Cincinnati Comprehensive Sickle Cell Center

辛辛那提综合镰状细胞中心

• 批准号: 7463051
• 负责人: Clinton H Joiner
• 金额: $ 7.04万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-11 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7463051
• 关键词: Academic Medical Centers; Address; Adolescent; Adult; Affect; Age; Arts; Awareness; Basic Science; Biological; Biotin; Care given by nurses; Caregivers; Caring; Carrier Proteins; Cations; Cell Cycle Kinetics; Cell Volumes; Cell physiology; Child Support; Childhood; Clinic; Clinical; Clinical Research; Clinical Services; Clinical Trials; Coagulation Process; Collaborations; Commit; Communication Programs; Communities; Comprehensive Health Care; Counseling; Dehydration; Diagnostic; Dipyridamole; Disease; Education; Endothelial Cells; Erythrocytes; Experimental Hematology; Family; Fees; Funding; Goals; Hematology; Hemoglobin; Hemoglobinopathies; Homocysteine; Homocystine; Hospitals; Human Resources; Hydration status; Individual; Institution; Knowledge; Label; Laboratories; Lead; Leadership; Life; Link; Magnesium; Medical; Medical center; Medicine; Molecular; Molecular Biology; Newborn Infant; Pathology; Pathway interactions; Patient Education; Patients; Pediatric Hospitals; Post-Translational Regulation; Primary Health Care; Protein Isoforms; Provider; Psychosocial Assessment and Care; Pyridoxine Deficiency; Range; Rate; Recording of previous events; Research; Research Personnel; Research Project Grants; Research Proposals; Resources; Screening procedure; Services; Sickle Cell; Sickle Cell Anemia; Social Work; Supplementation; Techniques; Teenagers; Testing; Therapeutic; Therapeutic Intervention; Transcriptional Regulation; Translational Research; Transmembrane Transport; Universities; base; collaborative trial; college; design; experience; follow-up; improved; in vivo; oncology; programs; psychologic; pyridoxine; sickling; social; success

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.

辛辛那提综合镰状细胞中心，基于血液学/肿瘤学分裂。在儿童医院医疗中心，隶属于辛辛那提大学医学院，为患有镰状细胞病影响的人提供了全方位的临床服务。在镰状细胞患者中升高的同型半胱氨酸（HCY）的发现与吡啶多毒素缺乏症有关的基础上，一项中心间协作研究建议研究了HEY升高与患者凝血和内皮细胞激活的相关性，并测试补充吡啶多毒素补充剂是否纠正了这些异常。一个具有分子生物学，膜运输，体内细胞动力学和临床研究方面具有专业知识的互动研究团队，将追求专注于SS RBC脱水的项目，这是镰状细胞病理学的关键因素，这是由两个异常的转运途径，KCL Cotransport（KCC）（KCC）和aciveling诱导的载体泄漏。项目2的临床研究测试了二吡啶胺的治疗潜力，二吡啶胺抑制了疾病诱导的阳离子泄漏，镁（抑制KCC）可以改善体内SS RBC水平。 Project 3使用该中心独特的生物素标签技术研究了体内SS RBC的水合变化的速率和机制。项目4探讨了正常和SS RBC中细胞体积对KCC翻译后调节的分子基础。项目5的重点是KCC的红细胞同工型及其转录调节。临床核心包括儿科和成人疾病，可为375多名患者提供全面的服务，以支持基础和临床研究工作，并参与中心协作 试验。教育和患者服务核心为患者和家庭提供教育和社会心理支持，并包括与镰状细胞意识小组和辛辛那提市政联盟合作的过渡计划，桥接儿科和成人临床计划。行政核心提供了整体的财政和计划管理，并成为中心活动，计划和沟通的焦点。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，教育和咨询，血红蛋白诊断实验室以及其他基础科学和临床研究项目的独立资助计划集成。辛辛那提综合镰状细胞中心有望领导全国性的努力，以开发和测试镰状细胞疾病的新疗法，以改善受影响个体的生活。