NEUROMUSCULAR AND CENTRAL NERVOUS SYSTEM DISEASES AND THEIR EXPERIMENTAL MODELS

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Immunocytochemical studies were conducted using specific antibodies to thymic peptides to investigate the interaction of the immune system with the central and peripheral nervous systems. Thymosin beta 4, an immunomodulating thymic polypeptide, was found to be a common antigen shared by macrophages, dendritic lymphoid cells and the myelin producing cells in the CNS (oligodendrocytes) and the PNS (Schwann cells). Prothymosin, a nuclear protein, and thymosin-a1, were found present in astrocytes of normal human brain and could play a role in cell proliferation and gliosis. The IgM of certain patients with paraproteinemic polyneuropathies has been identified as a specific antibody to acid intraneural injection of IgM in the sciatic nerve of the cat induced demyelination suggesting a direct role in the pathogenesis of the neuropathy. The nature of amyloid protein in patients with "sporadic" amyloid polyneuropathy was identified using specific antibodies to amyloid proteins; point mutations and direct sequencing of prealbumin genes, the precursor protein, were studied in the amyloid tissue using the polymerase chain reaction. The mechanism of inflammatory myopathy in monkeys with immunodeficiency (Simian AIDS) cause by SRV-1 and SIV-1 retroviruses, was studied. Antibodies to SRV-1 immunoreacted with inflammatory cells invading muscle fibers; SRV-1 was capable of infecting myoblasts in tissue culture without exerting a cytopathic effect in the muscle. The role of SIV-1 is similarly studied. The effect of aging on the neuromuscular system of monkeys from age 5 to 25 is being studied with a detailed morphological and morphometrical analysis of their muscle and nerve biopsies. The mechanism of muscle regeneration is studied examining markers on satellite cells including the role of adhesion on molecules such as laminin, N-CAM, and ICAM. The monoclonal antibody Leu-19 (NKH) that identifies natural killer cells was found to share common antigenic determinants with the satellite muscle cells. NKH also stains regenerating muscle fibers and could play a role in muscle regeneration. The induction of abnormal mitochondria in the muscle by several nucleoside analogues is investigated in the muscle fibers in tissue culture.