FIBRINOGEN RECEPTORS IN HEREDITARY THROMBOPATHIA

纯种巴吉度犬的血小板异常并伴有应激性出血 已被发现。 它被标记为Basset Hound血栓病（BHT）。 这种疾病有许多共同的特点与血小板无力症， 除了正常凝块收缩的存在之外。 一个主要的， 如在血栓无力症中一样，存在内在的聚集失败，但 糖蛋白（GP）IIb-IIIa膜含量正常的证据。 经过初步研究，纤维蛋白原受体是一个假设， BHT出现异常。 似乎糖蛋白 取向或暴露，通常导致血小板-纤维蛋白原 结合和聚集，在BHT血小板中先天性紊乱。 该计划的具体目标是测量血小板纤维蛋白原 结合，测定血小板外唾液酸转移酶活性，交叉试验 免疫电泳和分离功能性GP IIb-IIIa复合物 体外纤维蛋白原结合测定，并测量糖膜掺入， 确定核糖体后糖基化。 利用125 I-纤维蛋白原结合，交叉免疫电泳，高 分辨率二维电泳，外唾液酸转移酶测定， 唾液酸定量可以揭示BHT的发病机制， 大大推进了对血小板发展的认识， 膜受体 杂合复合物的分离和重组 BHT和正常糖蛋白IIb-IIIa亚基转化为功能性和 功能失调的单位应该精确地修复功能失调的部位。 因为 血小板在血管损伤的初始反应中的作用， 该提案在解剖血小板纤维蛋白原受体方面很重要， 因此，可以更好地理解血小板的现象， 聚合来

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.