COMPREHENSIVE SICKLE CELL CENTER

尽管镰状细胞性贫血(SCA)在分子水平上被描述为 水平，其蛋白表现为血管闭塞的病理生理学 危机(VOC)仍然模糊不清。正是这些事件导致了 镰状红细胞对微循环的损害和阻塞 涉及一系列复杂而动态的事件，这些事件可能依赖于 就像微循环张力一样，内皮的激活状态， 白血球、血小板和凝血的液体相 红细胞的表面和内部特征及其内容物 镰刀和胎儿血红蛋白。这项中心拨款将尝试解决 以上列举的领域以独特的方式和前瞻性的重点 在分水岭发生变化的关键时间窗口 红细胞的内部特征，即它的血红蛋白含量 S和F.我们将仔细研究这些生理变化是如何在 生命最初几年的血红蛋白含量会影响 血液中其他细胞成分的激活状态，凝血 因素和内皮，以及这些变化如何影响蛋白质临床 疾病的表现--VOC和疼痛的发生。这个 这些婴幼儿和青年镰刀痛的发生率和属性 将对儿童进行全面和前瞻性的纵向评估 学习。此外，我们的研究计划将在蜂窝和 分子水平：介入治疗潜在用途的理论基础 针对一种危及生命的镰刀并发症的策略 细胞疾病，急性胸部综合征，还调查了第二个和 为儿童晚期和儿童设计的干预计划 青春期早期，这将提高他们的韧性和知觉 控制他们的生活和疾病。因此，这笔中心赠款旨在 解决基础研究和翻译研究的各个方面 为我们的患者提供所需的支持，以独立和 富有成效的生活。这些研究项目将得到 综合镰刀细胞中心的传统方面包括 教育和咨询服务，诊断和实验室核心，以及 适当的统计和行政支持。

Although Sickle Cell Anemia (SCA) has been characterized at the molecular level, the pathophysiology of its protein manifestation the vasocclusive crisis (VOC) still remains obscure. The exact events that lead to microcirculatory impairment and obstruction by sickled erythrocytes involve a complex and dynamic sequence of events that dependent presumably as much on microcirculatory tone, the activation state of the endothelium, white cells, platelets, and the fluid phases of coagulation as it does on the surface and internal characteristics of the red cell and its content of sickle and fetal hemoglobin. This Center grant will attempt to address the areas enumerated above in a unique and prospective fashion with focus on the crucial window of time during which a watershed change occurs in the erythrocyte's internal characteristics i.e.-its hemoglobin content of S and F. We will meticulously correlate how these physiologic changes in hemoglobin content during the first few years of life will affect the state of activation of the other cellular elements of blood, coagulation factors and endothelium, and how these changes effect the protein clinical manifestations of the disease-VOC and the occurrence of pain. The incidence and the attributes of sickle pain in these infants and young children will be assessed in a comprehensive and prospective longitudinal study. Additionally, our research program will explore at the cellular and molecular level the rationale for potential use of interventional strategies directed at one of the life threatening complications of Sickle Cell Disease, the acute chest syndrome, and also investigate a second and interventional program designed for our children in late childhood and early adolescence which will increase their resilience and perceived control over their lives and illness. Thus, this Center Grant seeks to address various aspect of basic and translational research besides providing the support our patients require to lead independent and productive lives. The research projects will be supported by the traditional aspects of a Comprehensive Sickle Cell Center including education and counseling services, a diagnostic and laboratory core, and appropriate statistical and administrative support.