Degree 【 display / non-display 】

Degree 【 display / non-display 】

• 京都大学   医学博士

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Gastroenterology   inflammatory bowel disease

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   消化器内科学講座   教授  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• mucosal immunology

• cytokine

• Macrophage

• intestinal epithelial cells

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Ulcerative Colitis Preceding Asymptomatic Wilson’s Disease: A Case Report and Literature Review

  Jun Kunizaki, Yuko Yoto, Yoshinobu Nagaoka, Akira Ishii, Tomoe Kazama, Kohei Wagatsuma, Noriyuki Akutsu, Aki Ishikawa, Toju Tanaka, Shintaro Sugita, Takeshi Tsugawa, Hiroshi Nakase

  Gastro Hep Advances ( Elsevier BV )  4 ( 1 ) 100548 - 100548  2025

  DOI

• Involvement of Mediterranean fever gene mutations in colchicine-responsive enterocolitis: a retrospective cohort study

  Hiroshi Nakase, Kohei Wagatsuma, Taku Kobayashi, Takayuki Matsumoto, Motohiro Esaki, Kenji Watanabe, Reiko Kunisaki, Teruyuki Takeda, Katsuhiro Arai, Takashi Ibuka, Dai Ishikawa, Yuichi Matsuno, Hirotake Sakuraba, Nobuhiro Ueno, Kaoru Yokoyama, Masayuki Saruta, Ryota Hokari, Junji Yokoyama, Shu Tamano, Masanori Nojima, Tadakazu Hisamatsu, Shusaku Yoshikawa, Sohachi Nanjo, Akira Andoh, Takeshi Kimura, Makoto Ooi, Ryosuke Kiyomori, Nobuo Aoyama, Fumihito Hirai, Atsushi Yamaushi, Masanao Nakamura, Fumikazu Koyama, Shuhei Hosomi, Kazuki Kakimoto, Satoshi Motoya, Ryosuke Sakemi, Hideo Suzuki, Tadashi Hosoya, Ken Takeuchi, Manabu Shiraki, Hideyuki Koide, Ichiro Takeuchi, Yosuke Furui, Kento Yoshida, Ayaka Minemura, Asami Matsumoto, Kentaro Oka

  eBioMedicine ( Elsevier BV )  110   105454 - 105454  2024.12

  DOI

• A rare case of delayed duodenal perforation due to an over-the-scope clip.

  Yujiro Kawakami, Shinji Yoshii, Masahiro Taniguchi, Yoshiharu Masaki, Taro Sugawara, Yasutoshi Kimura, Hiroshi Nakase

  Endoscopy   56 ( S 01 ) E331-E333  2024.12  [International journal]

  DOI PubMed

• Unique endoscopic features of primary biliary diffuse large B‐cell lymphoma: A case report with literature review (with video)

  Tomoya Nakamura, Yoshiharu Masaki, Naohiro Kameyama, Yujiro Kawakami, Keisuke Ishigami, Yumemi Takada, Shuji Satoh, Taro Sugawara, Shintaro Sugita, Hiroshi Nakase

  DEN Open ( Wiley )  5 ( 1 )  2024.07

  　View Summary

  Abstract A 67‐year‐old man visited our hospital complaining of dark‐colored urine and upper abdominal pain. Magnetic resonance cholangiopancreatography showed stricture of the distal bile duct, and contrast‐enhanced computed tomography showed irregular thickening of the distal bile duct wall. However, no enlarged lymph nodes, pancreatic tumors, or other neoplastic lesions were apparent around the bile duct. Endoscopic ultrasonography and intraductal ultrasonography showed irregular thickening of the inner hypoechoic layer without the disappearance of the innermost thin hyperechoic layer. On the basis of these findings, we considered that the bile duct lesion was of non‐epithelial origin. Thus, we repeatedly performed bile duct biopsies from the same site under fluoroscopy to obtain a sample of the submucosal tissue. The pathological diagnosis was diffuse large B‐cell lymphoma, and the patient received systemic chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). After six courses of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, positron emission tomography‐computed tomography showed the disappearance of 18‐fluorodeoxyglucose uptake in the bile duct and endoscopic retrograde cholangiography showed improvement of the bile duct stricture. Endoscopic findings and repeated biopsies were useful in making the diagnosis of primary biliary diffuse large B‐cell lymphoma.

