Project: Research project

Project Details


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.
Effective start/end date5/1/774/30/16


  • Medicine(all)
  • Neuroscience(all)