PHAGOCYTIC CELL FUNCTION

这个项目的目的是确定遗传病的遗传基础。 影响中性粒细胞功能并与复发相关的疾病 感染，以及此类疾病的诊断和治疗。慢性 儿童肉芽肿疾病(CGD)是一组 常见的表型包括吞噬细胞不产生H202，反复出现 感染和肉芽肿形成。我们已经记录了流行性出血热 CGD(60%细胞色素X连锁缺陷)的四种不同遗传形式 B558 gp91-Phox亚基；细胞色素5%常染色体隐性(AR)缺陷 P22-Phox亚基；30%AR影响P47-Phox胞浆氧化酶因子；5%AR 影响p67Phox胞浆因子)。P67-Phox基因结构的研究 揭示了两种正常的等位基因HinDIII限制性内切酶模式，这将 可用于产前诊断和定位染色体1q25区域。在……里面 其他研究通过逆转录病毒载体表达p47-Phox提供了一种 这是这种形式的CGD最终遗传重组的重要工具。我们 已经记录了小剂量类固醇在管理 胃肠道和泌尿系梗阻性肉芽肿。我们有 记录早期外科手术切除肺的重要性 肝脓肿的曲霉菌感染和引流。回顾我们的CGD 患者病史表明预防性服用甲氧普林-磺胺可减少 细菌感染而不会引起真菌感染的增加。vbl.使用 一种中性粒细胞对真菌的体外杀灭试验，我们记录了 少量的正常中性粒细胞与较大的 CGD中性粒细胞杀灭曲霉菌丝的数量提供了理论基础 用于感染CGD患者的粒细胞输注。

The purpose of this project is to determine the genetic basis of inherited diseases affecting neutrophil function and associated with recurrent infections, and diagnosis and treatment of such disorders. Chronic Granulomatous Diseases of Childhood (CGD) are a group of diseases with common phenotype including absent H202 production by phagocytes, recurrent infections, and granuloma formation. We have documented the prevalence of the four distinct genetic forms of CGD (60% X-linked defect in cytochrome b558 gp9l-phox subunit; 5% autosomal recessive (AR) defect in cytochrome p22-phox subunit; 30% AR affecting p47-phox cytosolic oxidase factor; 5% AR affecting p67phox cytosolic factor). Studies of p67-phox gene structure reveals two normal allelic HinDIII restriction enzyme patterns which will be useful in prenatal diagnosis and mapping chromosome 1q25 region. In other studies expression of p47-phox by retroviral vector provides an important tool for eventual genetic reconstitution of this form of CGD. We have documented the effectiveness of low dose steroids in management of obstructive granulomas of gastrointestinal and urinary system. We have documented the importance of early surgical extirpation of pulmonary aspergillus infections and drainage of liver abscesses. Review of our CGD patients' histories indicated that prophylactic trimethaprim-sulfa reduces bacterial infections without causing an increase in fungal infection. Using an in vitro assay of fungal killing by neutrophils, we have documented that a small number of normal neutrophils act synergistically with a larger number of CGD neutrophils to kill aspergillus hyphae providing a rationale for use of granulocyte transfusions in infected CGD patients.