Drug hypersensitivity involves the activation of T cells in an HLA allele–restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell–priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO–specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ–restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO–specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO–induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.
The hazardous metabolic effects of treating schizophrenia patients with olanzapine comprise serotonin 2C receptor (5-HT2C) antagonists. Metabolic side effects of antipsychotic drugs, including lipid abnormalities, disturbed glucose metabolism, and weight gain, can have a major impact on treating psychiatric patients. The intent of this study was to investigate whether there is an associated link between the genetic polymorphism at -759C>T in the promoter region of the 5-hydroxytryptamine 2C receptor (HTR2C) gene and the metabolic syndrome driven by olanzapine in schizophrenia patients. A cross-sectional study that involved fifty hospitalized patients with schizophrenia. The patients were split into two groups (metabolic and non-metab
... Show MoreThis qualitative study was conducted on eight types of commercial baking yeast which available in local markets to estimate their fermentation activity as affecting the Bread industry and the impact of the salt added to DoughLeavening, The results showed a great variation in the fermentation capacity of yeast samples (their role in swelling the dough), most notably the sample value Y3 and least sample Y7 and reached 80% and 20% respectively, and the value of Leavening by using the two types of yeast with addition of three levels of salt (0 , 1 and 2%) have 20.0 , 19.7 and 15.7 of the sample Y3, compared with 10.5 , 10.3 and 8.8 of the sample Y7 for each of the levels of salt respectively, reflect
... Show MoreLiposomal amphotericin B (Amph B) has been used effectively to treat leishmaniosis, in spite of its high toxicity appeared in some patients. In our study, Amph B was administered in Leishmania donovani that infected BALB/c male mice using different concentrations to evaluate its efficacy challenge against infection as well as its effect in modulating immunity of the host. We observed that low doses with short duration of Amph B as a therapy regime significantly enhanced the induction of Th1 cytokine (INF-γ), but suppressed Th2 cytokine (IL-10) production. Groups of mice infected with L. donovani and treated with Amph B showed clearly increasing in INF-γ level and reduction in IL-10 level in concentration (3, 4, 5 mg/ml/kg) with best resul
... Show MoreThis work describes the effect of temperature on the phase transformation of titanium dioxide (TiO2) prepared using metal organic precursors as starting materials. X-ray diffraction (XRD) was used to investigate the structural properties of TiO2 gels calcined at different temperatures (300, 500, 700) ?C. the results showed that the samples have typical peaks of TiO2 polycrystalline brookite nanopowders after calcined at (300 ?C), which confirmed by (111), (121), (200), (012), (131), (220), (040), (231), (132) and (232) diffraction peaks. Also, XRD diffraction spectra showed the presence of crystallites of anatase with low proportion of rutile phase where calcined at (500 ?C), while rutile phase domains at (700 ?C). The crystallite size of
... Show MoreNigella sativa seeds (NSS) are reputed traditionally and scientifically as a potent agent that promote milk secretion (galactagogue), but their mechanism of action is studied trivially. One suggestion was that these seeds are bio-transformed to sex hormones within the ovaries. Therefore, this investigation was designated to throw light on the action of these seeds in the absence of ovaries i.e. in male rats. Thirty Norway male albino rats were used in this investigation. They were divided into experimental (n=20,fed NSS 2g/ Kg body weight /day for 14 days) and control (n=10, fed placebo for 14 days). After sacrifice mammary gland and blood samples were obtained. Experimental rats revealed a significant increase (p (0.01>in
... Show MoreDrilling solutions can be considered as an intricate mixture comprising of number of chemical additives which aid specific needs such as controlling the rheological properties and reducing corrosion. Inhibitors are substances that are added in small concentrations to corrosive environment to decrease the corrosion. Their applications can be found in drilling equipments. The effect of adding Zinc Sulphate and Carboxymethyl Cellulose to study their influence on the corrosion of carbon steel in Bentonite mud has been evaluated using Weight Loss Technique. This study focuses on determining rheological properties and corrosion characteristics. Results show CMC and ZnSO4 work as inhibitors when added to the Bentonite with inhibition
... Show MoreThis research aims to analyze the effect between letter of credit opening and implementation procedures which considered one of the most important Foreign services submitted by bank institutions to their customers on Time contracted time limit commitment contract by some Iraqi commercial banks, descriptive analytical method used in This research The questionnaires designed a tool main research to gather information to get to know the effect , Seventy questionnaire forms were distributed, sixty seven forms were analyzable , The answers were analyzed by the arithmetic mean and standard deviation and test the level of influence between variables simple linear regression. The result showe
... Show MoreThe current study examined the effect of different sample sizes to detect the Item differential functioning (DIF). The study has used three different sizes of the samples (300, 500, 1000), as well as to test a component of twenty polytomous items, where each item has five categories. They were used Graded Response Model as a single polytomous item response theory model to estimate items and individuals’ parameters. The study has used the Mantel-Haenszel (MH) way to detect (DIF) through each case for the different samples. The results of the study showed the inverse relationship between the sample size and the number of items, which showed a differential performer.