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)

Myelin oligodendrocyte glycoprotein (MOG) is a powerful encephalitogen for experimental autoimmune demyelination. However, the use of MOG peptides or recombinant proteins representing part of the protein fails to fully address the possible pathogenic role of the full-length myelin-derived protein expressing post-translational modifications. Immunization of mice with central nervous system tissues from wild-type (WT) and MOG-deficient (MOG(-/-)) mice demonstrates that MOG in myelin is necessary for the development of chronic demyelinating experimental autoimmune encephalomyelitis (EAE) in mice. While immunization with WT spinal cord homogenate (SCH) resulted in a progressive EAE phenotype, MOG(-/-) SCH induced a mild self-limiting acute disease. Following acute EAE with MOG(-/-) SCH, mice developed T cell responses to recombinant mouse MOG (rmMOG), indicating that MOG released from myelin is antigenic; however, the lack of chronic disease indicates that such responses were not pathogenic. Chronic demyelinating EAE was observed when MOG(-/-) SCH was reconstituted with a dose of rmMOG comparable to MOG in myelin (2.5% of total white matter-derived protein). These data reveal that while immunization with the full-length post-translational modified form of MOG in myelin promotes the development of a more chronic autoimmune demyelinating neurological disease, MOG (and/or other myelin proteins) released from myelin during ongoing disease do not induce destructive autoimmunity.
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PMID:Native myelin oligodendrocyte glycoprotein promotes severe chronic neurological disease and demyelination in Biozzi ABH mice. 1576 48

Alphaviruses are mosquito-borne, enveloped, plus-strand RNA viruses that cause a spectrum of diseases in humans that include fever, rash, arthritis, meningitis, and encephalomyelitis. Sindbis virus (SINV) is the prototype alphavirus, causes encephalomyelitis in mice, and provides a model system for studying the pathogenesis of alphavirus-induced neurological disease. Major target cells for SINV infection in the central nervous system (CNS) are neurons, and both host and viral factors determine the fate of infected neurons. Young animals are most susceptible to fatal disease. This correlates with the ability of SINV to induce apoptosis in immature neurons. In vitro, apoptotic death of neuroblastoma cells can be induced by fusion of the virus envelope with the endosomal membrane and does not require infectious virus. This fusion process activates acid sphingomyelinase that cleaves sphingomyelin to release ceramide, an initiator of apoptosis. Within an hour, poly(ADP-ribose) polymerase is activated, and this is followed by release of cytochrome c and activation of effector caspases. SINV-induced cell death can be delayed or prevented by treatment with antioxidants or caspase inhibitors and by intracellular expression of Bcl-2, Beclin-1, or protease inhibitors. Older animals survive infection unless infected with a neurovirulent strain of SINV. In these mice, anterior horn motor neurons die by a primarily necrotic process that is influenced by excitotoxic amino acids and inflammation, whereas hippocampal neurons can be either apoptotic or necrotic. Death also occurs in uninfected neurons in the vicinity of infected neurons and can be delayed or prevented by treatment with glutamate receptor antagonists.
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PMID:Neuronal cell death in alphavirus encephalomyelitis. 1579 51

Numerous studies on neuro-immuno-modulation indicate that the thymus is involved in many neurological diseases, including experimental allergic encephalomyelitis (EAE). Twenty Lewis rats were induced for EAE. At X, XII, XX and XXX days post-inoculation the animals were killed, and the thymus was recovered and harvested. Specimens of thymus were submitted to morphological light microscopy analysis (1% toluidine blue) and ultra-structural analysis (transmission electron microscopy). Significant morphometric data were collected by examining the images quantitatively and by statistically analysing the values. Our results show that the microenvironment of the thymus is severally involved in acute EAE. Thymocytes and reticular epithelial cells show many changes which are closely related to the pathogenesis of EAE. In particular we observed: (1) inside the cell an increase in intra-cytoplasmic vacuoles, and changes in the thickness of the nuclear membrane, mitochondria, rough endoplasmic reticulum, cellular inter-digitations and cellular electron-density; (2) outside the cell an increase in pericellular translucent halo, intercellular spaces, intercellular contacts and apoptotic and necrotic figures. The evidence of a thymic role in MS may suggest the intriguing therapeutic concept of thymectomy in the management of this neurological disease.
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PMID:Pathogenesis of some neurological immune ultrastructural and morphometrical observations on rat thymus. 1582 57

