SURFACE DEPENDENT REACTIONS IN THROMBOSIS & THROMBOLYSIS

该计划的总体重点是确定组件 以及维持平衡的过程的机制 在血液的流动性和凝固性之间。关联的组件 随着血液流动性的保持包括血浆中的元素， 循环血细胞、血管组织及其周围 纸巾。负责维护或更改 血液的流动性包括凝血反应、PRO和 与外周血液和血管相关的抗凝功能 细胞和血管-血液纤溶系统。这个项目中的项目 计划项目赠款以综合方式在全球范围内 与这些过程中的每一个相关的反应及其调节。 基本假设是，复合体的性质 有助于止血和纤溶的多方面系统有 具体体现在结构的详细知识中，并且可以从结构的详细知识中推断， 系统中各个组件之间的相互作用和反应。 这两项研究都集中在由提纯成分重建的系统上 以及天然生物材料和生物系统，包括机械和 血栓和血友病的人群研究。我们的战略是 结合我们处理分子相互作用的能力 并将这些知识与人类健康和 疾病。该计划由五个项目组成：1)启动 凝血酶原，2)血栓性疾病的遗传基础，3)血栓性疾病的性质 纤溶级联反应，4)人血小板凝血酶原酶的调节 活性；5)因子V/a磷酸化对辅因子的影响 功能。一个管理核心和一个细胞生物学核心支持这些 项目。总体而言，这些项目和核心在以下方面进行了整合 它们的目的和它们共享的试剂(天然的和重组的 蛋白质，核酸，合成抑制剂，多肽底物， 抗体和细胞)在化学和细胞研究中旨在 了解人类血栓形成和止血的过程。这个 建议的研究从分子遗传学的基础研究延伸出来， 细胞生物学和生物化学对人类病理学遗传学的影响 血栓性疾病和出血性疾病。建议的研究计划 过去研究成果的历史证据表明 存在着重大的智力和身体上的相互作用 主要调查人员和实验室之间的合作 计划项目提供了更有效的工具来生成 与科学和医学相关的信息比 是个别调查人员编造的。

The overall focus of this program is aimed at identifying the components of, and the mechanisms for the processes which maintain the balance between the fluidity and clotting of blood. The components associated with the maintenance of blood fluidity include elements of the plasma, the circulating blood cells, the vascular tissues and their surrounding tissues. The processes responsible for maintaining or altering the fluidity of blood include the coagulation reactions, the pro and anticoagulant functions associated with peripheral blood and vascular cells and the vascular-blood fibrinolytic system. The projects in this Program Project Grant address in an integrated fashion the global reactions associated with each of these processes and their regulation. The fundamental hypothesis is that the properties of the complex multifaceted systems contributing to hemostasis, and fibrinolysis are embodied in, and can be deduced from detailed knowledge of the structure, interactions and reactions of the individual components of the systems. The studies focus both upon systems reconstructed from purified components and on natural biomaterials and biosystems, including mechanistic and population studies of thrombophilia and hemophilia. Our strategy is to combine our talents dealing with the molecular interactions occurring on the surfaces and to correlate this knowledge with human health and disease. The program is composed of five projects 1) The Activation of Prothrombin, 2) The Genetic Basis of Thrombotic Disease, 3) Properties of Fibrinolytic Cascade, 4) Regulation of Human Platelet Prothrombinase Activity, and 5) The Effects of factor V/a Phosphorylation on Cofactor Function. An Administrative Core and a Cell Biology Core support these projects. Overall, these projects and cores re integrated with respect to their purpose and the reagents which they share (natural and recombinant proteins, nucleic acids, synthetic inhibitors, peptide substrates, antibodies and cells) in chemical and cellular studies aimed at understanding the processes of human thrombosis and hemostasis. The research proposed extends from fundamental studies of molecular genetics, cell biology and biochemistry to the genetics of the pathology of human thrombotic disease and bleeding disorders. The proposed research program and the historical evidence of past research accomplishments demonstrate that significant interactions, both intellectual and physical, exist between the principal investigators and the laboratories which make this program project grant a more effective vehicle for the generation of scientific and medically relevant information than the efforts of the individual investigators that make it up.