In vivo real-time visualization of therapeutic pharmacodynamics in Crohn's disease model mice using two photon laser scanning microscopy

2013 Fiscal Year Final Research Report

• Project/Area Number: 24791887
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Mie University
• Principal Investigator: INOUE Mikihiro 三重大学, 医学部附属病院, 助教 (30422835)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 二光子レーザー顕微鏡 / クローン病 / 生体内イメージング

Research Abstract

We attempted to visualize and analyze in vivo therapeutic response of infliximab (IFX) in the murine IBD model using two photon laser scanning microscopy (TPLSM).
The number of leukocytes infiltrating to subserosa and muscular layer was reduced in IFX-treated mice, compared with non-IFX, control mice. The length of colonic crypt was increased in IFX-treated mice, compared with non-IFX, control mice. Serial change in regenerative epithelial cells was not observed, which regenerated from the bottom of the crypt toward the top of the crypt (the luminal side). The fluorescence labeled anti-TNF-alpha antibody was observed in the mucosal stroma, suggesting the binding of labeled antibodies with free TNF- alpha in the colonic tissue. 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 cells.

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] Infantile Crohn's disease is one of the risk factors of Catheter-related Blood Stream Infection (2014)
  • Author(s): Koike Y, Uchida K, Inoue M, Ide S, Hashimoto K, Matsushita K, Otake K, Ohkita Y, Araki T, Kobayashi M, Mohri Y, Kusunoki M
  • Journal Title: Pediatr Int
  • 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] Predictive factors of negative outcome in initial atropine therapy for infantile hypertrophic pyloric stenosis (2013)
  • Author(s): Koike Y, Uchida K, Nakazawa M, Inoue M, Kusunoki M, Tsukamoto Y
  • Journal Title: Pediatr Int Volume: 55(5) Pages: 619-623
  • 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] Efficacy of Seprafilm for preventing adhesive bowel obstruction and cost-benefit analysis in pediatric patients undergoing laparotomy (2013)
  • Author(s): Inoue M, Uchida K, Otake K, Nagano Y, Ide S, Hashimoto K, Matsushita K, Koike Y, Mohri Y, Kusunoki M
  • Journal Title: J Pediatr Surg Volume: 48(7) Pages: 1528-1534
  • Peer Reviewed
• [Journal Article] Primary liver transplantation for biliary atresia after percutaneous transhepatic cholangio-drainage (2013)
  • Author(s): Koike Y, Uchida K, Hashimoto K, Matsushita K, Otake K, Inoue M, Kusunoki M
  • Journal Title: Journal of Pediatric Surgery Case Reports Volume: Vol.1,Issue7 Pages: 183-185
  • Peer Reviewed
• [Journal Article] Hairy polyp can be lethal even when small in size (2013)
  • Author(s): Koike Y, Uchida K, Inoue M, Ohtsu K, Tanaka T, Otake K, Tanaka K, Kusunoki M
  • Journal Title: Pediatr Int Volume: 55(3) Pages: 373-376
  • Peer Reviewed
• [Journal Article] Scar endometriosis in a patient with bladder exstrophy (2013)
  • Author(s): Kitajima T, Inoue M, Uchida K, Otake K, Kusunoki M
  • Journal Title: Int Surg Volume: 98(2) Pages: 145-148
