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)

Tissues from 13 exceptionally early cases of multiple sclerosis were studied to identify and characterize the primary demyelinating lesion, using a variety of histological and immunocytochemical methods. Multifactorial cluster analysis identified five significantly distinct lesion groups, which showed histological progression from simple microglial lesions, predominating in tissues from the earliest cases, to complex hypercellular fully demyelinated plaques, chiefly associated with cases of intermediate duration. Quiescent lesions showing evidence of remyelination were found at all stages of the disease studied, but hypocellular inactive plaques, were associated with older cases. Evidence is presented that initial demyelination is effected by activated resident microglia. Undegraded myelin is initially enveloped by membranes bearing fixed complexes of immunoglobulin and complement. In contrast with perivenous encephalomyelitis, in which demyelination was dominated by T-cell infiltration, multiple sclerosis lesions of comparable duration and maturity exhibited humoral immune reactions. Parenchymal CD4+ T-cell infiltration developed in association with subsequent plaque maturation. These results emphasize the need for lesion staging when multiple sclerosis tissues are being used in the investigation of pathogenic mechanisms, and suggest that further analysis of the oligoclonal B-cell response may be productive in the search for primary provoking antigens.
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PMID:The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion. 927 35

The effect of salt concentration in larval rearing water on the susceptibility of adult Aedes taeniorhynchus (Wiedemann) and Aedes sollicitans (Skuse) to infection with eastern equine encephalomyelitis (EEE) virus was tested in the laboratory. Ae. sollicitans was more susceptible to infection (79%, n = 82) and viral dissemination (16%) with EEE virus than was Ae. taeniorhynchus (42%, n = 184) and (5%), respectively, when fed on a chick with a viremia of 10(7) +/- 0.1 plaque-forming units/ml; however, infection rates in adults were not affected by rearing in salt concentrations ranging from fresh water to brackish water containing 2.4% sea salts (1 part fresh water and 2 parts seawater). When fed on the same viremic 6-d-old chicken, all 48 Aedes albopictus (Skuse), reared in fresh water, became infected. Similarly, Venezuelan equine encephalitis viral infection or dissemination rates did not vary among Ae. taeniorhynchus adults that were reared in water containing 0, 1, or 2% sea salts.
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PMID:Effect of salt concentration in larval rearing water on susceptibility of Aedes Mosquitoes (Diptera: Culicidae) to eastern equine and Venezuelan equine encephalitis viruses. 977 90

Theiler's murine encephalomyelitis viruses are picornaviruses that can infect the central nervous system. The DA strain produces an acute polioencephalomyelitis followed by a chronic demyelinating disease in its natural host, the mouse. The ability of DA virus to induce a demyelinating disease renders this virus infection a model for human demyelinating diseases such as multiple sclerosis. Here we describe the generation and characterization of DA virus mutants that contain specific mutations in the viral capsid protein VP1 at sites believed to be important contact regions for the cellular receptor(s). A mutant virus with a threonine-to-aspartate (T81D) substitution in VP1 loop I adjacent to the putative virus receptor binding site exhibited a large-plaque phenotype but had a slower replication cycle in vitro. When this mutant virus was injected into susceptible mice, an altered tropism was seen during the acute stage of the disease and the chronic demyelinating disease was not produced. A virus with a threonine-to-valine substitution (T81V) did not cause any changes in the pattern or extent of disease seen in mice, whereas a virus with a tryptophan substitution at this position (T81W) produced a similar acute disease but was attenuated for the development of the chronic disease. A change in amino acids in a hydrophobic patch located in the wall of the pit, VP1 position 91, to a hydrophilic threonine (V91T) resulted in a profound attenuation of the acute and chronic disease without persistence of virus. This report illustrates the importance of the loop I of VP1 and a site in the wall of the pit in pathogenesis and that amino acid substitutions at these sites result in altered virus-host interactions.
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PMID:Theiler's viruses with mutations in loop I of VP1 lead to altered tropism and pathogenesis. 1007 29

