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)

Neurological deficit in experimental allergic encephalomyelitis (EAE) and multiple sclerosis (MS) is probably a consequence of synergy between T and B cell responses to CNS antigens. During the demyelinating phase of chronic relapsing EAE in ABH mice, anti-myelin oligodendrocyte glycoprotein (MOG) responses were increased compared to the inflammatory acute phase, but such levels did not correlate with the severity of clinical disease. The pathogenicity of antibodies (Ab) to MOG, myelin basic protein (MBP), proteolipid protein (PLP) and galactocerebroside (GalC) was investigated in vivo following injection at the onset of EAE. An IgG2a monoclonal Ab (mAb), clone Z12, directed to MOG augmented clinical disease and demyelination in ABH and C57BL/6 mice, but not MOG knock-out mice. No effect was observed with F(ab(2))' fragments of Z12 or with the anti-MOG IgG1 mAbs, clones Y10 or 8-18C5. Cobra venom factor partially reduced the augmenting effect of mAb Z12 suggesting a role for complement. The pathogenic effect of anti-myelin Abs was not restricted to MOG since an anti-GalC mAb exacerbated inflammation in the CNS while an MBP mAb (clone 22) reduced clinical disease. Taken together, these data provide further evidence that myelin-reactive Abs generated during autoimmune neurological disease may play an important role not only in the pathogenesis of disease but also the regulation of myelin-targeted autoimmune disease.
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PMID:Pathological and regulatory effects of anti-myelin antibodies in experimental allergic encephalomyelitis in mice. 1196 Jun 47

Sarcocystis neurona is an important cause of equine protozoal myeloencephalitis (EPM) in horses in the Americas. An EPM-like neurological disease also has been reported from other mammals but it is difficult to induce this disease in the laboratory. A 4-month-old male domestic cat developed neurological signs 3 days following castration. The cat was euthanized 12 days later because of paralysis. Encephalomyelitis was the only lesion and was associated with numerous Sarcocystis schizonts and merozoites in the brain and spinal cord. The protozoa reacted positively with S. neurona-specific polyclonal rabbit antibody. Two unidentified sarcocysts were present in the cerebellum. It may be possible that stress of surgery triggered relapse of S. neurona infection in this cat.
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PMID:Clinical Sarcocystis neurona encephalomyelitis in a domestic cat following routine surgery. 1262 5

West Nile virus encephalomyelitis was diagnosed in 28 horses presented to the Ontario Veterinary College Veterinary Teaching Hospital between August 20 and October 15, 2002. The age range of affected horses was 5 months to 20 years (mean 6.9 years, median 6 years). Clinical signs were highly variable. Duration of hospitalization ranged from < 1 to 12 days (mean 5 days, median 5.4 days). Overall, 16 of the 28 (57%) horses were discharged and, of the 14 from which follow-up information was available, 13 (93%) were reported to be clinically normal 4 to 6 weeks following discharge, while the other horse had markedly improved. This pathogen is emerging as an important cause of neurological disease in Canada.
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PMID:West Nile virus encephalomyelitis in horses in Ontario: 28 cases. 1283 40

Multiple sclerosis (MS) is a chronic neurological disease of unknown etiology, but a genetic basis for the disease is undisputed. We have reported that CD24 is required for the pathogenicity of autoreactive T cells in experimental autoimmune encephalomyelitis, the mouse model of MS. Here we investigate the contribution of CD24 to MS by studying single-nucleotide polymorphism in the ORF among 242 MS patients and 207 population controls. This single-nucleotide polymorphism results in replacement of alanine (CD24a) with valine (CD24v) in the mature protein. We found that the CD24v/v renders a >2-fold increase in the relative risk of MS in the general population (P = 0.023). Among familial MS, the CD24v allele is preferentially transmitted into affected individuals (P = 0.017). Furthermore, 50% of CD24v/v patients with expanded disability status scale 6.0 reached the milestone in 5 years, whereas the CD24a/v (P = 0.00037) and CD24a/a (P = 0.0016) patients did so in 16 and 13 years, respectively. Moreover, our data suggest that the CD24v/v patients expressed higher levels of CD24 on peripheral blood T cells than did the CD24a/a patients. Transfection with CD24a and CD24v cDNA demonstrated that the CD24v allele can be expressed at higher efficiency than the CD24a alleles. Thus, CD24 polymorphism is a genetic modifier for susceptibility and progression of MS in the central Ohio cohort that we studied, perhaps by affecting the efficiency of CD24 expression on the cell surface.
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PMID:CD24 is a genetic modifier for risk and progression of multiple sclerosis. 1465 62

