Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O95477 (membrane-bound)
 29,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Jejunal biopsies were performed in 12 randomly chosen patients with multiple sclerosis. The jejunal mucosa was examined histologically, ultrastructurally, and by tissue immune techniques. Histology showed a normal mucosa in 7 patients, increased inflammatory-cell infiltration in 3, a partial villous atrophy in 1, and a subtotal villous atrophy in the remaining patient. Fine structural abnormalities were seen in 6 of 8 patients studied. These included microvillous changes, increase in theliolymphocytes and epithelial lysosomes, thickening of the connective tissue with or without collagen fibres, and numerous macrophages containing large amounts of membrane-bound electron-dense material. The latter was seen in 5 of the 8 mucosae examined.
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PMID:Small-bowel abnormalities in multiple sclerosis. 6 1

Lymphocytes from lymph nodes of Lewis rats with acute experimental allergic encephalomyelitis (EAE) contain high amounts of acid and neutral proteinases which hydrolyze myelin basic protein. The activity at neutral pH is also expressed by whole lymphocytes in isotonic medium, with about 50% more activity released by homogenization. Neutral proteinase activity in lymphocytes increases with the onset of acute EAE while the activity of those from Freund's adjuvant-injected controls increases somewhat later. The total neutral proteinase activity appears to be membrane-bound, most likely in the lysosomes, but half the total was associated with the nuclear fraction. The basic protein proteinase was compared with an enzyme described earlier, especially active toward polylysine, and some differences were noted. It appears that two enzymes may be present in lymphocytes which hydrolyze basic protein at a neutral pH. An increase in neutral proteinase activity was observed in some, but not all, lymphocyte preparations from patients in various stages of multiple sclerosis. The finding that whole activated lymphocytes are capable of hydrolyzing basic protein suggests that these cells which are believed to be precursors of mononuclear cells migrating into the central nervous system may be active agents in the early stages of myelin dissolution in experimental allergic encephalomyelitis. At present, such a mechanism is only theoretical, and the possibility that activated lymphocytes may be a factor in demyelination in multiple sclerosis is even more speculative.
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PMID:Baisc protein hydrolysis in lymphocytes of Lewis rats with experimental allergic encephalomyelitis. 8 Sep 45

Perivascular cells in CNS tissue from six multiple sclerosis (MS) patients and a patient with motor neuron disease were examined by light and electron microscopy. Lymph node tissue from one MS patient was also examined. CNS perivascular macrophages in both MA and motor neuron disease were found to closely resemble free macrophages elsewhere in the body except that they often contained unusually large primary lysosomes. Cytoplasmic inclusions consisting of membrane-bound stacks of curved linear profiles, presumed to be a product of myelin degradation, were constantly observed in microglia in MS plaques but were rarely observed in perivascular macrophages in the same area. Unidentified cylindrical bodies were observed within cysternae of rough endoplasmic reticulum in some lymph node cells. Quantitative studies of the perivascular cell population in one MS case revealed, in histologically normal white matter 260 lymphocytes and 178 plasma cells per cubic millimeter of fresh tissue. Typical chronic plaque tissue without obvious inflammatory cell cuffing contained 1772 plasma cells per cubic millimeter of fresh tissue. No plasma cells were observed in the CNS in motor neuron disease. The results of this study suggest that perivascular macrophages in the CNS represent a specialized population of monocyte-derived free macrophages, that these cells differ functionally from microglial cells, and that the digestion of myelin breakdown products in MS requires the participation of both cell types. The results also suggest that in some chronic MS cases there is a large, permanent population of CNS plasma cells that persists, like the elevated cerebrospinal fluid IgG level in this disease, for the life of the patient, that these cells, rather than inflammatory cells in fresh lesions, are the major source of this raised IgG, and that the existence of such a population of cells may indicate the continuing expression of antigens in chronic MS lesions in the absence of fresh lesion formation.
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PMID:Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. 20 24