  DOI

• Clinical performance of fecal calprotectin, lactoferrin, and hemoglobin for evaluating the disease activity of IBD and detecting colorectal tumors.

  Tsukasa Yamakawa, Takakazu Miyake, Yoshihiro Yokoyama, Tomoe Kazama, Yuki Hayashi, Daisuke Hirayama, Shinji Yoshii, Hiro-O Yamano, Satoshi Takahashi, Hiroshi Nakase

  JGH open : an open access journal of gastroenterology and hepatology   8 ( 6 ) e13077  2024.06  [International journal]

  　View Summary

  BACKGROUND AND AIM: Recently, noninvasive fecal markers have been used as indicators of intestinal inflammation in patients with inflammatory bowel disease (IBD). We conducted a clinical validation study to measure fecal calprotectin (Cp), lactoferrin (Lf), and hemoglobin (Hb) levels using an all-in-one kit in patients with IBD and colorectal tumors and aimed to clarify the utility of these fecal markers. METHODS: In this study, 104 patients were analyzed, including 25 patients with ulcerative colitis (UC), 20 with Crohn's disease (CD), 48 with colorectal tumors, and 13 healthy controls (HC). Of the 48 patients with colorectal tumors, 14 had invasive cancer. We validated the utility of fecal Cp, Lf, and Hb levels by simultaneously measuring fecal markers in patients with IBD and colorectal tumors. RESULTS: Fecal Cp and Lf had almost equivalent abilities in detecting clinical remission in patients with UC; however, fecal Cp was slightly superior to Lf. Regarding colorectal tumors, fecal Cp and Lf levels tended to be higher in patients with adenomas and colorectal cancer than in HCs. Although fecal Hb alone had the best sensitivity and specificity for detecting colorectal cancer, it had relatively low sensitivity for detecting advanced neoplasms and colorectal cancer. CONCLUSION: Fecal Cp and Lf can be used as almost equivalent biomarkers to assess the clinical activity in patients with UC. Fecal Hb is the most useful marker for screening colorectal cancer; however, adding fecal Cp and Lf may compensate for the low sensitivity of detecting for advanced colorectal tumors based on Hb alone.

  DOI PubMed

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Books and Other Publications 【 display / non-display 】

Books and Other Publications 【 display / non-display 】

• 特集炎症性腸疾患診療の最前線 潰瘍性大腸炎の内科治療

  仲瀬 裕志, 吉野琢哉, 松浦 稔( Part： Contributor)

  日本医師会雑誌  2015

• D.消化管全般にわたるもの 膠原病の消化器病変

  仲瀬 裕志( Part： Contributor)

  南江堂.  2015

• 内科診療Q＆A －下部消化管

  仲瀬 裕志, 千葉 勉( Part： Contributor, 便秘の分類と治療)

  東京：六法出版社.  1997

Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 難治性腸炎に対する間葉系幹細胞を用いた細胞療法—Mesenchymal stem cell therapy for intractable inflammatory bowel disease—研究者の最新動向

  永石 歓和, 仲瀬 裕志

  Precision medicine = プレシジョンメディシン / 「Precision medicine」編集委員会 編 ( 東京 : 北隆館 )  7 ( 7 ) 593 - 597  2024.06

• Mesenchymal stem cellsを知る—特集 最新医療に向け新薬の標的を知る

  永石 歓和, 仲瀬 裕志

  消化器病学サイエンス = Science of gastroenterology / 「消化器病学サイエンス」編集委員会 編 ( 東京 : 先端医学社 )  7 ( 1 ) 33 - 38  2023.03

• 座談会 膵臓がん克服のためにわれわれがなすべきこととは? : 現在,そして未来

  仲瀬 裕志, 潟沼 朗生, 正宗 淳, 福田 晃久

  消化器病学サイエンス = Science of gastroenterology / 「消化器病学サイエンス」編集委員会 編   6 ( 4 ) 205 - 214  2022.12

• 難治性炎症性腸管障害に関する調査研究 家族性地中海熱遺伝子関連腸炎の診断法の確立並びに病態解明

  仲瀬裕志, 平山大輔, 櫻井晃弘, 久松理一, 松本主之, 江崎幹宏, 国崎玲子, 松浦稔, 大宮美香, 荒木寛司, 渡辺憲治, 田中浩紀, 小林拓, 日比紀文, 竹内健, 鈴木康夫, 上野伸展, 大井秀久, 柿本一城, 細見周平, 新崎信一郎, 横山薫, 山本真義, 松野雄一, 細江直樹, 大井充, 新井勝大, 都築義和, 安藤朗, 石川大, 長末智寛, 櫻井俊之, 白木学, 酒見亮介, 松田耕一郎, 南條宗八, 吉川周作, 中村正直, 小山文一, 横山純二, 後藤田卓志, 櫻庭裕丈, 武田輝之, 大宮直木, 穂刈量太, 吉田雄一朗, 荒木俊光, 杉田昭

