161 resultados para Interleukin-12
Resumo:
Objective:
To determine whether polymorphisms in the interferon-? (IFN?)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA).
Methods:
Four microsatellite markers, located in a 118-kb interval that contains both the IFN? and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction–based fragment analysis.
Results:
Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [Pcorr] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32–0.78; P = 0.002, Pcorr = 0.03) but not in men with RA.
Conclusion:
Our results demonstrate that common polymorphisms in the IFN?/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis.
Resumo:
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has recently attracted attention as a potential therapeutic agent in the treatment of cancer. We assessed the roles of p53, TRAIL receptors, and cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP) in regulating the cytotoxic effects of recombinant TRAIL (rTRAIL) alone and in combination with chemotherapy [5-fluorouracil (5-FU), oxaliplatin, and irinotecan] in a panel of colon cancer cell lines. Using clonogenic survival and flow cytometric analyses, we showed that chemotherapy sensitized p53 wild-type, mutant, and null cell lines to TRAIL-mediated apoptosis. Although chemotherapy treatment did not modulate mRNA or cell surface expression of the TRAIL receptors death receptor 4, death receptor 5, decoy receptor 1, or decoy receptor 2, it was found to down-regulate expression of the caspase-8 inhibitor, c-FLIP. Stable overexpression of the long c-FLIP splice form but not the short form was found to inhibit chemotherapy/rTRAIL-induced apoptosis. Furthermore, siRNA-mediated down-regulation of c-FLIP, particularly the long form, was found to sensitize colon cancer cells to rTRAIL-induced apoptosis. In addition, treatment of a 5-FU-resistant cell line with 5-FU down-regulated c-FLIP expression and sensitized the chemotherapy-resistant cell line to rTRAIL. We conclude that TRAIL-targeted therapies may be used to enhance conventional chemotherapy regimens in colon cancer regardless of tumor p53 status. Furthermore, inhibition of c-FLIP may be a vital accessory strategy for the optimal use of TRAIL-targeted therapies.
Resumo:
Background
Little is known about the quality of life (QoL) of disabled children. We describe self-reported QoL of children with cerebral palsy, factors that influence it, and how it compares with QoL of the general population.
Methods
1174 children aged 8–12 years were randomly selected from eight population-based registers of children with cerebral palsy in six European countries and 743 (63%) agreed to participate; one further region recruited 75 children from multiple sources. Researchers visited these 818 children. 318 (39%) with severe intellectual impairment could not self-report; 500 (61%) reported their QoL using KIDSCREEN, an instrument with scores in ten domains, each with SD=10. Multivariable regression was used to relate QoL to impairments, pain, and sociodemographic characteristics. Comparisons were made with QoL data from the general population.
Findings
Impairments were not significantly associated with six KIDSCREEN domains. Comparison of least and most able groups showed that severely limited self-mobility was significantly associated with reduced mean score for physical wellbeing (7·6, 95% CI 2·7–12·4); intellectual impairment with reduced mean for moods and emotions (3·7, 1·5–5·9) and autonomy (3·3, 0·9–5·7); and speech difficulties with reduced mean for relationships with parents (4·5, 1·9–7·1). Pain was common and associated with lower QoL on all domains. Impairments and pain explained up to 3% and 7%, respectively, of variation in QoL. Children with cerebral palsy had similar QoL to children in the general population in all domains except schooling, in which evidence was equivocal, and physical wellbeing, in which comparison was not possible.
Interpretation
Parents can be reassured that most children aged 8–12 years with cerebral palsy will have similar QoL to other children. This finding should guide social and educational policy to ensure that disabled children participate fully in society. Because of its association with QoL, children's pain should be carefully assessed.
