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Exploration of new genes related to achivement of transplantation tolerance in living donor liver transplantation

Research Project

Project/Area Number 12307024
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionMie University (2001-2002)
Kyoto University (2000)

Principal Investigator

UEMOTO Shinji  Mie University Faculty of Medicine Professor, 医学部, 教授 (40252449)

Co-Investigator(Kenkyū-buntansha) LI Xiao-kang  国立成育医療センター研究所, 移植・外科研究部, 室長 (60321890)
INOMATA Yukihiro  Kumamoto University Faculty of Medicine Professor, 医学部, 教授 (50193628)
TANAKA Kouichi  Kyoto University Faculty of Medicine Professor, 医学研究科, 教授 (20115877)
YOKOI Hajime  Mie University Faculty of Medicine Assistant Professor, 医学部, 講師 (60174843)
KIMURA Hiromitsu  Department of collaborative Research National research Institute for Child Health and development Director, 共同研究管理室, 室長 (80115477)
貝原 聡  京都大学, 医学研究科, 講師 (70324647)
鈴木 盛一  国立生育医療センター研究所, 移植・外科研究部, 部長 (00111386)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥33,720,000 (Direct Cost: ¥30,900,000、Indirect Cost: ¥2,820,000)
Fiscal Year 2002: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2001: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2000: ¥21,500,000 (Direct Cost: ¥21,500,000)
Keywordsgene / DANmicroarray / living donor liver transplantation / Immunosuppression / transplant tolerance
Research Abstract

