Cincinnati Comprehensive Sickle Cell Center

辛辛那提综合镰刀细胞中心，总部设在血液科/肿瘤科。在儿童医院医学中心，并附属于辛辛那提大学医学院，为受镰状细胞疾病影响的人提供全方位的临床服务。在镰状细胞患者同型半胱氨酸(Hcy)升高与吡哆醇缺乏相关这一发现的基础上，一项中心间合作研究计划检查了患者HY升高与凝血和内皮细胞激活的相关性，并测试补充吡哆辛是否纠正了这些异常。一个在分子生物学、膜运输、体内细胞动力学和临床研究方面具有专业知识的互动研究团队将致力于SS RBC脱水的项目，SS RBC脱水是镰状细胞病理中的一个关键因素，它是由两种异常转运途径-KCl共转运(KCC)和镰刀诱导的阳离子泄漏-导致的。项目2的临床研究测试了双嘧达莫和镁在体内改善SS红细胞水合的治疗潜力。双嘧达莫抑制镰刀诱导的阳离子泄漏，镁则抑制KCC。项目3使用该中心独有的生物素标记技术，检查体内SS红细胞水化变化的速度和机制。项目4探索了正常和SS红细胞中细胞体积对KCC翻译后调节的分子基础。项目5重点研究KCC的红系异构体及其转录调控。临床核心包括儿科和成人项目，为超过375名患者提供全面服务，支持基础和临床研究工作，并参与中心间协作 审判。教育和患者服务核心为患者和家属提供教育和心理社会支持，并包括与镰状细胞意识小组和辛辛那提城市联盟合作的过渡计划，连接儿科和成人临床计划。行政核心提供全面的财务和方案管理，并作为中心活动、方案和沟通的协调中心。该提案中的项目和核心将与独立资助的新生儿血红蛋白病筛查随访、教育和咨询、血红蛋白诊断实验室等基础科学和临床研究项目相结合。辛辛那提综合镰状细胞中心准备领导全国努力开发和测试镰状细胞疾病的新疗法，以改善受影响个人的生活。

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.