  難治性炎症性腸管障害に関する調査研究 令和3年度 総括・分担研究報告書(Web)    2022

  J-GLOBAL

• Artificial intelligence-assisted endoscopy changes the definition of mucosal healing in ulcerative colitis

  Hiroshi Nakase, Takehiro Hirano, Kohei Wagatsuma, Tadashi Ichimiya, Tsukasa Yamakawa, Yoshihiro Yokoyama, Yuki Hayashi, Daisuke Hirayama, Tomoe Kazama, Shinji Yoshii, Hiro-o Yamano

  Digestive Endoscopy ( John Wiley and Sons Inc )  33 ( 6 ) 903 - 911  2021.09

  Book review, literature introduction, etc.  

  　View Summary

  The relevance of endoscopic monitoring of ulcerative colitis (UC) has been translated into the new concept of “mucosal healing (MH)” as the therapeutic goal to achieve because a large amount of scientific data have revealed the favorable prognostic value of a healed mucosa in determining the clinical outcome of UC. Recent interest in MH has skewed toward not only endoscopic remission but also histological improvement (so called histological MH). However, we should recognize that there have been no prospectively validated endoscopic scoring systems of UC activity in previous clinical trials. Artificial intelligence (AI)-assisted endoscopy has been developed for gastrointestinal cancer surveillance. Recently, several AI-assisted endoscopic systems have been developed for assessment of MH in UC. In the future, the development of a new endoscopic scoring system based on AI might standardize the definition of MH. Therefore, “The road to an exact definition of MH in the treatment of UC has begun only now”.

  DOI PubMed

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Industrial Property Rights 【 display / non-display 】

Industrial Property Rights 【 display / non-display 】

• ステント、当該ステントを消化管に留置する方法

  仲瀬裕志, 樋口浩和

  Patent

• 病変評価情報生成装置

  仲瀬裕志, 松浦稔, 吉野琢哉, 樋口浩和, 池本洋祐

  Patent

• 画像処理装置及び内視鏡装置

  仲瀬裕志, 松浦稔, 吉野琢哉, 樋口浩和, 池本洋祐

  Patent

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• クローン病肛門病変に対する間葉系幹細胞と細胞ファイバ技術を融合した細胞療法の開発

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  永石 歓和, 仲瀬 裕志

• DOT1L阻害によるインターフェロン応答の機序解明とがん免疫療法への応用

  基盤研究(B)

  Project Year :

  2022.04

  -

  2025.03

   

  鈴木 拓, 仲瀬 裕志, 新沼 猛, 北嶋 洋志

• Functional analysis of small intestinal paneth cells in RalGAPa2 KO mice

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2021.04

  -

  2024.03

   

  林 優希, 仲瀬 裕志

  　View Summary

  本邦におけるクローン病 (Crohn’s disease: CD) 患者数は増加の一途をたどっているが，疾患の原因は未だ明らかとなっておらず，根治的な治療法は存在しない．申請者の研究室ではこれまでに，大腸上皮における低分子量GTP蛋白質Ralの活性化が，NLRP3 inflammasome を介した大腸炎及び炎症性大腸発癌 (colitis-associated cancer: CAC) に極めて重要であることを報告してきた．さらに，申請者が行った予備検討で，小腸炎症においてもRalの活性化が確認されていることから，RalがCDの小腸病変とも関連している可能性が高いと考えた．一方，CD発症の原因の一つとして腸管免疫機構の破綻が考えられており，中でも小腸粘膜免疫におけるPaneth 細胞の役割が注目されている．本研究では，Ral活性化のPaneth細胞機能における役割を解析することにより，CDの病態解明に取り組む．
  令和3年度と令和4年度は，SAMP1/YitFcマウスの繁殖，SAMP1/YitFc × RalGAPa2 KOマウス，SAMP1/YitFc × RalGAPa2 KO × NLRP3 KOマウスの作成とphenotypeの同定を遂行中である．

