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 work is concerned with the study of the effect of cement types, particularly OPC and SRPC, which are the main cement types manufactured in Iraq. In addition, study the effect of mineral admixtures, which are HRM and SF on the resistance of high performance concrete (HPC) to internal sulphate attack. The HRM is used at (10%) and SF is used at (8 and 10)% as a partial replacement by weight of cement for both types. The percentages of sulphate investigated are (1,2 and 3)% by adding natural gypsum as a partial replacement by weight of fine aggregate. The tests carried out in this work are: compressive strength, flexural strength, ultrasonic pulse velocity, and density at the age of 7, 28, 90 and 120 days.
The r
... Show MoreBackground: obesity is a major global health problem with more than 200 million obese men and almost 300 million obese women. Melatonin is a well-known molecule for its involvement in circadian rhythm regulation and has multiple pathological actions including control of appetite, sleep wake cycle and metabolic syndrome.
Aim: to estimate the effect of melatonin supplements on obese patients on a calorie restricted diet in comparison to patients on lifestyle measures only in the form of weight loss, waist circumference and sleep quality.
Subjects and Method: one hundred patients with body mass index > 24 were collected, fifty patients were starte
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Abstract
The research hypothesizes is that the external Environment
has the responsibility concerning decisions making and behavioral
upon industrial firms. It is, Furthermore, an attempt to review the
problem of closures of private industrial firms in the country, during
the period (1976-1985), i.e. prior to and during the Iraqian- Iranian
war.
The behavioral approach of industrial geography has been
adopted as a theoretical background and the statistical test has
been practiced for the applied purposes.
As result, the research comes out with suggestions,
depending upon previous trials in the field of direction and
formulation of the of the private industrial sector. The chief point
among th
The current research seeks to identify the impact of Barman's model on acquisition of the concepts of jurisprudence of worship among students of the departments of Qur'anic sciences. To achieve the research objectives, the researcher relied on the experimental method through a design with partial control by relying on two experimental groups receiving teaching by using the Barman model and a control group receives teaching through the normal method. After applying the experiment, the study reached the following results: Students of the Department of Qur’anic Sciences in general need educational programs linked to the curriculum and built on scientific foundations, according to their needs and problems (psychological, cognitive, and soc
... 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 MoreTo evaluate the toxicity of benzalkonium chloride in aquaculture, the hemato-serological indices of Nile tilapia Oreochromis niloticus are used as biomarkers. Following exposure to three concentrations of benzalkonium chloride BAC 0.1, 0.25, 0.50, and 1 mg/l (BAC1,2,3 and 4) in aquaria for two durations 21 and 42 days, the microbiological assay in fish aquaria, in addition to blood parameters were assessed. Except for the mean difference between BAC2 and BAC3 (P > 0.05) at 42 days, the mean values of the bacterial counts revealed a significant difference between all compared groups (0.05 ≥ P ≤ 0.01). Following exposure to the lower concentrations of BAC (1, 2 and 3), the main blood parameters of Oreochromis niloticus namely red bl
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