigen, with an area under the curve of 0.75 (95% confidence interval: 0.65-0.83) versus 0.79 (95% confidence interval: 0.70-0.87). Combining the four miRNAs with carcinoembryonic antigen improved diagnostic accuracy, with an area under the curve of 0.82 (95% confidence interval: 0.74-0.89). Exosomal miRNAs derived from colorectal cancer organoids can serve as diagnostic biomarkers for colorectal cancer.
Evolving Trends in Pediatric Inflammatory Bowel Disease Management in Japan: A Decade of Nationwide Data. International-journal

Miki Urushiyama, Kunio Tarasawa, Rintaro Moroi, Hideya Iwaki, Yusuke Hoshi, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Fumihiko Kakuta, Hisashi Shiga, Shin Hamada, Yoichi Kakuta, Kiyohide Fushimi, Yoshitaka Kinouchi, Daiki Abukawa, Kenji Fujimori, Atsushi Masamune

JGH open : an open access journal of gastroenterology and hepatology　9　(5)　e70175　2025/05

DOI： 10.1002/jgh3.70175 　

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AIMS: This study aimed to investigate the trends in pediatric inflammatory bowel diseases (IBD) management in Japan over the past decade. METHODS: We retrospectively analyzed data from Japan's nationwide database from 2012 to 2022. Patients aged ≤ 15 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) were included. Trends in the use of biologics, capsule endoscopy, total parenteral nutrition (TPN), elemental diets, surgery, and granulocyte and monocyte apheresis (GMA) were examined using the Cochrane-Armitage and Jonckheere-Terpstra trend tests. RESULTS: Among the 8037 and 6153 pediatric UC and CD admissions, respectively, the use of biologics increased significantly (CD: from 46.0% to 53.6%; UC: from 15.0% to 33.0%, p < 0.0001). The use of capsule endoscopy in pediatric patients with CD increased markedly from 6.6% to 16.7% (p < 0.0001), whereas TPN use decreased from 8.4% to 3.0% (p < 0.0001). Surgery rates for patients with CD remained at approximately 5%, whereas those for patients with UC decreased (from 3.7% to 1.7%, p = 0.002). Elemental diets for pediatric patients with CD increased (from 54.4% to 66.2%, p < 0.0001). The use of GMA decreased significantly in patients with UC (from 12.1% to 2.7%, p < 0.0001). CONCLUSION: The use of biologics and capsule endoscopy has increased in pediatric patients with IBD, whereas the use of more invasive treatments has decreased. These trends suggest a shift toward less invasive and more targeted therapeutic strategies in managing pediatric patients with IBD in Japan.
急性出血性直腸潰瘍の前向きコホート研究止血時にゲルを用いる有用性を含めた検討

菅野武, 滝井孝英, 才津旭弘, 角田洋一, 関口裕美, 竹澤敬人, 正宗淳, 矢野智則

Gastroenterological Endoscopy　67　(Suppl.1)　946-946　2025/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
Safety and effectiveness of additional triamcinolone acetonide with endoscopic radial incision and cutting for benign stenosis of the lower gastrointestinal tract: A pilot study. International-journal

Rintaro Moroi, Kotaro Nochioka, Satoshi Miyata, Hideya Iwaki, Hirofumi Chiba, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Hisashi Shiga, Masaki Tosa, Yoichi Kakuta, Shoichi Kayaba, Seiichi Takahashi, Yoshitaka Kinouchi, Atsushi Masamune

DEN open　5　(1)　e70002　2025/04

DOI： 10.1002/deo2.70002 　

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OBJECTIVES: Radial incision and cutting (RIC) is being investigated as an alternative endoscopic dilation method for lower intestinal tract stenosis, providing a high technical success rate and improving subjective symptoms. However, several patients develop re-stenosis following RIC. In this pilot study, we aimed to evaluate the safety and efficacy of triamcinolone acetonide (TA) addition after RIC. METHODS: RIC with TA was performed in 20 patients with lower gastrointestinal tract stenosis. We evaluated the rate of adverse events 2 months after RIC with TA. We investigated the short- and long-term prognoses, as well as the improvement in subjective symptoms, using a visual analog scale. RESULTS: The delayed bleeding rate after RIC was 23.8%. Endoscopic hemostasis was achieved in all patients with delayed bleeding. No perforations were observed. The cumulative re-stenosis-free, re-intervention-free, and surgery-free rates 1 year after RIC were 52.9%, 63.7%, and 85.2%, respectively. Subjective symptoms, including abdominal pain, abdominal bloating, nausea, and dyschezia, significantly improved after RIC with TA. CONCLUSION: Although additional TA administration after RIC could be safe, additional TA may not be effective on luminal patency after dilation. Further investigation is warranted.
便潜血陽性を契機に発見された原発性硬化性胆管炎を合併した潰瘍性大腸炎の1例

有我泰樹, 岩城英也, 永井博, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器がん検診学会雑誌　63　(2)　225-226　2025/03
Publisher: (一社)日本消化器がん検診学会
ISSN： 1880-7666

eISSN： 2185-1190
消化管希少疾患に挑む:Bench to Bedside 家族性地中海熱疑診例におけるMEFV遺伝子変異陽性率と治療反応性の検討

内藤健夫, 松下良, 角田洋一, 岩城英也, 永井博, 下山雄丞, 諸井林太郎, 志賀永嗣, 正宗淳

日本消化器病学会雑誌　122　(臨増総会)　A65-A65　2025/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
日本から世界に発信する臨床研究から炎症性腸疾患の未来を考える児のNUDT15遺伝子型によるチオプリン服用中の妊娠・出産の安全性に関する多施設共同研究

角田洋一, 諸井林太郎, 志賀永嗣, 正宗淳

日本消化器病学会雑誌　122　(臨増総会)　A136-A136　2025/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
消化器,肝胆膵疾患におけるバイオマーカーの探索炎症性腸疾患おける抗インテグリンανβ6抗体の人種差に関する検討

角田洋一, 澤橋基, 内藤健夫, 正宗淳

日本消化器病学会雑誌　122　(臨増総会)　A182-A182　2025/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
炎症性腸疾患の非侵襲的病勢評価方法の進歩血清プロテオーム解析による既存検査系を活用した潰瘍性大腸炎の内視鏡的活動性を反映するバイオマーカーの探索と検証

伊藤啓紀, 角田洋一, 諸井林太郎, 正宗淳

日本消化器病学会雑誌　122　(臨増総会)　A190-A190　2025/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
カプセル内視鏡検査が鑑別に有用であった寄生虫症と寄生虫妄想症

乙竹秀明, 岩城英也, 永井博, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器内視鏡学会東北支部例会　173回　109-109　2025/02
Publisher: 日本消化器内視鏡学会-東北支部
1ヵ月で0-IIaからIIa+IIcへと形態変化したSM massive大腸癌の1例

目黒博志, 内藤健夫, 岩城英也, 永井博, 下山雄丞, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器内視鏡学会東北支部例会　173回　111-111　2025/02
Publisher: 日本消化器内視鏡学会-東北支部
消化器疾患診療の現状と近未来・下部消化管の部当院における入院重症UCの治療成績 JAK阻害剤は有効な選択肢となりえるか?

永井博, 志賀永嗣, 岩城英也, 下山雄丞, 内藤健夫, 諸井林太郎, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　218回　105-105　2025/02
Publisher: 日本消化器病学会-東北支部
消化器疾患における基礎研究の役割と展望炎症性腸疾患の新規治療戦略としての腸管上皮細胞内グルタミン酸保持

岩城英也, 保田悠乃介, 角田洋一, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　218回　120-120　2025/02
Publisher: 日本消化器病学会-東北支部
酸化マグネシウム内服中,クエン酸マグネシウム高張液服用により高マグネシウム血症を来した一例

近藤成美, 下山雄介, 岩城英也, 永井博, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　218回　141-141　2025/02
Publisher: 日本消化器病学会-東北支部
Endoscopic radial incision and cutting using balloonassisted enteroscopy for small intestinal stenosis related to Crohn's disease: a pilot study. International-journal

Rintaro Moroi, Kotaro Nochioka, Satoshi Miyata, Hideya Iwaki, Hirofumi Chiba, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Hisashi Shiga, Masaki Tosa, Yoichi Kakuta, Shoichi Kayaba, Seiichi Takahashi, Yoshitaka Kinouchi, Atsushi Masamune

Intestinal research　2025/01/21

DOI： 10.5217/ir.2024.00143 　

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BACKGROUND/AIMS: Radial incision and cutting (RIC) is an alternative dilation method for stenosis of the lower gastrointestinal tract. However, its safety and efficacy for the small intestine requiring balloon-assisted enteroscopy (BAE) remain limited. Therefore, this pilot study aimed to evaluate the safety and efficacy of RIC using BAE. METHODS: We included 10 patients with Crohn's disease and performed 12 sessions of RIC for 10 lesions. The rate of adverse events 1 month after RIC was the primary outcome, whereas short- and long-term prognoses and improvements in subjective symptoms that were evaluated using a visual analog scale were the secondary outcomes. RESULTS: The technical success rate for RIC, defined as scope passage immediately following the procedure, was 100% (12/12). The rates of delayed bleeding and perforation were 0% (0/12). One patient developed restenosis because of the worsening of Crohn's disease and underwent surgery 2 months after RIC. The cumulative restenosis-, reintervention-, and surgery-free rates at 1 year after RIC were 67.5%, 78.7%, and 90.0%, respectively. Abdominal pain, abdominal bloating, nausea, and difficulties in defecation significantly improved 4 weeks after RIC. CONCLUSIONS: RIC for small intestine using BAE has the potential to be safe and effective for relieving symptoms (jRCT identifier jRCTs022200040).
The outcomes of electronic personal health records in patients with heart failure or coronary artery disease

Kotaro Nochioka, Satoshi Yasuda, Takashi Shiroto, Saori Yamamoto, Haruka Sato, Yuhi Hasebe, Shigeo Godo, Makoto Nakano, Tomohiko Shindo, Kensuke Nishimiya, Kiyotaka Hao, Jun Takahashi, Keisuke Ido, Yoichi Kakuta, Hiroaki Shimizu, Hiroaki Shimokawa, Masaharu Nakayama

ESC Heart Failure　2024/11/14
Publisher: Wiley
DOI： 10.1002/ehf2.15079 　

ISSN： 2055-5822

eISSN： 2055-5822

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Abstract Background There are limited data on the efficacy of smartphone‐based personal health records (PHRs) in patients with cardiovascular disease. This study aimed to examine the processes, outcomes and challenges associated with the implementation of integrated PHRs in patients with heart failure (HF) or coronary artery disease (CAD). Methods This prospective single‐group study evaluated the effects of a PHR system with the capability to capture electronic health records and vital signs in patients with HF or CAD. The outcomes measured were the 6 ‐month changes in blood pressure (BP), body weight (BW), brain natriuretic peptide (BNP) levels, lipid profiles and haemoglobin (Hb) A1c levels. Results Between June 2021 and March 2022, we enrolled 111 patients (median age: 61 years and 47% women) with CAD and/or HF. Over 6 months, the PHR review count distribution was skewed: median 749 times (lowest 2, highest 5724)/180 days, suggesting both low and excessive PHR users. After 3 days, 23% of the patients discontinued inputting their vital signs and medication status. At 6 months, compared with patients who discontinued, those who continued to input their vital signs (N = 86) showed a significant decrease in their systolic BP and LDL‐C levels but not in the diastolic BP, BW, BNP, HDL‐C, triglyceride or HbA1c levels. Conclusions The implementation of smartphone‐based PHRs in daily practice is challenging for patients with HF or CAD. However, we observed positive indications of the benefits of PHR in these patients. Trial registration number UMIN000044369
【大腸の炎症を内視鏡で診る】Crohn病の内視鏡診療 RICを用いた内視鏡的拡張術

諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

消化器内視鏡　36　(11)　1539-1540　2024/11
Publisher: (株)東京医学社
ISSN： 0915-3217
【炎症性腸疾患update】[Chapter 3]IBD special situationのupdate IBD治療中の感染症合併に対する治療・対策

志賀永嗣, 角田洋一, 正宗淳

内科　134　(5)　1106-1109　2024/11
Publisher: (株)南江堂
ISSN： 0022-1961

eISSN： 2432-9452
【大腸の炎症を内視鏡で診る】Crohn病の内視鏡診療 RICを用いた内視鏡的拡張術

諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

消化器内視鏡　36　(11)　1539-1540　2024/11
Publisher: (株)東京医学社
ISSN： 0915-3217
【炎症性腸疾患2024】炎症性腸疾患の病態炎症性腸疾患の遺伝的背景

角田洋一, 内藤健夫, 岩城英也, 永井博, 下山雄丞, 諸井林太郎, 志賀永嗣, 木内喜孝, 正宗淳

胃と腸　59　(10)　1323-1330　2024/10
Publisher: (株)医学書院
ISSN： 0536-2180

eISSN： 1882-1219
【炎症性腸疾患2024】炎症性腸疾患に対する新たな内視鏡治療の試み Crohn病の腸管切除後吻合部狭窄に対するRadial Incision and Cutting法

諸井林太郎, 志賀永嗣, 岩城英也, 永井博, 下山雄丞, 内藤健夫, 角田洋一, 正宗淳

胃と腸　59　(10)　1599-1602　2024/10
Publisher: (株)医学書院
ISSN： 0536-2180

eISSN： 1882-1219
炎症性腸疾患の病態解明に向けた研究の展開血清自己抗体価測定による潰瘍性大腸炎の発症前診断能の検討

澤橋基, 角田洋一, 正宗淳

日本消化器病学会雑誌　121　(臨増大会)　A601-A601　2024/10
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
【炎症性腸疾患2024】炎症性腸疾患の病態炎症性腸疾患の遺伝的背景

角田洋一, 内藤健夫, 岩城英也, 永井博, 下山雄丞, 諸井林太郎, 志賀永嗣, 木内喜孝, 正宗淳

胃と腸　59　(10)　1323-1330　2024/10
Publisher: (株)医学書院
ISSN： 0536-2180

eISSN： 1882-1219
【炎症性腸疾患2024】炎症性腸疾患に対する新たな内視鏡治療の試み Crohn病の腸管切除後吻合部狭窄に対するRadial Incision and Cutting法

諸井林太郎, 志賀永嗣, 岩城英也, 永井博, 下山雄丞, 内藤健夫, 角田洋一, 正宗淳

胃と腸　59　(10)　1599-1602　2024/10
Publisher: (株)医学書院
ISSN： 0536-2180

eISSN： 1882-1219
ストレス潰瘍 2024 不眠状態と炎症性腸疾患増悪の因果関係を評価するための前向き観察研究

大山秀晃, 諸井林太郎, 佐久間篤, 永井博, 下山雄丞, 内藤健夫, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

潰瘍　51　68-68　2024/09
Publisher: (一社)日本潰瘍学会
ISSN： 2189-7956
ストレス潰瘍 2024 不眠状態と炎症性腸疾患増悪の因果関係を評価するための前向き観察研究

大山秀晃, 諸井林太郎, 佐久間篤, 永井博, 下山雄丞, 内藤健夫, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

潰瘍　51　68-68　2024/09
Publisher: (一社)日本潰瘍学会
ISSN： 2189-7956
Chronic poor sleep is associated with increased disease activity in patients with ulcerative colitis: Prospective observational study in Japan. International-journal

Hideaki Oyama, Rintaro Moroi, Atsushi Sakuma, Yusuke Shimoyama, Hiroshi Nagai, Takeo Naito, Hisashi Shiga, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Journal of Crohn's & colitis　2024/07/25

DOI： 10.1093/ecco-jcc/jjae116 　

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BACKGROUND AND AIM: Although sleep disorders are associated with the pathogenesis of inflammatory bowel disease, the causal relationship is unclear. Therefore, in this study we aimed to clarify the causal relationship between them. METHODS: We administered the Pittsburgh Sleep Questionnaire to participants during regular visits to evaluate their sleep condition and prospectively observed the participants. Participants were divided into poor sleep and non-poor sleep groups according to their first and second questionnaire scores. We compared inflammatory bowel disease relapse rates between the two groups. RESULTS: The study population included 139 patients with inflammatory bowel disease, including 60 with chronic poor sleep. Disease relapse rate was significantly higher in the poor sleep group than in the non-poor sleep group (28.3% vs. 8.9%; P=0.0033). Ulcerative colitis relapse rate was significantly higher in the poor sleep group than in the non-poor sleep group (34.5% vs. 10.3%, P=0.031). Multivariate analysis identified chronic poor sleep as a clinical factor that affected inflammatory bowel disease relapse (OR=6.69, 95% CI: 2.23-20.0, P=0.0007) and ulcerative colitis relapse (OR=8.89, 95% CI: 1.57-50.2, P=0.014). The Kaplan-Meier curve showed significantly lower cumulative treatment retention rates in the poor sleep group than in the non-poor sleep group (all patients, P=0.0061; ulcerative colitis, P=0.025). CONCLUSIONS: Concomitant chronic poor sleep may have a negative influence on the disease activity in patients with inflammatory bowel disease, especially in those with ulcerative colitis.
Differences in Clinical Practice and Disease Course between Elderly-Onset and Long-Standing Elderly Ulcerative Colitis: A Single-Center Study in Japan.

Motoi Sawahashi, Rintaro Moroi, Yoichi Kakuta, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Hisashi Shiga, Atsushi Masamune

The Tohoku journal of experimental medicine　2024/07/11

DOI： 10.1620/tjem.2024.J063 　
炎症性腸疾患にニューモシスチス肺炎を合併した2症例

木曽康平, 下山雄丞, 有我泰樹, 保田悠乃介, 小笠原かな子, 松下良, 矢野翔太, 大坂龍也, 澤橋基, 伊藤啓紀, 平塚敬士, 佐々木敦宏, 漆山みき, 岩城英也, 永井博, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　217回　92-92　2024/07
Publisher: 日本消化器病学会-東北支部
人工肛門造設を伴う腸管切除術により良好な経過を得られた腸管型ベーチェット病の一例

安田有希, 伊勢一郎, 齋藤達, 小野智之, 梶原大輝, 鈴木秀幸, 唐澤秀明, 渡辺和宏, 大山秀晃, 志賀永嗣, 角田洋一, 正宗淳, 亀井尚, 大沼忍, 海野倫明

日本消化器病学会東北支部例会プログラム・抄録集　217回　93-93　2024/07
Publisher: 日本消化器病学会-東北支部
人工肛門造設を伴う腸管切除術により良好な経過を得られた腸管型ベーチェット病の一例

安田有希, 伊勢一郎, 齋藤達, 小野智之, 梶原大輝, 鈴木秀幸, 唐澤秀明, 渡辺和宏, 大山秀晃, 志賀永嗣, 角田洋一, 正宗淳, 亀井尚, 大沼忍, 海野倫明

日本消化器病学会東北支部例会プログラム・抄録集　217回　93-93　2024/07
Publisher: 日本消化器病学会-東北支部
消化管疾患に対する内視鏡診療の進歩クローン病術後モニタリングにおけるカプセル内視鏡の位置づけ

永井博, 志賀永嗣, 諸井林太郎, 角田洋一, 正宗淳

日本消化器内視鏡学会東北支部例会　172回　69-69　2024/07
Publisher: 日本消化器内視鏡学会-東北支部
胃癌腹膜播種による下部直腸狭窄に対してproximal release型大腸ステントを留置した一例

高橋早友未, 永井博, 岩城英也, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器内視鏡学会東北支部例会　172回　101-101　2024/07
Publisher: 日本消化器内視鏡学会-東北支部
炎症性腸疾患にニューモシスチス肺炎を合併した2症例

木曽康平, 下山雄丞, 有我泰樹, 保田悠乃介, 小笠原かな子, 松下良, 矢野翔太, 大坂龍也, 澤橋基, 伊藤啓紀, 平塚敬士, 佐々木敦宏, 漆山みき, 岩城英也, 永井博, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　217回　92-92　2024/07
Publisher: 日本消化器病学会-東北支部
Genetically Predicted Higher Levels of Caffeic Acid Are Protective Against Ulcerative Colitis: A Comprehensive Metabolome Analysis

Takeo Naito, Ryuya Osaka, Yoichi Kakuta, Yosuke Kawai, Seik-Soon Khor, Junji Umeno, Katsushi Tokunaga, NCBN Controls WGS Consortium, Hantsue Ishibashi-Ueda, Tsutomu Tomita, Michio Noguchi, Ayako Takahashi, Yu-ichi Goto, Sumiko Yoshida, Kotaro Hattori, Ryo Matsumura, Aritoshi Iida, Yutaka Maruoka, Hiroyuki Gatanaga, Masaya Sugiyama, Satoshi Suzuki, Kengo Miyo, Yoichi Matsubara, Akihiro Umezawa, Kenichiro Hata, Tadashi Kaname, Kouichi Ozaki, Haruhiko Tokuda, Hiroshi Watanabe, Shumpei Niida, Eisei Noiri, Koji Kitajima, Yosuke Omae, Reiko Miyahara, Hideyuki Shimanuki, Yosuke Kawai, Katsushi Tokunaga, Hiroshi Nagai, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Masao Nagasaki, Yoshitaka Kinouchi, Atsushi Masamune

Inflammatory Bowel Diseases　2024/06/29

DOI： 10.1093/ibd/izae143 　

ISSN： 1078-0998 1536-4844

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<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>It is crucial to pinpoint the metabolites that cause Crohn’s disease (CD) and ulcerative colitis (UC) to comprehend their pathogenesis and identify possible targets for therapy. To achieve this goal, we performed the first metabolome-wide Mendelian randomization (MR) study of Japanese patients with CD and UC.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>As exposure datasets, genetic instruments with blood-circulating metabolites were obtained from the Tohoku Medical Megabank Organization, which includes 204 metabolites from the genome-wide association study data of 7843 Japanese individuals. As outcome datasets, we enrolled Japanese patients with CD (n = 1803), Japanese patients with UC (n = 1992), and healthy controls (n = 2022). The main analysis utilized the inverse variance–weighted method, while stability of the findings was evaluated through sensitivity analyses.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>After single nucleotide polymorphism (SNP) filtering, 169 SNPs for 45 metabolites were available for MR. Genetically predicted elevated circulating trans-glutaconic acid and tryptophan were associated with a lower CD risk (odds ratio [OR], 0.68; P = 5.95 × 10−3; and OR, 0.64; P = 1.90 × 10−2, respectively). Genetically predicted elevated caffeic acid was associated with a lower UC risk (OR, 0.67; P = 4.2 × 10−4), which remained significant after multiple testing correction. We identified a causal link between UC and 3-hydroxybutyrate (OR, 2.21; P = 1.41 × 10−2), trans-glutaconic acid (OR, 0.72; P = 1.77 × 10−2), and 2-hydroxyvaleric acid (OR, 1.31; P = 4.23 × 10−2). There was no evidence of pleiotropy or reverse causal effects for these candidate metabolites.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>In our metabolome-wide MR study, we discovered a notable protective effect of caffeic acid against UC.</jats:p> </jats:sec>
White spots around colorectal tumors are cancer-related findings and may aid endoscopic diagnosis: a prospective study in Japan. International-journal

Kai Korekawa, Yusuke Shimoyama, Fumiyoshi Fujishima, Hiroshi Nagai, Takeo Naito, Rintaro Moroi, Hisashi Shiga, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Clinical endoscopy　2024/06/21

DOI： 10.5946/ce.2024.027 　

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BACKGROUND/AIMS: During endoscopy, white spots (WS) are sometimes observed around benign or malignant colorectal tumors; however, few reports have investigated WS, and their significance remains unknown. Therefore, we investigated the significance of WS from clinical and pathological viewpoints and evaluated its usefulness in endoscopic diagnosis. METHODS: Clinical data of patients with lesions diagnosed as epithelial tumors from January 1, 2019, to December 31, 2020, were analyzed (n=3,869). We also performed a clinicopathological analysis of adenomas or carcinomas treated with endoscopic resection (n=759). Subsequently, detailed pathological observations of the WS were performed. RESULTS: The positivity rates for WS were 9.3% (3,869 lesions including advanced cancer and non-adenoma/carcinoma) and 25% (759 lesions limited to adenoma and early carcinoma). Analysis of 759 lesions showed that the WS-positive lesion group had a higher proportion of cancer cases and larger tumor diameters than the WS-negative group. Multiple logistic analysis revealed the following three statistically significant risk factors for carcinogenesis: positive WS, flat lesions, and tumor diameter ≥5 mm. Pathological analysis revealed that WS were macrophages that phagocytosed fat and mucus and were white primarily because of fat. CONCLUSIONS: WS are cancer-related findings and can become a new criterion for endoscopic resection in the future.
Clinical practice and outcome of patients with elderly-onset ulcerative colitis: Insights from a nationwide claims database study in Japan. International-journal

Rintaro Moroi, Yoichi Kakuta, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Hisashi Shiga, Yoshitaka Kinouchi, Atsushi Masamune

JGH open : an open access journal of gastroenterology and hepatology　8　(6)　e13103　2024/06

DOI： 10.1002/jgh3.13103 　

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BACKGROUND AND AIM: The number of older patients with ulcerative colitis is increasing; however, limited data exist regarding the differences between elderly- and non-elderly-onset ulcerative colitis. We aimed to compare the clinical practice and course of elderly-onset ulcerative colitis with those of non-elderly-onset ulcerative colitis. METHODS: We selected older patients with ulcerative colitis and divided them into the elderly- and non-elderly-onset ulcerative colitis groups according to their age at onset. We compared the cumulative systemic steroid-free, molecular targeting drug-free, and surgery-free rates between the two groups. We performed a multivariate analysis to identify the clinical factors related to systemic steroid administration, the use of molecular targeting drugs, surgery, and death. RESULTS: We collected data of 2669 and 277 elderly and non-elderly-onset ulcerative colitis patients, respectively. The cumulative systemic steroid-free rate of elderly-onset ulcerative colitis was significantly lower than that of non-elderly-onset ulcerative colitis. However, no difference was observed in the cumulative molecular targeting drugs and surgery-free rates between the two groups. Elderly-onset ulcerative colitis significantly increased the risk of systemic steroid administration and death but not the use of molecular targeting drugs and surgery. CONCLUSION: The disease severity of ulcerative colitis and clinical practice may not differ between the elderly- and non-elderly-onset groups. However, elderly-onset ulcerative colitis was associated with increased mortality risk. Thus, we need to pay attention to the patients' condition and appropriate timing of surgery for patients with elderly-onset ulcerative colitis.
Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.

Motoki Makuuchi, Yoichi Kakuta, Junji Umeno, Toshimitsu Fujii, Tetsuya Takagawa, Takashi Ibuka, Miki Miura, Yu Sasaki, Sakuma Takahashi, Hiroshi Nakase, Hiroki Kiyohara, Keiichi Tominaga, Yosuke Shimodaira, Sakiko Hiraoka, Nobuhiro Ueno, Shunichi Yanai, Takeo Yoshihara, Kazuki Kakimoto, Katsuyoshi Matsuoka, Ryohei Hayashi, Sohachi Nanjo, Itaru Iwama, Yoh Ishiguro, Hirofumi Chiba, Katsuya Endo, Takashi Kagaya, Tomohiro Fukuda, Yasuhisa Sakata, Takahiro Kudo, Tomohisa Takagi, Kenichi Takahashi, Makoto Naganuma, Masaru Shinozaki, Noriyuki Ogata, Hiroki Tanaka, Kazuyuki Narimatsu, Haruka Miyazaki, Takashi Ishige, Motoyuki Onodera, Yu Hashimoto, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Hisashi Shiga, Yoshitaka Kinouchi, Akira Andoh, Tadakazu Hisamatsu, Atsushi Masamune

Journal of gastroenterology　2024/04/08

DOI： 10.1007/s00535-024-02099-7 　

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BACKGROUND: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. METHODS: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. RESULTS: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. CONCLUSIONS: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.
Rupture of ectopic varices of the ascending colon occurring after pancreatic cancer surgery: A case report and literature review. International-journal

Yushi Inomata, Takeo Naito, Takashi Hiratsuka, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Yoichi Kakuta, Kimiko Kayada, Yuki Ohara, Naoki Asano, Shuichi Aoki, Michiaki Unno, Atsushi Masamune

DEN open　4　(1)　e255　2024/04

DOI： 10.1002/deo2.255 　

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A 69-year-old woman, a long-term survivor of subtotal stomach-preserving pancreatoduodenectomy with the splenic vein resection for pancreatic cancer, visited our hospital with a chief complaint of bloody stools. Previously, she was diagnosed with varices in the ascending colon due to left-sided portal hypertension after pancreatoduodenectomy by computed tomography and colonoscopy. After emergency hospitalization, she went into shock, and blood tests showed acute progression of severe anemia. Computed tomography showed a mosaic-like fluid accumulation from the ascending colon to the rectum. She was diagnosed with ruptured varices in the ascending colon. Emergency colonoscopy was performed, and treatment with endoscopic injection sclerotherapy using N-butyl-2-cyanoacrylate was successful. Ectopic varices occur at any location other than the esophagus and stomach, and colonic varices are rare among them. They are mostly caused by portal hypertension due to liver cirrhosis. However, with the trend of improving the prognosis for patients with pancreatic cancer, we should occasionally pay attention to the development of ectopic varices including colonic varices in patients who have undergone pancreatoduodenectomy with superior mesenteric and splenic veins resection. Treatment methods for colonic varices varied from case to case, including conservative therapy, interventional radiology, and endoscopic procedure. In this case, endoscopic injection sclerotherapy was successfully performed without any complications. To the best of our knowledge, this is the first study to report successful treatment with endoscopic injection sclerotherapy for varices in the ascending colon caused by left-sided portal hypertension after pancreatoduodenectomy. Colonic varices should be considered in patients with obscure gastrointestinal bleeding after pancreatoduodenectomy.
Prescribing in pregnant women with inflammatory bowel disease and its relationship to congenital malformations in Japan. International-journal

Sayumi Takahashi, Yoichi Kakuta, Taku Obara, Tomofumi Ishikawa, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Hisashi Shiga, Nariyasu Mano, Yoshitaka Kinouchi, Atsushi Masamune

Journal of gastroenterology and hepatology　2024/03/27

DOI： 10.1111/jgh.16549 　

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BACKGROUND AND AIM: Inflammatory bowel disease (IBD) frequently affects younger patients and poses various challenges concerning pregnancy and childbirth. Maintaining good disease control throughout pregnancy is crucial, but expectant and pregnant patients may worry about the fetal impact of medications, leading to treatment discontinuation due to uncertainty about this issue. This study investigated the real-world drug-prescribing practices for pregnant patients with IBD in Japan and their potential connection to major congenital malformations (MCMs). METHODS: Overall, 277 female IBD patients who gave birth between 2010 and 2019 were selected from the JMDC claims database. The prescribing patterns of IBD medications and MCMs in the patients' offspring were analyzed. RESULTS: Among pregnant IBD patients, 74.4% received at least one medication from 90 days before pregnancy to 90 days after delivery. Trends in medication prescriptions during pregnancy in 2010-2019 revealed consistent use of oral 5-ASA, variable use of topical medications, a decrease in systemic steroids, and an increase in biologics. The prevalence of MCMs in children born to IBD-affected mothers did not differ significantly between those who did and did not receive IBD medications (8.6% vs 6.8%). Although circulatory system MCMs were slightly more common in the IBD medication group (4.9% vs 1.4%), this difference was not significant. Logistic regression analysis did not reveal an association between MCM risk and first-trimester use of IBD medications, including corticosteroids and biologics. CONCLUSIONS: This study provides insights into medication patterns in pregnant IBD patients and suggests no increased risk of MCMs associated with first-trimester IBD medication use.
Live-attenuated vaccination in patients with inflammatory bowel disease while continuing or after elective switch to vedolizumab. International-journal

Hisashi Shiga, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Intestinal research　2024/03/26

DOI： 10.5217/ir.2023.00203 　

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BACKGROUND/AIMS: Vedolizumab (VDZ) is a gut-selective agent with a favorable safety profile. We aimed to assess the feasibility of elective switch from other advanced therapies to VDZ and subsequent live-attenuated vaccination while continuing VDZ in patients with inflammatory bowel diseases (IBD). METHODS: We measured antibody titers specific for measles, rubella, mumps, and varicella viruses in IBD patients under immunosuppressive therapy. Those with negative titers and without vaccination history were judged unimmunized. Patients were administered vaccines while continuing VDZ or switched to VDZ if receiving other advanced therapies and then administered vaccines. Co-primary outcomes were the rate of maintaining disease severity after vaccination and the rate without vaccine-induced infection. RESULTS: Among 107 unimmunized patients, 37 agreed to receive live-attenuated vaccines while continuing VDZ (17 patients) or after switching to VDZ (20 patients). In the 20 patients who electively switched to VDZ, disease severity was maintained except for 1 patient who developed intestinal infection. After 54 weeks, 18 patients (90%) continued to receive VDZ, excluding 2 patients who reverted to their originally administered biologics. In all 37 patients administered live-attenuated vaccines under VDZ treatment, disease severity was maintained after vaccination. Antibody titers became positive or equivocal in 34 patients (91.9%). There were no cases of vaccine-induced infection during a median observation period of 121 weeks. CONCLUSIONS: While live-attenuated vaccines are contraindicated under immunosuppressive therapy, they may be safely administered while receiving VDZ immunotherapy. Switching from other advanced therapies to VDZ and subsequently receiving live-attenuated vaccines may be a safe alternative in unimmunized patients.
A Phase II Clinical Trial to Study the Safety of Triamcinolone after Endoscopic Radial Incision and Cutting Dilatation for Benign Stenosis of the Lower Gastrointestinal Tract: A Study Protocol.

Rintaro Moroi, Hisashi Shiga, Kotaro Nochioka, Hirofumi Chiba, Yusuke Shimoyama, Motoyuki Onodera, Takeo Naito, Masaki Tosa, Yoichi Kakuta, Yuichiro Sato, Shoichi Kayaba, Seichi Takahashi, Satoshi Miyata, Yoshitaka Kinouchi, Atsushi Masamune

The Kurume medical journal　2024/03/19

DOI： 10.2739/kurumemedj.MS7012005 　

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BACKGROUND: Lower gastrointestinal tract stenosis is commonly diagnosed and is typically treated with surgery or endoscopic balloon dilation (EBD). Radial incision and cutting (RIC) is a novel treatment approach that has several benefits compared with EBD and surgery. Although RIC has demonstrated a high technical success rate and has been shown to improve subjective symptoms, previous studies revealed that restenosis after RIC remain unsolved. Herein, we report the design of a prospective, multicenter, single-arm, interventional, phase II trial to evaluate the safety of local triamcinolone acetonide (TA) administration and its feasibility in preventing restenosis after RIC for lower gastrointestinal tract stenosis. METHODS: The major inclusion criteria are age 20-80 years and the presence of benign stenosis in the lower gastrointestinal tract accessible by colonoscope. We will perform RIC followed by local administration of TA to 20 participants. The primary outcome is the safety of local TA administration, which will be assessed by determining the frequency of adverse events of special interest. The secondary outcomes are the technical success rate of RIC, duration of procedure, improvement in subjective symptoms, and duration of hospitalization. The outcomes, improvement in subjective symptoms, and long-term results will be evaluated using descriptive statistics, Student's t-test, and Kaplan-Meier curve, respectively. DISCUSSION: This explorative study will provide useful information regarding the safety of TA administration after RIC, which may contribute to further investigations.
リキッドバイオプシーがもたらす新たな消化器病治療戦略オルガノイド由来miRNAを用いた大腸腫瘍のリキッドバイオプシー法の有用性の検証

佐々木敦宏, 黒羽正剛, 永井博, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会雑誌　121　(臨増総会)　A182-A182　2024/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
難治性クローン病に対するリサンキズマブの短期有効性の評価

漆山みき, 永井博, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会雑誌　121　(臨増総会)　A340-A340　2024/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
潰瘍性大腸炎術後に生じた小腸炎にウパダシチニブ投与が著効した一例。

松下良, 内藤健夫, 角田洋一, 志賀永嗣, 諸井林太郎, 下山雄丞, 永井博, 正宗淳

日本消化器内視鏡学会東北支部例会　171回　107-107　2024/02
Publisher: 日本消化器内視鏡学会-東北支部
潰瘍性大腸炎術後、ストマ周囲に壊疽性膿皮症を発症した一例

保田悠乃介, 永井博, 猪股優志, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　216回　47-47　2024/02
Publisher: 日本消化器病学会-東北支部
Thiopurines exert harmful effects on spermatogenesis in Nudt15R138C knock-in mice.

Yoshihiro Yokota, Takayuki Imai, Masahiro Kawahara, Osamu Inatomi, Atsushi Nishida, Yoichi Kakuta, Atsushi Masamune, Akira Andoh

Journal of gastroenterology　59　(2)　109-118　2024/02

DOI： 10.1007/s00535-023-02059-7 　

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BACKGROUND: The association between thiopurine use and testicular reproductive functions remains unclear. In this study, we investigated whether thiopurines affect testicular functions based on the NUDT15 genotypes using Nudt15R138C knock-in mice. METHODS: The male Nudt15R138C knock-in mice (9-12 weeks) were treated with mercaptopurine (MP: 0.5 mg/kg/day) for 4 or 12 weeks. To examine reversibility, some mice were maintained for a further 12 weeks under MP-free condition. RESULTS: After MP treatment for 4 weeks, Nudt15R138C/R138C mice exhibited a significant reduction of testis weight compared to Nudt15+/+ mice and Nudt15+/R138C mice. The epithelial height and diameter of seminiferous tubules were significantly reduced in Nudt15R138C/R138C mice compared to Nudt15+/+ and Nudt15+/R138C mice. Apoptotic cells were significantly increased in Nudt15R138C/R138C mice, and most of apoptotic cells were spermatogonia. There were no significant changes in sperm counts and sperm morphology in MP-treated Nudt15R138C/R138C mice after 4-week MP treatment. On the other hand, after MP treatment for 12 weeks, the Nudt15+/R138C mice, but not Nudt15+/+ mice, exhibited a significant reduction in the testis weight and atrophic changes of seminiferous tubules, but these changes disappeared after 12-week rearing under MP-free condition. Despite a significant increase in abnormal sperm rate, there were no changes in the ability to conceive. No differences in serum levels of follicle-stimulating hormone or testosterone were observed between MP-treated Nudt15+/R138C and Nudt15+/+ mice after 12-week MP treatment. CONCLUSIONS: Thiopurines exert harmful effects on testicular reproductive function according to host NUDT15 genotypes.
Clinical Practice and Safety of Endoscopic Balloon Dilation for Crohn's Disease-Related Strictures: A Nationwide Claim Database Analysis in Japan. International-journal

Rintaro Moroi, Kunio Tarasawa, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Hisashi Shiga, Shin Hamada, Yoichi Kakuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

Gastroenterology research and practice　2024　1291965-1291965　2024

DOI： 10.1155/2024/1291965 　

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Introduction: Although endoscopic balloon dilation (EBD) is a common therapeutic approach for managing strictures associated with Crohn's disease (CD), the clinical application and complication rates of EBD remain unclear. Methods: We collected admission data for patients who underwent EBD using a nationwide database. We compared EBD outcomes between ileal and colonic strictures, CD and ulcerative colitis, and CD and anastomotic strictures arising from cancer-related surgery. Subsequently, propensity score matching was employed to facilitate comparisons between each group. Results: The median duration of hospital stay was 4 days. Endoscopic hemostasis and urgent surgery rates after EBD for CD-related strictures were considerably low (0.035% and 0.11%, respectively). Most patients with CD underwent only one EBD procedure during a single admission. Although no significant differences in patient backgrounds and severe complications were observed between ileal and colonic stricture in CD, multiple EBD procedures were more commonly performed for ileal strictures than for colonic stricture. Moreover, EBD for ileal stricture was more frequently conducted in high-volume centers than in low-volume centers. Regarding severe complications after EBD, no significant differences were observed between CD-related strictures and ulcerative colitis or anastomotic strictures related to cancer surgery. Conclusion: Our findings support the safe and effective use of EBD for both ileal and colonic strictures associated with CD. The clinical practice and safety outcomes of EBD for CD-related strictures were comparable to those for strictures stemming from other etiologies.
Dickkopf 1 is expressed in normal fibroblasts during early stages of colorectal tumorigenesis. International-journal

Yushi Inomata, Masatake Kuroha, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Hisashi Shiga, Yoichi Kakuta, Hideaki Karasawa, Shinobu Onuma, Yoshitaka Kinouchi, Atsushi Masamune

Cancer medicine　13　(2)　e6992　2024/01

DOI： 10.1002/cam4.6992 　

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BACKGROUND AND PURPOSE: Colorectal cancer progression from adenoma to cancer is a time-intensive process; however, the interaction between normal fibroblasts (NFs) with early colorectal tumors, such as adenomas, remains unclear. Here, we analyzed the response of the microenvironment during early tumorigenesis using co-cultures of organoids and NFs. MATERIALS AND METHODS: Colon normal epithelium, adenoma, cancer organoid, and NFs were established and co-cultured using Transwell inserts. Microarray analysis of NFs was performed to identify factors expressed early in tumor growth. Immunostaining of clinical specimens was performed to localize the identified factor. Functional analysis was performed using HCT116 cells. Serum DKK1 levels were measured in patients with colorectal cancer and adenoma. RESULTS: Colorectal organoid-NF co-culture resulted in increased organoid diameter and cell viability in normal epithelial and adenomatous organoids but not in cancer organoids. Microarray analysis of NFs revealed 18 genes with increased expression when co-cultured with adenoma and cancer organoids. Immunohistochemical staining revealed DKK1 expression in the tumor stroma from early tumor growth. DKK1 stimulation reduced HCT116 cell proliferation, while DKK1 silencing by siRNA transfection increased cell proliferation. Serum DKK1 level was significantly higher in patients with advanced cancer and adenoma than in controls. Serum DKK1 level revealed area-under-the-curve values of 0.78 and 0.64 for cancer and adenoma, respectively. CONCLUSION: These findings contribute valuable insights into the early stages of colorectal tumorigenesis and suggest DKK1 as a tumor suppressor. Additionally, serum DKK1 levels could serve as a biomarker to identify both cancer and adenoma, offering diagnostic possibilities for early-stage colon tumors. The present study has a few limitations. We considered using DKK1 as a candidate gene for gene transfer to organoids and NFs; however, it was difficult due to technical problems and the slow growth rate of NFs. Therefore, we used cancer cell lines instead. In addition, immunostaining and ELISA were based on the short-term collection at a single institution, and further accumulation of such data is desirable. As described above, most previous reports were related to advanced cancers, but in this study, new findings were obtained by conducting experiments on endoscopically curable early-stage tumors, such as adenomas.
Clinical Utilization of Generic Drugs and Biosimilars for Ulcerative Colitis Treatment: Insights from a Nationwide Database Study in Japan. International-journal

Rintaro Moroi, Yoichi Kakuta, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Hisashi Shiga, Yoshitaka Kinouchi, Atsushi Masamune

Inflammatory intestinal diseases　9　(1)　29-39　2024

DOI： 10.1159/000536146 　

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INTRODUCTION: Limited data exist regarding the prevalence and clinical practice involving generic drugs and biosimilars for treating ulcerative colitis (UC) in Japan. We aimed to clarify the clinical usage of these generic drugs and biosimilars for UC treatment in Japan using a nationwide database. METHODS: We collected data from 30,675 UC cases, along with their prescriptions for both generic drugs or biosimilars and their original counterparts, using a medical claim database provided by DeSC Healthcare, Inc. We calculated the prescription and penetration rates of generic drugs and biosimilars and demonstrated the transition of these rates. Additionally, the cumulative retention rates between infliximab originator and biosimilar were compared using the Kaplan-Meier method. RESULTS: The prescription rate of generic mesalazine increased from approximately 10% in 2015 to over 30% in 2021. Although the prescription rate of generic molecular targeting drugs (MTDs) also increased from approximately 0.15% in 2014 to 2.5% in 2021, the increment was lower than that of generic mesalazine. The penetration rates of generic 5-aminosalicylic acid and tacrolimus ranged from over 30% to approximately 50%. Infliximab biosimilar achieved an approximate 20% penetration rate, whereas adalimumab achieved <5%. The cumulative retention rates did not differ between infliximab originator and biosimilar. CONCLUSIONS: The penetration rates of generics and biosimilars for UC treatment are relatively low compared with those for treatment in other fields and the goal of the Ministry of Health, Labor, and Welfare. Several countermeasures are necessary for the widespread use of generics and biosimilars, ultimately contributing to cost-effective and sustainable healthcare delivery.
The Efficacy of Combination Therapy with Ustekinumab and Budesonide for Crohn's Disease: A Randomized Controlled Trial. International-journal

Rintaro Moroi, Kasumi Hishinuma, Yumi Sugawara, Kotaro Nochioka, Yusuke Shimoyama, Takeo Naito, Hisashi Shiga, Yoichi Kakuta, Yoshitaka Kinouchi, Ichiro Tsuji, Atsushi Masamune

Inflammatory intestinal diseases　9　(1)　40-46　2024

DOI： 10.1159/000535070 　

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INTRODUCTION: Limited data exist on the efficacy of combination therapy with ustekinumab and budesonide in patients with Crohn's disease. Our objective was to compare the clinical outcomes of ustekinumab and budesonide combination therapy with those of ustekinumab monotherapy. METHODS: In this phase 2 single-center, double-blind, randomized controlled trial, we assigned 19 patients with Crohn's disease with a Crohn's disease activity index (CDAI) equal to or greater than 220 and less than 450 in a 1:1 ratio to receive ustekinumab and budesonide or ustekinumab for 32 weeks. The primary endpoint was the clinical remission rate at 8 weeks. The secondary endpoints were the clinical remission rate at 32 weeks and mucosal healing rates at 8 and 32 weeks. RESULTS: Of 19 patients, the mean age was 37.8 years, and 42.1% were women (CDAI ≥220 and <450). There was no difference between combination therapy and ustekinumab monotherapy in terms of clinical remission rates (50.0% vs. 30.0%, p = 0.39 at 8 weeks and 37.5% vs. 20.0%, p = 0.41) and mucosal healing rates (75.0% vs. 90.0%, p = 0.40 and 37.5% vs. 60.0%, p = 0.34 at 8 and 32 weeks, respectively). The most common adverse event was an exacerbation of Crohn's. There were no differences in safety profiles between the two groups. CONCLUSIONS: Our study showed no difference between ustekinumab monotherapy and ustekinumab and budesonide combination therapy in terms of the induction and maintenance of remission (trial registration number: jRCTs021200013).
Small bowel cancer in a patient with Crohn's disease diagnosed preoperatively by double-balloon enteroscopy.

