STUDIES OF SICKLING MECHANISMS AND RED CELL MEMBRANES

提出的研究目的是：(1)进一步定义分子 脱氧-血红蛋白S聚合和胶凝机理的作图 每个四聚体亚基的分子间接触位置，作用的研究 聚合反应中的非S血红蛋白及Hb解离效应 红细胞聚合中的平衡和杂化形成，以及 HBs与S和C的相互作用；(2)功能性质的进一步研究 含HBS的红细胞，(3)功能检查 SS、CC和RBC膜的异常(及其结构基础) 其他异常红细胞。这些研究旨在进一步推动我们的 了解镰刀的机械原理，以帮助设计和 应用抗呕吐剂，以确定生理条件 对患有各种镰状障碍的人是危险的还是有利的，以及对 探讨红细胞膜的病理生理学 改善这些疾病中的细胞存活和功能。

The proposed research is aimed at (1) further definition of the molecular mechanisms of deoxy-Hb S polymerization and gelation, by mapping of intermolecular contact sites for each tetramer subunit, studies of the role of non S Hbs in polymerization, and the effect of Hb dissociation equilibria and hybrid formation in polymerization in red cells, and interactions of Hbs S and C; (2) further studies of functional properties of HbS-containing-red cells, (3) examination of the functional abnormalities (and their structural basis) of rbc membranes in SS, CC and other abnormal red cells. These studies are designed to further our knowledge of the mechanisms of sickling, to aid in the design and application of antisickling agents, to determine physiological conditions dangerous or favorable to persons with various sickling disorders, and to explore the pathophysiology of the red cell membranes with the overall aim of improving cell survival and function in these disorders.