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 single amino acid substitution in the sequence of the encephalitogenic determinant for Lewis rats destroyed its ability to induce experimental allergic encephalomyelitis (EAE) but generated a potent immunoregulatory sequence capable of suppressing the development of both clinical and histologic signs of EAE. The EAE-inducing determinant (synthetic peptide S6) H-Ala-Gln-Gly-His-Arg-Pro-Gln-Asp-Glu-Asn-OH (residues 75 to 84) of the bovine MBP induced clinical and histologic signs of EAE when it was administered at doses of 0.5 micrograms or higher. Gly substituted for the C-terminal Asn during the synthesis of peptide S6 generated the homologous sequence designated by peptide S79. Peptide S79 failed to induce either clinical or histologic signs of EAE even when it was administered at dosages up to 1000 times higher than those of S6. Similarly, rats pretreated with a single dose of S79 were not only unresponsive to an encephalitogenic challenge but also were capable of transferring unresponsiveness to syngeneic recipients with viable donor lymphocytes. The induction of unresponsiveness that was abrogated by pretreatment with cyclophosphamide suggests the development of an S79-sensitive lymphocyte subset that regulates MBP-induced EAE in Lewis rats.
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PMID:Experimental allergic encephalomyelitis in Lewis rats: immunoregulation of disease by a single amino acid substitution in the disease-inducing determinant. 616 28

To test the ability of different spinal cord fractions to reproduce the clinicopathological features of relapsing experimental allergic encephalomyelitis (R-EAE), groups of young guinea pigs were inoculated with: (1) spinal cord myelin; (2) delipidated myelin; (3) reconstituted myelin and (4) MBP plus myelin lipids. The four sets of antigens induced acute EAE in most of the animals tested. During an observation period of 18 months, only one clinical relapse was observed in animals sensitized with myelin and with MBP plus myelin lipids. Extensive CNS demyelination was found in relapsing animals injected with myelin. No demyelinated lesions were observed in non-relapsing animals. By contrast, half of the surviving guinea pigs injected with MBP plus myelin lipids had demyelinated lesions, irrespective of whether they relapsed or not. The inability of the spinal cord myelin fractions to fully reproduce the R-EAE model suggest that other non-myelin antigens may be involved in the pathogenesis of multiple relapses.
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PMID:Relapsing experimental allergic encephalomyelitis induced with isolated myelin and with myelin basic protein plus myelin lipids. 616 79

Sera of normal subjects and patients wtih multiple sclerosis (MS) have been frequently found to contain picomolar quantities of endogenous myelin basic protein-serum factors (MBP-SFs). These serum factors, collectively representing a heterogeneous spectrum, were detected and measured by means of a competitive inhibition radioimmunoassay (RIA) designed to distinguish their respective binding affinities with anti-MBP reagent antiserum. Anti-MBP antibodies in these same normal and patient sera were also detected and their differing binding affinities determined. In general, when sera of normal subjects were found to contain free MBP-SFs, the reagent anti-MBP antibodies in the reagent antiserum used to detect them were of relatively high binding affinity (8 X 10(8) M-1). When normal sera were found to contain free anti-MBP antibodies, the affinities of such antibodies were invariably lower (0.06-0.7 X 10(8) M-1). In contrast, sera of patients with active MS and exhibiting clinical fluctuations in their disease, infrequently contained high or medium high affinity MBP-SFs, whereas higher affinity anti-MBP antibodies were commonly detected. These patterns of MBP-SFs and anti-MBP antibodies in normal and MS human sera resemble those previously observed in studies of normal Lewis rats and rats developing experimental allergic encephalomyelitis (EAE). The findings here reported provide additional support for the view that circulating endogenous MBP-SFs may function as neuroautotolerogens that restrict expansion of MBP-reactive lymphoid cell clones having potentially injurious effector activity for central nervous system (CNS) tissue.
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PMID:Endogenous myelin basic protein-serum factors (MBP-SFs) and anti-MBP antibodies in humans. Occurrence in sera of clinically well subjects and patients with multiple sclerosis. 617 Jul 39