Kai Korekawa, Takeo Naito, Fumiyoshi Fujishima, Hiroshi Nagai, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Yoichi Kakuta, Atsushi Masamune

Clinical journal of gastroenterology　16　(6)　836-841　2023/12

DOI： 10.1007/s12328-023-01846-2 　

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A 53-year-old female patient, who had been treated for Crohn's disease for approximately 20 years, was admitted to our hospital with a chief complaint of persistent bloody stools. Colonoscopy, computed tomography, and magnetic resonance enterography revealed two stenoses of the ileum and multiple enlarged lymph nodes around the oral-side ileal stenosis. We accordingly performed transoral double-balloon enteroscopy and found ileal stenosis with an irregular mucosal surface. Based on pathological examination of the stenosis, adenocarcinoma of the small bowel was diagnosed for the oral-side stenosis. The stenosis on the anal side was benign. The two stenoses were resected simultaneously, and lymph node dissection was performed on the cancerous lesion. The diagnosis of the cancerous lesion was pStage IIIB, and immunohistochemical staining was positive for tumor protein 53. Patients with Crohn's disease are at a high risk of small bowel cancer, but no surveillance protocol has been established to date. We encountered a case of Crohn's disease in which radical surgery was possible, owing to preoperative pathological diagnosis, by using balloon-assisted enteroscopy. In this paper, we report a case that suggests the importance of performing balloon-assisted enteroscopy when small bowel stenosis is detected in patients with Crohn's disease.
【潰瘍性大腸炎に対する同種同効薬を使い分ける!】抗TNFα抗体製剤の使い分けは?

志賀永嗣, 角田洋一, 正宗淳

IBD Research　17　(4)　279-285　2023/12
Publisher: (株)先端医学社
ISSN： 1881-6533
Usefulness and difficulties with the thiopurine pharmacogenomic NUDT15 genotyping test: Analysis of real-world data in Japan.

Yoichi Kakuta, Motohiro Kato, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Hisashi Shiga, Yoshitaka Kinouchi, Atsushi Masamune

Journal of pharmacological sciences　153　(3)　161-169　2023/11

DOI： 10.1016/j.jphs.2023.09.002 　

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The usefulness of NUDT15 genotyping as a pharmacogenomic test for thiopurine has been established. The first such test developed to date, NUDT15 genotyping was approved for reimbursement in Japan in February 2019 for all indicated patients. We retrospectively examined claims data in Japan and confirmed that the proportion of patients who undergo genotyping before initiating a new thiopurine regimen has increased; furthermore, genotyping has improved the rate of treatment continuation and reduced on-treatment hospitalization. However, the genotyping rate before thiopurine induction was >50% for patients with inflammatory bowel disease and <20% for those with other immune-related diseases, indicating significant variation by disease field. Additionally, over 10% of tests were found to have been performed inappropriately, such as multiple genotyping of the same patient or testing more than 2 weeks after starting treatment. Although NUDT15 genotyping for patients requiring thiopurine treatment has been shown to improve thiopurine treatment continuation rate, measures are required to address the systematic issues identified in our analysis.
Effectiveness of Antibiotics for Uncomplicated Diverticulitis: A Retrospective Investigation Using a Nationwide Database in Japan. International-journal

Rintaro Moroi, Kunio Tarasawa, Hiroshi Nagai, Yusukue Shimoyama, Takeo Naito, Hisashi Shiga, Shin Hamada, Yoichi Kakuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

Digestion　1-9　2023/10/19

DOI： 10.1159/000534167 　

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INTRODUCTION: The efficacy of antibiotics for diverticulitis without abscess or peritonitis (uncomplicated diverticulitis) is controversial. We aimed to investigate the effectiveness of antibiotics for uncomplicated diverticulitis. METHODS: We collected admission data for patients with acute uncomplicated diverticulitis using a nationwide database. We divided eligible admissions into two groups according to antibiotic initiation within 2 days after admission (antibiotic group vs. nonantibiotic group). We conducted propensity score matching and compared the rates of surgery (intestinal resection and stoma creation), in-hospital death, and medical costs between the groups. We also performed multivariate analysis to identify the clinical factors that affect surgery. RESULTS: We enrolled 131,936 admissions; among these, we obtained 6,061 pairs after propensity score matching. Rates of both intestinal resection and stoma creation in the antibiotic group were lower than those in the nonantibiotic group (0.61 vs. 3.09%, p < 0.0001, and 0.08 vs. 0.26%, p = 0.027, respectively). Median costs in the antibiotic group were higher than those in the nonantibiotic group (315,820 JPY vs. 300,175 JPY, p < 0.0001, respectively). Multivariate analysis showed that non-initiation of antibiotics within 2 days after admission was a clinical factor that increased the risk of intestinal resection (odds ratio [OR] = 5.19, 95% confidence interval [CI]: 4.38-6.16, p < 0.0001) and stoma creation (OR = 2.68, 95% CI: 1.53-4.70, p = 0.0006). CONCLUSION: Our results indicated that antibiotics for uncomplicated diverticulitis expected to have moderate to severe disease activity may reduce the risk of intestinal resection and stoma creation. Further investigations are warranted.
小児IBDの探究-その奥へ- 非小児期発症例と比較した小児期発症炎症性腸疾患の臨床的特徴と長期予後の検討

漆山みき, 虻川大樹, 諸井林太郎, 篠崎まみ, 成重勇太, 星雄介, 角田文彦, 角田洋一, 正宗淳

日本小児栄養消化器肝臓学会雑誌　37　(Suppl.)　53-53　2023/10
Publisher: (一社)日本小児栄養消化器肝臓学会
ISSN： 1346-9037
炎症性腸疾患モデルのxCT阻害による抗炎症作用

岩城英也, 関根弘樹, 村上昌平, 加藤伸史, 北村洋, 魏范研, 佐藤英世, 福田真嗣, 曽我朋義, 角田洋一, 正宗淳, 本橋ほづみ

日本生化学会大会プログラム・講演要旨集　96回　[1T08a-238)]　2023/10
Publisher: (公社)日本生化学会
Long-term prognosis and clinical practice for new-onset ulcerative colitis in the era of biologics: A Japanese retrospective study. International-journal

Rintaro Moroi, Yoichi Kakuta, Taku Obara, Yusuke Shimoyama, Takeo Naito, Hisashi Shiga, Yoshitaka Kinouchi, Atsushi Masamune

JGH open : an open access journal of gastroenterology and hepatology　7　(10)　682-689　2023/10

DOI： 10.1002/jgh3.12957 　

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BACKGROUND AND AIM: There is a scarcity of data on long-term outcomes in patients with new-onset ulcerative colitis (UC) in the era of biologics. We aimed to clarify the long-term prognosis of UC and the clinical practice of prescriptions for UC. METHODS: We collected 6689 new-onset UC cases using a medical claim database provided by DeSC Healthcare, Inc. We investigated the surgery-free, systemic steroid-free, and molecular targeting drug-free rates and compared their differences based on UC-onset age. We used multivariate analysis to identify clinical factors affecting long-term prognosis and investigated the transition of prescriptions for UC. RESULTS: The surgery-free, systemic steroid-free, and molecular targeting drug-free rates at 5 years post-UC diagnosis were 98.5%, 61.0%, and 88.7%, respectively. Pediatric patients had higher surgery-free rates compared with elderly patients and non-pediatric/non-elderly patients (P = 0.022), whereas the systemic steroid-free and molecular targeting drug-free rates were significantly lower (P< 0.0001, P < 0.0001, respectively). The retention rate of the first molecular targeting drug did not differ between drugs. The prescription rates of systemic steroid, immunomodulator, and molecular targeting drug increased from the second quarter in 2014 to the fourth quarter in 2021 (29.8%-39.1%, 6.8%-17.7%, and 7.6%-16.4%, respectively). CONCLUSIONS: We clarified the long-term prognosis and clinical practice of new-onset UC cases. The long-term outcome after UC onset might improve because of increasing use of new therapeutic agents. Further investigations are warranted.
Comparative effectiveness of tacrolimus and infliximab in hospitalized patients with ulcerative colitis. International-journal

Takahiro Takahashi, Hisashi Shiga, Kunio Tarasawa, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Yoichi Kakuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

Clinical and translational gastroenterology　2023/09/27

DOI： 10.14309/ctg.0000000000000642 　

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INTRODUCTION: Cyclosporine or infliximab (IFX) have been used to avoid surgery in patients with severe refractory ulcerative colitis (UC). Tacrolimus (Tac) is occasionally used as an alternative to cyclosporine; however, the comparative efficacy of Tac and IFX has not been reported. We aimed to compare the effectiveness of Tac and IFX in hospitalized UC patients. METHODS: In a propensity score (PS)-matched cohort derived from a large nationwide database, 4-year effectiveness was compared between patients initiated on Tac or IFX. The primary outcome was the colectomy rate during the index hospitalization. We also analyzed the cumulative medication discontinuation, UC-related re-hospitalization, and colectomy rates after discharge. RESULTS: Among 29,239 hospitalized patients, 4,565 were extracted for eligibility, of whom 2,170 were treated with Tac and the remaining 2,395 with IFX. After PS matching, 1,787 patients were selected for each group. During the index hospitalization, excluding patients who switched to another molecular-targeted agent, the colectomy rate was higher in the Tac group than the IFX group (7.8% vs 4.2%, P <0.01). Among patients discharged without colectomy, the cumulative medication discontinuation (28.4% vs 17.1%, P <0.01) and re-hospitalization (22.4% vs 15.4%, P <0.01) rates were higher in the Tac group than the IFX group; however, there was no difference in the cumulative colectomy rate (3.3% vs 2.7%). CONCLUSIONS: Although Tac and IFX were effective for avoiding surgery in hospitalized UC patients, IFX was more effective than Tac. IFX also had higher long-term effectiveness. Future prospective studies comparing the efficacy of Tac and IFX is warranted.
【IBDに生じる腸管外合併症の病態と治療を探る!】IBDに伴う血栓症や血管炎はどのようなメカニズムで発症し,どう治療するのか?

内藤健夫, 角田洋一, 正宗淳

IBD Research　17　(3)　180-185　2023/09
Publisher: (株)先端医学社
ISSN： 1881-6533
HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn's disease patients. International-journal

Fumiko Shimoda, Takeo Naito, Yoichi Kakuta, Yosuke Kawai, Katsushi Tokunaga, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Masao Nagasaki, Yoshitaka Kinouchi, Atsushi Masamune

The pharmacogenomics journal　2023/07/17

DOI： 10.1038/s41397-023-00312-z 　

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Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early infliximab (IFX) treatment failure in the Caucasian Crohn's disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese biologics-naive CD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The C allele of rs2097432 significantly increased the risk of early discontinuation of IFX [Hazard ratio (HR) = 2.23 and P-value = 0.026]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B which attenuates macrophage-mediated inflammation, reached genome-wide significance (HR = 6.04 and P-value = 7.93E-9). Pathway analysis suggested association of signaling by PDGF and FCGR activation signaling with IFX persistence (P-value = 8.56E-5 and 5.80E-4, respectively).
ベスト・アウトカムをめざした消化器病診療潰瘍性大腸炎に対するフィルゴチニブの寛解導入成績(短期有効性)

永井博, 志賀永嗣, 諸井林太郎, 角田洋一, 正宗淳

日本消化器病学会東北支部例会・日本消化器内視鏡学会東北支部例会プログラム・抄録集　215回・170回　74-74　2023/07
Publisher: 日本消化器病学会-東北支部
術前診断に苦慮した潰瘍性大腸炎合併大腸腫瘍の一例

小笠原かな子, 永井博, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会東北支部例会・日本消化器内視鏡学会東北支部例会プログラム・抄録集　215回・170回　175-175　2023/07
Publisher: 日本消化器病学会-東北支部
Genetics of inflammatory bowel disease in East Asia: From population to individual. International-journal

Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Journal of gastroenterology and hepatology　38　(7)　1116-1122　2023/07

DOI： 10.1111/jgh.16244 　

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Genetic analysis of inflammatory bowel disease has identified many disease susceptibility genes in a large number of cases, mainly in Europe and North America. However, because of the ethnic differences in genetic background, analysis in various ethnic groups is needed. Although genetic analysis in East Asia began at the same time as in the West, the total number of patients analyzed has remained limited in Asia. To address these issues, meta-analyses across East Asian countries are underway, and the genetic analysis of inflammatory bowel disease in East Asians is entering a new phase. New findings on the genetic background factors associated with inflammatory bowel disease originating from East Asia have also been made, such as the association between chromosomal mosaic alteration and this disease. Genetic analysis has been conducted mainly through studies that consider patients as a group. Some of these results, such as the identified relationship between the NUDT15 gene and thiopurine-related adverse events, are beginning to be applied to the actual treatment of individuals. Meanwhile, genetic analyses of rare diseases have focused on the development of diagnostic methods and therapies by identifying causative gene mutations. Recently, genetic analysis has been moving from research on populations and pedigrees to the stage of identifying and using personal genetic information of each patient, which is important for personalized medical care. To achieve this, close collaboration between specialists in complex genetic analysis and clinicians will be critical.
【遺伝を考える】(II章)遺伝学的診断個別診療分野における遺伝学的診断の進歩消化器領域

正宗淳, 角田洋一

日本医師会雑誌　152　(特別1)　S156-S159　2023/06
Publisher: (公社)日本医師会
ISSN： 0021-4493
【分類不能腸炎(IBDU)の現状と将来展望】炎症性腸疾患における血清学的バイオマーカー診断の現状

角田洋一, 岡崎創司, 澤橋基, 猪股優志, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 木内喜孝, 白井剛志, 藤井博司, 正宗淳

胃と腸　58　(6)　783-788　2023/06
Publisher: (株)医学書院
ISSN： 0536-2180

eISSN： 1882-1219
無投薬で6年経過したのち,検診を契機に肛門管癌と診断されたクローン病の1例

大山秀晃, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器がん検診学会雑誌　61　(Suppl総会)　469-469　2023/06
Publisher: (一社)日本消化器がん検診学会
ISSN： 1880-7666

eISSN： 2185-1190
【遺伝を考える】(II章)遺伝学的診断個別診療分野における遺伝学的診断の進歩消化器領域

正宗淳, 角田洋一

日本医師会雑誌　152　(特別1)　S156-S159　2023/06
Publisher: (公社)日本医師会
ISSN： 0021-4493
当院における消化管狭窄に対する内視鏡的バルーン拡張術に関する検討

大坂龍也, 諸井林太郎, 下田楓美子, 下山雄丞, 内藤健夫, 志賀永嗣, 角田洋一, 正宗淳

Gastroenterological Endoscopy　65　(Suppl.1)　884-884　2023/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
当院における消化管狭窄に対する内視鏡的バルーン拡張術に関する検討

大坂龍也, 諸井林太郎, 下田楓美子, 下山雄丞, 内藤健夫, 志賀永嗣, 角田洋一, 正宗淳

Gastroenterological Endoscopy　65　(Suppl.1)　884-884　2023/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
消化器疾患とビッグデータ消化器疾患解析におけるビッグデータとしての診断群分類包括評価の有用性の検討

諸井林太郎, 角田洋一, 正宗淳

日本消化器病学会雑誌　120　(臨増総会)　A39-A39　2023/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
3次元オルガノイド培養モデルを用いた大腸腫瘍と線維芽細胞の相互関係の検証

猪股優志, 黒羽正剛, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会雑誌　120　(臨増総会)　A316-A316　2023/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
自施設および大規模データから見たtacrolimusとinfliximabの効果比較

高橋隆宏, 志賀永嗣, 岩城英也, 高橋早友未, 幕内大貴, 大山秀晃, 是川海, 猪股優志, 下田楓美子, 矢野恒太, 下山雄丞, 内藤健夫, 諸井林太郎, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会雑誌　120　(臨増総会)　A325-A325　2023/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
当院における高齢潰瘍性大腸炎患者の予後と難治例の治療選択に関する検討

澤橋基, 角田洋一, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 正宗淳

日本消化器病学会雑誌　120　(臨増総会)　A339-A339　2023/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
The Impact of Concomitant Ulcerative Colitis on the Clinical Course in Patients with Primary Sclerosing Cholangitis: An Investigation Using a Nationwide Database in Japan. International-journal

Rintaro Moroi, Kota Yano, Kunio Tarasawa, Yusuke Shimoyama, Takeo Naito, Hisashi Shiga, Shin Hamada, Yoichi Kakuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

Inflammatory intestinal diseases　7　(3-4)　147-154　2023/03

DOI： 10.1159/000529338 　

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INTROODUCTION: Primary sclerosing cholangitis (PSC) is a rare disease, especially in Asian countries. PSC often develops during ulcerative colitis (UC). Little is known about the severity of PSC in patients with UC. Thus, this study aimed to investigate the impact of concomitant UC on the clinical course of patients with PSC using a nationwide database in Japan. METHODS: We collected data on patients who were admitted for PSC using a nationwide database and divided eligible admissions according to concomitant UC (PSC-UC group vs. PSC-alone group). We conducted propensity score matching and compared the rates of liver transplantation, biliary drainage, and other clinical events between the two groups. We also conducted a multivariate analysis to identify the clinical factors that affect biliary drainage, cholangiocarcinoma, and liver transplantation. RESULTS: We enrolled 672 patients after propensity score matching. The rate of liver transplantation in the PSC-UC group was lower than that in the PSC-alone group (2.2 vs. 5.4%, p = 0.002), whereas the rate of biliary drainage did not differ between the two groups (38.1 vs. 33.8%, p = 0.10). On multivariate analysis, concomitant UC was identified as a clinical factor that decreased the risk of liver transplantation (odds ratio = 0.40, 95% confidence interval: 0.23-0.68, p = 0.0007). DISCUSSION: Concomitant UC in patients with PSC may decrease the risk of liver transplantation. The milder disease activity of PSC with UC is more likely compared to that of PSC without UC.
希少疾患の内視鏡像 Cronkhite-canada症候群の内視鏡像の推移

下山雄丞, 角田洋一, 正宗淳

日本消化器内視鏡学会東北支部例会　169回　81-81　2023/02
Publisher: 日本消化器内視鏡学会-東北支部
膵癌術後,上行結腸に発生した異所性静脈瘤破裂に対して緊急内視鏡的硬化療法により救命しえた1例

猪股優志, 内藤健夫, 下山雄丞, 諸井林太郎, 志賀永嗣, 角田洋一, 加宅田公子, 大原祐樹, 浅野直喜, 青木修一, 海野倫明, 正宗淳

日本消化器内視鏡学会東北支部例会　169回　119-119　2023/02
Publisher: 日本消化器内視鏡学会-東北支部
JAK阻害薬高用量使用下で敗血症を発症した高齢潰瘍性大腸炎の1例

澤橋基, 角田洋一, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　214回　82-82　2023/02
Publisher: 日本消化器病学会-東北支部
IBDの治療の最前線、外科的治療戦略も含めて潰瘍性大腸炎の入院例におけるタクロリムスとインフリキシマブの比較

高橋隆宏, 志賀永嗣, たら澤邦男, 下山雄丞, 内藤健夫, 諸井林太郎, 角田洋一, 藤森研司, 正宗淳

日本消化管学会雑誌　7　(Suppl.)　153-153　2023/01
Publisher: (一社)日本消化管学会
ISSN： 2433-3840

eISSN： 2435-8967
IBDの治療の最前線、外科的治療戦略も含めて潰瘍性大腸炎の入院例におけるタクロリムスとインフリキシマブの比較

高橋隆宏, 志賀永嗣, たら澤邦男, 下山雄丞, 内藤健夫, 諸井林太郎, 角田洋一, 藤森研司, 正宗淳

日本消化管学会雑誌　7　(Suppl.)　153-153　2023/01
Publisher: (一社)日本消化管学会
ISSN： 2433-3840

eISSN： 2435-8967
Collection of patient-generated health data with a mobile application and transfer to hospital information system via QR codes

Chong Song, Yoichi Kakuta, Kenichi Negoro, Rintaro Moroi, Atsushi Masamune, Erina Sasaki, Naoki Nakamura, Masaharu Nakayama

Computer Methods and Programs in Biomedicine Update　3　100099-100099　2023
Publisher: Elsevier BV
DOI： 10.1016/j.cmpbup.2023.100099 　

ISSN： 2666-9900
Severity of acute pancreatitis in patients with inflammatory bowel disease in the era of biologics: A propensity-score-matched analysis using a nationwide database in Japan. International-journal

Rintaro Moroi, Kunio Tarasawa, Mio Ikeda, Ryotaro Matsumoto, Yusuke Shimoyama, Takeo Naito, Tetsuya Takikawa, Hisashi Shiga, Shin Hamada, Yoichi Kakuta, Kazuhiro Kikuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

JGH open : an open access journal of gastroenterology and hepatology　7　(1)　40-47　2023/01

DOI： 10.1002/jgh3.12849 　

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BACKGROUND AND AIM: Acute pancreatitis (AP) is a rare extraintestinal manifestation of inflammatory bowel disease (IBD). Several studies from Western countries have reported that the severity of AP in patients with IBD is similar to that in the general population; however, its severity in patients from Eastern countries in the era of biologics remains unclear. This study aimed to investigate the severity of AP in patients with IBD and the effect of biologics on the severity of AP using a nationwide database. METHODS: We divided 1138 eligible AP admissions from the Diagnosis Procedure Combination database system into IBD and non-IBD groups after propensity score matching, and compared the severity of AP. We divided the IBD group into ulcerative colitis (UC) and Crohn's disease (CD) subgroups and compared each with the non-IBD group. Logistic regression analysis was conducted to identify the clinical factors affecting acute pancreatitis. RESULTS: IBD and UC groups had lower rate of severe AP compared to the non-IBD group (13.7% vs 28.3%, P < 0.0001 and 11.0% vs 28.3%, P < 0.0001, respectively). There were no differences in the rates of severe AP between the CD and non-IBD groups. Multivariate analysis showed that biologics did not affect the severity of AP. CONCLUSION: The severity of AP in patients with IBD may be lower than that in the general population; biologics for IBD may not worsen its severity. Further prospective studies are required to clarify the severity of AP in patients with IBD.
Depression is associated with increased disease activity in patients with ulcerative colitis: A propensity score-matched analysis using a nationwide database in Japan. International-journal

Hideaki Oyama, Rintaro Moroi, Kunio Tarasawa, Yusuke Shimoyama, Takeo Naito, Atsushi Sakuma, Hisashi Shiga, Yoichi Kakuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

JGH open : an open access journal of gastroenterology and hepatology　6　(12)　876-885　2022/12

DOI： 10.1002/jgh3.12836 　

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BACKGROUND AND AIM: The incidence and prevalence of psychiatric disorders are elevated in patients with inflammatory bowel disease (IBD). Whether psychiatric disorders could affect the clinical course of IBD is uncertain and controversial. We aimed to evaluate the impact of psychiatric disorders, particularly depression, on the clinical course of IBD using a nationwide database in Japan. METHODS: We collected data on admissions with IBD using the Diagnosis Procedure Combination database system introduced in Japan. We divided eligible admissions into IBD with and without depression groups using propensity score matching and compared the rates of surgery, use of molecular targeted drugs and biologics, systemic steroid administrations, and in-hospital death. We also conducted a logistic regression analysis to identify clinical factors affecting surgery, the use of molecular targeted drugs and biologics, and systemic steroid administrations. RESULTS: The rates of surgery, use of two or more molecular targeted drugs, systemic steroid administrations, and in-hospital deaths in the ulcerative colitis (UC) with depression group were higher than in the UC without depression group. Multivariate analysis of UC showed that depression increased the odds of systemic steroid administrations, use of two or more molecular targeted drugs, and surgery. However, analysis of Crohn's disease showed that only steroid administrations were associated with depression. CONCLUSION: Our study demonstrated an association between a worse clinical course of UC and depression. Although this result indicates that depression might be associated with increased disease activity in patients with UC, the causal relationship is still unclear. Further prospective studies are warranted.
Current Status and Future Prospects of Inflammatory Bowel Disease Genetics. International-journal

Yoichi Kakuta, Takeo Naito, Yoshitaka Kinouchi, Atsushi Masamune

Digestion　104　(1)　1-9　2022/11/02

DOI： 10.1159/000527340 　

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BACKGROUND: The genetic background of inflammatory bowel diseases (IBDs) has been explored using genetic analysis techniques, such as genome-wide association studies for the population and whole-exome sequencing analyses of family lineages in cases of very early onset. SUMMARY: The results of genetic analysis for IBD indicated the involvement of innate and adaptive immune system variations and epithelial abnormalities in the pathogenesis of IBD. Several associated genes were also reported, indicating that IBD occurs in a heterogeneous population with an extremely diverse background. The genetic background of IBDs is currently being studied to understand not only its onset but also its prognosis, response to treatment, and adverse effects. In the future, it will be possible to use an individual's genetic information for determining appropriate treatment. In Japan, the NUDT15 polymorphism test is performed before administering thiopurine preparations. However, because of racial differences in genetic analysis, biased analysis toward some racial groups may result in overlooking important genetic backgrounds of IBD. KEY MESSAGE: Studies of IBDs in a more diverse range of races are expected to elucidate genetic factors through a transethnic analysis, thereby aiding the development of novel treatments and precision medicine for IBDs.
シスチン/グルタミン酸トランスポーターxCTの阻害による慢性炎症性腸疾患モデルでの抗炎症作用

岩城英也, 関根弘樹, 村上昌平, 加藤伸史, 北村大志, 魏范研, 福田真嗣, 曽我朋義, 角田洋一, 正宗淳, 本橋ほづみ

日本生化学会大会プログラム・講演要旨集　95回　1T08a-07　2022/11
Publisher: (公社)日本生化学会
シスチン/グルタミン酸トランスポーターxCTの阻害による慢性炎症性腸疾患モデルでの抗炎症作用

岩城英也, 関根弘樹, 村上昌平, 加藤伸史, 北村大志, 魏范研, 福田真嗣, 曽我朋義, 角田洋一, 正宗淳, 本橋ほづみ

日本生化学会大会プログラム・講演要旨集　95回　1T08a-07　2022/11
Publisher: (公社)日本生化学会
Long-term effectiveness of ustekinumab comparable to antitumor necrosis factor agents in patients with Crohn's disease. International-journal

Hisashi Shiga, Kunio Tarasawa, Rintaro Moroi, Motoki Makuuchi, Takahiro Takahashi, Yusuke Shimoyama, Masatake Kuroha, Yoichi Kakuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

Journal of gastroenterology and hepatology　37　(11)　2105-2112　2022/11

DOI： 10.1111/jgh.15992 　

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BACKGROUND: Ustekinumab (UST), an antibody against the p40 subunit of interleukin-12/23, has been proven to be effective in patients with Crohn's disease (CD). However, large, long-term comparative studies of UST against anti--tumor necrosis factor (TNF) agents are lacking. We compared the effectiveness of anti-TNF agents and UST in CD patients without prior use of biologics. METHODS: We used a large nationwide anonymized Japanese database containing administrative medical claims data and various related patient data. In a propensity score-matched cohort with similar clinical characteristics, 2-year effectiveness was compared between patients treated with infliximab or adalimumab (anti-TNF group) and those treated with UST (UST group). Primary outcomes were cumulative rates of hospitalization, surgery, and persistence. RESULTS: Among 53 540 CD patients, 7047 were extracted for eligibility, of which 5665 were treated with an anti-TNF agent and 1382 with UST. After propensity score matching, the cumulative hospitalization rates were comparable between anti-TNF and UST groups (P = 0.85; 25.3% vs 26.5% at 1 year, 33.8% vs 39.8% at 2 years). The cumulative surgery rates were also comparable between these groups (P = 0.46; 5.5% vs 5.1% at 1 year, 8.3% vs 8.4% at 2 years). The persistence rate at 1 year was higher in UST group (90.8% vs 92.5%), and that at 2 years was higher in anti-TNF group (81.2% and 74.6%); however, there was no significant difference in the cumulative persistence rate (P = 0.55). CONCLUSIONS: Anti-TNF agents and UST appear to have comparable effectiveness for CD patients without prior use of biologics.
Reduced antiviral seropositivity among patients with inflammatory bowel disease treated with immunosuppressive agents. International-journal

Hisashi Shiga, Takahiro Takahashi, Manabu Shiraki, Yasuhiro Kojima, Tsuyotoshi Tsuji, Sho Takagi, Keiichiro Hiramoto, Naonobu Yokoyama, Mikako Sugimura, Masahiro Iwabuchi, Katsuya Endo, Motoyuki Onodera, Yuichirou Sato, Yosuke Shimodaira, Eiki Nomura, Tatsuya Kikuchi, Hirofumi Chiba, Shinya Oomori, Hisaaki Kudo, Kazuki Kumada, Satoshi Nagaie, Soichi Ogishima, Fuji Nagami, Yusuke Shimoyama, Rintaro Moroi, Masatake Kuroha, Yoichi Kakuta, Takashi Ishige, Yoshitaka Kinouchi, Atsushi Masamune

Scandinavian journal of gastroenterology　58　(4)　1-8　2022/10/12

DOI： 10.1080/00365521.2022.2132831 　

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BACKGROUND: Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy. AIMS: To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy. METHODS: This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays. RESULTS: A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients. CONCLUSIONS: IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.
IBDのTreat to Target戦略における内視鏡検査の意義と課題クローン病における内視鏡的寛解の予測因子としてのバイオマーカー

志賀永嗣, 角田洋一, 正宗淳

Gastroenterological Endoscopy　64　(Suppl.2)　1990-1990　2022/10
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
IBD病態を踏まえた今後の治療ストラテジー抗EPCR抗体価と潰瘍性大腸炎の病態および治療反応性との関連に関する検討

角田洋一, 白井剛志, 正宗淳

Gastroenterological Endoscopy　64　(Suppl.2)　2023-2023　2022/10
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
免疫抑制療法下の炎症性腸疾患患者ではCOVID-19ワクチンの免疫応答が低下する

志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会雑誌　119　(臨増大会)　A446-A446　2022/10
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Serum leucine-rich alpha-2 glycoprotein as a predictive factor of endoscopic remission in Crohn's disease. International-journal

Izuru Abe, Hisashi Shiga, Hirofumi Chiba, Teruko Miyazawa, Shinya Oomori, Yusuke Shimoyama, Rintaro Moroi, Masatake Kuroha, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Journal of gastroenterology and hepatology　37　(9)　1741-1748　2022/09

DOI： 10.1111/jgh.15907 　

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BACKGROUND AND AIM: The usefulness of fecal calprotectin (FC) and serum leucine-rich alpha-2 glycoprotein (LRG) assessing the activity of Crohn's disease (CD) remains to be fully demonstrated in Asia. The present study aimed to elucidate whether FC and LRG could predict endoscopic remission (ER) in Japanese patients with CD. METHODS: Between October 2018 and July 2021, we prospectively observed treatment courses of CD patients treated with biologic agents. The optimal cutoff values of Crohn's Disease Activity Index (CDAI), serum C-reactive protein (CRP), serum albumin (Alb), FC, and LRG levels for predicting ER at week 52 were calculated using receiver operating characteristic (ROC) curves. We also analyzed the correlations between the achievement of clinical remission (CR) or biomarker remission (BR) at week 12/24/52 and ER at week 52. RESULTS: Among 53 patients who completed 52 weeks of observation, 20 (37.7%) achieved ER at week 52. Using the calculated cutoff values, patients who achieved CR (CDAI ≤ 112) or BR (CRP ≤ 0.42 mg/dL, Alb ≥ 3.8 g/dL, FC ≤ 287 μg/g, or LRG ≤ 13.6 μg/mL) at week 12/24/52 had a higher ER rate at week 52. FC-BR at week 12/24 showed low sensitivity (0.58/0.60) but high specificity (0.78/0.74) for predicting ER; LRG-BR at week 12/24 also showed low sensitivity (0.68/0.74) but high specificity (0.87/0.78). However, FC-BR and LRG-BR at week 52 had improved sensitivity (0.80/0.84) while specificity remained (0.79/0.85). CONCLUSIONS: From the early phase of biologic treatment, both FC and LRG had high specificity for predicting ER at week 52. LRG showed higher sensitivity than FC.
Endoscopic radial incision and cutting for benign stenosis of the lower gastrointestinal tract: An investigation of novel endoscopic treatment in multicenter trial. International-journal

Rintaro Moroi, Hisashi Shiga, Kotaro Nochioka, Hirofumi Chiba, Yusuke Shimoyama, Masatake Kuroha, Masaki Tosa, Yoichi Kakuta, Shoichi Kayaba, Seiichi Takahashi, Yoshitaka Kinouchi, Atsushi Masamune

Journal of gastroenterology and hepatology　37　(8)　1554-1560　2022/08

DOI： 10.1111/jgh.15882 　

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BACKGROUND AND AIM: The standard therapies for benign gastrointestinal stenosis are endoscopic balloon dilation or surgery; each have their advantages and disadvantages. In contrast, radial incision and cutting (RIC) is a novel approach for such stenosis. This study aimed to investigate the feasibility, safety, and effectiveness of RIC. METHODS: We enrolled 20 patients with benign stenosis of the lower gastrointestinal tract developed by various causes and conducted RIC. We evaluated the re-intervention free rate 52 weeks after RIC, technical success rate, adverse events, procedure time, and improvement of symptoms using a visual analog scale. RESULTS: We performed 20 sessions of first RIC for 20 lesions and seven sessions of additional RIC due to re-stenosis. The cumulative re-intervention-free survival rate 52 weeks after the first RIC was 55.8%. The technical success rate of the first RIC was 100% (20/20) while that of the additional RIC was 85.7% (6/7). One case developed perforation during the additional RIC and urgent surgery was performed. The additional RIC tended to show worse results in adverse events and procedure time compared with the first RIC. The patients' symptoms including abdominal bloating and dyschezia were significantly improved. CONCLUSIONS: Although RIC demonstrated a higher technical success rate for lower gastrointestinal stricture and subsequent improvement of patient symptoms, several issues including preventing delayed bleeding, perforation, and the long-term prognosis should be solved and clarified in further investigations.
潰瘍性大腸炎内視鏡スコアと血液検査データの相関の検討

田森大登, 諸井林太郎, 下山雄丞, 内藤健夫, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　213回　77-77　2022/07
Publisher: 日本消化器病学会-東北支部
Effectiveness of colonic stent placement for obstructive colorectal cancers: An analysis of short-term results using a nationwide database in Japan. International-journal

Rintaro Moroi, Kunio Tarasawa, Yusuke Shimoyama, Masatake Kuroha, Hisashi Shiga, Yoichi Kakuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

Journal of gastroenterology and hepatology　37　(7)　1316-1325　2022/07

DOI： 10.1111/jgh.15857 　

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BACKGROUND AND AIMS: Self-expandable metallic stent (SEMS) is widely used for obstructive colorectal cancer (OCC). Both SEMS and urgent surgery have several merits and demerits. This study aimed to clarify the efficacy of SEMS by comparing the mortality rate after the hospitalization between SEMS and urgent surgery for OCC. METHODS: We collected OCC patients' data using the Diagnosis Procedure Combination (DPC) database system. We divided eligible patients into the SEMS and urgent surgery groups using propensity score matching and compared in-hospital death rates, length of hospitalization, and medical costs. We also conducted logistic regression analysis to identify clinical factors affecting in-hospital deaths. RESULTS: We enrolled 17 140 cases after propensity score matching. SEMS reduced the in-hospital death rate compared with urgent surgery (2.0% vs 3.6%, P < 0.0001). Length of hospitalization was shorter in the SEMS group than in the urgent surgery group (16 vs 25 days, P < 0.0001). Medical costs were lower in the SEMS group than in the urgent surgery group (1 663 550 vs 2 424 082 JPY, P < 0.0001). Multivariate analysis also showed that SEMS reduced in-hospital death (odds ratio = 0.58, 95% confidence interval: 0.50-0.70, P < 0.0001). CONCLUSION: Self-expandable metallic stent placement for OCC might reduce the mortality rate in short term and shorten the length of hospitalization. These results facilitate considering SEMS with careful judgment for its indication when treating OCC patients.
Validity of Diagnostic Algorithms for Inflammatory Bowel Disease in Japanese Hospital Claims Data. International-journal

Sayumi Takahashi, Taku Obara, Yoichi Kakuta, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Hisashi Shiga, Yoshitaka Kinouchi, Atsushi Masamune

International journal of environmental research and public health　19　(13)　2022/06/28

DOI： 10.3390/ijerph19137933 　

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Inflammatory bowel disease (IBD) diagnoses are increasing in Japan. Some patients have symptoms that are difficult to control, and further research on IBD is needed. Claims databases, which have a large sample size, can be useful for IBD research. However, it is unclear whether the International Classification of Diseases, Tenth Revision (ICD-10) codes alone can correctly identify IBD. We aimed to develop algorithms to identify IBD in claims databases. We used claims data from the Department of Gastroenterology, Tohoku University Hospital from 1 January 2016 to 31 December 2020. We developed 11 algorithms by combining the ICD-10 code, prescription drug, and workup information. We had access to the database which contains all the information for Crohn's disease and ulcerative colitis patients who visited our department, and we used it as the gold standard. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value for each algorithm. We enrolled 19,384 patients, and among them, 1012 IBD patients were identified in the gold standard database. Among 11 algorithms, Algorithm 4 (ICD-10 code and ≥1 prescription drugs) showed a strong performance (PPV, 94.8%; sensitivity, 75.6%). The combination of an ICD-10 code and prescription drugs may be useful for identifying IBD among claims data.
Development of severe colitis in Takayasu arteritis treated with tocilizumab. International-journal

Kae Ishii, Tsuyoshi Shirai, Yoichi Kakuta, Tomoaki Machiyama, Hiroko Sato, Tomonori Ishii, Hideo Harigae, Hiroshi Fujii

Clinical rheumatology　41　(6)　1911-1918　2022/06

DOI： 10.1007/s10067-022-06108-z 　

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Relapse of Takayasu arteritis (TAK) is frequent, and the use of biologics is required in refractory cases. Tocilizumab (TCZ), a biological agent used in TAK, is known to increase the incidence of diverticulitis in patients with rheumatoid arthritis. Adverse events of TCZ in TAK have been poorly recognised. This study aimed to investigate the occurrence of severe colitis among patients with TAK receiving TCZ. We enrolled 116 patients with TAK who met the criteria of the American College of Rheumatology and visited our department between 2018 and 2020. The occurrence of severe colitis and its clinical characteristics were retrospectively evaluated. TCZ was introduced in 34 of 116 patients (29.3%). Severe colitis that required hospitalisation was observed in three of the 34 patients receiving TCZ (8.8%). All patients were female and had Numano type V artery lesions, and the ascending colon was commonly affected. Wide lesions that reached the sigmoid colon, colonic perforation, bacteraemia, or positive stool cultures were observed in some patients. All patients received antibiotics and intestinal rest, and TCZ was resumed in one patient. IL-6 plays a physiological role in the intestine, including recovery from ischaemic damage. In addition to infectious aetiology, blocking the physiological roles of IL-6 by TCZ is considered important for the development of colitis in TAK. Severe colitis is an important adverse event in patients with TAK who receive TCZ. The risk of bloodstream infection associated with colitis should be recognised, especially in patients who have undergone vascular surgery. Key Points • Severe colitis was observed in 8.8% of patients with TAK receiving tocilizumab • Patients had type V artery lesions and ascending colon involvement and were under long-term use of corticosteroids • Inhibition of the physiological roles of IL-6 in the intestinal tract might also be involved.
A pilot study investigating the safety and feasibility of endoscopic dilation using a radial incision and cutting technique for benign strictures of the small intestine: a study protocol. International-journal

Rintaro Moroi, Hisashi Shiga, Kotaro Nochioka, Yusuke Shimoyama, Masatake Kuroha, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Pilot and feasibility studies　8　(1)　85-85　2022/04/19

DOI： 10.1186/s40814-022-01046-8 　

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BACKGROUND: Small benign intestinal stenosis is usually treated by endoscopic balloon dilation (EBD) or surgery. Although EBD and surgery are able to resolve the stenosis in most cases, they are associated with several problems such as insufficient dilation and surgical stress, respectively. On the contrary, a novel approach called radial incision and cutting (RIC) is reported to have several benefits when compared to EBD and surgery. We can currently adopt RIC only for the strictures in the colon or terminal ileum and not for those stenotic lesions present further in the small intestine where balloon-assisted endoscopy is utilized, because the long-type electric knife is currently not approved for use in Japan. We will herein conduct a pilot study to investigate the safety and feasibility of RIC for treating the benign stenoses of the small intestine using the long-type electric knife. METHODS: This will be a single-center, single-arm, interventional trial. The major criteria for inclusion will be age ranging from 20 to 80 years and the presence of benign stenosis in the small intestine. We will perform RIC on 10 participants. The primary outcome is the safety of this procedure, which will be assessed by measuring the frequency of adverse events of special interest. The secondary outcomes will be technical success rate, improvement in subjective symptoms, procedure time, and duration of hospitalization. DISCUSSION: This pilot study will provide useful information that will aid in adopting RIC for treating the benign strictures present in the small intestine. TRIAL REGISTRATION: jRCT Identifier, jRCTs022200040 . Registered on 1 March 2021.
A Pilot Study for Return of Individual Pharmacogenomic Results to Population-Based Cohort Study Participants.

