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)

Autoantibodies with in-vitro demyelinating capacity induced in Hartley and strain 13 guinea pigs with homologous central nervous system (CNS) tissue were used to characterize the target autoantigen M2. Using the Dot Immunobinding technique, M2 was found to be a component of CNS myelin different from basic protein (BP) and from cerebroside. The expression of M2 on oligodendrocytes, cells known to produce CNS myelin, also confirmed that M2 was a component of CNS myelin. Furthermore, the autoradiography of immunoprecipitates formed with radiolabelled guinea pig myelin and analysed in sodium dodecyl sulphate gels showed that M2 was specific to CNS myelin and absent in peripheral nervous system (PNS) myelin. On electrophoresis M2 appeared as two CNS myelin protein bands at the 27 and 54 KD molecular weight levels, distinct from the major protein bands of proteolipid and BP. M2 bands were of glycoprotein nature, as was demonstrated by affinity chromatography of CNS myelin on wheat germ agglutinin (WGA)-Sepharose. A monoclonal antibody induced by BP-free CNS glycoproteins recognized the same bands as anti-M2 serum in guinea pig CNS myelin. This would imply that both M2 bands share common determinants. M2 bands similar to the above in guinea pig were also shown in rat, rabbit and bovine CNS myelin with guinea pig antibodies. The same type of anti-M2 antibodies were induced in rabbit immunized with homologous CNS tissue. Although only a minor component of myelin, M2 is strongly immunogenic compared to BP. M2 antigen could thus be the target of chronic demyelinating processes such as experimental allergic encephalomyelitis.
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PMID:The M2 autoantigen of central nervous system myelin, a glycoprotein present in oligodendrocyte membrane. 243 74

Antibody responses to the myelin/oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) were determined in the sera of Hartley guinea pigs with chronic relapsing experimental allergic encephalomyelitis (CREAE) using an enzyme-linked immunoassay. The sera were also tested for in vivo demyelinating activity by infusion into the subarachnoid space of normal rats. In contrast to the MBP titres, the anti-MOG antibody titres showed good correlation with the in vivo demyelinating activity of the sera (r = 0.91, P less than 0.001). This result suggests that antibodies directed against MOG may be involved in the pathogenesis of demyelination in CREAE.
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PMID:Antibody responses in chronic relapsing experimental allergic encephalomyelitis: correlation of serum demyelinating activity with antibody titre to the myelin/oligodendrocyte glycoprotein (MOG). 244 77

In this study the authors have developed a model with which can be studied directly the influence of circulating anti-myelin antibody on the clinical and pathologic course of inflammatory T-cell-mediated experimental allergic encephalomyelitis (EAE) in the rat. EAE was induced by passive transfer of either myelin basic protein (MBP)-activated spleen cells derived from sensitized donors or long-term-cultured MBP-specific T-cell lines. At the onset of the disease, monoclonal antibodies against a myelin/oligodendrocyte glycoprotein (MOG) were injected intravenously. This antigen is exposed on the surface of central nervous system myelin and oligodendrocytes. Intravenous injection of the antibody in the course of T-cell-mediated transfer EAE augmented the severity and duration of clinical signs and resulted in the formation of large, confluent demyelinated plaques.
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PMID:Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. 245 Apr 62

We used a new version of experimental autoimmune encephalomyelitis (EAE) in the rat to investigate immunotherapy of demyelination during autoimmune disease of the central nervous system (CNS). Encephalitis was induced by immunization of rats with myelin basic protein (MBP), and demyelination by systemic injection of a monoclonal antibody, 8-18C5, specific for a myelin/oligodendrocyte glycoprotein (MOG). Antibody injection resulted in hyperacute disease progression and extensive demyelination throughout the CNS. Immunotherapy of antibody-induced demyelination was possible with another monoclonal antibody, pta-3, specific for activated rat T cells. These findings demonstrate the synergy of T cell-mediated and antibody-dependent processes in rat CNS demyelination in vivo. Histologically, immunotherapy reduced the numbers of meningeal mononuclear cell inflammatory foci, but not parenchymal inflammation in the early phase of demyelinating disease. Animals which had received pta-3 antibody had less inflammation than untreated rats in the convalescent phase. Multiple pta-3 treatments most effectively suppressed inflammation. Furthermore, antibody-treated rats with demyelination developed a series of neurologic signs, including pronounced spasticity; that were not observed in control EAE rats and thus appears to be associated with the demyelinating process.
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PMID:Demyelinating experimental allergic encephalomyelitis (EAE) in the rat: treatment with a monoclonal antibody against activated T cells. 245 46

