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.
Abstract: This study was aimed to investigate the effect of two doses of pregabalin (PGB) on hormonal level and sexual activity in female albino rats. Ninety female rats with age (9-10 weeks) and weight (200±20 g) were divided into three major groups of thirty rats. First group was considered as control G1, the second G2 and third G3 groups were exposed to PGB into two doses 150, and 300 mg/kg body weight per day respectively. Each major group was divided into three subgroups (subgroup A, B, and C of each has ten rats), the treatments last for one month for subgroup A, two months for subgroup B, and three months for subgroup C. Five rats from each subgroup were placed separately into two breeding cages with two isolated males and wait
... Show MoreAn experiment in the semester, the second semester of the academic year (2022-2023), and the data used was not processed (the second test for two independent, inaccurate samples, the Bermon correlation coefficient, and the Spearman correlation coefficient), and the following results were reached: There is a statistically significant difference at the level of ( 0) average, 05) between the third grade who studied the plan for asking cluster questions, and between the average of those who studied the special feature according to the traditional method of selecting achievement, and enjoyed completing the specialization, choosing the experimental group, because the strategy of asking cluster questions is one of the externalities that... Lear
... Show MoreThe aim of this study is to provide an overview of various models to study drug diffusion for a sustained period into and within the human body. Emphasized the mathematical compartment models using fractional derivative (Caputo model) approach to investigate the change in sustained drug concentration in different compartments of the human body system through the oral route or the intravenous route. Law of mass action, first-order kinetics, and Fick's perfusion principle were used to develop mathematical compartment models representing sustained drug diffusion throughout the human body. To adequately predict the sustained drug diffusion into various compartments of the human body, consider fractional derivative (Caputo model) to investiga
... Show MoreCheckpoint inhibitors are a type of immune therapy used to treat different types of cancers. These drugs block different checkpoint proteins, for example, CTLA-4, PD-1, and PD-L1 inhibitors.
They block proteins that stop the immune system from attacking the cancer cells. Checkpoints are also described as a type of monoclonal antibody that antagonizes binding between B7 to CTLA-4 and PD-L1 to PD-1.
Immune checkpoint inhibitors are used to treat BARCA mutated triple-negative breast cancer (TNBCS) in patients who do not respond to chemotherapy, and also in the treatment of highly mutated and solid tumors such as brain tumors, liver, and pancreatic cancers.
Immune checkpoint inhibitors exhibit an effect on solid tumo
... Show MoreThe research investigates the political effect and its directions on the architectural thoughts and its achievements and how can this political system affect all fields of life in communities including architectural urban design. The problem of the research lies in the ambiguity effects of the ideological national directions of the Nazi Party on the architecture and urban design of the city of Berlin, then determining the aims of the research to discuss the concepts of politics and architecture and their relation to the way of thinking that plays a role in the process of design that works on property and achieving the suitable urban environments for those communities. After that, the Nazi's party's thought would be studied and analyzed,
... Show MoreThe plant licorice is considered important plants as nutritionally and medically and economically, as a rich in phytochemical, vitamins and minerals, and being widely available, Research indicated the presence of many nutrients such as (proteins, Carbohydrates, vitamins and minerals) as well as presence of Glycyrrhizin which responsible of sweet taste, that allowing the possibility to use it as natural intensity sweetener with few calories in Sweetening of many food. This research is aimed to study the Stability of Glycyrrhizin toward the various manufacturing conditions such as (thermal treatment, pH of foods and microwaves), so three factorial experiments was implemented to find out the Stability as following: 100C° - 121C° - Microwa
... Show MoreThe dynamic behavior of laced reinforced concrete (LRC) T‐beams could give high‐energy absorption capabilities without significantly affecting the cost, which was offered through a combination of high strength and ductile response. In this paper, LRC T‐beams, composed of inclined continuous reinforcement on each side of the beam, were investigated to maintain high deformations as predicted in blast resistance. The beams were tested under four‐point loading to create pure bending zones and obtain the ultimate flexural capacities. Transverse reinforcement using lacing reinforcement and conventional vertical stirrups were compared in terms of deformation, strain, and toughness changes of the tes
Experimental and numerical studies have been conducted on the effects of bed roughness elements such as cubic and T-section elements that are regularly half-channel arrayed on one side of the river on turbulent flow characteristics and bed erosion downstream of the roughness elements. The experimental study has been done for two types of bed roughness elements (cubic and T-section shape) to study the effect of these elements on the velocity profile downstream the elements with respect to different water flow discharges and water depths. A comparison between the cubic and T-section artificial bed roughness showed that the velocity profile downstream the T-section increased in smooth side from the river and decrease in the rough side
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