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)

In order to assess whether experimental allergic encephalomyelitis (EAE), a putative animal model for multiple sclerosis (MS), is an ongoing chronic disorder, we have studied the permeability of spinal cords of Lewis rats with EAE to 3H-uridine- or 3H-thymidine-labeled lymphoid cells obtained from thymuses of naive donors or from draining lymph nodes of donors injected with guinea pig spinal cord + complete Fruend's adjuvant (CFA), guinea pig myelin basic protein + CFA, or with CFA alone. During the acute clinical phase of EAE there is a high-level infiltration of 3H-thymidine- or 3H-uridine-labeled cells into the spinal cords. After clinical recovery from EAE up to 58 days post-inoculation, there is a low-level infiltration of 3H-thymidine-labeled cells into the spinal cords. A similar infiltration into the spinal cords by 3H-uridine-labeled cells was not detected. Donor cells from animals immunized with CFA alone showed similar levels of infiltration into the spinal cords of animals with EAE as donor cells from animals immunized with the encephalitogenic emulsion. Spinal cords from recipients immunized with CFA alone showed no increased permeability to labeled cells. Heat-killed labeled cells did not migrate into the spinal cords of animals with EAE. We conclude that a) EAE is a chronic disease and in this regard is a valid model for MS; and B) in the chronic phase of EAE, recently divided cells (3H-thymidine-labeled cells) show higher levels of migration into the target tissue than 3H-uridine-labeled cells.
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PMID:Chronic permeability of the central nervous system to mononuclear cells in experimental allergic encephalomyelitis in the Lewis rat. 30 23

Central nervous system (CNS) lesions were studied from weanling hamsters inoculated with the HBS strain of subacute sclerosing panencephalitis (SSPE) virus. The animals showed clincial signs of acute encephalitis between 8 and 18 days post-inoculation (PI), but all survivors were clinically recovered by day 21 PI. Nevertheless, 13 of 14 hamster brains examined by light and electron microscopy between days 21 and 59 PI had chronic lesions which contained morphologic evidence of persistent viral infection. The lesions developed preferentially in the subependymal areas of the lateral and fourth ventricles and involved degeneration of ependyma with subsequent damage to adjacent parenchyma. All CNS cell types were involved in degeneration. Viral inclusions occurred in both CNS parenchymal cells and in inflammatory cells. Giant cells were particularly common. No budding virus was seen in chronically infected animals, a finding in accord with previous studies. Demyelination was a common constituent of most lesions. It occurred in the presence of inflammatory cells and macrophages, and in later lesions, some remyelination was seen. It is suggested that the damage to myelin is a secondary phenomenon and is not a cellular immune reaction. The possible reasons underlying the latent nature of the virus and the similarities between this condition, canine distemper encephalomyelitis and human SSPE are discussed. It is concluded that the experimental chronic disease is a valid model for the study of human SSPE and may have usefulness in the understanding of other chronic CNS conditions of man, e.g. multiple sclerosis. Additional Key Words: Latent infection; Paramyxovirus; Slow Viruses; Demyelination; Inmmunologic defects; Multiple Sclerosis.
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PMID:Experimental subacute sclerosing panencephalitis in the hamster: ultrastructure of the chronic disease. 61 54

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterized by inflammation and demyelination in the central nervous system (CNS). Administration of transforming growth factor-beta (TGF-beta) has been shown to inhibit EAE. In this study, the possible role of endogenous TGF-beta in the regulation of relapsing EAE produced by the transfer of myelin basic protein-specific T cell lines was assessed. Although TGF-beta is not present in the normal CNS, this cytokine was detected by immunohistology in areas of central nervous system inflammation in both acute and chronic disease. The administration of anti-TGF-beta at the disease onset led to a worsening of the clinical course of EAE and more extensive pathological lesions. These findings provide direct evidence for a role of endogenous TGF-beta in the remissions seen in chronic relapsing EAE.
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PMID:Evidence of endogenous regulatory function of transforming growth factor-beta 1 in experimental allergic encephalomyelitis. 137 98

A body of literature exists implicating the major histocompatibility complex class II E molecule in development of immune tolerance and/or immunosuppression. To define better the regulatory mechanisms underlying susceptibility to experimental autoimmune encephalomyelitis, an autoimmune condition displaying major histocompatibility complex-II dependence, disease was induced in transgenic mice expressing a major histocompatibility complex-II E alpha d-transgene. This was compared with experimental autoimmune encephalomyelitis induced in age-matched E-negative, non-transgenic mice of the same strain. The results showed that experimental autoimmune encephalomyelitis could be induced by adoptive transfer methodology in both transgenic and non-transgenic mice of the A.CA (H-2f) strain. Virtually no differences were observed between the two mouse types with regard to disease onset, course, and neuropathology. The main difference noted was within nonirradiated recipient subgroups where the nonirradiated transgenic A.CA mice demonstrated greater inflammation and demyelination than the nonirradiated, non-transgenic mice throughout the disease course. Thus, the results did not support the idea that the E molecule, per se, is involved in the induction of tolerance or immunosuppressive mechanisms protecting against autoimmunity. In addition, histologic changes in the central nervous system of the A.CA strain, both transgenic and non-transgenic, differed in several respects from the changes observed in other more commonly studied susceptible strains. In A.CA mice, polymorphonuclear cells were a more prominent component of the acute inflammatory infiltrate and in chronic disease, large aggregates of lipid-laden macrophages and cholesterol clefts were present within white matter lesions. The present approach, using genetic manipulation of the immune system, may have relevance to the study of disease mechanisms in other putative autoimmune demyelinating disorders such as multiple sclerosis.
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PMID:Autoimmune demyelination in transgenic E alpha d-positive A.CA mice. Comparison with E-negative A.CA mice. 157 54

