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1998 Fiscal Year Final Research Report Summary

Molecular biological modification of the target organ

Research Project

Project/Area Number 09470247
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, Assistant Professor, 医学部, 講師 (60240206)

Co-Investigator(Kenkyū-buntansha) CARLOS Del Carpio  Toyohashi University of Technology, Assistant Professor, エコロジー工学系, 講師 (20231053)
KOBAYASHI Takaaki  School of Medicine, Staff, 医学部, 医員
HAYASHI Shuji  School of Medicine, Nagoya University, Research Assistance, 医学部, 助手 (30218573)
Project Period (FY) 1997 – 1998
KeywordsApoptosis / Organ transplantation / Fas antigen / Free radical / super oxide dismutase (SOD) / フリーラジカル
Research Abstract

The ultimate goal of the clinical organ transplantation is to establish an immunological tolerance of the recipient. Ideally, this is to be achieved not by interfering the recipient's immunological defense mechanism but by altering the immunogeneicity of the donor graft, thus minimizing the risk of immunosuppression of the recipient. This concept is the basis of the present research.
The graft is a target organ which is succumbed to immunological attack by the recipient. From the aspect of molecular biology, this type of cytotoxicity of the graft organ results from apoptosis of the cell. We hypothesize that prevention of apoptosis can be achieved by modulating the apoptosis-associated molecules with the use of genetic manipulation. We used hepatocytes and endothelial cells as the target cells. We have found that tacrolimus, commonly used immunoxsuppressant, is capable of reducing Fas antigen expression of the hepatocytes. The endothelial cells are known to be the prime target of both ischemia reperfusion injury and immunological cytotoxicity. This type of cytotoxicity is also noted to be as a result of apoptosis. We were able to transfect human copper, zinc-super oxide dismutase (Cu, Zn-SOD) into the endothelial cells. These cells became resistant to the free radical which is the principal form of cytotoxicity associated with preservation injury of the graft. Simultaneously, we found that cytosolic calcium is increased in association with endothelial cell apoptosis which suggests calcium blocking as a useful means for prevention of apoptosis.
We, therefore, believe that biological manipulation of the apoptosis-associated molecules can prevent cytotoxicity in organ transplantation which may ultimately establish immunological tolerance.

