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Analysis of rejection mechanism, aiming for the establishment of novel immunosuppression in small bowel transplantation

Research Project

Project/Area Number 09307025
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

INOMATA Yukihiro  Kyoto University, Dpt.of Transplantation Immunology, Associate Professor, 医学研究科, 助教授 (50193628)

Co-Investigator(Kenkyū-buntansha) SUZUKI Seiichi  National Childrens, Medical Reserch Center, Dpt.of Experimental Surgery and Bio, 実験外科生体工学部, 部長 (00111386)
WAKATSUKI Yoshio  Kyoto University, Dpt.of Geriatric Medicine, Lecturer, 医学研究科, 講師 (40220826)
ASONUMA Kastuhiro  Kyoto University, Dpt.of Transplantation Immunology, Assistant, 医学研究科, 助手 (40202626)
UEMOTO Shinji  Kyoto University, Dpt.of Transplantation Immunology, Assistant, 医学研究科, 助手 (40252449)
TANAKA Koichi  Kyoto University, Dpt.of Transplantation Immunology, Professor, 医学研究科, 教授 (20115877)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥25,700,000 (Direct Cost: ¥25,700,000)
Fiscal Year 1998: ¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1997: ¥17,800,000 (Direct Cost: ¥17,800,000)
Keywordssmall bowel transplantation / pig / rejection / apoptosis / Tacrolimus / TUNEL法 / 免疫抑制 / FTY720
Research Abstract

Background : The experience with clinical living donor SBT(small bowel transplantation) motivate us to research on the following problems, which have been the obstacles to the improvement of graft and/or patient survival.
Earlier and definite diagnosis of rejection
More sophisticated way to control rejection
Pig SBT model : Pigs are adopted for our experiment because of the anatomical, physiological and immunological similarity between humans and pigs. We established one-staged orthotopic SBT model using donors and recipients which showed alloreactivity with mixed lymphocyte reaction.
Sampling of specimens :
a) drug administration and blood sampling through central line
b) fiberscopy (using clinical pediatric fiber) and biopsy
We established techniques above with pig SBT model and are performing these safely and regularly, which enable us to monitor the rejection process at the same level for clinical transplantation.
Results : Based on the macroscopic and microscopic findings, severity of rej … More ection and its relationship to ABC (apoptotic body counts) were analyzed under the immunosuppression with Tacrolimus, which has been the key drug for clinical SBT.Samples from grafts with rejection presented higher ABC (6.59/l0crypts) than those from non-rejected grafts (ABC ; 0.773/l0crypts), which showed statistical difference. There was no correlation between the severity of rejection and ABC.
Immunohistochemical studies were performed to analyze the induction pathway to apoptosis. Infiltration of CD8+ lymphocytes and FasL+ lymphocytes around crypts and increased expression of TNF receptor on epithelial cells were observed at the same time with, or prior to, macroscopic and/or histological rejection.
Future prospects and plans : The rejection in pig SBT now can be analyzed more in detail with the indicators above. Using the indicators, we are moving on to the further research projects such as local administration of immunosuppressants or tolerance induction. These indicators will be applied for our coming clinical SBT cases for the diagnosis of rejection. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (58 results)

All Other

All Publications (58 results)

