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[在亲缘关系密切的狐-犬物种系统中异种肾移植的未受影响的原发性排斥反应]

[The unaffected primary rejection of xenogeneic kidney transplants in the closely related fox-dog species system].

作者信息

Prange C H, Kessler M, Bach D, Huth F, Prange M

出版信息

Z Exp Chir. 1979;12(1):26-46.

PMID:37659
Abstract

The present study reports of three kinds of experiments of unaffected primary rejection of xenogenous kidney transplanats in the close-related fox-dog species system. The issue is whether there is a relation between the amount of grafted parenchyma and the immune induced potency, that is whether the course of rejection of transplanted single kidneys (group I a) differs from the course after en-bloc transplantation of both kidneys (group I b). In group II alterations of blood chemism and behavior of humoral antibodies are followed in dogs to which a fox kidney was transplanted, while keeping their own functioning kidneys. This experiment is to give information whether the uremic syndrome influences the development of humoral immunity, and what changes of blood chemism may primarily be related to destruction of the graft, under the condition of absent uremia. Untreated graft recipients survived for 5,4 +/- 0,49 days (n = 5) when single kidneys were transplanted (group I a), and 5,2 +/- 0,75 days (n = 5) when both kidneys were grafted en-bloc (group I b). As to the rejecting reactions, both groups are almost equal: the increasing functional failure causes a fast increase of creatinine and urea nitrogen; alkaline phosphatase and LDH show distinct alterations, related to the progress of the graft's destruction. Decrease of albumin level and loss of cholinesterase activity indicate an impaired hepatic function as reaction to uremic intoxication. Gamma-globulins and leucocytes show alterations that can be related to non-specific inflammatory reactions. The immunologically specific initial lymphopenia suggests that after revascularization these cells migrate to the graft, and later react with antigenic structures of vascular endothelium and still later with those of the organ cells. Cytotoxic antibodies appear on the 4th postoperative day in increasing amount. Post mortem histologic examination shows round cell infiltrates in the vastly necrotic renal parenchyma. When the recipient's kidneys are kept in situ and a fox kidney is transplanted (group II) uremia is avoided and the animals survive. During the 30-days period of observation, that is longer than the term of rejection, the titer of cytotoxic antibodies remains stable or tends to increase. LDH and alkaline phosphatase show characteristic changes that are considered sequels from destructed transplantate. The experiments show, aside from certain reservations, that the donor-host combination fox-dog is suitable to serve as preclinic model for human transplantation using xenogenous donors of organs, i. e. anthropoid primates.

摘要

本研究报告了在密切相关的狐 - 犬物种系统中进行的三种关于异种肾移植未受影响的原发性排斥反应的实验。问题在于移植实质的量与免疫诱导能力之间是否存在关联,即单肾移植(I a组)的排斥过程是否与双肾整块移植(I b组)后的排斥过程不同。在II组中,对移植了狐肾且保留自身功能肾的犬只,跟踪其血液化学成分的变化和体液抗体的行为。该实验旨在获取信息,即在无尿毒症的情况下,尿毒症综合征是否会影响体液免疫的发展,以及血液化学成分的哪些变化可能主要与移植物的破坏有关。单肾移植时(I a组),未经治疗的移植物受体存活5.4±0.49天(n = 5),双肾整块移植时(I b组)存活5.2±0.75天(n = 5)。至于排斥反应,两组几乎相同:功能衰竭的加剧导致肌酐和尿素氮迅速升高;碱性磷酸酶和乳酸脱氢酶显示出与移植物破坏进程相关的明显变化。白蛋白水平降低和胆碱酯酶活性丧失表明肝功能受损,这是对尿毒症中毒的反应。γ - 球蛋白和白细胞显示出与非特异性炎症反应相关的变化。免疫特异性初始淋巴细胞减少表明血管再通后这些细胞迁移至移植物,随后与血管内皮的抗原结构反应,再后来与器官细胞的抗原结构反应。细胞毒性抗体在术后第4天出现且数量不断增加。尸检组织学检查显示,在大量坏死的肾实质中有圆形细胞浸润。当受体的肾脏原位保留并移植狐肾时(II组),可避免尿毒症,动物存活。在30天的观察期内,即长于排斥期,细胞毒性抗体的滴度保持稳定或趋于升高。乳酸脱氢酶和碱性磷酸酶显示出特征性变化,被认为是移植组织破坏的后续表现。实验表明,除某些保留意见外,狐 - 犬供体 - 受体组合适合作为使用异种器官供体(即类人灵长类动物)进行人类移植的临床前模型。

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