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)

Strains of the murine coronavirus mouse hepatitis virus type 4 (MHV-4) which contained a mutation in the E2 peplomer glycoprotein were obtained by selection for resistance to neutralization by monoclonal antibodies. Characterization of six variants representing two independent epitopes on E2, E2B and E2C, by in vitro neutralization and antibody-binding assays demonstrated that selection for an alteration in epitope E2B also resulted in changes in epitope E2C and vice versa. We observed a mutation frequency of approximately 10(-4.3) to 10(-4.6), which is consistent with the expected occurrence of single point mutations. The variant virus strains were attenuated with respect to neurovirulence when compared with wild-type MHV-4. Mice normally develop encephalomyelitis and die after wild-type MHV-4 infection. Mice receiving 2- to 3-log-higher doses of the variant strains survived and developed demyelinating disease. As the disease progressed, evidence of remyelination and ongoing demyelination was observed up to 65 days after infection. Virus reisolated 15 days after infection retained the variant phenotype. The data indicate that the E2 glycoprotein plays a central role in determining the cellular tropism and virulence of MHV-4 in the mouse.
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PMID:Site-specific alteration of murine hepatitis virus type 4 peplomer glycoprotein E2 results in reduced neurovirulence. 301 6

The effect of a circulating monoclonal antibody recognizing an antigen located on the surface of myelin sheaths (myelin/oligodendroglia glycoprotein, MOG) on clinical and histopathological expression of experimental allergic encephalomyelitis (EAE) was tested in a model of EAE passively transferred by monospecific T lymphocytes. Intravenous injection of anti-MOG antibody at the onset of the disease massively augmented clinical impairment as well as primary demyelination. The structure of the CNS lesions depended on the balance between encephalitogenic T cells and anti-MOG antibody: when EAE was induced with high numbers of T cells, circulating anti-MOG antibody resulted in ubiquitous perivenous demyelination in the spinal cord and medulla oblongata. On the contrary, focal confluent demyelinated lesions were observed in animals injected with low numbers of T cells (even as few as 10(4] and anti-MOG antibody. Our studies, thus, indicate that the formation of inflammatory demyelinating lesions may be due to a synergistic action of cellular and humoral immune mechanisms.
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PMID:Experimental allergic encephalomyelitis: the balance between encephalitogenic T lymphocytes and demyelinating antibodies determines size and structure of demyelinated lesions. 325 87

The factors contributing to chronic relapsing inflammatory disease processes of the central nervous system (CNS) and demyelination are poorly understood. In addition to cellular immune reactions, humoral factors such as antibodies might quantitatively or qualitatively influence the disease process. We therefore investigated the effects of administration of a monoclonal antibody specific for a CNS autoantigen on both acute and chronic experimental autoimmune encephalomyelitis (EAE) in mice and rats. This monoclonal antibody, 8-18C5, specific for a myelin/oligodendrocyte glycoprotein, was observed to accelerate clinical and pathologic changes of CNS autoimmune disease. In SJL mice with chronic relapsing EAE, injection of antibody into animals recovering from an attack induced fatal relapses; in Lewis rats, acute EAE was enhanced and associated with a hyperacute inflammatory response with demyelination, a feature not commonly seen in acute EAE. The demonstration that relapses and demyelination can be induced by administration of a white matter-reactive monoclonal antibody offers new possibilities to study processes resulting in CNS damage during autoimmune disease. Furthermore, these findings support the immunopathogenic potential of antibody to myelin components in inflammatory CNS disease processes and, specifically, in causing demyelination.
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PMID:A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. 350 Sep 78