The purpose of this study was to detect the diagnostic value of diffusion-weighted magnetic resonance imaging in different pediatric cerebral diseases involving the cerebral white and gray matter and to compare the diffusion properties with age-matched normal children. Conventional and diffusion-weighted magnetic resonance imaging were performed in 21 children with various neurologic disorders and 25 normal control subjects. Apparent diffusion coefficients were measured from the brain lesions and 12 normal-appearing white and gray matter areas in the study group. Twelve normal-appearing areas were also measured in the control group. Apparent diffusion coefficient values obtained from the normal subjects were similar to values described in the literature but were significantly different from the control subjects. Apparent diffusion coefficient values for the neurodegenerative disease group (n = 8), the anoxic encephalopathy group (n = 4), the subacute sclerosing panencephalitis group (n = 4), the acute disseminated encephalomyelitis group (n = 3), and the encephalitis group (n = 2) were respectively between 0.29-1.85 x 10(-5) cm2/s, 0.13-1.87 x 10(-5) cm2/s, 0.96-1.57 x 10(-5) cm2/s, 0.49-0.73 x 10(-5) cm2/s, and 0.42-1.50 x 10(-5) cm2/s. Although this study is limited because of the size of the patient sample and disease heterogeneity, diffusion-weighted magnetic resonance imaging provides useful and complementary information regarding the degree of involvement in different pediatric neurologic disorders.
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PMID:Diagnostic value of diffusion-weighted magnetic resonance imaging in pediatric cerebral diseases. 1586 33

Common variable immunodeficiency (CVID) is a primary disorder characterized by impaired antibody production. CVID patients may develop recurrent infections, autoimmune disorders, and malignant lymphomas, but to our knowledge, there is no report on CVID patients who develop acute disseminated encephalomyelitis (ADEM) or the Lennox-Gastaut syndrome. We describe a 1-yr-old female CVID patient with ADEM who evolutionally manifested the Lennox-Gastaut syndrome. She was admitted with convulsions and T2-weighted magnetic resonance imaging (MRI) revealed high-intensity areas in the right temporal lobe and the left fronto-parietal region but she became conscious soon. Her serum findings showed severe hypogammaglobulinemia and a follow up MRI revealed that these areas had diminished. Consequently, she was diagnosed as having CVID with ADEM. After 5 months, she fell to having tonic and absence seizures and we diagnosed her as having the Lennox-Gastaut syndrome from electroencephalograms (EEG) and the seizure pattern. She is now 7 yr old and her tonic seizures are controlled with valproic acid, clobazam, and immunoglobulin replacement therapy which is administrated every 2 wk. It is well known that the immune and neurologic systems have a close relationship. We suspect that a genetic defect in the immune system of our patient might also be associated with the neurologic disorders of ADEM and the Lennox-Gastaut syndrome.
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PMID:A common variable immunodeficient patient who developed acute disseminated encephalomyelitis followed by the Lennox-Gastaut syndrome. 1594 1

In 1972 Guido Biozzi selectively bred mice to study the immunopathological mechanisms underlying polygenic diseases. One line, the Biozzi antibody high (AB/H) mouse (now designated the ABH strain) was later found to be highly susceptible to many experimentally induced diseases such as autoimmune encephalomyelitis, autoimmune neuritis, autoimmune uveitis, as well as virus-induced demyelination and has thus been a key mouse strain to study human inflammatory neurological diseases. In this paper we discuss the background of the Biozzi ABH mouse and review how studies with these mice have shed light on the pathogenic mechanisms operating in chronic neurological disease.
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PMID:Biozzi mice: of mice and human neurological diseases. 1610 27

Infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in an acute encephalomyelitis associated with demyelination. T cells are critical in controlling viral replication, but also contribute to central nervous system (CNS) pathogenesis. To reveal a role for innate effectors in anti-viral immunity and neurological disease, JHMV pathogenesis was studied in mice deficient in interleukin-15 (IL-15-/-) and natural killer (NK) cells. Clinical disease, CNS inflammation and demyelination in infected IL-15-/- mice were similar to wild-type mice. Despite the absence of NK cells and suboptimal CD8+ T cell responses, IL-15-/- mice controlled JHMV replication as efficiently as wild-type mice. Similar kinetics of class I and class II upregulation on microglia further suggested no role of NK cells in regulating major histocompatibility complex (MHC) molecule expression on resident CNS cells. IL-15 and NK cells thus appear dispensable for anti-viral immunity and CNS pathogenesis during acute JHMV infection.
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PMID:Mouse hepatitis virus pathogenesis in the central nervous system is independent of IL-15 and natural killer cells. 1651 Jan 64

