ELECTRON MICROSCOPY OF MYOPATHIES

肌病的电子显微镜检查

• 批准号: 3393459
• 负责人: ANDREW George ENGEL
• 金额: $ 19.8万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-05-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3393459
• 关键词: acetylcholine; autoantibody; autoimmune disorder; biopsy; bungarotoxins; complement pathway; dermatomyositis; disease /disorder classification; electron microscopy; electrophysiology; freeze etching; histochemistry /cytochemistry; human subject; immunochemistry; inflammation; membrane activity; membrane structure; monoclonal antibody; muscle disorder diagnosis; muscular dystrophy; myasthenia gravis; myofibrils; necrosis; neurochemistry; neuromuscular junction; neuromuscular transmission

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.

本提案寻求支持继续调查的支持 人类和实验引起的肌肉疾病的计划。 疾病 通过分析光显微镜和 肌肉纤维中的超微结构反应，神经肌肉连接， 肌内神经和血管。 研究了个体疾病 通过合并的光学组织化学组合系统地， 免疫细胞化学，相和电子显微镜，免疫电子 显微镜和冻结电子显微镜。 只要可能， 观察通过形态计量方法定量，并与 可用的生理和生化数据。 两个主要主题 续期与神经肌肉传播的缺陷有关 肌肉纤维损伤的机制。 在获得的肌无力中/ 免疫病理机制的相对贡献，导致 将评估端板乙酰胆碱受体（ACHR）缺乏。 在 先天性肌关系综合征归因于乙酰胆碱受损 重新合成或动员，将寻求超微结构相关性 为了刺激神经肌肉传播的失败。 在 三个在临床和形态上不同的肌无力综合征 与先天板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 将进行。 在兰伯特 - 伊顿肌无力综合症中 假设将检验，突触前膜活性区代表 病原自身抗体的靶标。 在Duchenne营养不良和其他 将研究肌病性坏死和前肌纤维以定义 补体膜攻击的超微结构结合位点 复杂的。 将研究炎症性肌病的发病机理 通过肌肉中单核细胞的单克隆抗体分析；子集 这些涉及肌肉纤维破坏的细胞将被定义，并 该机制的超微结构方面将被阐明。 在 皮肤肌炎将测试假说是病理特征 该疾病是由循环自身抗体介导的。