Cincinnati Comprehensive Sickle Cell Center

辛辛那提综合镰状细胞中心，位于血液学/肿瘤学部门。隶属于辛辛那提大学医学院的儿童医院医学中心，为镰状细胞病患者提供全方位的临床服务。基于镰状细胞患者高同型半胱氨酸（Hcy）升高与吡哆醇缺乏症相关的发现，一项中心间合作研究计划检查了患者高同型半胱氨酸与凝血和内皮细胞活化的相关性，并测试了补充吡哆醇是否能纠正这些异常。一个具有分子生物学、膜运输、体内细胞动力学和临床研究专业知识的互动研究团队将专注于SS红细胞脱水，这是镰状细胞病理的一个关键因素，它由两种异常运输途径——KCl共运输（KCC）和镰状细胞诱导的阳离子泄漏引起。项目2的临床研究测试了抑制镰状细胞诱导的阳离子泄漏的双嘧达莫和抑制KCC的镁在体内改善SS红细胞水化的治疗潜力。项目3使用本中心独有的生物素标记技术，研究体内SS红细胞水合变化的速率和机制。项目4探索正常和SS红细胞中细胞体积对KCC翻译后调控的分子基础。项目5主要研究KCC的红系亚型及其转录调控。临床核心包括儿科和成人项目，为超过375名患者提供全面的服务，支持基础和临床研究工作，并参与中心间的合作

The Cincinnati Comprehensive Sickle Cell Center, based in the Division of Hematology/Oncology. at Children's Hospital Medical Center and affiliated with the University of Cincinnati College of Medicine, provides a full range of clinical services to people affected by sickle cell disease. Building on the finding that elevated homocysteine (Hcy) in sickle cell patients is associated with pyridoxine deficiency, an inter-Center collaborative research proposal examines the correlation of elevated Hey with activation of coagulation and endothelial cells in patients, and tests whether pyridoxine supplementation corrects these abnormalities. An interactive research team with expertise in molecular biology, membrane transport, in vivo cell kinetics, and clinical research will pursue projects focused on SS RBC dehydration, a key factor in sickle cell pathology, which results from two abnormal transport pathways, KCl cotransport (KCC) and sickling-induced cation leaks. The clinical study of Project 2 tests the therapeutic potential of dipyridamole, which inhibits sickling-induced cation leaks, and magnesium, which inhibits KCC, to improve SS RBC hydration in vivo. Project 3 examines the rate and mechanisms of hydration changes of SS RBC in vivo, using biotin label techniques unique to this Center. Project 4 explores the molecular basis of post-translational regulation of KCC by cell volume in normal and SS RBC. Project 5 focuses on the erythroid isoforms of KCC and their transcriptional regulation. A Clinical Core includes Pediatric and Adult Progra ms to provide comprehensive services to over 375 patients, to support basic and clinical research efforts, and to participate in inter-Center collaborative trials. An Education and Patient Services Core provides educational and psychosocial support for patients and families, and includes a Transition Program bridging the Pediatric and Adult Clinical Programs, in collaboration with the Sickle Cell Awareness Group and the Urban League of Cincinnati. An Administrative Core provides overall fiscal and programmatic management and serves as the focal point for Center activities, programs, and communication. The projects and cores in this proposal will be integrated with independently funded programs of newborn hemoglobinopathy screening follow-up, education and counseling, a Hemoglobin Diagnostic Laboratory, and other basic science and clinical research projects. The Cincinnati comprehensive Sickle Cell Center is poised to lead in the national effort to develop and test new therapies for sickle cell disease to improve the lives of affected individuals.