The therapeutic effect of the ether phospholipid SRI 62-834, which lacks the characteristics of an immunosuppressive agent, was compared with those of two immunosuppressive drugs, cyclosporin and valine2-dihydrocyclosporin, in a rat model of chronic relapsing experimental allergic encephalomyelitis (CR-EAE). Drug treatment was initiated at the beginning of the first spontaneous remission on day 15 and was discontinued on day 31. Whereas the untreated rats experienced two paralytic relapses around days 21 and 31, the progression of CR-EAE was prevented during the period of drug administration. Protection with both cyclosporin and its derivative was complete, but SRI 62-834 only attenuated the clinical disease. The absence of paralytic symptoms was reflected by a distinct reduction in mononuclear cell infiltration in the central nervous system at days 21 and 31 in treated animals. The main difference between the two drug classes became apparent after withdrawal of therapy. Discontinuation of SRI 62-834 resulted in a long-lasting beneficial effect, with the rats remaining clinically normal and showing no histopathological changes. However, cyclosporin only delayed the clinical symptoms which reappeared after cessation of treatment. The exacerbated paralytic relapse, which followed about 1 week later and was associated with severe perivascular cell infiltrates and tissue destruction, subsequently became chronic in several animals. By contrast, withdrawal of valine2-dihydrocyclosporin partially prevented disease relapse and markedly reduced severity of symptoms without progression of a chronic disease. These results demonstrate the clear differences in the mode of action of these compounds in CR-EAE and suggest that SRI 62-834 could be an interesting candidate for the treatment of multiple sclerosis.
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PMID:SRI 62-834, a cyclic ether analogue of the phospholipid ET-18-OCH3, displays long-lasting beneficial effect in chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. Comparison with cyclosporin and (Val2)-dihydrocyclosporin effects in clinical, functional and histological studies. 162 33

Chronic relapsing experimental allergic encephalomyelitis was induced by the passive transfer of [14C]thymidine-labeled myelin basic protein (MBP)-sensitized lymphocytes from MBP-immunized mice to naive syngeneic recipients. Labeled lymphocytes were localized and quantitated in the central nervous system during acute and chronic disease and clinical relapses. The results have shown that MBP-immune T cells home to the central nervous system endothelium 24 hours prior to and during initial clinical disease (5 to 7 days posttransfer). Unexpectedly, labeled MBP-immune cells never migrated far from blood vessels and, despite the presence of massive parenchymal inflammatory cell infiltration, almost invariably remained within the perivascular area. Quantitation revealed that labeled cells represented a minority (usually 1% to 4%) of the inflammatory cells during acute and early chronic disease. Furthermore, labeled cells could not be demonstrated in the central nervous system at the time of clinical relapse. We conclude that in this model, MBP-immune lymphocytes act exclusively from a perivascular location to orchestrate the influx of inflammatory cells that are predominantly of recipient derivation.
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PMID:Homing to central nervous system vasculature by antigen-specific lymphocytes. I. Localization of 14C-labeled cells during acute, chronic, and relapsing experimental allergic encephalomyelitis. 169 31

Relapsing experimental autoimmune encephalomyelitis (R-EAE) can be induced in SJL/J mice by immunization with spinal cord homogenate and adjuvant. The specific Ag(s) responsible for acute disease and subsequent relapses in this model is unknown. Myelin basic protein (BP), an encephalitogenic peptide of BP (BP 87-99), and proteolipid protein (PLP) can each induce R-EAE in SJL/J mice, and a peptide of PLP (PLP 139-151) has been reported to induce acute EAE. To determine the encephalitogens in cord-immunized mice with R-EAE, the in vitro proliferative responses of lymph node cells (LNC) and central nervous system mononuclear cells to BP, BP peptides, and PLP peptides were examined during acute EAE and during relapses. LNC responded only to PLP peptides 139-151 and 141-151 and did not respond to BP or its peptides during acute or chronic disease. Central nervous system mononuclear cells also preferentially responded to PLP 139-151 and 141-151 during acute and relapsing disease. A PLP 139-151 peptide-specific Th cell line was selected from LNC of cord-immunized donors. Five million peptide-specific line cells transferred severe relapsing demyelinating EAE to naive recipients. We conclude that PLP peptide 139-151 is the major encephalitogen for R-EAE in cord-immunized SJL/J mice. We demonstrate for the first time that Th cells specific for this peptide are sufficient to transfer relapsing demyelinating EAE. The predominance of a PLP immune response rather than a BP response in SJL/J mice suggests that genetic background may determine the predominant myelin Ag response in human demyelinating diseases such as multiple sclerosis.
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PMID:Lymphocytes from SJL/J mice immunized with spinal cord respond selectively to a peptide of proteolipid protein and transfer relapsing demyelinating experimental autoimmune encephalomyelitis. 170 88

