| Project/Area Number |
06454614
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | The Tokyo University of Pharmacy and Life Sciences |
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Principal Investigator |
OKA Kitaro The Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Prof., 薬学部, 教授 (40057336)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Toshihiko The Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Associat, 薬学部, 助教授 (90173252)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1994: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | kidney transplantation / glucocorticoid / drug selection / prednisolone / methylprednisolone / peripheral blood lymphocyte / survival rate / allograft / glucocorticoid / methylprednisolone / peripheal blcal lymphoeytes / グルココルチコイド耐性 / メチルプレドニゾロン / プレドニゾロン / 慢性腎不全 / 腎移植 / 生着率 / 免疫抑制剤 / 生体腎移植 / 死体腎移植 / シクロスポリン |
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| Research Abstract |
Prophylactic effects of clinically available glecocorticoids on acute and chronic kidney allograft rejection differed steroid by steroid. There are two steroids which are used for immuno suppressive maintenance therary for kidney transplantation : prednisolone and methylprednisolone. In both living related and cadaveric allografts, methylprednisolone was much superior to prednisolone when their clinical outcomes were compared by 2-years graft survival rates. Our comparative study was carried out with ramdomely selected two treatment groups of recipients, prednisolone/cyclospoline and methylprednisolone/cyclospoline. Observed survival rates for 2 years following transplantation in methylprednisolone group was significantly higher than that of the prednisolone group. This difference related to the prednisolone-specific steroid resistance in chronic renal foilure patients. Almost all chronic renal failure patients are sensitive to methylprednisolone, whereas 20-30% of them are highly resistant to prednisolone. We tested the steroid susceptibilities of peripheral blood lymphocytes taken from the chronic renal failure patients to make differentiation invitro between resistant and sensitive patients. According to our clinical tests, better allograft survival rate was obtained when methylprednisolone to which the patients showed superior susceptibility was used. A possible cause of prednisolone resistant was considered to be resulted from acquired resistance of lymphocytes to escape apoptotic cell death induced by steroid. However, prednisolone-resitant lymphocytes were still susceptible to methylprednisolone. As a result, lymphocyte susceptibilities to apoptotic cell death differed steroid by steroid so that the two steroids gave different clinical outcomes of kidney transplantation.
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