Kinuko Ohneda, Masahiro Hiratsuka, Hiroshi Kawame, Fuji Nagami, Yoichi Suzuki, Kichiya Suzuki, Akira Uruno, Mika Sakurai-Yageta, Yohei Hamanaka, Makiko Taira, Soichi Ogishima, Shinichi Kuriyama, Atsushi Hozawa, Hiroaki Tomita, Naoko Minegishi, Junichi Sugawara, Inaho Danjoh, Tomohiro Nakamura, Tomoko Kobayashi, Yumi Yamaguchi-Kabata, Shu Tadaka, Taku Obara, Eiji Hishimuma, Nariyasu Mano, Masaki Matsuura, Yuji Sato, Masateru Nakasone, Yohei Honkura, Jun Suzuki, Yukio Katori, Yoichi Kakuta, Atsushi Masamune, Yoko Aoki, Masaharu Nakayama, Shigeo Kure, Kengo Kinoshita, Nobuo Fuse, Masayuki Yamamoto

JMA journal　5　(2)　177-189　2022/04/15

DOI： 10.31662/jmaj.2021-0156 　

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INTRODUCTION: Pharmacogenomic (PGx) testing results provide valuable information on drug selection and appropriate dosing, maximization of efficacy, and minimization of adverse effects. Although the number of large-scale, next-generation-sequencing-based PGx studies has recently increased, little is known about the risks and benefits of returning PGx results to ostensibly healthy individuals in research settings. METHODS: Single-nucleotide variants of three actionable PGx genes, namely, MT-RNR1, CYP2C19, and NUDT15, were returned to 161 participants in a population-based Tohoku Medical Megabank project. Informed consent was obtained from the participants after a seminar on the outline of this study. The results were sent by mail alongside sealed information letter intended for clinicians. As an exception, genetic counseling was performed for the MT-RNR1 m.1555A > G variant carriers by a medical geneticist, and consultation with an otolaryngologist was encouraged. Questionnaire surveys (QSs) were conducted five times to evaluate the participants' understanding of the topic, psychological impact, and attitude toward the study. RESULTS: Whereas the majority of participants were unfamiliar with the term PGx, and none had undergone PGx testing before the study, more than 80% of the participants felt that they could acquire basic PGx knowledge sufficient to understand their genomic results and were satisfied with their potential benefit and use in future prescriptions. On the other hand, some felt that the PGx concepts or terminology was difficult to fully understand and suggested that in-person return of the results was desirable. CONCLUSIONS: These results collectively suggest possible benefits of returning preemptive PGx information to ostensibly healthy cohort participants in a research setting.
炎症性腸疾患診療でPharmacogenomicsをどう活用するか

角田洋一, 内藤健夫, 木内喜孝, 正宗淳

日本臨床薬理学会学術総会抄録集　43　1-C-S05-3　2022
Publisher: 一般社団法人日本臨床薬理学会
DOI： 10.50993/jsptsuppl.43.0_1-c-s05-3 　

eISSN： 2436-5580

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クローン病や潰瘍性大腸炎といった炎症性腸疾患では新たな治療選択肢が次々と実用化されている。しかしこれらの新規治療の大部分は有効率・寛解率に大きな違いが無く、治療反応性も患者個人でさまざまである。そのため、新たな治療は過去の治療にとって代わるものではないため、各患者に適切な治療をより早期に導くことが重要となる。現時点で、各種薬剤を選択する明確なバイオマーカーは存在していないため、各医師・患者で治療選択方法は異なっている。Pharmacogenomicsは、このような多数の治療から適切な治療を選択する個別化医療の実現に重要な一つの要素と考えられ様々な検討が行われてきた。しかしながら、治療効果、継続率などと強い相関を示し臨床の現場で活用できるような遺伝的マーカーの発見には至っていない。これは、これらの治療予後の多くが遺伝的素因以外の要素である病態や併用薬、治療歴、アドヒアランスなどの臨床的な要素の影響を強く受けるためである。一方で、より薬物動態に直接強くかかわる因子、例えば血中トラフ値、抗薬物抗体の産生、用量依存性の副作用などに関連する遺伝的背景の存在はよく知られている。NUDT15遺伝子多型検査はその一つであり、アザチオプリンおよび６－メルカプトプリンからなるチオプリン製剤の全脱毛や白血球減少を予測する検査として、日本で実用化されている数少ないPharmacogenomics検査として知られている。2019年2月の実用化後、実際にこの検査がチオプリン治療の予後を改善しているか全国49施設で診療目的にNUDT15遺伝子多型検査が行われた症例1509例と、遺伝子検査なしで過去に始めた症例1206例について後ろ向きに調査を行い検討した。その結果、チオプリン投与開始後２年間での治療継続率は遺伝子検査をしないで始めた症例と比較して有意に遺伝子検査を行った群で高いことが確認された（p=0.0003）。しかしNUDT15遺伝子多型はチオプリンという一つの薬剤の治療選択には重要であるが、多数ある炎症性腸疾患の治療薬の１つにすぎないため、Pharmacogenomicsの活用は限定的と考えられてしまう。しかし、チオプリンを使えるかどうかで、たとえば、チオプリンの併用が望ましい薬剤とそれ以外の選択順位が変わる可能性があるなど、他の治療の選択にも大きな影響がある。そこで、実際の炎症性腸疾患治療選択におけるPharmacogenomicsの活用と戦略についてまとめる。
Loss of CAPS2/Cadps2 leads to exocrine pancreatic cell injury and intracellular accumulation of secretory granules in mice. International-journal

Yotaroh Sato, Miho Tsuyusaki, Hiromi Takahashi-Iwanaga, Rena Fujisawa, Atsushi Masamune, Shin Hamada, Ryotaro Matsumoto, Yu Tanaka, Yoichi Kakuta, Yumi Yamaguchi-Kabata, Tamio Furuse, Shigeharu Wakana, Takuya Shimura, Rika Kobayashi, Yo Shinoda, Ryo Goitsuka, So Maezawa, Tetsushi Sadakata, Yoshitake Sano, Teiichi Furuichi

Frontiers in molecular biosciences　9　1040237-1040237　2022

DOI： 10.3389/fmolb.2022.1040237 　

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The type 2 Ca2+-dependent activator protein for secretion (CAPS2/CADPS2) regulates dense-core vesicle trafficking and exocytosis and is involved in the regulated release of catecholamines, peptidergic hormones, and neuromodulators. CAPS2 is expressed in the pancreatic exocrine acinar cells that produce and secrete digestive enzymes. However, the functional role of CAPS2 in vesicular trafficking and/or exocytosis of non-regulatory proteins in the exocrine pancreas remains to be determined. Here, we analyzed the morpho-pathological indicators of the pancreatic exocrine pathway in Cadps2-deficient mouse models using histochemistry, biochemistry, and electron microscopy. We used whole exosome sequencing to identify CADPS2 variants in patients with chronic pancreatitis (CP). Caps2/Cadps2-knockout (KO) mice exhibited morphophysiological abnormalities in the exocrine pancreas, including excessive accumulation of secretory granules (zymogen granules) and their amylase content in the cytoplasm, deterioration of the fine intracellular membrane structures (disorganized rough endoplasmic reticulum, dilated Golgi cisternae, and the appearance of empty vesicles and autophagic-like vacuoles), as well as exocrine pancreatic cell injury, including acinar cell atrophy, increased fibrosis, and inflammatory cell infiltration. Pancreas-specific Cadps2 conditional KO mice exhibited pathological abnormalities in the exocrine pancreas similar to the global Cadps2 KO mice, indicating that these phenotypes were caused either directly or indirectly by CAPS2 deficiency in the pancreas. Furthermore, we identified a rare variant in the exon3 coding region of CADPS2 in a non-alcoholic patient with CP and showed that Cadps2-dex3 mice lacking CAPS2 exon3 exhibited symptoms similar to those exhibited by the Cadps2 KO and cKO mice. These results suggest that CAPS2 is critical for the proper functioning of the pancreatic exocrine pathway, and its deficiency is associated with a risk of pancreatic acinar cell pathology.
Analysis of the disease activity of ulcerative colitis with and without concomitant primary sclerosing cholangitis: An investigation using a nationwide database in Japan. International-journal

Kota Yano, Rintaro Moroi, Hisashi Shiga, Kunio Tarasawa, Yusuke Shimoyama, Masatake Kuroha, Shin Hamada, Yoichi Kakuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

JGH open : an open access journal of gastroenterology and hepatology　6　(1)　50-56　2022/01

DOI： 10.1002/jgh3.12693 　

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Aims: Primary sclerosing cholangitis (PSC) is a relatively common complication of ulcerative colitis (UC). Only a few studies have investigated the impact of PSC on the clinical course of UC, and their conclusions are contradictory. Therefore, we aimed to compare the disease activity of UC with and without PSC. Methods and Results: We collected UC patient data using the Diagnosis Procedure Combination database system in Japan and classified eligible admissions into two groups based on their diagnosis of either UC alone or UC associated with PSC. We then compared therapeutic details (medical treatment and surgery) between the two groups. Multivariable logistic regression analysis and propensity score matching was also performed. The rates of systemic steroid injection and infliximab administration in patients with PSC were lower than those in patients without PSC (21% vs. 28%, P = 0.012, 9.6% vs. 16%, P = 0.01, respectively). The rates of surgery, colorectal cancer, duration of hospital stay, and in-hospital mortality did not differ between the two groups. Multivariable analysis revealed that concomitant PSC was a clinical factor that reduced the odds of systemic steroid injection (odds ratio [OR] = 0.66, 95% confidence interval [CI]: 0.49-0.90, P = 0.008) and infliximab (OR = 0.48, 95% CI: 0.32-0.74, P = 0.0008) administration. Conclusion: UC patients with PSC might have less UC disease activity than those with UC alone.
QRコードにより電子カルテと連携したブラウザベースのカスタマイズ可能な問診ツールの作成

宋ちゅう, 佐々木恵利奈, 中村直毅, 角田洋一, 中山雅晴

医療情報学連合大会論文集　41回　1031-1033　2021/11
Publisher: (一社)日本医療情報学会
ISSN： 1347-8508

eISSN： 2433-698X
Ulcerative colitis-related postoperative enteritis treated with anti-tumor necrosis factor therapy: two case reports and a literature review.

Fumiko Shimoda, Masatake Kuroha, Hirofumi Chiba, Izuru Abe, Kota Yano, Yushi Inomata, Takahiro Takahashi, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Yoichi Kakuta, Fumiyoshi Fujishima, Atsushi Masamune

Clinical journal of gastroenterology　14　(5)　1396-1403　2021/10

DOI： 10.1007/s12328-021-01485-5 　

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Several case reports have described severe postoperative enteritis shortly after total colectomy for ulcerative colitis. The very low incidence of this condition makes diagnosis and treatment difficult, and the appropriate treatment strategy is unclear. We report two cases of enteritis after surgery for ulcerative colitis, which were treated with anti-tumor necrosis factor-α therapy. Case 1 involved a 22-year-old man with symptoms, such as nausea 40 days after total colectomy. Gastrointestinal endoscopy revealed patchy obliteration of the vascular pattern, erosions in the duodenum, and superficial ulcers in the small intestine. His symptoms and endoscopic findings immediately improved upon administration of infliximab; clinical remission lasted 5 years with continuous administration. Case 2 involved a 64-year-old man, who had a large amount of watery diarrhea from ileostomy that increased 5 days after total colectomy; gastrointestinal endoscopy revealed extensive ulcers in the small intestine. Symptoms and endoscopic findings improved with prednisolone, but relapsed with tapering of the corticosteroid. Administration of adalimumab resulted in marked improvement of enteritis. However, the small intestine developed a pinhole stricture, and partial resection of the small intestine was performed. Our experience with two cases indicates that anti-tumor necrosis factor-α therapy may play an important role in ulcerative colitis-related postoperative enteritis.
特集炎症性腸疾患の分子標的治療を総括する Ⅶ.生物学的製剤と Treat to Target( T2T)

志賀永嗣, 阿部出, 下山雄丞, 諸井林太郎, 黒羽正剛, 角田洋一, 正宗淳

INTESTINE　25　(3)　285-290　2021/09/20
Publisher: 日本メディカルセンター
DOI： 10.19020/int.0000000618 　

ISSN： 1883-2342

eISSN： 2433-250X
Analysis of the Long-Term Prognosis in Japanese Patients with Ulcerative Colitis Treated with New Therapeutic Agents and the Correlation between Prognosis and Disease Susceptibility Loci. International-journal

Kasumi Hishinuma, Rintaro Moroi, Daisuke Okamoto, Yusuke Shimoyama, Masatake Kuroha, Hisashi Shiga, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Inflammatory intestinal diseases　6　(3)　154-164　2021/09

DOI： 10.1159/000518371 　

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Background: New therapeutic agents, including biologics and small-molecule drugs, are widely used to treat ulcerative colitis (UC). This study evaluates long-term prognosis in Japanese patients treated with these agents and the association between prognosis and genetic susceptibility to UC. Methods: We evaluated surgery-free rates using the Kaplan-Meier method in the total cohort and in patients treated with prednisolone and new therapeutic agents. Multivariate analysis was performed to identify clinical factors affecting surgical rates using Cox's proportional hazard model. The rate of use of new therapeutic agents was compared using the Kaplan-Meier method, and multivariate analysis was conducted to investigate the correlation between the single-nucleotide polymorphism (SNP) rs117506082 and long-term prognosis. Results: Surgery-free survival decreased over time. There was no significant difference in this parameter between patients who were administered prednisolone and those who were administered new therapeutic agents. Poor response to prednisolone and treatment without topical 5-aminosalicylic acid were poor prognostic factors. Shorter time from diagnosis to initiation of treatment with new therapeutic agents was a risk factor for colectomy. The AA genotype of SNP rs117506082 was associated with a shorter time to surgery and increased use of new therapeutic agents. Conclusions: The use of new therapeutic agents might improve long-term prognosis in patients with more severe UC. Previously identified genetic risk factors were not significantly associated with a higher rate of colectomy.
Immunoglobulin subtype-coated bacteria are correlated with the disease activity of inflammatory bowel disease. International-journal

Yutaro Masu, Yoshitake Kanazawa, Yoichi Kakuta, Yusuke Shimoyama, Motoyuki Onodera, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Tomoya Kimura, Hisashi Shiga, Yoshitaka Kinouchi, Atsushi Masamune

Scientific reports　11　(1)　16672-16672　2021/08/17

DOI： 10.1038/s41598-021-96289-5 　

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Immune response involving various immunoglobulin (Ig) isotypes and subtypes to microbiome is involved in the pathogenesis and disease activity of inflammatory bowel diseases (IBDs). To clarify the presence of Ig-coated bacteria in the intestine and its association with disease activity in ulcerative colitis (UC) and Crohn's disease (CD), we extracted and classified Ig-coated bacteria from fecal samples of 42 patients with IBD and 12 healthy controls (HCs) using flow cytometry and 16S ribosomal RNA sequence analysis. The percentage of bacteria coated with IgA and IgM was higher in patients with IBD than in HCs, and IgG-coated bacteria were found only in patients with IBD. Moreover, the percentages of bacteria coated with IgG1, IgG2, IgG3, and IgM in UC samples and IgG3, IgG4, and IgM in CD samples were correlated with disease activities. The proportions of Bacteroides ovatus and Streptococcus increased during the active phase of CD. Hence, the detailed analysis of Ig-coated bacteria and Ig subtypes using flow cytometry could aid in developing useful indicators of disease activity and identifying more disease-related bacteria, which could become novel treatment targets for IBDs.
Efficacy of urgent colonoscopy for colonic diverticular bleeding: A propensity score-matched analysis using a nationwide database in Japan International-journal

Rintaro Moroi, Kunio Tarasawa, Hisashi Shiga, Kota Yano, Yusuke Shimoyama, Masatake Kuroha, Yoichi Kakuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

Journal of Gastroenterology and Hepatology (Australia)　36　(6)　1598-1604　2021/06

DOI： 10.1111/jgh.15316 　

ISSN： 0815-9319

eISSN： 1440-1746
Localized intestinal AL amyloidosis detected as bright green using autofluorescence endoscopy

Masatake Kuroha, Tsuneaki Yoshinaga, Masahide Yazaki, Fumiyoshi Fujishima, Tomoyuki Handa, Kaoru Suzuki, Kasumi Hishinuma, Yutaro Masu, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Yoshitake Kanazawa, Hisashi Shiga, Yoichi Kakuta, Atsushi Masamune

Clinical Journal of Gastroenterology　14　(3)　815-819　2021/06

DOI： 10.1007/s12328-021-01378-7 　

ISSN： 1865-7257

eISSN： 1865-7265
Liquid Biopsy for Colorectal Adenoma: Is the Exosomal miRNA Derived From Organoid a Potential Diagnostic Biomarker? International-journal

Tomoyuki Handa, Masatake Kuroha, Hiroshi Nagai, Yusuke Shimoyama, Takeo Naito, Rintaro Moroi, Yoshitake Kanazawa, Hisashi Shiga, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Clinical and translational gastroenterology　12　(5)　e00356　2021/05/12

DOI： 10.14309/ctg.0000000000000356 　

eISSN： 2155-384X
【炎症性腸疾患診療の新たな展開】潰瘍性大腸炎病因と病態

角田洋一, 正宗淳

臨牀と研究　98　(5)　521-524　2021/05
Publisher: 大道学館出版部
ISSN： 0021-4965
【消化管低侵襲治療up dateと未来】大腸・小腸良性狭窄に対する治療法の進歩主にRICについて

諸井林太郎, 志賀永嗣, 後岡広太郎, 下山雄丞, 千葉宏文, 黒羽正剛, 土佐正規, 角田洋一, 萱場尚一, 高橋成一, 木内喜孝, 正宗淳

消化器・肝臓内科　9　(2)　201-206　2021/02
Publisher: (有)科学評論社
ISSN： 2432-3446
Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease. International-journal

Kaoru Suzuki, Yoichi Kakuta, Takeo Naito, Tetsuya Takagawa, Hiroyuki Hanai, Hiroshi Araki, Yu Sasaki, Hirotake Sakuraba, Makoto Sasaki, Tadakazu Hisamatsu, Satoshi Motoya, Takayuki Matsumoto, Motoyuki Onodera, Yoh Ishiguro, Hiroshi Nakase, Akira Andoh, Sakiko Hiraoka, Masaru Shinozaki, Toshimitsu Fujii, Takehiko Katsurada, Taku Kobayashi, Mikihiro Fujiya, Takafumi Otsuka, Naoki Oshima, Yasuo Suzuki, Yuichirou Sato, Ryota Hokari, Mitsunori Noguchi, Yuki Ohta, Minoru Matsuura, Yosuke Kawai, Katsushi Tokunaga, Masao Nagasaki, Hisaaki Kudo, Naoko Minegishi, Daisuke Okamoto, Yusuke Shimoyama, Rintaro Moroi, Masatake Kuroha, Hisashi Shiga, Dalin Li, Dermot P B McGovern, Yoshitaka Kinouchi, Atsushi Masamune

Inflammatory bowel diseases　28　(1)　21-31　2021/01/27

DOI： 10.1093/ibd/izab004 　

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BACKGROUND: Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called "mesalamine allergy," which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the genetic background of mesalamine intolerance in the first genome-wide association study of Japanese patients with IBD. METHODS: Two independent pharmacogenetic IBD cohorts were analyzed: the MENDEL (n = 1523; as a discovery set) and the Tohoku (n = 788; as a replication set) cohorts. Genome-wide association studies were performed in each population, followed by a meta-analysis. In addition, we constructed a polygenic risk score model and combined genetic and clinical factors to model mesalamine intolerance. RESULTS: In the combined cohort, mesalamine-induced fever and/or diarrhea was significantly more frequent in ulcerative colitis vs Crohn's disease. The genome-wide association studies and meta-analysis identified one significant association between rs144384547 (upstream of RGS17) and mesalamine-induced fever and diarrhea (P = 7.21e-09; odds ratio = 11.2). The estimated heritability of mesalamine allergy was 25.4%, suggesting a significant correlation with the genetic background. Furthermore, a polygenic risk score model was built to predict mesalamine allergy (P = 2.95e-2). The combined genetic/clinical prediction model yielded a higher area under the curve than did the polygenic risk score or clinical model alone (area under the curve, 0.89; sensitivity, 71.4%; specificity, 90.8%). CONCLUSIONS: Mesalamine allergy was more common in ulcerative colitis than in Crohn's disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event.
Long-term efficacy and tolerability of dose-adjusted thiopurine treatment in maintaining remission in inflammatory bowel disease patients with NUDT15 heterozygosity. International-journal

Takato Maeda, Hirotake Sakuraba, Hiroto Hiraga, Shukuko Yoshida, Yoichi Kakuta, Hidezumi Kikuchi, Shogo Kawaguchi, Keisuke Hasui, Tetsuya Tatsuta, Daisuke Chinda, Tatsuya Mikami, Shinsaku Fukuda

Intestinal research　20　(1)　90-100　2021/01/22

DOI： 10.5217/ir.2020.00133 　

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Background/Aims: Thiopurines are key drugs for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). Recently, NUDT15 polymorphism (R139C, c.415C > T) has been shown to be associated with thiopurineinduced adverse events in Asian populations. In patients with the C/T genotype, low-dose thiopurine treatment is recommended, but its long-term efficacy and tolerability remain unclear. This study aimed to uncover the long-term efficacy and appropriate dosage of thiopurine for IBD patients with the C/T genotype. Methods: A total of 210 patients with IBD (103 UC and 107 CD) determined to have NUDT15 R139C variants were enrolled. Clinical data were retrospectively reviewed from medical records. Results: Of 46 patients (21.9%) with the C/T genotype, 30 patients (65.2%) were treated with thiopurines. Three of whom (10.0%) discontinued thiopurine treatment due to adverse events and 27 of whom continued. The median maintenance dosage of 6-mercaptopurine was 0.25 mg/kg/day (range, 0.19-0.36 mg/kg/day), and 6-thioguanine nucleotides level was 230 (104-298) pmol/8 × 108 red blood cells. Cumulative thiopurine continuation rates for 120 months for patients with the C/C and C/T genotypes were not significantly different (P= 0.895). Cumulative non-relapse rates in the patients with UC treated with thiopurine monotherapy and surgery-free rates in CD patients treated with combination therapy (thiopurines and anti-tumor necrosis factor-α agents) for maintenance remission were not significantly different at 60 months (C/C vs. C/T, P= 0.339 and P= 0.422, respectively). Conclusions: Low-dose thiopurine treatment is an effective and acceptable treatment for patients with C/T genotype.
炎症性腸疾患における内視鏡検査と治療戦略日本人クローン病における便中カルプロテクチンを指標とした治療戦略の有用性

阿部出, 志賀永嗣, 高橋隆宏, 角田洋一, 正宗淳

日本消化器内視鏡学会東北支部例会　165回　43-43　2021/01
Publisher: 日本消化器内視鏡学会-東北支部
炎症性消化管疾患の最前線多様化する炎症性腸疾患の治療戦略-外科手術も含めて- クローン病の腸管狭窄に対するRadial Cutting and Incision法を用いた内視鏡的切開拡張術の検討

諸井林太郎, 志賀永嗣, 下山雄丞, 黒羽正剛, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　5　(Suppl.)　149-149　2021/01
Publisher: (一社)日本消化管学会
ISSN： 2433-3840
高齢者潰瘍性大腸炎治療指針の検証診断群分類別包括評価(DPC)データを用いた本邦における高齢者潰瘍性大腸炎治療の現状

矢野恒太, 諸井林太郎, 志賀永嗣, 下山雄丞, 黒羽正剛, 角田洋一, タラ澤邦男, 藤森研司, 伏見清秀, 木内喜孝, 正宗淳

日本消化管学会雑誌　5　(Suppl.)　238-238　2021/01
Publisher: (一社)日本消化管学会
ISSN： 2433-3840
Thiopurine Use During Pregnancy Has Deleterious Effects on Offspring in Nudt15(R138C) Knock-In Mice Peer-reviewed

Yoichi Kakuta

Cellular and Molecular Gastroenterology and Hepatology　12　(1)　335-337　2021/01

DOI： 10.1016/J.JCMGH.2021.03.006 　

ISSN： 2352-345X
The clinical practice of ulcerative colitis in elderly patients: An investigation using a nationwide database in Japan International-journal

Rintaro Moroi, Hisashi Shiga, Kunio Tarasawa, Kota Yano, Yusuke Shimoyama, Masatake Kuroha, Yoichi Kakuta, Kiyohide Fushimi, Kenji Fujimori, Yoshitaka Kinouchi, Atsushi Masamune

JGH Open　5　(8)　842-848　2021

DOI： 10.1002/jgh3.12541 　

eISSN： 2397-9070
A simple prediction score for in-hospital mortality in patients with nonvariceal upper gastrointestinal bleeding

Tamotsu Matsuhashi, Waku Hatta, Takuto Hikichi, Sho Fukuda, Tatsuya Mikami, Tetsuya Tatsuta, Jun Nakamura, Yasuhiko Abe, Yusuke Onozato, Yohei Ogata, Atsushi Masamune, Motoki Ohyauchi, Hirotaka Ito, Norihiro Hanabata, Yasumitsu Araki, Takumi Yanagita, Hidemichi Imamura, Tsuyotoshi Tsuji, Kae Sugawara, Yohei Horikawa, Shuichi Ohara, Yutaka Kondo, Takahiro Dohmen, Yoichi Kakuta, Tomohiro Nakamura, Katsunori Iijima

Journal of Gastroenterology　56　(8)　758-768　2021

DOI： 10.1007/s00535-021-01797-w 　

ISSN： 0944-1174

eISSN： 1435-5922
【潰瘍性大腸炎診療の診断から治療をマスターする】潰瘍性大腸炎と鑑別を要する疾患はどのようなものがあるのか? 免疫関連疾患

志賀永嗣, 下山雄丞, 諸井林太郎, 黒羽正剛, 角田洋一, 正宗淳

消化器・肝臓内科　9　(1)　16-23　2021/01
Publisher: (有)科学評論社
ISSN： 2432-3446
Capsule Endoscopy Is Useful for Postoperative Tight Control Management in Patients with Crohn’s Disease International-journal

Hisashi Shiga, Izuru Abe, Jun Kusaka, Yusuke Shimoyama, Rintaro Moroi, Masatake Kuroha, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Digestive Diseases and Sciences　2021

DOI： 10.1007/s10620-021-06841-6 　

ISSN： 0163-2116

eISSN： 1573-2568
Comprehensive Analysis of microRNA Profiles in Organoids Derived from Human Colorectal Adenoma and Cancer International-journal

Hiroshi Nagai, Masatake Kuroha, Tomoyuki Handa, Hideaki Karasawa, Shinobu Ohnuma, Takeo Naito, Rintaro Moroi, Yoshitake Kanazawa, Hisashi Shiga, Shin Hamada, Yoichi Kakuta, Takeshi Naitoh, Yoshitaka Kinouchi, Tooru Shimosegawa, Atsushi Masamune

Digestion　102　(6)　1-10　2021

DOI： 10.1159/000513882 　

ISSN： 0012-2823

eISSN： 1421-9867
Long-term endoscopic remission in Crohn’s disease after allogeneic hematopoietic stem cell transplantation for diffuse large B cell lymphoma: case report and literature review

Yushi Inomata, Masatake Kuroha, Tomoyuki Handa, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Yoichi Kakuta, Satoshi Ichikawa, Noriko Fukuhara, Yuichiro Sato, Taro Takahashi, Atsushi Masamune

Clinical Journal of Gastroenterology　14　(4)　1108-1114　2021

DOI： 10.1007/s12328-021-01389-4 　

ISSN： 1865-7257

eISSN： 1865-7265
IBDクリニカルカンファレンス(第8回) 若年者女性UCの5-ASA不耐例

富永圭一, 角田洋一, 梁井俊一, 菅谷武史, 宮川麻希

IBDクリニカルカンファレンス　2　(4)　121-128　2020/12
Publisher: (株)先端医学社
ISSN： 2434-222X
基本の基本診断編 NUDT15

角田洋一

IBDクリニカルカンファレンス　2　(4)　134-135　2020/12
Publisher: (株)先端医学社
ISSN： 2434-222X
TL1A (TNFSF15) genotype affects the long-term therapeutic outcomes of anti-TNFα antibodies for Crohn's disease patients International-journal

Katsuya Endo, Yoichi Kakuta, Rintaro Moroi, Katsutoshi Yamamoto, Hisashi Shiga, Masatake Kuroha, Takeo Naito, Yoshitaka Kinouchi, Atsushi Masamune

JGH Open　4　(6)　1108-1113　2020/12

DOI： 10.1002/jgh3.12398 　

eISSN： 2397-9070
An Integrated Genomic and Transcriptomic Analysis Reveals Candidates of Susceptibility Genes for Crohn’s Disease in Japanese Populations International-journal Peer-reviewed

Yoichi Kakuta, Ryo Ichikawa, Yuta Fuyuno, Atsushi Hirano, Junji Umeno, Takehiro Torisu, Kazuhiro Watanabe, Akihiro Asakura, Takeru Nakano, Yasuhiro Izumiyama, Daisuke Okamoto, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Takeshi Naito, Motohiro Esaki, Yosuke Kawai, Katsushi Tokunaga, Minoru Nakamura, Takayuki Matsumoto, Masao Nagasaki, Yoshitaka Kinouchi, Michiaki Unno, Atsushi Masamune

Scientific Reports　10　(1)　10236-10236　2020/12/01

DOI： 10.1038/s41598-020-66951-5 　

eISSN： 2045-2322
Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis International-journal Peer-reviewed

Tomoyuki Mutoh, Tsuyoshi Shirai, Tomonori Ishii, Yuko Shirota, Fumiyoshi Fujishima, Fumiaki Takahashi, Yoichi Kakuta, Yoshitake Kanazawa, Atsushi Masamune, Yoshikatsu Saiki, Hideo Harigae, Hiroshi Fujii

Nature Communications　11　(1)　1253-1253　2020/12/01

DOI： 10.1038/s41467-020-15088-0 　

eISSN： 2041-1723
Serum C-reactive protein and albumin are useful biomarkers for tight control management of Crohn’s disease in Japan International-journal Peer-reviewed

Hisashi Shiga, Izuru Abe, Motoyuki Onodera, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Yoichi Kakuta, Katsuya Endo, Yoshitaka Kinouchi, Atsushi Masamune

Scientific Reports　10　(1)　511-511　2020/12/01

DOI： 10.1038/s41598-020-57508-7 　

eISSN： 2045-2322
妊娠中チオプリン服用を継続した炎症性腸疾患患者より生まれた児における副作用の検討

高川哲也, 角田洋一, 小島健太郎, 小柴良司, 藤本晃士, 佐藤寿行, 河合幹夫, 上小鶴孝二, 横山陽子, 宮嵜孝子, 樋田信幸, 渡辺憲治, 中村志郎

日本消化器病学会雑誌　117　(臨増大会)　A761-A761　2020/10
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
炎症性腸疾患の新規治療薬の効果と安全性日本人潰瘍性大腸炎患者の新規治療薬登場後の時代における予後解析

菱沼佳純, 諸井林太郎, 下山雄丞, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本大腸肛門病学会雑誌　73　(9)　A35-A35　2020/09
Publisher: (一社)日本大腸肛門病学会
ISSN： 0047-1801

eISSN： 1882-9619
Repertoire analysis of memory T-cell receptors in Japanese patients with inflammatory bowel disease International-journal

Yoichi Kakuta, Takeru Nakano, Takeo Naito, Kazuhiro Watanabe, Yasuhiro Izumiyama, Daisuke Okamoto, Ryo Ichikawa, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Takeshi Naitoh, Yoshitaka Kinouchi, Michiaki Unno, Atsushi Masamune

JGH Open　4　(4)　624-631　2020/08/01

DOI： 10.1002/jgh3.12305 　

eISSN： 2397-9070
Genetic analysis of ulcerative colitis in Japanese individuals using population-specific SNP array International-journal Peer-reviewed

Daisuke Okamoto, Yosuke Kawai, Yoichi Kakuta, Takeo Naito, Takehiro Torisu, Atsushi Hirano, Junji Umeno, Yuta Fuyuno, Dalin Li, Takeru Nakano, Yasuhiro Izumiyama, Ryo Ichikawa, Keiichiro Hiramoto, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Hisashi Shiga, Katsushi Tokunaga, Minoru Nakamura, Motohiro Esaki, Takayuki Matsumoto, Dermot P.B. McGovern, Masao Nagasaki, Yoshitaka Kinouchi, Atsushi Masamune

Inflammatory Bowel Diseases　26　(8)　1177-1187　2020/08/01

DOI： 10.1093/ibd/izaa033 　

ISSN： 1078-0998

eISSN： 1536-4844
消化器疾患におけるバイオマーカーの探索 High Resolution Melt(HRM)解析でNUDT15遺伝子codon18を簡易にdiplotypingすることで白血球減少症をより詳細に予測する方法の開発

泉山泰宏, 角田洋一, 正宗淳

日本消化器病学会雑誌　117　(臨増総会)　A36-A36　2020/07
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
トランスクリプトーム解析を用いた日本人クローン病疾患感受性遺伝子の同定

市川遼, 角田洋一, 冬野雄太, 平野敦士, 梅野淳嗣, 鳥巣剛弘, 中野健, 泉山泰宏, 岡本大祐, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 志賀永嗣, 江崎幹宏, 中村稔, 松本主之, 木内喜孝, 正宗淳

日本消化器病学会雑誌　117　(臨増総会)　A208-A208　2020/07
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
人種最適化アレイを用いた日本人潰瘍性大腸炎患者の遺伝的背景の解析

岡本大祐, 角田洋一, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 志賀永嗣, 冬野雄太, 平野敦士, 梅野淳嗣, 鳥巣剛弘, 中村稔, 松本主之, 江崎幹宏, 木内喜孝, 正宗淳

日本消化器病学会雑誌　117　(臨増総会)　A209-A209　2020/07
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
抗TNF製剤の投与歴で分けたUstekinumabの有効性と安全性

志賀永嗣, 高橋隆宏, 阿部出, 菱沼佳純, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 正宗淳

日本消化器病学会雑誌　117　(臨増総会)　A222-A222　2020/07
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
当院におけるCrohn病に対するadalimumab倍量投与の治療成績

菱沼佳純, 黒羽正剛, 矢野恒太, 下田楓美子, 猪股優志, 阿部出, 枡悠太郎, 半田智之, 鈴木郁, 中野健, 岡本大祐, 市川遼, 泉山泰宏, 諸井林太郎, 金澤義丈, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会雑誌　117　(臨増総会)　A224-A224　2020/07
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Rare genotype of his/his in NUDT15 codon 139 and thiopurine-associated adverse events in a case of ulcerative colitis Peer-reviewed

Kei Tomiyoshi, Hiroki Sato, Kentaro Tominaga, Yuzo Kawata, Daisuke Okamoto, Yoichi Kakuta, Junji Yokoyama, Shuji Terai

Internal Medicine　59　(13)　1611-1613　2020/07/01

DOI： 10.2169/internalmedicine.4261-19 　

ISSN： 0918-2918

eISSN： 1349-7235
Variants That Affect Function of Calcium Channel TRPV6 Are Associated With Early-Onset Chronic Pancreatitis International-journal Peer-reviewed

Atsushi Masamune, Hiroshi Kotani, Franziska Lena Sörgel, Jian Min Chen, Shin Hamada, Reiko Sakaguchi, Emmanuelle Masson, Eriko Nakano, Yoichi Kakuta, Tetsuya Niihori, Ryo Funayama, Matsuyuki Shirota, Tatsuya Hirano, Tetsuya Kawamoto, Atsuki Hosokoshi, Kiyoshi Kume, Lara Unger, Maren Ewers, Helmut Laumen, Peter Bugert, Masayuki X. Mori, Volodymyr Tsvilovskyy, Petra Weißgerber, Ulrich Kriebs, Claudia Fecher-Trost, Marc Freichel, Kalliope N. Diakopoulos, Alexandra Berninger, Marina Lesina, Kentaro Ishii, Takao Itoi, Tsukasa Ikeura, Kazuichi Okazaki, Tom Kaune, Jonas Rosendahl, Masao Nagasaki, Yasuhito Uezono, Hana Algül, Keiko Nakayama, Yoichi Matsubara, Yoko Aoki, Claude Férec, Yasuo Mori, Heiko Witt, Tooru Shimosegawa

Gastroenterology　158　(6)　1626-1641.e8　2020/05

DOI： 10.1053/j.gastro.2020.01.005 　

ISSN： 0016-5085

eISSN： 1528-0012
アザチオプリンとNUDT15 p.Arg139Cys遺伝子多型

角田洋一

リウマチ科　63　(4)　462-468　2020/04
Publisher: (有)科学評論社
ISSN： 0915-227X
【炎症性腸疾患における免疫調節薬の有用性と課題】炎症性腸疾患における治療前スクリーニング NUDT15遺伝子多型測定の意義と課題

角田洋一, 木内喜孝, 正宗淳

日本消化器病学会雑誌　117　(3)　195-207　2020/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Key Wordキーワード(No.29) NUDT15

角田洋一

消化器病学サイエンス　4　(1)　48-48　2020/03
Publisher: (株)先端医学社
ISSN： 2432-7549
Thiopurine-mediated impairment of hematopoietic stem and leukemia cells in Nudt15 ^R138C knock-in mice International-journal Peer-reviewed

Goichi Tatsumi, Masahiro Kawahara, Takayuki Imai, Ai Nishishita-Asai, Atsushi Nishida, Osamu Inatomi, Akihiko Yokoyama, Yoichi Kakuta, Katsuyuki Kito, Akira Andoh

Leukemia　34　(3)　882-894　2020/03/01

DOI： 10.1038/s41375-019-0583-9 　

ISSN： 0887-6924

eISSN： 1476-5551
【新薬で変わるか?クローン病薬物治療】チオプリン製剤によるクローン病治療副作用のマネジメントも含めて

角田洋一

消化器の臨床　23　(1)　30-35　2020/02
Publisher: (株)ヴァンメディカル
ISSN： 1344-3070
Long-Term Prognosis of Japanese Patients with Crohn's Disease Treated by Switching Anti-Tumor Necrosis Factor-α Antibodies. International-journal Peer-reviewed

Rintaro Moroi, Hisashi Shiga, Katsuya Endo, Katsutoshi Yamamoto, Masatake Kuroha, Yoshitake Kanazawa, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Inflammatory intestinal diseases　5　(1)　11-19　2020/02

DOI： 10.1159/000504803 　

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Introduction: The long-term prognosis of Japanese patients with Crohn's disease (CD) treated by switching anti-tumor necrosis factor-α (anti-TNFα) antibodies remains unclear. Objective: This study aimed to clarify the long-term prognosis and clinical factors that affect the long-term prognosis and outcomes of such patients. Methods: This retrospective, observational, single-center cohort study analyzed Japanese patients with CD treated by switching between infliximab and adalimumab in the Tohoku University Hospital between March 2003 and December 2017. Cumulative relapse-free survival and cumulative surgery-free survival rates were analyzed using the Kaplan-Meier method. Clinical factors that affected the long-term outcomes were identified using both a log-rank test and the Cox proportional hazards model. Results: The cumulative relapse-free survival rates were 68.6, 33.7, and 22.9% at 1, 3, and 5 years, respectively. The surgery-free survival rates were 91.7, 75.7, and 57.4% at 1, 3, and 5 years, respectively. The cumulative relapse-free survival rate was significantly higher in the group with ileal lesions (HR = 0.12; 95% CI 0.0066-0.64, p = 0.0086), stricture (HR = 0.24; 95% CI 0.0094-0.59, p = 0.0021), and a penetrating type (HR = 0.34; 95% CI 0.14-0.84, p = 0.020). Intolerance (HR = 0.29; 95% CI 0.12-0.63, p = 0.0013) and switching after surgery (HR = 0.41; 95% CI 0.17-0.87, p = 0.019) were clinical factors that reduced the risk of recurrence. The cumulative surgery-free survival rate was significantly higher in the group that switched after surgery (HR = 0.28; 95% CI 0.074-0.91, p = 0.034) and used concomitant thiopurine (HR = 0.32; 95% CI 0.10-0.90, p = 0.030). Conclusion: We should clarify the reason for switching anti-TNFα antibodies and investigate bowel complications before switching. Surgical reset of bowel complications including stricture and fistula could reduce the risk of recurrence after switching anti-TNFα antibodies. Concomitant thiopurine administration might reduce the risk of bowel surgery after switching anti-TNFα antibodies.
FACTORS ASSOCIATED WITH FIBROSIS DURING COLORECTAL SUBMUCOSAL DISSECTION (ESD): DOES PRETREATMENT BIOPSY POTENTIALLY ELICT SUBMUCOSAL FIBROSIA AND AFFECT ESD OUTCOMES?