• 肝細胞癌の分子標的治療と概日時計の関連

  基盤研究(C)

  Project Year :

  2020.04

  -

  2023.03

   

  阿久津 典之, 佐々木 茂, 仲瀬 裕志

  　View Summary

  1. ヒト肝細胞癌における時計遺伝子発現の検討 肝細胞癌10症例の癌部および非癌部の組織よりRNAを作成しcDNAを合成。その後Comparative CT法を用いて相対的発現を解析した。Clock, Bmal1, Per1,Per2 Cry1の発現を癌部と非癌部で解析したところ、Per1およびPer2が癌部と非癌部で有意な発現の違いをあることが分かった。背景因子での違いがないかさらなる検 討を行っている。 2. 正常肝細胞および肝癌細胞株における時計遺伝子発現と炎症性サイトカインに対する反応 肝癌細胞株HepG2, Hep3B, HLE, HLF, HuH7, PLC/PRF/5のcDNAを用いて、Clock, Bmal1, Per1,Per2 Cry1の発現を解析し、細胞株間での発現に差があることがわ かり、Per1やPer2の発現が低い細胞株と、高い細胞株を用いて、種々の炎症性サイトカイン(IL-1β, IL-4, IL-13, TNF-α, IFN-γ, IL-10, TGF-β)の添加を行 い、RNAおよびタンパクを回収。時計遺伝子の変化を解析している。 3. 分子標的薬の正常肝細胞および肝癌細胞株における時計遺伝子の発現と炎症性サイトカインに対する反応 肝癌細胞株 (Hep3B, HLF, HuH7)にレンバチニブ1μMを投与 し、37°Cで48時間培養した後に、時計遺伝子Bmal1、Rev-erbα、Rev-erbβ、Per1、Per2、 Cry1の発現についてqPCR法、western blotting法を用い検討した。

• Development of human biopsy-derived intestinal organoids monolayers and application for pharmaceutical research

  Grant-in-Aid for Challenging Research (Pioneering)

  Project Year :

  2020.04

  -

  2022.03

   

  Mizuguchi Hiroyuki

  　View Summary

  The human small intestine is the key organ for absorption, metabolism, and excretion of orally administered drugs. To preclinically predict these reactions in drug discovery research, a cell model that can precisely recapitulate the in vivo human intestinal monolayer is desired. Here, we developed a monolayer platform using human biopsy-derived duodenal organoids for application to pharmacokinetic studies. The human duodenal organoid-derived monolayer was prepared by a simple method in 3 to 8 days. It consisted of polarized absorptive cells and had tight junctions. It showed much higher cytochrome P450 (CYP) 3A4 and carboxylesterase (CES) 2 activities than the existing models (Caco-2 cells). It also showed efflux activity of P-glycoprotein (P-gp) and inducibility of CYP3A4. This monolayer assay system can be a general platform for a wide range of applications including pharmaceutical research.

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Presentations 【 display / non-display 】

Presentations 【 display / non-display 】

• 「消化器幹細胞の進歩とその応用」 消化管上皮ならびに腫瘍におけるHesの役割．

  上尾太郎, 妹尾 浩, 仲瀬 裕志

  第17回日本消化器関連学会週間 

  Presentation date： 2009

• 「日本から発信するIBD治療の工夫と標準化」 炎症性腸疾患治療におけるタクロリムス治療の今後の展望．

  仲瀬 裕志, 松浦 稔, 千葉 勉

  第97回日本消化器病学会総会. 

  Presentation date： 2011

• Long-term outcome of treatment with tacrolimus therapy in Japanese patients with inflammatory bowel disease.

  Nakase H, Tamaki H, Inoue S, Matsuura M, Nishio A, Chiba

  UEGW 2005 

  Presentation date： 2005

• 「炎症性腸疾患におけるInnate Immunity, Acquired Immunityとその接点」 ヒト単球細胞におけるMycobacterium paratuberculosisの感染性およびクローン病患者における抗IS900血清抗体価の検討．

  玉置敬之, 仲瀬裕志, 岡崎和一

  第42回日本消化器免疫学会 

  Presentation date： 2005

• Development of an oral drug delivery system targeting immuo-regulating cells in the inflammatory bowel disease: A new therapeutic strategy

  Hiroshi Nakase, Tsutomu Chiba

  88th Congress of the Japanese Society of Gastroenterology 

  Presentation date： 2002

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