Sublingual immunotherapy with a grass pollen tablet is efficacious irrespective of the patients' baseline sensitization to either single or multiple grass pollen allergens. Seric IgG responses may contribute to SLIT-induced clinical tolerance in a fraction (i.e. 17%) of patients, but additional immune mechanisms are involved in most patients. Consequently, antibody responses cannot be used as a marker of SLIT efficacy at an individual patient level.
These observations suggest that both death receptor and caspase-mediated apoptosis processes are activated in this sepsis model. Bcl-2 overexpression before endotoxin challenge prevents myocardial dysfunction in rats and improves survival rate in mice.
As a part of our glycoantigen synthetic program for diagnosis and basic analysis of yeast-related pathogenic mechanisms, a library of 1-->2 oligomannosides suitable for immunoanalysis was prepared. The use of biotin sulfone, an oxidized form of biotin, offers a convenient solution for both oligosaccharide synthesis and immobilization on microspheres and surface plasmon resonance sensors. The application of this new strategy for the analysis of anti- Candida albicans antibody response through multiple-analyte profiling technology (Luminex) and with surface plasmonic analysis using biotin tagged synthetic oligosaccharides on avidin coated surfaces was validated using monoclonal antibodies.
The interaction of various antiglucocorticoids with the glucocorticoid receptor from intact rat thymocytes was investigated. Reversible antiglucocorticoids (RU 486, cortexolone, progesterone) underwent more limited nuclear transfer than potent glucocorticoids (dexamethasone, triamcinolone acetonide, progesterone). This behavior was correlated with an impeded dissociation of cytosolic antiglucocorticoid receptor complexes preformed in intact cells, as assayed by high-performance size exclusion chromatography in physiological conditions (i.e., isotonic molybdate-free buffer). Antagonist-receptor complexes remained in a 7-8-nm form whatever the antiglucocorticoid tested (including dexamethasone mesylate and trifluoroperazine, a nonsteroidal antiglucocorticoid) and the incubation time at 37 degrees C, whereas agonist-receptor complexes were rapidly converted into 5-nm species. This stabilization was not detectable by conventional sucrose gradient centrifugation because of artifactual dissociation of untransformed complexes, a pitfall overcome by resorting to vertical tube centrifugation. Moreover, the low amount of nuclear antiglucocorticoid receptor complexes was also in the undissociated form, in contrast with nuclear agonist-receptor complexes. Immunological probes demonstrated that the 90-kDa non-steroid-binding component was associated with the antiglucocorticoid-stabilized receptor. Thus, whatever their chemical structure and their affinity for the receptor, antiglucocorticoids stabilize the oligomeric form of the glucocorticoid receptor in intact cells. Our data, demonstrating for the first time that all antiglucocorticoids probably act via a common mechanism, suggest a key role for subunit dissociation during in vivo receptor activation.
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