Yoichi Kakuta

Gastrointestinal Endoscopy　2020
Pretreatment screening for inflammatory bowel diseases; significance and problems in genotyping of NUDT15

Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Journal of Japanese Society of Gastroenterology　117　(3)　195-207　2020

DOI： 10.11405/nisshoshi.117.195 　

ISSN： 0446-6586

eISSN： 1349-7693
チオプリン不耐症例を判別するNUDT15遺伝子検査の有用性

角田洋一

自己抗体と自己免疫　2020　2020

ISSN： 1344-3372
ESDアフターケアが一番大事 eCura systemとその公開後のリアルワールドにおける早期胃癌内視鏡的根治度C-2患者のマネージメント

八田和久, 後藤田卓志, 角田洋一, 根来健一, 小池智幸, 正宗淳

消化器内視鏡　32　(9)　1330-1333　2020
Publisher: (株)東京医学社
ISSN： 0915-3217
チオプリン製剤を始めるときはNUDT15遺伝子多型をみてから

角田洋一

SRL宝函　41　(3)　4-11　2020
Publisher: (株)エスアールエル
ISSN： 0912-0912
Genetic background of IBD-How can we find monogenic IBDs?

角田洋一

Pharma Medica　38　(11)　17-20　2020
Publisher:
ISSN： 0289-5803
炎症性腸疾患実地医家が理解すべき疾患背景と診療のプロセス炎症性腸疾患の病態遺伝的要因や疾患感受性遺伝子とはどのようなものか?

角田洋一

Medical Practice　37　(12)　1825-1830　2020
Publisher: (株)文光堂
ISSN： 0910-1551
Reduction Input Time of Data Using Templates and a Smartphone App

佐々木恵利奈, 根来健一, 諸井林太郎, 角田洋一, 中村直毅, 中山雅晴, 中山雅晴

医療情報学　40　(3)　145-150　2020
Publisher:
ISSN： 0289-8055
Factors Associated with Fibrosis during Colorectal Endoscopic Submucosal Dissection: Does Pretreatment Biopsy Potentially Elicit Submucosal Fibrosis and Affect Endoscopic Submucosal Dissection Outcomes? International-journal

Masatake Kuroha, Hisashi Shiga, Yoshitake Kanazawa, Hiroshi Nagai, Tomoyuki Handa, Ryo Ichikawa, Motoyuki Onodera, Takeo Naito, Rintaro Moroi, Tomoya Kimura, Katsuya Endo, Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa, Atsushi Masamune

Digestion　102　(4)　590-598　2020

DOI： 10.1159/000510145 　

ISSN： 0012-2823

eISSN： 1421-9867
Endoscopic radial incision and cutting for Crohn's Disease-associated intestinal stricture: a pilot study. International-journal Peer-reviewed

Rintaro Moroi, Hisashi Shiga, Masatake Kuroha, Yoshitake Kanazawa, Kotaro Nochioka, Yoichi Kakuta, Yoshitaka Kinouchi, Atsushi Masamune

Endoscopy international open　8　(1)　E81-E86　2020/01

DOI： 10.1055/a-1027-6921 　

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Background and study aims Intestinal stricture associated with Crohn's disease (CD) is usually treated by endoscopic balloon dilation (EBD) or stricture plasty. Although EBD is effective and safe for such strictures, refractory stricture after EBD poses a problem. Hence, other novel approaches for these refractory strictures are required. On the other hand, the efficacy of radial incision and cutting (RIC) method for esophageal stricture after esophagogastric surgery is reported. In this pilot study, we adopted the RIC technique for five CD patients with refractory intestinal stricture to dilate their strictures. We conducted the RIC procedure using an electric needle knife with a ceramic tip on the top of the needle. Four cases were of anastomotic stricture after ileocecal resection and the remaining one case was of stricture due to mucosal healing. The RIC procedure was successful for all five patients. Average procedure time was 18.6 minutes. One patient developed delayed bleeding after RIC. There were no cases of perforation. RIC could be an alternative therapy for intestinal stricture associated with CD. Further studies should be conducted to clarify its efficacy and safety.
High-resolution melt analysis enables simple genotyping of complicated polymorphisms of codon 18 rendering the NUDT15 diplotype. Peer-reviewed

Yoichi Kakuta, Yasuhiro Izumiyama, Daisuke Okamoto, Takeru Nakano, Ryo Ichikawa, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Hisaaki Kudo, Naoko Minegishi, Yosuke Kawai, Katsushi Tokunaga, Masao Nagasaki, Yoshitaka Kinouchi, Yasuo Suzuki, Atsushi Masasmune

Journal of gastroenterology　55　(1)　67-77　2020/01

DOI： 10.1007/s00535-019-01638-x 　

ISSN： 0944-1174

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BACKGROUND: The genetic variants of NUDT15 have been verified to induce adverse events (AEs) of thiopurines. Codon 139 variants are frequently observed in Asians, while multiple variants are seen in codon 18 which also cause AEs including the European ancestry. The purpose of this study is to establish a technique capable of the simple genotyping of NUDT15 codon 18 and to evaluate its efficacy. METHODS: A high-resolution melt (HRM) technique is performed to simply determine genotypes. The accuracy of HRM analysis was evaluated with DNAs from 1245 Japanese patients with inflammatory bowel diseases. Subsequently, another group of 572 patients was analyzed to verify the method. The diplotypes and the frequency of their AEs were estimated on the basis of codon 18 and 139 genotypes. RESULTS: The HRM analysis enabled the correct identification of the three main genotypes, ref/ref, ref/ins, and ref/V18I, in 1236 of 1241 cases. All rare genotypes including ref/del were identified as the impossible-to-determine group, the proper diagnosis rate was 99.6%. In the verification test using other samples, the diagnosis rate was 99.7%. By estimating diplotypes using both codon 18 and 139 genotypes, 2.74% and 2.13% of Japanese patients with Arg/Arg and Arg/Cys of codon 139 have a lower enzymatic activity of NUDT15 and a higher risk for adverse responses than those estimated by codon 139 genotypes alone. CONCLUSIONS: Our study showed that HRM method enables simple genotyping of complicated codon 18 variants essential to haplotype estimation of the NUDT15.
Correction to: High-resolution melt analysis enables simple genotyping of complicated polymorphisms of codon 18 rendering the NUDT15 diplotype. Peer-reviewed

Yoichi Kakuta, Yasuhiro Izumiyama, Daisuke Okamoto, Takeru Nakano, Ryo Ichikawa, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Hisaaki Kudo, Naoko Minegishi, Yosuke Kawai, Katsushi Tokunaga, Masao Nagasaki, Yoshitaka Kinouchi, Yasuo Suzuki, Atsushi Masamune

Journal of gastroenterology　55　(1)　132-132　2020/01

DOI： 10.1007/s00535-019-01646-x 　

ISSN： 0944-1174

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The correct name of the last author should be.
スマートフォンアプリを利用したテンプレート書式入力の省力化

佐々木恵利奈, 菅原綾子, 根来健一, 諸井林太郎, 角田洋一, 中村直毅, 中山雅晴

医療情報学連合大会論文集　39回　895-896　2019/11
Publisher: (一社)日本医療情報学会
ISSN： 1347-8508

eISSN： 2433-698X
スマートフォンアプリを利用したテンプレート書式入力の省力化

佐々木恵利奈, 菅原綾子, 根来健一, 諸井林太郎, 角田洋一, 中村直毅, 中山雅晴

医療情報学連合大会論文集　39回　438-438　2019/11
Publisher: (一社)日本医療情報学会
ISSN： 1347-8508
臨床検査アップデート Nudix hydrolase 15(NUDT15)遺伝子多型検査

角田洋一

Modern Media　65　(8)　156-161　2019/08
Publisher: 栄研化学(株)
ISSN： 0026-8054
A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn's Disease in Japanese Individuals. International-journal Peer-reviewed

Yoichi Kakuta, Yosuke Kawai, Takeo Naito, Atsushi Hirano, Junji Umeno, Yuta Fuyuno, Zhenqiu Liu, Dalin Li, Takeru Nakano, Yasuhiro Izumiyama, Ryo Ichikawa, Daisuke Okamoto, Hiroshi Nagai, Shin Matsumoto, Katsutoshi Yamamoto, Naonobu Yokoyama, Hirofumi Chiba, Yusuke Shimoyama, Motoyuki Onodera, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Kenichi Negoro, Jun Yasuda, Motohiro Esaki, Katsushi Tokunaga, Minoru Nakamura, Takayuki Matsumoto, Dermot P B McGovern, Masao Nagasaki, Yoshitaka Kinouchi, Tooru Shimosegawa, Atsushi Masamune

Journal of Crohn's & colitis　13　(5)　648-658　2019/04/26

DOI： 10.1093/ecco-jcc/jjy197 　

ISSN： 1873-9946

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BACKGROUND AND AIMS: Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn's disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel. METHODS: Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions. RESULTS: Genotype data of 4 335 144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10-26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10-19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p <1 × 10-6], and rs488200 located upstream of RAP1A was significantly associated with CD [pcombined = 4.36 × 10-8, OR = 1.31]. Transcriptome analysis of CD4+ effector memory T cells from lamina propria mononuclear cells of CD patients revealed a significant association of rs488200 with RAP1A expression. CONCLUSIONS: RAP1A is a novel susceptibility locus for CD in the Japanese population.
Long-term prognosis of Japanese patients with biologic-naïve Crohn's disease treated with anti-tumor necrosis factor-α antibodies. International-journal Peer-reviewed

Moroi R, Endo K, Yamamoto K, Naito T, Onodera M, Kuroha M, Kanazawa Y, Kimura T, Kakuta Y, Masamune A, Kinouchi Y, Shimosegawa T

Intestinal research　17　(1)　94-106　2019/01

DOI： 10.5217/ir.2018.00048 　

ISSN： 1598-9100

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BACKGROUND/AIMS: Few reports have described the long-term treatment outcomes of the anti-tumor necrosis factor-α antibody for Japanese Crohn's disease (CD) patients. The aim of this study was to evaluate them and clarify the clinical factors that affect the long-term prognosis of the anti-tumor necrosis factor-α treatments. METHODS: This was a retrospective, observational, single-center cohort study. Japanese CD patients treated with either infliximab or adalimumab as a first-line therapy were analyzed. The cumulative retention rates of the biologics, relapse-free survival, and surgery-free survival were analyzed using Kaplan-Meier methods. The clinical factors associated with the long-term outcomes were estimated by both the log-rank test and Cox proportional hazard model. RESULTS: The cumulative retention rate was significantly higher in the group with a concomitant elemental diet of ≥900 kcal/day, baseline C-reactive protein (CRP) levels <2.6 mg/dL, and baseline serum albumin levels ≥3.5 g/dL, respectively. The baseline serum albumin levels were also associated with both relapse-free and surgery-free survival. The lack of concomitant use of an elemental diet ≥900 kcal/day was identified as the only independent risk factor for the withdrawal of the biologics. CONCLUSIONS: Baseline CRP levels and serum albumin levels could affect the long-term outcomes in CD patients. Concomitant elemental diet of ≥900 kcal/day could have a positive influence on clinical treatment course.
Correction: Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease. International-journal Peer-reviewed

Chiba H, Kakuta Y, Kinouchi Y, Kawai Y, Watanabe K, Nagao M, Naito T, Onodera M, Moroi R, Kuroha M, Kanazawa Y, Kimura T, Shiga H, Endo K, Negoro K, Nagasaki M, Unno M, Shimosegawa T

PloS one　14　(2)　e0212148　2019

DOI： 10.1371/journal.pone.0212148 　

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[This corrects the article DOI: 10.1371/journal.pone.0194036.].
潰瘍性大腸炎緩解維持療法の現状 NUDT15 R139C C/Tヘテロ症例におけるチオプリン製剤を用いた潰瘍性大腸炎の治療成績

渡辺憲治, 高川哲也, 角田洋一, 藤森絢子, 小島健太郎, 小柴良司, 藤本晃士, 佐藤寿行, 河合幹夫, 上小鶴孝二, 横山陽子, 宮嵜孝子, 樋田信幸, 堀和敏, 池内浩基, 中村志郎

日本大腸肛門病学会雑誌　71　(抄録号)　A69-A69　2018/09
Publisher: (一社)日本大腸肛門病学会
ISSN： 0047-1801

eISSN： 1882-9619
NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study. Peer-reviewed

Yoichi Kakuta, Yosuke Kawai, Daisuke Okamoto, Tetsuya Takagawa, Kentaro Ikeya, Hirotake Sakuraba, Atsushi Nishida, Shoko Nakagawa, Miki Miura, Takahiko Toyonaga, Kei Onodera, Masaru Shinozaki, Yoh Ishiguro, Shinta Mizuno, Masahiro Takahara, Shunichi Yanai, Ryota Hokari, Tomoo Nakagawa, Hiroshi Araki, Satoshi Motoya, Takeo Naito, Rintaro Moroi, Hisashi Shiga, Katsuya Endo, Taku Kobayashi, Makoto Naganuma, Sakiko Hiraoka, Takayuki Matsumoto, Shiro Nakamura, Hiroshi Nakase, Tadakazu Hisamatsu, Makoto Sasaki, Hiroyuki Hanai, Akira Andoh, Masao Nagasaki, Yoshitaka Kinouchi, Tooru Shimosegawa, Atsushi Masamune, Yasuo Suzuki

Journal of gastroenterology　53　(9)　1065-1078　2018/09

DOI： 10.1007/s00535-018-1486-7 　

ISSN： 0944-1174

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BACKGROUND: Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs. METHODS: Overall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation. RESULTS: We confirmed the association of NUDT15 p.Arg139Cys with leukopenia and alopecia (p = 2.20E-63, 1.32E-69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms (p = 6.39E-04, OR = 1.89). Time to leukopenia was significantly shorter, and when leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of leukopenia frequency with estimated enzyme activities based on the diplotypes (r2 = 0.926, p = 0.0087), there were no significant differences in the AUCs of diplotypes from those of codon 139 to predict severe AEs (AUC = 0.916, 0.921, for acute severe leukopenia, AUC = 0.990, 0.991, for severe alopecia, respectively). CONCLUSIONS: Genotyping of NUDT15 codon 139 was sufficient to predict acute severe leukopenia and alopecia in Japanese patients with IBD.
IBD治療のピットフォール(第18回) チオプリン製剤とNUDT15遺伝子多型

角田洋一, 木内喜孝

IBD Research　12　(2)　119-124　2018/06
Publisher: (株)先端医学社
ISSN： 1881-6533
Long-term course of inflammatory bowel disease after the Great East Japan Earthquake. International-journal Peer-reviewed

Miyazawa T, Shiga H, Kinouchi Y, Takahashi S, Tominaga G, Takahashi H, Takagi S, Obana N, Kikuchi T, Omori S, Sato Y, Takahashi S, Umemura K, Endo K, Kakuta Y, Matsuura M, Kimura T, Kuroha M, Shimosegawa T

Journal of gastroenterology and hepatology　33　(12)　1956-1960　2018/05

DOI： 10.1111/jgh.14286 　

ISSN： 0815-9319

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BACKGROUND AND AIM: This study analyzed inflammatory bowel disease activity for 2 years after the Great East Japan Earthquake. METHODS: We compared the relapse rates of patients with ulcerative colitis or Crohn's disease 1 and 2 years after the earthquake with rates immediately after the earthquake. To evaluate continuous disease courses, we also performed multivariate time-to-event analyses from the time of the earthquake to the onset of additional treatments. RESULTS: Of 903 patients with ulcerative colitis or Crohn's disease in our previous study, we could evaluate 2-year courses in 677 patients (394 ulcerative colitis and 283 Crohn's disease). Compared with the relapse rates of ulcerative colitis and Crohn's disease immediately after the earthquake (15.8% and 7.0%, respectively), those in the corresponding periods in 2012 (2.5% and 1.1%, respectively) and 2013 (2.3% and 2.5%, respectively) significantly decreased. There were 226 patients who required additional treatments after the earthquake. Multivariate time-to-event analyses revealed that only patients who had experienced the death of family members or friends were likely to need additional treatments (hazard ratio = 1.77, 95% confidence interval = 1.25-2.47). No other factors had a significant influence. CONCLUSIONS: The relapse rates 1 and 2 years after the earthquake significantly decreased. The factors that influenced long-term relapse were different from those that influenced short-term relapse.
Periostin attenuates tumor growth by inducing apoptosis in colitisrelated colorectal cancer Peer-reviewed

Yusuke Shimoyama, Keiichi Tamai, Rie Shibuya, Mao Nakamura, Mai Mochizuki, Kazunori Yamaguchi, Yoichi Kakuta, Yoshitaka Kinouchi, Ikuro Sato, Akira Kudo, Tooru Shimosegawa, Kennichi Satoh

Oncotarget　9　(28)　20008-20017　2018/04/13
Publisher: Impact Journals LLC
DOI： 10.18632/oncotarget.25026 　

ISSN： 1949-2553
炎症性腸疾患に対する抗TNF-α抗体治療薬導入により見えてきた臨床課題 Crohn病に対する抗TNF-α抗体の長期的治療成績から考える最適な投与戦略

諸井林太郎, 遠藤克哉, 角田洋一

日本消化器病学会雑誌　115　(臨増総会)　A96-A96　2018/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Residual Lesions on Capsule Endoscopy Is Associated with Postoperative Clinical Recurrence in Patients with Crohn’s Disease Peer-reviewed

Jun Kusaka, Hisashi Shiga, Masatake Kuroha, Tomoya Kimura, Yoichi Kakuta, Katsuya Endo, Yoshitaka Kinouchi, Tooru Shimosegawa

Digestive Diseases and Sciences　63　(3)　768-774　2018/03/01
Publisher: Springer New York LLC
DOI： 10.1007/s10620-018-4942-6 　

ISSN： 1573-2568 0163-2116
Tacrolimus Dose Optimization Strategy for Refractory Ulcerative Colitis Based on the Cytochrome P450 3A5 Polymorphism Prediction Using Trough Concentration after 24 Hours Peer-reviewed

Motoyuki Onodera, Katsuya Endo, Takeo Naito, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Yoichi Kakuta, Kenichi Negoro, Yoshitaka Kinouchi, Tooru Shimosegawa

Digestion　97　(1)　90-96　2018/03/01
Publisher: S. Karger AG
DOI： 10.1159/000484227 　

ISSN： 1421-9867 0012-2823
Effective and less invasive diagnostic strategy for gastrointestinal GVHD. International-journal Peer-reviewed

Endo K, Fujishima F, Kuroha M, Moroi R, Onodera M, Naito T, Kanazawa Y, Kimura T, Shiga H, Kakuta Y, Kinouchi Y, Shimosegawa T

Endoscopy international open　6　(3)　E281-E291　2018/03

DOI： 10.1055/s-0043-122226 　

ISSN： 2364-3722

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Background and study aims: Rectosigmoidoscopy with biopsy has been regarded to be a useful procedure to diagnose gastrointestinal graft-versus-host disease (GVHD). However, little is known about the specific colonoscopic features of gastrointestinal GVHD. In this study, we focused on the 4 unique colonoscopic findings - orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect - which are possible specific findings of gastrointestinal GVHD. We aimed to estimate the usefulness of these four unique colonoscopic findings in the rectosigmoid portion to diagnose gastrointestinal GVHD. Patients and methods: Seventy patients who were histologically diagnosed with gastrointestinal GVHD at our institute were retrospectively enrolled. Colonoscopic findings were reviewed, focusing on the four characteristic findings. The percentage of the positive cases for the characteristic findings was calculated. The final scoping portion and the number of cases showing any of the four characteristic findings in the rectosigmoid portion were also evaluated. The relationships between biopsy sites and the histological findings were also evaluated. Results: Orange peel appearance was observed in 66 cases (94.3 %). Spotty redness was observed in 45 cases (64.3 %). Small mucosal sloughing was observed in 49 cases (70.0 %). Diffuse mucosal defect was observed in six cases (8.6 %). The number of cases that were concurrently positive for one, two, and three findings were 16 (20.8 %), 20 (26.0 %), and 34 (48.6 %), respectively. Fifty-eight cases (82.9 %) were investigated up to the rectosigmoid portion, and 12 (17.1 %) were investigated beyond the sigmoid colon. All of the cases showed at least 1 of the 4 characteristics in the rectosigmoid portion. The percentage of crypt apoptosis in the biopsy specimen from orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect were 87.5 %, 83.3 %, 87.2 %, and 88.9 %, respectively. Conclusion: Orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect are the characteristic colonoscopic findings useful for diagnosis of gastrointestinal GVHD. These findings are frequently observed in the rectosigmoid portion. The histological detection rates for crypt cell apoptosis from these findings are high. Identifying the four characteristic findings on rectosigmoidoscopy and taking biopsies from these areas could be essential for the diagnostic strategy for gastrointestinal GVHD.
Clinical and genetic risk factors for decreased bone mineral density in Japanese patients with inflammatory bowel disease. International-journal Peer-reviewed

Naito T, Yokoyama N, Kakuta Y, Ueno K, Kawai Y, Onodera M, Moroi R, Kuroha M, Kanazawa Y, Kimura T, Shiga H, Endo K, Nagasaki M, Masamune A, Kinouchi Y, Shimosegawa T

Journal of gastroenterology and hepatology　33　(11)　1873-1881　2018/03

DOI： 10.1111/jgh.14149 　

ISSN： 0815-9319

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BACKGROUND AND AIM: Patients with inflammatory bowel disease (IBD) are at a high risk of low bone mineral density (BMD). Reportedly, clinical and genetic factors cause low BMD in Caucasians; however, studies in non-Caucasian populations remain scarce. METHODS: Clinical risk factors for low BMD were investigated in 266 Japanese patients with IBD, and a genome-wide association analysis (GWAS) was performed using linear regression with associated clinical factors as covariates. Genotyping was performed using a population-optimized genotyping array (Japonica array® ). After quality control, the genotype data of 4 384 682 single-nucleotide polymorphisms (SNPs) from 254 patients with IBD were used for GWAS. RESULTS: Body mass index, age, and disease duration were independently associated with the BMD of the femoral neck (P = 1.41E - 13, 1.04E - 5, and 1.58E - 3, respectively), and body mass index and sex were associated with the BMD of the lumbar spine (P = 6.90E - 10 and 6.84E - 3, respectively). In GWAS, 118 and 42 candidate SNPs of the femoral neck and lumbar spine, respectively, were identified. Among 118, 111 candidate SNPs of the femoral neck were located within the SLC22A23 gene, which is a known IBD susceptibility gene (minimum P = 1.42E - 07). Among 42, 18 candidate SNPs of the lumbar spine were located within the MECOM gene, which is associated with osteopenia (minimum P = 5.86E - 07). Interestingly, none of the known loci showed a significant association with BMD. CONCLUSIONS: Although clinical risk factors for low BMD in IBD were similar to those in the general population, genetic risk factors were rather different.
免疫チェックポイント阻害薬が原因と考えられた腸炎の2例

泉山泰宏, 木村智哉, 中野健, 岡本大祐, 市川遼, 永井博, 松本信, 下山雄丞, 千葉宏文, 横山直信, 山本勝利, 小野寺基之, 内藤健夫, 黒羽正剛, 金澤義丈, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会雑誌　2　(Suppl.)　289-289　2018/02
Publisher: (一社)日本消化管学会
ISSN： 2433-3840

eISSN： 2435-8967
大腸ESDのこれまでとこれから大腸ESD術中の粘膜下層線維化リスク因子についての検討術前生検により粘膜下層の線維化をきたすのか?

黒羽正剛, 志賀永嗣, 金澤義文, 半田智之, 市川遼, 小野寺基之, 内藤健夫, 諸井林太郎, 木村智哉, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会雑誌　2　(Suppl.)　124-124　2018/02
Publisher: (一社)日本消化管学会
ISSN： 2433-3840

eISSN： 2435-8967
SMOKING NEGATIVELY AFFECTS DISEASE COURSE REGARDLESS OF SMOKING AMOUNT AND MAY BE ASSOCIATED WITH PANETH CELL PHENOTYPE IN JAPANESE CROHN'S DISEASE PATIENTS Peer-reviewed

Naito Takeo, Liu Ta-Chiang, Kakuta Yoichi, Moroi Rintaro, Kuroha Masatake, Kimura Tomoya, Kanazawa Yoshitake, Kinouchi Yoshitaka, Stappenbeck Thaddeus S, Shimosegawa Tooru

INFLAMMATORY BOWEL DISEASES　24　S39　2018/02

ISSN： 1078-0998
Pharmacogenetics of thiopurines for inflammatory bowel disease in East Asia: prospects for clinical application of NUDT15 genotyping Peer-reviewed

Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa

Journal of Gastroenterology　53　(2)　172-180　2018/02/01
Publisher: Springer Tokyo
DOI： 10.1007/s00535-017-1416-0 　

ISSN： 1435-5922 0944-1174
SMOKING NEGATIVELY AFFECTS DISEASE COURSE REGARDLESS OF SMOKING AMOUNT AND MAY BE ASSOCIATED WITH PANETH CELL PHENOTYPE IN JAPANESE CROHN'S DISEASE PATIENTS Peer-reviewed

Naito Takeo, Liu Ta-Chiang, Kakuta Yoichi, Moroi Rintaro, Kuroha Masatake, Kimura Tomoya, Kanazawa Yoshitake, Kinouchi Yoshitaka, Stappenbeck Thaddeus S, Shimosegawa Tooru

GASTROENTEROLOGY　154　(1)　S56　2018/01

DOI： 10.1053/j.gastro.2017.11.155 　

ISSN： 0016-5085
Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease. International-journal Peer-reviewed

Hirofumi Chiba, Yoichi Kakuta, Yoshitaka Kinouchi, Yosuke Kawai, Kazuhiro Watanabe, Munenori Nagao, Takeo Naito, Motoyuki Onodera, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Kenichi Negoro, Masao Nagasaki, Michiaki Unno, Tooru Shimosegawa

PloS one　13　(3)　e0194036　2018

DOI： 10.1371/journal.pone.0194036 　

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BACKGROUND: Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. METHODS: CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score ([Formula: see text]) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing [Formula: see text] >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. RESULTS: We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of [Formula: see text] (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 ([Formula: see text] = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). CONCLUSIONS: We confirmed the existence of cis-regulated ASM around IBD susceptibility genes and the association between ASM SNP (rs36221701) genotype and SMAD3 expression, a susceptibility gene for IBD. These results give us supporting evidence that DNA methylation mediates genetic effects on disease susceptibility.
Increased expression of IL12B mRNA transcribed from the risk haplotype for Crohn's disease is a risk factor for disease relapse in Japanese patients Peer-reviewed

Yoichi Kakuta, Tomoya Kimura, Kenichi Negoro, Masatake Kuroha, Hisashi Shiga, Katsuya Endo, Yoshitaka Kinouchi, Tooru Shimosegawa

JOURNAL OF GASTROENTEROLOGY　52　(12)　1230-1239　2017/12

DOI： 10.1007/s00535-017-1322-5 　

ISSN： 0944-1174

eISSN： 1435-5922
A coding variant in FTO confers susceptibility to thiopurine-induced leukopenia in East Asian patients with IBD Peer-reviewed

Han Sang Kim, Jae Hee Cheon, Eun Suk Jung, Joonhee Park, Sowon Aum, Soo Jung Park, Sungho Eun, Jinu Lee, Ulrich Ruether, Giles S. H. Yeo, Marcella Ma, Kyong Soo Park, Takeo Naito, Yoichi Kakuta, Ji Hyun Lee, Won Ho Kim, Min Goo Lee

GUT　66　(11)　1926-1935　2017/11

DOI： 10.1136/gutjnl-2016-311921 　

ISSN： 0017-5749

eISSN： 1468-3288
Endoscopic removal of migrated colonic self-expandable metallic stent using a sliding tube Peer-reviewed

Rintaro Moroi, Yoichi Kakuta, Katsuya Endo, Masatake Kuroha, Shoichi Kayaba, Yoshitaka Kinouchi, Tooru Shimosegawa

ENDOSCOPY　49　(10)　E240-E241　2017/10

DOI： 10.1055/s-0043-114406 　

ISSN： 0013-726X

eISSN： 1438-8812
Risk factors associated with postoperative recurrence and repeat surgery in Japanese patients with Crohn's disease Peer-reviewed

Jun Kusaka, Hisashi Shiga, Masatake Kuroha, Tomoya Kimura, Yoichi Kakuta, Katsuya Endo, Yoshitaka Kinouchi, Tooru Shimosegawa

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE　32　(10)　1407-1413　2017/10

DOI： 10.1007/s00384-017-2867-8 　

ISSN： 0179-1958

eISSN： 1432-1262
ATP-binding cassette subfamily B member 1 1236C/T polymorphism significantly affects the therapeutic outcome of tacrolimus in patients with refractory ulcerative colitis Peer-reviewed

Motoyuki Onodera, Katsuya Endo, Yoichi Kakuta, Masatake Kuroha, Tomoya Kimura, Keiichiro Hiramoto, Yoshitake Kanazawa, Kenichi Negoro, Hisashi Shiga, Yoshitaka Kinouchi, Tooru Shimosegawa

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY　32　(9)　1562-1569　2017/09

DOI： 10.1111/jgh.13753 　

ISSN： 0815-9319

eISSN： 1440-1746
抗TNFα製剤が著効した潰瘍性大腸炎関連小腸炎の2例

千葉宏文, 内藤健夫, 木村智哉, 泉山泰宏, 中野健, 岡本大祐, 市川遼, 松本信, 永井博, 横山直信, 山本勝利, 小野寺基之, 日下順, 平本圭一郎, 黒羽正剛, 金澤義丈, 角田洋一, 遠藤克哉, 木内喜孝, 藤島史喜, 下瀬川徹

Gastroenterological Endoscopy　59　(Suppl.1)　1092-1092　2017/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
肥厚性皮膚骨膜症を合併した非特異性多発性小腸潰瘍(CEAS)の一例

永井博, 木村智哉, 松本信, 下山雄丞, 千葉宏文, 山本勝利, 横山直信, 小野寺基之, 日下順, 内藤健夫, 川上瑶子, 平本圭一郎, 黒羽正剛, 金澤義丈, 角田洋一, 遠藤克哉, 梅野淳嗣, 江崎幹宏, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy　59　(Suppl.1)　1094-1094　2017/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
von Hippel-Lindau病に発症した小腸GISTの一例

小野寺基之, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy　59　(Suppl.1)　1145-1145　2017/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
潰瘍性大腸炎に対するタクロリムス治療の治療効果とCYP3A5、ABCB1遺伝子多型との関連

小野寺基之, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　114　(臨増総会)　A254-A254　2017/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
LRRK2 but not ATG16L1 is associated with Paneth cell defect in Japanese Crohn's disease patients. International-journal Peer-reviewed

Liu TC, Naito T, Liu Z, VanDussen KL, Haritunians T, Li D, Endo K, Kawai Y, Nagasaki M, Kinouchi Y, McGovern DP, Shimosegawa T, Kakuta Y, Stappenbeck TS

JCI insight　2　(6)　e91917　2017/03

DOI： 10.1172/jci.insight.91917 　

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BACKGROUND. Morphological patterns of Paneth cells are a prognostic biomarker in Western Crohn's disease (CD) patients, and are associated with autophagy-associated ATG16L1 and NOD2 variants. We hypothesized that genetic determinants of Paneth cell phenotype in other ethnic CD cohorts are distinct but also involved in autophagy. METHODS. We performed a hypothesis-driven analysis of 56 single nucleotide polymorphisms (SNPs) associated with CD susceptibility or known to affect Paneth cell function in 110 Japanese CD patients who underwent ileal resection. We subsequently performed a genome-wide association analysis. Paneth cell phenotype was determined by defensin-5 immunofluorescence. Selected genotype-Paneth cell defect correlations were compared to a Western CD cohort (n = 164). RESULTS. The average percentage of abnormal Paneth cells in Japanese CD was similar to Western CD (P = 0.87), and abnormal Paneth cell phenotype was also associated with early recurrence (P = 0.013). In contrast to Western CD, ATG16L1 T300A was not associated with Paneth cell defect in Japanese CD (P = 0.20). Among the 56 selected SNPs, only LRRK2 M2397T showed significant association with Paneth cell defect (P = 3.62 × 10-4), whereas in the Western CD cohort it was not (P = 0.76). Pathway analysis of LRRK2 and other candidate genes with P less than 5 × 10-4 showed connections with known CD susceptibility genes and links to autophagy and TNF-α networks. CONCLUSIONS. We found dichotomous effects of ATG16L1 and LRRK2 on Paneth cell defect between Japanese and Western CD. Genes affecting Paneth cell phenotype in Japanese CD were also associated with autophagy. Paneth cell phenotype also predicted prognosis in Japanese CD. FUNDING. Helmsley Charitable Trust, Doris Duke Foundation (grant 2014103), Japan Society for the Promotion of Science (KAKENHI grants JP15H04805 and JP15K15284), Crohn's and Colitis Foundation grant 274415, NIH (grants 1R56DK095820, K01DK109081, and UL1 TR000448).
NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases Peer-reviewed

Toshiyuki Sato, Tetsuya Takagawa, Yoichi Kakuta, Akihiro Nishio, Mikio Kawai, Koji Kamikozuru, Yoko Yokoyama, Yuko Kita, Takako Miyazaki, Masaki Iimuro, Nobuyuki Hida, Kazutoshi Hori, Hiroki Ikeuchi, Shiro Nakamura

Intestinal Research　15　(3)　328-337　2017
Publisher: Korean Association for the Study of Intestinal Diseases
DOI： 10.5217/ir.2017.15.3.328 　

ISSN： 2288-1956 1598-9100
Usefulness of a peripherally inserted central catheter for total parenteral nutrition in patients with inflammatory bowel disease Peer-reviewed

Hirofumi Chiba, Katsuya Endo, Yasuhiro Izumiyama, Takeru Nakano, Daisuke Okamoto, Ryo Ichikawa, Hiroshi Nagai, Shin Matsumoto, Naonobu Yokoyama, Katsutoshi Yamamoto, Yusuke Shimoyama, Takeo Naito, Motoyuki Onodera, Jun Kusaka, Keiichiro Hiramoto, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa

Journal of Japanese Society of Gastroenterology　114　(9)　1639-1648　2017
Publisher: Japanese Society of Gastroenterology
DOI： 10.11405/nisshoshi.114.1639 　

ISSN： 1349-7693 0446-6586
炎症性腸疾患患者における骨量減少に関わるリスク因子の検討

横山直信, 角田洋一, 黒羽正剛, 木村智哉, 遠藤克哉, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　113　(臨増大会)　A762-A762　2016/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
潰瘍性大腸炎に対するタクロリムス治療による腎機能障害の検討

小野寺基之, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　113　(臨増大会)　A768-A768　2016/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
MicroRNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6 Peer-reviewed

Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Seiichi Takahashi, Yoshitaka Kinouchi, Tooru Shimosegawa

WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY　8　(7)　532-542　2016/07

DOI： 10.4251/wjgo.v8.i7.532 　

ISSN： 1948-5204
NUDT15 R139C causes thiopurine-induced early severe hair loss and leukopenia in Japanese patients with IBD Peer-reviewed

Y. Kakuta, T. Naito, M. Onodera, M. Kuroha, T. Kimura, H. Shiga, K. Endo, K. Negoro, Y. Kinouchi, T. Shimosegawa

PHARMACOGENOMICS JOURNAL　16　(3)　280-285　2016/06

DOI： 10.1038/tpj.2015.43 　

ISSN： 1470-269X

eISSN： 1473-1150
No Association Between CEL-HYB Hybrid Allele and Chronic Pancreatitis in Asian Populations Peer-reviewed

Wen-Bin Zou, Arnaud Boulling, Atsushi Masamune, Prachand Issarapu, Emmanuelle Masson, Hao Wu, Xiao-Tian Sun, Liang-Hao Hu, Dai-Zhan Zhou, Lin He, Yann Fichou, Eriko Nakano, Shin Hamada, Yoichi Kakuta, Kiyoshi Kume, Hiroyuki Isayama, Sumit Paliwal, K. Radha Mani, Seema Bhaskar, David N. Cooper, Claude Ferec, Tooru Shimosegawa, Giriraj R. Chandak, Jian-Min Chen, Zhao-Shen Li, Zhuan Liao

GASTROENTEROLOGY　150　(7)　1558-+　2016/06

DOI： 10.1053/j.gastro.2016.02.071 　

ISSN： 0016-5085

eISSN： 1528-0012
大腸ESD穿孔症例の臨床背景と特徴

千葉宏文, 黒羽正剛, 永井博, 松本信, 横山直信, 山本勝利, 下山雄丞, 内藤健夫, 小野寺基之, 日下順, 川上瑶子, 只野敏浩, 木村智哉, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy　58　(Suppl.1)　672-672　2016/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
当院におけるバルーン内視鏡による小腸腫瘍の診断成績

松本信, 遠藤克哉, 黒羽正剛, 木村智哉, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy　58　(Suppl.1)　702-702　2016/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
A case of a ruptured submucosal aneurysm of the small intestine identified using double-balloon enteroscopy Peer-reviewed

Hirofumi Chiba, Katsuya Endo, Fumiyoshi Fujishima, Hideo Ohtsuka, Takeshi Naitoh, Masatake Kuroha, Tomoya Kimura, Hisashi Shiga, Yoichi Kakuta, Yoshitaka Kinouchi, Michiaki Unno, Tooru Shimosegawa

Clinical Journal of Gastroenterology　9　(2)　49-54　2016/04/01
Publisher: Springer Tokyo
DOI： 10.1007/s12328-016-0639-6 　

ISSN： 1865-7265 1865-7257
IBDモニタリングツールをいかに使いこなすか? NUDT15 R139C多型検査を用いたチオプリン導入ストラテジーの検討

角田洋一, 内藤健夫, 下瀬川徹

日本消化器病学会雑誌　113　(臨増総会)　A79-A79　2016/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
クローン病術後症例の中長期予後に対する生物学的製剤の治療効果

日下順, 志賀永嗣, 永井博, 松本信, 下山雄丞, 千葉宏文, 山本勝利, 横山直信, 小野寺基之, 内藤健夫, 川上瑶子, 只野敏浩, 黒羽正剛, 木村智哉, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　113　(臨増総会)　A266-A266　2016/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
A Comparison of Short- and Long-Term Therapeutic Outcomes of Infliximab- versus Tacrolimus-Based Strategies for Steroid-Refractory Ulcerative Colitis Peer-reviewed

Katsuya Endo, Motoyuki Onodera, Hisashi Shiga, Masatake Kuroha, Tomoya Kimura, Keiichiro Hiramoto, Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa

GASTROENTEROLOGY RESEARCH AND PRACTICE　2016　3162595　2016

DOI： 10.1155/2016/3162595 　

ISSN： 1687-6121

eISSN： 1687-630X
Colorectal endoscopic submucosal dissection (ESD) performed by experienced endoscopists with limited experience in gastric ESD Peer-reviewed

Hisashi Shiga, Masatake Kuroha, Katsuya Endo, Tomoya Kimura, Yoichi Kakuta, Yoshitaka Kinouchi, Shoichi Kayaba, Tooru Shimosegawa

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE　30　(12)　1645-1652　2015/12

DOI： 10.1007/s00384-015-2334-3 　

ISSN： 0179-1958

eISSN： 1432-1262
Variants in pancreatic carboxypeptidase genes CPA2 and CPB1 are not associated with chronic pancreatitis. International-journal Peer-reviewed

Eriko Nakano, Andrea Geisz, Atsushi Masamune, Tetsuya Niihori, Shin Hamada, Kiyoshi Kume, Yoichi Kakuta, Yoko Aoki, Yoichi Matsubara, Karolin Ebert, Maren Ludwig, Markus Braun, David A Groneberg, Tooru Shimosegawa, Miklós Sahin-Tóth, Heiko Witt

American journal of physiology. Gastrointestinal and liver physiology　309　(8)　G688-94-94　2015/10/15

DOI： 10.1152/ajpgi.00241.2015 　

ISSN： 0193-1857

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Genetic alterations in the carboxypeptidase A1 gene (CPA1) are associated with early onset chronic pancreatitis (CP). Besides CPA1, there are two other human pancreatic carboxypeptidases (CPA2 and CPB1). Here we examined whether CPA2 and CPB1 alterations are associated with CP in Japan and Germany. All exons and flanking introns of CPA2 and CPB1 were sequenced in 477 Japanese patients with CP (234 alcoholic, 243 nonalcoholic) and in 497 German patients with nonalcoholic CP by targeted next-generation sequencing and/or Sanger sequencing. Secretion and enzymatic activity of CPA2 and CPB1 variants were determined after transfection into HEK 293T cells. We identified six nonsynonymous CPA2 variants (p.V67I, p.G166R, p.D168E, p.D173H, p.R237W, and p.G388S), eight nonsynonymous CPB1 alterations (p.S65G, p.N120S, p.D172E, p.R195H, p.D208N, p.F232L, p.A317V, and p.D364Y), and one splice-site variant (c.687+1G>T) in CPB1. Functional analysis revealed essentially complete loss of function in CPA2 variants p.R237W and p.G388S and CPB1 variants p.R110H and p.D364Y. None of the CPA2 or CPB1 variants, including those resulting in a marked loss of function, were overrepresented in patients with CP. In conclusion, CPA2 and CPB1 variants are not associated with CP.
BiologicsナイーブのCrohn病に対するInfliximab・Adalimumabの長期的治療成績

遠藤克哉, 山本勝利, 木村智哉, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　112　(臨増大会)　A925-A925　2015/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn's disease through affecting the ADCC activity (vol 65, pg 265, 2013) Peer-reviewed

Rintaro Moroi, Katsuya Endo, Yoshitaka Kinouchi, Hisashi Shiga, Yoichi Kakuta, Masatake Kuroha, Yoshitake Kanazawa, Yosuke Shimodaira, Takahiko Horiuchi, Seiichi Takahashi, Tooru Shimosegawa

