Multiple Sclerosis Research Today is a free monthly online journal that collates and summarizes the latest research about Multiple Sclerosis, including details on diagnosis, symptoms, treatment, prognosis. | ||||||
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Genes implicated in multiple sclerosis pathogenesis from consilience of genotyping and expression profiles in relapse and remission.Arthur AT, Armati PJ, Bye C, , Heard RN, Stewart GJ, Pollard JD, Booth DR Department of Medicine and the Nerve Research Foundation, the University of Sydney, Sydney, Australia. ariela@med.usyd.edu.au BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Although the pathogenesis of MS remains unknown, it is widely regarded as an autoimmune disease mediated by T-lymphocytes directed against myelin proteins and/or other oligodendrocyte epitopes. METHODS: In this study we investigated the gene expression profiles of peripheral blood cells from patients with RRMS during the relapse and the remission phases utilizing gene microarray technology. Dysregulated genes encoded in regions associated with MS susceptibility from genomic screens or previous transcriptomic studies were identified. The proximal promoter region polymorphisms of two genes were tested for association with disease and expression level. RESULTS: Distinct sets of dysregulated genes during the relapse and remission phases were identified including genes involved in apoptosis and inflammation. Three of these dysregulated genes have been previously implicated with MS susceptibility in genomic screens: TGFbeta1, CD58 and DBC1. TGFbeta1 has one common SNP in the proximal promoter: -508 T>C (rs1800469). Genotyping two Australian trio sets (total 620 families) found a trend for over-transmission of the T allele in MS in females (p < 0.13). Upregulation of CD58 and DBC1 in remission is consistent with their putative roles in promoting regulatory T cells and reducing cell proliferation, respectively. A fourth gene, ALOX5, is consistently found over-expressed in MS. Two common genetic variants were confirmed in the ALOX5 putative promoter: -557 T>C (rs12762303) and a 6 bp tandem repeat polymorphism (GGGCGG) between position -147 and -176; but no evidence for transmission distortion found. CONCLUSION: The dysregulation of these genes tags their metabolic pathways for further investigation for potential therapeutic intervention. Published 22 April 2008 in BMC Med Genet, 9: 17. Articles on Multiple Sclerosis published 20 March 2008: Callosal contributions to simultaneous bimanual finger movements. J Neurosci, 28(12): 3227-33. Corpus callosum (CC) is involved in the performance of bimanual motor tasks. We asked whether its functional role could be investigated by combining a motor behavioral study on bimanual movements in multiple sclerosis (MS) patients with a quantitative magnetic resonance diffusion tensor imaging (DTI) analysis of CC, which is shown to be damaged in this disease. MS patients and normal subjects were asked to perform sequences of bimanual finger opposition movements at different metronome rates; ... [Abstract] [Full-text] Articles on Multiple Sclerosis published 17 March 2008: A longitudinal study of variations in and predictors of fatigue in multiple sclerosis. J Neurol Neurosurg Psychiatry, 79(4): 454-7. OBJECTIVES: To describe variations in fatigue over the course of 2 years in a sample of persons with multiple sclerosis (MS), and to investigate the predictive value of the following variables on variations in fatigue: sex, age, sense of coherence, living with a partner, living with children, work status, immunomodulatory treatment, mood, disease severity, disease course, time since diagnosis and time. METHODS: Every 6 months, 219 outpatients at an MS specialist clinic were assessed using the ... [Abstract] [Full-text] Use of combined conventional and quantitative MRI to quantify pathology related to cognitive impairment in multiple sclerosis. J Neurol Neurosurg Psychiatry, 79(4): 437-41. BACKGROUND: Cognitive impairment is one of the frequent and early findings in multiple sclerosis (MS). OBJECTIVE: To determine the relation between cognitive abnormalities and the extent of macroscopic and microscopic tissue damage in the corpus callosum (CC), revealed by conventional magnetic resonance imaging (MRI), magnetisation transfer imaging (MTI) and diffusion tensor imaging (DTI). METHODS: Conventional dual-echo, DTI and MTI of the brain were obtained from 36 patients with relapsing ... [Abstract] [Full-text] Evolution of different MRI measures in patients with active relapsing-remitting multiple sclerosis over 2 and 5 years: a case-control study. J Neurol Neurosurg Psychiatry, 79(4): 407-14. BACKGROUND: There is growing evidence for the concept of multiple sclerosis (MS) as an inflammatory neurodegenerative disease, with a different pattern of atrophy evolution in grey matter (GM) and white matter (WM) tissue compartments. OBJECTIVE: We aimed to investigate the evolution of different MRI measures in early relapsing-remitting patients with MS and in normal controls (NCs) over 2 years. We also evaluated the progression of these MRI measures in a subset of patients who were followed ... [Abstract] [Full-text] Articles on Multiple Sclerosis published 12 March 2008: Lobular panniculitis at the site of glatiramer acetate injections for the treatment of relapsing-remitting multiple sclerosis. A report of two cases. J Cutan Pathol, 35(4): 407-10. Lipoatrophy and localized panniculitis have been described as rare complications of daily subcutaneous glatiramer acetate injections for the treatment of relapsing-remitting multiple sclerosis (MS). We describe the biopsies from two MS patients in a single neurologist's practice who developed clinical lesions of lipoatrophy at the sites of subcutaneous glatiramer acetate injections. These biopsies showed a lobular panniculitis with lipoatrophy that more closely resembled lupus panniculitis than ... [Abstract] [Full-text] Articles on Multiple Sclerosis published 6 March 2008: Mechanisms of disease: sodium channels and neuroprotection in multiple sclerosis-current status. Nat Clin Pract Neurol, 4(3): 159-69. Sodium channels can provide a route for a persistent influx of sodium ions into neurons. Over the past decade, it has emerged that sustained sodium influx can, in turn, trigger calcium ion influx, which produces axonal injury in neuroinflammatory disorders such as multiple sclerosis (MS). The development of sodium channel blockers as potential neuroprotectants in MS has proceeded rapidly, and two clinical trials are currently ongoing. The route from the laboratory to the clinic includes some ... [Abstract] [Full-text] Articles on Multiple Sclerosis published 29 February 2008: Multiple sclerosis: pathogenesis and MR imaging features of T1 hypointensities in murine model. Radiology, 246(3): 790-5. PURPOSE: To prospectively determine how T1 hypointensities (T1 black holes) on brain magnetic resonance (MR) images are generated by the immune system by using a Theiler murine encephalitis virus-induced model of multiple sclerosis and high-field-strength MR imaging. MATERIALS AND METHODS: All animal protocols and experiments were approved by the institutional animal care and use committee. Volumetric MR imaging studies were conducted at 7 T in six C57BL/6 mice and in immune differentiation ... [Abstract] [Full-text] Diffusion-tensor MR imaging of cortical lesions in multiple sclerosis: initial findings. Radiology, 246(3): 880-6. PURPOSE: To prospectively perform a direct measurement of fractional anisotropy (FA) and mean diffusivity (MD) in cortical lesions of patients with multiple sclerosis (MS). MATERIALS AND METHODS: The study was approved by the institutional review board and was HIPAA compliant; informed consent was obtained. Magnetic resonance (MR) images, including double inversion-recovery (DIR), phase-sensitive inversion-recovery (PSIR), and diffusion-tensor images, were acquired from nine MS patients with ... [Abstract] [Full-text] © 2004-2008 Multiple Sclerosis Research Today. All Rights Reserved. |
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