In vivo real-time characterization of the murine intestine of inflammatory bowel disease model using two photon laser scanning microscopy

• Project/Area Number: 24659588
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Mie University
• Principal Investigator: KUSUNOKI Masato 三重大学, 医学(系)研究科(研究院), 教授 (50192026)
• Co-Investigator(Kenkyū-buntansha): TANAKA Koji 三重大学, 医学部附属病院, 講師 (10345986) ; INOUE Yasuhiro 三重大学, 医学部附属病院, 講師 (20324535) ; UCIDA Keiichi 三重大学, 医学部附属病院, 准教授 (30293781) ; OKUGAWA Yoshinaga 三重大学, 医学部附属病院, 助教 (30555545) ; ARAKI Toshimitu 三重大学, 医学部附属病院, 講師 (70343217)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 二光子レーザー顕微鏡 / 炎症性腸疾患 / 生体内イメージング / 二光子励起顕微鏡 / 炎症性腸疾患モデル / Infliximab / infliximab

Research Abstract

We attempted to visualize in vivo therapeutic response of infliximab (IFX) and tacrolimus (FK506) in the murine IBD model using two photon laser scanning microscopy and to analyze their histopathological response morphologically.
The number of leukocyte infiltrates within the crypt and the number of crypt loss were decreased in IFX-treated mice. The length of colonic crypt was increased in IFX-treated mice. Serial change in regenerative epithelial cells was not observed. The findings in FK506-treated mice were similar to those in IFX-treated mice. The fluorescence labeled anti-TNF-alpha antibody was observed in the mucosal stroma, suggesting the binding of labeled antibodies with free TNF-alpha. It was also observed in the surface of leukocytes within the postcapillary venules or those infiltrating into the damaged crypt, suggesting the binding of labeled antibodies with the membrane binding TNF- alpha of the surface TNF- alpha producing leukocytes.