Cellular clone (MAK 14-7), producing antibodies against the virus of Venezuela equine encephalomyelitis (VEE), strain 230, was isolated using the standard hybridomata technology. Monoclonal antibodies neutralized the viral hemagglutinating activity leaving the infectious one intact. Monoclonal antibodies from MAD 14-7 reacted specifically with viral glycoprotein E1 as registered by the immunoprecipitation technique. The topography of antigenic determinants of viral E1/E2 glycoprotein dimer forming the virions outer spikes is discussed in connection with the results obtained.
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PMID:[Identification of monoclonal antibodies against protein E1 of venezuelan equine encephalomyelitis virus blocking the hemagglutinating but not the infective activity of virions]. 384 54

Monoclonal hybridoma antibodies directed against the polypeptides of murine hepatitis virus-4 (JHM strain) were tested for their ability to alter the course of a normally lethal intracerebral virus challenge. Three monoclonal antibodies directed against two distinct epitopes on the E2 glycoprotein of MHV-4 protected mice against lethal virus challenge and converted the infection from fatal encephalomyelitis to demyelination. A single neutralizing antibody directed against a third epitope on E2 as well as seven nonneutralizing antibodies to E2, E1, and N polypeptides did not protect against challenge. In mice which received protective antibody, MHV-4 infection was not blocked, however, virus grew to lower titers in liver and brain, and virus replication in the CNS was more restricted than in unprotected mice. Decreased involvement of neurons in the brains of protected mice was observed, and no evidence of neuronal infection in the spinal cords was found. In contrast, oligodendrocytes were infected in the presence of protective antibody, and evidence of demylination associated with mononuclear cell infiltration was found. These studies demonstrate that antibody to a single epitope on a viral glycoprotein can substantially alter the course and phenotype of disease.
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PMID:Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. 619 89

Four monoclonal antibodies that react with Sindbis virus glycoproteins have been examined for (i) their effects on virus infectivity, (ii) their ability to recognize conformational changes in glycoprotein structure, and (iii) their cross-reaction with several different alphaviruses. Two of the monoclonal antibodies reacted with the native forms of the E1 glycoprotein but did not neutralize virus infectivity. One of the anti-E1 antibodies formed an infectious virus-antibody complex. The other two monoclonal antibodies reacted with the E2 glycoprotein in both an unfolded as well as a native structure. One of these antibodies reacted with Semliki Forest virus. The anti-E1, but not the anti-E2, antibodies cross-reacted with three serologically related equine encephalomyelitis viruses.
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PMID:Properties of monoclonal antibodies directed against the glycoproteins of Sindbis virus. 628 77

Different models of experimental autoimmune encephalomyelitis (EAE) have been successfully applied to investigate and manifold aspects of the autoimmune pathogenesis of multiple sclerosis. Studies using myelin-specific T-cell lines that transfer EAE to naive recipient animals established that only activated lymphocytes are able to cross the endothelial blood-brain barrier and cause autoimmune disease within the local parenchyma. All encephalitogenic T cells are CD4+ Th1-type lymphocytes that recognize autoantigenic peptides in the context of MHC class II molecules. In the case of myelin basic protein (MBP) specific EAE in the Lewis rat, the T-cell response is directed against one strongly dominant peptide epitope. The encephalitogenic T cells preferentially use one particular set of T-cell receptor genes. Although MBP is a strong encephalitogen in many species, a number of other brain protein are now known to induce EAE. These include mainly myelin components (PLP, MAG, and MOG), but also, the astroglial S-100 beta protein. Encephalitogenic T cells produce only inflammatory changes in the central nervous system, without extensive primary demyelination. Destruction of myelin and oligodendrocytes in these models requires additional effector mechanisms such as auto-antibodies binding to myelin surface antigens such as the myelin-oligodendrocyte glycoprotein.
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PMID:Animal models. 751 26