We investigated the fine structural details of the presence of apparently newly formed oligodendrocytes within reactive astrocytes in white matter lesions obtained by biopsy from seven cases (3 multiple sclerosis (MS); 3 progressive multifocal leukoencephalopathy (PML); 1 with nonspecific reactive changes next to a sarcoid granuloma). Intact oligodendrocytes were found within astrocytic cytoplasm in two acute MS lesions and also in the reactive white matter lesion. The internalized cells appeared to lie within membrane-bound vacuoles. Formation of rudimentary junctions was observed between the internalized cells and host astrocytes. Sometimes more than one oligodendrocyte was seen in the same astrocyte. Our study suggests that this newly recognized interaction between astrocytes and oligodendrocytes is not restricted to acute MS lesions and probably represents emperipolesis rather than phagocytosis. This apparently nonspecific finding may be expected in any lesion with a proliferation of astrocytes and oligodendrocytes. The precise mechanism of this phenomenon or its functional significance is not entirely clear.
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PMID:Occurrence of oligodendrocytes within astrocytes in demyelinating lesions. 174 Jun 73

Central nervous system (CNS) tissue was studied by immunocytochemistry and electron microscopy from three cases of multiple sclerosis (MS) in which evidence of ongoing myelin breakdown could be documented. The study focussed upon the role of glial cells in the pathogenesis of demyelination. In acute MS, demyelination involved the vesicular dissolution of myelin from intact axons and a paucity of fibrillary astrogliosis. Foamy macrophages, many of them probably derived from transformed and recently proliferated microglia, contained recognizable myelin debris and lipid droplets and were abundant throughout the lesions. These cells formed the major phagocytic population and stained positively for class II major histocompatibility complex antigens (HLA-DR; Ia). In acute MS lesions, rounded astrocytes were encountered which possessed membrane-bound compartments enclosing phagocytosed fragments of myelin basic protein-positive debris. Despite the superficial resemblance of these cells to foamy macrophages, the presence of intermediate filaments, glycogen granules and diffuse glial fibrillary acidic protein positivity supported an astroglial identity. Astrocyte processes were involved in myelin removal and invested recently demyelinated axons. Hypertrophic fibrous astrocytes were common in chronic active lesions, were capable of myelin degradation and on occasion, contained myelin debris attached to clathrin-coated pits. These astrocytes were sometimes Ia+. Oligodendrocytes were depleted from the center of active lesions but were numerous at the lesion margin, suggesting survival and proliferation. They stained positively for myelin-associated glycoprotein, a marker for immature oligodendrocytes. However, they were invariably Ia-. The findings confirm and further support a role for the astrocyte as both an antigen presenting cell and a phagocyte in the CNS during MS.
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PMID:Multiple sclerosis: a role for astroglia in active demyelination suggested by class II MHC expression and ultrastructural study. 230 80

Membrane-bound proteolysis may be implicated in the pathogenesis of demyelinating disorders including multiple sclerosis (MS). We previously found that the extent of myelin basic protein (MBP) degradation by the calcium-activated neutral protease did not differ for isolated human control myelin or MS myelin. Hence we suggested that, if involved in demyelination, the myelin neutral protease must be activated in vivo by an increased availability of free calcium. The postulate was therefore tested that immunoglobulin (Ig) binding to myelin results in activation of the myelin neutral protease, possibly through release of free calcium from calcium-binding sites of myelin. Isolated myelin from the brains of controls and patients with MS were incubated with purified Igs eluted from the brains of patients with MS or controls and degradation of MBP was assessed by quantitative electroimmunoblotting. Such degradation was significantly greater in myelin incubated in the presence of MS Igs than in myelin incubated without added Igs or in the presence of control Igs. Furthermore, the degree of MBP degradation in myelin incubated with control Igs was similar to that observed in myelin incubated without added Igs. Accordingly, it is suggested that Ig in MS brain potentiates myelin breakdown. Moreover activation of membrane-bound proteolysis by Ig binding to myelin appears to represent a hitherto undescribed pathway for demyelination in MS.
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PMID:Multiple sclerosis brain immunoglobulins stimulate myelin basic protein degradation in human myelin: a new cause of demyelination. 247 68

Previous studies have shown that zinc levels in erythrocytes are significantly elevated in patients with multiple sclerosis (MS). To examine the correlation between erythrocyte Zn levels and disease activity, we measured erythrocyte Zn levels longitudinally. Levels were dramatically decreased during a clinically documented exacerbation of MS. To determine the localization of increased Zn levels in MS erythrocytes, we employed standard techniques for the isolation of nonhemoglobin erythrocyte membrane ghosts. Patients with MS had three times more Zn in ghost material than did controls. Chloroform-methanol extraction in erythrocyte ghosts followed by determination of Zn levels indicated that most of the membrane-bound Zn was associated with the lipid-soluble fraction. Non-lipid-associated Zn and total membrane protein concentration were similar in MS and control samples. Results suggest that mechanisms which govern cellular availability, compartmentalization of Zn, or the binding of Zn to cell surface membranes may be altered in patients with MS, and that these mechanisms vary with disease activity.
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PMID:Zinc in multiple sclerosis. II: Correlation with disease activity and elevated plasma membrane-bound zinc in erythrocytes from patients with multiple sclerosis. 381 99

