ELECTRON MICROSCOPY OF MYOPATHIES

本提案寻求支持继续进行调查， 人类和实验诱导的肌肉疾病的程序。 的疾病 通过光镜分析， 肌纤维，神经肌肉接头， 肌肉神经和血管。 研究了个别疾病 系统地结合光镜组织化学， 免疫细胞化学，相和电子显微镜，免疫电子 显微镜和冷冻断裂电子显微镜。 尽可能 观察结果通过形态测定方法进行定量，并与 可用的生理和生化数据。 会议的两个主题是： 更新期与神经肌肉传递缺陷有关， 肌纤维损伤的机制。 获得性重症肌无力/ 免疫病理机制的相对贡献， 将评估终板乙酰胆碱受体（AChR）缺乏。 中 乙酰胆碱受损型先天性肌无力综合征 再合成或动员，将寻求超微结构相关性 因为刺激导致神经肌肉传递的失败。 在 三种临床和形态学上不同的肌无力综合征 与先天性终板AChR缺乏相关，详细分析 终板超微结构、AChR分布和胆碱能结合位点 将被执行。 在Lambert-Eaton肌无力综合征中， 假设将被测试，突触前膜活动区代表 致病性自身抗体的目标。 在杜氏营养不良和其他 将研究坏死和坏死前肌纤维的肌病，以确定 补体膜攻击的超微结构结合位点 复杂. 炎症性肌病的发病机制将被调查 通过肌肉中单核细胞的单克隆抗体分析;亚群 这些细胞参与肌纤维破坏将被定义， 将阐明这种机制的超微结构方面。 在 皮肌炎的假设将被测试，病理特征 是由循环自身抗体介导的。

The present proposal seeks support for the continuation of an investigative program of human and experimentally induced muscle diseases. The diseases are approached through analysis of the light microscopic and ultrastructural reactions in the muscle fiber, neuromuscular junction, intramuscular nerves and blood vessels. Individual diseases are studied systematically by combined light microscopic histochemistry, immunocytochemistry, phase and electron microscopy, immunoelectron microscopy and freeze-fracture electron microscopy. Whenever possible, the observations are quantitated by morphometric methods and correlated with available physiologic and biochemical data. The two main themes for the renewal period pertain to defects of neuromuscular transmission and mechanisms of muscle fiber injury. In acquired myasthenia gravis/the relative contributions of the immunopathologic mechanisms which result in end-plate acetylcholine receptor (AChR) deficiency will be evaluated. In a congenital myasthenic syndrome attributed to impaired acetylcholine resynthesis or mobilization, an ultrastructural correlate will be sought for the stimulation induced failure of neuromuscular transmission. In three clinically and morphologically distinct myasthenic syndromes associated with congenital end-plate AChR deficiency, detailed analyses of end-plate ultrastructure, AChR distribution and cholinergic binding sites will be carried out. In the Lambert-Eaton myasthenic syndrome the hypothesis will be tested that presynaptic membrane active zones represent the target of pathogenic autoantibodies. In Duchenne dystrophy and other myopathies necrotic and prenecrotic muscle fibers will be studied to define the ultrastructural binding site of the complement membrane attack complex. The pathogenesis of inflammatory myopathies will be investigated by monoclonal antibody analysis of the mononuclear cells in muscle; subsets of these cells involved in muscle fiber destruction will be defined, and the ultrastructural aspects of this mechanism will be elucidated. In dermatomyositis the hypothesis will be tested that the pathologic features of the disease are mediated by a circulating autoantibody.