IMMUNOGENETICS　67　(9)　545-545　2015/09

DOI： 10.1007/s00251-015-0861-2 　

ISSN： 0093-7711

eISSN： 1432-1211
Common variants at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with chronic pancreatitis in Japan Peer-reviewed

Atsushi Masamune, Eriko Nakano, Shin Hamada, Yoichi Kakuta, Kiyoshi Kume, Tooru Shimosegawa

GUT　64　(8)　1345-1346　2015/08

DOI： 10.1136/gutjnl-2015-309802 　

ISSN： 0017-5749

eISSN： 1468-3288
大腸憩室出血症例に対する内視鏡施行タイミングと臨床経過に関する検討

下山雄丞, 遠藤克哉, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy　57　(Suppl.1)　798-798　2015/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
東日本大震災から長期間にわたる炎症性腸疾患患者の活動度の変化

宮澤輝子, 志賀永嗣, 平本圭一郎, 松下勝則, 黒羽正剛, 木村智哉, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　112　(臨増総会)　A346-A346　2015/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
当院において死亡転機を辿ったクローン病症例の臨床的特徴

横山直信, 遠藤克哉, 千葉宏文, 山本勝利, 下山雄丞, 内藤健夫, 日下順, 小野寺基之, 只野敏浩, 川上瑤子, 松下勝則, 宮澤輝子, 平本圭一郎, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 木内善孝, 下瀬川徹

日本消化器病学会雑誌　112　(臨増総会)　A382-A382　2015/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
高齢者潰瘍性大腸炎(UC)の臨床的特徴と問題点

黒羽正剛, 遠藤克哉, 横山直信, 山本勝利, 千葉宏文, 下山雄丞, 内藤健夫, 日下順, 小野寺基之, 只野敏浩, 川上瑶子, 平本圭一郎, 松下勝則, 宮澤輝子, 木村智哉, 志賀永嗣, 角田洋一, 根来健一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　112　(臨増総会)　A382-A382　2015/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
De novo Crohn's Disease Following Orthotopic Liver Transplantation: A Case Report and Literature Review Peer-reviewed

Takeo Naito, Hisashi Shiga, Katsuya Endo, Masatake Kuroha, Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa

INTERNAL MEDICINE　54　(2)　199-204　2015

DOI： 10.2169/internalmedicine.54.3156 　

ISSN： 0918-2918

eISSN： 1349-7235
Ileocecal ulcers accompanied by relapsing polychondritis: a case report Peer-reviewed

Yoko Kawakami, Katsuya Endo, Tomonori Ishii, Sho Haneda, Fumiyoshi Fujishima, Yoichi Kakuta, Hisashi Shiga, Yoshitaka Kinouchi, Tooru Shimosegawa

SPRINGERPLUS　3　714　2014/12

DOI： 10.1186/2193-1801-3-714 　

ISSN： 2193-1801
Variants in the Interferon Regulatory Factor-2 Gene Are Not Associated With Pancreatitis in Japan Peer-reviewed

Eriko Nakano, Atsushi Masamune, Kiyoshi Kume, Yoichi Kakuta, Tooru Shimosegawa

PANCREAS　43　(7)　1125-1126　2014/10

DOI： 10.1097/MPA.0000000000000207 　

ISSN： 0885-3177

eISSN： 1536-4828
難治性クローン病病態から考えた治療アプローチ TNFSF15高発現アリルは疾患の重症度や治療反応性に関与する

角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　111　(臨増大会)　A605-A605　2014/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Endoscopic submucosal dissection for colorectal neoplasia during the clinical learning curve Peer-reviewed

Hisashi Shiga, Katsuya Endo, Masatake Kuroha, Yoichi Kakuta, Seiichi Takahashi, Yoshitaka Kinouchi, Tooru Shimosegawa

SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES　28　(7)　2120-2128　2014/07

DOI： 10.1007/s00464-014-3443-8 　

ISSN： 0930-2794

eISSN： 1432-2218
Modulation of endoplasmic reticulum (ER) stress-induced autophagy by C/EBP homologous protein (CHOP) and inositol-requiring enzyme 1 alpha (IRE1 alpha) in human colon cancer cells Peer-reviewed

Yosuke Shimodaira, Seiichi Takahashi, Yoshitaka Kinouchi, Katsuya Endo, Hisashi Shiga, Yoichi Kakuta, Masatake Kuroha, Tooru Shimosegawa

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　445　(2)　524-533　2014/03

DOI： 10.1016/j.bbrc.2014.02.054 　

ISSN： 0006-291X

eISSN： 1090-2104
PRSS1 c.623G>C (p.G208A) variant is associated with pancreatitis in Japan. Peer-reviewed

Masamune A, Nakano E, Kume K, Takikawa T, Kakuta Y, Shimosegawa T

GUT　63　(2)　366-366　2014/02

DOI： 10.1136/gutjnl-2013-304925 　

ISSN： 0017-5749

eISSN： 1468-3288
Refractory Sclerosing Mesenteritis Involving the Small Intestinal Mesentery: A Case Report and Literature Review Peer-reviewed

Katsuya Endo, Rintaro Moroi, Mikako Sugimura, Fumiyoshi Fujishima, Takeshi Naitoh, Naoki Tanaka, Hisashi Shiga, Yoichi Kakuta, Seiichi Takahashi, Yoshitaka Kinouchi, Tooru Shimosegawa

INTERNAL MEDICINE　53　(13)　1419-1427　2014

DOI： 10.2169/internalmedicine.53.1813 　

ISSN： 0918-2918

eISSN： 1349-7235
Acute onset collagenous colitis with unique endoscopic findings. International-journal Peer-reviewed

Moroi R, Endo K, Kuhroha M, Shiga H, Kakuta Y, Kinouchi Y, Shimosegawa T

Case reports in gastrointestinal medicine　2014　986092-986092　2014

DOI： 10.1155/2014/986092 　

ISSN： 2090-6528

More details Close

We experienced a rare case of 72-year-old woman with acute onset collagenous colitis (CC) induced by lansoprazole. The patient developed acute abdominal pain, watery diarrhea, and melena that are quite rare in usual CC. We could find the characteristic colonoscopic findings such as active long liner ulcers in the patient. We also observed the healing courses of these unique findings. Our case indicates two important points of view. (1) CC sometimes develops with acute onset symptoms which resemble those of ischemic colitis. (2) Colonoscopy would be useful and necessary to distinguish acute onset CC and ischemic colitis.
Mutations in Tetratricopeptide Repeat Domain 7A Result in a Severe Form of Very Early Onset Inflammatory Bowel Disease. Peer-reviewed

Avitzur Y, Guo C, Mastropaolo LA, Bahrami E, Chen H, Zhao Z, Elkadri A, Dhillon S, Murchie R, Fattouh R, Huynh H, Walker JL, Wales PW, Cutz E, Kakuta Y, Dudley J, Kammermeier J, Powrie F, Shah N, Walz C, Nathrath M, Kotlarz D, Puchaka J, Krieger J, Racek T, Kirchner T, Walters TD, Brumell JH, Griffiths AM, Rezaei N, Rashtian P, Najafi M, Monajemzadeh M, Pelsue S, McGovern DP, Uhlig HH, Schadt E, Klein C, Snapper SB, Muise AM

GASTROENTEROLOGY　146　(4)　1028-1039　2014/01

DOI： 10.1053/j.gastro.2014.01.015 　

ISSN： 0016-5085

eISSN： 1528-0012
Variants in CPA1 are strongly associated with early onset chronic pancreatitis. Peer-reviewed

Witt H, Beer S, Rosendahl J, Chen JM, Chandak GR, Masamune A, Bence M, Szmola R, Oracz G, Macek M Jr, Bhatia E, Steigenberger S, Lasher D, Bühler F, Delaporte C, Tebbing J, Ludwig M, Pilsak C, Saum K, Bugert P, Masson E, Paliwal S, Bhaskar S, Sobczynska-Tomaszewska A, Bak D, Balascak I, Choudhuri G, Nageshwar Reddy D, Rao GV, Thomas V, Kume K, Nakano E, Kakuta Y, Shimosegawa T, Durko L, Szabó A, Schnúr A, Hegyi P, Rakonczay Z Jr, Pfützer R, Schneider A, Groneberg DA, Braun M, Schmidt H, Witt U, Friess H, Algül H, Landt O, Schuelke M, Krüger R, Wiedenmann B, Schmidt F, Zimmer KP, Kovacs P, Stumvoll M, Blüher M, Müller T, Janecke A, Teich N, Grützmann R, Schulz HU, Mössner J, Keim V, Löhr M, Férec C, Sahin-Tóth M

NATURE GENETICS　45　(10)　1216-U359　2013/10

DOI： 10.1038/ng.2730 　

ISSN： 1061-4036

eISSN： 1546-1718
FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn's disease through affecting the ADCC activity. Peer-reviewed

Moroi R, Endo K, Kinouchi Y, Shiga H, Kakuta Y, Kuroha M, Kanazawa Y, Shimodaira Y, Horiuchi T, Takahashi S, Shimosegawa T

IMMUNOGENETICS　65　(4)　265-271　2013/04

DOI： 10.1007/s00251-013-0679-8 　

ISSN： 0093-7711
Identification of novel missense CTRC variants in Japanese patients with chronic pancreatitis. Peer-reviewed

Masamune A, Nakano E, Kume K, Kakuta Y, Ariga H, Shimosegawa T

GUT　62　(4)　653-654　2013/04

DOI： 10.1136/gutjnl-2012-303860 　

ISSN： 0017-5749

eISSN： 1468-3288
Unique findings on endoscopy with narrow-band imaging in colonic lesions of Henoch-Schonlein purpura. Peer-reviewed

Endo K, Moroi R, Shiga H, Takahashi S, Kakuta Y, Kinouchi Y, Shimosegawa T

Endoscopy　45　(2)　E65-E66　2013

DOI： 10.1055/s-0032-1325978 　

ISSN： 0013-726X 1438-8812
Life-event stress induced by the Great East Japan Earthquake was associated with relapse in ulcerative colitis but not Crohn's disease: a retrospective cohort study. Peer-reviewed

Shiga H, Miyazawa T, Kinouchi Y, Takahashi S, Tominaga G, Takahashi H, Takagi S, Obana N, Kikuchi T, Oomori S, Nomura E, Shiraki M, Sato Y, Takahashi S, Umemura K, Yokoyama H, Endo K, Kakuta Y, Aizawa H, Matsuura M, Kimura T, Kuroha M, Shimosegawa T

BMJ OPEN　3　(2)　22　2013

DOI： 10.1136/bmjopen-2012-002294 　

ISSN： 2044-6055
Short and long-term outcomes of endoscopic balloon dilatation for Crohn's disease strictures. Peer-reviewed

Endo K, Takahashi S, Shiga H, Kakuta Y, Kinouchi Y, Shimosegawa T

WORLD JOURNAL OF GASTROENTEROLOGY　19　(1)　86-91　2013/01

DOI： 10.3748/wjg.v19.i1.86 　

ISSN： 1007-9327
Changes of faecal microbiota in patients with Crohn's disease treated with an elemental diet and total parenteral nutrition. Peer-reviewed

Shiga H, Kajiura T, Shinozaki J, Takagi S, Kinouchi Y, Takahashi S, Negoro K, Endo K, Kakuta Y, Suzuki M, Shimosegawa T

DIGESTIVE AND LIVER DISEASE　44　(9)　736-742　2012/09

DOI： 10.1016/j.dld.2012.04.014 　

ISSN： 1590-8658
Two cases of diffuse duodenitis associated with ulcerative colitis. International-journal Peer-reviewed

Endo K, Kuroha M, Shiga H, Kakuta Y, Takahashi S, Kinouchi Y, Shimosegawa T

Case reports in gastrointestinal medicine　2012　396521-396521　2012

DOI： 10.1155/2012/396521 　

ISSN： 2090-6528

More details Close

Endo K, Kuroha M, Shiga H, Kakuta Y, Takahashi S, Kinouchi Y, Shimosegawa T, Case reports in gastrointestinal medicine, 2012, vol. 2012, pp. 396521
炎症性腸疾患の妊娠・出産に関する臨床的検討

遠藤克哉, 高橋成一, 下平陽介, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 荒井壮, 金澤義丈, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　108　(11)　1858-1871　2011/11
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
[Clinical courses and pregnancy outcomes in Japanese women with inflammatory bowel disease]. Peer-reviewed

Endo K, Takahashi S, Shimodaira Y, Nagasawa H, Moroi R, Kuroha M, Arai T, Kanazawa Y, Shiga H, Kakuta Y, Kinouchi Y, Shimosegawa T

Journal of Japanese Society of Gastroenterology　108　(11)　1858-1871　2011/11

DOI： 10.11405/nisshoshi.108.1858 　

ISSN： 0446-6586
日本人炎症性腸疾患患者におけるXBP1遺伝子の解析

長澤仁嗣, 角田洋一, 下平陽介, 諸井林太郎, 黒羽正剛, 荒井壮, 金澤義丈, 志賀永嗣, 遠藤克哉, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　108　(臨増大会)　A846-A846　2011/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
潰瘍性大腸炎合併妊娠、出産に関する臨床的検討

遠藤克哉, 高橋成一, 下平陽介, 諸井林太郎, 長澤仁嗣, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　108　(臨増大会)　A856-A856　2011/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Increased expression of NKX2.3 mRNA transcribed from the risk haplotype for ulcerative colitis in the involved colonic mucosa. Peer-reviewed

Arai T, Kakuta Y, Kinouchi Y, Kimura T, Negoro K, Aihara H, Endo K, Shiga H, Kanazawa Y, Kuroha M, Moroi R, Nagasawa H, Shimodaira Y, Takahashi S, Shimosegawa T

HUMAN IMMUNOLOGY　72　(7)　587-591　2011/07

DOI： 10.1016/j.humimm.2011.03.023 　

ISSN： 0198-8859
Genetic background is different between sentinel and recurrent acute pancreatitis. Peer-reviewed

Masamune A, Ariga H, Kume K, Kakuta Y, Satoh K, Satoh A, Shimosegawa T

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY　26　(6)　974-978　2011/06

DOI： 10.1111/j.1440-1746.2011.06691.x 　

ISSN： 0815-9319
日本人潰瘍性大腸炎患者におけるNKX2-3リスクハプロタイプの同定と機能解析

荒井壮, 木内喜孝, 角田洋一, 下平陽介, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 金澤義丈, 志賀永嗣, 遠藤克哉, 根来健一, 相原裕之, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　108　(臨増総会)　A163-A163　2011/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
クローン病合併妊娠・出産に関する臨床的検討

遠藤克哉, 高橋成一, 下平陽介, 諸井林太郎, 長澤仁嗣, 黒羽正剛, 荒井壮, 金澤義丈, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　108　(臨増総会)　A263-A263　2011/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Infliximab投与中にサイトメガロウイルス初感染を生じたクローン病の一例

金澤義丈, 下平陽介, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 荒井壮, 志賀永嗣, 遠藤克哉, 角田洋一, 高橋成一, 木内喜孝

日本消化器病学会雑誌　108　(臨増総会)　A341-A341　2011/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
[Maintenance therapy with biologic agents for Crohn's disease: impact of scheduled maintenance therapy with infliximab]. Peer-reviewed

Endo K, Shiga H, Kakuta Y, Takahashi S, Kinouchi Y, Shimosegawa T

Journal of Japanese Society of Gastroenterology　108　(3)　401-409　2011/03

DOI： 10.11405/nisshoshi.108.401 　

ISSN： 0446-6586
[Long-term prognosis of Crohn's disease]. Peer-reviewed

Kinouchi Y, Kakuta Y, Takahashi S, Shimosegawa T

Journal of Japanese Society of Gastroenterology　108　(3)　381-387　2011/03

DOI： 10.11405/nisshoshi.108.381 　

ISSN： 0446-6586
Magnifying endoscopy findings in follicular lymphoma of the rectum using narrow band imaging. Peer-reviewed

Kuroha M, Endo K, Sato Y, Shiga H, Kakuta Y, Takahashi S, Kinouchi Y, Shimosegawa T

ENDOSCOPY　43　E346-E347　2011

DOI： 10.1055/s-0030-1256843 　

ISSN： 0013-726X
collagenous colitisにおけるNarrow Band Imagingを用いた拡大内視鏡所見の検討

諸井林太郎, 遠藤克哉, 長澤仁嗣, 黒羽正剛, 荒井壮, 木村智哉, 志賀永嗣, 梅村賢, 高橋秀一郎, 角田洋一, 根来健一, 高木承, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy　52　(Suppl.2)　2511-2511　2010/09
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
白血病に対する臍帯血移植を契機に寛解に至ったCrohn病の一例

荒井壮, 遠藤克哉, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 角田洋一, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　107　(臨増大会)　A859-A859　2010/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
日本人クローン病感受性候補遺伝子TNFSF15、HLA-DQB1、IL12Bと再燃率との関連について

角田洋一, 木内喜孝, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 荒井壮, 木村智哉, 志賀永嗣, 遠藤克哉, 根来健一, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　107　(臨増大会)　A874-A874　2010/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
日本人クローン病におけるIL12Bリスクハプロタイプの同定と機能解析

木村智哉, 角田洋一, 遠藤克哉, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　107　(臨増総会)　A324-A324　2010/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
術中内視鏡検査が腸管切除範囲決定に有用であった多発性小腸輪状狭窄を呈した3例

諸井林太郎, 遠藤克哉, 長澤仁嗣, 黒羽正剛, 荒井壮, 木村智哉, 高橋秀一郎, 梅村賢, 角田洋一, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　107　(臨増総会)　A280-A280　2010/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
日本人IBDにおけるNKX2-3の感受性候補遺伝子解析

荒井壮, 角田洋一, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 木村智哉, 遠藤克哉, 梅村賢, 高橋秀一郎, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　107　(臨増総会)　A323-A323　2010/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Scheduled maintenance therapy with infliximab improves the prognosis of Crohn's disease: a single center prospective cohort study in Japan. Peer-reviewed

Takahashi S, Takagi S, Shiga H, Umemura K, Endo K, Kakuta Y, Takahashi S, Kinouchi Y, Shimosegawa T

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　220　(3)　207-215　2010/03

DOI： 10.1620/tjem.220.207 　

ISSN： 0040-8727

eISSN： 1349-3329
-651C/T promoter polymorphism in the CD14 gene is associated with severity of acute pancreatitis in Japan. Peer-reviewed

Masamune A, Kume K, Kikuta K, Watanabe T, Hirota M, Satoh K, Kanno A, Suzuki N, Kakuta Y, Shimosegawa T

JOURNAL OF GASTROENTEROLOGY　45　(2)　225-233　2010/02

DOI： 10.1007/s00535-009-0163-2 　

ISSN： 0944-1174

eISSN： 1435-5922
Involvement of NF-kappa B pathway in TL1A gene expression induced by lipopolysaccharide. Peer-reviewed

Endo K, Kinouchi Y, Kakuta Y, Ueki N, Takahashi S, Shimosegawa T

CYTOKINE　49　(2)　215-220　2010/02

DOI： 10.1016/j.cyto.2009.09.006 　

ISSN： 1043-4666
A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. Peer-reviewed

Asano K, Matsushita T, Umeno J, Hosono N, Takahashi A, Kawaguchi T, Matsumoto T, Matsui T, Kakuta Y, Kinouchi Y, Shimosegawa T, Hosokawa M, Arimura Y, Shinomura Y, Kiyohara Y, Tsunoda T, Kamatani N, Iida M, Nakamura Y, Kubo M

NATURE GENETICS　41　(12)　1325-U92　2009/12

DOI： 10.1038/ng.482 　

ISSN： 1061-4036
インフリキシマブ投与後にleukocytoclastic vasculitisを発症したクローン病の一例

松浦真樹, 黒羽正剛, 荒井壮, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 梅村賢, 高橋秀一郎, 遠藤克哉, 角田洋一, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　106　(臨増大会)　A863-A863　2009/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
経過中にサイトメガロウイルス感染を合併したクローン病の1例

志賀永嗣, 遠藤克哉, 木内喜孝, 高橋成一, 根来健一, 角田洋一, 相澤宏樹, 植木紳夫, 松浦真樹, 木村智哉, 荒井壮, 黒羽正剛, 下瀬川徹

日本消化器病学会雑誌　106　(臨増大会)　A864-A864　2009/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
炎症性腸疾患に合併したSAPHO症候群の2例

木村智哉, 遠藤克哉, 黒羽正剛, 荒井壮, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 角田洋一, 高橋秀一郎, 梅村賢, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　106　(臨増大会)　A867-A867　2009/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
HLA-B is the best candidate of susceptibility genes in HLA for Japanese ulcerative colitis. Peer-reviewed

Aizawa H, Kinouchi Y, Negoro K, Nomura E, Imai G, Takahashi S, Takagi S, Kakuta Y, Tosa M, Mochida A, Matsumura Y, Endo K, Shimosegawa T

TISSUE ANTIGENS　73　(6)　569-574　2009/06

DOI： 10.1111/j.1399-0039.2009.01241.x 　

ISSN： 0001-2815
カプセル内視鏡により小腸の広範囲に白色絨毛を指摘しえた蛋白漏出性胃腸症の一例

遠藤克哉, 黒羽正剛, 荒井壮, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 角田洋一, 高橋秀一郎, 梅村賢二, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy　51　(Suppl.1)　919-919　2009/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
非特異性多発性小腸潰瘍症が疑われた1例

志賀永嗣, 遠藤克哉, 木内喜孝, 高橋成一, 根来健一, 角田洋一, 相澤宏樹, 植木紳夫, 松浦真樹, 木村智哉, 荒井壮, 黒羽正剛, 下瀬川徹

Gastroenterological Endoscopy　51　(Suppl.1)　920-920　2009/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
日本人クローン病感受性遺伝子TNFSF15の機能解析

植木紳夫, 角田洋一, 黒羽正剛, 荒井壮, 木村智哉, 相澤宏樹, 松浦正樹, 志賀永嗣, 遠藤克哉, 梅村賢, 高橋秀一郎, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　106　(臨増総会)　A257-A257　2009/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
インフリキシマブ投与で改善を認めた単純性潰瘍の一例

植木紳夫, 遠藤克哉, 黒羽正剛, 荒井壮, 木村智哉, 相澤宏樹, 松浦正樹, 志賀永嗣, 角田洋一, 梅村賢, 高橋秀一郎, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　106　(臨増総会)　A376-A376　2009/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
家族性大腸腺腫症の術後回腸人工肛門に発生した小腸癌の1例(第2報) Ileostomy carcinoma症例における回腸人工肛門の病理組織学的検討

梅村賢, 野村栄樹, 三浦康, 黒羽正剛, 荒井壮, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 高橋秀一郎, 遠藤克哉, 角田洋一, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 佐々木巌, 下瀬川徹

日本消化器病学会雑誌　106　(臨増総会)　A397-A397　2009/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
日本人潰瘍性大腸炎とKIR3DL1遺伝子との相関について

相澤宏樹, 木内喜孝, 高橋成一, 根来健一, 角田洋一, 遠藤克哉, 相原裕之, 梅村賢, 高橋秀一郎, 植木紳夫, 志賀永嗣, 松浦真樹, 木村智哉, 荒井壮, 黒羽正剛, 下瀬川徹

日本消化器病学会雑誌　106　(臨増総会)　A428-A428　2009/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
TNFSF15 transcripts from risk haplotype for Crohn's disease are overexpressed in stimulated T cells. Peer-reviewed

Kakuta Y, Ueki N, Kinouchi Y, Negoro K, Endo K, Nomura E, Takagi S, Takahashi S, Shimosegawa T

HUMAN MOLECULAR GENETICS　18　(6)　1089-1098　2009/03

DOI： 10.1093/hmg/ddp005 　

ISSN： 0964-6906
Colitic cancerの診断と治療 Colitic cancer、Dysplasiaの拡大内視鏡診断

相澤宏樹, 高木承, 植木紳夫, 志賀永嗣, 松浦真樹, 遠藤克哉, 角田洋一, 梅村賢, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本大腸肛門病学会雑誌　61　(9)　657-657　2008/09
Publisher: (一社)日本大腸肛門病学会
ISSN： 0047-1801

eISSN： 1882-9619
Useful endoscopic findings for early diagnosis of ulcerative colitis associated colorectal cancer. Peer-reviewed

Sato Y, Takagi S, Aizawa H, Yokoyama H, Takahashi S, Kakuta Y, Tosa M, Mochida A, Nomura E, Takahashi S, Kinouchi Y, Shimosegawa T

ENDOSCOPY　40　E71-E72　2008/09

DOI： 10.1055/s-2007-995494 　

ISSN： 0013-726X

eISSN： 1438-8812
HLA-DRB1 alleles influence clinical phenotypes in Japanese patients with ulcerative colitis. Peer-reviewed

Matsumura Y, Kinouchi Y, Nomura E, Negoro K, Kakuta Y, Endo K, Aizawa H, Takagi S, Takahashi S, Shimosegawa T

TISSUE ANTIGENS　71　(5)　447-452　2008/05

DOI： 10.1111/j.1399-0039.2008.01031.x 　

ISSN： 0001-2815
クローン病との鑑別を要したウイルス関連血球貪食症候群(virus-associated hemophagocytic syndrome:VAHS)の一例

志賀永嗣, 野村栄樹, 高木承, 高橋成一, 横山大, 梅村賢, 遠藤克哉, 角田洋一, 松村吉史, 相澤宏樹, 植木紳夫, 松浦真樹, 木村智哉, 荒井壮, 木内喜孝, 富永現, 下瀬川徹

日本消化器病学会雑誌　105　(臨増総会)　A207-A207　2008/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
日本人クローン病とATG16L1,IL23R,MYO9B,IRGM遺伝子との相関について

相澤宏樹, 高橋成一, 根来健一, 角田洋一, 遠藤克哉, 野村栄樹, 相原裕之, 横山大, 梅村賢, 松村吉史, 植木紳夫, 志賀永嗣, 松浦真樹, 木村智哉, 荒井壮, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　105　(臨増総会)　A243-A243　2008/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Butyrophilin-like 2 gene is associated with ulcerative colitis in the Japanese under strong linkage disequilibrium with HLA-DRB1*1502. Peer-reviewed

Mochida A, Kinouchi Y, Negoro K, Takahashi S, Takagi S, Nomura E, Kakuta Y, Tosa M, Shimosegawa T

TISSUE ANTIGENS　70　(2)　128-135　2007/08

DOI： 10.1111/j.1399-0039.2007.00866.x 　

ISSN： 0001-2815
クローン病感受性遺伝子TNFSF15遺伝子型と臨床表現型・長期予後との関連について

松浦真樹, 野村栄樹, 角田洋一, 根来健一, 高木承, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　104　(臨増総会)　A143-A143　2007/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
日本人クローン病におけるTNFSF15遺伝子多型とHLA-DQB1との関連について

角田洋一, 木内喜孝, 根来健一, 木村智哉, 松浦真樹, 植木紳夫, 相澤宏樹, 志賀永嗣, 遠藤克哉, 松村吉史, 土佐正規, 持田淳弘, 野村栄樹, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　104　(臨増総会)　A143-A143　2007/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
メサラジン・プレドニゾロン注腸併用療法を施行し無事出産しえた初発潰瘍性大腸炎の1例

遠藤克哉, 高木承, 木村智哉, 相澤宏樹, 植木伸夫, 志賀永嗣, 松浦真樹, 角田洋一, 松村吉史, 土佐正規, 持田淳弘, 横山大, 野村栄樹, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　104　(臨増総会)　A222-A222　2007/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
地中海熱の一例

木村智哉, 高橋成一, 野村栄樹, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 遠藤克哉, 松村吉史, 角田洋一, 土佐正規, 持田淳弘, 横山大, 根来健一, 高木承, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　104　(臨増総会)　A223-A223　2007/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Association study of TNFSF15 polymorphisms in Japanese patients with inflammatory bowel disease. Peer-reviewed

Kakuta Y, Kinouchi Y, Negoro K, Takahashi S, Shimosegawa T

Gut　55　(10)　1527-1528　2006/10

DOI： 10.1136/gut.2006.100297 　

ISSN： 0017-5749
IL-10 deficiency leads to somatic mutations in a model of IBD. Peer-reviewed

Sato Y, Takahashi S, Kinouchi Y, Shiraki M, Endo K, Matsumura Y, Kakuta Y, Tosa M, Motida A, Abe H, Imai G, Yokoyama H, Nomura E, Negoro K, Takagi S, Aihara H, Masumura K, Nohmi T, Shimosegawa T

CARCINOGENESIS　27　(5)　1068-1073　2006/05

DOI： 10.1093/carcin/bgi327 　

ISSN： 0143-3334
消化器疾患における遺伝素因と環境因子生活習慣・労働との関わり第6染色体短腕に存在する日本人潰瘍性大腸炎感受性遺伝子についての検討

野村栄樹, 角田洋一, 木内喜孝

日本消化器病学会雑誌　103　(臨増総会)　A41-A41　2006/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
造血幹細胞移植後GVHD腸炎におけるTMA腸炎合併の有無に関した大腸内視鏡所見の検討

遠藤克哉, 高木承, 大森信弥, 角田洋一, 松村吉史, 阿部浩子, 今井豪, 土佐正規, 持田淳弘, 佐藤雄一郎, 白木学, 野村栄樹, 高橋秀一郎, 横山大, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy　47　(Suppl.2)　2029-2029　2005/09
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
日本人潰瘍性大腸炎におけるHLA-DRB1と罹患範囲との関連について

角田洋一, 木内喜孝, 根来健一, 野村栄樹, 土佐正規, 阿部浩子, 今井豪, 遠藤克哉, 松村吉史, 持田淳弘, 佐藤雄一郎, 白木学, 高橋秀一郎, 横山大, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　102　(臨増大会)　A759-A759　2005/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
炎症性腸疾患におけるIBD5の解析

土佐正規, 根来健一, 角田洋一, 阿部浩子, 野村栄樹, 進藤克哉, 松村吉史, 高橋秀一郎, 今井豪, 持田淳弘, 佐藤雄一郎, 白木学, 横山大, 相原裕之, 高木承, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　102　(臨増総会)　A238-A238　2005/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693

Show all ︎Show first 5

Misc. 232

難治性クローン病に対するリサンキズマブの短期有効性の評価

漆山みき, 永井博, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会雑誌(Web)　121　2024

ISSN： 1349-7693
オルガノイド由来miRNAを用いた大腸腫瘍のリキッドバイオプシー法の有用性の検証

佐々木敦宏, 黒羽正剛, 永井博, 下山雄丞, 内藤健夫, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会雑誌(Web)　121　2024

ISSN： 1349-7693
IBDのTreat to Target戦略における内視鏡検査の意義と課題クローン病における内視鏡的寛解の予測因子としてのバイオマーカー

志賀永嗣, 角田洋一, 正宗淳

Gastroenterological Endoscopy　64　(Suppl.2)　1990-1990　2022/10
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
IBD病態を踏まえた今後の治療ストラテジー抗EPCR抗体価と潰瘍性大腸炎の病態および治療反応性との関連に関する検討

角田洋一, 白井剛志, 正宗淳

Gastroenterological Endoscopy　64　(Suppl.2)　2023-2023　2022/10
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
消化器内科学潰瘍性大腸炎の診断に有用な新たな自己抗体マーカー

角田洋一

医学のあゆみ　282　(11)　1013-1014　2022/09
Publisher: 医歯薬出版(株)
ISSN： 0039-2359
ポリープ様の形態を呈した腸管子宮内膜症の1例

漆山みき, 志賀永嗣, 下山雄丞, 内藤健夫, 諸井林太郎, 角田洋一, 正宗淳

日本消化器内視鏡学会東北支部例会　168回　95-95　2022/07
Publisher: 日本消化器内視鏡学会-東北支部
逸脱した大腸ステントに対してスライディングチューブを用いて回収し得た一例

佐々木敦宏, 諸井林太郎, 下山雄丞, 内藤健夫, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器内視鏡学会東北支部例会　168回　114-114　2022/07
Publisher: 日本消化器内視鏡学会-東北支部
潰瘍性大腸炎内視鏡スコアと血液検査データの相関の検討

田森大登, 諸井林太郎, 下山雄丞, 内藤健夫, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　213回　77-77　2022/07
Publisher: 日本消化器病学会-東北支部
【Common diseaseとなった潰瘍性大腸炎の現状と診療のコツ】チオプリン製剤とは何か?どのような症例にどう使うのか?

志賀永嗣, 角田洋一, 正宗淳

臨床消化器内科　37　(7)　779-785　2022/06
Publisher: (株)日本メディカルセンター
ISSN： 0911-601X

eISSN： 2433-2488
【真に業務改善に貢献する最新IT考】如何なる方法で成果を挙げたか電子カルテシステムとスマートフォンの問診アプリケーション間の双方向連携によるデータ入力の効率化

佐々木恵利奈, 中村直毅, 角田洋一

新医療　49　(5)　20-23　2022/05
Publisher: (株)エムイー振興協会
ISSN： 0910-7991
炎症性消化管疾患の最前線 IBD治療と外科・内科のコラボレーションクローン病に対する生物学的製剤switch症例の検討

下田楓美子, 諸井林太郎, 下山雄丞, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　6　(Suppl.)　106-106　2022/01
Publisher: (一社)日本消化管学会
ISSN： 2433-3840

eISSN： 2435-8967
炎症性腸疾患におけるチオプリン関連PGx検査の現状と問題点

角田洋一, 木内喜孝, 正宗淳

日本臨床薬理学会学術総会抄録集　42回　2-2　2021/12
Publisher: (一社)日本臨床薬理学会
eISSN： 2436-5580
小腸・IBD基礎研究の最前線マウスモデルからみたNUDT15遺伝子多型と妊娠中のチオプリン服用

今井隆行, 河原真大, 稲富理, 角田洋一, 安藤朗

日本小腸学会学術集会プログラム・抄録集　59回　53-53　2021/11
Publisher: 日本小腸学会
ISSN： 2434-2912

eISSN： 2434-7019
The Linkage of Clinical Data Between Hospital Information System and Smartphone App Using QR code

佐々木恵利奈, 中村直毅, 角田洋一, 根来健一, 諸井林太郎, SONG Chong, SONG Chong, 中山雅晴, 中山雅晴

日本医療情報学会春季学術大会プログラム・抄録集　25th　2021
Browser-based Customizable Questionnaire Tool Connect to Electronic Medical Records via QR Codes

SONG Chong, SONG Chong, 佐々木恵利奈, 中村直毅, 角田洋一, 中山雅晴, 中山雅晴

医療情報学連合大会論文集(CD-ROM)　41st　2021

ISSN： 2433-698X
炎症性消化管疾患の最前線多様化する炎症性腸疾患の治療戦略-外科手術も含めて- クローン病の腸管狭窄に対するRadial Cutting and Incision法を用いた内視鏡的切開拡張術の検討

諸井林太郎, 志賀永嗣, 下山雄丞, 黒羽正剛, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　5　(Suppl.)　149-149　2021/01
Publisher: (一社)日本消化管学会
ISSN： 2433-3840

eISSN： 2435-8967
高齢者潰瘍性大腸炎治療指針の検証診断群分類別包括評価(DPC)データを用いた本邦における高齢者潰瘍性大腸炎治療の現状

矢野恒太, 諸井林太郎, 志賀永嗣, 下山雄丞, 黒羽正剛, 角田洋一, タラ澤邦男, 藤森研司, 伏見清秀, 木内喜孝, 正宗淳

日本消化管学会雑誌　5　(Suppl.)　238-238　2021/01
Publisher: (一社)日本消化管学会
ISSN： 2433-3840

eISSN： 2435-8967
炎症性腸疾患における内視鏡検査と治療戦略日本人クローン病における便中カルプロテクチンを指標とした治療戦略の有用性

阿部出, 志賀永嗣, 高橋隆宏, 角田洋一, 正宗淳

日本消化器内視鏡学会東北支部例会　165回　43-43　2021/01
Publisher: 日本消化器内視鏡学会-東北支部
妊娠中チオプリン服用を継続した炎症性腸疾患患者より生まれた児における副作用の検討

高川哲也, 角田洋一, 小島健太郎, 小柴良司, 藤本晃士, 佐藤寿行, 河合幹夫, 上小鶴孝二, 横山陽子, 宮嵜孝子, 樋田信幸, 渡辺憲治, 中村志郎

日本消化器病学会雑誌　117　(臨増大会)　A761-A761　2020/10
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
炎症性腸疾患の新規治療薬の効果と安全性日本人潰瘍性大腸炎患者の新規治療薬登場後の時代における予後解析

菱沼佳純, 諸井林太郎, 下山雄丞, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本大腸肛門病学会雑誌　73　(9)　A35-A35　2020/09
Publisher: (一社)日本大腸肛門病学会
ISSN： 0047-1801

eISSN： 1882-9619
消化器疾患におけるバイオマーカーの探索 High Resolution Melt(HRM)解析でNUDT15遺伝子codon18を簡易にdiplotypingすることで白血球減少症をより詳細に予測する方法の開発

泉山泰宏, 角田洋一, 正宗淳

日本消化器病学会雑誌　117　(臨増総会)　A36-A36　2020/07
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
トランスクリプトーム解析を用いた日本人クローン病疾患感受性遺伝子の同定

市川遼, 角田洋一, 冬野雄太, 平野敦士, 梅野淳嗣, 鳥巣剛弘, 中野健, 泉山泰宏, 岡本大祐, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 志賀永嗣, 江崎幹宏, 中村稔, 松本主之, 木内喜孝, 正宗淳

日本消化器病学会雑誌　117　(臨増総会)　A208-A208　2020/07
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
人種最適化アレイを用いた日本人潰瘍性大腸炎患者の遺伝的背景の解析

岡本大祐, 角田洋一, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 志賀永嗣, 冬野雄太, 平野敦士, 梅野淳嗣, 鳥巣剛弘, 中村稔, 松本主之, 江崎幹宏, 木内喜孝, 正宗淳

日本消化器病学会雑誌　117　(臨増総会)　A209-A209　2020/07
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
日本人炎症性腸疾患患者のメモリーT細胞受容体レパトア解析

中野健, 角田洋一, 内藤健夫, 渡辺和宏, 泉山泰宏, 岡本大祐, 市川遼, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 志賀久嗣, 内藤剛, 木内善孝, 海野倫明, 正宗敦

日本消化器病学会雑誌　117　(臨増総会)　A221-A221　2020/07
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
抗TNF製剤の投与歴で分けたUstekinumabの有効性と安全性

志賀永嗣, 高橋隆宏, 阿部出, 菱沼佳純, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 正宗淳

日本消化器病学会雑誌　117　(臨増総会)　A222-A222　2020/07
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
当院におけるCrohn病に対するadalimumab倍量投与の治療成績

菱沼佳純, 黒羽正剛, 矢野恒太, 下田楓美子, 猪股優志, 阿部出, 枡悠太郎, 半田智之, 鈴木郁, 中野健, 岡本大祐, 市川遼, 泉山泰宏, 諸井林太郎, 金澤義丈, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会雑誌　117　(臨増総会)　A224-A224　2020/07
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
【新薬で変わるか?クローン病薬物治療】チオプリン製剤によるクローン病治療副作用のマネジメントも含めて

角田洋一

消化器の臨床　23　(1)　30-35　2020/02
Publisher: (株)ヴァンメディカル
ISSN： 1344-3070
Reduction Input Time of Data Using Templates and a Smartphone App

佐々木恵利奈, 根来健一, 諸井林太郎, 角田洋一, 中村直毅, 中山雅晴, 中山雅晴

日本医療情報学会春季学術大会プログラム・抄録集　24th (Web)　2020
人種最適化アレイを用いた日本人潰瘍性大腸炎患者の遺伝的背景の解析

岡本大祐, 角田洋一, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 志賀永嗣, 冬野雄太, 冬野雄太, 平野敦士, 梅野淳嗣, 鳥巣剛弘, 中村稔, 松本主之, 江崎幹宏, 木内喜孝, 正宗淳

日本消化器病学会雑誌(Web)　117　2020

ISSN： 1349-7693
トランスクリプトーム解析を用いた日本人クローン病疾患感受性遺伝子の同定

市川遼, 角田洋一, 冬野雄太, 平野敦士, 梅野淳嗣, 鳥巣剛弘, 中野健, 泉山泰宏, 岡本大祐, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 志賀永嗣, 江崎幹宏, 中村稔, 松本主之, 木内喜孝, 正宗淳

日本消化器病学会雑誌(Web)　117　2020

ISSN： 1349-7693
難治性炎症性腸管障害に関する調査研究 IBDの遺伝子解析プロジェクト:総括

松本主之, 角田洋一, 梅野淳嗣, 高川哲也

難治性炎症性腸管障害に関する調査研究令和元年度総括・分担研究報告書(Web)　2020
難治性炎症性腸管障害に関する調査研究「IBDの遺伝子解析プロジェクト」腸管ベーチェット病および単純性潰瘍におけるGenome Wide Association Study(GWAS)

松本主之, 江崎幹宏, 冬野雄太, 平野敦士, 梅野淳嗣, 角田洋一, 仲瀬裕志, 久松理一, 櫻庭裕丈, 国崎玲子, 平井郁仁, 猿田雅之

難治性炎症性腸管障害に関する調査研究令和元年度総括・分担研究報告書(Web)　2020
術後に潰瘍性大腸炎からクローン病に診断を変更した1例

高橋隆宏, 黒羽正剛, 志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会東北支部例会誌　208th　2020
日本人潰瘍性大腸炎患者の新規治療薬登場後の時代における予後解析

菱沼佳純, 諸井林太郎, 下山雄丞, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本大腸肛門病学会雑誌(Web)　73　(9)　2020

ISSN： 1882-9619
炎症性腸疾患の最新治療の現状と今後難治性潰瘍性大腸炎に対する寛解導入成績の4剤間比較

高橋隆宏, 志賀永嗣, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 正宗淳

日本消化管学会雑誌　4　(Suppl.)　239-239　2020/01
Publisher: (一社)日本消化管学会
ISSN： 2433-3840
クローン病の消化管狭窄に対する内視鏡的バルーン拡張術の現状と問題点の解析

下田楓美子, 諸井林太郎, 志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会東北支部例会誌　208th　82-82　2020
Publisher: 日本消化器病学会-東北支部
薬物による粘膜障害当科における免疫チェックポイント阻害薬による腸炎の臨床病理学的特徴

猪股優志, 志賀永嗣, 泉山泰宏, 角田洋一, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　208回　94-94　2020/01
Publisher: 日本消化器病学会-東北支部
炎症性腸疾患の最新治療の現状と今後難治性潰瘍性大腸炎に対する寛解導入成績の4剤間比較