The Daniels strain of Theiler's murine encephalomyelitis produces a chronic disease which is an animal model for human demyelinating disorders. Previously, we selected a neutralization-resistant virus variant producing an altered and diminished central nervous system disease in immunocompetent mice which was evident during the later stage of infection (after 4 weeks) (A. Zurbriggen and R. S. Fujinami, J. Virol. 63:1505-1513, 1989). The exact epitope determining neurovirulence was precisely mapped to a capsid protein, VP-1, and represents a neutralizing region (A. Zurbriggen, J. M. Hogle, and R. S. Fujinami, J. Exp. Med. 170:2037-2049, 1989). Here, we present experiments with immunoincompetent animals to determine viral replication, spread, and targeting to the central nervous system in the absence of detectable antibodies or functional T cells. Nude mice were infected orally, and the virus was monitored by plaque assay, immunohistochemistry, and in situ hybridization. Early during the infection (1 week), the variant virus induced an acute disease comparable to that induced by the wild-type virus in these nude mice. Alterations in tropism in the central nervous system were not apparent when wild-type parental Daniels strain virus was compared with the variant virus. Moreover, variant virus replicated in tissue culture (BHK-21 cells) to similarly high titers in a time course identical to that of the wild-type virus (A. Zurbriggen and R. S. Fujinami, J. Virol. 63:1505-1513, 1989). However, replication of the variant virus versus the wild-type virus within the spinal cord of athymic nude mice infected per os was substantially restricted by 6 weeks postinfection. Therefore, the reduced neurovirulence in the later stage (6 weeks) of the disease is most likely due to a diminished growth rate or spread of the variant virus in the central nervous system rather than to marked differences in viral tropism.
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PMID:Restricted virus replication in the spinal cords of nude mice infected with a Theiler's virus variant. 198 66

T and B cell responses to myelin basic protein (MBP) and its relevant peptide fragments were examined throughout the course of MBP-induced relapsing experimental allergic encephalomyelitis (REAE) in (SJL X PL)F1 mice. T cell reactivity, measured by the antigen-driven proliferation of lymph node T cells in vitro, was directed predominantly against the encephalitogenic MBP-P2 peptide (amino acids 1 to 37) at all stages of disease. Levels of responsiveness did not correlate with disease expression, but declined over time to a relapse level that was four- to sixfold lower than that observed during peak acute stage reactivity. Relapse responses were further distinguished by the detection of host I-E restrictions on Lyt-1+ T cell recognition of P2, P2 recognition by acute-stage T cells occurring solely in the context of host I-A molecules. These data imply an increase in the heterogeneity of relapse T cell responses to MBP to include clones restricted by additional class II glycoproteins. A role for additional CNS autoantigens in the stimulation of relapse T cells is also considered. Serum antibody responses to MBP or the P2 fragment fluctuated randomly throughout R-EAE when total antibody activity (IgM plus IgG) was measured. However, analysis of individual isotypes of IgG immunoglobulins revealed an apparent correlation between peak antigen-binding activity and disease expression which may reflect either an effector or regulatory role for humoral immunity in recurrent EAE. Patterns of early antibody reactivity also distinguished F1 mice that developed or failed to develop disease signs after immunization, the latter exhibiting a consistent drop in antigen-binding activity 4 to 5 days before the usual onset of acute-stage paralysis. The results are considered with regard to possible mechanisms of chronic disease regulation in an environment of functional T cell suppression.
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PMID:Kinetics and specificity of T and B cell responses in relapsing experimental allergic encephalomyelitis. 243 47

In strain-13 guinea-pigs inoculated for chronic relapsing experimental allergic encephalomyelitis (CR-EAE), IgG1 and IgG2 subclass antibody responses were investigated using single radial immunodiffusion and enzyme-linked immunosorbent assays (ELISA) for IgG1 and IgG2 specific for whole cord, myelin, myelin basic protein and Mycobacterium tuberculosis. The early acute stage revealed no increase in IgG1 but was associated with increased levels of IgG2 specific for neural and adjuvant components. Throughout the chronic phase of the disease, there were increased levels of IgG of both subclasses specific for the antigens tested but a preferential synthesis of IgG1. Levels of both IgG1 and IgG2 specific for neuroantigens were lowest in those guinea-pigs which did not develop signs of chronic disease. Immediate skin sensitivity against a wide range of neural antigens was not demonstrated though positive results may have been masked by the ability of myelin basic protein to induce non-specific mast cell degranulation and by altered histamine responsiveness in disease. Guinea-pigs with chronic paralysis had a lower skin sensitivity to histamine, compound 48/80 and M. tuberculosis than those in remission.
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PMID:IgG subclass responses and immediate skin sensitivity in guinea-pigs with chronic relapsing experimental allergic encephalomyelitis. 244 54


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