Disease relevance of Multiple Sclerosis

• Inhibition of IL-12 synthesis or activity may be beneficial in diseases associated with pathologic Th1 responses, such as multiple sclerosis or Crohn's disease [1].
• Initial clinical trials of oral tolerance in multiple sclerosis, rheumatoid arthritis, and uveitis have demonstrated positive clinical effects with no apparent toxicity and decreases in T cell autoreactivity [2].
• In patients with acute optic neuritis, treatment with a three-day course of high-dose intravenous methylprednisolone (followed by a short course of prednisone) reduces the rate of development of multiple sclerosis over a two-year period [3].
• MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction [4].
• We addressed this by using the AMPA/kainate antagonist NBQX to treat mice sensitized for experimental autoimmune encephalomyelitis, a demyelinating model that mimics many of the clinical and pathologic features of multiple sclerosis [5].

Psychiatry related information on Multiple Sclerosis

• L-Arginine is the only endogenous nitrogen-containing substrate of NO synthase (NOS), and it thus governs the production of NO during nervous system development as well as in disease states such as stroke, multiple sclerosis, Parkinson's disease, and HIV dementia [6].
• We assessed decision-making capacity and emotional reactivity in 20 patients with multiple sclerosis (MS) and in 16 healthy subjects using the Gambling Task (GT), a model of real-life decision making, and the skin conductance response (SCR) [7].
• The prevalence and nature of emotional disturbance in patients with multiple sclerosis (MS) was studied prospectively in 64 MS patients and 23 spinal cord-injured (SCI) control patients by administration of the 28-item subscale General Health Questionnaire (GHQ) [8].
• Recent evidence indicates that tumor necrosis factor-alpha (TNF-alpha) is up-regulated following brain injury and in neurodegenerative disorders such as stroke, multiple sclerosis, Parkinson's disease, and Alzheimer's disease [9].
• Neuropsychological test, behavioural performance and ERP data all indicated that verbal working memory is especially susceptible to impairment by multiple sclerosis, while visuospatial working memory is less susceptible [10].

High impact information on Multiple Sclerosis

• To clarify whether HLA-DRB1 itself, nearby genes in the region encoding the MHC or combinations of these loci underlie susceptibility to multiple sclerosis, we genotyped 1,185 Canadian and Finnish families with multiple sclerosis (n = 4,203 individuals) with a high-density SNP panel spanning the genes encoding the MHC and flanking genomic regions [11].
• Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group [12].
• PTPRC (CD45) is not associated with the development of multiple sclerosis in U.S. patients [13].
• A point mutation in PTPRC is associated with the development of multiple sclerosis [14].
• A putative vulnerability locus to multiple sclerosis maps to 5p14-p12 in a region syntenic to the murine locus Eae2 [15].

Chemical compound and disease context of Multiple Sclerosis

• Thus, progressive multiple sclerosis may be stabilized by short-term, intensive immunosuppression with cyclophosphamide plus ACTH [16].
• A 77G allele of the gene encoding CD45, also known as the protein tyrosine phosphatase receptor-type C gene (PTPRC), has been associated with multiple sclerosis (MS) [17].
• Glutamate excitotoxicity in a model of multiple sclerosis [5].
• Lipid-array analysis showed lipid-specific antibodies against sulfatide, sphingomyelin and oxidized lipids in cerebrospinal fluid (CSF) derived from individuals with multiple sclerosis [18].
• At a concentration of 10 microM, lidocaine is able to 'unmask' subclinical lesions in multiple sclerosis; thus, the endogenous pentapeptide may well contribute to the fast changes of symptoms [19].

Biological context of Multiple Sclerosis

• A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group [20].
• A tritium-labeled probe that detects measles virus nucleotide sequences was hybridized in situ to cells infected with measles virus and to sections of brain tissue from patients with subacute sclerosing panencephalitis and from patients with multiple sclerosis [21].
• Additionally, hyperactivation of signaling proteins downstream of the TCR, a marked increase in cytokine production by Sts1/2(-/-) T cells, and increased susceptibility to autoimmunity in a mouse model of multiple sclerosis is observed [22].
• Immunodominant T cell epitopes of myelin basic protein (MBP) may be target antigens for major histocompatibility complex class II-restricted, autoreactive T cells in multiple sclerosis (MS) [23].
• Genetic susceptibility to multiple sclerosis linked to myelin basic protein gene [24].
• Multiple environmental, viral, bacterial and other risk factors in multiple sclerosis  

Anatomical context of Multiple Sclerosis

• Cachectin, or tumor necrosis factor-alpha (TNF-alpha), is a principal mediator of the inflammatory response and may be important in the pathogenesis and progression of multiple sclerosis, an inflammatory disease of the central nervous system [25].
• Less than 1 per cent of lymphocytes from the spinal fluid of patients with multiple sclerosis expressed interleukin-2 receptors, as compared with 9.8 per cent of cells from subjects with other inflammatory neurologic diseases (P less than 0.01) [26].
• Myelin failure in multiple sclerosis: breaking the spell of Notch [27].
• Syncytin-mediated neuroinflammation and death of oligodendrocytes, with the ensuing neurobehavioral deficits, were prevented by the antioxidant ferulic acid in a mouse model of multiple sclerosis [28].
• Here, we report that the HERV-W encoded glycoprotein syncytin is upregulated in glial cells within acute demyelinating lesions of multiple sclerosis patients [28].

Gene context of Multiple Sclerosis

• IL-2 may have a role in the inflammatory neural lesions of multiple sclerosis patients and in the growth of brain glia during injury or disease [29].
• Here we tested whether the Notch pathway is re-expressed in the adult CNS in multiple sclerosis (MS), an inflammatory demyelinating disease in which remyelination is typically limited [30].
• Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions [31].
• The lymphotoxin (LT)/tumor necrosis factor (TNF) family has been implicated in the neurologic inflammatory diseases multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE) [32].
• All the isoforms (14-21 kD) of MBP were present, but the microheterogeneity (a posttranslational event) was changed resulting in a higher proportion of the less cationic components reminiscent of the changes in MBP found in multiple sclerosis [33].
• Pathway analysis of the genes implicated in multiple sclerosis  
• INTERPRETATION: Variation in the HLA-C gene influences susceptibility to multiple sclerosis independently of any effect attributable to the nearby HLA-DRB1 gene [34].

Analytical, diagnostic and therapeutic context of Multiple Sclerosis

• Microarray analysis of multiple sclerosis (MS) lesions obtained at autopsy revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin-6 and -17, interferon-gamma and associated downstream pathways [35].
• Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for multiple sclerosis (MS) [36].
• Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction [37].
• Thus, identification of HSA as a novel checkpoint, even after activation and expansion of self-reactive T cells, provides a novel approach for immunotherapy of autoimmune neurologic diseases, such as multiple sclerosis [38].
• Epidemiological studies suggest that multiple sclerosis (MS) might be triggered by an infectious agent [39].

References