  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Yokoyama I Takagi H: "Apoptosis in Pig Endothelial Cells After Reperfusion and Its Prevention by Induction of Human Cu,Zn-SOD cDNA" Transplantation Proceeding. 29・. 1364-1364 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] I Yokoyama,Shuji Hayashi,Hiroshi Takagi: "Hepatocyte apoptosis and cytosolic calcium dynamics in ischemic injury." Transplantation Proceeding. 29・8. 3514-3514 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokoyama I,Tabuchi Y,Takagi H: "Measurement of portal venous flow velocity with an implantable miniature Doppler probe in pig liver transplantation" Transplant International. 10・2. 116-120 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Itsuo Yokoyama,Akemi Hayakawa,Hiroshi Takagi: "Fas antigen expression of hepatocytes and its modification by immunosuppressants." Digestive Diseases & Sciences. 42・1. 2471-2475 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 横山逸男、高木 弘: "同種移植における拒絶反応と細胞死" 医学のあゆみ. 182・2. 119-122 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasushi Namii,Itsuo Yokoyama,Hiroshi Takagi: "Evidence that the adenoviral vector containing the CTLA4-Ig gene improves transgene expression and graft survival." Transplantation Proceedings. 29・3. 1738-1739 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Tachi,Itsuo Yokoyama,Hiroshi Takagi: "Variability of cytotoxicity to pig cultured cells and its determinant factor in human sera." Transplantation Proceedings. 30・1. 71-73 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] C Koike,I Yokoyama,H Takagi: "Direct gene replacement of the mouse α(1,3)-galactosylferase gene with human α(1,2) fucosyltransferase gene : Converting α-galactosyl epitopes into Hantigens" Xenotransplantation. 4・. 147-153 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T Kobayashi,I Yokoyama,H Takagi: "TAP1,TAP2,LMP2,DMA,and DMB genetic polymorphisms in renal transplantation." Transplantation Proceedings. 30・1. 29-30 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 林 衆治、横山逸男、高木 弘: "同種移植及び異種移植における遺伝子制御に関する研究" 今日の移植. 11・2. 157-164 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S Hayashi,I Yokoyama,H Takagi: "Establishment of complement-resistant retroviral vector by homologous restriction factor 20 gene." Gene Therapy. 5・. 282-285 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi,I Yokoyama H Takagi: "Feasibility of Double-Expression Retroviral Vector Using Complement regulatory Factor Gene" Journal of Surgical Research. 78・. 64-67 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S Hayashi,I Yokoyama,H Takagi: "Protection of xeno-hepatocytes from complement-mediated cytolysis by transduction with homologous restriction factor 20 gene using retroviral vector." European Surgical Research. 30・3. 161-167 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A Katayama,I Yokoyama,T Muramatsu,H Takagi: "Porcinr α-1.3-galactosyltransferase : full lengt cDNA cloning,genomic organization,and analysis of splicing variants" Glycoconjugate Journal. 15・. 583-589 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K Uchiyama,H Muramatsu,I Yokoyama,T Muramatsu: "Human N-Acetylglucosamine-6-O-Sulfo transferase Involved in the Biosynthesis of 6-Sulo Sialyl Lewis X : Molecular Cloning,chromosomal mappimg,and Expression in Various Organs and Tumor Cells" The Japanese Biochemical Society. 124・. 670-678 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Hayashi,I Yokoyama,and H.Takagi: "Technique of Triple Splir-Liver Transplantation in Pigs Using Interior Vena Cava Reconstruction and Intraoperative Intrahepatic Portosystemic Shunt" Transplantation Proceedings. 30・7. 3229-3231 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S Hayashi,M.G.Lin,I Yokoyama,H Takagi: "Auxiliary orthotopic Xenogeneic Liver Transplantation Using Pigs for Fulminant Hepatic failure : With Special Reference to the Technique and Immunosuppression" Transplantation Proceedings. 30・. 3836-3836 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Nagasaka,I Yokoyama,and H.Takagi: "Inhibitory Effect of α(1,2) Fucosyltransferase Recombinant Adenoviral Vector on αGal Expression" Transplantation Proceedings. 30・. 3837-3838 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小川晴子、小林孝彰、門松健治、横山逸男、高木 弘、村松 喬: "異種移植における抗原の制御" Organ Biology. 5・4. 25-33 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shuji Hayashi,Takaharu,I Yokoyama Nagasaka,Taiki Kojima,I Yokoyama: "Combination splitting using both in situ and ex situ Techniques in triple split liver transplantation in pigs" Transplantation International. 11・. 408-412 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokoyama I Takagi H: "Apoptosis in Pig Endothelial Cells-After Reperfusion and Its Prevention by Induction of Human Cu, Zn-SOD cDNA" Transplantation Proceeding. 29. 1364-1364 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokoyama I,Shuji Hayashi, Hiroshi Takagi: "Hepatocyte apoptosis and cytosolic calcium dynamics in ischemic injury." Transplantation Proceeding. 29. 3514-3514 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokoyama I,Tabuchi Y,Takagi H: "Measurement of portal venous flow velocity with an implantable miniature Doppler probe in pig liver transplantation" Transplant International. 