FIBRINOGEN RECEPTORS IN HEREDITARY THROMBOPATHIA

伴应激性出血的纯种牧羊犬的血小板紊乱 已被检测到。它被贴上了巴塞特猎犬血栓病(BHT)的标签。 这种疾病与血栓减少症有许多共同的特征。 人类除了存在正常的凝块回缩。初选， 与血栓减少症一样，存在着固有的聚集功能障碍，但 膜糖蛋白(GP)IIb-IIIa含量正常的证据。 经过初步研究，有一种假设认为纤维蛋白原受体是 出现BHT异常。看来这种糖蛋白很可能 定向或暴露，通常导致血小板纤维蛋白原 结合和聚集，在BHT血小板中是先天紊乱的。 该计划的具体目的是检测血小板纤维蛋白原。 结合，测定血小板胞外唾液酸转移酶活性，传导交叉 免疫电泳法分离IN功能性GP IIb-IIIa复合体 体外纤维蛋白原结合实验，并测定糖膜掺入 测定核糖体后糖基化。 利用125I-纤维蛋白原结合，交叉免疫电泳法，高 分辨率双向电泳，胞外唾液酸转移酶检测， 唾液酸定量可揭示BHT的发病机制。 实质上促进了对血小板发育的理解 膜受体。杂化络合物的分离和重组 BHT和正常糖蛋白IIb-IIIa亚基转化为功能性和 功能障碍的单位应该准确地修复功能障碍的部位。因为 关于血小板在对血管损伤的初始反应中的作用，这 建议在解剖血小板纤维蛋白原受体和 因此，可能会导致对血小板现象的更好理解 聚合。

A platelet disorder in line-bred Basset Hounds with stress related bleeding has been detected. It has been labeled Basset Hound thrombopathia (BHT). This disorder has many characteristics in common with thrombasthenia in humans except for the presence of normal clot retraction. A primary, intrinsic failure of aggregation exists as in thrombasthenia, but there is evidence for a normal membrane content of glycoprotein (GP) IIb-IIIa. After preliminary studies, a hypothesis that fibrinogen receptors are abnormal in BHT was developed. It appears likely that the glycoprotein orientation or exposure, usually resulting in platelet-fibrinogen association and aggregation, is congenitally disturbed in BHT platelets. The specific aims of the program are to measure platelet fibrinogen binding, assay platelet ectosialyltransferase activity, conduct crossed immunoelectrophoresis and isolate functional GP IIb-IIIa complex for in vitro fibrinogen binding assay, and measure sugar membrane incorporation to determine post-ribosomal glycosylation. Utilization of 125I-fibrinogen binding, crossed immunoelectrophoresis, high resolution two-dimensional electrophoresis, ectosialyltransferase assays, and sialic acid quantitation may reveal the pathogenesis of BHT and substantially forward the understanding of the development of platelet membrane receptors. The isolation and recombination of hybrid complexes of BHT and normal glycoprotein IIb-IIIa subunits into functional and dysfunctional units should fix precisely the site of dysfunction. Because of the role of platelets in the initial response to vascular injury, this proposal is important in dissecting the platelet fibrinogen receptor and may, thereby, result in a better understanding of the phenomena of platelet aggregation.