In dogs with neurological disturbances without myoclonus and extraneural signs, the clinical diagnosis of distemper is difficult perform. Considering the great infectious potential of the disease, the possibility of carrying out an antemortem diagnosis of distemper is important, particularly in hospitalized patients with neurological disease. The present study was carried out to evaluate RT-PCR for antemortem CDV detection in hospitalized dogs with neurological disturbances without the typical findings of distemper. We investigated five dogs with canine distemper virus (CDV) encephalomyelitis, in which the clinical diagnosis was not performed owing to the absence of characteristic signs of the disease, such as myoclonus and systemic signs. We observed an apparent high sensitivity of RT-PCR in urine samples for detection of CDV: four out of five urine samples were RT-PCR positive. The results of the present study suggest that urine is a good biological sample for antemortem CDV detection by RT-PCR in dogs with distemper encephalomyelitis in which the clinical diagnosis is likely to be difficult owing to the absence of suggestive distemper signs. The use of two different body fluids (urine and CSF) may increase the RT-PCR sensitivity for antemortem diagnosis of distemper in such cases.
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PMID:Antemortem diagnosis of CDV infection by RT-PCR in distemper dogs with neurological deficits without the typical clinical presentation. 1683 10

The aim of the study was to search for novel targets of autoantibodies in patients with paraneoplastic neurological syndromes (PNS). PNS are mediated by immune reactions against autoantigen(s) shared by the cancer cells and the nervous system. By serological screening of a rat cerebellum cDNA expression library using anti-Hu-positive sera from three patients with paraneoplastic encephalomyelitis (PEM), we identified an open reading frame encoding an isoform of the BTB-kelch protein KLHL7. Immunohistochemical studies demonstrated that the KLHL7 protein is expressed in the nuclei of neurones, but not in other tissues including various cancers. However, the KLHL7 protein was detected in the nuclei of cancer cell lines. Antibodies to KLHL7 were detected by an immunoprecipitation assay in sera from 12 of 254 (4.7%) patients with various cancers and 2 of 170 blood donors (1.2%). None of 50 sera from patients with multiple sclerosis were positive for KLHL7 antibodies. Sixteen patients with classical PNS and anti-Hu or anti-Yo antibodies were also negative for KLHL7 antibodies. Seven cancer patients with KLHL7 antibodies had various signs of neurological disease that could be related to cancer, whereas the remaining five seropositive cancer patients had no clinical signs of possible PNS. The present results indicate that KLHL7 antibodies are associated with various cancers, and in some patients also with neurological disease. Whether KLHL7 antibodies can be used as paraneoplastic markers for PNS remains to be determined.
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PMID:Detection of autoantibodies to the BTB-kelch protein KLHL7 in cancer sera. 1691 2

Vascular endothelial growth factor A (VEGF-A) stimulates angiogenesis, but is also pro-inflammatory and plays an important role in the development of neurological disease, where it can have both attenuating and exacerbating effects. VEGF-B, a related molecule, is highly expressed in the central nervous system and seems to be important in neurological injury. A few studies have indicated that VEGF-A may play a role in the pathogenesis of multiple sclerosis (MS), but the role of VEGF-B has not been studied. We have studied the expression of VEGF-A, -B and their receptors by mRNA in situ hybridization, immunohistochemistry and real-time PCR in spinal cord from LEW rats with experimental autoimmune encephalomyelitis (EAE) and in cerebrospinal fluid (CSF) and blood samples from MS patients. Whereas VEGF-A is downregulated in glia in EAE, the infiltrating inflammatory cells are positive for VEGF-A. Expression of VEGF-B and the VEGF receptors is unaltered. In addition, the levels of VEGF-A mRNA in mononuclear cells [corrected] in CSF are lower in MS patients compared with controls. These results demonstrate a complex regulation of VEGF-A during neuroinflammation and suggest that VEGF-B is not involved in the pathogenesis of MS.
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PMID:Decreased expression of VEGF-A in rat experimental autoimmune encephalomyelitis and in cerebrospinal fluid mononuclear cells from patients with multiple sclerosis. 1708 17


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