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.
This study was done to find the potential renal protective effects of sildenafil and its underlying mechanisms in mice with adenine-induced CKD. For the experiment, 40 male mice were split into four groups. The control group (A) received the same food without medication until the research ends, while the other three collections (B, C, and D) were given adenine (0.25% w/w in feed daily for 8 weeks), groups (C and D) were given sildenafil (0.5 and 2.5 mg/kg) respectively orally every day for 30 days, and then blood samples were taken to assess the function of the kidneys (Urea, total protein, and creatinine), total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) in addition to kidney histopathology, as w
... Show MoreBackground: - Aspergillus fumigatus is a ubiquitous and opportunistic fungal pathogen causing sever invasive aspergillosis, an important source of morbidity and mortality in
immunocompromised hosts (human and animals) .The present study was conducted to obtain more clarification about the toxicity and histopathological effects of this pathogen in albino mice
Material and Methods :- fourteen male mice( 6-10) weeks old ,( 20 – 28) gm weight , divided into two groups , test group ( n= 8) , intranasally infected with 25μl (710 conidia / ml normal
saline ) of A. fumigatus for 7 successive days , compared with uninfected group ( n=6) . the weight of all animals were measured at the beginning and at the end of th
The speed of skills has become linked to modern methods of individual and group play, and each of them has begun to serve the other tactically. Through the follow-up of the researchers, they noticed that there is a significant weakness in the speed of performance and slowness in mental preparation, which plays a major role in understanding mental readiness, which is linked to the speed of making decisions during the game, as well as the weakness of the physical speed of the female players, which in turn has an impact on the skill performance of the players of the Iraqi clubs, which are the main supporter of the national team. The study aimed to identify the effect of interactive speed training on the performance of some skills among
... Show MoreBackground: pulmonary function can change with age for normal individual's .Spirometric measurement for the ratio of forced expiratory volume in one second (FEV1), the forced vital capacity and the ratio (FEV1/FVC) can reveal airway obstruction and the consequence change in pulmonary performance. These parameters can be different for different race /ethnic and gender.
Methods: Pulmonary function test were carried out on 29normal male and 37 normal female the test parameters were FEV1 and FVC from which the ratio of FEV1/FVC %was calculated in relation to age. Iraqi average for FEV1 and FVC and FEV1/FVC % has also been obtained
Results: results of these tests reveled that the ratio of FEV1/FVC % is almost th
In the current research, we investigated the absorption spectrum for R590 and C480 dyes in ethanol solvent for different dye solution concentrations of 10-4, 10-5 and 10-6M. These dyes have been prepared and studied before and after gamma irradiation (first, second ionization) using cesium-137 source with absorbed doses of 18.36 Gy (time exposure of 10 days) and 73.44 Gy (with time exposure of 40 days). We noticed that the absorption intensity was decreased with decreasing concentration, before gamma irradiation while the absorption spectrum peak shifted towards the short wavelength (blue shift). It was also found that the intensity of absorption spectrum increased and shifted the absorption spectrum peak towards the long wavelength (red
... Show MoreThe study seeks to investigate the effect of Dunn Dunn learning style model on students’ achievement. Besides, the way of developing students’ deductive thinking by testing the null hypothesis: there is no significant difference between experimental group who takes Dunn Dunn model as style in studying geography and control group that follows a traditional method in studying geography at the level of (0,05). Additionally, there is no significant difference between experimental group who takes Dunn Dunn model as style in studying geography and control group that follows a traditional method in studying geography at the level of (0,05) on testing developing deductive thinking skills. The researcher adopted a quasi-experimental posttest
... Show MoreElectrospun nanofiber membranes are employed in a variety of applications due to its unique features. the nanofibers' characterizations are effected by the polymer solution. The used solvent for dissolving the polymer powder is critical in preparing the precursor solution. In this paper, the Polyacrylonitrile (PAN)-based nanofibers were prepared in a concentration of 10 wt.% using various solvents (NMP, DMF, and DMSO). The surface morphology, porosity, and the mechanical strength of the three prepared 10 wt.% PAN-based nanofibers membranes (PAN/NMP, PAN/DMF, and PAN/DMSO) were characterized using the Scanning Electron Microscopy (SEM), Dry-wet Weights method, and Dynamic Mechanical Analyzer (DMA). Using DMF as a solvent resulted in a lon
... Show More