COMPARATIVE STUDY OF COAGULATION AND VASCULAR DISEASE

凝血与血管疾病的比较研究

• 批准号: 3334310
• 负责人: WINIFRED J DODDS
• 金额: $ 16.51万
• 依托单位: NYSDOH/HEALTH RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3334310
• 关键词: animal colony; biological signal transduction; blood coagulation disorders; coagulation factor VIII; congenital blood disorder; cyclic AMP; diagnosis quality /standard; disease /disorder model; dogs; enzyme linked immunosorbent assay; gene expression; genes; genetic models; guinea pigs; hemophilia As; hemorrhagic disorders; hemostasis; hemostatics; hypothyroidism; laboratory mouse; nucleic acid sequence; platelet aggregation; platelet disorder; platelets; thrombocytopathy; thrombosis; thyroid hormones; von Willebrand factor; von Willebrand's disease

DESCRIPTION: (Adapted from investigator's abstract). Colonies of animals with inherited coagulation and platelet function defects are maintained for genetic, biochemical, and physiological studies; production of agents for coagulation tests; and evaluation of hemostasis. These include dos with hemophilia A, hemophilia B, von Willebrand's disease (vWD), factor VII deficiency, thrombasthenia, and thrombopathia. Studies with these naturally occurring animal models examine basic mechanisms of hemostasis and thrombosis in comparison to analogous human diseases. The continued diagnosis, characterization and maintenance of animal models of spontaneous hemorrhagic and thrombotic diseases is a major objective for the next period. Our research efforts will focus on: (1) utilization of well-defined canine models of vWD and hemophilia to study the FVIII/vWF complex including determination of the complementary DNA sequence for the canine vWF gene; (2) the action of thyroid hormone (T4) on vWF gene expression; and (3) continue ongoing characterization studies related to signaling pathways in thrombopathic platelets. Consultation about the comparative aspects of hemostasis research and bleeding disorders as well as collaboration with other investigators in research projects will also continue. Reagents, genetic material and other animal products will be provided based on availability. Specific aims for the period include: comparative molecular genetic analysis of canine and human von Willebrand factor/vWF; establish whether endothelial cells are the exclusive site of synthesis, storage, and release of canine vWF; identify functional domains of canine vWF; examine the stability of canine FVIII coagulant in the absence of vWF in type III canine vWD; utilize a new sensitive ELISA assay to characterize vWF in a variety of species and assess vWF gene expression and the thyroid endocrine axis in mutant hypothyroid mice. Platelet studies will focus on definition of the biochemical defect of canine thrombopathia, specifically the role of cAMP in regulating platelet signal transduction.

描述：（根据研究者的摘要进行了改编）。 动物的菌落 维持遗传的凝血和血小板功能缺陷 遗传，生化和生理研究；代理的生产 凝血测试；和止血的评估。 这些包括dos 血友病A，血友病B，冯·威勒布兰氏病（VWD），因子VII 缺乏症，血栓性和血小板病。 这些研究 自然发生的动物模型检查止血的基本机制 与类似的人类疾病相比，血栓形成。 动物模型的持续诊断，表征和维护 自发出血和血栓性疾病是一个主要目标 下一个时期。 我们的研究工作将重点介绍：（1）利用 定义明确的VWD和血友病的犬模型研究FVIII/VWF 复合物，包括确定互补DNA序列 犬VWF基因； （2）甲状腺激素（T4）对VWF基因的作用 表达; （3）继续进行与 血小板病血小板中的信号通路。 关于 止血研究和出血疾病的比较方面 随着研究项目中与其他研究人员的合作 继续。 试剂，遗传物质和其他动物产品将是 根据可用性提供。 该期间的具体目的包括：比较分子遗传 分析犬和人类von Willebrand因子/VWF；确定是否 内皮细胞是合成，存储和释放的专有位点 犬vwf;识别犬VWF的功能域；检查 在III型中没有VWF的情况下，犬FVIII凝结剂的稳定性 犬VWD;利用新的敏感ELISA分析来表征vwf 种类种类并评估VWF基因表达和甲状腺内分泌 突变型甲状腺功能减退小鼠的轴。 血小板研究将重点放在定义上 犬类血栓性疾病的生化缺陷，特别是 调节血小板信号转导的扎营。