Cellular transfer of experimental autoimmune encephalomyelitis (EAE) was effected in mice with lymph node cells (LNC) from appropriately immunized donors. Pretreatment of LNC with anti-Lyt-1 and Lyt-2,3 antibodies indicated that the transfer of both EAE and a cell-mediated immune response in vitro to MBP was dependent on a subpopulation of T lymphocytes expressing the phenotype associated with the helper and cell-mediated delayed hypersensitivity functions, Lyt-1+, 2-.
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PMID:Transfer of murine experimental autoimmune encephalomyelitis and cell-mediated immunity to myelin protein is effected by Lyt-1 cells. 618 38

Oligoclonal IgG bands have recently been reported to occur in cerebrospinal fluid (CSF) and serum of rabbits with experimental allergic encephalomyelitis (EAE). To examine the specificity of these bands, a) individual bands eluted from rabbit CSF and sera were tested by radioimmunoassay (RIA) for anti-MBP activity and b) rabbit sera were absorbed with the neuroantigens used for sensitization. RIA of eluates from sequential agar gel slices of the entire IgG region of serum or CSF from MBP sensitized rabbits showed that anti-MBP activity occurred throughout the IgG region and did not localize to specific band-containing fractions. Furthermore, there was no change in banding patterns following absorption of EAE rabbit sera with washed brain homogenates, soluble MBP or MBP conjugated to Sepharose beads. Therefore, our results indicate that the oligoclonal IgG response in EAE is not preferentially directed against the sensitizing neuroantigen, and we raise the possibility of nonspecific B cell activation.
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PMID:Oligoclonal IgG in rabbits with experimental allergic encephalomyelitis: non-reactivity of the bands with sensitizing neural antigens. 618 58

The measurement of myelin basic protein serum factors (MBP-SFs) and anti-MBP antibodies in specimens from a patient with post-herpes simplex acute disseminated encephalomyelitis (ADE) is described. Transitory appearance of high affinity anti-MBP antibodies in the absence of detectable MBP-SFs was observed. This pattern was similar to that found previously in acute multiple sclerosis and experimental allergic encephalomyelitis. These findings are consistent with the hypothesis that a possible normal role of MBP-SFs is as neuroautotolerogens, preventing autoreactive lymphocyte clones from damaging myelin.
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PMID:Endogenous myelin basic protein-serum factors (MBP-SFS) and anti-MBP antibodies in a patient with post-herpes simplex virus acute disseminated encephalomyelitis. 619 14

Theiler's murine encephalomyelitis virus (TMEV) produces a chronic inflammatory demyelinating disease in its natural host, the mouse. A delayed-type hypersensitivity (DTH) response to viral antigens generally correlates with susceptibility to the disease and is thought to play an important role in the pathogenesis of demyelination in this model of human multiple sclerosis (MS). The hallmark of DTH responses is the recruitment by activated Th-1 cells of lymphoid cells and especially macrophages in infected areas. It is believed that soluble factors released by these cells would produce tissue damage, particularly myelin breakdown. In the present study, we compared TMEV-infected macrophages and microglia, isolated from both susceptible SJL/J and resistant C57BL/6 mice, for their ability to secrete proteolytic enzymes capable of degrading myelin basic protein. In addition, we studied whether supernatants from infected microglia/macrophages were also capable of killing oligodendrocytes in the same in vitro system. As detected by SDS-PAGE, MBP-degrading proteolytic activity was found only in supernatants from infected SJL/J microglia and macrophages, but not in supernatants collected from infected C57BL/6 microglia and macrophages, or in supernatants from mock-infected SJL/J and C57BL/6 cells. Similarly, incubation of E20.1 cells, an immortalized line of oligodendrocytes, with infected SJL/J, but not C57BL/6 supernatants, resulted in cytotoxic activity. When cells from resistant C57BL/6 mice were treated with LPS, they became susceptible to infection and also secreted proteolytic enzymes. The proteolytic activity released from infected microglia and macrophages was found to be dose-dependent, was inactivated by heat, and was inhibited by phenylmethylsulphonyl fluoride (PMSF). These results indicate that a serine protease is released from infected microglia and macrophages and suggest a role for proteases in TMEV-induced myelin injury.
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PMID:Release of myelin basic protein-degrading proteolytic activity from microglia and macrophages after infection with Theiler's murine encephalomyelitis virus: comparison between susceptible and resistant mice. 749 98

