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)

We selected murine coronavirus JHM variants specifically changed in defined antigenic sites of the peplomer protein E2. Variants were isolated from the supernatants of monoclonal antibody hybridoma cell cultures which continued to secrete neutralizing antibodies after being infected with JHM. Comparative antigenic analysis and biological tests were performed in order to refine an operational epitope map and to characterize functional domains important for pathogenicity. The reaction patterns (neutralization, inhibition of cell fusion, immunofluorescence and binding in ELISA) between the variant viruses and the panel of monoclonal antibodies were very similar. Four groups of variants were characterized each of which revealed distinct changes affecting one defined antigenic site. These observations indicated that at least four independently mutable antigenic sites were associated with domains involved in cell fusion, neutralization and pathogenicity (E2-Aa, -Ab, -Ba and -Bb). JHM variants with alterations in the E2-Aa, -Ab or -Bb sites were similar to wild-type virus. These variants caused acute hepatitis and encephalomyelitis in mice. In contrast, JHM variants with changes in site E2-Ba had a strong propensity to induce chronic disease accompanied by demyelination persisting for several months.
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PMID:The peplomer protein E2 of coronavirus JHM as a determinant of neurovirulence: definition of critical epitopes by variant analysis. 244 29

Infections of rodents by murine coronaviruses can lead to chronic diseases of the central nervous system. These infections are interesting systems to study mechanisms which could be relevant for the pathogenesis of certain human diseases. One major factor influencing the outcome of infection is related to the virus. To understand the virological basis for neurovirulence we compared JHM-virus isolates with different biological properties. JHM-Wt causes only acute disease, JHM-Ts43 a demyelinating encephalomyelitis and a virus shedded from persistently infected cells (JHM-Pi) is not virulent at all. The spread of these viruses in glial cell cultures reflects their different neurovirulence for animals. The peplomer E2 of these viruses reveals structural and antigenic differences. We characterised the epitopes of E2 with a panel of monoclonal antibodies. Four epitopes are associated with regions important for neutralisation, cell fusion and attachment. More than five epitopes are not related to such functions. Epitopes differ in their location and accessibility on the E2 protein subunits between JHM-Wt, JHM-Ts43 and JHM-Pi. To identify epitopes in regions important for pathogenesis, we performed animal studies with variants selected by monoclonal antibodies. Variants changed in a defined epitope (E2-Ba) induce in Balb/c mice a chronic disease. Variants changed in only one of the other three neutralisation epitopes induce acute disease. These results support and extend the observation that the peplomer protein E2 is a major determinant for virulence and antigenic variability of coronaviruses 1,4,5,6,8,10,17,19,22,23. Increasing evidence had been obtained that certain structural features of this protein are important for the cell tropism of the virus. Furthermore, this protein influences strongly the type and specificity of immune responses against viral and host antigens. The highly advanced knowledge on structure and replication of coronaviruses will be of great value to analyze further mechanisms leading to inflammatory demyelinating diseases associated with a persistent virus infection.
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PMID:Coronavirus JHM induced demyelinating disease: specific domains on the E2-protein are associated with neurovirulence. 244 42

We report the use of the ELISA technique to measure IgG specific for whole cord, myelin, myelin basic protein and Mycobacterium tuberculosis in the cerebrospinal fluid (CSF) of Strain 13 guinea pigs in different stages of chronic relapsing experimental allergic encephalomyelitis (CR-EAE). Specific antibody levels to all 4 antigen preparations were related to the severity of clinical signs, with the highest levels of IgG in the CSF of guinea pigs in relapse or in stable chronic disease. Total IgG levels in the CSF, though elevated throughout the course of CR-EAE, did not show any association with the category of disease. Control animals inoculated with complete Freund's adjuvant (CFA) alone showed CSF IgG levels specific for M. tuberculosis that were not significantly different from those in animals with chronic EAE, indicating that CFA may itself induce a late-acting increase in blood-brain barrier permeability.
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PMID:Autoantibody responses in the cerebrospinal fluid of guinea pigs with chronic relapsing experimental allergic encephalomyelitis. 246 68

