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.
15 local isolates of Pseudomonas were obtained from 35 samples from several sources such as soil, water and some high-fat foods. The ability of isolates to produce lipase was measured by the size of the clarification zone formed around the colonies on the lipase production medium and by measuring the enzymatic activity and specific enzymatic activity, the isolate M3 was found to be the most efficient for production of the enzyme, This isolate was identified by microscopic, morphological, some biochemical tests and genetic diagnosis of 16S gene sequences by using the (PCR) technique, and then comparing the results obtained with the National Center for Biotechnology Inform
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The global vision for the future of mankind and societies to achieve supremacy, empowerment and victory is limited to the sincerity of the sincere Islamic vision and its evidence, and this true vision is presented through the texts of the Noble Qur’an, the Sunnah of the Prophet and the concrete reality to achieve victory and empowerment of Islam, and does not respond by tracking the movement of history and its interventions.
The Islamic nation is a nation of survival and continuity with God’s promise and it needs to wake up and alert, and leadership that takes its hand into the path of victory and empowerment, and that this promise fulfills conditions of the most important of these is a promis
... Show MoreIncreased diseases and obesity currently due to increased production and excessive consumption of foods manufactured from non-food sweeteners without attention to the risk of consuming those additional high calories due to consuming these refreshing products such as juices and other various drinks, especially in the summer season by most segments of Iraqi society, especially workers, children and school students the aim of this study. Therefore, the study designed to replace sucrose with 0.03, 0.04 and 0.05% of each of the white stevia crystals and milled dry stevia leaves in the laboratory manufacture of juices and its effect on the general and sensory characteristics and the extent of their acceptability among the specialized r
... Show MoreThis research sought to present a concept of cross-sectional data models, A crucial double data to take the impact of the change in time and obtained from the measured phenomenon of repeated observations in different time periods, Where the models of the panel data were defined by different types of fixed , random and mixed, and Comparing them by studying and analyzing the mathematical relationship between the influence of time with a set of basic variables Which are the main axes on which the research is based and is represented by the monthly revenue of the working individual and the profits it generates, which represents the variable response And its relationship to a set of explanatory variables represented by the
... Show Morethe current study Included, evaluation the impact of Nitrofurantoin drug on liver in albino mice, 128 male albino mice have been used . Animals treared with (150,200 Mg/Kg) for 8 weeks . NFI caused histological changes in liver represented by , swelling of hepatocytes, disappearance of radial arrangement , vaculation of liver cells , increasing of kupffer cells and appearance of giant cells. NFT caused Congestion of blood vessels and infiltration of inflammatory cells in liver in all used concentrations.
This study includes the direct influence of (single & multi) dose of Cold Atmospheric Plasma (CAP) on the no. of platelets for mice for different exposure time (15, 30, 60, and 120) sec. the influence of CAP on mice was measured after 1, 2, 3, 7, and 14 day from exposure.
The results obtained in this study indicate that the effect of low doses of CAP on platelets was stimulatory effect in the first few hours from exposure (1day) but the high dose was inhibitory, It was found that after two weeks of exposure that the number of platelets became normal comparable to the control one, and this indicates that plasma effect was removed after this period.
The importance of internal audit in the growing demand for services in the public and private economic units, and in the rapid growth of its systems professional, has also been recognition of the importance of internal audit quality and the quality of information provided in a long time, as well as the importance of achieving the greatest possible quality in his work to reduce accounting risks of financial reports misleading or fraudulent, which is one of the important features of the audit.
The internal audit quality are linked with the ability of auditors to detect errors in the financial statements, and their willingness to express an opinion technical neutral and non-aligned based on the results of th
... Show MoreMany studies have been made and still concerning the field of translation. Since the mid-90's a considerable amount of researches has tackled the problem of gender and its effect on the process and the product of translation. Simon (1996, p 508) points out that when comparing women and men as translators and writers through history, women seem to be the weaker side. This paves the way to feminist movements which produce prominent studies concerning gender as a concept and translator's gender as practice on the quality and the accuracy of the translation.
Flotow (in Meschia, 2012, p 1-4) outlines several issues that can be
... Show MoreA new, simple and sensitive spectrophotometric method was described for the determination of famotidine (FAM) as a pure material and in pharmaceutical formulation. This method was based on diazotization and coupling reaction between famotidine and diazotized solution of metochlopramide hydrochloride (DMPH) in the presence of phosphate buffer solution to give a compound of azo dye having orange color soluble in water with high absorptivity at a wave length of 478 nm. The data shows that FAM and DMPH combine in the molar ratio of 1:1 at PH 7.0 .The method obeys Beer's law over concentration range of 1-40 ?g.ml-1 of famotidine with a correlation coefficient of 0.9955 and a detection limit of 0.10 ?g.ml-1. The apparent molar absorptivity re
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