Thirty-three monoclonal antibodies (Mabs) interacting with the structural proteins of Eastern equine encephalomyelitis (EEE) virus were prepared. The mutual arrangement of the antigenic sites on the E1 and E2 glycoproteins was studied by competitive radioimmunoassay. At least four nonoverlapping sites were found on the E1. The E2 glycoprotein contained at least seven partially overlapping antigenic sites. Mabs to the sites E2-2 and E2-3 neutralized viral infectivity and blocked hemagglutination. Mabs to the site E2-1 blocked hemagglutination. Mabs to sites E2-2, 3, and 7 protected mice against lethal infection although the protective Mabs to sites E2-2b and E2-7 did not neutralize the virus. The antibodies to the other three sites of E2 and to all sites of E1 did not have any biological activity. The experimental results indicate the dominant role of E2 in antiviral immunity, over 98% of the observed protective effect being associated with the E2-2 site.
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PMID:[The antigenic structure of the eastern equine encephalomyelitis virus studied by using monoclonal antibodies]. 752 Nov

Experimental allergic encephalomyelitis (EAE) has long been studied as an animal model of the human demyelinating disease Multiple Sclerosis. However, EAE induced in the Lewis rat by injection of myelin basic protein (MBP), or MBP-specific T-lymphocytes, is primarily an inflammatory condition of the central nervous system (CNS) with little or no demyelination. In EAE models in which demyelination does result, it is either not very widespread or is unpredictable in its degree and location. In this study we have produced antibody-augmented demyelinating EAE (ADEAE) in the Lewis rat by injection of activated MBP-specific T-lymphoblasts, followed by injection 4 days later of a monoclonal antibody against myelin/oligodendrocyte glycoprotein, an extrinsic protein of myelin. We have documented the extent and location of inflammatory cell infiltrates and demyelination throughout the CNS using histochemistry, immunofluorescence, and image analysis. Perivascular inflammatory infiltrates were seen in the deep cerebellar white matter and in the folia. Perivascular, periventricular, and subpial inflammation was widespread throughout the pons/medulla and at all levels of the spinal cord. Very little inflammation was apparent in the forebrain. MBP immunofluorescence demonstrated extensive areas of periventricular demyelination in the forebrain around the third ventricle. Both periventricular and perivascular lesions were commonly observed in the cerebellum and pons/medulla. The extent of demyelination in the spinal cord increased caudally with large confluent areas of subpial demyelination seen throughout the lumbar cord. The extensive and reproducible distribution of inflammatory demyelinating lesions in ADEAE provide the possibility to select areas of the CNS for more detailed analysis of the cellular changes that accompany demyelination and remyelination.
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PMID:The distribution of inflammatory demyelinated lesions in the central nervous system of rats with antibody-augmented demyelinating experimental allergic encephalomyelitis. 752 34

Myelin/oligodendrocyte glycoprotein (MOG) is expressed specifically in the central nervous system (CNS) by myelinating glial cells, the oligodendrocytes. The external location of MOG on myelin sheaths and its late expression during myelinogenesis argue for a role of MOG in the completion of myelin and maintenance of its integrity. MOG is a target autoantigen in demyelinating diseases, such as experimental autoimmune encephalomyelitis (EAE) in animals and multiple sclerosis (MS) in humans. We previously located the gene encoding MOG to the major histocompatibility complex (MHC), both in human, by cytogenetics, and in mouse, by analysis of recombinants. To refine the position, we have now selected yeast artificial chromosome clones (YAC) which contain the MOG gene. Physical mapping of the human MOG and the mouse Mog genes by characterization of these YAC clones indicated that the gene is located at the distal end of the major histocompatibility complex (MHC) class Ib region in both species. The human MOG gene lies 60 kilobases (kb) telomeric to HLA-F in a head-to-head orientation; the mouse Mog gene lies 25 (kb) telomeric to H2-M5 in a tail-to-head orientation. These orthologous genes provide markers for comparative analysis of the evolution of the MHC in the two species. The physical mapping of MOG should facilitate analysis of its role in hereditary neurological diseases, and the YAC clones identified here will permit the identification of new genes in the region.
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PMID:Physical mapping of the human and mouse MOG gene at the distal end of the MHC class Ib region. 759 Sep 72


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