ELECTRON MICROSCOPY OF MYOPATHIES

本提议寻求支持继续进行调查 人类和实验诱发肌肉疾病的计划。这些疾病 通过对光学显微镜和光学显微镜的分析来探讨 肌肉纤维、神经肌肉接头的超微结构反应 肌内神经和血管。研究个别疾病 系统地通过结合光镜组织化学， 免疫细胞化学，位相和电子显微镜，免疫电子 显微镜和冷冻断口电子显微镜。只要有可能， 观测数据通过形态测量方法进行量化，并与 现有的生理和生化数据。本次大会的两大主题 更新期属于神经肌肉传递缺陷和 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导致 将评估终板乙酰胆碱受体(AChR)缺乏症。在一个 先天性肌无力综合征归因于乙酰胆碱受损 重新合成或动员，将寻求超微结构的相关性 治疗刺激性神经肌肉传递障碍。在……里面 三种临床和形态截然不同的肌无力综合征 与先天性终板AChR缺乏症相关的详细分析 终板超微结构、AChR分布和胆碱能结合部位 将会被执行。在Lambert-Eaton肌无力综合征中 将检验突触前膜活动区代表 致病性自身抗体的靶标。在杜兴营养不良症和其他 肌病、坏死性和先坏死性肌肉纤维将被研究以确定 补体膜攻击的超微结构结合部位 很复杂。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抗分析.亚群 这些参与肌肉纤维破坏的细胞将被定义，并且 这一机制的超微结构方面将被阐明。在……里面 皮肌炎的假说将检验其病理特征 这种疾病的致病因素是由循环中的自身抗体介导的。

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.