Serum immunomodulatory factors in gastrointestinal diseases. A 30-50-kD serum fraction in Crohn's disease capable of modulating lymphocyte activation.
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We tested the hypothesis that serum factors present in Crohn's disease interfere with the process of lymphocyte activation. The mitogen-induced proliferation and the expression of early activation antigens by normal lymphocytes cultured in the presence of either Crohn's disease sera or sera from different controls were evaluated. The mitogen-induced proliferation was significantly impaired in the presence of Crohn's disease sera. These sera markedly inhibited the mitogen-induced interleukin-2 receptor (IL-2R) expression (48% inhibition), while the effect of sera on the expression of the transferrin receptor and the 4F2 antigen was much less pronounced. Diafiltration experiments showed that the inhibitory effect was confined to a 30-50-kD serum fraction. Such a serum property was not related to the patients' disease activity and disappeared after surgical removal of the affected bowel. The capability of inhibiting the mitogen-induced IL-2R expression was not restricted to Crohn's disease and was observed with sera from other inflammatory and neoplastic gastrointestinal disorders. This study indicates that a marked inhibition of the IL-2R is a mechanism underlying the immunosuppressive property of the serum in Crohn's disease and in other gastrointestinal conditions. (+info)
Prediction of severe adverse drug reactions using pharmacogenetic biomarkers.
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Severe adverse drug reactions (ADRs) are a major issue for drug therapy because they can cause serious disorders and be life-threatening. Many severe ADRs appear to be idiosyncratic and unpredictable. Genetic factors may underlie susceptibility to severe ADRs, and identification of predisposing genotypes may improve drug therapy by facilitating prescreening of carriers for specific genetic biomarkers. In this review, we clarify the current status of ADRs in Japan from open ADR data sources. Then, we introduce recent progress in the field of pharmacogenetic biomarkers for severe cutaneous ADRs, liver injury, and statin-induced myopathy. Key challenges for discovery of predictable risk alleles for these severe ADRs are also discussed. (+info)
The farnesoid X receptor regulates adipocyte differentiation and function by promoting peroxisome proliferator-activated receptor-gamma and interfering with the Wnt/beta-catenin pathways.
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The expression of thyroid hormone transporters in the human fetal cerebral cortex during early development and in N-Tera-2 neurodifferentiation.
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