高橋隆宏, 志賀永嗣, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 正宗淳

日本消化管学会雑誌　4　(Suppl.)　239-239　2020/01
Publisher: (一社)日本消化管学会
ISSN： 2433-3840
高齢者潰瘍性大腸炎の特徴と問題点

市川遼, 黒羽正剛, 諸井林太郎, 金澤義丈, 志賀永嗣, 角田洋一, 正宗淳

日本消化器病学会雑誌　116　(臨増大会)　A775-A775　2019/11
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
大腸癌三次元オルガノイド培養を用いたエクソソーム研究

黒羽正剛, 阿部出, 半田智之, 枡悠太郎, 鈴木郁, 菱沼佳純, 中野健, 岡本大祐, 泉山泰宏, 市川遼, 諸井林太郎, 金澤義丈, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会雑誌　116　(臨増大会)　A817-A817　2019/11
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
スマートフォンアプリを利用したテンプレート書式入力の省力化

佐々木恵利奈, 菅原綾子, 根来健一, 諸井林太郎, 角田洋一, 中村直毅, 中山雅晴

医療情報学連合大会論文集　39回　895-896　2019/11
Publisher: (一社)日本医療情報学会
ISSN： 1347-8508
クローン病の内視鏡診療の課題と新展開クローン病の消化管狭窄に対するバルーン拡張術の現状と再狭窄例に対する新たなアプローチ

諸井林太郎, 角田洋一, 正宗淳

Gastroenterological Endoscopy　61　(Suppl.2)　2062-2062　2019/10
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
炎症性腸疾患の治療と遺伝子多型検査―NUDT15遺伝子多型検査がなぜ求められたか

角田洋一

臨床化学　48　297　2019/08/28

ISSN： 0370-5633
臨床検査アップデート Nudix hydrolase 15(NUDT15)遺伝子多型検査

角田洋一

Modern Media　65　(8)　156-161　2019/08
Publisher: 栄研化学(株)
ISSN： 0026-8054
日本から発信する!IBDのゲノム医療 IBDの病因と病態にかかわる遺伝的背景

内藤健夫, 角田洋一, 正宗淳

IBD Research　13　(2)　88‐94　2019/06/10

ISSN： 1881-6533
【日本から発信する!IBDのゲノム医療】IBDの病因と病態にかかわる遺伝的背景

内藤健夫, 角田洋一, 正宗淳

IBD Research　13　(2)　88-94　2019/06
Publisher: (株)先端医学社
ISSN： 1881-6533
【炎症性腸疾患診療のupdate-診断・治療の最新知見】炎症性腸疾患の病因・病態遺伝子関連

角田洋一

臨床消化器内科　34　(7)　716-721　2019/05
Publisher: (株)日本メディカルセンター
ISSN： 0911-601X
小腸疾患診療の現状と今後の展望当科で経験した後天性von Willebrand症候群による小腸出血症例の検討

諸井林太郎, 角田洋一, 正宗淳

日本消化器病学会雑誌　116　(臨増総会)　A193-A193　2019/03
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
後天性von Willebrand症候群により小腸出血をきたしたと考えられ内視鏡的止血術を施行した2例

鈴木郁, 諸井林太郎, 阿部出, 半田智之, 菱沼佳純, 枡悠太郎, 泉山泰宏, 市川遼, 岡本大祐, 中野健, 永井博, 小野寺基之, 黒羽正剛, 金澤義丈, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　206回　88-88　2019/02
Publisher: 日本消化器病学会-東北支部
炎症性腸疾患に対する新規治療薬の位置付け潰瘍性大腸炎に対するゴリムマブの使用成績と位置付け

小野寺基之, 志賀永嗣, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　3　(Suppl.)　179-179　2019/02
Publisher: (一社)日本消化管学会
ISSN： 2433-3840

eISSN： 2435-8967
免疫チェックポイント阻害薬時代の消化管診断と治療当院における免疫チェックポイント阻害剤による腸炎の難治例も含めた治療効果、内視鏡所見に関する検討

泉山泰宏, 志賀永嗣, 小野寺基之, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　3　(Suppl.)　195-195　2019/02
Publisher: (一社)日本消化管学会
ISSN： 2433-3840

eISSN： 2435-8967
乾癬性関節炎、掌蹠膿疱症性関節炎治療中に発症した小腸原発メトトレキサート関連リンパ増殖性疾患の1例

阿部出, 小野寺基之, 泉山泰宏, 市川遼, 岡本大祐, 中野健, 永井博, 松本信, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　3　(Suppl.)　264-264　2019/02
Publisher: (一社)日本消化管学会
ISSN： 2433-3840

eISSN： 2435-8967
当院で経験した小腸大腸病変を有するT細胞リンパ腫の臨床所見と内視鏡所見の検討

岡本大祐, 小野寺基之, 阿部出, 半田智之, 枡悠太郎, 鈴木郁, 菱沼佳純, 中野健, 泉山泰宏, 市川遼, 永井博, 松本信, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤善丈, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　3　(Suppl.)　294-294　2019/02
Publisher: (一社)日本消化管学会
ISSN： 2433-3840

eISSN： 2435-8967
炎症性腸疾患に対する新規治療薬の位置付け潰瘍性大腸炎に対するゴリムマブの使用成績と位置付け

小野寺基之, 志賀永嗣, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　3　(Suppl.)　179-179　2019/02
Publisher: (一社)日本消化管学会
ISSN： 2433-3840
免疫チェックポイント阻害薬時代の消化管診断と治療当院における免疫チェックポイント阻害剤による腸炎の難治例も含めた治療効果、内視鏡所見に関する検討

泉山泰宏, 志賀永嗣, 小野寺基之, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　3　(Suppl.)　195-195　2019/02
Publisher: (一社)日本消化管学会
ISSN： 2433-3840
乾癬性関節炎、掌蹠膿疱症性関節炎治療中に発症した小腸原発メトトレキサート関連リンパ増殖性疾患の1例

阿部出, 小野寺基之, 泉山泰宏, 市川遼, 岡本大祐, 中野健, 永井博, 松本信, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　3　(Suppl.)　264-264　2019/02
Publisher: (一社)日本消化管学会
ISSN： 2433-3840
当院で経験した小腸大腸病変を有するT細胞リンパ腫の臨床所見と内視鏡所見の検討

岡本大祐, 小野寺基之, 阿部出, 半田智之, 枡悠太郎, 鈴木郁, 菱沼佳純, 中野健, 泉山泰宏, 市川遼, 永井博, 松本信, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤善丈, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　3　(Suppl.)　294-294　2019/02
Publisher: (一社)日本消化管学会
ISSN： 2433-3840
難治性炎症性腸管障害に関する調査研究炎症性腸疾患患者におけるチオプリン関連副作用とNUDT15遺伝子多型との相関性に関する多施設共同研究(MENDEL Study)

角田洋一, 木内喜孝, 中村志郎, 高川哲也, 花井洋行, 池谷賢太郎, 櫻庭裕丈, 西田淳史, 佐々木誠人, 岡庭紀子, 久松理一, 小林拓, 小野寺馨, 石黒陽, 篠崎大, 長沼誠, 平岡佐規子, 荒木寛司, 佐々木悠, 志賀永嗣, 本谷聡, 小野寺基之, 松岡克善, 藤谷幹浩, 佐藤雄一郎, 桂田武彦, 梁井俊一, 穂苅量太, 石原俊治, 新井勝大, 野口光徳, 中川倫夫, 加藤順, 杉田昭, 松浦稔, 遠藤克哉, 内藤健夫, 諸井林太郎, 黒羽正剛, 木村智哉, 金澤義丈, 安藤朗, 鈴木康夫, 下瀬川徹

難治性炎症性腸管障害に関する調査研究平成30年度総括・分担研究報告書(Web)　2019
Reduction Input Time of Templates Using a Smartphone App

佐々木恵利奈, 菅原綾子, 根来健一, 諸井林太郎, 角田洋一, 中村直毅, 中山雅晴, 中山雅晴

医療情報学連合大会論文集(CD-ROM)　39th　2019

ISSN： 2433-698X
乾癬性関節炎,掌蹠膿疱症性関節炎治療中に発症した小腸原発メトトレキサート関連リンパ増殖性疾患の1例

阿部出, 小野寺基之, 泉山泰宏, 市川遼, 岡本大祐, 中野健, 永井博, 松本信, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 志賀永嗣, 角田洋一, 木内喜考, 正宗淳

日本消化管学会雑誌　3　(Supplement)　2019

ISSN： 2435-8967
当院における免疫チェックポイント阻害剤による腸炎の難治例も含めた治療効果,内視鏡所見に関する検討

泉山泰宏, 志賀永嗣, 小野寺基之, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　3　(Supplement)　2019

ISSN： 2435-8967
当院で経験した小腸大腸病変を有するT細胞リンパ腫の臨床所見と内視鏡所見の検討

岡本大祐, 小野寺基之, 阿部出, 半田智之, 枡悠太郎, 鈴木郁, 菱沼佳純, 中野健, 泉山泰宏, 市川遼, 永井博, 松本信, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤善丈, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　3　(Supplement)　2019

ISSN： 2435-8967
潰瘍性大腸炎に対するゴリムマブの使用成績と位置付け

小野寺基之, 志賀永嗣, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　3　(Supplement)　2019

ISSN： 2435-8967
難治性炎症性腸管障害に関する調査研究 IBDの遺伝子解析プロジェクト:総括

松本主之, 角田洋一, 梅野淳嗣, 高川哲也

難治性炎症性腸管障害に関する調査研究平成30年度総括・分担研究報告書(Web)　2019
難治性炎症性腸管障害に関する調査研究「IBDの遺伝子解析プロジェクト」腸管ベーチェット病および単純性潰瘍におけるGenome Wide Association Study(GWAS)

松本主之, 江崎幹宏, 冬野雄太, 平野敦士, 梅野淳嗣, 角田洋一, 仲瀬裕志, 久松理一, 櫻庭裕丈, 国崎玲子, 平井郁仁

難治性炎症性腸管障害に関する調査研究平成30年度総括・分担研究報告書(Web)　2019
繰り返す発熱・腹痛発作を契機に診断しMEFV遺伝子変異を確認しえた家族性地中海熱の一例

片山智文, 遠藤克哉, 岡本大祐, 角田洋一, 津守孝彦, 佐藤格, 佐藤倫紀, 福士大介, 小岩井明信, 支倉翔太郎, 二瓶憲, 支倉さやか, 近藤史帆, 小暮高之, 高須充子, 廣田衛久, 目黒敬義, 佐藤賢一

日本消化器病学会東北支部例会誌　206th　2019
クローン病の消化管狭窄に対するバルーン拡張術の現状と再狭窄例に対する新たなアプローチ

諸井林太郎, 角田洋一, 正宗淳

Gastroenterological Endoscopy (Web)　61　(Supplement2)　2019

ISSN： 1884-5738
大腸癌三次元オルガノイド培養を用いたエクソソーム研究

黒羽正剛, 阿部出, 半田智之, 枡悠太郎, 鈴木郁, 菱沼佳純, 中野健, 岡本大祐, 泉山泰宏, 市川遼, 諸井林太郎, 金澤義丈, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会雑誌(Web)　116　2019

ISSN： 1349-7693
肛門管癌が合併したクローン病の1例

半田智之, 黒羽正剛, 阿部出, 菱沼佳純, 枡悠太郎, 鈴木郁, 中野健, 泉山泰弘, 市川遼, 岡本大祐, 諸井林太郎, 金澤義丈, 木村智哉, 志賀永嗣, 角田洋一, 渡辺和宏, 木内喜孝, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　207th　49-49　2019
Publisher: 日本消化器病学会-東北支部
炎症性腸疾患の病因・病態 1 遺伝子関連

角田洋一

臨床消化器内科　34　(7)　716‐721　2019

DOI： 10.19020/CG.0000000787 　

ISSN： 0911-601X
炎症性腸疾患における既存治療を見直すチオプリンの副作用を予測するNUDT15遺伝子多型検査の有用性について

角田洋一, 木内喜孝, 正宗淳, MENDEL Study Group

日本消化器病学会雑誌　115　(臨増大会)　A553-A553　2018/10
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
炎症性腸疾患患者の骨塩低下は臨床的なリスク要因が少ない患者ほど遺伝的影響を強く受ける

横山直信, 内藤健夫, 角田洋一, 木内喜孝, 小池智幸, 正宗淳, 下瀬川徹

日本消化器病学会雑誌　115　(臨増大会)　A721-A721　2018/10
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
当科で経験したクロンカイトカナダ症候群の3例

枡悠太郎, 諸井林太郎, 小野寺基之, 内藤健夫, 黒羽正剛, 木村智哉, 金澤義丈, 角田洋一, 小池智幸, 正宗淳, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　115　(臨増大会)　A726-A726　2018/10
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
潰瘍性大腸炎に対するインフリキシマブ、アダリムマブの治療成績の比較検討

小野寺基之, 角田洋一, 正宗淳

日本消化器病学会雑誌　115　(臨増大会)　A766-A766　2018/10
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586
炎症性腸疾患における既存治療を見直すチオプリンの副作用を予測するNUDT15遺伝子多型検査の有用性について

角田洋一, 木内喜孝, 正宗淳, MENDEL Study Group

日本消化器病学会雑誌　115　(臨増大会)　A553-A553　2018/10
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586
炎症性腸疾患患者の骨塩低下は臨床的なリスク要因が少ない患者ほど遺伝的影響を強く受ける

横山直信, 内藤健夫, 角田洋一, 木内喜孝, 小池智幸, 正宗淳, 下瀬川徹

日本消化器病学会雑誌　115　(臨増大会)　A721-A721　2018/10
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586
当科で経験したクロンカイトカナダ症候群の3例

枡悠太郎, 諸井林太郎, 小野寺基之, 内藤健夫, 黒羽正剛, 木村智哉, 金澤義丈, 角田洋一, 小池智幸, 正宗淳, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　115　(臨増大会)　A726-A726　2018/10
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586
IBD治療のピットフォール第18回チオプリン製剤とNUDT15遺伝子多型

角田洋一, 木内喜孝

IBD Research　12　(2)　119‐124-124　2018/06/10
Publisher: (株)先端医学社
ISSN： 1881-6533
IBDと疾患感受性遺伝子 GWAS論文の読み方―専門用語の意味するもの,結果の解釈の仕方―

角田洋一

消化器病学サイエンス　2　(2)　69‐74-74　2018/06/01
Publisher: (株)先端医学社
ISSN： 2432-7549
炎症性腸疾患の病因と病態日本人炎症性腸疾患の遺伝的要因・疾患感受性遺伝子

角田洋一, 木内喜孝

日本臨床　76　59‐64　2018/04/28

ISSN： 0047-1852
炎症性腸疾患に対する抗TNF-α抗体治療薬導入により見えてきた臨床課題 Crohn病に対する抗TNF-α抗体の長期的治療成績から考える最適な投与戦略

諸井林太郎, 遠藤克哉, 角田洋一

日本消化器病学会雑誌　115　(臨増総会)　A96-A96　2018/04
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586
潰瘍性大腸炎に対するインフリキシマブ、タクロリムスによる寛解導入療法後の粘膜治癒に関する長期予後の検討

小野寺基之, 角田洋一, 正宗淳

Gastroenterological Endoscopy　60　(Suppl.1)　749-749　2018/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207
当院における免疫チェックポイント阻害剤による腸炎の現状

泉山泰宏, 木村智哉, 市川遼, 岡本大祐, 中野健, 松本信, 永井博, 千葉宏文, 横山直信, 山本勝利, 下山雄丞, 内藤健夫, 小野寺基之, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 木内喜孝, 小池智幸, 正宗淳, 下瀬川徹

Gastroenterological Endoscopy　60　(Suppl.1)　773-773　2018/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
潰瘍性大腸炎に対するインフリキシマブ、タクロリムスによる寛解導入療法後の粘膜治癒に関する長期予後の検討

小野寺基之, 角田洋一, 正宗淳

Gastroenterological Endoscopy　60　(Suppl.1)　749-749　2018/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207
当院における免疫チェックポイント阻害剤による腸炎の現状

泉山泰宏, 木村智哉, 市川遼, 岡本大祐, 中野健, 松本信, 永井博, 千葉宏文, 横山直信, 山本勝利, 下山雄丞, 内藤健夫, 小野寺基之, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 木内喜孝, 小池智幸, 正宗淳, 下瀬川徹

Gastroenterological Endoscopy　60　(Suppl.1)　773-773　2018/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207
【炎症性腸疾患(第2版)-病因解明と診断・治療の最新知見-】炎症性腸疾患の病因と病態日本人炎症性腸疾患の遺伝的要因・疾患感受性遺伝子

角田洋一, 木内喜孝

日本臨床　76　(増刊3 炎症性腸疾患)　59-64　2018/04
Publisher: (株)日本臨床社
ISSN： 0047-1852
免疫チェックポイント阻害薬が原因と考えられた腸炎の2例

泉山泰宏, 木村智哉, 中野健, 岡本大祐, 市川遼, 永井博, 松本信, 下山雄丞, 千葉宏文, 横山直信, 山本勝利, 小野寺基之, 内藤健夫, 黒羽正剛, 金澤義丈, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会雑誌　2　(Supplement)　289-289　2018/02/01
Publisher: (一社)日本消化管学会
ISSN： 2433-3840
大腸ESDのこれまでとこれから大腸ESD術中の粘膜下層線維化リスク因子についての検討術前生検により粘膜下層の線維化をきたすのか?

黒羽正剛, 志賀永嗣, 金澤義文, 半田智之, 市川遼, 小野寺基之, 内藤健夫, 諸井林太郎, 木村智哉, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会雑誌　2　(Suppl.)　124-124　2018/02
Publisher: (一社)日本消化管学会
ISSN： 2433-3840
Probiotics development for clinical application : Current status and future perspective

角田洋一, 下瀬川徹

医学のあゆみ　264　(1)　123-127　2018/01/06
Publisher: 医歯薬出版
ISSN： 0039-2359
大腸ESD術中の粘膜下層線維化リスク因子についての検討-術前生検により粘膜下層の線維化をきたすのか?-

黒羽正剛, 志賀永嗣, 金澤義文, 半田智之, 市川遼, 小野寺基之, 内藤健夫, 諸井林太郎, 木村智哉, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会雑誌　2　(Supplement)　2018

ISSN： 2435-8967
Crohn病に対する抗TNF-α抗体の長期的治療成績から考える最適な投与戦略

諸井林太郎, 遠藤克哉, 角田洋一

日本消化器病学会雑誌(Web)　115　2018

ISSN： 1349-7693
NUDT15 R139C C/Tヘテロ症例におけるチオプリン製剤を用いた潰瘍性大腸炎の治療成績

渡辺憲治, 高川哲也, 角田洋一, 藤森絢子, 小島健太郎, 小柴良司, 藤本晃士, 佐藤寿行, 河合幹夫, 上小鶴孝二, 横山陽子, 宮嵜孝子, 樋田信幸, 堀和敏, 池内浩基, 中村志郎

日本大腸肛門病学会雑誌(Web)　71　(9)　2018

ISSN： 1882-9619
当院における免疫チェックポイント阻害剤による腸炎の現状

泉山泰宏, 木村智哉, 市川遼, 岡本大祐, 中野健, 松本信, 永井博, 千葉宏文, 横山直信, 山本勝利, 下山雄丞, 内藤健夫, 小野寺基之, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 木内喜孝, 小池智幸, 正宗淳, 下瀬川徹

Gastroenterological Endoscopy (Web)　60　(Supplement1)　2018

ISSN： 1884-5738
潰瘍性大腸炎に対するインフリキシマブ,タクロリムスによる寛解導入療法後の粘膜治癒に関する長期予後の検討

小野寺基之, 角田洋一, 正宗淳

Gastroenterological Endoscopy (Web)　60　(Supplement1)　2018

ISSN： 1884-5738
チオプリンの副作用を予測するNUDT15遺伝子多型検査の有用性について

角田洋一, 角田洋一, 木内喜孝, 木内喜孝, 正宗淳

Gastroenterological Endoscopy (Web)　60　(Supplement2)　2018

ISSN： 1884-5738
難治性炎症性腸管障害に関する調査研究「IBDの遺伝子解析プロジェクト」腸管ベーチェット病および単純性潰瘍におけるGenome Wide Association Study(GWAS)

松本主之, 江崎幹宏, 冬野雄太, 平野敦士, 角田洋一, 仲瀬裕志, 久松理一

難治性炎症性腸管障害に関する調査研究平成29年度総括・分担研究報告書　237‐238　2018
難治性炎症性腸管障害に関する調査研究 NUDT15 R139Cヘテロ接合体IBD患者におけるチオプリン維持量と目標6‐TGN値の検討

中村志郎, 高川哲也, 高川哲也, 角田洋一, 佐藤寿行, 藤森絢子, 小柴良司, 藤本晃士, 河合幹夫, 河合幹夫, 上小鶴孝二, 横山陽子, 木田裕子, 宮嵜孝子, 樋田信幸, 渡辺憲治, 渡辺憲治, 池内浩基, 中村志郎, 中村志郎

難治性炎症性腸管障害に関する調査研究平成29年度総括・分担研究報告書　234‐236　2018
難治性炎症性腸管障害に関する調査研究炎症性腸疾患患者におけるチオプリン関連副作用とNUDT15遺伝子多型との相関性に関する多施設共同研究(MENDEL Study)

角田洋一, 木内喜孝, 中村志郎, 高川哲也, 花井洋行, 池谷賢太郎, 櫻庭裕丈, 西田淳史, 佐々木誠人, 岡庭紀子, 久松理一, 小林拓, 小野寺馨, 石黒陽, 篠崎大, 長沼誠, 平岡佐規子, 荒木寛司, 佐々木悠, 志賀永嗣, 本谷聡, 小野寺基之, 松岡克善, 藤谷幹浩, 佐藤雄一郎, 桂田武彦, 梁井俊一, 穂苅量太, 石原俊治, 新井勝大, 野口光徳, 中川倫夫, 加藤順, 杉田昭, 松浦稔, 遠藤克哉, 内藤健夫, 諸井林太郎, 黒羽正剛, 木村智哉, 金澤義丈, 安藤朗, 鈴木康夫, 下瀬川徹

難治性炎症性腸管障害に関する調査研究平成29年度総括・分担研究報告書　231‐233　2018
難治性炎症性腸管障害に関する調査研究特殊型炎症性腸疾患におけるアダリムマブとステロイドの前向き無作為化比較試験 Castle Study:国内多施設共同試験

渡辺憲治, 松本主之, 仲瀬裕志, 久松理一, 平井郁仁, 小林清典, 国崎玲子, 長堀正和, 竹内健, 大藤さとこ, 福島若菜, 梁井俊一, 稲場勇平, 藤谷幹浩, 櫻庭裕丈, 角田洋一, 勝野達郎, 大森鉄平, 小林拓, 秋山純一, 本田穣, 佐藤公, 佐々木誠人, 谷田諭史, 加賀谷尚史, 馬場重樹, 安藤朗, 深田憲将, 岡崎和一, 細見周平, 湯川知洋, 鎌田紀子, 山上博一, 宮嵜孝子, 樋田信幸, 中村志郎, 松浦稔, 平田敬, 石田哲也, 松本吏弘, 金城福則, 金城徹, 上野義隆, 田中信治, 渡辺知佳子, 穂苅量太, 高橋索真, 進士明宏, 北村和哉, 辻川知之, 山下真幸, 長沼誠, 猿田雅之, 本谷聡, 鈴木康夫, 上野文昭, 日比紀文, 渡辺守

難治性炎症性腸管障害に関する調査研究平成29年度総括・分担研究報告書　197‐199　2018
Diplotype分類に基づいたNUDT15活性レベルと炎症性腸疾患患者のチオプリン誘発性白血球減少症及び全脱毛の相関

高川哲也, 佐藤寿行, 角田洋一, 西尾昭宏, 河合幹夫, 上小鶴孝二, 横山陽子, 木田裕子, 宮嵜孝子, 飯室正樹, 樋田信幸, 堀和敏, 池内浩基, 中村志郎

日本消化器病学会雑誌　114　(臨増大会)　A793-A793　2017/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586
日本人IBD患者の骨粗鬆症リスク因子の解明と遺伝的背景の検討

横山直信, 角田洋一, 小野寺基之, 内藤健夫, 平本圭一郎, 黒羽正剛, 金澤義丈, 木村智哉, 遠藤克哉, 木内善孝, 下瀬川徹

日本消化器病学会雑誌　114　(臨増大会)　A790-A790　2017/09
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
DICHOTOMOUS EFFECTS OF ATG16L1 AND LRRK2 IN MODULATING PANETH CELL DEFECT IN JAPANESE AND NORTH AMERICAN CROHN'S DISEASE PATIENTS

Ta-Chiang Liu, Takeo Naito, Zhenqiu Liu, Kelli VanDussen, Talin Haritunians, Dalin Li, Katsuya Endo, Yosuke Kawai, Masao Nagasaki, Yoshitaka Kinouchi, Dermot McGovern, Tooru Shimosegawa, Yoichi Kakuta, Thaddeus S. Stappenbeck

GASTROENTEROLOGY　152　(5)　S982-S982　2017/04

ISSN： 0016-5085

eISSN： 1528-0012
POPULATION-OPTIMIZED SNP ARRAY REVEALS RAP1A AS A NOVEL CANDIDATE SUSCEPTIBILITY GENE FOR CROHN'S DISEASE IN JAPANESE INDIVIDUALS

Yoichi Kakuta, Yosuke Kawai, Takeo Naito, Atsushi Hirano, Junji Umeno, Keiichiro Hiramoto, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Katsuya Endo, Yoshitaka Kinouchi, Motohiro Esaki, Masao Nagasaki, Tooru Shimosegawa

GASTROENTEROLOGY　152　(5)　S78-S78　2017/04

ISSN： 0016-5085

eISSN： 1528-0012
肥厚性皮膚骨膜症を合併した非特異性多発性小腸潰瘍(CEAS)の一例

永井博, 木村智哉, 松本信, 下山雄丞, 千葉宏文, 山本勝利, 横山直信, 小野寺基之, 日下順, 内藤健夫, 川上瑤子, 平本圭一郎, 黒羽正剛, 金澤義丈, 角田洋一, 遠藤克哉, 梅野淳嗣, 江崎幹宏, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy (Web)　59　(Supplement1)　1094(J‐STAGE)-1094　2017/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 1884-5738
von Hippel‐Lindau病に発症した小腸GISTの一例

小野寺基之, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy (Web)　59　(Supplement1)　1145(J‐STAGE)-1145　2017/04
Publisher: (一社)日本消化器内視鏡学会
ISSN： 1884-5738
【炎症性腸疾患-最近の診断・治療-】炎症性腸疾患における遺伝要因

角田洋一, 遠藤克哉, 木内喜孝

日本臨床　75　(3)　482-487　2017/03
Publisher: (株)日本臨床社
ISSN： 0047-1852
Genetics of inflammatory bowel disease in Japanese

角田洋一, 遠藤克哉, 木内喜孝

日本臨床 = Japanese journal of clinical medicine　75　(3)　482-487　2017/03
Publisher: 日本臨床社
ISSN： 0047-1852
抗TNFα製剤が著効した潰瘍性大腸炎関連小腸炎の2例

千葉宏文, 内藤健夫, 木村智哉, 泉山泰宏, 中野健, 岡本大祐, 市川遼, 松本信, 永井博, 横山直信, 山本勝利, 小野寺基之, 日下順, 平本圭一郎, 黒羽正剛, 金澤義丈, 角田洋一, 遠藤克哉, 木内喜孝, 藤島史喜, 下瀬川徹

Gastroenterological Endoscopy (Web)　59　(Supplement1)　1092(J‐STAGE)-1092　2017
Publisher: (一社)日本消化器内視鏡学会
ISSN： 1884-5738
潰瘍性大腸炎に対するタクロリムス治療におけるCYP3A5遺伝子多型を予測した投与量最適化の工夫

小野寺基之, 遠藤克哉, 平本圭一郎, 黒羽正剛, 金澤義丈, 木村智哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　13th　202　2017

ISSN： 2189-9037
難治性炎症性腸管障害に関する調査研究炎症性腸疾患患者におけるチオプリン関連副作用とNUDT15遺伝子多型との相関性に関する多施設共同研究(MENDEL Study)

角田洋一, 木内喜孝, 内藤健夫, 花井洋行, 飯田貴之, 佐々木誠人, 岡庭紀子, 中村志郎, 高川哲也, 西田淳史, 久松理一, 小林拓, 篠崎大, 小野寺馨, 石黒陽, 志賀永嗣, 櫻庭裕丈, 平岡佐規子, 長沼誠, 穂苅量太, 桂田武彦, 梁井俊一, 本谷聡, 石原俊治, 藤谷幹浩, 新井勝大, 中川倫夫, 加藤順, 野口光徳, 遠藤克哉, 安藤朗, 鈴木康夫, 下瀬川徹

難治性炎症性腸管障害に関する調査研究平成28年度総括・分担研究報告書(Web)　286‐287 (WEB ONLY)　2017
炎症性腸疾患 V.特論炎症性腸疾患における遺伝要因

角田洋一, 遠藤克哉, 木内喜孝

日本臨床　75　(3)　482‐487　2017

ISSN： 0047-1852
難治性炎症性腸管障害に関する調査研究日本人IBD患者のチオプリン関連副作用予測におけるNUDT15遺伝子多型の優位性(FTO及びRUNX1遺伝子との比較)

中村志郎, 高川哲也, 佐藤寿行, 角田洋一, 西尾昭宏, 河合幹夫, 上小鶴孝二, 横山陽子, 木田裕子, 宮嵜孝子, 樋田信幸, 堀和敏, 池内浩基, 中村志郎

難治性炎症性腸管障害に関する調査研究平成28年度総括・分担研究報告書(Web)　288‐289 (WEB ONLY)　2017
ABCB1 1236C > T polymorphism affects the therapeutic efficacy of Tacrolimus in patients with refractory ulcerative colitis

Motoyuki Onodera, Katsuya Endo, Keiichirou Hiramoto, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Yoichi Kakuta, Yoshitaka Kinouchi, Toru Shimosegawa

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY　31　173-173　2016/11

ISSN： 0815-9319

eISSN： 1440-1746
【増え続ける腸疾患大腸がん炎症性腸疾患腸内常在菌】増え続ける炎症性腸疾患検査データから考える治療の選択とタイミング

角田洋一

アニムス　21　(4)　9,24-15,24　2016/11
Publisher: アニムス編集委員会
ISSN： 1342-0119
炎症性腸疾患を解き明かす―今後の解決すべき問題に向けて―1 炎症性腸疾患はなぜ増加し続けているのか

木村智哉, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

GI Forefront　12　(1)　20‐23-23　2016/09/30
Publisher: (株)メディカルレビュー社
ISSN： 1349-9629
【「炎症性腸疾患を解き明かす-今後の解決すべき問題に向けて-」】炎症性腸疾患はなぜ増加し続けているのか

木村智哉, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

The GI Forefront　12　(1)　20-23　2016/09
Publisher: (株)メディカルレビュー社
ISSN： 1349-9629
日本人を含めたアジア人特有のチオプリンに対する高感受性 NUDT15遺伝子多型を投与前に調べることで、副作用やリスク症例への投与を回避できると考えられる

角田洋一, 安藤朗

日本医事新報　(4816)　54-55　2016/08
Publisher: (株)日本医事新報社
ISSN： 0385-9215
Paneth Cell Phenotype is Associated With Novel Genetic Determinants and Clinical Outcome in Japanese Crohn's Disease Patients

Takeo Naito, Ta-Chiang Liu, Yoichi Kakuta, Richard Head, Zhenqiu Liu, Talin Haritunians, Dalin Li, Katsuya Endo, Yoshitaka Kinouchi, Dermot McGovern, Thaddeus Stappenbeck, Tooru Shimosegawa

GASTROENTEROLOGY　150　(4)　S75-S75　2016/04

ISSN： 0016-5085

eISSN： 1528-0012
腸内細菌からIBDの病態を探る!ゲノム解析から明らかになったIBD発症への腸内フローラの関与

角田洋一, 木内喜孝, 下瀬川徹

IBD Research　10　(1)　16‐21-21　2016/03/10
Publisher: (株)先端医学社
ISSN： 1881-6533
炎症性腸疾患疾患感受性遺伝子―最近の知見

角田洋一, 木内喜孝

医学のあゆみ　256　(10)　1009‐1014-1014　2016/03/05
Publisher: 医歯薬出版
ISSN： 0039-2359
Genetics of inflammatory bowel disease : an up-to-date review

角田洋一, 木内喜孝

医学のあゆみ　256　(10)　1009-1014　2016/03/05
Publisher: 医歯薬出版
ISSN： 0039-2359
【炎症性腸疾患のいま】疫学と研究の進展炎症性腸疾患疾患感受性遺伝子最近の知見

角田洋一, 木内喜孝

医学のあゆみ　256　(10)　1009-1014　2016/03
Publisher: 医歯薬出版(株)
ISSN： 0039-2359
難治性炎症性腸管障害に関する調査研究的確な診断・治療の確立プロジェクト-バイオマーカープロジェクト総括

金井隆典, 長沼誠, 仲瀬裕志, 中村志郎, 安藤朗, 角田洋一

難治性炎症性腸管障害に関する調査研究平成27年度総括・分担研究報告書　2016
高齢者潰瘍性大腸炎の手術適応についての検討

黒羽正剛, 遠藤克哉, 内藤健夫, 日下順, 小野寺基之, 只野敏浩, 川上瑶子, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　12th　139　2016

ISSN： 2189-9037
5ASA不耐潰瘍性大腸炎の治療経過と予後の検討

木村智哉, 遠藤克哉, 永井博, 松本信, 千葉宏文, 横山直信, 下山雄丞, 山本勝利, 内藤健夫, 小野寺基之, 日下順, 川上瑶子, 只野敏浩, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　12th　230　2016

ISSN： 2189-9037
難治性炎症性腸管障害に関する調査研究炎症性腸疾患患者におけるチオプリン関連副作用とNUDT15遺伝子多型との相関性に関する多施設共同研究(MENDEL Study)

角田洋一, 木内喜孝, 内藤健夫, 黒羽正剛, 木村智哉, 志賀永嗣, 遠藤克哉, 安藤朗, 鈴木康夫, 下瀬川徹

難治性炎症性腸管障害に関する調査研究平成27年度総括・分担研究報告書　122‐123　2016
ニューモシスチス肺炎を合併した潰瘍性大腸炎の1例

日下順, 木村智哉, 黒羽正剛, 志賀永嗣, 角田洋一, 遠藤克哉, 下瀬川徹, 木内喜孝

東北医学雑誌　127　(2)　179-179　2015/12/25
Publisher: 東北医学会
ISSN： 0040-8700
【炎症性腸疾患(IBD)の最新治療】炎症性腸疾患関連遺伝子について

角田洋一, 木内喜孝, 下瀬川徹

BIO Clinica　30　(14)　1354-1358　2015/12
Publisher: (株)北隆館
ISSN： 0919-8237
炎症性腸疾患―ファーストタッチから長期マネジメントまで炎症性腸疾患の病態を疾患感受性遺伝子から紐解く

角田洋一, 遠藤克哉, 志賀永嗣, 木内喜孝, 下瀬川徹

内科　116　(4)　547-551　2015/10/01
Publisher: (株)南江堂
ISSN： 0022-1961

eISSN： 2432-9452
炎症性腸疾患の病態を疾患感受性遺伝子から紐解く (特集炎症性腸疾患 : ファーストタッチから長期マネジメントまで)

角田洋一, 遠藤克哉, 志賀永嗣

内科　116　(4)　547-551　2015/10
Publisher: 南江堂
ISSN： 0022-1961
消化器疾患と遺伝子異常炎症性腸疾患の遺伝子異常(単一遺伝子疾患を含めて)

角田洋一, 木内喜孝, 下瀬川徹

分子消化器病　12　(3)　240-245　2015/09/01
Publisher: (株)先端医学社
ISSN： 1348-995X
潰瘍性大腸炎に対するタクロリムス治療におけるUCEISを用いた長期予後の予測

小野寺基之, 遠藤克哉, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　57　(Supplement 1)　736-736　2015/04/15
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
アダリムマブ投与を行った潰瘍性大腸炎術後に発症した難治性小腸炎の一例

内藤健夫, 遠藤克哉, 小野寺基之, 日下順, 川上瑶子, 只野敏浩, 平本圭一郎, 松下勝則, 宮澤輝子, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　57　(Supplement 1)　830-830　2015/04/15
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
Genotyping of NUDT15 R139c Could Be a Companion Diagnostic Test for Thiopurine-Induced Leucopenia and Hair Loss in Japanese Patients With IBD

Takeo Naito, Yoichi Kakuta, Motoyuki Onodera, Tomoya Kimura, Masatake Kuroha, Hisashi Shiga, Katsuya Endo, Kenichi Negoro, Yoshitaka Kinouchi, Tooru Shimosegawa

GASTROENTEROLOGY　148　(4)　S700-S700　2015/04

ISSN： 0016-5085

eISSN： 1528-0012
DNA Methylation Profiles of CD4+Effector Memory T-Cells Show Distinct Differences Between Crohn's Disease and Ulcerative Colitis

Katsunori Matsushita, Yoichi Kakuta, Yoshitaka Kinouchi, Kenichi Negoro, Katsuya Endo, Hisashi Shiga, Tooru Shimosegawa

GASTROENTEROLOGY　148　(4)　S701-S701　2015/04

ISSN： 0016-5085

eISSN： 1528-0012
炎症性腸疾患―病態研究から標的治療への展開―病態研究から標的治療へ GWASから明らかになった新しい治療標的

角田洋一, 木内喜孝, 志賀永嗣, 遠藤克哉, 下瀬川徹

最新医学　70　(2)　205-210　2015/02/10
Publisher: (株)最新医学社
ISSN： 0370-8241
Thiopurine-induced leucopenia and hair loss were inevitable in Japanese IBD patients homozygous for NUDT15 R139C: a case series

T. Naito, Y. Kakuta, M. Onodera, T. Kimura, M. Kuroha, H. Shiga, K. Endo, K. Negoro, Y. Kinouchi, T. Shimosegawa

JOURNAL OF CROHNS & COLITIS　9　S428-S428　2015/02

ISSN： 1873-9946

eISSN： 1876-4479
Novel Therapeutic Targets for Inflammatory Bowel Disease from Recent GWAS Results

角田洋一, 木内喜孝, 志賀永嗣

最新医学　70　(2)　205-210　2015/02
Publisher: 最新医学社
ISSN： 0370-8241
肛門管にかかる大腸上皮性腫瘍に対するESDの治療成績

黒羽正剛, 志賀永嗣, 木村智哉, 諸井林太郎, 横山直信, 山本勝利, 千葉宏文, 下山雄丞, 内藤健夫, 日下順, 小野寺基之, 只野敏浩, 川上瑶子, 平本圭一郎, 松下勝則, 宮澤輝子, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　57　(Supplement 1)　901　2015

ISSN： 0387-1207
当院の高齢IBDの特徴

平本圭一郎, 平本圭一郎, 黒羽正剛, 下山雄丞, 千葉宏文, 山本勝利, 横山直信, 小野寺基之, 日下順, 内藤健夫, 川上瑤子, 只野敏浩, 木村智哉, 志賀永嗣, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

日本消化器病学会大会(Web)　57th　(臨増大会)　SHOP‐412 (WEB ONLY)-A924　2015
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
クローン病に対するInfliximab倍量投与の中長期予後

志賀永嗣, 遠藤克哉, 千葉宏文, 下山雄丞, 横山直信, 山本勝利, 内藤健夫, 日下順, 小野寺基之, 川上瑶子, 只野敏浩, 平本圭一郎, 松下勝則, 宮澤輝子, 黒羽正剛, 木村智哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会大会(Web)　57th　(臨増大会)　SHOP‐421 (WEB ONLY)-A927　2015
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
肛門管mixed adenoneuroendocrine carcinoma(MANEC)の一例

内藤健夫, 黒羽正剛, 永井博, 松本信, 横山直信, 千葉宏文, 山本勝利, 日下順, 小野寺基之, 川上瑶子, 只野敏浩, 木村智哉, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

早期大腸癌研究会プログラム・抄録集　28th　2　2015

ISSN： 1349-841X
初発クローン病における上部消化管病変の頻度と予後についての検討

下山雄丞, 遠藤克哉, 小野寺基之, 日下順, 内藤健夫, 川上瑶子, 只野敏浩, 平本圭一郎, 松下勝則, 宮澤輝子, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 飯島克則, 小池智幸, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　11th　253　2015
大腸ESDにおける導入時の治療成績と安全性―胃ESDの経験は必須か?―

志賀永嗣, 黒羽正剛, 遠藤克哉, 千葉宏文, 横山直信, 下山雄丞, 山本勝利, 内藤健夫, 日下順, 小野寺基之, 川上瑶子, 只野敏浩, 平本圭一郎, 松下勝則, 宮澤輝子, 木村智哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　11th　209　2015
難治性炎症性腸管障害に関する調査研究「日本人IBDにおけるチオプリンの早期白血球減少と脱毛はNUDT15遺伝子多型で予測可能である」

木内喜孝, 角田洋一, 遠藤克哉, 志賀永嗣, 黒羽正剛, 下瀬川徹

難治性炎症性腸管障害に関する調査研究平成26年度総括・分担研究報告書　175-176　2015
インフリキシマブ(IFX)無効にて回腸嚢切除術に至った潰瘍性大腸炎(UC)術後難治性回腸嚢炎の一例

千葉宏文, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 遠藤克哉, 下瀬川徹, 木内喜孝

東北医学雑誌　126　(2)　184-184　2014/12/25
Publisher: 東北医学会
ISSN： 0040-8700
UCEIS (Ulcerative Colitis Endoscopic Index of Severity)を用いた近年の潰瘍性大腸炎手術例の特徴

小野寺基之, 遠藤克哉, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　56　(Supplement 2)　3154-3154　2014/09/10
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
消化器疾患と網羅的遺伝子解析遺伝子多型解析は消化器疾患診療に何をもたらしたか

角田洋一, 木内喜孝, 下瀬川徹

分子消化器病　11　(2)　156-160　2014/06/01
Publisher: (株)先端医学社
ISSN： 1348-995X
Autophagy Is Induced by ER Stress Through Ire1 alpha and Chop in Human Colon Cancer Cells

Yosuke Shimodaira, Seiichi Takahashi, Yoshitaka Kinouchi, Katsuya Endo, Yoichi Kakuta, Tooru Shimosegawa

GASTROENTEROLOGY　146　(5)　S282-S282　2014/05

ISSN： 0016-5085

eISSN： 1528-0012
Functional Characterization of the CD40 IBD Risk SNP rs6074022: Integrated Gwas, eQTL, and mQTL Defines IBD Patient Subgroups With Altered Pathobiology and Distinct Natural History of Disease

Rivkah Gonsky, Richard Deem, Yoichi Kakuta, Dermot P. McGovern, Stephan Targan

GASTROENTEROLOGY　146　(5)　S874-S874　2014/05

ISSN： 0016-5085

eISSN： 1528-0012
RBP-J Gene May Be Associated With Bone Mineral Density of IBD Patients

Yoichi Kakuta, Arushi M. deFonseka, Jane F. McGovern, Talin Haritunians, Dalin Li, Dermot P. McGovern

GASTROENTEROLOGY　146　(5)　S873-S873　2014/05

ISSN： 0016-5085

eISSN： 1528-0012
外国人留学生に発症し,大腸内視鏡所見が診断に大きく寄与した腸結核の一例

小野寺基之, 遠藤克哉, 日下順, 内藤健夫, 川上瑤子, 只野敏弘, 平本圭一郎, 松下勝則, 宮澤輝子, 下平陽介, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　56　(Supplement 1)　1267-1267　2014/04/15
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
歯状線に接した直腸上皮性腫瘍に対するESDの有用性と安全性の検討

只野敏浩, 志賀永嗣, 内藤健夫, 日下順, 小野寺基之, 川上瑤子, 松下勝則, 宮澤輝子, 平本圭一郎, 下平陽介, 黒羽正剛, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　56　(Supplement 1)　1181-1181　2014/04/15
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
腸管限局性と考えられた大腸AA型アミロイドーシスの2例

川上瑶子, 黒羽正剛, 小野寺基之, 日下順, 内藤健夫, 只野敏浩, 平本圭一郎, 松下勝則, 宮澤輝子, 下平陽介, 志賀永嗣, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　56　(Supplement 1)　1266-1266　2014/04/15
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
Q&A―専門医に聞くIBD―IBDは遺伝しますか?

