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A study of molecular diagnosis and treatment for chronic cardiac allograft rejection.

Research Project

Project/Area Number 10557122
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Thoracic surgery
Research InstitutionOsaka University

Principal Investigator

SHIRAKURA Ryota  Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (00116047)

Co-Investigator(Kenkyū-buntansha) FUKUSHIMA Norihide  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30263247)
SAWA Yoshiki  Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (00243220)
MIYAGAWA Shuji  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90273648)
SAKAKIDA Satoru  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90311753)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥9,200,000 (Direct Cost: ¥9,200,000)
KeywordsChronic rejection / Rat / Heterotopic heart transplantation / Quantitative RT-PCR / 定量的RT-PCR法
Research Abstract

This study was performed as three parts described as below.
1 : We have measured the dynamics of 65 different immune gene expressions using real-time quantitative RT-PCR in retransplanted rat hearts developing cardiac allograft vasculopathy (CAV). This retransplantation model provided better opportunities to investigate the molecular mechanism, because the correlation between the occurrence of chronic rejection and the expression pattern of the identified gene was more stringent than those in other animal models. In summary of this part of the study, the importance of selective chemokine/receptor systems including IP10-CXCR3, RANTES-CCR5, and MCP1-CCR2 was indicated in addition to the implication of cytokines produced by activated T cells (IFN-γ and Fas ligand), growth factors for vascular smooth muscle cells (PDGF-β, TGF-β) in the progression of CAV.
2 : The developed technology using real-time RT-PCR was applied to the investigation of Myasthenia Gravis in clinical situation and provid … More ed the data suggesting the implication of suppressed class II transactivator gene-expression of dysregulation of MHC class II antigen on thymoma cells in pathogenesis of the disease. This results also indicated the feasibility of this method in clinical diagnosis of various diseases includeing CAV.
3 : Experimental gene therapy was performed using beta-adrenergic receptor gene and hepatocyte growth factor gene. In both cases, ischemia-reperfusion injury was attenuated by the introduction of either gene into a whole heart in vivo. It is conceivable that the technique should provide the way to treat CAV in clinical situation, because CAV is a local disorder under systemic immunosuppression.
Clinical heart transplantation in Japan has just began and it was impossible to apply the technique developed in this study on the clinical diagnosis of chronic rejection as originally planed. Nonetheless, this study provided several new methods applicable to the diagnosis and the treatment of CAV in clinical situation. Less

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] M.Tori, et al.: "Initial T-cell activation required for transplant vasculopathy in retransplanted rat cardiac allografts."Transplantation. 70(5). 737-746 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Kitagawa-Sakakida, et al.: "Active cell migration in retransplanted rat cardiac allograftsduring the course of chronic rejection."J Heart Lung Transplantation. 19(6). 584-590 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kadota, et al.: "Altered T cell development in human thymoma is related to impairement of MHC class II transactivator expression induced by interferon-gamma (IFN-γ).."Clinical and Experimental Immunology. 121. 59-68 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 岩田圭司 他: "ラット容量負荷肥大心におけるHGF/c-Metの発現についての検討"心筋の構造と代謝 -1999-. 22. 161-164 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 榊田悟 他: "心臓移植後の慢性拒絶反応"The Circulation Frontier. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kawahira,, et al.: "In vivo transfer of a β2-adrenergic receptor gene into the pressure-overloaded rat heart enhances cardiac response to β-adrenergic agonist."Circulation. 98. II262-II268 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kawahira,, et al.: "Gene transfection of beta 2-adrenergic receptor into the normal rat heart enhances cardiac response to beta-adrenergic agonist"J Thorac Cardiovasc Surg. 118. 446-451 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Ueda, et al.: "Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart.."Ann Thorac Surg. 67. 1726-1731 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 榊田悟,藤原大美: "新移植免疫学 第3章 移植抗原認識機構と急性拒絶反応"中外医学社. 24 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 榊田悟: "新移植免疫学 第4章 慢性拒絶反応と異種移植片拒絶反応"中外医学社. 21 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kawahira, et.al.: "In vivo transfer of a β2-adrenergic receptor gene into the pressure-overloaded rat heart enhances cardiac response to β-adrenergic agonist."Circulation. 98. II262-II268 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kawahira, et.al.: "Gene transfection of beta 2-adrenergic receptor into the normal rat heart enhances cardiac response to beta-adrenergic agonist."J Thorac Cardiovasc Surg. 118. 446-451 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Ueda, et.al.: "Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart."Ann Thorac Surg. 67. 1726-1731 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Kadota, et al.: "Altered T cell development in human thymoma is related to impairement of MHC class II transactivator expression induced by interferon-gamma (IFN-g)."Clinical and Experimental Immunology. 121. 59-68 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Tori, et al.: "Initial T-cell activation required for transplant vasculopathy in retransplanted rat cardiac allografts."Transplantation. 70. 737-746 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Kitagawa-Sakakida, et al.: "Active cell migration in retransplanted rat cardiac allograftsduring the course of chronic rejection."J Heart Lung Transplant. 19. 584-590 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Tori,S.Kitagawa-Sakakida,Z.Li,H.Izutani,K.Horiguchi,T.Ito,H.Matsuda,R.Shirakura: "Initial T-cell activation required for transplant vasculopathy in retransplanted rat cardiac allografts."Transplantation. 70・5. 737-746 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Kitagawa-Sakakida,M.Tori,Z.Li,K.Horiguchi,H.Izutani,H.Matsuda,R.Shirakura: "Active cell migration in retransplanted rat cardiac allografts during the course of chronic rejection."Journal of Heart and Lung Transplantation. 19・6. 584-590 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Kadota,S.Okumura,S.Miyoshi,S.Kitagawa-Sakakida,...S.Shirakura, et al.: "Altered T cell development in human thymoma is related to impairement of MHC class II transactivator expression induced by interferon-gamma (IFN-γ)."Clinical and Experimental Immunology. 121. 59-68 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 岩田圭司,澤芳樹,大竹重彰,西村元延,榊田悟,松田暉: "ラット容量負荷肥大心におけるHGF/c-Metの発現についての検討"心筋の構造と代謝-1999-. 22. 161-164 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 榊田悟,藤原大美: "新移植免疫学 第3章 移植抗原認識機構と急性拒絶反応"中外医学社. 24 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 榊田悟: "新移植免疫学 第4章 慢性拒絶反応と異種移植片拒絶反応"中外医学社. 21 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y. Kawahira,Y. Sawa, et al.: "In vivo transfer of a β2-adrenergic receptor gene into the pressure-overloaded rat heart enhances cardiac response to β-adrenergic agonist"Circulation. 98. II262-II268 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Kawahira,Y. Sawa et al.: "Gene transfection of beta 2-adrenergic receptor into the normal rat heart enhances cardiac response to beta-adrenergic agonist"J Thorac Cardiovasc Surg. 118. 446-451 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Ueda,Y. Sawa et al.: "Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart"Ann Thorac Sung. 67. 1726-1731 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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