Multiple sclerosis (MS) can be divided into 4 clinical forms: relapsing-remitting (RR), primary progressive (PP), secondary progressive (SP), and progressive relapsing (PR). Since PP-MS is notably different from the other forms of MS, both clinically and pathologically, the question arises whether PP-MS is immunologically similar to the other forms. The pathogenesis of the PP-MS remains unclear, partly due to a lack of highly relevant animal models. Using an encephalitogenic peptide from myelin oligodendrocyte glycoprotein (MOG)92-106, we have established animal models that mimic different forms of MS in 2 strains of H-2s mice, SJL/J and A.SW. We induced experimental allergic encephalomyelitis (EAE) using MOG92-106 in the presence or absence of supplemental Bordetella pertussis (BP). Although, SJL/J mice developed RR-EAE whether BP was given or not, A.SW mice developed PP-EAE without BP and SP-EAE with BP. Histologically, SJL/J mice developed mild demyelinating disease with T cell infiltration, while A.SW mice developed large areas of plaque-like demyelination with immunoglobulin deposition and neutrophil infiltration, but with minimal T cell infiltration. In A.SW mice without BP, high titer serum anti-MOG antibody was detected and the anti-MOG IgG2a/IgG1 ratio correlated with survival times of mice. We hypothesized that, in A.SW mice, a Th2 response favors production of myelinotoxic antibodies, leading to progressive forms with early death. Our new models indicate that a single encephalitogen could induce either RR-, PP-, or SP- forms of demyelinating disease in hosts with immunologically different humoral immune responses.
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PMID:Antibody association with a novel model for primary progressive multiple sclerosis: induction of relapsing-remitting and progressive forms of EAE in H2s mouse strains. 1088 59

Viral growth characteristics that favor rapid and prodigious virion production may increase virus transmission but be detrimental to infected hosts. Several arboviruses, including eastern equine encephalomyelitis (EEE) virus, negatively affect the survival of their infected mosquito vectors. To test the hypothesis that the mosquito virulent properties of EEE virus are caused by the presence of intrinsic viral growth properties, we investigated the effects of infecting dose on the survival of intrathoracically inoculated Culiseta melanura (Coquillett). Daily survival of age-matched females inoculated with either a low initial dose of 10(1.5) plaque-forming units (PFUs) per mosquito or a high initial dose of 10(5.5) PFUs per mosquito was monitored for 8 wk. Compared with diluent inoculated controls, mosquitoes from both dosage groups displayed highly significant decreases in survival. No significant differences in daily survival were detected between the two infected groups. Virus production within inoculated mosquitoes was assessed by sampling mosquitoes every 12 h for 96 h after inoculation. Rapid virus amplification occurred in both dosage groups, and by 24 h after exposure the mean viral loads in mosquitoes inoculated with the low dose were comparable to those inoculated with the high dose. Likewise, although detectable virions appeared sooner in the saliva of high dosage mosquitoes, by 72 h after inoculation no significant differences in virus transmission were detected between the two exposure groups. These results indicate that the virulence of EEE virus for its enzootic North American mosquito vector is not dosage dependent and likely reflects the inherent growth properties of this virus within infected mosquitoes.
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PMID:Effects of initial dose on eastern equine encephalomyelitis virus dependent mortality in intrathoracically inoculated Culiseta melanura (Diptera: Culicidae). 1112 35

A series of recently published articles by a group of Austrian, German and American neuropathologists have proposed the existence of several different pathogenetic pathways in multiple sclerosis (MS). These studies were based on both biopsy and autopsy material. A review of the available published clinical, imaging and cerebrospinal fluid data suggest that some the cases used in those studies were more probably instances of disseminated encephalomyelitis rather than MS. This has serious implications regarding the specificity and significance of the findings in regard to MS pathogenesis. The specific myelinoclastic sequence and the variable clinical course of MS are determined by the individual's genetic endowment and immunologic history. Regardless of pathogenetic pathway and clinical course, the final pathologic picture of MS is always the same. The MS brain is genetically programmed to produce a unique, pathognomonic change, the plaque with sharply demarcated borders.
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PMID:The pathogenesis of multiple sclerosis: a commentary. 1115 2

The demyelinating plaque is the paradigmatic lesion of multiple sclerosis (MS), but only recently attention has been given to axonal damage and to its role in the pathophysiology of disease. Albeit the possible relevance of axonal loss in MS and its experimental models, the amount and timing of axonal sufferance has been addressed only in experimental autoimmune encephalomyelitis (EAE) of rodents. In this report we observed that, in the marmoset model of EAE, axonal damage occurs early during the demyelinating process as assessed by immunoreactivity for amyloid precursor protein (APP) and non-phosphorylated neurofilaments (SMI-32 positive) detected mostly in early active lesions compared to late active and normal appearing white matter. The rare occurrence of morphological features of axonal transection, such as APP or SMI-32 positive spheroids and swellings, as well as an increase of neurofilament density in the demyelinated axons without accumulation of electron dense organelles or osmiophilic bodies, at electron microscopy, suggests that early axonal damage may be, at least in part, a reversible process. These findings are of relevance for the development of therapies, which can protect axons and enhance their function and survival.
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PMID:Demyelination and axonal damage in a non-human primate model of multiple sclerosis. 1123 Oct 31

