Induction of donor specific unresponsiveness by combined treatment with donor bone marrow cell infusion, and FK506 in cadaveric renal allotransplantation.
Induction of donor specific unresponsiveness by combined treatment with donor bone marrow cell infusion, and FK506 in cadaveric renal allotransplantation.
批准号:
04670748
负责人:
WATANABE Koji
金额:
$0.96万
依托单位国家:
日本
项目类别:
Grant-in-Aid for General Scientific Research (C)
财政年份:
1992
资助国家:
日本
项目状态:
已结题
起止时间:
1992 至 1994
中文摘要
我们通过术前分级淋巴细胞照射(FLI)、肾移植前骨髓细胞(BMC)输注和短期小剂量免疫抑制剂FK506联合治疗,成功地延长了组织不相容的比格犬的皮肤和肾脏同种异体移植。为了将该方案应用于尸体肾移植,我们研究了几个要点作为流程;首先,我们采用PCR-SSO分型的方法,用所有的单点登录探针建立了DLA- dna分型,得到了相同的DLA错配对。其次,采用自行研制的冰水系统对保存3天的肾脏进行大面积冷却,直至术中血运重建,可显著改善同种异体移植的效果。第三,我们对术后免疫抑制进行如下调整;FK506以0.16mg/kg/d的剂量ig给药14 d,随后以0.08mg/kg/d的剂量ig给药14 d,再继续以0.04mg/kg/d的剂量ig给药至术后90 d。事实上,通过这些治疗,同种异体移植保存肾脏的存活率已经大大提高。然后,在移植时联合FLI和BMC输注治疗的效果已被研究。
英文摘要
We succeeded in the prolongation of skin and kidney allografts from bone marrow donors in histoincompatible beagle dogs by combined treatment with preoperative fractionated lymphoid irradiation (FLI) , bone marrow cell (BMC) infusion from the kidney donors shortly before kidney grafting, and shortterm administration of small doses of immunosuppressant, FK506. To apply this protocol to the cadaveric renal transplantation, we have investigated the several points as fllows ; First, we established the DLA-DNA typing using ll SSO probes by the method of PCR-SSO typing by which the same DLA mismatched pairs were obtained. Second, the results of allografting of 3-days preserved kidneys was remarkably improved by extensively cooling the transplants with ice-water system made by ourselves until revascularization in the course of operation. Third, we adapted the postoperative immunosuppression as follows ; i.m.administration of FK506 at the dose of 0.16mg/kg/d for 14 days, followed by 0.08mg/kg/d for 14 days, then continued to give the dose of 0.04mg/kg/d until 90 days postoperatively. In fact, by these treatment the survival rate of allografted preserved kidneys have been greatly improved. Then, the effect of combined treatment with FLI,and, BMC infusion at the time of grafting has been under investigation.
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伊東一郎他.: "北里自家繁殖mongrel犬の主要組織適合抗原(DLA)DRB1遺伝子の解析." MHC & IRS(日本組織適合性学会誌). 1. 115- (1994)
Ito 等人:“北里家养杂种狗主要组织相容性抗原 (DLA) DRB1 基因的分析。”MHC & IRS(日本组织相容性学会杂志)1. 115-(1994)。
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K.Watanabe, I.Ito, F.Otani, F.Obata, K.Sato, K.Ishida, Y.Masaki, S.Maruyama, and K.Kashiwagi: "Factors influencing long-term operational tolerance in dogs treated with fractionated lymphoid irradiation, donor bone marrow cell infusion and FK506." Transpla
K.Watanabe、I.Ito、F.Otani、F.Obata、K.Sato、K.Ishida、Y.Masaki、S.Maruyama 和 K.Kashiwagi:“影响分次治疗犬长期操作耐受性的因素
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K.Watanabe, I.Ichiro, K.Sato, K.Ishida, Y.Nakayama, A.Kakita, and Y.Masaki.: "Induction of transplatation tolerance by donor bone marrow transplantation in adult beagle dogs." J.Jpn.Surg.Soc. (Japanese). 95. 301 (1994)
K.Watanabe、I.Ichiro、K.Sato、K.Ishida、Y.Nakayama、A.Kakita 和 Y.Masaki.:“通过成年比格犬供体骨髓移植诱导移植耐受。”
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大谷文雄 他: "イヌMHC(DLA)のPCR・SSO法によるタイピングと新しい抗原型の発見" 第2回日本組織適合性学会大会. 抄録集. 72 (1993)
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渡部浩二他.: "成犬において導入した同種移植片に対する免寛容の機序" 日本免疫学会総会・学術集会記録.22. 301 (1992)
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