Seventy recipients were enrolled in elective weaning immunosuppression at Kyoto University Hospital. Twenty-four recipients achieved complete withdrawal of immunosuppression, 37 were during weaning, and 9 encountered rejection. Fifty-four recipients were enrolled in nonelective weaning of immunosuppression. Thirty-four recipients achieved complete withdrawal, 7 were during weaning, and 13 encountered rejection. At Mie University Hospital, 3 recipients were enrolled in nonelective weaning because of EB virus infection. One recipient achieved complete withdrawal, but remaining 2 encountered rejection.
Total RNA was extracted from peripheral blood lymphocytes of recipients who accomplished complete withdrawal of immunosuppression and normal volunteers. RNA was analyzed by cDNA microarray (Agilent) comparing mRNA expression of recipients with that of normal volunteers. Number of genes with up-regulated mRNA expression was 120, and that with down-regulated expression was 169. Genes with up-regulated or down-regulated expression were divided into subgroups according to gene-related function. Number of up-regulated or down-regulated genes were 4/3 for [Apoptosis], 2/2 for [Cell cycle], 2/7 for [Cytokine], 4/4 for [DNA metabolism], 1/0 for [Heat shock protein], 3/7 for [Receptor], 16/18 for [Signal transduction], 7/14 for [Stress], 8/13 for [Transcription], 9/14 for [Transporter], and 72/113 for undetermined factor, respectively.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Y.Yano, M.Hara, T.Miyahara, K.Shibata, T.Onitsuka, Y.Nawa, X-K.Li, et al.: "Microchimeric cells from the peripheral blood associated with cardiac grafts are bone marrow derived long-lived and maintain acquired tolerance to minor histocompatibility antigen H-Y"Transplantation. 71・10. 1456-1462 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Ohba, XK.Li, Y.Kita, S.Enosawa, N.Funeshima, H.Nagai, HQ.Zhang, et al.: "Long-term graft acceptance in rat heart transplantation by CLTA4Ig gene transfection combined with FTY720 treatment"World J Surg. 25・4. 391-398 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Takatsuki, S.Uemoto, Y.Inomata, H.Egawa, T.Kiuchi, S.Fujita, et al.: "Weaning of immunosuppression in living donor liver transplant recipients"Transplantation. 72・3. 449-454 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Takatsuki, S.Uemoto, Y.Inomata, S.Sakamoto, M.Hayashi, M.Ueda, et al.: "Analysis of alloreactivity and intragraft cytokine profiles in living donor liver tansplant recipients with graft acceptance"Transplant immu.. 8. 279-286 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] L Guo, M.Fujino, H.Kimura, N.Funeshima, Y.Kitazawa, et al.: "Simultaneous Blockade of Co-stimulatory signals, CD28 and ICOS, induced a stable tolerance in rat heart transplantation"Transplant immu. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] L Guo, X-K, Li, N.Funeshima, M Fujino, Y.Nagata, H.Kimura, H.Amemiya, et al.: "Prologend survival in rat liver transplantation with mouse monoclonal antibody against an inducible co-stimulator (ICOS)"Transplantation. 73・7. 1027-1032 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Yano, M.Hara, T.Miyahara, K.Shibata, T.Onitsuka, Y.Nawa, X-K.Li, S.Suzuki, H.Amemiya, H.Kimura: "Microchimeric cells from the peripheral blood associated with cardiac grafts are bone marrow derived, long-lived and maintain acquired tolerance to minor histocompatibility antigen H-Y"Transplantation. 71(10). 1456-1462 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Ohba, X-K.Li, Y.Kita, S.Enosawa, N.Funeshima, H.Nagai, HQ.Zhang, T.Okuyama, S.Ogoshi, S.Sasaguri, H.Amemiya, S.Suzuki: "Long-term graft acceptance in rat heart transplantation by CTLA4Ig gene transfection combined with FTY720 treatment"World J Surg. 25(4). 391-398 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Takatsuki, S.Uemoto, Y.Inomata, H.Egawa, T.Kiuchi, S.Fujita, M.Hayashi, T.Kanematsu, K.Tanaka: "Weaning of immunosuppression in living donor liver transplant recipients"Transplantation. 72(3). 449-454 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Takatsuki, S.Umemoto, Y.Inomata, S.Sakamoto, M.Hayashi, M.Ueda, T.Kanematsu, K.Tanaka: "Analysis of alloreactivity and intragraft cytokine profiles in living donor liver transplant recipients with graft acceptance"Transplant immu. 8. 279-286 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] L.Guo, M.Fujino, H.Kimura, N.Funeshima, Y.Kitazawa, Y.Harihara, K.Tezuka, M.Makuuchi, S.Suzuki and X-K.Li: "Simultaneous Blockade of Co-stimulatory Signals, CD28 and ICOS, Induced a Stable Tolerance in Rat Heart Transplantation"Transplant Immunology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] L.Guo, X-K.Li, N.Funeshima, M.Fujino, Y.Nagata, H.Kimura, H.Amemiya, S.Enosawa, T.Tsuji, Y.Harihara, M.Makuuchi, S.Suzuki: "Prolonged survival in rat liver transplantation with mouse monocronal antibody against an inducible co-stimulator(ICOS)"Transplantation. 73(7). 1027-1032 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] L.Guo, et al.: "Simultaneous Blockade of Co-stimulatory Signals, CD28 and ICOS, Induced a Stable Tolerance in Rat Heart Transplantation"Transplant Immunology. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] L Guo, et al.: "Prolonged survival in rat liver transplantation woth mouse monoclonal antibody against an inducible co-stimulator (ICOS)"Transplantation. 73. 1027-1032 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] X-K.Li, et al.: "Prolongation of transgene by co-expression of cytokine response modifier A in rodent liver after adenoviral gene transfer"Molecular Therapy. 5. 262-268 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Fujino, et al.: "Distinct Pathways of Apoptosis Triggered by FY720, Etoposide and Anti-Fas Antibody in Human T-Lymphoma Cell Line (Jurkat Cells)"J Pharmacol Exp Ther. 300. 939-945 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 藤(舟島)直子: "ラット心移植モデルにおけるテロメラーゼ活性によるリンパ球活性化の評価"移植. 37. 260-266 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mitsuhisa.TAKATSUKI, et.al: "Analysis of alloreactivity and intragraft cytokine profiles in living donor liver transplant recipients with graft acceptance"Transplant Immunology. 8. 279-286 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mitsuhisa.TAKATSUKI, et.al: "Weaning of immunosuppression in living donor liver transplant recipients"Transplantation. 72. 449-454 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] X-K.Li, et.al: "Fulminant Hepatitis by Fas-Ligand Expression in MRL-lpr/lpr Mice Grafted with Fas-Positive Livers and Wild-Type Mice with Fas-Mulant Livers"Transplantation. 71. 503-508 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.FUJINO, et.al: "In vitro prevention of cell-mediated xenograft rejection via the Fas/FasL-Pathway in CrmA-transducted porcine kidney cells"Xenotransplantation. 8. 115-124 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.FUJINO, et.al: "Selective repopulation of mice liver after fas-resistant hepatocytes transplantation"Cell Transplantation. 10. 353-361 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] X-K.Li, et.al: "Fulminant Hepatitis by Fas-Ligand Expression in MRL-lpr/lpr Mice Grafted with Fas-Positive Livers and Wild-Type Mice with Fas-Mutant Livers."Transplantation. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] X-K.Li, et.al: "Induction of lymphocyte apoptosis in rat liver allograft with ongoing rejection by FTY720."Clinical and Experimental Immunology. 123(2). 331-339 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] X-K.Li, et.al: "Inhibition of Fas-mediated fulminant hepatitis in CrmA gene-transfected mice."Biochem Biophys Res Commun.. 273. 101-109 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Koichi Tanaka: "Current status of living donor liver transplantation in adults"Current Opinion in Organ Transplantation. 5・2. 74-79 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] SHINJI UEMOTO,: "Living donor liver transplantation for fulminant hepatic failure"Transplantation. 70・1. 152-157 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 上本伸二: "小児生体部分肝移植"臨床外科. 55・1. 55-59 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高槻光寿: "生体肝移植後の免疫抑制剤減量・離脱の試み"今日の移植. 13・1. 19-23 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 田中紘一: "マイクロキメリズムと臓器移植"免疫Immunology Frontier. 10・2. 35-39 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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