ELECTRON MICROSCOPY OF MYOPATHIES

Project: Research project

Description

This 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 of 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. In four newly
recognized congenital myasthenic syndromes the mechanisms that lead to
failure of neuromuscular transmission will be further investigated: In
the syndrome associated with high conductance and fast closure of the
AChR ion channel, the hypothesis will be tested that the transmission
defect is conditioned by an endplate myopathy and focal AChR deficiency.
In the syndrome with decreased release of ACh quanta, additional evidence
will be sought that the disorder stems from a paucity of synaptic
vesicles and that this could be due to a deficiency of a synaptic vesicle
membrane associated protein. In the syndrome with a putative abnormality
of ACh-AChR interaction, a search will be made for any ultrastructural
correlate that might result in a reduced amplitude of the miniature
endplate current. In the syndrome of AChR deficiency and short channel
open time, detailed analysis of endplate ultrastructure, and of the
distribution of alpha-bungarotoxin binding sites, AChR subunits alpha,
delta and epsilon, and of the AChR-associated 43 kD protein will be
carried out. In the recently recognized eosinophilia-myalgia syndrome, a
disabling inflammatory disease now attributed to sensitization to a
contaminant of L-tryptophan preparations, immunocytochemical and
ultrastructural studies will be done to define immune effector mechanisms
and their targets. An experimental model of microvascular injury to
skeletal muscle induced by sensitization to cultured human endothelial
cells will be investigated. The immunoelectron microscopic localization
of dystrophin in normal human skeletal muscle will be reinvestigated to
clarify whether it is, or is not, associated with subcellular organelles
other than the plasma membrane. In the newly discovered mitochondrial
encephalomyopathy due to coenzyme Q10 deficiency, the hypothesis will be
tested that the disorder is caused by a defect in the mitochondrial
biosynthesis of coenzyme Q10.
StatusFinished
Effective start/end date5/1/774/30/16

Funding

  • National Institutes of Health
  • National Institutes of Health: $473,571.00
  • National Institutes of Health: $475,898.00
  • National Institutes of Health: $497,415.00
  • National Institutes of Health
  • National Institutes of Health: $333,004.00
  • National Institutes of Health
  • National Institutes of Health: $510,033.00
  • National Institutes of Health: $273,703.00
  • National Institutes of Health: $549,907.00
  • National Institutes of Health
  • National Institutes of Health: $538,189.00
  • National Institutes of Health
  • National Institutes of Health: $506,480.00
  • National Institutes of Health: $262,122.00
  • National Institutes of Health: $510,847.00
  • National Institutes of Health
  • National Institutes of Health: $217,892.00
  • National Institutes of Health: $546,998.00
  • National Institutes of Health: $482,586.00
  • National Institutes of Health: $485,267.00
  • National Institutes of Health: $524,388.00
  • National Institutes of Health
  • National Institutes of Health: $320,193.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $296,037.00
  • National Institutes of Health: $526,412.00
  • National Institutes of Health: $490,358.00
  • National Institutes of Health

Fingerprint

Congenital Myasthenic Syndromes
Muscular Diseases
Cholinergic Receptors
Electron Microscopy
Muscles
Mutation
Genes
Proteins
Light
Safety
coenzyme Q10
Phenotype
Neuromuscular Junction
Acetylcholinesterase
Muscle Weakness
Autoantibodies
Blood Vessels
Microelectrodes
Electromyography
Eosinophilia-Myalgia Syndrome

ASJC

  • Medicine(all)
  • Neuroscience(all)