NORTHERN CALIFORNIA COMPREHENSIVE SICKLE CELL CENTER

北方加州综合镰状细胞病中心的目标 （NCCSCC）是1）赞助和促进血红蛋白病研究， 基础和临床水平，以及2）提供血红蛋白病 检测，咨询和教育受影响的人群， 最现代的方法。为达致这些目标，我们设立了一个 儿童医院CORE血红蛋白结构和诊断实验室 奥克兰研究所（CHORI）和CORE临床研究计划， 西湾（UCSF/弗朗西斯科总医院）和东湾 （奥克兰儿童医院，高地医院）。这些方案提供 血红蛋白病检测、咨询和教育以及稳定的， 一组500多名镰状细胞病患者 (SCD)参与NCCSCC研究项目的人。临床研究 项目的目的是a）测试核心减压在 无菌性骨坏死的管理，B）观察是否急性上升， 血清分泌型磷脂酶AD预示急性胸部综合征， 证明早期治疗干预的合理性，3）评估 潜在的新疗法（羟基脲+丁酸苯酯或克霉唑， 异丁酰胺，口服镁，口服螯合剂和各种形式的干 细胞移植）。更多基础细胞和分子生物学研究 项目将a）利用我们新开发的SCD转基因小鼠模型 （完全缺乏小鼠珠蛋白链）来探索 SC的病理生理学并评估潜在的新治疗，B）采用 全基因组扫描，以确定与珠蛋白簇无关的基因 在近交系中改变SCD的严重程度和球蛋白链转换 小鼠，c）使用人B珠蛋白YAC特异性转基因小鼠模型， 定义顺式作用调节序列的作用， 人B珠蛋白基因家族的阶段特异性表达，和d） 建立一个合作研究企业，以探索 补体、凝血酶和其他激动剂对镰状红细胞粘附的影响 血管内皮的最终目标是确定一个潜在的作用， 镰状血管闭塞的相互作用。这些项目将 在2个核心临床机构，CHORI和实验室进行， UCSF和劳伦斯伯克利国家实验室。节目将 由中心工作人员协调，并由内部和外部评估 审查机构。

The objectives of the Northern California Comprehensive Sickle Cell Center (NCCSCC) are 1) to sponsor and facilitate hemoglobinopathy research at both fundamental and clinical levels and 2) to provide hemoglobinopathy detection, counseling, and education to affected populations using the most modern methods. To pursue these objectives, we have established a CORE hemoglobin structure and diagnosis laboratory at Childrens' Hospital Oakland Research Institute (CHORI) and CORE clinical research programs in the West Bay (UCSF/San Francisco General Hospital) and in the East Bay (Childrens' Hospital Oakland, Highland Hospital). These programs provide hemoglobinopathy detection, counseling and education as well as a stable, well characterized group of over 500 patients with sickle cell disease (SCD) who participate in NCCSCC research projects. Clinical research projects aim to a) test the efficacy of core decompression in the management of aseptic necrosis of bone, b) see whether an acute rise in serum secretory phospholipase AD heralds the acute chest syndrome and justifies early therapeutic intervention, and 3) evaluate the efficacy of potential new therapies (hydroxyurea + phenyl butyrate or clotrimazole, isobutyramide, oral magnesium, oral chelation and various forms of stem cell transplantation). More basic cell and molecular biology research projects will a) exploit our newly developed transgenic mouse model of SCD (which completely lacks mouse globin chains) to explore the pathophysiology of SC and evaluate potential new treatments, b) employ a genome a genome-wide scan to identify genes unlinked to the globin cluster that alter SCD severity and globin chain switching in inbred strains of mice, c) use a human b globin YAC specific transgenic mouse model to define the role of cis-acting regulatory sequences that direct tissue-and stage-specific expression of the human b globin gene family, and d) establish a collaborative research venture to explore the effects of complement, thrombin, and other agonists on the adherence of sickle RBC to vascular endothelium with the ultimate goal of defining a potential role for these interactions in sickle vaso-occlusion. These projects will be carried out at the 2 CORE clinical facilities, CHORI, and laboratories at UCSF and Lawrence Berkeley National Laboratory. Programs will be coordinated by Center staff and evaluated by both internal and external review bodies.