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.
From 211 urine samples, Gram negative bacteria were isolated from only 61 urine samples with isolation percentage 28.9%. Escherichia coli were isolated percentage 70.49% while Klebsiella pneumoniae and Psendomonas aeruginosa were 8.19% and 6.55%, respectively.Proteus spp. Were isolated from 9 (14.75%), P. mirablis and P. vulgaris were isolates percentage 11.47% and 3.27%, respectively. Uroepithelial Cell Adhesin (UCA) fimbriae expression by P.mirabilis isolates was detected by the high capacity to adhesion to human uroepithetial cells, the isolate p.mirabilis U7 was adhesion to human uroepithelial cells mean no.30.2 bacteria/cell when grown on luria broth at 37C for 24h, but then grown it’s on luria agar at 37C for 24h the adhesion
... Show MoreTNF-α-induced osteoclastogenesis is central to post-menopausal and inflammatory bone loss, however, the effect of phytoestrogens on TNF-α-induced bone resorption has not been studied. The phytoestrogens genistein, daidzein, and coumestrol directly suppressed TNF-α-induced osteoclastogenesis and bone resorption. TRAP positive osteoclast formation and resorption area were significantly reduced by genistein (10(-7) M), daidzein (10(-5) M), and coumestrol (10(-7) M), which was prevented by the estrogen antagonist ICI 182,780. TRAP expression in mature TNF-α-induced osteoclasts was also significantly reduced by these phytoestrogen concentrations. In addition, in the presence of ICI 182,780 genistein and coumestrol (10(-5) -10(-6) M) augmente
... Show MoreThe study aimed to explore the effectiveness of using rational judgment strategy in teaching science to develop scientific thinking for second-grade students. The researcher utilized the quasi-experimental approach based on (the pre/post designing) of two groups: experimental and control. As for tools: a test of scientific thinking prepared by the researcher that proved its verification of their validity and reliability. The test applied on a random sample of (66) students, divided into two groups: (34) experimental, and (32) control. The results showed that the experimental group outperformed the control group in the post-application of the scientific thinking test, In each skill separately, and in the total skills. The study recommende
... Show MoreFor the first time in Iraq, two species of monogenetic tretamtodes of the genus Dactylogyrus were recorded from gills of Alburnus caeruleus from Tigris river at Al-Zaafaraniya, south of Baghdad during June 1995. The first species, Dactylogyrus sphyrna is characterized by having the seventh pair of marginal hooklets almost twice as large as other marginal hooklets, powerful inner and outer processes of median hooks especially the inner one which is expanded terminally, one connecting bar and long spirally twisted copulatory organ. The second species, Daclytogyrus phoxini differs from the first one by having marginal hooklets of the same size, inner and outer processes of median hooks are not powerful, two connecting bars
... Show MorePurpose – The main purpose of this research is to highlight the main role of strategic leadership skills for top managements in accessing to effective management in accordance with the (VUCA Prime) methodology in (VUCA) environment as Miniature virtual environment, which refers to (Volatility), (Uncertainty), (Complexity), and (Ambiguity).
methodology – To achieve the research objective, this study selected the quantitative approach in research design, Questionnaire was used as the main instrument for data collection, the sample comprised the opinion poll (106) individual who functions as a head department. (Structural equation modelling by (Smart Pls3)
... Show MoreThe Contemporary Business Environment is Surrounded by many quick and continues variable and changes which has an effect on the economic units. These variables and changes like the high competition which need many tools to help them to continue and achieve The critical success. So to achieve this they have many competitive strategies like cost leadership strategy, differentiation strategy and focus strategy.
Budget is regarded one of main tools to execute objectives polices and programs of the economic units, beside show how the economic units had execute the available economic resources.
Activity based on budgeting is regarded one of the modern technique in the m
... Show Moreتحتل أدوات السياسة المالية (الإنفاقية والإيرادية) مكانة مهمة بين أدوات السياسات الاقتصادية الأخرى لما تتمتع به من تأثيرات اقتصادية واجتماعية على مجمل النشاط الاقتصادي .
وفي بحثنا هذا سنركز على الآثار الاجتماعية لأدوات السياسة المالية (الإنفاق العام والإيراد العام) لما للتنمية الاجتماعية من أهمية متزايدة في عالمنا اليوم خاصة فيما يتعلق بمقوماتها غير المادية المتمثلة في خدما
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Praise be to Allah, the Lord of the Worlds, the best prayer and the best prayer, on our master Muhammad, and on his pure God, and his companions and the faithful, and who followed them by charity to the day of religion. This relationship between emphasis, is a sincere, and this harmony, such as the relationship between water, and the green, but it is good, but, with greenery, it is better, and as well as alone, is a beautiful view, but the most beautiful, with the most beautiful. From here he was starting on myself in writing the fundamentalist research of jurisprudence, to show the depth of this interconnection. The doctrine as a new term, then the taj al-Din al-Suobki came after three centuries, and a
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