VCAM-1 is an adhesion molecule that is important to leukocyte movement across the blood-brain barrier and is involved in the formation of destructive CNS inflammatory lesions in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). We examined VCAM-1 expression in the CNS of animals with passively induced EAE and found abundant expression not only on the CNS endothelium but also on astrocytes. We show that tumor necrosis factor receptor-1 (TNFR1) signaling is required for VCAM-1 expression by astrocytes, not the vascular endothelium. In addition, we demonstrate that VCAM-1 expression by astrocytes is crucial for T cell entry into the CNS parenchyma and is required for manifestation of neurological disease.
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PMID:TNFR1-dependent VCAM-1 expression by astrocytes exposes the CNS to destructive inflammation. 1514 10

Since the discovery of Viliuisk encephalomyelitis (VE) in 1887, scientists have tried to understand the natural history and aetiology of this endemic neurological disorder among the native Sakha population of Central Siberia. Familial aggregation and segregation analysis suggested a genetic influence on VE incidence. However, recent studies have implicated an unknown virus, possibly from the alpha herpesvirus family, as a possible cause for this disease. As VE is a neurological disease characterized by the inflammatory reactions systematically observed in the spinocerebellar fluid and in the brain tissue of deceased patients, we examined 17 single nucleotide polymorphisms (SNPs) across seven inflammation-related candidate gene regions, including chemokine receptors type 2 and 5 (CCR2/CCR5), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6, IL-10, stromal cell-derived factor (SDF) and chemokine regulated upon activation, normal T-cell expressed and presumably secreted (RANTES). Our main objective was to analyse the degree of genetic association between VE and candidate genes that have been previously implicated in other inflammatory diseases. Samples were collected from 83 affected families comprising 88 verified VE cases, 156 family members, and an additional 69 unrelated, unaffected inhabitants of the same geographical area. This collection included substantially all of the cases that are currently on the VE Registry. The experimental design included both case-control and transmission/disequilibrium test (TDT)-based familial association analyses. None of 17 SNPs analysed was significantly associated with VE occurrence. Exclusion of these eight genes based on the lack of association has important implications for identifying the disease agent, as well as prescribing therapy and understanding Viliuisk encephalomyelitis.
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PMID:Evaluating association and transmission of eight inflammatory genes with Viliuisk encephalomyelitis susceptibility. 1518 25

Multiple sclerosis (MS) is a debilitating neurological disease characterized by a progressive loss of motor and sensory function, eventually leading to paralysis and death. The primary cause of neurological impairment is demyelination of the central nervous system (CNS) caused by an inflammatory autoimmune response. Previous studies have shown that the severity of MS is reduced during pregnancy, suggesting that the increased level of sex hormones may reduce the autoimmune response. Recently, we have shown that estrogen treatment confers protection from experimental autoimmune encephalomyelitis (EAE), which is an animal model for MS. However, the cellular basis of estrogen's action remains unknown. In the current study, we demonstrate that estrogen treatment led to the induction of a novel subpopulation of regulatory cells in spleen and CNS, which also occurs naturally in pregnant mice. These previously uncharacterized cells display a low level expression of CD45 (CD45(dim)) and no detectable expression of many cell surface markers related to TCR signaling, including CD3 and TCR. However, these cells retained expression of VLA-4, an extracellular protein involved in cellular migration. Several lines of evidence suggest that these novel cells, defined as CD45(dim)VLA-4(+) cells, may play a role in the protective effects of estrogen in EAE. Injection of purified CD45(dim)VLA-4(+) cells conferred protection from spontaneous EAE (Sp-EAE). In contrast, injection of CD45(high)VLA-4(+) cells exacerbated the disease course. CD45(dim)VLA-4(+) cells also suppressed antigen-specific proliferation of primed lymphocytes in coculture. A better understanding of how CD45(dim)VLA-4(+) cells suppress the harmful immune response of EAE may help in explaining the induction of immune tolerance during pregnancy and lead to novel therapeutic approaches to combat MS and other autoimmune diseases.
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PMID:Estrogen treatment induces a novel population of regulatory cells, which suppresses experimental autoimmune encephalomyelitis. 1519 45

