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  • SAGE Publications  (2)
  • 1995-1999  (2)
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  • SAGE Publications  (2)
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  • 1995-1999  (2)
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  • 1
    Online Resource
    Online Resource
    Relationship between tumour necrosis factor-alpha (TNFα) production and a specific multiple sclerosis (MS) associated TNF gene haplotype
    SAGE Publications ; 1999
    In:  Multiple Sclerosis Journal Vol. 5, No. 3 ( 1999-06), p. 165-170
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 5, No. 3 ( 1999-06), p. 165-170
    Abstract: Objective: To determine if monocyte TNFa production from patients homozygous for a specific MS associated TNF gene haplotype is different from that produced in patients either heterozygous for, or without this haplotype. Background: The balance between pro- and anti-inflammatory cytokines is important in the clinical outcome of inflammatory reactions. Levels of TNFa, a pro-inflammatory cytokine, is raised in MS as well as being found in acute and chronic MS lesions. A previous population based study in Northern Ireland with polymorphisms spanning the TNF gene region identified a conserved MS associated haplotype in relation to three markers (130: 118: 127 TNF d: a: b) for which 19 MS patients were homozygous. Methods: Venous blood collected in EDTA to give a concentration of 10 7 3 M was drawn from 16 patients with the conserved MS associated haplotype, 19 patients heterozygous for the haplotype and 17 patients without the haplotype. Mononuclear cells were separated and cultured by standard techniques and levels of TNFa and of TNF binding proteins I and II were determined by commercial enzyme-linked immunosorbent assays. Results: There were no significant differences in TNFa production in the 3 h (P=0.28) or 24 h cultures (P=0.18) or following stimulation with interferon-g (P=0.17) between the group positive for the conserved haplotype and the group negative for this haplotype. There was also no significant difference when compared to the heterozygote group. No association was found between the MS associated haplotype and levels of either TNF binding protein. A greater proportion of patients with the conserved haplotype had a benign clinical course (P=0.06). Conclusion: We conclude that whilst a trend exists, we have found no significant association between peripheral TNFa production and a specific MS associated TNF haplotype in this population. Paradoxically this haplotype may also predict a more favourable clinical course.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/135245859900500305
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1999
    detail.hit.zdb_id: 2008225-3
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Lack of association of transforming growth factor (TGF)-b1 and b2 gene polymorphisms with multiple sclerosis (MS) in Northern Ireland
    SAGE Publications ; 1999
    In:  Multiple Sclerosis Journal Vol. 5, No. 2 ( 1999-04), p. 105-109
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 5, No. 2 ( 1999-04), p. 105-109
    Abstract: Objective: To examine the influence of TGF-b genes on MS susceptibility. Background: TGF-b, of which three homologous isoforms exist (1, 2 and 3), is a strongly immunosuppressive cytokine - inhibiting expression of pro-inflammatory cytokines and blocking cytokine induction of adhesion molecules. TGF-b delays onset of EAE and TGF-b1 gene knockout mice develop fatal multifocal inflammatory disease. High TGF-b levels exist during MS remission whilst E-selectin, whose expression is inhibited by TGF-b, is found at higher levels in primary progressive disease (PPMS) and it is postulated that the unremitting course of PPMS may be due to low levels of TGF-b. Methods: Gene association studies using separate polymorphic microsatellite markers for TGF-b1 and TGF-b2 were performed, incorporating 151 relapsing-remitting or secondary progressive MS (RR/SPMS) patients, 104 PPMS patients and 159 normal controls (Nor). Forward primers were 5' end-labelled with 6-Fam, PCR products were analysed on an Applied Biosystems 373A fluorescent fragment analyser and Genescan 672 software was used for allele sizing. Results: No significant differences existed in allele frequencies between either MS group and controls regarding the TGF-b1 marker: RR/SPMS vs Nor (P=0.48, df=8); PPMS vs Nor (P=0.34, df=8). Similarly there were no associations demonstrated with the TGF-b2 marker: RR/SPMS vs Nor (P=0.24, df=2); PPMS vs Nor (P=0.53, df=2). Conclusion: These data indicate that TGF-b1 and b2 genes are not loci influencing MS susceptibility, either RR/SPMS or PPMS, in this population.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/135245859900500207
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1999
    detail.hit.zdb_id: 2008225-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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