Plasma IgG, IgA and IgM responses in various stages of chronic relapsing experimental allergic encephalomyelitis (CR-EAE) were investigated by ELISA and rocket immunoelectrophoresis. Autoantibody levels were elevated in acute EAE but immunoglobulin responses were maximal in chronic disease. Plasma IgG and IgA specific for the whole cord, myelin and MBP correlated closely with the clinical signs of post-acute disease; in age-matched groups, levels were lower in animals in remission or with no further disease than in those in relapse or with a stable chronic disease course. Sequential sampling revealed a significant increase in neuroantigen-specific IgG (with MBP as the dominant autoantigen) during the onset of a relapse. Lipid-specific antibody levels were raised throughout CR-EAE but constituted only a small proportion of the total response against neural antigens. Determination of total immunoglobulin concentrations suggested a general suppression of IgG responses in guinea pigs in remission. The strong correlations found between antibody levels and the severity of chronic disease provide further evidence that antibody-mediated mechanisms can play a major role in the pathogenesis of CR-EAE.
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PMID:Plasma immunoglobulin responses and disease severity in chronic relapsing experimental allergic encephalomyelitis. 246 98

Using murine monoclonal antibodies to mark total T cells, we have found rapid migration of T cells into the CSF in progressive multiple sclerosis patients, suggesting that the ongoing inflammatory responses in the CNS may depend on the continued movement of cells from the periphery into the target organ. Cloning experiments have indicated that the T cells present in the CSF during viral and post-viral encephalomyelitis represent sequestered populations of antigen-specific cells. In more chronic disease processes, these cells may also have restricted clonality as measured by the frequency of different T-cell receptor gene rearrangements on Southern blotting. It is known that there is restricted clonality of the B-cell immunoglobulin response in the CSF compartment with inflammatory CNS diseases, and with infections the majority of these so-called oligoclonal antibodies are directed against the exciting antigen and are synthesized in the CNS. Although we believe that T cells in the CNS originate from the blood, during the course of an inflammatory response the antigen and clonally-restricted populations found in the CSF may represent either selective migration or selective accumulation in the CNS. Selective migration might occur at the endothelial barrier as these cells can express Class II MHC antigens and act as antigen-presenting cells in the CNS (McCarron et al. 1985). Selective accumulation of T cells in the CNS might occur after non-specific migration of cells into the CNS followed by proliferation and expansion of T cells that have been induced by antigens in the brain. Antigen-presenting cells that are present in situ, such as astrocytes, may also play a role in the selective expansion of T cells in the CSF (Fontana et al. 1984). Alternatively, it is possible that T cells are induced to expand in the target CNS tissue non-specifically, e.g., via the CD2 pathway. In this regard, we have observed that CSF T cells exhibit alterations in stimulation by anti-T112 + anti-T113 monoclonal antibodies. The mechanism of damage to CNS tissue by immune cells is essentially unknown. For example there are no clear links between antibodies present in the CNS and CNS damage in SSPE where high titers of anti-measles antibodies are present. Whereas we did not observe high frequencies of measles-reactive cells in the CSF of a subject with SSPE, we did observe MHC non-restricted cytotoxic T cells which expressed TCR-gamma chains rather than alpha-beta chains.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:T cells in multiple sclerosis and inflammatory central nervous system diseases. 332 24

JHM virus, when inoculated into neonatal rats, can cause either a rapidly fatal acute encephalomyelitis or, after longer incubation periods, a paralytic disease. The cerebrospinal fluid (CSF) and serum anti-JHM virus IgG concentrations present in rats prior to onset of clinical symptoms or during the acute and paralytic phases of disease were compared. High CSF/serum ratios, indicative of local antibody production in the CNS, were noted only where disease was demonstrable suggesting that local antibody production accompanied the infection but did not prevent the neurological disease. Among animals in which neurologic symptoms had not become manifest, only those with elevated CSF/serum ratios were found to have histological CNS lesions. Immunofluorescent microscopy indicated that viral antigens were present in both glia and neurons. Antigen-positive cells were frequently present in histologically normal CNS tissue, while regions of necrosis were antigen negative. Testing for the presence of viral RNA with JHM cDNA probes revealed that the virus was rapidly disseminated throughout the CNS, presumably establishing centers of infection prior to the development of recognizable tissue damage. Viral RNA was also detected in the CNS following recovery from paralysis and as late as 5 months postinfection, where no disease occurred. These findings indicate that, although infection by JHM virus can spread rapidly throughout the CNS, formation of lesions during chronic disease is a slower process. The current data and previous observations suggest that JHM virus can remain in a latent state for periods of at least several months in rats without apparent neurologic disease despite the absence of any known provirus phase in the replicative strategy of coronaviruses.
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PMID:In vivo and in vitro models of demyelinating disease. IX. Progression of JHM virus infection in the central nervous system of the rat during overt and asymptomatic phases. 609 33