  • [Publications] Y.Inomata: "Living Donor Liver Transplantation : An 8-Year Experience With 379 Consecutive Cases" Transplantation Proceedings. 31. 381 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Fujimoto: "Living-Related Small Transplant ; Management of Rejection and Infection" Transplantation Proceeding. 30. 179 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Fujimoto: "Living-Related Donor Small Bowel Transplatnation : First Case in Japan" Transplantation Proceedings. 30. 3441-3442 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Asonuma K: "Growth and quality of life after living-related liver transplantation in children." Pediatric Transplantation. 2. 64-69 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 小柴貴明: "小腸保存-臨床経験をもとに-" Organ Biology. 5. 1 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Egawa H: "Application of in situ hybridization. technique for quantitative. assessment of ongoing symptomatic Epstem-Barr virus infection after living related liver transplantation" Clinical Transplantation. 12. 116-122 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 猪股裕紀洋: "小腸移植の現況-生体小腸移植の経験をふまえて-" 日本小児栄養消化器病学会. 12. 24-30 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 瓜生原健嗣: "微細小血管の吻合" 外科治療. 301-305 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 田中紘一: "小腸移植" 日本医師会雑誌. 119. 11 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 林 道廣: "脳死移植の現況と将来" 現代医療. 30. (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Tanaka: "Present status and prospective view of living related liver transplantation." J. HepatoBiliary pancreatic Surgery. 4. 51-70 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Azuma: "Atypical Epstein-Barr virus infection during and after intermittent FK506 therapy." Acta Pediatrica Japonica. 39. 222-225 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Inomata: "Impact of the Development of a Liver Transplant program on the Treatment of Biliary Atresia in an Institution in Japan" Jounal of Pediatric Surgery. 32. 1201-1205 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] E.Hatano: "Hepatic preservation whith histidine-tryptophan-ketoglutarate solution in living-related and cadaveric liver transplantation." Clincal Science. 93. 81-88 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Nishizawa: "Efficiency of Pentoxifylline in Donor Pretreatment in Rat Liver Transplantation" Journal of Surgical Research. 72. 170-176 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] N.Shinkura: "Presence of Anti-Fkbp12 Astoantibodies in Patients with Liver Allografts" Transplantation. 64. 1336-1342 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Kiuchi: "Living-donor Liver Transplantation in Kyoto, 1997" Clinical Transplants. 191-198 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 猪股裕紀洋: "免疫抑制療法" Pharma Medica. 15. 27-35 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 猪股裕紀洋: "生体小腸移植の経験から" 今日の移植. 10. 537-543 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 上本伸二: "生体肝移植とEBウイルス関連腫瘍" 小児がん. 34. 223-227 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 猪股裕紀洋: "生体肝移植の基礎と臨床" 小児科臨床. 50. 2530-2540 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Kiuchi: "A hepatic graft tuberculosis tranplanted from a living-related donor." Transplantation.63. 905-907 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Inomata: "Living Donor Liver Transplantation : An 8-Year Experience With 379 Consecutive Cases" Transplantation Proceedings. 31. 381 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Asonuma.K: "Growth and quality of life after living-related liver transplantation in children." Pediatric Transplantation. 2. 64-69 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Egawa H.: "Application of in situ hybridization technique for quantitative assessment of ongoing symptomatic Epstein-Barr virus infection after living related liver transplantation." Clinical Transplantation. 12. 116-122 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Uemoto.S: "Living-related small bowel transplantation ; the first case in Japan." Pediatric Transplantation. 2. 40-44 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Fujimoto: "Living-Related Small Transplant ; Management of Rejection and Infection" Transplantation Proceeding. 30(179). 149 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Fujimoto: "Living-Related Donor Small Bowel Transplatnation : First Case in Japan" Transplantation Proceedings. 30. 3441-3442 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Tanaka: "Present status and prospects of living related liver transplantation" J.HepatoBiliary pancreatic Surgery. 4. 51-70 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Azuma: "Atypical Epstein-Barr virus infection during and after intermittent FK506 therapy" Acta Pediatrica Japonica. 39. 222-225 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Inomata: "Impact of the Development of a Liver Transplant Program on the Treatment of Biliary Atresia in an Institution in Japan" Journal of Pediatric Surgery. 32(8). 1201-1205 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] E.Hatano: "Hepatic preservation with histidine-tryptophan-ketoglutarate solution in living-related and cadaveric liver transplantation" Clincal Science. 93. 81-88 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Nishizawa: "Efficiency of Pentoxifylline in Donor Pretreatment in Rat Liver Transplantation." Journal of Surgical Research. 72. 170-176 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] N.Shinkura: "Presence of ANTI-FKBP12 Autoantibodies in Patients with Liver Allografts" Transplantation. 64(9). 1336-1342 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Kiuchi: "Living-donor Liver Transplantation in Kyoto, 1997" Clinical Transplants. 191-198 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T,Kiuchi: "A hepatic graft tuberculosis tranplanted from a living-related donor." Transplantation.63(6). 905-907 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Inomata: "Living Donor Liver Transplantation:An8-Year Experience With 379 Consecutive Cases" Transplantation Proceedings. 31. 381 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Fujimoto: "Living-Related Small Transplant;Management of Rejection and Infection" Transplantation Proceeding. 30. 179 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Fujimoto: "Living-Related Donor Small Bowel Transplatnation:First Case in Japan" Transplantation Proceedings. 30. 3441-3442 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Asonuma K: "Growth and quality of life after living-related liver transplantation in children." Pediatric Transplantation. 2. 64-69 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 小柴貴明: "小腸保存-臨床経験をもとに-" Organ Biology. 5. 1 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Egawa H: "Application of in situ hybridization technique for quantilative assessment of ongoing symptomatic Epstein-Barr virus intection after living related liver transplantation." Clinical Transplantation. 12. 116-122 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 猪股裕紀洋: "小腸移植の現況-生体小腸移植の経験をふまえて-" 日本小児栄養消化器病学会. 12(1). 24-30 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 瓜生原健嗣: "微細小血管の吻合" 外科治療. 301-305 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中紘一: "小腸移植" 日本医師会雑誌. 119. 11 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 林 道廣: "脳死移植の現況と将来" 現代医療. 30(9). (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Kiuchi: "Living-donor Liver Transplantation in Kyoto,1997" Clinical Transplants. 191-198 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 猪股裕紀洋: "免疫抑制療法" Pharma Medica. 15. 27-35 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 猪股裕紀洋: "生体小腸移植の経験から" 今日の移植. 10(4). 537-543 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 上本伸二: "生体肝移植とEBウイルス関連腫瘍" 小児がん. 34(2). 223-227 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 猪股裕紀洋: "生体肝移植の基礎と臨床" 小児科臨床. 50. 2530-2540 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Kiuchi: "A hepatic gragt tuberculosis tranplanted from a living-related donor." Transplantation. 63(6). 905-907 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Tanaka: "Present status and prospective view of living related liver transplantation." J.Hepato Biliary pancreatic Surgery. 4. 51-70 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Azuma: "Atypical Epstein-Barr virus infection during and after intermittent FK506 therapy." Acta Pediatrica Japonica. 39. 222-225 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Inomata: "Impact of the Development of a Liver Transplant Program on the Treatment of Biliary Atresia in an Institution in Japan" Journal of Pediatric Surgery. 32(8). 1201-1205 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] E.Hatano: "Hepatic preservation whith histidine-tryptophan-ketoglutarate solution in living-related and cadaveric liver transplantation." Clincal Science. 93. 81-88 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Nishizawa: "Efficiency of Pentoxifylline in Donor Pretreatment in Rat Liver Transplantation." Journal of Surgical Research. 72. 170-176 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Shinkura: "Presence of Anti-Fkbp12 Astoantibodies in Patients with Liver Allografts" Transplantation. 64(9). 1336-1342 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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