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.
Background: intravenous regional anaesthesia (IVRA) is an effective method of producing anaesthesia of the extremities. Disadvantages are the rapid loss of anaesthesia after the deflation of the tourniquet and the rapid development of postoperative pain. It is important to search for agents with longer durations of action, better nerve fibre selectivity, lesser degrees of motor blockade and lower incidences of systemic toxicity.Objectives: This study was designed to evaluate and compare the clinical effects of intravenous regional anaesthesia, with lidocaine alone, or in a combination with ketamine and atracurium for better analgesia, and to examine the possible clinical advantages of using muscle relaxants (i.e., atracurium) with intrav
... Show MoreType 2 diabetes Nephropathy complication is one of the most commonest metabolic disorders that becomes an advanced serum level of hormone altered. The objective is to study the effect of leptin levels in Type 2 diabetes nephropathy (D.N) complication and healthy subject. This study was done in National Diabetes Center (NDC), AL-Mustansriya University;on a total (64) individuals whase age were ranged from(45-60) years,of which (38) patients of type 2 diabetes nephropathy, and (26) healthy( controls). The collected data ,information concerning the individuals used in the present study were: age, sex , body mass index (BMI) and blood samples to
... Show MoreThis research focused on clarifying the relationship strategic decisions for operations management & performance excellence organizational, The research emerges from a problem which explained by many application questions. Special questionnaire has been prepared for this purpose distributed (72) to sample of management levels (Top, middle) in the General company for mining industries and aquatic Insullation & the General company of batteries industry, The research has tried to test a number hypotheses related to the relation and regression among the variables of the research, and the differences among the <
... Show MoreIn this paper, a Sokol-Howell prey-predator model involving strong Allee effect is proposed and analyzed. The existence, uniqueness, and boundedness are studied. All the five possible equilibria have been are obtained and their local stability conditions are established. Using Sotomayor's theorem, the conditions of local saddle-node and transcritical and pitchfork bifurcation are derived and drawn. Numerical simulations are performed to clarify the analytical results
The present study aims at knowing the effect of discussion method for students of fifth grade in preparatory school.
Methodology of the Study:
In order to achieve the objective of the study, the researcher chooses non-randomly the preparatory school affiliated to the District Chamchamal \ Suliemnaniya. The sample attained 64 students in 32 per group (control and experimental) groups. The researcher used the discussion method which was applied on experimental group. She uses the traditional method on the control group.
The researcher matched the two group in ago, intelligence, marks at the Kurdish Language in the previous year , pretest and posts for the indepe
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The study aims to find out the impact of expectations and perceptions in determining the position of the customer service quality received by him. Represent the expectations and perceptions customer’s key of service quality determinants. The customer's requirements and needs main pivot, who must be built all events and activities and efforts of service organizations, including the hotel and organizations that operate in an environment known as highly competitive , intensification and complexity of the conditions set by the customer and increasing day after day. The study sample of three Luxury hotels in Kurdistan region of Iraq a model. The use of service quality m
... Show MoreThis study included the isolation and diagnosis of Pseudomonas aeruginosa from cases of burns samples. 100 samples were collected from resident patients at Al-Kindi Teaching Hospital, who suffer from different types of burns. Pseudomonas aeruginosa was isolated and diagnosed with 39% of the total samples. The cold and hot aqueous and alcoholic extract of flaxseeds oil was prepared and its inhibitory efficacy has been studied on the growth of isolated Pseudomonas aeruginosa. It is revealed that both extracts of flaxseeds oil had a high inhibitory effect on Pseudomonas aeruginosa growth. The Minimum Inhibitory Concentration (MIC) of flaxseed oil on the studied bacteria was also estimated, which was 25 mg/ml. In conclusion, the efficacy of fla
... Show More1-Objective:- Polyphenols are biochemical compounds with antioxidant activity against differences diseases related to Lipid peroxidation such as diabetes mellitus. Polyphenols distributed widely in medical plants, the aim of the study is to extract and analyze some polyphenolic compounds from grape seeds and examine their effects on (STZ) induced diabetic mice. 2-Methods:- In the present study , a group of polyphenols has been extracted from Iraq
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