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Strategic approach with the aid of molecular biology in regulation of xenograft rejection

Research Project

Project/Area Number 11470243
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionNagoya University

Principal Investigator

YOKOYAMA Itsuo  School of Medicine, Nagoya University, Assistant Professor, 医学部, 講師 (60240206)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Takaaki  School of Medicine, Nagoya University, Research Associate, 医学部, 助手 (70314010)
HAYASHI Shuji  School of Medicine, Nagoya University, Research Associate, 医学部, 助手 (30218573)
波井 康  名古屋大学, 医学部, 医員
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2000: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1999: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsTransplantation / Xenotransplantation / discordant transplantation / 1-3 alpha galactose / apoptosis / galactosidase / hyperacute rejection / galactosyl transferase / ガラクトース(α1-3Gal / Fas / Bax / bcl-2 / Caspase / Fasリガンド / アデノウィルス / リポゾーム / エンドベータガラクトシダーゼ
Research Abstract

Approximately seven hundred millions of people die each year in Japan, in which end-stage failure of vital organs such as heart, liver and kidney. Definitive treatment for such diseases is yet established and an ultimate way of saving patients with such diseases is implantation of artificial organs that fulfill the complicated function of the organ. Organ transplantation is a currently available definitive treatment for those end-stage diseases, though not an ultimate form of remedy. Allotransplantation between the human is now widely performed, although a limited number of organ sauce and an unnecessary burden on the recipients are the two obstacles for its development. Xenotransplantation can be an alternate method of organ transplantation such as pig to human transplantation since the donor organ can be supplied unlimitedly. However, a vigorous rejection occurs in the xenotransplantation in the pig to human, so called discordant transplantation. The aim of the present study was to investigate how we could overcome the hyperacute rejection.
The mechanism of hyeracute rejection has been partially understood and the key event is an interaction between the 1-3 alpha galactose of the pig organ and the natural antibody of the human serum. The findings that we obtained are the followings : 1) the effect of cell death inducing factors and the viability of the xeno-graft ; 2) Apoptosis of the xeno-graft (endothelial cells) cells and its induction mechanism, or interaction of the cell-surface receptors, super-oxide and caspases ; 3) clonins of the 1-3 alpha galactosyl transferase and its degrading enzyme of galactosidase.
We believe that he results of the present study can contribute more effective regulation of the hyperacute rejection in the discordant xenotransplantation that can be applicable to future clinical use.