Haemagglutinating encephalomyelitis virus, strain 67N, was used to inoculate 1-, 2-, 4- and 8-week-old rats by the intracerebral (i.c.), intranasal (i.n.), intraperitoneal (i.p.), subcutaneous (s.c.), intravenous (i.v.) and oral routes with graded doses. The routes of infection, in descending order of efficacy, were: i.ci.ns.ci.pi.v. and oral. Rats aged 1 and 2 weeks were generally similar in terms of mortality and mean time to death, regardless of inoculation route, except for the oral route, which had little effect. In comparison with the 1- and 2-week-old rats, the 4-week-old rats were less susceptible to the virus by all routes. Eight-week-old rats inoculated by the i.ci.n. or s.c. routes died, but all those inoculated by other routes survived. To follow the spread of virus in the central nervous system, 4-week-old rats inoculated by the i.c. route were examined. The virus was first detected in the brain on day 1 and in the spinal cord on day 2. The viral titres in both tissues reached a plateau of 10(7) plaque-forming units (PFU)/0.2 g by day 4, at which time clinical signs had developed. By immunohistochemical analysis, virus-specific antigen was found first in the pyramidal cells of the hippocampus and cerebral cortex, and later in the large-sized neurons of the pons and spinal cord. Still later (day 4) immunolabelling was found in Purkinje cells of the cerebellum, but not in the ependymal cells, choroid plexus or other glial cells.
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PMID:Susceptibility of rats of different ages to inoculation with swine haemagglutinating encephalomyelitis virus (a coronavirus) by various routes. 1143 11

Mice with targeted deletion of L-selectin gene (L-sel(-/-)) were used to investigate the role of adhesion molecule in immunologic responses following virus infection in the central nervous system (CNS). L-Sel(-/-) mice from a resistant H-2(b) genetic background and parental wild-type H-2(b) (C57BL/6) mice were infected with Theiler's murine encephalomyelitis virus (TMEV) intracerebrally and the kinetics of virus replication and infiltration of immune cells in the CNS determined. The levels of infectious TMEV, as measured by plaque assay at 3, 7, 14, and 28 days after infection were between 4 and 6 log(10) PFU of virus per gram of CNS tissues at days 3 and 7 post-infection, and then decreased to undetectable levels by day 14 after infection in both strains of mice. The L-sel(-/-) mice had decreased numbers of CD8(+) T lymphocytes (17.72%+/-2.4) infiltrating into the CNS at 7 days post-infection when compared to wild-type mice (31.02%+/-7.5). In addition, the L-sel(-/-) mice had significantly lower levels of TMEV-specific serum IgG resulting in lower virus neutralizing activity of the serum when compared to wild-type mice. However, the L-sel(-/-) mice had 2.5-fold increase in B lymphocytes in the CNS (8.29%+/-1.1) when compared to wild-type mice (3.2%+/-0.4). Taken together, these data indicate that L-selectin plays a role in recruitment of B and CD8(+) T lymphocytes into the CNS following virus infection, which, however, did not affect the ability of the mice to clear TMEV infection.
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PMID:Theiler's virus-infected L-selectin-deficient mice have decreased infiltration of CD8(+) T lymphocytes in central nervous system but clear the virus. 1143 72

We evaluated the effect of triethylamine (TEA) on the recovery of infectious virus from pools of mosquitoes for two South American alphaviruses (eastern equine encephalomyelitis and Venezuelan equine encephalomyelitis subtypes IIIC and ID), one flavivirus (Ilheus) and two bunyaviruses (Mirim [Guama group] and Itaqui [group C]). Mosquitoes were inoculated intrathoracically with virus, held for 7-10 d at 26 degrees C, and handled under one of four regimens before testing for the presence of virus by plaque assay. Mosquitoes were killed by freezing at - 70 degrees C for 3 min and tested immediately for the presence of virus; killed by freezing at -70 degrees C for 3 min and then held at room temperature for 1 h before testing for the presence of virus; anesthetized with TEA and assayed immediately for the presence of virus; or anesthetized with TEA and then held at room temperature for 1 h before being assayed for the presence of virus. For each of the viruses tested, viral titers in mosquitoes anesthetized with TEA were similar to those in mosquitoes killed by freezing at-70 degrees C. Likewise, there was no significant difference in viral titers in mosquitoes anesthetized with TEA and held at room temperature for 1 h or in mosquitoes frozen at -70 degrees C and held at room temperature for 1 h before being processed for virus by isolation. Triethylamine is advantageous for the handling of mosquitoes in a field environment. The elimination of the need for a cold chain, without compromising virus recovery, increases the feasibility of conducting research projects requiring the isolation of live virus from mosquitoes in remote tropical environments.
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PMID:Effect of triethylamine on the recovery of selected South American alphaviruses, flaviviruses, and bunyaviruses from mosquito (Diptera: Culicidae) pools. 1234 65


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