木内喜孝, 角田洋一, 志賀永嗣, 遠藤克哉

IBD Res　8　(1)　62-65　2014/03/10
Publisher: (株)先端医学社
ISSN： 1881-6533
ESD初学者による大腸ESD導入時の治療成績と安全性

志賀永嗣, 遠藤克哉, 黒羽正剛, 内藤健夫, 日下順, 小野寺基之, 川上瑶子, 只野敏浩, 奈良志博, 松下勝則, 宮澤輝子, 下平陽介, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　10th　206　2014
腸管ベーチェット病と単純性潰瘍の臨床的相違点に関する検討

日下順, 遠藤克哉, 小野寺基之, 内藤健夫, 川上瑶子, 只野敏浩, 奈良志博, 平本圭一郎, 松下勝則, 宮澤輝子, 下平陽介, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会大会(Web)　56th　(臨増大会)　SHOP‐274 (WEB ONLY)-A900　2014
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
IBDに関するQ&A 「IBDは遺伝しますか」

木内喜孝, 角田洋一, 志賀永嗣, 遠藤克哉

IBD Research　2014
糖尿病患者の健康寿命を延ばす―先手を打つ実臨床 I 癌で手遅れにしないために糖尿病日常診療で無症候性の消化器癌を見つけ出す早期大腸癌の最新治療と無症候性進行腸癌の発見

志賀永嗣, 木内喜孝, 高橋成一, 遠藤克哉, 角田洋一, 下瀬川徹

糖尿病診療マスター　11　(5)　477-480　2013/07/15
Publisher: (株)医学書院
DOI： 10.11477/mf.1415101549 　

ISSN： 1347-8176

eISSN： 1347-8389
FCGR3A-158 Polymorphism Influences the Biological Response to Infliximab in Crohn's Disease Through Affecting the Adcc Activity

Rintaro Moroi, Katsuya Endo, Yoshitaka Kinouchi, Hisashi Shiga, Yoichi Kakuta, Masatake Kuroha, Yoshitake Kanazawa, Yosuke Shimodaira, Seiichi Takahashi, Tooru Shimosegawa

GASTROENTEROLOGY　144　(5)　S816-S816　2013/05

ISSN： 0016-5085

eISSN： 1528-0012
An Overexpressed XBP1 Haplotype Shows a Protective Association With Inflammatory Bowel Disease in Japanese Patients

Hitoshi Nagasawa, Yoichi Kakuta, Seiichi Takahashi, Katsuya Endo, Hisashi Shiga, Yoshitake Kanazawa, Rintaro Moroi, Yosuke Shimodaira, Teruko Miyazawa, Keiichiro Hiramoto, Katsunori Matsushita, Yoshihiro Nara, Yoko Kawakami, Toshihiro Tadano, Yoshitaka Kinouchi, Tooru Shimosegawa

GASTROENTEROLOGY　144　(5)　S469-S469　2013/05

ISSN： 0016-5085

eISSN： 1528-0012
Transethnic Fine-Mapping of the IL12B Locus Identifies Two Independent Signals Associated With IBD Susceptibility and Disease Behaviors

Yoichi Kakuta, Marla Dubinsky, Dalin Li, Kyuyoung Song, Suk-Kyun Yang, Byong Duk Ye, Stephen S. Rich, Suna Onengut-Gumuscu, Esther A. Torres, Deepa Panikkath, Talin Haritunians, Stephan R. Targan, Jerome I. Rotter, Kent D. Taylor, Dermot P. McGovern

GASTROENTEROLOGY　144　(5)　S467-S467　2013/05

ISSN： 0016-5085

eISSN： 1528-0012
Mutational Analysis of the Chymotrypsin C (CTRC) and Interferon Regulatory Factor 2 (IRF2) Genes in Japanese Patients With Chronic Pancreatitis

Eriko Nakano, Atsushi Masamune, Kiyoshi Kume, Yoichi Kakuta, Tooru Shimosegawa

GASTROENTEROLOGY　144　(5)　S459-S459　2013/05

ISSN： 0016-5085

eISSN： 1528-0012
ゲノムワイド関連解析からみえてきた消化器疾患わが国のクローン病の発症要因と治療抵抗性

角田洋一, 木内喜孝, 高橋成一, 下瀬川徹

GI Res　20　(3)　196-202　2012/06/01
Publisher: (株)先端医学社
ISSN： 0918-9408
確定診断困難な輪状狭窄を呈する多発性小腸潰瘍の1例

遠藤克哉, 植木紳夫, 志賀永嗣, 角田洋一, 高橋成一, 木内喜孝, 下瀬川徹

栄養-評価と治療　29　(1)　77-77　2012
Publisher: (株)メディカルレビュー社
ISSN： 0915-759X
内視鏡的バルーン拡張術にて回腸に滞留したカプセル内視鏡を回収しえたNSAID起因性小腸潰瘍の1例

下平陽介, 遠藤克哉, 奈良志博, 平本圭一郎, 松下勝則, 宮澤輝子, 諸井林太郎, 長澤仁嗣, 黒羽正剛, 志賀永嗣, 角田洋一, 高橋成一, 木内喜孝, 下瀬川徹

栄養-評価と治療　29　(1)　84　2012

ISSN： 0915-759X
Genetics of Ulcerative Colitis

木内喜孝, 角田洋一, 遠藤克哉, 志賀永嗣, 高橋成一, 下瀬川徹

Prog Med　31　(10)　2327-2331　2011/10/10

ISSN： 0287-3648
【潰瘍性大腸炎診療の現状と今後の展望】潰瘍性大腸炎の病態はどこまで解明されたか? 潰瘍性大腸炎の遺伝子異常

木内喜孝, 角田洋一, 遠藤克哉, 志賀永嗣, 高橋成一, 下瀬川徹

Progress in Medicine　31　(10)　2327-2331　2011/10
Publisher: (株)ライフ・サイエンス
ISSN： 0287-3648
【臨床に役立つ腸管免疫学の最新のトピックス】 IBDの遺伝子異常 GWASがもたらした病態研究の糸口

木内喜孝, 荒井壮, 金澤義丈, 角田洋一, 遠藤克哉, 志賀永嗣, 高橋成一, 下瀬川徹

Intestine　15　(5)　415-421　2011/09
Publisher: (株)日本メディカルセンター
ISSN： 1883-2342
遺伝子多型による消化器疾患の理解遺伝子多型解析から炎症性腸疾患の病因解明は可能か

木内喜孝, 角田洋一, 高橋成一, 下瀬川徹

分子消化器病　8　(3)　212-219　2011/09/01
Publisher: (株)先端医学社
ISSN： 1348-995X
ここまで明らかになったクローン病の感受性遺伝子

角田洋一, 木内喜孝, 高橋成一, 下瀬川徹

IBD Research　5　(2)　10-16　2011/06/10
Publisher: 先端医学社
IBDの疾患感受性遺伝子を知り,治療につなげるここまで明らかになったクローン病の感受性遺伝子

角田洋一, 木内喜孝, 高橋成一, 下瀬川徹

IBD Res　5　(2)　82-88　2011/06/10
Publisher: (株)先端医学社
ISSN： 1881-6533
Increased Expression of NKX2.3 mRNA Transcribed From Risk Haplotype for Inflammatory Bowel Disease in the Involved Colonic Mucosa

Takashi Arai, Yoichi Kakuta, Yoshitaka Kinouchi, Kenichi Negoro, Katsuya Endo, Hisashi Shiga, Seiichi Takahashi, Tooru Shimosegawa

GASTROENTEROLOGY　140　(5)　S270-S270　2011/05

ISSN： 0016-5085
大腸腫瘍に対するESDと腹腔鏡下手術との比較

志賀永嗣, 遠藤克哉, 高橋成一, 下平陽介, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 金澤義丈, 荒井壮, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　53　(Supplement 1)　910-910　2011/03/15
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
【クローン病の長期予後改善をめざして】クローン病の長期予後

木内喜孝, 角田洋一, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　108　(3)　381-387　2011/03
Publisher: (一財)日本消化器病学会
DOI： 10.11405/nisshoshi.108.381 　

ISSN： 0446-6586

eISSN： 1349-7693
【クローン病の長期予後改善をめざして】生物学的製剤によるクローン病の寛解維持療法 infliximab計画的維持投与の治療効果を中心に

遠藤克哉, 志賀永嗣, 角田洋一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　108　(3)　401-409　2011/03
Publisher: (一財)日本消化器病学会
DOI： 10.11405/nisshoshi.108.401 　

ISSN： 0446-6586

eISSN： 1349-7693
Long-term prognosis of Crohn's disease

Yoshitaka Kinouchi, Yoichi Kakuta, Seiichi Takahashi, Tooru Shimosegawa

Journal of Japanese Society of Gastroenterology　108　(3)　381-387　2011/03

DOI： 10.11405/nisshoshi.108.381 　

ISSN： 0446-6586
Maintenance therapy with biologic agents for Crohn's disease: Impact of scheduled maintenance therapy with infliximab

Katsuya Endo, Hisashi Shiga, Yoichi Kakuta, Seiichi Takahashi, Yoshitaka Kinouchi, Tooru Shimosegawa

Journal of Japanese Society of Gastroenterology　108　(3)　401-409　2011/03

DOI： 10.11405/nisshoshi.108.401 　

ISSN： 0446-6586
小腸狭窄性病変に対する診断アプローチ~バルーン内視鏡の有用性~

遠藤克哉, 黒羽正剛, 志賀永嗣, 角田洋一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　7th　2011

ISSN： 2189-9037
オートファジーとクローン病

高橋成一, 黒羽正剛, 角田洋一, 遠藤克哉, 志賀永嗣, 木内喜孝

IBD Research　2011
難治性炎症性腸管障害に関する調査研究日本人クローン病における疾患感受性遺伝子と寛解維持期間との関係について

木内喜孝, 角田洋一, 高橋成一, 根来健一, 遠藤克哉, 志賀久嗣, 下瀬川徹

難治性炎症性腸管障害に関する調査研究平成22年度総括・分担研究報告書　197-198　2011
IBDの疾患感受性遺伝子を知り,治療につなげるオートファジーとクローン病

高橋成一, 黒羽正剛, 角田洋一, 遠藤克哉, 志賀永嗣, 木内喜孝

IBD Res　5　(2)　96-103　2011
Publisher: (株)先端医学社
ISSN： 1881-6533
臨床に役立つ腸管免疫学の最新のトピックス III IBDの遺伝子異常―GWASがもたらした病態研究の糸口

木内喜孝, 荒井壮, 金澤義丈, 角田洋一, 遠藤克哉, 志賀永嗣, 高橋成一, 下瀬川徹

Intestine　15　(5)　415-421　2011

ISSN： 1883-2342
炎症性腸疾患への今日的アプローチ遺伝子異常面からみた炎症性腸疾患

角田洋一, 木内喜孝, 高橋成一, 下瀬川徹

成人病と生活習慣病　40　(12)　1351-1356　2010/12/15
Publisher: (株)東京医学社
ISSN： 1347-0418
遺伝子異常面からみた炎症性腸疾患 (特集炎症性腸疾患への今日的アプローチ) -- (病因・病態生理)

角田洋一, 木内喜孝, 高橋成一

成人病と生活習慣病　40　(12)　1351-1356　2010/12
Publisher: 東京医学社
ISSN： 1347-0418
慢性C型肝炎に合併した小腸原発T細胞性悪性リンパ腫の一例

黒羽正剛, 遠藤克哉, 長澤仁嗣, 諸井林太郎, 荒井壮, 井上淳, 近藤泰輝, 角田洋一, 根来健一, 相原裕之, 福島耕治, 高橋成一, 上野義之, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy　52　(Suppl.2)　2480-2480　2010/09
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
直腸原発follicular lymphomaの一例

黒羽正剛, 遠藤克哉, 長澤仁嗣, 諸井林太郎, 荒井壮, 木村智哉, 角田洋一, 梅村賢, 高橋秀一郎, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　107　2010

ISSN： 0446-6586
難治性炎症性腸管障害に関する調査研究日本人特有の疾患関連遺伝子解析 Allelic expression imbalanceを用いた感受性遺伝子機能解析

木内喜孝, 角田洋一, 高橋成一, 根来賢一, 植木紳夫, 遠藤克哉, 志賀永嗣, 下瀬川徹

難治性炎症性腸管障害に関する調査研究平成19-21年度総合研究報告書　124-125　2010
難治性炎症性腸管障害に関する調査研究日本人特有の疾患関連遺伝子解析 Allelic expression imbalanceを用いた感受性遺伝子機能解析

木内喜孝, 角田洋一, 高橋成一, 根来健一, 植木紳夫, 遠藤克哉, 志賀永嗣, 下瀬川徹

難治性炎症性腸管障害に関する調査研究平成21年度総括・分担研究報告書　118-119　2010
臨床検査の分子生物学第4回消化器領域における遺伝子多型検査

角田洋一, 木内喜孝, 遠藤克哉, 根来健一, 高橋成一, 下瀬川徹

分子消化器病　6　(4)　370-374　2009/12/01
Publisher: (株)先端医学社
ISSN： 1348-995X
炎症性腸疾患―最新知見―ゲノムワイド相関研究から明らかになった新しい治療標的

木内喜孝, 高橋成一, 角田洋一, 下瀬川徹

最新医学　64　(9)　1774-1780　2009/09/10
Publisher: 最新医学社
ISSN： 0370-8241
ここまで明らかになった!IBDの病因・病態 IBD genetics‐わが国と欧米の違い‐

根来健一, 角田洋一, 遠藤克也, 高橋成一, 木内喜孝, 下瀬川徹

IBD Res　3　(3)　205-215　2009/09/10
Publisher: (株)先端医学社
ISSN： 1881-6533
【炎症性腸疾患最新知見】基礎から臨床へゲノムワイド相関研究から明らかになった新しい治療標的

木内喜孝, 高橋成一, 角田洋一, 下瀬川徹

最新医学　64　(9)　1774-1780　2009/09
Publisher: (株)最新医学社
ISSN： 0370-8241
Genome-wide association studies in inflammatory bowel disease unravel a new molecular pathway

木内喜孝, 高橋成一, 角田洋一

最新医学　64　(9)　1774-1780　2009/09
Publisher: 最新医学社
ISSN： 0370-8241
クローン病感受性遺伝子TNFSF15遺伝子多型における機能解析

角田洋一, 木内喜孝, 植木紳夫, 遠藤克哉, 根来健一, 高橋成一, 下瀬川徹

東北医学雑誌　121　(1)　59-61　2009/06/25
Publisher: 東北医学会
ISSN： 0040-8700

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日本人のクローン病(CD)において2005年に遺伝子データベースが設定され、約8万SNPをマーカーとした大規模な相関解析により9番染色体長腕に存在するTNFSF15遺伝子が感受性遺伝子候補であると報告された。TNFSF15遺伝子の発現と遺伝子多型と発現量の変化について、その多型の機能的な解析をin vivoに近い状態で検討し、その結果を反映するvitro系を作成して遺伝子多型が発現制御に影響するメカニズムの解明を試みた。その結果、TNFSF15遺伝子のCDリスクアリルはTリンパ球特異的に転写活性が亢進していることがvivoに近い状態とvitroの両方で確認され、vitroでの検討でその変化をもたらす多型が5'領域にある-360Tアリルであることが予測された。またEMSAの結果から-360Tアリルに特異的な転写因子の結合が確認されたことから、CD非リスクアリルに何らかの抑制的な転写因子又はその複合体などの結合が考えられた。以上より、TNFSF15遺伝子多型がCDの感受性に影響する因子の一部を示していると考えられた。
炎症性腸疾患の新規治療を探る疾患感受性遺伝子解析は治療標的にたどり着けるか?

木内喜孝, 高橋成一, 角田洋一, 下瀬川徹

分子消化器病　6　(2)　117-122　2009/06/01
Publisher: (株)先端医学社
ISSN： 1348-995X
Genotype-Phenotype Analysis of the SNP (Rs6887695) Located Telomeric to Il12b Reveals Association with Colonic Disease of Japanese Crohn's Disease

Tomoya Kimura, Yoichi Kakuta, Yoshitaka Kinouchi, Seiichi Takahashi, Kenichi Negoro, Katsuya Endo, Ken Umemura, Hiroki Aizawa, Nobuo Ueki, Hisashi Shiga, Masaki Matsuura, Takashi Arai, Tooru Shimosegawa

GASTROENTEROLOGY　136　(5)　A208-A208　2009/05

ISSN： 0016-5085
Candidate Gene Analysis of KIR3DL1 in Japanese Ulcerative Colitis

Hiroki Aizawa, Yoshitaka Kinouchi, Kenichi Negoro, Yoichi Kakuta, Seiichi Takahashi, Katsuya Endo, Nobuo Ueki, Hisahi Shiga, Masaki Matsuura, Tomoya Kimura, Takashi Arai, Tooru Shimosegawa

GASTROENTEROLOGY　136　(5)　A212-A212　2009/05

ISSN： 0016-5085
クローン病の治療と長期予後経腸成分栄養によるクローン病緩解維持療法

高橋秀一郎, 高木承, 遠藤克哉, 角田洋一, 根来健一, 高橋成一, 木内喜孝

月刊消化器科　48　(3)　249-255　2009/03/28
Publisher: (有)科学評論社
ISSN： 0289-8756
日本人クローン病におけるIRGM遺伝子との相関解析

角田洋一, 相澤宏樹, 木村智哉, 黒羽正剛, 荒井壮, 梅村賢, 高橋秀一郎, 遠藤克哉, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　106　2009

ISSN： 0446-6586
【炎症性腸疾患の分子医学】遺伝子変異による発症メカニズム

角田洋一, 木内喜孝, 高橋成一, 下瀬川徹

BIO Clinica　23　(13)　1174-1177　2008/11
Publisher: (株)北隆館
ISSN： 0919-8237
colitic cancerに随伴するdysplasiaを拡大観察しえた1例

相澤宏樹, 高木承, 樋渡信夫, 高橋秀一郎, 梅村賢, 遠藤克哉, 角田洋一, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹

胃と腸　43　(9)　1374-1374　2008/08/25
Publisher: (株)医学書院
DOI： 10.11477/mf.1403101454 　

ISSN： 0536-2180

eISSN： 1882-1219
IBDの最新の話題~基礎編~第6回疾患関連遺伝子はどこまで明らかにされたか

木内喜孝, 角田洋一, 野村栄樹, 高橋成一, 下瀬川徹

IBD Res　2　(2)　149-154　2008/06/10
Publisher: (株)先端医学社
ISSN： 1881-6533
IBDの最新の話題基礎編疾患関連遺伝子はどこまで明らかにされたか

木内喜孝, 角田洋一, 野村栄樹, 高橋成一, 下瀬川徹

IBD Research　2　(2)　149-154　2008/06
Publisher: (株)先端医学社
ISSN： 1881-6533
Lack of association between IRGM and Crohn's disease in Japanese patients demonstrates population-specific differences in inflammatory bowel disease

Hiroki Aizawa, Yoshitaka Kinouchi, Kenichi Negoro, Yoichi Kakuta, Eiki Nomura, Seiichi Takahashi, Tooru Shimosegawa

GASTROENTEROLOGY　134　(4)　A460-A460　2008/04

ISSN： 0016-5085
クローン病感受性遺伝子TL1Aの発現制御に関する検討

遠藤克哉, 木内喜孝, 荒井壮, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 角田洋一, 松村吉史, 横山大, 梅村賢, 野村栄樹, 根来健一, 相原裕之, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　105　2008

ISSN： 0446-6586
家族性大腸腺腫症(FAP)の術後回腸人工肛門に発生した小腸癌の1例

梅村賢, 野村栄樹, 荒井壮, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 遠藤克哉, 角田洋一, 松村吉史, 横山大, 根来健一, 高木承, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　105　2008

ISSN： 0446-6586
炎症性腸疾患の分子医学「遺伝子変異による発症メカニズム」

角田洋一, 木内喜孝, 高橋成一, 下瀬川徹

BioClinica　23　(13)　18-21　2008
炎症性腸疾患の分子医学 2 遺伝子変異による発症メカニズム

角田洋一, 木内喜孝, 高橋成一, 下瀬川徹

Bio Clin　23　(13)　1174-1177　2008

ISSN： 0919-8237
遺伝子・蛋白の網羅的解析から消化器疾患に迫る多遺伝子性疾患の遺伝的解析―IBDを中心に―

木内喜孝, 角田洋一, 遠藤克哉, 高橋成一, 下瀬川徹

分子消化器病　4　(3)　213-219　2007/09/01
Publisher: (株)先端医学社
ISSN： 1348-995X
炎症性腸疾患 UP TO DATE 炎症性腸疾患の疾患感受性遺伝子

角田洋一, 高橋成一, 木内喜孝, 下瀬川徹

綜合臨床　56　(8)　2451-2453　2007/08/01
Publisher: (株)永井書店
ISSN： 0371-1900
Susceptibility gene of inflammatory bowel disease

角田洋一, 高橋成一, 木内喜孝

綜合臨床　56　(8)　2451-2453　2007/08
Publisher: 永井書店
ISSN： 0371-1900
クローン病診療の新展開クローン病診療の進歩クローン病の遺伝子異常と遺伝子情報の治療応用

角田洋一, 野村栄樹, 根来健一, 木内喜孝, 高橋成一, 下瀬川徹

モダンフィジシャン　27　(7)　901-904　2007/07/15
Publisher: (株)新興医学出版社
ISSN： 0913-7963
【クローン病診療の進歩】クローン病診療の新展開クローン病の遺伝子異常と遺伝子情報の治療応用

角田洋一, 野村栄樹, 根来健一, 木内喜孝, 高橋成一, 下瀬川徹

Modern Physician　27　(7)　901-904　2007/07
Publisher: (株)新興医学出版社
ISSN： 0913-7963
Crohn病患者の肛門周囲膿瘍に対するプルリフロキサシン(PUFX)の有用性の検討

梅村賢, 高木承, 高橋秀一郎, 横山大, 松浦真樹, 植木紳夫, 相沢宏樹, 志賀永嗣, 遠藤克哉, 松村吉史, 角田洋一, 土佐正規, 持田淳弘, 阿部浩子, 今井豪, 佐藤雄一郎, 野村栄樹, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

Pharma Med　25　(6)　181-184　2007/06/10
Publisher: (株)メディカルレビュー社
ISSN： 0289-5803

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Crohn病に合併した肛門周囲膿瘍14例に対してPUFXを7〜37日間投与し、治療効果をPerianal disease activity index(PDAI)で評価した。PDAIの平均スコアは治療前に比べて治療後有意に低下(改善)し、項目別では[排膿][疼痛/活動性][硬変の程度]のスコアが有意に低下した。
HLA-Drb1 may influence disease phenotype in Japanese patients with ulcerative colitis

Yoichi Kakuta, Yoshifumi Matsumura, Eiki Nomura, Kenichi Negoro, Sho Takagi, Seiichi Takahashi, Yoshitaka Kinouchi, Tooru Shimosegawa

GASTROENTEROLOGY　132　(4)　A450-A451　2007/04

ISSN： 0016-5085
Analysis of genetic interaction between Tnfsf15 and dqbI*04 in Japanese patients with Crohn's disease

Yoichi Kakuta, Yoshitaka Kinouchi, Kenichi Negoro, Eiki Nomura, Sho Takagi, Seitchi Takahashi, Toont Shimosegawa

GASTROENTEROLOGY　132　(4)　A447-A447　2007/04

ISSN： 0016-5085
Tnfsf15 genotype is associated with anal lesions and frequent relapse in Crohn's disease

Eiki Nomura, Masaki Matsuura, Yoichi Kakuta, Kenichi Negoro, Sho Takagi, Seiichi Takahashi, Yoshitaka Kinouchi, Tooru Shimosegawa

GASTROENTEROLOGY　132　(4)　A450-A450　2007/04

ISSN： 0016-5085
PHA刺激時ヒトTリンパ球においてクローン病リスクTNFSF15対立遺伝子は非リスク対立遺伝子に比較し発現が亢進する

角田洋一, 木内喜孝, 根来健一, 木村智哉, 松浦真樹, 植木紳夫, 相澤宏樹, 志賀永嗣, 遠藤克哉, 松村吉史, 土佐正規, 持田淳弘, 野村栄樹, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　104　2007

ISSN： 0446-6586
造血幹細胞移植後腸炎における大腸内視鏡所見による鑑別診断能の検討

遠藤克哉, 高木承, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 角田洋一, 松村吉史, 土佐正規, 持田淳弘, 横山大, 野村栄樹, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy　49　(Suppl.2)　2358-2358　2007
Publisher: (一社)日本消化器内視鏡学会
ISSN： 0387-1207

eISSN： 1884-5738
難治性炎症性腸管障害に関する調査研究〈疾患関連遺伝子の追究〉遺伝子多型を用いた炎症性腸疾患感受性・疾患修飾遺伝子の検討

木内喜孝, 杉村一仁, 角田洋一, 松浦真樹, 土佐正規, 野村栄樹, 高橋成一, 根来健一, 高木承, 下瀬川徹, 井上詠

難治性炎症性腸管障害に関する調査研究平成18年度研究報告書　99-101　2007
Analysis of positional candidate gene HLA-B in Japanese patients with ulcerative colitis

Eiki Nomura, Yoshitaka Kinouchi, Go Imai, Yoichi Kakuta, Hiroko Abe, Masaki Tosa, Atsuhiro Mochida, Kenichi Negoro, Sho Takagi, Seiichi Takahashi, Nobuo Hiwatashi, Tooru Shimosegawa

GASTROENTEROLOGY　130　(4)　A588-A588　2006/04

ISSN： 0016-5085
Candidate gene analysis of RUNX1 and PAdi4 in Japanese patients with inflammatory bowel disease

Masaki Tosa, Yoshitaka Kinouchi, Kenichi Negro, Eiki Nomura, Yoichi Kakuta, Hiroko Abe, Go Imani, Atsuhiro Mochida, Sho Takagi, Seiichi Takahashi, Toom Shimosegawa

GASTROENTEROLOGY　130　(4)　A593-A593　2006/04

ISSN： 0016-5085
Case-control association study of TNFSF15 Polymorphisms in the Japanese patients with Crohn's disease and ulcerative colitis

Yoichi Kakuta, Yoshitaka Kinouchi, Kenichi Negoro, Masaki Matsuura, Hiroko Abe, Go Imai, Atsuhiro Mochida, Masaki Tosa, Eiki Nomura, Sho Takagi, Seiichi Takahasi, Tooru Shimosegawa

GASTROENTEROLOGY　130　(4)　A585-A585　2006/04

ISSN： 0016-5085
潰瘍性大腸炎緩解維持療法におけるメサラジン週末注腸療法の有用性

横山大, 高木承, 栗山進一, 高橋秀一郎, 高橋広喜, 岩渕正広, 志賀永嗣, 松村吉史, 角田洋一, 阿部浩子, 今井豪, 土佐正規, 持田淳弘, 佐藤雄一郎, 野村栄樹, 根来健一, 高橋成一, 木内喜孝, 辻一郎, 下瀬川徹

日本消化器病学会雑誌　103　(臨増総会)　A297-A297-A297　2006
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
日本人クローン病とTL1A遺伝子多型との相関について

角田洋一, 木内喜孝, 根来健一, 野村栄樹, 松浦真樹, 植木紳夫, 相澤宏樹, 志賀永嗣, 遠藤克哉, 松村吉史, 土佐正規, 阿部浩子, 持田淳弘, 今井豪, 佐藤雄一郎, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　103　(臨増総会)　A204-A204-A204　2006
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
Cronkhite-Canada症候群と膜性腎症を合併した2例

志賀永嗣, 高木承, 野村栄樹, 相澤宏樹, 植木紳夫, 松浦真樹, 松村吉史, 角田洋一, 遠藤克哉, 土佐正規, 阿部浩子, 持田淳弘, 今井豪, 佐藤雄一郎, 横山大, 高橋成一, 木内喜孝, 下瀬川徹, 尾花伸哉

日本消化器病学会雑誌　103　(臨増大会)　A876-A876-A876　2006
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
日本人炎症性腸疾患とBTNL2遺伝子多型との相関について

持田淳弘, 木内喜孝, 根来健一, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 遠藤克哉, 角田洋一, 松村吉史, 阿部浩子, 今井豪, 土佐正規, 佐藤雄一郎, 横山大, 野村栄樹, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　103　(臨増大会)　A848-A848-A848　2006
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
日本人潰瘍性大腸炎とTNFSF15遺伝子多型との相関について

角田洋一, 木内喜孝, 根来健一, 野村栄樹, 松浦真樹, 植木紳夫, 相澤宏樹, 志賀永嗣, 遠藤克哉, 松村吉史, 土佐正規, 阿部浩子, 持田淳弘, 今井豪, 佐藤雄一郎, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　103　(臨増大会)　A847-A847-A847　2006
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693
A CASE OF FECALITH IN THE RECTUM AFTER LOOP SIGMOID COLOSTOMY ASSOCIATED WITH CROHN’S DISEASE

野村栄樹, 高木承, 志賀永嗣, 今井豪, 相澤宏樹, 松村吉史, 角田洋一, 阿部浩子, 高橋成一, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy　48　(12)　2799-2805　2006
Publisher: (一社)日本消化器内視鏡学会
DOI： 10.11280/gee1973b.48.2799 　

ISSN： 0387-1207

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39歳男性。患者は23歳時にクローン病と診断され、前医にて3回の小腸切除術を受けた。その後、35歳時に肛門周囲膿瘍、難治性痔瘻で著者らの施設を受診、S状結腸瘻(双孔式人工肛門)造設術を受けた。今回、肛門部痛、残便感で受診となり、大腸内視鏡ではS状結腸瘻より口側に異常はなかったものの、残存直腸内には約7cmの糞石が2個認められた。破砕を試みるもスネアでの把持が不可能であり、肛門部は線維性狭窄を来し肛門からの排泄は不可能であった。注腸造影を行なったところ、直腸内の口側に70×55mm大、肛門側に68×58mm大の陰影欠損がみられ、CTでは直腸内に高吸収結節影として描出される2個の糞石を認めた。直腸切断術を勧めるも患者に拒否され、そのため内視鏡下に45mm径のジャンボスネアと電気水圧衝撃波法を併用して糞石を破砕・除去した。更に再発防止で定期的なグリセリン浣腸を行なった結果、以後、再発はみられていない。
抗TNF-α抗体療法を施行したクローン病症例の検討

高橋秀一郎, 高木承, 横山大, 遠藤克哉, 松村吉史, 角田洋一, 阿部浩子, 今井豪, 土佐正規

日本消化器病学会雑誌　102　2005

ISSN： 0446-6586
日本人潰瘍性大腸炎とHLA-B遺伝子との相関解析

今井豪, 木内喜孝, 野村栄樹, 角田洋一, 松村吉史, 遠藤克哉, 土佐正規, 阿部浩子, 持田淳弘, 佐藤雄一郎, 白木学, 高橋秀一郎, 横山大, 根来健一, 高木承, 相原裕之, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　102　(臨増大会)　A760-A760-A760　2005
Publisher: (一財)日本消化器病学会
ISSN： 0446-6586

eISSN： 1349-7693

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Books and Other Publications 2

これだけは読んでおきたい！消化器医のための重要論文240篇

角田洋一

2019/11
Atlas of Diagnostic imaging on Digestive Diseases

Yoichi Kakuta

2017/07

Presentations 118

小腸疾患診療の現状と今後の展望当科で経験した後天性von Willebrand症候群による小腸出血症例の検討

諸井林太郎, 角田洋一, 正宗淳

日本消化器病学会雑誌　2019/03
潰瘍性大腸炎に対するゴリムマブの使用成績と位置付け

小野寺基之, 志賀永嗣, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　2019/02
当院における免疫チェックポイント阻害剤による腸炎の難治例も含めた治療効果,内視鏡所見に関する検討

泉山泰宏, 志賀永嗣, 小野寺基之, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　2019/02
当院で経験した小腸大腸病変を有するT細胞リンパ腫の臨床所見と内視鏡所見の検討

岡本大祐, 小野寺基之, 阿部出, 半田智之, 枡悠太郎, 鈴木郁, 菱沼佳純, 中野健, 泉山泰宏, 市川遼, 永井博, 松本信, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤善丈, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　2019/02
乾癬性関節炎、掌蹠膿疱症性関節炎治療中に発症した小腸原発メトトレキサート関連リンパ増殖性疾患の1例

阿部出, 小野寺基之, 泉山泰宏, 市川遼, 岡本大祐, 中野健, 永井博, 松本信, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　2019/02
免疫チェックポイント阻害薬時代の消化管診断と治療当院における免疫チェックポイント阻害剤による腸炎の難治例も含めた治療効果、内視鏡所見に関する検討

泉山泰宏, 志賀永嗣, 小野寺基之, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　2019/02
炎症性腸疾患に対する新規治療薬の位置付け潰瘍性大腸炎に対するゴリムマブの使用成績と位置付け

小野寺基之, 志賀永嗣, 内藤健夫, 諸井林太郎, 黒羽正剛, 金澤義丈, 木村智哉, 角田洋一, 木内喜孝, 正宗淳

日本消化管学会雑誌　2019/02
後天性von Willebrand症候群により小腸出血をきたしたと考えられ内視鏡的止血術を施行した2例

鈴木郁, 諸井林太郎, 阿部出, 半田智之, 菱沼佳純, 枡悠太郎, 泉山泰宏, 市川遼, 岡本大祐, 中野健, 永井博, 小野寺基之, 黒羽正剛, 金澤義丈, 志賀永嗣, 角田洋一, 木内喜孝, 正宗淳

日本消化器病学会東北支部例会プログラム・抄録集　2019/02
目指せ!消化器病専門医-初期研修医からの報告繰り返す発熱・腹痛発作を契機に診断しMEFV遺伝子変異を確認しえた家族性地中海熱の一例

片山智文, 遠藤克哉, 岡本大祐, 角田洋一, 津守孝彦, 佐藤格, 佐藤倫紀, 福士大介, 小岩井明信, 支倉翔太郎, 二瓶憲, 支倉さやか, 近藤史帆, 小暮高之, 高須充子, 廣田衛久, 目黒敬義, 佐藤賢一

日本消化器病学会東北支部例会プログラム・抄録集　2019/02
NUDT15 genotypeに基づく炎症性腸疾患チオプリン療法の最適化

高川哲也, 角田洋一, 中村志郎

日本消化器病学会雑誌　2018/10
潰瘍性大腸炎に対するインフリキシマブ、アダリムマブの治療成績の比較検討

小野寺基之, 角田洋一, 正宗淳

日本消化器病学会雑誌　2018/10
当科で経験したクロンカイトカナダ症候群の3例

枡悠太郎, 諸井林太郎, 小野寺基之, 内藤健夫, 黒羽正剛, 木村智哉, 金澤義丈, 角田洋一, 小池智幸, 正宗淳, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2018/10
炎症性腸疾患における既存治療を見直すチオプリンの副作用を予測するNUDT15遺伝子多型検査の有用性について

角田洋一, 木内喜孝, 正宗淳, MENDEL Study Group

日本消化器病学会雑誌　2018/10
炎症性腸疾患患者の骨塩低下は臨床的なリスク要因が少ない患者ほど遺伝的影響を強く受ける

横山直信, 内藤健夫, 角田洋一, 木内喜孝, 小池智幸, 正宗淳, 下瀬川徹

日本消化器病学会雑誌　2018/10
潰瘍性大腸炎緩解維持療法の現状 NUDT15 R139C C/Tヘテロ症例におけるチオプリン製剤を用いた潰瘍性大腸炎の治療成績

渡辺憲治, 高川哲也, 角田洋一, 藤森絢子, 小島健太郎, 小柴良司, 藤本晃士, 佐藤寿行, 河合幹夫, 上小鶴孝二, 横山陽子, 宮嵜孝子, 樋田信幸, 堀和敏, 池内浩基, 中村志郎

日本大腸肛門病学会雑誌　2018/09
潰瘍性大腸炎に対するインフリキシマブ、タクロリムスによる寛解導入療法後の粘膜治癒に関する長期予後の検討

小野寺基之, 角田洋一, 正宗淳

Gastroenterological Endoscopy　2018/04
当院における免疫チェックポイント阻害剤による腸炎の現状

泉山泰宏, 木村智哉, 市川遼, 岡本大祐, 中野健, 松本信, 永井博, 千葉宏文, 横山直信, 山本勝利, 下山雄丞, 内藤健夫, 小野寺基之, 諸井林太郎, 黒羽正剛, 金澤義丈, 角田洋一, 木内喜孝, 小池智幸, 正宗淳, 下瀬川徹

Gastroenterological Endoscopy　2018/04
炎症性腸疾患に対する抗TNF-α抗体治療薬導入により見えてきた臨床課題 Crohn病に対する抗TNF-α抗体の長期的治療成績から考える最適な投与戦略

諸井林太郎, 遠藤克哉, 角田洋一

日本消化器病学会雑誌　2018/03
大腸ESD術中の粘膜下層線維化リスク因子についての検討―術前生検により粘膜下層の線維化をきたすのか?―

黒羽正剛, 志賀永嗣, 金澤義文, 半田智之, 市川遼, 小野寺基之, 内藤健夫, 諸井林太郎, 木村智哉, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会雑誌　2018/02/01
免疫チェックポイント阻害薬が原因と考えられた腸炎の2例

泉山泰宏, 木村智哉, 中野健, 岡本大祐, 市川遼, 永井博, 松本信, 下山雄丞, 千葉宏文, 横山直信, 山本勝利, 小野寺基之, 内藤健夫, 黒羽正剛, 金澤義丈, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会雑誌　2018/02/01
Diplotype分類に基づいたNUDT15活性レベルと炎症性腸疾患患者のチオプリン誘発性白血球減少症及び全脱毛の相関

高川哲也, 佐藤寿行, 角田洋一, 西尾昭宏, 河合幹夫, 上小鶴孝二, 横山陽子, 木田裕子, 宮嵜孝子, 飯室正樹, 樋田信幸, 堀和敏, 池内浩基, 中村志郎

日本消化器病学会雑誌　2017/09
日本人IBD患者の骨粗鬆症リスク因子の解明と遺伝的背景の検討

横山直信, 角田洋一, 小野寺基之, 内藤健夫, 平本圭一郎, 黒羽正剛, 金澤義丈, 木村智哉, 遠藤克哉, 木内善孝, 下瀬川徹

日本消化器病学会雑誌　2017/09
抗TNFα製剤が著効した潰瘍性大腸炎関連小腸炎の2例

千葉宏文, 内藤健夫, 木村智哉, 泉山泰宏, 中野健, 岡本大祐, 市川遼, 松本信, 永井博, 横山直信, 山本勝利, 小野寺基之, 日下順, 平本圭一郎, 黒羽正剛, 金澤義丈, 角田洋一, 遠藤克哉, 木内喜孝, 藤島史喜, 下瀬川徹

Gastroenterological Endoscopy (Web)　2017/04
内視鏡を用いた腸内微生物叢へのアプローチ潰瘍性大腸炎患者における大腸部位別の腸内細菌叢と内視鏡的活動性との関係性について

角田洋一, 横山直信, 下瀬川徹

Gastroenterological Endoscopy　2017/04
潰瘍性大腸炎に対するタクロリムス治療の治療効果とCYP3A5、ABCB1遺伝子多型との関連

小野寺基之, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2017/03
潰瘍性大腸炎患者における大腸部位別の腸内細菌叢と内視鏡的活動性との関係性について

角田洋一, 横山直信, 下瀬川徹

Gastroenterological Endoscopy (Web)　2017
von Hippel‐Lindau病に発症した小腸GISTの一例

小野寺基之, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy (Web)　2017
肥厚性皮膚骨膜症を合併した非特異性多発性小腸潰瘍(CEAS)の一例

永井博, 木村智哉, 松本信, 下山雄丞, 千葉宏文, 山本勝利, 横山直信, 小野寺基之, 日下順, 内藤健夫, 川上瑤子, 平本圭一郎, 黒羽正剛, 金澤義丈, 角田洋一, 遠藤克哉, 梅野淳嗣, 江崎幹宏, 木内喜孝, 下瀬川徹

Gastroenterological Endoscopy (Web)　2017
潰瘍性大腸炎に対するタクロリムス治療におけるCYP3A5遺伝子多型を予測した投与量最適化の工夫

小野寺基之, 遠藤克哉, 平本圭一郎, 黒羽正剛, 金澤義丈, 木村智哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　2017
炎症性腸疾患患者における骨量減少に関わるリスク因子の検討

