***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Mendelian r and omization ( MR ) permits causal inference between exposures and a disease . It can be compared with r and omized controlled trials . Whereas in a r and omized controlled trial the r and omization occurs at entry into the trial , in MR the r and omization occurs during gamete formation and conception . Several factors , including time since conception and sampling variation , are relevant to the interpretation of an MR test . Particularly important is consideration of the “ missingness ” of genotypes that can be originated by chance , genotyping errors , or clinical ascertainment . Testing for Hardy-Weinberg equilibrium ( HWE ) is a genetic approach that permits evaluation of missingness . In this paper , the authors demonstrate evidence of nonconformity with HWE in real data . They also perform simulations to characterize the sensitivity of HWE tests to missingness . Unresolved missingness could lead to a false rejection of causality in an MR investigation of trait-disease association . These results indicate that large-scale studies , very high quality genotyping data , and detailed knowledge of the life-course genetics of the alleles/genotypes studied will largely mitigate this risk . The authors also present a Web program ( http://www.oege.org/software/hwe-mr-calc.shtml ) for estimating possible missingness and an approach to evaluating missingness under different genetic models OBJECTIVE Inflammation-induced articular cartilage degradation is a major problem in rheumatoid arthritis ( RA ) . Type 1 T cell activity ( characterized by interferon-gamma/interleukin-2 [ IL-2 ] production ) , and consequently , the production of the proinflammatory cytokines IL-1 and tumor necrosis factor alpha ( TNF alpha ) , have been reported to play a major role in cartilage damage . IL-10 and IL-4 , both produced by type 2 T cells , are cytokines with the capacity to down-regulate proinflammatory responses . The present study was undertaken to investigate the way in which these cytokines affect activated mononuclear cells ( MNC ) of RA patients in relation to human articular cartilage degradation in vitro . METHODS MNC from synovial fluid and peripheral blood of RA patients were stimulated with bacterial antigen and treated with IL-10 and /or IL-4 . Bacterial antigen is known to activate type 1 T cells and to induce proinflammatory IL-1/TNF alpha-dependent cartilage damage . Cytokine production and effects of conditioned media , as well as effects of IL-10 and IL-4 on proteoglycan ( PG ) turnover ( as a measure for cartilage damage ) , were determined . RESULTS IL-10 and IL-4 inhibited proinflammatory cytokine production of stimulated RA MNC and completely reversed inhibition of cartilage PG synthesis induced by these stimulated RA MNC . IL-10 was more potent than IL-4 in this respect , and the combination of IL-10 and IL-4 had an additive effect . In addition , IL-10 directly stimulated cartilage PG synthesis . CONCLUSION IL-10 reverses the cartilage degradation induced by antigen-stimulated MNC , and IL-4 has an additive effect on this process . Furthermore , IL-10 has a direct stimulatory effect on PG synthesis , and IL-4 , as a growth factor for type 2 T cells , can reduce the ratio of type 1 to type 2 T cell activity . These results provide evidence in favor of the use of a combination of the two cytokines in the treatment of RA 
    Output:
    
Conclusions These results suggest that the IL-10 - 1082 G/A polymorphism confers susceptibility to JIA