The electron microscopic features of 11 stereotaxic brain biopsies that demonstrated inflammatory primary demyelination consistent both morphologically and clinically with multiple sclerosis are addressed. Degeneration of inner oligodendroglial loops and uniform widening of inner myelin lamellae antedated complete destruction of myelin sheaths. Perivascular lymphocytes, macrophages, and plasma cells were in intimate contact with myelin sheaths. Astrocytes proliferated even away from demyelinated areas. In areas of chronic, established demyelination, oligodendrocyte numbers were greatly decreased, and fields of completely demyelinated axons were seen among astrocytic processes. Axonal injury, evidenced by the formation of axonal swellings, was apparent in maximally affected areas. At the edge of acute lesions with demyelinated axons, oligodendrocytes were preserved morphologically. Thinly myelinated axons indicative of central nervous system-type remyelination by oligodendrocytes were observed primarily at the edges of plaques. An unusual inclusion observed in presumed macrophages was "polelike" bodies 0.04- to 0.7-microns thick. Linearly arrayed, their presumably proteinaceous crystalline substance was moderately electron-dense. Many were membrane-bound and appeared to arise from the endoplasmic reticulum. We conclude that disturbance of the myelinating function of oligodendrocytes may be a critical event in the pathogenesis of multiple sclerosis.
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PMID:Ultrastructure of multiple sclerosis. 819 43

Recent evidence indicates that membrane-bound costimulatory molecules of the B7 family are important for T-cell activation and are upregulated in IFN gamma-stimulated human microglia and in multiple sclerosis active lesions. In this study we have performed a detailed analysis of B7-1 and B7-2 expression and regulation in cultured mouse glial cells using immunocytochemical and semi-quantitative reverse transcriptase-polymerase chain reaction techniques. In an immortalized mouse microglial cell line (BV-2), expression of B7-1 and B7-2 was enhanced by interferon-gamma (IFN gamma). IFN gamma was a weak inducer of B7-2 mRNA and immunoreactivity in microglia primary cultures obtained from the neonatal mouse brain, whereas lipopolysaccharide, tumour necrosis factor-alpha, colony-stimulating factors and interleukin-1 beta did not affect microglial B7-2 expression. Combined IFN gamma and lipopolysaccharide treatment very effectively upregulated the B7-2 gene expression and immunoreactivity in microglia, but not in astrocytes. In both glial cell types, expression of B7-1 was not induced by any of the above agents. Among known microglia/macrophage deactivators, interleukin-10, prostaglandin E2 and cAMP-elevating agents, but not transforming growth factor-beta 1 and interleukin-4, inhibited B7-2 transcripts and immunoreactivity in IFN gamma/LPS-stimulated microglia, thus suggesting possible paracrine and autocrine mechanisms for regulating the expression of this important T-cell costimulatory signal in the brain.
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PMID:Analysis of B7-1 and B7-2 costimulatory ligands in cultured mouse microglia: upregulation by interferon-gamma and lipopolysaccharide and downregulation by interleukin-10, prostaglandin E2 and cyclic AMP-elevating agents. 900 48

The matrix metalloproteinases (MMPs) are a family of at least 14 zinc-dependent enzymes which are known to degrade the protein components of extracellular matrix. In addition, MMPs and related enzymes can also process a number of cell surface cytokines, receptors, and other soluble proteins. In particular we have shown that the release of the pro-inflammatory cytokine, tumor necrosis factor-alpha, from its membrane-bound precursor is an MMP-dependent process. MMPs are expressed by the inflammatory cells which are associated with CNS lesions in animal models of multiple sclerosis (MS) and in tissue from patients with the disease. MMP expression will contribute to the tissue destruction and inflammation in MS. Drugs which inhibit MMP activity are effective in animal models of MS and may prove to be useful therapies in the clinic.
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PMID:Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview. 904 8


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