COMBINED CLINICAL, VIRAL, AND IMMUNOLOGICAL STUDIES OF NEUROMUSCULAR DISEASES

进行临床和实验室研究以确定病因 （感染、免疫力和/或遗传学） 神经肌肉系统和设计有效的治疗方法。目前的研究 涉及多发性肌炎、皮肌炎、包涵体 肌炎，脊髓灰质炎后综合征，脱髓鞘性多发性神经病， 与HIV感染相关的神经肌肉疾病，代谢性 肌病、低钾性周期性麻痹、营养不良、肌无力 重症、糖尿病性神经病变和僵人综合征。发病机制 脊髓灰质炎后综合征的研究是通过一系列的电- 生理学、病毒学、免疫学和组织学研究。 在这些患者的组织中寻找持久性或突变型脊髓灰质炎病毒 使用组织培养、PCR和原位杂交。 机制 脊髓灰质炎后疲劳，这是许多患者常见的致残症状， 通过分析神经内分泌轴，磁共振检查 光谱学和睡眠研究。 β-淀粉样蛋白前体序列 在家族性和散发性乳腺癌患者中进行了蛋白基因检测， 包涵体肌炎。神经肌肉疾病谱 与艾滋病毒感染有关的研究， 病毒和诱导的细胞因子在神经病或肌病的原因， 通过多种免疫细胞化学研究进行原位研究 杂交和PCR。抗逆转录病毒药物ddC被发现导致 一种独特的神经病，其特征是异常线粒体， 通过各种形态学、分子和生物化学研究。 的 强直性脊柱炎患者抗GAD抗体的细胞毒性基础 研究了综合征和抗体滴度的变化 在体内和体外以及在治疗过程中。随机对照临床 使用高剂量静脉注射免疫球蛋白进行试验， 多发性肌炎、皮肌炎、包涵体肌炎， 慢性炎性和副蛋白血症脱髓鞘性多发性神经病， 僵硬人综合征、重症肌无力与糖尿病自身免疫 神经病变 一项对照研究使用二氯苯甲酰胺，一种碳酸 脱水酶抑制剂，已在低钾血症患者中进行 周期性麻痹另一项使用左旋肉碱的对照研究是 还在AZT诱导的线粒体肌病患者中进行， 肉毒碱耗尽

Clinical and laboratory studies are conducted to determine the etiology (infection, immunity and/or genetics) of chronic diseases of the neuromuscular system and design effective therapies. Current studies involve patients with polymyositis, dermatomyositis, inclusion body myositis, post-polio syndrome, demyelinating polyneuropathies, neuromuscular diseases associated with HIV infection, metabolic myopathies, hypokalemic periodic paralysis, dystrophies, myastenia gravis, diabetic neuropathies and stiff-man syndrome. The pathogenesis of post-polio syndrome is explored with a series of electro- physiological, virological, immunological and histological studies. Persistent or mutant poliovirus is sought in these patient's tissues using tissue cultures, PCR, and in situ hybridization. The mechanism of post-polio fatigue, a common and disabling symptom in many patients, is examined by analysis of the neuroendocrine axis, Magnetic Resonance Spectroscopy and sleep studies. Sequence of the beta-amyloid presursor protein gene was performed in patients with familial and sporadic inclusion body myositis. The spectrum of neuromuscular disorders associated with HIV infection has been studied, and the role of the virus and induced cytokine in the cause of neuropathy or myopathy is investigated with a variety of immunocytochemical studies, in situ hybridization and PCR. The antiretroviral drug ddC was found to cause a unique neuropathy characterized by abnormal mitochondria as determined by various morphological, molecular and biochemical studies. The cytotoxic basis of anti-GAD antibodies in patients with stiff-man syndrome is investigated and changes in the antibody titers are studied in vivo and in vitro and during therapy. Randomized-controlled clinical trials are conducted using high-dose Intravenous immunoglobulin in patients with polymyositis, dermatomyositis, inclusion body myositis, chronic inflammatory and paraproteinemic demyelinating polyneuropathies, stiff-man syndrome, myasthenia gravis and diabetic autoimmune neuropathy. A controlled study using dichlorophenamide, a carbonic anhydrase inhibitor, has been conducted in patients with hypokalemic periodic paralysis. Another controlled study using L-carnitine has been also conducted in patients with AZT-induced mitochondrial myopathy with carnitine depletion.