Research Products

• [Journal Article] The impact of postoperative infliximab maintenance therapy on preventing the surgical recurrence of Crohn's disease : a single-center paired case-control study (2014)
  • Author(s): Araki T, Uchida K, Okita Y, Fujikawa H, Inoue M, Ohi M, Tanaka K, Inoue Y, Mohri Y, Kusunoki M
  • Journal Title: Surg Today Volume: 44(2) Pages: 291-296
  • Peer Reviewed
• [Journal Article] Risk factors for surgical site infection in Japanese patients with ulcerative colitis : a multicenter prospective study (2014)
  • Author(s): Araki T, Okita Y, Uchino M, Ikeuchi H, Sasaki I, Funayama Y, Fukushima K, Futami K, Maeda K, Iiai T, Itabashi M, Hase K, Motoya S, Kitano A, Mizushima T, Maeda K, Kobayashi M, Mohri Y, Kusunoki M
  • Journal Title: Surg Today Volume: 44(6) Pages: 1072-1078
  • Peer Reviewed
• [Journal Article] Sexual activity after ileal pouch-anal anastomosis in Japanese patients with ulcerative colitis (2014)
  • Author(s): Yoshida K, Araki T, Uchida K, Okita Y, Fujikawa H, Inoue M, Tanaka K, Inoue Y, Mohri Y, Kusunoki M
  • Journal Title: Surg Today Volume: 44(1) Pages: 73-79
  • Peer Reviewed
• [Journal Article] Redo Ileal pouch-anal anastomosis combined with anti-TNF-αmaintenance therapy for Crohn's disease with pelvic fistula : report of two cases (2014)
  • Author(s): Araki T, Okita Y, Fujikawa H, Ohi M, Tanaka K, Inoue Y, Uchida K, Mohri Y, Kusunoki M
  • Journal Title: Surg Today Volume: Jan 18
  • Peer Reviewed
• [Journal Article] Predictive factors for development of chronic pouchitis after ileal pouch-anal anastomosis in ulcerative colitis (2013)
  • Author(s): Okita Y, Araki T, Tanaka K, Hashimoto K, Kondo S, Kawamura M, Koike Y, Otake K, Fujikawa H, Inoue M, Ohi M, Inoue Y, Uchida K, Mohri Y, Kusunoki M
  • Journal Title: Digestion Volume: 88(2) Pages: 101-109
  • Peer Reviewed
• [Journal Article] Full mucosal proctectomy initiated below the dentate line may prevent the development of a perianal fistula after ileal pouch-anal anastomosis for ulcerative colitis (2013)
  • Author(s): Araki T, Okita Y, Fujikawa H, Inoue Y, Mohri Y, Kusunoki M
  • Journal Title: Dig Surg Volume: 30(3) Pages: 219-224
  • Peer Reviewed
• [Journal Article] Characteristics of extremely early-onset pouchitis after proctocolectomy with ileal pouch-anal anastomosis (2013)
  • Author(s): Okita Y, Araki T, Tanaka K, Shimura T, Kawamura M, Fujikawa H, Inoue M, Inoue Y, Uchida K, Mohri Y, Kusunoki M
  • Journal Title: J Gastrointest Surg Volume: 17(3) Pages: 533-539
  • Peer Reviewed
• [Journal Article] History of and current issues affecting surgery for pediatric ulcerative colitis (2013)
  • Author(s): Uchida K, Araki T, Kusunoki M
  • Journal Title: Surg Today Volume: 43(11) Pages: 1219-1231
  • Peer Reviewed
• [Journal Article] Self-reported assessment of health-related quality of life in children who underwent restorative proctocolectomy with ileal J-pouch anal anastomosis for ulcerative colitis (2013)
  • Author(s): Uchida K, Kawamata A, Hashimoto K, Inoue M, Otake K, Koike Y, Matsushita K, Fujikawa H, Okita Y, Araki T, Tanaka K, Kusunoki M
  • Journal Title: Pediatr Surg Int Volume: 29(3) Pages: 287-291
  • Peer Reviewed
• [Journal Article] Intravital imaging of gastrointestinal diseases in preclinical models using two-photon laser scanning microscopy (2013)
  • Author(s): Tanaka K, Toiyama Y, Inoue Y, Uchida K, Araki T, Mohri Y, Mizoguchi A, Kusunoki M
  • Journal Title: Surg Today Volume: 43(2) Pages: 123-129
  • NAID: 10031167976
  • Peer Reviewed