横山直信, 角田洋一, 黒羽正剛, 木村智哉, 遠藤克哉, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2016/09
潰瘍性大腸炎に対するタクロリムス治療による腎機能障害の検討

小野寺基之, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2016/09
増え続ける炎症性腸疾患～検査データから考える治療の選択とタイミング～ Invited

角田洋一

第14回メディエンスフォーラム２０１６　2016/07/09
クローン病術後症例の中長期予後に対する生物学的製剤の治療効果

日下順, 志賀永嗣, 永井博, 松本信, 下山雄丞, 千葉宏文, 山本勝利, 横山直信, 小野寺基之, 内藤健夫, 川上瑶子, 只野敏浩, 黒羽正剛, 木村智哉, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2016/03
IBDモニタリングツールをいかに使いこなすか? NUDT15 R139C多型検査を用いたチオプリン導入ストラテジーの検討

角田洋一, 内藤健夫, 下瀬川徹

日本消化器病学会雑誌　2016/03
高齢者潰瘍性大腸炎の手術適応についての検討

黒羽正剛, 遠藤克哉, 内藤健夫, 日下順, 小野寺基之, 只野敏浩, 川上瑶子, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　2016
潰瘍性大腸炎に合併した静脈血栓症7例の検討

只野敏浩, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　2016
5ASA不耐潰瘍性大腸炎の治療経過と予後の検討

木村智哉, 遠藤克哉, 永井博, 松本信, 千葉宏文, 横山直信, 下山雄丞, 山本勝利, 内藤健夫, 小野寺基之, 日下順, 川上瑶子, 只野敏浩, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　2016
炎症性腸疾患(IBD)の最新治療 2 炎症性腸疾患関連遺伝子について

角田洋一, 木内喜孝, 下瀬川徹

Bio Clin　2015/12/10
当院の高齢IBDの特徴

平本圭一郎, 平本圭一郎, 黒羽正剛, 下山雄丞, 千葉宏文, 山本勝利, 横山直信, 小野寺基之, 日下順, 内藤健夫, 川上瑤子, 只野敏浩, 木村智哉, 志賀永嗣, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

日本消化器病学会大会(Web)　2015/09
BiologicsナイーブのCrohn病に対するInfliximab・Adalimumabの長期的治療成績

遠藤克哉, 山本勝利, 木村智哉, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会大会(Web)　2015/09
クローン病に対するInfliximab倍量投与の中長期予後

志賀永嗣, 遠藤克哉, 千葉宏文, 下山雄丞, 横山直信, 山本勝利, 内藤健夫, 日下順, 小野寺基之, 川上瑶子, 只野敏浩, 平本圭一郎, 松下勝則, 宮澤輝子, 黒羽正剛, 木村智哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会大会(Web)　2015/09
肛門管にかかる大腸上皮性腫瘍に対するESDの治療成績

黒羽正剛, 志賀永嗣, 木村智哉, 諸井林太郎, 横山直信, 山本勝利, 千葉宏文, 下山雄丞, 内藤健夫, 日下順, 小野寺基之, 只野敏浩, 川上瑶子, 平本圭一郎, 松下勝則, 宮澤輝子, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2015/04/15
大腸憩室出血症例に対する内視鏡施行タイミングと臨床経過に関する検討

下山雄丞, 遠藤克哉, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2015/04/15
潰瘍性大腸炎に対するタクロリムス治療におけるUCEISを用いた長期予後の予測

小野寺基之, 遠藤克哉, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2015/04/15
アダリムマブ投与を行った潰瘍性大腸炎術後に発症した難治性小腸炎の一例

内藤健夫, 遠藤克哉, 小野寺基之, 日下順, 川上瑶子, 只野敏浩, 平本圭一郎, 松下勝則, 宮澤輝子, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2015/04/15
当院において死亡転機を辿ったクローン病症例の臨床的特徴

横山直信, 遠藤克哉, 千葉宏文, 山本勝利, 下山雄丞, 内藤健夫, 日下順, 小野寺基之, 只野敏浩, 川上瑤子, 松下勝則, 宮澤輝子, 平本圭一郎, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 木内善孝, 下瀬川徹

日本消化器病学会雑誌　2015/03
高齢者潰瘍性大腸炎(UC)の臨床的特徴と問題点

黒羽正剛, 遠藤克哉, 横山直信, 山本勝利, 千葉宏文, 下山雄丞, 内藤健夫, 日下順, 小野寺基之, 只野敏浩, 川上瑶子, 平本圭一郎, 松下勝則, 宮澤輝子, 木村智哉, 志賀永嗣, 角田洋一, 根来健一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2015/03
東日本大震災から長期間にわたる炎症性腸疾患患者の活動度の変化

宮澤輝子, 志賀永嗣, 平本圭一郎, 松下勝則, 黒羽正剛, 木村智哉, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2015/03
肛門管mixed adenoneuroendocrine carcinoma(MANEC)の一例

内藤健夫, 黒羽正剛, 永井博, 松本信, 横山直信, 千葉宏文, 山本勝利, 日下順, 小野寺基之, 川上瑶子, 只野敏浩, 木村智哉, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

早期大腸癌研究会プログラム・抄録集　2015
初発クローン病における上部消化管病変の頻度と予後についての検討

下山雄丞, 遠藤克哉, 小野寺基之, 日下順, 内藤健夫, 川上瑶子, 只野敏浩, 平本圭一郎, 松下勝則, 宮澤輝子, 黒羽正剛, 木村智哉, 志賀永嗣, 角田洋一, 飯島克則, 小池智幸, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　2015
大腸ESDにおける導入時の治療成績と安全性―胃ESDの経験は必須か?―

志賀永嗣, 黒羽正剛, 遠藤克哉, 千葉宏文, 横山直信, 下山雄丞, 山本勝利, 内藤健夫, 日下順, 小野寺基之, 川上瑶子, 只野敏浩, 平本圭一郎, 松下勝則, 宮澤輝子, 木村智哉, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　2015
当科におけるクローン病に対するアダリムマブの治療成績

遠藤克哉, 松下勝則, 志賀永嗣, 木村智哉, 黒羽正剛, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　2015
TNFSF15高発現アリルは疾患の重症度や治療反応性に関与する

角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2014/09/10
UCEIS (Ulcerative Colitis Endoscopic Index of Severity)を用いた近年の潰瘍性大腸炎手術例の特徴

小野寺基之, 遠藤克哉, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2014/09/10
難治性クローン病病態から考えた治療アプローチ TNFSF15高発現アリルは疾患の重症度や治療反応性に関与する

角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2014/09
消化器診療に遺伝子多型検査は有用か？ Invited

角田洋一

奥州消化器病研究会勉強会　2014/06/28
腸管限局性と考えられた大腸AA型アミロイドーシスの2例

川上瑶子, 黒羽正剛, 小野寺基之, 日下順, 内藤健夫, 只野敏浩, 平本圭一郎, 松下勝則, 宮澤輝子, 下平陽介, 志賀永嗣, 遠藤克哉, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2014/04/15
歯状線に接した直腸上皮性腫瘍に対するESDの有用性と安全性の検討

只野敏浩, 志賀永嗣, 内藤健夫, 日下順, 小野寺基之, 川上瑤子, 松下勝則, 宮澤輝子, 平本圭一郎, 下平陽介, 黒羽正剛, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2014/04/15
外国人留学生に発症し,大腸内視鏡所見が診断に大きく寄与した腸結核の一例

小野寺基之, 遠藤克哉, 日下順, 内藤健夫, 川上瑤子, 只野敏弘, 平本圭一郎, 松下勝則, 宮澤輝子, 下平陽介, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2014/04/15
遺伝子多型とIBD診療

角田洋一

レミケード最新情報報告会２０１４in仙台　2014/02/13
腸管ベーチェット病と単純性潰瘍の臨床的相違点に関する検討

日下順, 遠藤克哉, 小野寺基之, 内藤健夫, 川上瑶子, 只野敏浩, 奈良志博, 平本圭一郎, 松下勝則, 宮澤輝子, 下平陽介, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会大会(Web)　2014
粘膜下層癌を伴った大腸鋸歯状病変の1例

日下順, 志賀永嗣, 黒羽正剛, 木村智哉, 角田洋一, 遠藤克哉, 木内喜孝, 下瀬川徹

早期大腸癌研究会プログラム・抄録集　2014
タクロリムス・インフリキシマブの短期・長期成績から考える難治性潰瘍性大腸炎の治療戦略

遠藤克哉, 志賀永嗣, 黒羽正剛, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　2014
ESD初学者による大腸ESD導入時の治療成績と安全性

志賀永嗣, 遠藤克哉, 黒羽正剛, 内藤健夫, 日下順, 小野寺基之, 川上瑶子, 只野敏浩, 奈良志博, 松下勝則, 宮澤輝子, 下平陽介, 角田洋一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　2014
Clinical courses and pregnancy outcomes in Japanese women with inflammatory bowel disease

遠藤克哉, 高橋成一, 下平陽介, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 荒井壮, 金澤義丈, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2011/11

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炎症性腸疾患(IBD)と妊娠・出産の相互関係について、本邦の患者を対象とした報告はいまだ少ない。本研究では、最近10年間に当院で経験したIBD合併妊娠54例・73回(潰瘍性大腸炎38例・49回、クローン病16例・24回)の臨床経過を解析した。解析結果から、妊娠がIBDに与える影響は少ないが、クローン病は活動性が高い状態で妊娠した場合には増悪する可能性が高いと考えられた。一方、IBDが妊娠に与える影響も少ないが、潰瘍性大腸炎活動期妊娠では「妊娠・出産異常」率が高い傾向にあった。IBDでは寛解期妊娠が望ましく、妊娠中には安全性が高い薬剤を用いた治療を継続するべきと考えられた。(著者抄録)
日本人炎症性腸疾患患者におけるXBP1遺伝子の解析

長澤仁嗣, 角田洋一, 下平陽介, 諸井林太郎, 黒羽正剛, 荒井壮, 金澤義丈, 志賀永嗣, 遠藤克哉, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2011/09/15
潰瘍性大腸炎合併妊娠,出産に関する臨床的検討

遠藤克哉, 高橋成一, 下平陽介, 諸井林太郎, 長澤仁嗣, 黒羽正剛, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2011/09/15
クローン病合併妊娠・出産に関する臨床的検討

遠藤克哉, 高橋成一, 下平陽介, 諸井林太郎, 長澤仁嗣, 黒羽正剛, 荒井壮, 金澤義丈, 志賀永嗣, 角田洋一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2011/03/15
Infliximab投与中にサイトメガロウイルス初感染を生じたクローン病の一例

金澤義丈, 下平陽介, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 荒井壮, 志賀永嗣, 遠藤克哉, 角田洋一, 高橋成一, 木内喜孝

日本消化器病学会雑誌　2011/03/15
日本人潰瘍性大腸炎患者におけるNKX2‐3リスクハプロタイプの同定と機能解析

荒井壮, 木内喜孝, 角田洋一, 下平陽介, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 金澤義丈, 志賀永嗣, 遠藤克哉, 根来健一, 相原裕之, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2011/03/15
小腸狭窄性病変に対する診断アプローチ~バルーン内視鏡の有用性~

遠藤克哉, 黒羽正剛, 志賀永嗣, 角田洋一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化管学会総会学術集会プログラム・抄録集　2011
日本人クローン病感受性候補遺伝子TNFSF15,HLA‐DQB1,IL12Bと再燃率との関連について

角田洋一, 木内喜孝, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 荒井壮, 木村智哉, 志賀永嗣, 遠藤克哉, 根来健一, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2010/09/15
白血病に対する臍帯血移植を契機に寛解に至ったCrohn病の一例

荒井壮, 遠藤克哉, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 角田洋一, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2010/09/15
collagenous colitisにおけるNarrow Band Imagingを用いた拡大内視鏡所見の検討

諸井林太郎, 遠藤克哉, 長澤仁嗣, 黒羽正剛, 荒井壮, 木村智哉, 志賀永嗣, 梅村賢, 高橋秀一郎, 角田洋一, 根来健一, 高木承, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2010/09/10
慢性C型肝炎に合併した小腸原発T細胞性悪性リンパ腫の一例

黒羽正剛, 遠藤克哉, 長澤仁嗣, 諸井林太郎, 荒井壮, 井上淳, 近藤泰輝, 角田洋一, 根来健一, 相原裕之, 福島耕治, 高橋成一, 上野義之, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2010/09/10
日本人クローン病におけるIL12Bリスクハプロタイプの同定と機能解析

木村智哉, 角田洋一, 遠藤克哉, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2010/03/15
術中内視鏡検査が腸管切除範囲決定に有用であった多発性小腸輪状狭窄を呈した3例

諸井林太郎, 遠藤克哉, 長澤仁嗣, 黒羽正剛, 荒井壮, 木村智哉, 高橋秀一郎, 梅村賢, 角田洋一, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2010/03/15
直腸原発follicular lymphomaの一例

黒羽正剛, 遠藤克哉, 長澤仁嗣, 諸井林太郎, 荒井壮, 木村智哉, 角田洋一, 梅村賢, 高橋秀一郎, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2010/03/15
日本人IBDにおけるNKX2‐3の感受性候補遺伝子解析

荒井壮, 角田洋一, 長澤仁嗣, 諸井林太郎, 黒羽正剛, 木村智哉, 遠藤克哉, 梅村賢, 高橋秀一郎, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2010/03/15
腺癌と神経内分泌腫瘍が混在した直腸腫瘍の1例

志賀永嗣, 遠藤克哉, 角田洋一, 高橋成一, 木内喜孝

早期大腸癌研究会プログラム・抄録集　2010
経過中にサイトメガロウイルス感染を合併したクローン病の1例

志賀永嗣, 遠藤克哉, 木内喜孝, 高橋成一, 根来健一, 角田洋一, 相澤宏樹, 植木紳夫, 松浦真樹, 木村智哉, 荒井壮, 黒羽正剛, 下瀬川徹

日本消化器病学会雑誌　2009/09/15
インフリキシマブ投与後にleukocytoclastic vasculitisを発症したクローン病の一例

松浦真樹, 黒羽正剛, 荒井壮, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 梅村賢, 高橋秀一郎, 遠藤克哉, 角田洋一, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2009/09/15
日本人クローン病におけるIRGM遺伝子との相関解析

角田洋一, 相澤宏樹, 木村智哉, 黒羽正剛, 荒井壮, 梅村賢, 高橋秀一郎, 遠藤克哉, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2009/09/15
炎症性腸疾患に合併したSAPHO症候群の2例

木村智哉, 遠藤克哉, 黒羽正剛, 荒井壮, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 角田洋一, 高橋秀一郎, 梅村賢, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2009/09/15
カプセル内視鏡により小腸の広範囲に白色絨毛を指摘しえた蛋白漏出性胃腸症の一例

遠藤克哉, 黒羽正剛, 荒井壮, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 角田洋一, 高橋秀一郎, 梅村賢, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2009/04/15
非特異性多発性小腸潰瘍症が疑われた1例

志賀永嗣, 遠藤克哉, 木内喜孝, 高橋成一, 根来健一, 角田洋一, 相澤宏樹, 植木紳夫, 松浦真樹, 木村智哉, 荒井壮, 黒羽正剛, 下瀬川徹

Gastroenterol Endosc　2009/04/15
家族性大腸腺腫症の術後回腸人工肛門に発生した小腸癌の1例(第2報)Ileostomy carcinoma症例における回腸人工肛門の病理組織学的検討

梅村賢, 野村栄樹, 三浦康, 黒羽正剛, 荒井壮, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 高橋秀一郎, 遠藤克哉, 角田洋一, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 佐々木巌, 下瀬川徹

日本消化器病学会雑誌　2009/03/20
インフリキシマブ投与で改善を認めた単純性潰瘍の一例

植木紳夫, 遠藤克哉, 黒羽正剛, 荒井壮, 木村智哉, 相澤宏樹, 松浦正樹, 志賀永嗣, 角田洋一, 梅村賢, 高橋秀一郎, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2009/03/20
日本人クローン病感受性遺伝子TNFSF15の機能解析

植木紳夫, 角田洋一, 黒羽正剛, 荒井壮, 木村智哉, 相澤宏樹, 松浦正樹, 志賀永嗣, 遠藤克哉, 梅村賢, 高橋秀一郎, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2009/03/20
日本人潰瘍性大腸炎とKIR3DL1遺伝子との相関について

相澤宏樹, 木内喜孝, 高橋成一, 根来健一, 角田洋一, 遠藤克哉, 相原裕之, 梅村賢, 高橋秀一郎, 植木紳夫, 志賀永嗣, 松浦真樹, 木村智哉, 荒井壮, 黒羽正剛, 下瀬川徹

日本消化器病学会雑誌　2009/03/20
Colitic cancer,Dysplasiaの拡大内視鏡診断

相澤宏樹, 高木承, 植木紳夫, 志賀永嗣, 松浦真樹, 遠藤克哉, 角田洋一, 梅村賢, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本大腸こう門病学会雑誌　2008/09
Colitic cancerの診断と治療 Colitic cancer、Dysplasiaの拡大内視鏡診断

相澤宏樹, 高木承, 植木紳夫, 志賀永嗣, 松浦真樹, 遠藤克哉, 角田洋一, 梅村賢, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本大腸肛門病学会雑誌　2008/09
家族性大腸腺腫症(FAP)の術後回腸人工肛門に発生した小腸癌の1例

梅村賢, 野村栄樹, 荒井壮, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 遠藤克哉, 角田洋一, 松村吉史, 横山大, 根来健一, 高木承, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2008/03/20
クローン病感受性遺伝子TL1Aの発現制御に関する検討

遠藤克哉, 木内喜孝, 荒井壮, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 角田洋一, 松村吉史, 横山大, 梅村賢, 野村栄樹, 根来健一, 相原裕之, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2008/03/20
クローン病との鑑別を要したウイルス関連血球貪食症候群(virus‐associated hemophagocytic syndrome:VAHS)の一例

志賀永嗣, 野村栄樹, 高木承, 高橋成一, 横山大, 梅村賢, 遠藤克哉, 角田洋一, 松村吉史, 相澤宏樹, 植木紳夫, 松浦真樹, 木村智哉, 荒井壮, 木内喜孝, 富永現, 下瀬川徹

日本消化器病学会雑誌　2008/03/20
日本人クローン病とATG16L1,IL23R,MYO9B,IRGM遺伝子との相関について

相澤宏樹, 高僑成一, 根来健一, 角田洋一, 遠藤克哉, 野村栄樹, 相原裕之, 横山大, 梅村賢, 松村吉史, 植木紳夫, 志賀永嗣, 松浦真樹, 木村智哉, 荒井壮, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2008/03/20
PHA刺激時ヒトTリンパ球においてクローン病リスクTNFSF15対立遺伝子は非リスク対立遺伝子に比較し発現が亢進する

角田洋一, 木内喜孝, 根来健一, 木村智哉, 松浦真樹, 植木紳夫, 相澤宏樹, 志賀永嗣, 遠藤克哉, 松村吉史, 土佐正規, 持田淳弘, 野村栄樹, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2007/09/20
造血幹細胞移植後腸炎における大腸内視鏡所見による鑑別診断能の検討

遠藤克哉, 高木承, 木村智哉, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 角田洋一, 松村吉史, 土佐正規, 持田淳弘, 横山大, 野村栄樹, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2007/09/15
地中海熱の一例

木村智哉, 高橋成一, 野村栄樹, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 遠藤克哉, 松村吉史, 角田洋一, 土佐正規, 持田淳弘, 横山大, 根来健一, 高木承, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2007/03/20
日本人クローン病におけるTNFSF15遺伝子多型とHLA‐DQB1との関連について

角田洋一, 木内喜孝, 根来健一, 木村智哉, 松浦真樹, 植木紳夫, 相澤宏樹, 志賀永嗣, 遠藤克哉, 松村吉史, 土佐正規, 持田淳弘, 野村栄樹, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2007/03/20
クローン病感受性遺伝子TNFSF15遺伝子型と臨床表現型・長期予後との関連について

松浦真樹, 野村栄樹, 角田洋一, 根来健一, 高木承, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2007/03/20
メサラジン・プレドニゾロン注腸併用療法を施行し無事出産しえた初発潰瘍性大腸炎の1例

遠藤克哉, 高木承, 木村智哉, 相澤宏樹, 植木伸夫, 志賀永嗣, 松浦真樹, 角田洋一, 松村吉史, 土佐正規, 持田淳弘, 横山大, 野村栄樹, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

日本消化器病学会雑誌　2007/03/20
Cronkhite‐Canada症候群と膜性腎症を合併した2例

志賀永嗣, 高木承, 野村栄樹, 相澤宏樹, 植木紳夫, 松浦真樹, 松村吉史, 角田洋一, 遠藤克哉, 土佐正規, 阿部浩子, 持田淳弘, 今井豪, 佐藤雄一郎, 横山大, 高橋成一, 木内喜孝, 下瀬川徹, 尾花伸哉

日本消化器病学会雑誌　2006/09/10
日本人炎症性腸疾患とBTNL2遺伝子多型との相関について

持田淳弘, 木内喜孝, 根来健一, 相澤宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 遠藤克哉, 角田洋一, 松村吉史, 阿部浩子, 今井豪, 土佐正規, 佐藤雄一郎, 横山大, 野村栄樹, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2006/09/10
日本人潰瘍性大腸炎とTNFSF15遺伝子多型との相関について

角田洋一, 木内喜孝, 根来健一, 野村栄樹, 松浦真樹, 植木紳夫, 相澤宏樹, 志賀永嗣, 遠藤克哉, 松村吉史, 土佐正規, 阿部浩子, 持田淳弘, 今井豪, 佐藤雄一郎, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2006/09/10
第6染色体短腕に存在する日本人潰よう性大腸炎感受性遺伝子についての検討

野村栄樹, 角田洋一, 木内喜孝

日本消化器病学会雑誌　2006/03/20
潰よう性大腸炎緩解維持療法におけるメサラジン週末注腸療法の有用性

横山大, 高木承, 栗山進一, 高橋秀一郎, 高橋広喜, 岩淵正広, 志賀永嗣, 松村吉史, 角田洋一, 阿部浩子, 今井豪, 土佐正規, 持田淳弘, 佐藤雄一郎, 野村栄樹, 根来健一, 高橋成一, 木内喜孝, 辻一郎, 下瀬川徹

日本消化器病学会雑誌　2006/03/20
日本人クローン病とTL1A遺伝子多型との相関について

角田洋一, 木内喜孝, 根来健一, 野村栄樹, 松浦真樹, 植木紳夫, 相沢宏樹, 志賀永嗣, 遠藤克哉, 松村吉史, 土佐正規, 阿部浩子, 持田淳弘, 今井豪, 佐藤雄一郎, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2006/03/20
潰瘍性大腸炎緩解維持療法におけるメサラジン週末注腸療法の有用性

横山大, 高木承, 栗山進一, 高橋秀一郎, 高橋広喜, 岩渕正広, 志賀永嗣, 松村吉史, 角田洋一, 阿部浩子, 今井豪, 土佐正規, 持田淳弘, 佐藤雄一郎, 野村栄樹, 根来健一, 高橋成一, 木内喜孝, 辻一郎, 下瀬川徹

日本消化器病学会雑誌　2006/03
消化器疾患における遺伝素因と環境因子生活習慣・労働との関わり第6染色体短腕に存在する日本人潰瘍性大腸炎感受性遺伝子についての検討

野村栄樹, 角田洋一, 木内喜孝

日本消化器病学会雑誌　2006/03
日本人潰よう性大腸炎におけるHLA‐DRB1とり患範囲との関連について

角田洋一, 木内喜孝, 根来健一, 野村栄樹, 土佐正規, 阿部浩子, 今井豪, 遠藤克哉, 松村吉史, 持田淳弘, 佐藤雄一郎, 白木学, 高橋秀一郎, 横山大, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2005/09/10
日本人潰よう性大腸炎とHLA‐B遺伝子との相関解析

今井豪, 木内喜孝, 野村栄樹, 角田洋一, 松村吉史, 遠藤克哉, 土佐正規, 阿部浩子, 持田淳弘, 佐藤雄一郎, 白木学, 高橋秀一郎, 横山大, 根来健一, 高木承, 相原裕之, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2005/09/10
造血幹細胞移植後GVHD腸炎におけるTMA腸炎合併の有無に関した大腸内視鏡所見の検討

遠藤克哉, 高木承, 大森信弥, 角田洋一, 松村吉史, 阿部浩子, 今井豪, 土佐正規, 持田淳弘, 佐藤雄一郎, 白木学, 野村栄樹, 高橋秀一郎, 横山大, 根来健一, 相原裕之, 高橋成一, 木内喜孝, 下瀬川徹

Gastroenterol Endosc　2005/09/05
日本人潰瘍性大腸炎とHLA-B遺伝子との相関解析

今井豪, 木内喜孝, 野村栄樹, 角田洋一, 松村吉史, 遠藤克哉, 土佐正規, 阿部浩子, 持田淳弘, 佐藤雄一郎, 白木学, 高橋秀一郎, 横山大, 根来健一, 高木承, 相原裕之, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2005/09
日本人潰瘍性大腸炎におけるHLA-DRB1と罹患範囲との関連について

角田洋一, 木内喜孝, 根来健一, 野村栄樹, 土佐正規, 阿部浩子, 今井豪, 遠藤克哉, 松村吉史, 持田淳弘, 佐藤雄一郎, 白木学, 高橋秀一郎, 横山大, 相原裕之, 高木承, 高橋成一, 下瀬川徹

日本消化器病学会雑誌　2005/09
炎症性腸疾患におけるIBD5の解析

土佐正規, 根来健一, 角田洋一, 阿部浩子, 野村栄樹, 遠藤克哉, 松村吉史, 高橋秀一郎, 今井豪

日本消化器病学会雑誌　2005/03/20
抗TNF‐α抗体療法を施行したクローン病症例の検討

高橋秀一郎, 高木承, 横山大, 遠藤克哉, 松村吉史, 角田洋一, 阿部浩子, 今井豪, 土佐正規

日本消化器病学会雑誌　2005/03/20
当科における腸管悪性リンパ腫および鑑別を要したリンパ球増殖性病変の検討

野村栄樹, 高木承, 相沢宏樹, 植木紳夫, 志賀永嗣, 松浦真樹, 遠藤克哉, 角田洋一, 松村吉史, 阿部浩子, 今井豪, 土佐正規, 持田淳弘, 佐藤雄一郎, 根来健一, 高橋成一, 木内喜孝, 下瀬川徹, 一迫玲

早期大腸癌研究会抄録集　2005

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Industrial Property Rights 1

チオプリン製剤による副作用の危険性の判定方法

角田洋一, 内藤健夫, 木内喜孝, 下瀬川徹

特許第6644478号

Property Type: Patent

Research Projects 22

Analysis of factors contributing to pathogenesis and severity of inflammatory bowel disease using comprehensive copy number estimation of the Defensin gene cluster

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

2024/04/01 - 2027/03/31
炎症性腸疾患患者のチオプリンに暴露された胎児の遺伝的選択・変異に関する検討

志賀永嗣, 角田洋一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業基盤研究(C)

Category: 基盤研究(C)

Institution: 東北大学

2022/04/01 - 2025/03/31
炎症性腸疾患の疾患活動度をモニターする唾液マーカーの探索

兼平正史, 八幡祥生, 齋藤正寛, 角田洋一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業基盤研究(C)

Category: 基盤研究(C)

Institution: 東北大学

2022/04/01 - 2025/03/31
Establishing evidence for achieving safe pregnancy and childbirth in patients requiring immunomodulatory treatment

Offer Organization: AMED

2022/04 - 2025/03
潰瘍性大腸炎感受性遺伝子MIR622の感受性メカニズムの解明と臨床的応用の探索

木内喜孝, 角田洋一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業基盤研究(C)

Category: 基盤研究(C)

Institution: 東北大学

2021/04/01 - 2024/03/31

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潰瘍性大腸炎の発症にかかわる遺伝子解析において、日本人に最適化した新しい手法での解析から申請者は新たにMIR622遺伝子上流に存在する一塩基多型（SNPs）の相関を発見した。これらのSNPsはmiR-622のプロモーター領域のDNAおよびヒストンメチル化領域の近傍に存在するため、このSNPsはmiR-622の発現に影響している可能性がある。過去に肝細胞でmiR-622のターゲット遺伝子としてCXCR4が報告されているが、CXCR4陽性の形質細胞が潰瘍性大腸炎の腸管局所の炎症に応じて増加していることも報告されており、SNPsでmiR-622発現低下からCXCR4の発現が増加し潰瘍性大腸炎の発症に関与している、あるいはそのようなサブグループが存在する可能性がある。そこで、新たに発見された日本人疾患感受性SNPがmiR-622をどのように調整し、発病そして病態に関与するかを解明し、病勢を反映するバイオマーカーとしての可能性や、miR-622補充による核酸医薬の可能性までを明らかにする。今年度はメチル化を介したSNPによるmiR-622発現の変化に関する検討（検討１）について検体を収集している。同時にバイサルファイトシーケンスの条件について検討した。またmiR-622のターゲット遺伝子に関する検討（検討２）では、CXCR4以外のmiR-622のターゲットがないか、予測ソフトウエアTargetScan,picTar等を使用し解析を行った。血清中miR-622の病態モニタリング用バイオマーカーとしての有用性の検討（検討３）では必要な検体の収集を行っている。
Functional analysis of disease susceptibility gene RAP1A using organoid monolayer from Crohn's Disease

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2021/04/01 - 2024/03/31
ゲノム不安定性による体細胞モザイクを介したクローン病の発症・病態変化の解析

角田洋一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業基盤研究(C)

Category: 基盤研究(C)

Institution: 東北大学

2021/04/01 - 2024/03/31

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染色体異常モザイク（mCA）は、造血器悪性腫瘍のリスクを高めるとともに、様々な疾患のリスクとなりうることが知られている。本研究ではクローン病（CD）や潰瘍性大腸炎（UC）などの炎症性腸疾患（IBD）におけるmCAの存在について解析を行い、造血器悪性腫瘍の発症やIBD表現型の変化と関連があるかを検討する。今年度はIBD患者3,339名の末梢血中のDNAのアレイ解析データを使用してmCAを解析し、mCAの臨床的および遺伝的リスク因子の探索を行った。 mCAは、既報通り加齢とともに増加していた。IBD患者は若年がメインのため、５０歳以下にに限定した解析を行った。その結果、潰瘍性大腸炎に比較してクローン病でのmCAの発生率が高いことが示された（オッズ比＝2.15、P＝1.17e-2）。これらのモザイク変異のほとんどはコピー数以上を伴わないヘテロ接合性の欠如（CN-LOH)であり、３番染色体と６番染色体に有意に多く認められた。また、それとは独立して20歳未満でのチオプリンへの曝露が、mCAの新規独立危険因子として同定された。（オッズ比＝5.68、P＝1.60e-3）。一方、罹病期間や、抗ＴＮＦα抗体製剤の使用、その他の臨床因子は有意な関連は認められなかった。Gene ontology enrichment解析により、CD患者のmCAに特異的に存在する遺伝子は、粘膜免疫反応に関連する因子と有意に関連していることが明らかになった。ゲノムワイド関連研究の結果、ERBIN、CD96、AC068672.2がCD患者のmCAと有意に関連していた（それぞれ、P = 1.56e-8, 1.65e-8, 4.92e-8 ）。
Development of a method for measuring the activity of the newly identified thiopurine metabolizing enzyme NUDT15

Shiga Hisashi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2019/04/01 - 2022/03/31

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This study was conducted to develop a method to directly measure the activity of NUDT15, a thiopurine metabolizing enzyme. 6TGTP is metabolized by NUDT15, and the metabolite is 6TGMP, so a method to measure these was first developed. Then, erythrocytes were collected from subjects of each genotype, 6TGTP was added, and the metabolite 6TGMP was measured after a certain time, and differences by genotype could be detected. Although this showed that it was possible to compare the enzyme activities, the results varied greatly depending on the time and method of storage of the specimens, and the results varied more than the genotype differences.
NUDT15遺伝子型に基づき個人に最適化された安全かつ有効的なチオプリンによる免疫調節療法の開発 Competitive

角田洋一

Offer Organization: 日本医療研究開発機構

System: 免疫アレルギー疾患等実用化研究事業

2019/04 - 2022/03
An integrated genomic and transcriptomic analysis to reveals susceptibility genes for Cronh's disease in Japanese populations

Kinouchi Yoshitaka

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2018/04/01 - 2021/03/31

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eQTL for the efector memory T cells (TEM) located in the lamina propria mononuclear cells (LPMCs), which play an important role in Crohn’s disease (CD), are not yet available. We conducted RNA sequencing and eQTL analyses of TEM cells located in the LPMCs from IBD patients (n=20). Genome-wide association study (GWAS) was performed using genotyping data of 713 Japanese CD patients and 2,063 controls. We compared the results of GWAS and eQTL of TEM, and also performed a transcriptome-wide association study using eQTL from Genotype Tissue Expression project. By eQTL analyses of TEM, correlations of possible candidates were confrmed in 22,632 pairs and 2,463 genes. Among these candidates, 19 SNPs which showed signifcant correlation with tenascin-XA (TNXA) expression were signifcantly associated with CD in GWAS. By TWAS, TNFSF15(FDR=1.35e-13) in whole blood in lymphocytes was signifcantly associated with CD.
高ずり応力を伴う循環器難病に随伴する出血性合併症予知法の開発 Competitive

堀内久徳

Offer Organization: 日本医療研究開発機構

System: 難治性疾患等実用化研究事業

2018/04 - 2021/03
Analysis of TCR Repertoire of lamina propria lymphocytes in ileum and colon in inflammatory bowel disease

Kimura Tomoya, Kakuta Yoichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

Category: Grant-in-Aid for Young Scientists (B)

Institution: Tohoku University

2017/04/01 - 2019/03/31

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The present study analyzed T cell receptor (TCR) repertoire in lamina propria mononuclear cells (LPMC) and peripheral blood monocytes (PBMC) of Japanese patients with inflammatory bowel disease (IBD). We collected PBMC and LPMC from 11 cases of IBD and PBMC from 10 healthy controls and performed a repertoire analysis of TCRα and β using the next generation sequencer. Though TCR diversities in LPMC and PBMC were similar in the IBD patients, there was a decrease in TCR diversity in PBMC compared to the that in healthy subjects. The decrease in TCR diversity in PBMC in Crohn’s disease (CD) patients tended to be greater compared to that in ulcerative colitis (UC) patients. The disease-specific TCR clone has not been identified; however, repeated analysis of PBMC may enable the identification of the IBD-specific clone, since a decrease in TCR diversity was also confirmed in PBMC, which is easier to sample.
チオプリン不耐例を判別するNUDT15 R139C遺伝子多型検査キットの開発を軸とした炎症性腸疾患におけるゲノム医療実用化フレームワークの確立 Competitive

角田洋一

Offer Organization: 日本医療研究開発機構

System: ゲノム創薬基盤推進研究事業

2016/09 - 2019/03
Genome-wide association study of inflammatory bowel disease using population optimized array and reference panel in Japanese

Kakuta Yoichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2015/04/01 - 2018/03/31

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Several GWASs revealed more than 200 susceptibility loci for IBD. We built a 1KJPN panel containing genomic variations obtained by whole-genome resequencing of 1070 Japanese individuals,and developed the Japonica Array optimized for genotyping and imputing the Japanese population. To clarify the Japanese-specific genetic background of Crohn’s disease (CD), we performed GWAS using a population-optimized SNP array and imputation. Genotyping data of 7,934,670 SNPs from 737 Japanese CD patients and 2188 controls were analyzed. SNPs located in three known loci, TNFSF15, MHC, and ZNF365, 4p14 showed significant associations with CD. Locus rs488200, located on an intron of RAP1A, was the top hit of novel candidate loci (p=8.85E-8, OR=1.43). A previous report indicated that the underexpression of the RAP1A gene increases the risk of CD because Rap1 regulates T-cell circulation, thereby preventing the onset of colitis in a mouse model. RAP1A is a novel candidate susceptibility gene for CD.
Gene-microbiota interaction of inflammatory bowel disease

Kakuta Yoichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2015/04/01 - 2017/03/31

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To see the interaction between the genetic background and gut microbiota in Japanese patients with inflammatory bowel disease (IBD), we investigated the ‘typical’ signature of genetics and microbiota of IBD. The genetic background was known to be associated with IBD, but we found that it was associated with abnormal Paneth cells in Japanese CD. We also investigated the gut microbiota from 16 Japanese patients with ulcerative colitis, the diversity of microbiota was significantly different between the involved region and non-involved region even in the same patient. From the above, further analysis will be needed to prepare the model to see the gene-environmental interaction in IBD.
Analysis of allele specific DNA methylation of the susceptibility genes to inflammatory bowel disease

KINOUCHI Yoshitaka

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2014/04/01 - 2017/03/31

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We expect that SNPs in the susceptibility loci for inflammatory bowel disease (IBD) affect the DNA methylation around the SNPs in a cis manner and alter the gene expression. We also expect that this alteration is one of the mechanisms how associated SNPs affect the susceptibility to multifactorial diseases. In this study, allele specific DNA methylations of the genome DNA of lamina propria T cell were examined using Japonica array. We determined 218 sites of allele specific DNA methylation in the genome except imprinting regions. Among 218 regions, two are in the IBD susceptibility loci. In one of the two region, differences of the m-RNA expression between alleles were determined. In this study, we showed, for the first time, that the allele specific DNA methylation and allele specific expression exist in the susceptibility gene for IBD.
Trans-ethnic association and functional studies of the susceptibility genes of inflammatory bowel disease Competitive

角田洋一

Offer Organization: 日本学術振興会

System: 若手研究者海外派遣プログラム

2012/10 - 2013/10
Autophagy and inflammatory bowel disease. Competitive

角田洋一

Offer Organization: 上原記念生命科学財団

System: リサーチフェローシップ

2012/04 - 2013/03
To determine a disease pathway related with NKX2.3 in inflammatory bowel disease

KINOUCHI Yoshitaka, KAKUTA Yoichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2011 - 2013

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NKX2.3 is expressed in endothelial cells and is considered to be one of the candidate susceptibility genes to inflammatory bowel diseases. In this study, to investigate how NKX2.3 influences disease susceptibilities to inflammatory bowel diseases, we determined the genes regulated by NKX2.3 in endothelial cells using expression analysis and ChIP on Chip. A total of 34 genes including MAdCAM-1 were determined in these analyses. Enriched GO terms were revealed to be inflammatory response and cell proliferation using DAVID. To determine the binding site in the promoter region of the MAdCAM-1, the promoter assay using pGL4 plasmid and electrophoretic mobility shift assay were performed. But we have not found the binding site in the promoter region of the MAdCAM-1.
日本人潰瘍性大腸炎感受性遺伝子SLC26A3の遺伝子多型機能解析

角田洋一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業若手研究(B)

Category: 若手研究(B)

Institution: 東北大学

2011 - 2011

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潰瘍性大腸炎の発症には遺伝的素因が関与していることが疫学的研究から明らかになっている。2009年に行ったゲノムワイド相関解析によって、いくつかの日本人潰瘍性大腸炎の感受性遺伝子が新たに報告された。しかし、ゲノムワイド相関解析では相関を示す遺伝子多型を決められた多型セットから抽出するだけであり、実際に相関を示している多型がその多型とは限らない。また、その多型が疾患と相関するかどうかをみているだけであり、疾患の病態や病型、治療反応性などとの関連は不明である。本研究では、その中の一つであるSLC26A3遺伝子について、その相関がどのようなものであるかを明らかにし、感受性を示すメカニズムを探ることを目的とした。遺伝子解析をより詳細に行うため、SLC26A3遺伝子の上流にあるrs2108225について、臨床データや他の感受性遺伝子の遺伝子型とともに検討を行った。対象は東北大学病院を受診した潰瘍性大腸炎患者260人と、健常人ボランティア654人とし、まず各群での対立遺伝子頻度の違いについてカイ二乗検定で検討を行った。その結果、対立遺伝子Cの頻度が、患者群で69.6%、健常人群で64.1%であり、有意に患者群で頻度が多いことが確認された。(p値0.0262,オッズ比1.28)。また、他の感受性遺伝子候補との関連を見るため、これまでに報告したNKX2.3遺伝子、HLA-B*52遺伝子について、それぞれのリスクキャリアとそれ以外に分けて相関解析を行った。その結果、NKX2.3遺伝子については、NKX2.3遺伝子リスクキャリアのみにおいてSLC26A3が相関を示した(p=0.00472,オッズ比=1.44)。また、HLA-B*52については、B*52キャリアと非キャリアでSLC26A3対立遺伝子頻度が有意に異なり(p=0.0212)、B*52キャリアでは相関を示さず、非キャリアでのみ相関を示した(p=0.00167,オッズ比=1.69)。このことから、SLC26A3は、他の感受性遺伝子との相互作用がある可能性が示唆された。
TNFSF15 derived from T cells may play an important role in the pathogenesis of Crohn's disease.

KAKUTA Yoichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

Category: Grant-in-Aid for Young Scientists (B)

Institution: Tohoku University

2009 - 2010

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We analyzed the transcriptional mechanisms of TL1A induced by LPS using the human monocytic cell line U937, LPS induces TL1A expression through the transcriptional activation via a NF-kappa B pathway. The NF-kappa B binding site in the 5' flanking region of TL1A was identified.
Functional analyses of TNFSF15 as a susceptibility gene for Crohn's disease.

KINOUCHI Yoshitaka, KAKUTA Yoichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2008 - 2010

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TNFSF15 is a susceptibility gene for Crohn's disease (CD). We speculated that one or more of the SNPs associated with CD may act as cis-regulatory SNPs. To reveal the effects of the SNPs on the transcriptional activity of TNFSF15, we first examined the allelic expression imbalance of TNFSF15 in peripheral blood mononuclear cells (PBMCs). When PBMCs stimulated by phytohemagglutinin (PHA) were examined, the allelic ratio of mRNA transcribed from the risk haplotype to the non-risk haplotype increased, compared with the ratio without stimulation. When peripheral blood T cells and Jurkat cells stimulated by phorbol 12-myristate 13-acetate + ionomycin were examined, an allelic expression imbalance similar to that observed in PBMCs stimulated by PHA was confirmed. The promoter assay in stimulated Jurkat cells showed that the luciferase activity of the promoter region (-979 to +35) of the risk haplotype was significantly higher than that of the non-risk haplotype, and deletion and mutagenesis analysis demonstrated that this difference resulted from the -358T/C SNP. The promoter activity of -358C (risk allele) was higher than that of -358T (non-risk allele) in stimulated T cells. This effect of -358T/C on the transcriptional activity in stimulated T cells may confer susceptibility to CD.

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