Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A relatively simple preparation of guinea pig brain myelin, free of gross contamination by other cellular elements has been described. Electron microscopic evidence of the predominance of membranous (lamellar) forms was used as the criterion of purity of this fraction. The slight mitochondrial contamination of the myelin fraction was confirmed by its low succinic dehydrogenase activity. Quantitative bio-assay of the encephalitogenic activity of myelin showed it to have a higher specific activity than whole guinea pig brain. The low encephalomyelitic activity of the other subcellular constituents (nuclei and mitochondria) which were removed from myelin by ultracentrifugation in 30 per cent sucrose could be explained by a small amount of myelin contamination. A basic protein of high specific encephalitogenic activity has been isolated from myelin by methods previously applied to whole brain. Although the protein is similar to nuclear histones, the following facts point to certain significant differences. Nuclei prepared by a different procedure from the one developed for the isolation of myelin were found to be non-encephalitogenic. Although basic protein could be extracted readily from these nuclei by dilute HCl, the same extraction procedure yielded little extractable protein from whole myelin. Myelin which had been defatted by cold chloroform-methanol yielded a basic protein which was highly encephalitogenic. The evidence presented thus supports the view that there exists in myelin a new basic protein responsible for the induction of experimental allergic encephalomyelitis, which is distinctly different from nuclear histones. The possible relationship of this protein to myelin structure and function has been discussed.
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PMID:The encephalomyelitic activity of myelin isolated by ultracentrifugation. 1446 Dec 28

Poly(ADP-ribose) polymerase (PARP) activity has been implicated in the pathogenesis of several central nervous system (CNS) disorders. For example, the presence of extensive poly(ADP)ribosylation in CNS tissues from animals with experimental allergic encephalomyelitis (EAE) indicates that PARP activity may be involved in this inflammatory disease process. Using PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N, N-dimethylacetamide.HCl], a selective PARP inhibitor, we studied the mechanisms through which PARP activity may contribute to the onset of acute EAE. PLSJL mice immunized with myelin antigens were treated with PJ34, and the effects on the progression of EAE and several other parameters relevant to the disease process were assessed. PJ34 exerted therapeutic effects at the onset of EAE that were associated with reduced CNS inflammation and the maintenance of neurovascular integrity. Expression of genes encoding the intercellular adhesion molecule-1 (ICAM-1) and the inflammatory mediators interferon-gamma, tumor necrosis factor-alpha, and inducible nitric-oxide synthase were decreased in CNS tissues from drug-treated animals. Administration of PJ34 biased the class of myelin basic protein (MBP)-specific antibodies elicited from IgG2a to IgG1 and IgG2b and modulated antigen-specific T-cell reactivity. Therefore, the mode of action of PJ34 at the onset of EAE is likely mediated by a shift in the MBP-specific immune response from a proinflammatory Th1 toward an anti-inflammatory Th2 phenotype.
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PMID:The therapeutic effects of PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide.HCl], a selective inhibitor of poly(ADP-ribose) polymerase, in experimental allergic encephalomyelitis are associated with immunomodulation. 1515 42