• [Journal Article] Intravital imaging of gastrointestinal diseases in preclinical models using two-photon laser scanning microscopy. (2013)
  • Author(s): Tanaka K, Toiyama Y, Inoue Y, Uchida K, Araki T, Mohri Y, Mizoguchi A, Kusunoki M.
  • Journal Title: Surg Today. Volume: 43 Issue: 2 Pages: 123-129
  • DOI: 10.1007/s00595-012-0283-9
  • NAID: 10031167976
  • Peer Reviewed
• [Journal Article] Risk factors for surgical site infection in Japanese patients with ulcerative colitis: a multicenter prospective study. (2013)
  • Author(s): Araki T, Okita Y, Uchino M, Ikeuchi H, Sasaki I, Funayama Y, Fukushima K, Futami K, Maeda K, Iiai T, Itabashi M, Hase K, Motoya S, Kitano A, Mizushima T, Maeda K, Kobayashi M, Mohri Y, Kusunoki M.
  • Journal Title: Surg Today. Volume: Dec 12
  • Peer Reviewed
• [Journal Article] Predictive factors for development of chronic pouchitis after ileal pouch-anal anastomosis in ulcerative colitis. (2013)
  • Author(s): Okita Y, Araki T, Tanaka K, Hashimoto K, Kondo S, Kawamura M, Koike Y, Otake K, Fujikawa H, Inoue M, Ohi M, Inoue Y, Uchida K, Mohri Y, Kusunoki M.
  • Journal Title: Digestion. Volume: 88 Issue: 2 Pages: 101-109
  • DOI: 10.1159/000353151
  • Peer Reviewed
• [Journal Article] Full mucosal proctectomy initiated below the dentate line may prevent the development of a perianal fistula after ileal pouch-anal anastomosis for ulcerative colitis. (2013)
  • Author(s): Araki T, Okita Y, Fujikawa H, Inoue Y, Mohri Y, Kusunoki M.
  • Journal Title: Dig Surg. Volume: 30 Issue: 3 Pages: 219-224
  • DOI: 10.1159/000351443
  • Peer Reviewed
• [Journal Article] Identification of patients with developing ulcerative colitis-associated neoplasia by nitrative DNA damage marker 8-nitroguanin expression in rectal mucosa. (2013)
  • Author(s): Saigusa S, Araki T, Tanaka K, Hashimoto K, Okita Y, Fujikawa H, Okugawa Y, Toiyama Y, Inoue Y, Uchida K, Mohri Y, Kusunoki M.
  • Journal Title: J Clin Gastroenterol Volume: 47 Issue: 9 Pages: e80-e86
  • DOI: 10.1097/mcg.0b013e31828f51e1
  • Peer Reviewed
• [Presentation] 潰瘍性大腸炎に対する腹腔鏡下大腸全摘術の術後回復に与える影響の検討 (2013)
  • Author(s): 荒木俊光, 大北喜基, 藤川裕之, 廣純一郎, 大竹耕平, 川本文, 大井正貴, 井上幹大, 問山裕二, 小林美奈子, 田中光司, 井上靖浩, 内田恵一, 毛利靖彦, 楠正人
  • Organizer: 第26回日本内視鏡外科学会総会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 潰瘍性大腸炎に対する多施設共同手術部位感染症サーベイランス (2013)
  • Author(s): 荒木俊光, 大北喜基, 内野基, 池内浩基, 佐々木巌, 舟山裕士, 福島浩平, 二見喜太郎, 前田清, 飯合恒夫, 板橋道朗, 小林美奈子, 毛利靖彦, 楠正人
  • Organizer: 第26回日本外科感染症学会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 二光子励起顕微鏡を用いたマウス敗血症モデルにおけるNeutrophil Extracellular Trapsの生体内可視化 (2013)
  • Author(s): 田中光司, 小池勇樹, 志村匡信, 井出正造, 今岡裕基, 近藤哲, 北嶋貴仁, 問山裕二, 小林美奈子, 井上幹大, 井上靖浩, 荒木俊光, 内田恵一, 毛利靖彦, 楠正人
  • Organizer: 第26回日本外科感染症学会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 二光子励起顕微鏡を用いたマウス敗血症モデルにおける組織末梢循環不全とAntithrombin III製剤効果の生体内可視化 (2013)
  • Author(s): 田中光司, 志村匡信, 井出正造, 今岡裕基, 近藤哲, 北嶋貴仁, 問山裕二, 奥川喜永, 小林美奈子, 井上幹大, 井上靖浩, 荒木俊光, 内田恵一, 毛利靖彦, 楠正人
  • Organizer: 第75回日本臨床外科学会総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 大腸癌合併潰瘍性大腸炎に対する外科治療成績 (2013)
  • Author(s): 荒木俊光, 井上靖浩, 大北喜基, 藤川裕之, 川本文, 川村幹雄, 三枝晋, 廣純一郎, 問山裕二, 小林美奈子, 大井正貴, 田中光司, 内田恵一, 毛利靖彦, 楠正人
  • Organizer: 第51回日本癌治療学会学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] 炎症性腸疾患モデルマウスを用いた粘膜障害と修復再生過程の二光子レーザー顕微鏡下観察 (2012)
  • Author(s): 田中光司、森本雄貴、松下航平、川村幹雄、奥川喜永、問山裕二、小池勇樹、三枝 晋、沖上正人、橋本 清、井上靖浩、荒木俊光、内田恵一、毛利靖彦、楠 正人
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 東京
• [Patent(Industrial Property Rights)] 個体内部の組織学的イメージ像を観察・取得する方法 (2013)
  • Inventor(s): 溝口 明、山口 輪作
  • Industrial Property Rights Holder: 有限会社 楠屋
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-05-17