The myelin/oligodendrocyte glycoprotein (MOG) is a target antigen for autoantibody-mediated demyelination in chronic relapsing experimental allergic encephalomyelitis (CREAE) in the Strain 13 guinea pig. Anti-idiotypic antibodies directed against a demyelinating MOG-specific monoclonal antibody (8-18C5) have identified a cross-reactive idiotype in 10/10 CREAE sera. In nine of these sera inhibition studies demonstrated that this idiotype was at or in close proximity to the combination site of guinea pig anti-MOG autoantibodies. This cross-reactive anti-MOG idiotype may represent an important target for the anti-idiotypic regulation of demyelinating antibody responses in CREAE.
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PMID:Identification of a common idiotype on myelin oligodendrocyte glycoprotein-specific autoantibodies in chronic relapsing experimental allergic encephalomyelitis. 247 Jul 82

The role of complement in the pathogenesis of demyelination and inflammation has been investigated in a synergistic model of acute experimental allergic encephalomyelitis (EAE) in the Lewis rat. Depletion of serum complement with cobra venom factor (CVF) suppressed the clinical expression of acute inflammatory EAE induced either by immunization with 50 micrograms guinea pig basic protein (MBP) in Freund's complete adjuvant, or by the passive transfer of 10(7), but not 5 X 10(7) MBP activated spleen cells. Despite the suppression of clinical disease in actively induced EAE, treatment with CFF only had a significant effect on the severity of CNS inflammation in early disease (12 days postimmunization) when the number of inflammatory foci was reduced by 35%. Three days later this difference had resolved and no significant difference could be detected in the severity of CNS inflammation, although control animals exhibited severe disease, the CVF treated group being clinically normal. Demyelination in these models is initiated by systemic injection of the antimyelin oligodendrocyte glycoprotein (MOG) monoclonal antibody, 8-18C5, which in vitro lyses oligodendrocytes in a dose, Fc and complement-dependent manner and in vivo induces extensive CNS demyelination in rats with EAE. Treatment with CVF reduced the ability of this antibody to initiate demyelination in vivo and furthermore, its F(ab)2' fragment had no effect on the clinical course of EAE and was unable to initiate demyelination in normal animals. Complement-dependent mechanisms are therefore involved both in the clinical expression of acute inflammatory lesions and in the pathogenesis of antibody-mediated demyelination in EAE.
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PMID:The role of complement in the pathogenesis of experimental allergic encephalomyelitis. 247 95

Experimental autoimmune encephalomyelitis (EAE) can be transferred adoptively with T cells sensitized to the basic protein of myelin (BP). However, in the guinea pig, the chronic form of EAE has not been found to be inducible with BP alone, nor has it been adoptively transferred. An antibody response to the central nervous system (CNS) myelin autoantigens was looked for in serum and target CNS tissue in S13 guinea pigs with isologous CNS tissue-induced chronic EAE. Antibody activity was estimated by an immunoenzymatic technique and by autoradiography, using immunoprecipitated and electrophoresed relevant radiolabelled antigens. In serum, IgG antibody response to BP and M2 reached its maximum level 30 to 40 d after immunization and then declined progressively until it became undetectable. On the other hand, while anti-BP antibodies were seldom detected in CNS tissue acid extract, anti-M2 IgG antibodies were always present in CNS tissue of chronic EAE animals, and the amount of these antibodies were related to the severity of symptoms and lesions. No antibody response to proteolipid or to galactocerebroside was detected in serum or CNS tissue. BP-immunized controls showed no chronic EAE and no response to M2 in their serum or CNS tissue. Inasmuch as M2 has been shown to be a glycoprotein of CNS myelin, and anti-M2 antibodies to have a demyelinating property, the latter would be responsible for CNS tissue demyelination in chronic EAE. A shared role of BP and M2 in the induction of chronic EAE in the guinea pig is suggested.
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PMID:Chronic experimental autoimmune encephalomyelitis in the guinea pig. Presence of anti-M2 antibodies in central nervous system tissue and the possible role of M2 autoantigen in the induction of the disease. 276 95