  • 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] 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] Transumbilical single-incision laparoscopic ileocecal resection for Crohn's disease in a child (2013)
  • Author(s): Inoue M, Uchida K, Otake K, Okigami M, Okita Y, Hiro J, Araki T, Kusunoki M
  • Journal Title: Asian J Endosc Surg Volume: 6(1) Pages: 48-51
  • Peer Reviewed
• [Journal Article] Double balloon enteroscopy for pediatric inflammatory bowel disease (2012)
  • Author(s): Uchida K, Yoshiyama S, Inoue M, Koike Y, Yasuda H, Fujikawa H, Okita Y, Araki T, Tanaka K, Kusunoki M
  • Journal Title: Pediatr Surg Int Volume: 54(6) Pages: 806-809
  • Peer Reviewed
• [Journal Article] Unique capsule endoscopic appearance of segmental intestinal dilatation in a child (2012)
  • Author(s): Uchida K, Otake K, Inoue M, Koike Y, Matsushita K, Hashimoto K, Saigusa S, Tanaka K, Inoue Y, Kusunoki M
  • Journal Title: Pediatr Int Volume: 54(5) Pages: 727-729
  • Peer Reviewed
• [Journal Article] Use of Endoscopic Surgical Spacer to Improve Safety During Thoracoscopic Repair of Congenital Diaphragmatic Hernia (2012)
  • Author(s): Inoue M, Uchida K, Otake K, Ishino Y, Koike Y, Kusunoki M
  • Journal Title: J Laparoendosc Adv Surg Tech A Volume: 22(3) Pages: 304-306
  • Peer Reviewed
• [Presentation] 小児炎症性腸疾患に対する単孔式内視鏡手術と Reduced Port Surgery (2013)
  • Author(s): 井上 幹大, 内田 恵一, 廣 純一郎, 森 浩一郎, 井出正造, 小池 勇樹, 藤川 裕之, 大竹 耕平, 大北 喜基, 荒木 俊光, 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
  • Year and Date: 20131128-30
• [Presentation] 大腸手術における Reduced Port Surgeryの意義と定義 大腸全摘出・J 型回腸嚢肛門吻合術に対する Reduced Port Surgeryの意義 (2013)
  • Author(s): 廣 純一郎, 荒木 俊光, 井上 靖浩, 大北 喜基, 藤川 裕之, 川本 文, 井上 幹大, 問山 裕二, 田中 光司, 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
  • Year and Date: 20131128-30
• [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総会
  • Place of Presentation: 神戸国際会議場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
  • Year and Date: 20131125-26
• [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
  • Year and Date: 20131121-23
• [Presentation] クローン病の肛門病変の治療と成績 新生児・乳児期発症クローン病の肛門病変と治療 (2013)
  • Author(s): 内田 恵一, 井上 幹大, 大竹 耕平, 小池 勇樹, 藤川 裕之, 大北 喜基, 荒木 俊光, 廣 純一郎, 大井 正貴, 問山 裕二, 三枝 晋, 田中 光司, 井上 靖浩, 毛利 靖彦, 楠 正人
  • Organizer: 第68回日本大腸肛門病学会学術集会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 20131115-16
• [Presentation] 回盲部切除後の寛解維持療法としてインフリキシマブ投与を行った小児クローン病症例の検討 (2013)
  • Author(s): 井上 幹大, 内田 恵一, 井出 正造, 橋本 清, 小池 勇樹, 藤川 裕之, 大北 喜基, 大竹 耕平, 荒木 俊光, 楠 正人
  • Organizer: 第50回日本小児外科学会学術集会
  • Place of Presentation: 京王プラザホテル回
  • Year and Date: 20130530-0601
• [Presentation] 小児内視鏡手術の展望小児に対するReduced Port Surgery による腹腔鏡下大腸全摘回腸嚢肛門吻合術 (2013)
  • Author(s): 井上 幹大, 廣 純一郎, 井出 正造, 橋本 清, 小池 勇樹, 藤川 裕之, 大竹 耕平, 大北 喜基, 荒木俊光, 内田 恵一, 楠 正人
  • Organizer: 第50回日本小児外科学会学術集会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 20130530-0601
• [Presentation] 小児における小腸ダブルバルーン内視鏡施行時の放射線被爆 (2013)
  • Author(s): 井上 幹大, 内田 恵一, 井出 正造, 今岡 裕基, 小池 勇樹, 大竹耕平, 楠 正人
  • Organizer: 第40回日本小児内視鏡研究会
  • Place of Presentation: 聖マリアンナ医科大学
  • Year and Date: 2013-07-06