CLINICAL STUDIES OF ABNORMAL HOST DEFENSE

这个项目的目的是研究宿主异常的患者。 防守。在97财年，我们继续对自然历史进行长期研究 吞噬功能异常患者的发病机制。 这些人包括儿童慢性肉芽肿疾病的患者， 高免疫球蛋白E-复发性感染综合征(约伯综合征)，白细胞 粘连缺乏症和其他反复感染的患者 不属于特定定义的疾病类别。今年我们 继续干扰素疗效的IV期临床试验- 伽玛刀对慢性阻塞性肺疾病儿童生长发育的影响 儿童肉芽肿性疾病，未发现任何不良反应 反应。 我们继续对一名15岁有复发性生命的女孩进行研究。 威胁细菌感染，谁是难以抵抗的影响 体内和体外的内毒素内毒素(LPS)。我们的研究 这位患者表现出对内毒素的异常发热反应， 肿瘤坏死因子-α、白介素6、白介素8、乳铁蛋白和粒细胞集落刺激因子的缺陷反应 已于今年完成并出版。我们现在正专注于我们的 关注内毒素低反应性的分子基础 这位病人。初步数据显示，缺陷涉及NFKB 系统。尽管尚未确定确切的缺陷，但 数据表明与蛋白质有关的一个激酶系统参与其中 磷酸化。

The purpose of this project is to study patients with abnormal host defense. In FY'97 we continued our long term studies on natural history and disease pathogenesis on patients with abnormal phagocyte function. These included patients with chronic granulomatous disease of childhood, hyperimunoglobulin E-recurrent infection syndrome (Job's), leukocyte adhesion deficiency and other patients with recurrent infections who do not fall into a specifically defined disease category. This year we continued the phase IV clinical trial on the effect of interferon- gamma on the growth and development of children with chronic granulomatous disease of childhood and failed to note any adverse reactions. We have continued our studies on a 15 yo girl with recurrent life threatening bacterial infections who is refractory to the effects of endotoxin lipopolysaccharide (LPS) in vivo and in vitro. Our studies in this patient demonstrating abnormal febrile response to LPS and defective responses for TNF-alpha, IL-6, IL-8, lactoferrin and G-CSF were completed and published this year. We are now focusing our attention to the molecular basis for endotoxin hyporesponsiveness in this patient. Preliminary data indicates the defect involves the NFKB system. Although the precise defect has not yet been identified the data suggest involvement of a kinase system involved in protein phosphorylation.