The oligodendrocyte (Od), a glial cell that produces myelin in the central nervous system, may be a target for autoreactive T cells in autoimmune demyelinating processes, although not expressing major histocompatibility complex (MHC) products. To analyze Od-T-cell interactions, we selected from normal SJL/J mouse splenocytes sensitized in vitro by Lewis rat Od a T-cell clone, named C2, exhibiting a surface phenotype of mature T cell (Thy 1+, CD3+, CD8+, CD4-, asialo-GM1-). C2 T cells displayed a specific cytotoxicity to syngeneic Od as well as to rat Od, but not to astrocytes or lymphoblasts, or to YAC-1 cells, a target for natural killer and lymphokine-activated killer activity. The T-cell receptor of clone C2 was found to be a CD3-associated alpha/beta-chain heterodimer similar to that usually expressed by antigen-specific MHC-restricted mature T cells. Attempts to block the C2-mediated cytolysis by a series of monoclonal antibodies showed that both the CD3-T-cell receptor complex and the CD8 accessory molecule were required for OD-T-cell interaction and confirmed the lack of involvement of polymorphic MHC products as epitope-presenting structures. Antibodies directed against a surface Od glycoprotein, previously shown to elicit demyelinating autoantibodies in experimental autoimmune encephalomyelitis, fully blocked the cytotoxicity of T-cell clone C2 to its Od target. These data suggest that an epitope of a surface Od glycoprotein may be directly and specifically recognized and killed by autoreactive T cells expressing an alpha/beta receptor without conventional MHC restriction.
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PMID:Oligodendrocyte-specific autoreactive T cells using an alpha/beta T-cell receptor kill their target without self restriction. 278 60

We examined a variety of strains of Sindbis virus for the genetic changes responsible for differences in neurovirulence in mice. SV1A (a low passage of the AR339 strain of Sindbis virus), a neuroadapted Sindbis virus (NSV), and two laboratory strains of Sindbis virus (HRSP and Toto1101) were examined. NSV causes severe encephalomyelitis with hind-limb paralysis and high mortality after intracerebral inoculation in weanling mice. In contrast, SV1A causes only mild, nonfatal disease in weanling mice; however, in suckling mice, SV1A causes a fatal encephalomyelitis after either intracerebral or subcutaneous inoculation. The two laboratory strains used have a greatly reduced neurovirulence for suckling mice and are avirulent for weanling mice. The nucleotide sequences and encoded amino acid sequences of the structural glycoproteins of these four strains were compared. Hybrid genomes were constructed by replacing restriction fragments in a full-length cDNA clone of Sindbis virus, from which infectious RNA can be transcribed in vitro, with fragments from cDNA clones of the various strains. These recombinant viruses allowed us to test the importance of each amino acid difference between the various strains for neurovirulence in weanling and suckling mice. Glycoproteins E2 and E1 were of paramount importance for neurovirulence in adult mice. Recombinant viruses containing the nonstructural protein region and the capsid protein region from an avirulent strain and the E1 and E2 glycoprotein regions from NSV were virulent, although they were less virulent than NSV. Furthermore, changes in either E2 (His-55 in NSV to Gln in SV1A) or E1 (Ala-72 in NSV to Val in SV1A and Asp-313 in NSV to Gly in SV1A) reduced virulence. For virulence in suckling mice, we found that a number of changes in E2 and E1 can lead to decreased virulence and that in fact, a gradient of virulence exists.
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PMID:Molecular basis of Sindbis virus neurovirulence in mice. 283 15

Intracerebral inoculation of murine coronavirus JHM into 2- to 3-day-old Wistar Furth rats causes an acute encephalomyelitis, while inoculations at 10 days of age usually result in hind leg paralysis. To examine the distribution of viral antigens within this infected central nervous system (CNS) tissue, we used the avidin-biotin-peroxidase method to detect monoclonal and polyclonal antibodies bound to JHM structural proteins; in addition we used the Western blot technique to detect viral proteins. Our study demonstrated the following characteristics: Infected neuronal and glial cells produced viral nucleocapsid and E2 glycoprotein. The synthesis of these viral structural proteins was not restricted to cells in any particular part of the central nervous system. While JHM E2 proteins could be detected in individual cells of JHM-infected CNS tissue, the relative level of detectable E2 protein in the total CNS tissue of infected rats was reduced by more than 13-fold compared with JHM-infected tissue culture cells. Hippocampus neuronal cells provided a sensitive indication of JHM infection. These cells invariably contained antigens in both acutely and chronically infected animals. The distribution of cells containing viral antigens differed markedly for JHM-induced acute encephalitis and chronic demyelinating disease. Acutely infected brains had large lesions containing low levels of viral antigen scattered throughout the brain. One percent to ten percent of histologically normal cells in many parts of the brain contained viral antigens; in addition, more neuronal cells than glial cells were observed to be antigen-positive. The hippocampus appeared normal with hematoxylin-eosin staining; however, a scattered infection of neuronal cells was apparent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of JHM central nervous system infections in rats. 301 91


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