In immature Strain 13 guinea pigs sensitized to syngeneic spinal cord, a chronic allergic encephalomyelitis is elicited reminiscent of demyelinating diseases of man and which features relapses or progressive downhill course and extensive areas of demyelination in the central nervous system. However, juvenile recipients of syngeneic lymphocytes from similarly sensitized juveniles show only the acute form of experimental allergic encephalomyelitis. Neuropathologically, the CNS of affected animals displayed mild changes only and minimal demyelination. These observations indicate that the age-dependent differences seen between the acute disease of adults and the chronic disease of juveniles may be due to differences in availability of modulating or reparatory factors, rather than differences in the central nervous system organ or in the immune response itself.
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PMID:Adoptive transfer of experimental allergic encephalomyelitis from immature guinea pig donors. 663 43

Disease induced by 3 virulent strains of Canine Distemper Virus (CDV) was compared in specific pathogen-free Beagle dogs. All strains produced an encephalomyelitis but variation was observed in the severity, clinical course and resulting neuropathology. Infection with Snyder Hill strain of CDV was consistently acute; dogs either succumbed 14 to 19 days post-inoculation (PI) or recovered. Lesions in the neuraxis were those of a polioencephalomyelitis. In contrast, CDV strain A75-17 produced subacute to chronic disease in which demyelination was the predominant finding. Some dogs succumbed, generally around 28 to 42 days PI. Total recovery was again recorded for some members of the group. Others developed persistent central nervous system (CNS) infection but remained clinically stable until electively killed with barbiturate, up to 62 days PI. CDV strain R252 also induced delayed, predominantly white matter disease with a mixed pattern of mortalities, persistent infections and recoveries, similar to A75-17. Neutralizing antibody responses correlated with the disease course. Dogs which died had low serum titres or lacked serum antibody. Recovering dogs had the earliest and highest titres. A few dogs with persistent CNS infection had antibody in the cerebrospinal fluid also. Current concepts of the pathogenesis of canine distemper encephalomyelitis (CDE) are discussed and a basis for the strain-dependent clinical and pathological expression of CDE is proposed. Viral strain appears to be an important factor in this common disease of the canine CNS.
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PMID:Canine distemper encephalomyelitis: variation with virus strain. 669 31

Chronic relapsing experimental allergic encephalomyelitis (EAE), an animal disease closely resembling multiple sclerosis, was induced in young guinea pigs by sensitization with guinea pig spinal cord tissue together with complete Freund's adjuvant and a high amount of mycobacterium tuberculosis. Sensitization of animals with myelin basic protein leads to an acute form of EAE, but not to a chronic demyelinating disease. The present study was designed to trace the factors of spinal cord tissue responsible for chronic disease and demyelination by using fractionated spinal cord tissue for sensitization. The following preparations were tested for encephalitogenic activity: a) total guinea pig spinal cord homogenized in chloroform/methanol (C/M), b) C/M residue (protein fraction), c) C/M extract (lipid fraction) and d) bovine brain gangliosides. C/M treated spinal cord preparations were less encephalitogenic as compared to untreated spinal cord. The protein fraction showed very little encephalitogenic activity, the histological changes were limited to perivascular inflammation without demyelination. A crude lipid fraction induced some chronic inflammation. Neither the purified lipid fraction nor gangliosides produced any EAE symptoms. The conclusion can be made that protein is necessary for the induction of chronic relapsing EAE, whereas lipid or a protein-lipid complex seems to be responsible for the demyelinating component of this disease.
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PMID:Fractionation of spinal cord tissue affects its activity to induce chronic relapsing experimental encephalomyelitis. 693 26

Experimental allergic encephalomyelitis (EAE) is considered the animal disease model for multiple sclerosis (MS) in humans. However, EAE is an acute disease whereas MS is a chronic disease. The on-off nature in both diseases of autoimmune reactivity suggests a regulatory response by the host, a response which can effect the autoreactive T cell by modulating-up or modulating-down. This review discusses various aspects of this regulation, seen after administration of autoantigen, of antibody directed at the T cell receptor (TcR), and of fragments of the TcR itself.
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PMID:The ups and downs of EAE. 768 9


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