The murine leukemia virus (MLV) TR1.3 provides an excellent model to study the wide range of retrovirus-induced central nervous system (CNS) pathology and disease. TR1.3 rapidly induces thrombotic events in brain microvessels and causes cell-specific syncytium formation of brain capillary endothelial cells (BCEC). A single amino acid substitution, W102G, in the MLV envelope protein (Env) regulates the pathogenic effects. The role of Env in determining this disease phenotype compared to the induction of spongiform encephalomyelitis with a longer latency, as seen in several other MLV and in human retroviruses, was determined by studying in vitro-attenuated TR1.3. Virus cloned from this selection, termed TRM, induced progressive neurological disease characterized by ataxia and paralysis and the appearance of spongiform neurodegeneration throughout the brain stem and spinal cord. This disease was associated with virus replication in both BCEC and highly ramified glial cells. TRM did not induce syncytium formation, either in vivo or in vitro. Sequence and mutational analyses demonstrated that TRM contained a reversion of Env G102W but that neurological disease mapped to the single amino acid substitution Env S159P. The results demonstrate that single nucleotide changes within disparate regions of Env control dramatically different CNS disease patterns.
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PMID:Disparate regions of envelope protein regulate syncytium formation versus spongiform encephalopathy in neurological disease induced by murine leukemia virus TR. 1525 11

An apparently novel neurological disease clinically characterized by shaking, tremors, seizures, staggering gait, and ataxia was first observed in farmed mink kits in Denmark in 2000 and subsequently in Sweden, Denmark, and Finland in 2001, and again in Denmark in 2002. Lymphoplasmacytic encephalomyelitis was found in the affected kits. The lesions were most severe in the brainstem and cerebellum and consisted of neuronal degeneration and necrosis, neuronophagia, focal and diffuse gliosis, perivascular cuffs formed by lymphocytes, plasma cells and macrophages, and segmental loss of Purkinje cells. Testing was conducted to determine the cause of the disease, including general virological investigations (virus culture, negative-staining electron microscopy, immunoelectron microscopy, polymerase chain reaction for herpesviruses, adenoviruses, pestiviruses, and coronaviruses), tests for specific viral diseases (canine distemper, Borna disease, Louping ill, West Nile virus infection, tick-borne encephalitis, Aleutian disease), tests for protozoa (Toxoplasma gondii, Neospora caninum, Encephalitozoon cuniculi), bacteria (general culture, listeria, Clamydophila psittaci), and intracerebral inoculation of neonatal mice. The results of all these investigations were negative. One group of 3 mink kits inoculated intracerebrally with brain homogenate of affected mink developed clinical signs and histological lesions similar to those observed in naturally infected mink. Based on the histopathological features, it is postulated that the disease is caused by a yet unidentified virus.
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PMID:Investigations into shaking mink syndrome: an encephalomyelitis of unknown cause in farmed mink (Mustela vison) kits in Scandinavia. 1530 41

In developing guidelines for the improved management of herpesvirus infections of the central nervous system (CNS), the International Herpes Management Forum (IHMF) has considered human herpesvirus (HHV) type 6 and type 7 disease. Although HHV-6 is generally asymptomatic, it has been associated with exanthema subitum, febrile convulsions and encephalitis in infants and immunocompromised adults and may play a role in multiple sclerosis, Guillain-Barre syndrome and acute disseminated encephalomyelitis. As HHV-6 is present in the brain tissue of healthy individuals, its role as an aetiological agent in CNS disorders is unclear. While polymerase chain reaction (PCR) is a method useful for diagnosis of other viral CNS infections, it has no value for diagnosing HHV-6. HHV-7 has not been shown to cause a specific disease but is associated with febrile convulsions and has been implicated as a cause of encephalitis. Ganciclovir and foscarnet, either alone or in combination, may be used for the management of HHV-6-related neurological disease. Although ganciclovir is unlikely to be effective against HHV-7-related CNS disease, foscarnet may be useful but prospective trials are needed.
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PMID:Human herpesvirus type 6 and human herpesvirus type 7 infections of the central nervous system. 1531 97


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