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1998 Fiscal Year Final Research Report Summary

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
Keywordssmall bowel transplantation / pig / rejection / apoptosis / Tacrolimus
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

  • Research Products

    (36 results)

All Other

All Publications (36 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-12-08  

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