The Activation of Prothrombin

这个项目的目标是描述血液凝固系统的生理学和病理学特征。 可量化的术语。我们为这些分析开发了三种方法，其中包括：数值 凝血蛋白质组的模型、凝血蛋白质组的数值概括 使用纯化的蛋白质，以及体外全血和微血管伤口流动的研究。我们在寻找 定量透明的描述与医学的生物/病理观察相一致 最终可用于人类血栓形成和治疗的诊断、预防和治疗 出血性疾病。在要求的更新中，我们将在封闭式血液凝固系统中进行评估， 血浆蛋白质组附加成分对凝血酶等的影响 选民。将特别强调来自自然来源的组织因子、蛋白质S和细胞 血小板、单核细胞和内皮细胞的贡献。我们将把我们的方法应用于开放系统， 最初在两个人工系统中使用流动动力学，以研究 从静脉到切变条件下蛋白水解性凝血复合体的组成 动脉血。这些实验将使用全内反射荧光和一种新的 设计的工具，实时血栓剖面仪。流动中的实验将使用 生物物理技术，并使用现代数学技术来描述流动 动力学。流动反应将在一系列系统中进行研究，从涂有合成材料的人造毛细管。 膜或内皮细胞，并最终到达人体血管的动脉和静脉段。这个 开发的系统将被用来评估抗凝剂和抗血小板药物对 凝血反应。我们预期后一项研究将提供证据，以确定口岸和 控制这些点所需的新试剂的质量。项目1与每个 该方案的其余五个项目项目赠款提供智力、物质和物质支持 在人类生物学中凝血和纤溶的合作研究。 相关性：静脉和动脉血栓是美国的主要健康问题，与 每年大约有一百万人死亡。出血性疾病，特别是血友病A和B 谢天谢地，虽然不那么频繁，但对受影响的人来说，仍然是主要的健康问题。该项目旨在提供 有助于识别血栓和出血性疾病风险的基本知识， 并提供可用于诊断、预防和治疗的方法和信息 出血和凝血的疾病。^^

The goal of this project is to characterizethe physiology and pathology of the blood coagulation system in quantifiable terms. We have developed three approaches for these analyseswhich include: numerical models of the blood coagulation proteome, numerical recapitulations of the blood coagulation proteome using purified proteins, and studies of whole blood in vitro and flowing from microvascular wounds. We seek quantitatively transparent descriptions convergent with the biological/pathologic observations of medicine which can ultimately be useful for the diagnosis, prophylaxis and therapy of human thrombotic and lemorrhagic disease. In the renewal requested, we will evaluate, in the closed blood coagulation systems, the influence of additional components of the plasma proteome on the generation of thrombin and other constituents. Special emphasis will be focused on tissue factor from natural sources, protein S, and cellular contributions by platelets, monocytes and endothelial cells. We will apply our methods to open systems, initially using flow dynamics in two artificial systems, to investigate the binding and presentation of the components of the proteolytic coagulation complexes under conditions of shear ranging from venous to arterial. These experiments will be conducted using total internal reflectance fluorescence and a newly devised tool the Real Time Thrombosis Profiler. Experiments in flow will be quantitatively analyzed using biophysical techniques and evaluated using modern mathematical techniques used to describe flow dynamics. Flow reactions will be studied in systems ranging from artificial capillaries coated with synthetic . membrane films or endothelial cells, and ultimately to human vascular arterial and venous segments. The systems developed will be utilized to evaluate the influence of anticoagulants and antiplatelet agents on the coagulation response. We anticipate the latter studies will provide evidence for identifying control points and the qualities of new agents required for control of these points. Project 1 is integrated with each of the remaining five projects of this program project grant providing both intellectual material and physical support in the collaborative studies of coagulation and fibrinolysis in human biology. Relevance: Venous and arterial blood clots are major health problems in the United States associated with approximately one million deaths each year. Hemorrhagic diseases, especially hemophilia A and B are thankfully less frequent, but still major health issues for those affected. This project seeks to provide fundamental knowledge which will be useful to identify those at risk for thrombotic and bleeding diseases, and provide methods and information that can be useful in the diagnosis, prophylaxis and therapy of bleeding and clotting diseases. ^^