10. 116-120 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokoyama I,Akemi Hayakawa, Hiroshi Takagi: "Fas antigen expression of hepatocytes and its modification by immunosuppressants." Digestive Diseases & Sciences. 42. 2471-2475 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasushi Namii, Itsuo Yokoyama, Hiroshi Takagi: "Evidence that the adenoviral vector containing the CTLA4-Ig gene improves transgene expression and graft survival." Transplantation Proceedings. 29. 1738-1739 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S Hayashi, I Yokoyama, H Takagi: "Adenovirus-mediated gene transfer to the xenogeneic liver in liver xenotransplan-tation : the transduction of complement regulatory factor genes (DAF and HRF20)." Transplantation Proceedings. 29. 2211-2211 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S Hayashi, I Yokoyama, H Takagi: "Effect of CTLA4-Ig gene transfer using adenoviral vector in organ and cell transplantation." Transplantation Proceedings. 29. 2212-2212 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A Katayama, I Yokoyama, H Takagi: "Studies of alpha-Gal dependent hyperacute xenotransplant rejection using double knockout embryonic stem cells." Transplantation Proceedings. 29. 2262-2262 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H Asano, I Yokoyama, H.Inoko, H Takagi: "Significance of tumor necrosis factor microsatellite polymorphism in renal transplantation." Tissue Antigens. 50. 484-488 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T Nagasaka, I Yokoyama, T Muramatsu, H Takagi: "alpha-Galactosyl oligosaccharides conjugated with polyethylene glycol as potential inhibitors of hyperacute rejection upon xenotransplantation" Biochemical and Biophysical Research Communications. 232. 731-736 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasutomi M,I Yokoyama, Takagi H: "Evaluation of tetrahydropyranyladriamycin as an immunosuppressant in concordant xenotransplantation" The Journal of Heart Lung Tranplantation. 16. 283-289 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuji Tachi, Itsuo Yokoyama, Hiroshi Takagi: "Variability of cytotoxicity to pig cultured cells and its determinant factor in human sera." Transplantation Proceedings. 30. 71-73 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] C Koike, I Yokoyama, H Takagi: "Direct gene replacement of the mouse alpha(1,3)-galactosylferase gene with human alpha(1,2)fucosyltransferase gene : Converting alpha-galactosyl epitopes into H antigens" Xenotransplantation. 4. 147-153 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T Kobayashi, I Yokoyama, H Takagi: "TAP1, TAP2, LMP2, DNA,and DMB genetic polymorphisms in renal transplantation." Transplantation Proceedings. 30. 29-30 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S Hayashi, I Yokoyama, H Takagi: "Establishment of complement-resistant retroviral vector by homologous restriction factor 20 gene." Gene Therapy. 5. 282-285 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S Hayashi, I Yokoyama, H Takagi: "Feasibility of Double-Expression Retroviral Vector Using Complement regulatory Factor Gene" Journal of Surgical Research. 78. 64-67 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S Hayashi, I Yokoyama, H Takagi: "Protection of xeno-hepatocytes from complement-mediated cytolysis by transduction with homologous restriction factor 20 gene using retroviral vector" European Surgical Research. 30. 161-167 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A Katayama, I Yokoyama, T Muramatsu, H Takagi: "Porcinr alpha-1.3-galactosyltransferase : full length cDNA cloning, genomic organization, and analysis of splicing variants" Glycoconjugate Journal. 15. 583-589 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K Uchiyama, H Muramatsu, I Yokoyama, T Muramatsu: "Human N-Acetylglucosamine-6-O-Sulfotransferase Involved in the Biosynthesis of 6-Sulo Sialyl Lewis X : Molecular Cloning, chromosomal mapping, and Expression in Various Organs and Tumor Cells" The Japanese Biochemical Society. 124. 670-678 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Hayashi, I Yokoyama, and H.Takagi: "Technique of Triple Splir-Liver Transplantation in Pigs Using Inferior Vena Cava Reconstruction and Intraoperative Intrahepatic Portosystemic Shunt" Transplantation Proceedings. 30. 3229-3231 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S Hayashi, M.C.Lin, I Yokoyama, H Takagi: "Auxiliary orthotopic Xenogeneic Liver Transplantation Using Pigs for Fulminant Hepatic failure : With Special Reference to the Technique and Immunosuppression" Transplantation Proceedings. 30. 3836-3836 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Nagasaka, I Yokoyama, and H.Takagi: "Inhibitory Effect of alpha(1,2)Fucosyltransferase Recombinant Adenoviral Vector on alpha Gal Expression" Transplantation Proceedings. 30. 3837-3838 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shuji Hayashi, Itsuo Yokoyama, Hiroshi Takagi: "Combination splitting using both in situ and ex situ Techniques in triple split liver transplantation in pigs" Transplantation International. 11. 408-412 (1998)

    • 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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