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Study of Renal Transplantation by a New Immunosuppressive Method

Research Project

Project/Area Number 06304038
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section総合
Research Field Urology
Research InstitutionKinki University

Principal Investigator

KURITA Takashi  Department of Urology, Kinki University School of Medicine, Prof., 医学部, 教授 (10088528)

Co-Investigator(Kenkyū-buntansha) KAMIDONO Sadao  Department of Urology, Koube University School of Medicine, Prof., 医学部, 教授 (30030935)
KAWABE Kazuki  Department of Urology, Tokyo University School of Medicine, Prof., 医学部, 教授 (20124670)
OKUYAMA Akihiko  Department of Urology, Osaka University School of Medicine, Prof., 医学部, 教授 (20093388)
TOHMA Hiroshi  Department of Urology, Tokyo Women's Medical college, Prof., 教授 (90075549)
KOSHIBA Ken  Department of Urology, Kitazato University School of Medicine, Prof., 医学部, 教授 (40050380)
津川 龍三  金沢医科大学, 教授 (80064509)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥30,000,000 (Direct Cost: ¥30,000,000)
Fiscal Year 1996: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1995: ¥10,100,000 (Direct Cost: ¥10,100,000)
Fiscal Year 1994: ¥14,400,000 (Direct Cost: ¥14,400,000)
KeywordsT-cell associated cytokines / rat kidney transplantation / lymphocyte activation signal / microchimerism / FK506 / FTY720 / HGF / micro chinerism / HGF / IL-4 / トランスジェニックマウス / ethylcarbodiimide / 骨髄移植 / 増殖因子 / NO / SMA-SOD / 免疫抑制法 / 腎移植
Research Abstract

Induction of tolerance by transferrance of chemically modified alloantigens was reported last year. To analyze this mechanism, we examined T-cell associated cytokines within renal allografts in the tolerance model by RT-PCR.No expression of cytokines of mRNAs was observed in isografts. In contrast, allografts demonstrated expression of both Th1 (IL-2, gamma-INF) and Th2 (IL-4, IL-10) associated cytokines mRNAs. In addition, the expression of IL-2 mRNA in treated allografts was low compared with taht in untreated ones. This results suggested that induction of tolerance may be responsible for immunoredirection of Th1/Th2 function in allografts. Recently, a novel immunosuppressive agent, FTY720 is explored. We studied the immunosuppressive effect and mechanism of FTY720. This agent induced dramatic decrease of peripheral lymphocytes in native rats while other leukocytes showed no significant changes. Enhancement of renal allograft survival was observed by oral administration of FTY720. In … More terestingly, pretreatment with FTY720 was more effective than posttransplant administration. Detection for apoptosis was tried because we found atrophic spleens in long-term survival rats receiving FTY720. No apoptosis was detected in spleens of FTY720-treated transplanted rats. Thereafter, production Th1 associated cytokines was examined in spleens during rejection (posttransplant day 5). We detected IL-2 mRNA in spleens of untreated transplanted rats by RT-PCR.However, no expression of this mRNA in spleens of treated transplanted rats with FTY720. We speculated that long-term survival rats may require functional change of spleens. In the clinical study, serial biopsies of renal grafts and pharmacokinetics study of FK506 were carried out in patients receiving FK506. We emphasized the immportance of monitoring blood concentration of FK506. Frequent measurements should be carried out to decrease renal toxicity induced by FK506. On the other hand, we analyzed the microchimerism in blood and skin of recipients compared with MLR response. Microchimerism dose not seem to be associated with index of MLR response after transplantation. Further study is necessary to confirm this results. For monitoring rejection, HGE of blood was measured in recipients. Blood HGF had a trend to elevate during rejection. We are in progress in investigating the localization of HGF within rejected allografts by immunostaining. Less

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] 西岡伯: "ラット移植モデルにおけるEthylcarbodiimideが誘導する免疫低応答性の検討." 移植. 31. 4-13 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 今西正昭: "ドナー骨髄細胞の胸腺内移入による免疫寛容誘導とメカニズムについての検討." 移植. 31. 285-293 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Watanade et al: "Tolerance in dogs with FLI,BMC and FK506" Transplant Proc.27(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishioka T: "Hyporesponsiveness in the rat allografts induced by ethylcarbodiimide.19GC01 : Jpn J Trasplantation" 31. 4-13 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Imanishi M: "Induction of tolerance by intrathymic injection of donor bone marrow and its mechanism." Jpn J Transplantation. 31. 285-293 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Watanabe K,et al.: "Tolerance in dogs with FLT,BMC and FK506." Transplant Proc. 27 (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 西岡伯: "ラット移植モデルEthylcarbodiimideが誘導する免疫低応答性の検討" 移植. 31. 4-13 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 今西正昭: "ドナー骨髄細胞の胸腺内移入による免疫寛容誘導とメカニズムについての検討" 移植. 31. 285-293 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Watanabe et al: "Tolerance indogs with FLT, MNC and FK506" Transplant. Proc.27(in press). (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 国方聖司、秋山隆弘、栗田孝 他: "関西地区における小児腎移植の臨床的検討" 日本泌尿器科学会雑誌. 87. 50-55 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kazunari Tanabe et al: "Long-term renal function in cyclosporine (CsA)-treated renal allograft recipients" Urology. 46. 321-327 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 高田晋吾、高原史郎、奥山明彦 他: "生体腎移植後急性拒絶反応における血中HGF濃度の検討" 今日の移植. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] M. Kyo, S. Takahara et al: "Histopathological classifioation and clinical effects of kidney transplant rejection treated with DSG" Transplant Proc. 27. 1012-1013 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K. Watanabe, I. Ito et al: "Factors influencing long-tern operational tolerance in dogs treated with fractionated lymphoid irradiation, donor bone marrow cell infusion and FK 506" Transplant Proc. 27. 221-224 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 佐久間 孝雄: "小児腎移植におけるシクロスポリン血中濃度と急性拒絶反応および移植腎の予後について" 日本泌尿器科学会雑誌. 86. 1450-1459 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] RP Lowry and T Takeuchi: "The Th1, Th2 paradigm and transplantation tolerance" R.G. Landes Company, Austin, 134 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 高原史郎: "FK506の血中濃度モニタリング" 医学のあゆみ. 168. 222-225 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kameoka H.,Takahara S.et al.: "Serum and Urinary Neopterin as Markers in Renal Transplant Patients." International Urology and Nephrology. 26. 107-115 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Moutabarrik A.,Nakanishi I.,Takahara S.et al.: "Interleukin-8 serum and urine concentration after kidney transplantation." Transplant international. 7. S539-S541 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 室崎伸和、高原史郎、小角幸人、ほか: "FK506長期使用例におけるserial biopsyによる腎毒性の検討" 腎移植血管外科. 7(in press). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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