1990 Fiscal Year Final Research Report Summary
Immunosuppressive Therapy and Preservation in Liver Transplantation
| Project/Area Number |
01480311
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
TAKAGI Hiroshi Nagoya Univ. School of Med., Professor, 医学部, 教授 (70154755)
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| Co-Investigator(Kenkyū-buntansha) |
TOMITA Tadao Nagoya Univ. School of Med., Professor, 医学部, 教授 (50078763)
HABA Toshihito Nagoya Univ. School of Med., Assistant Professor, 医学部, 助手 (30228522)
HAYASHI Shuji Nagoya Univ. School of Med., Assistant Professor, 医学部, 助手 (30218573)
HARADA Akio Nagoya Univ. School of Med., Assistant Professor, 医学部, 助手 (50198909)
NONAMI Toshiaki Nagoya Univ. School of Med., Assistant Professor, 医学部, 助手 (80189422)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Liver preservation / Endothelial cell / Factor VIII related antigen / FK506 / UW-solution / ^<31>P-NMR |
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| Research Abstract |
I. Liver Preservation :
1. ^<31>P-NMR Study of Phospholipid Metabolites in Hypothermic-Preserved Liver.
Liver was perfused by Euro-Collins- or UW-solution, quickly resected and preserved at 4'C. By the ^<31>P-NMR study, it was clearly demonstrated that alpha-glycerophosphate (alpha-GP) increased in livers preserved in both solutions, but much pronounced in EC-solution. Thus, alpha-GP may reflect the extent of phospholipid degradation and correlate with organ viability.
2. Microvascular Changes of the Liver Preserved in UW-solution.
Livers preserved in UW solution or in Euro-Collins solution were examined with an immunohistochemical method using anti-Factor VIII related antigen (FRA). In EC group, endothelial cell damages was severe and FRA expression on the endothelium was diminished. Furthermore, sinusoid in zone III was filled with FRA-positive contents. In UW group, these changes were mild and only a few FRA-positive contents were recognized. Thus, UW solution prevents endothelial cell damage and microcirculatory injury in zone III during preservation period.
II. Immunosuppressant, FK506 :
1. Pathological and Immunohistochemical Examination in the Rat Treated with FK506.
Rats were administered FK506 for 4 days, and sacrificed on day 2, 5, 7, 9, and 11. Liver and pancreas were resected, fixed in PLP and immunostained using anti-FRA MoAb. Endothelium of sinusoid was not damaged and the levels of GOT and GPT showed S little increase. However, it was clearly demonstratedin UW group that endothelium of the vessels in pancreas was detached from basement membrane and lost its expression of FRA, and that serum amylase level markedly increased during FK506 administration. These change were reversible by the cessation of the FK506 administration. Thus, FK506 has a toxicity on vascular endothelium of pancreas and that has a possibility to cause pancreatitis.
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