Report

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

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Azumi M. et al.: "Antibacterial activity of multiple antigen peptides homologous to a loop region In human Lactoferrin."J Peptide Res. 54. 237-241 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogawa h, et al.: "Suppression of porcine xenoantigen expression by dominant-negative effegt of α1,3 galactory Itransferase (α 1,3GT) splicing variants."Transplant Proc.. 32. 287-288 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morozumi K, et al.: "Immunohistolgical study on the graft following allo-and xeno-transplantation In recipients with preformed antibody."Transplant Proc.. 32. 841-842 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi T, et al.: "Significance of transporter with Antigen Processing Gene Polymorphism living related renal tansplantation."Human Immunology. 61. 670-674 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogawa H, et al.: "Molecular cloning of endo-beeta-galactosidase C and It's application In removing alfagalactosyl xenoantigen blood vessels In the pig kidney."J Biol Biochem. 25. 19368-19371 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 小川晴子: "糖鎖を切断するEndo Galによる異種移植-拒絶反応の制御"細胞工学. 19. 844-848 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 横山逸男: "異種移植"診断と治療社. 143-148 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 小林孝彰: "肝移植の展望"診断と治療社. 149-156 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Azumi M, Kojima T, Yokoyama I, Tajiro H, Yoshikawa K, Saga S, Del Carpio C.A.: "Antibacterial activity of multiple antigen peptides homologous to a loop region In human Lactoferrin."J Peptide Res. 54. 237-241 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogawa H, Kobayashi T, Yokoyama I, Nagasaka T, Namii Y, Kadomatsu K, Muramatsu T, Takagi A.: "Suppression of porcine xenoantigen expression by dominant-negative effegt of α1,3 galactory Itransferase (α1, 3GT) splicing variants."Transplant.Proc.. 32. 287-288 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Morozumi K., Oikawa T, Usami T, Takeuchi O, Koyama A, Kimura G, Kobayashi T, Yokoyama I, Hayashi S, Nagasaka Y, Namii Y, Nakao A, Takagi H.: "Immunohistilogical study on the groft following allo-and xeno-transplantation In recipients preformed antibody."Transplant.Proc.. 32. 841-842 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi T, Yokoyama I, Inoko H, Hayashi S, Morozumi K, Uchida K, Nakao A.: "Significance of transporter with Antigen Processing Gene Polymorphism living related renal transplantation."Human Immunology. 61. 670-674 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogawa H, Muramatsu H, Kobayashi T, Morozumi K, Yokoyama I, Kurosawa A, Muramatsu T.: "Molecular cloning of endo-beeta-galactosidase C and It's application In removing alfa-galactosyl xenoantigen blood vessels In the pig kidney."J Biol Biochem. 25. 19368-19371 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogawa H., Kobayashi T, Yokoyama I, Nakao A, Muramatsu T.: "Tousa wo setsudannsuru Endo Gal C ni yoru Ishuishoku kyozehannou no seigyo"Saiboukougaku. 19. 844-848 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Itsuo Yokoyama: "Ishuishoku"Shindan to tiryousha. 143-148 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi Takaaki: "Kannishoku no tenbou"Shindan to tiryousha. 149-156 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Azumi M. et al.: "Antibacterial activity of multiple antigen peptides homologous to a loop region In human Lactoferrin."J Peptide Res. 54. 237-241 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ogawa h, et al.: "Suppression of porcine xenoantigen expression by dominant-negative effegt of α1,3 galactory Itransferase(α 1,3GT)splicing variants."Transplant Proc.. 32. 287-288 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Morozumi K, et al.: "Immunohistological study on the graft following allo-and xeno-transplantation In recipients with preformed antibody."Transplant Proc.. 32. 841-842 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi T, et al.: "Significance of transporter with Antigen Processing Gene Polymorphism living related renal transplantation."Human Immunology. 61. 670-674 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ogawa H, et al.: "Molecular cloning of endo-beeta-galactosidase C and It's application In removing alfa-galactosyl xenoantigen blood vessels In the pig kidney."J Biol Biochem. 25. 19368-19371 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小川晴子: "糖鎖を切断するEndo Galによる異種移植-拒絶反応の制御"細胞工学. 19. 844-848 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 横山逸男: "異種移植"診断と治療社. 143-148 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 小林孝彰: "肝移植の展望"診断と治療社. 149-156 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kojima T, Del Carpio C A, Tajiri H, Yoshikawa, Saga S, Yokoyama I: "Inhibition of complement-medited immune hemolysis by peptides derived from constant domain of immunoglobulin"Brief Communications. 637-638 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayashi S, Yokoyama I, Namii Y, Emi N, Uchida K, Takagi H.: "Inhibition of hepatic metastasis in murine colon cancer transfected with tissue plasminogen activator gene."Cancer Gene Therapy. 6・4. 380-384 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayakawa A, Yokoyama I, Tajiri H, Okamoto T, Nakashima I: "Protein Kinase C-dependent anti-apoptotic mechanism that is associated with high sensitivity to anti-Fas antibody in ovarian cancer cell lines"Cancer Letters. 140. 113-119 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yokoyama I, Negita M, Hayakawa A, Hayashi S, Kobayashi T, Namii Y, Nagasaka T, Takagi H: "Cytosolic calcium dynamics and free radical-induced apoptosis of the endothelial cells."Transplantation Proceedings. 31. 808-809 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Morozumi K, Kobayashi T, Usami T, Oikawa T Matsuda H, Yokoyama I, Takagi H: "Significance of histochemical expression of Hanganutzi-Deicher antigen in pig, baboon and human tissues."Transplantation Proceedings. 31・1/2. 942-944 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayashi S, Namii Y, Mei G-L, Liu D-K, Yokoyama I, Hamada H, Takagi H.: "Effect of adenovirus-mediated gene transfer with CTLA4Ig gene in organ transplantation."Transplantation Proceedings. 31. 1944-1945 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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