Therapies with immunosuppressive drugs in autoimmune experimental diseases often down-regulate disease but sometimes may lead to paradoxical disease exacerbation. To elucidate possible mechanisms behind such phenomena the effects were studied of mitoxantrone (Mx) and cyclosporin A (CsA) given at high and low doses on clinical course, and on autoreactive T- and B-cell responses in actively induced experimental allergic encephalomyelitis (EAE) in Lewis rats. Treatment with Mx and high dose CsA abrogated EAE and decreased dramatically the measured immune responses compared to vehicle-treated control EAE rats. Low-dose CsA treatment caused a disease relapse 20-30 days post immunization (p.i.). This relapse was accompanied by increased numbers of cells spontaneously producing IFN-gamma in the CNS and regional lymph nodes. Furthermore, anti-myelin and anti-MBP secreting cells were increased as were numbers of primed T cells that produced IFN-gamma in response to myelin antigens. It was concluded that these aspects of the myelin autoreactive immune response correlated well with clinical disease and are useful in evaluating immunotherapeutic intervention. Low-dose CsA treatment may interfere with systemic down-regulatory mechanisms acting on both T- and B-cell myelin-directed autoimmunity.
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PMID:Immunopharmacologic modulation of experimental allergic encephalomyelitis: low-dose cyclosporin-A treatment causes disease relapse and increased systemic T and B cell-mediated myelin-directed autoimmunity. 750 25

Cells from 25 mice at different stages of experimental autoimmune encephalomyelitis (EAE) adoptively transferred using lymph node cells sensitized to a synthetic encephalitogenic peptide of myelin basic protein (p87-99) were examined for reactivity to a different encephalitogenic myelin antigen, proteolipid protein (PLP). Cellular reactivity to a synthetic encephalitogenic peptide of PLP (pPLP) was found in 3/5 mice with acute EAE, 4/9 with chronic EAE, 1/6 mice with EAE in remission, and 0/5 during relapse. No proliferation to pPLP was seen in naive mice or in healthy mice immunized with p87-99. Two of 13 mice developed typical EAE after the serial transfer of cells from animals with p87-99-induced EAE had been activated with pPLP in vitro. Controls consisted of recipients of (a) pPLP-activated cells from naive donors or donors immunized with a nonencephalitogenic MBP peptide, (b) cells from mice immunized with MBP activated in vitro with irrelevant antigen, or (c) ovalbumin-activated cells serially transferred from mice with adoptively transferred EAE. No control mice developed signs. These results suggest that during the course of myelin breakdown caused by an immune response to one myelin component (MBP), autoimmune reactivity to at least one additional myelin antigen (PLP) can arise. Furthermore, the acquired cellular reactivity to additional myelin components may be sufficient in some cases to induce disease itself, perhaps lending insight into mechanisms involved in disease progression.
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PMID:Development of reactivity to new myelin antigens during chronic relapsing autoimmune demyelination. 751 16

The pathogenesis of multiple sclerosis (MS) is thought to involve a T-cell-mediated autoimmune process. Experimental allergic encephalomyelitis (EAE), an animal model resembling MS, can be induced by immunization with myelin antigens such as myelin basic protein. The T-cell antigen receptor (TCR) usage in EAE is highly restricted in some strains of animals and experimental treatments targeting the TCR have been successful in EAE. Examination of the TCR beta-chain variable-region (V beta) usage of MBP-specific T-cell lines in MS patients has produced conflicting results. Our previous studies of TCR alpha-chain variable-region usage in monozygotic twins demonstrated a general skewing of the TCR repertoire in individuals with MS. This skewing became apparent only after stimulation with antigens; in peripheral blood lymphocyte preparations from individuals with MS V alpha 8-bearing T cells were preferentially selected by stimulation with myelin basic protein. In the present study we examined complementarity-determining region 3 of those V alpha 8-positive TCRs. Marked sequence heterogeneity was found in all individuals with severe MS. In contrast, restricted areas of complementarity-determining region 3 were found in healthy control individuals and in individuals with a mild form of MS. Sequences from tetanus toxoid-specific V alpha 8-positive T cells generated from the same individuals were relatively homogeneous within individuals regardless of disease activity and were distinct from the sequences of complementarity-determining region 3 in myelin basic protein-stimulated lines. These findings suggest that disease severity may be associated with increased heterogeneity of myelin antigen-specific T cells and could reflect an impaired ability of the immune system to down-regulate these anti-self responses.
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PMID:Heterogeneity of T-cell receptor alpha-chain complementarity-determining region 3 in myelin basic protein-specific T cells increases with severity of multiple sclerosis. 751 5


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