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 The study aims to clarify the value of auditing economic units and how it can be measured, which is one of the most important challenges to matching the Value Relevance of Accounting Information. The problem of the study was identified with questions that revolve around the extent to which it is possible to measure the value of auditing in Iraqi economic units and the extent to which the value of auditing affects the adequacy of accounting information. Through reviewing the studies discussing this topic, it was found that auditing can provide value through the performance of the auditor and adding value to the economic unit subject to audit. The study recommended the need to study the situational factors of auditing, whether exter
... Show MoreSloped solar chimney system is a solar chimney power plant with a sloped collector. Practically, the sloped collector can function as a chimney, then the chimney height can be reduced and the construction cost would be reduced.The continuity, Naver-stockes, energy and radiation transfer equations have been solved and carried out by Fluent software. The governing equations are solved for incompressible, 3-D, steady, turbulent standard model with Boussiuesq approximation to develop for the sloped solar chimney system in this study and evaluate the performance of solar chimney power plant in Baghdad city of Iraq numerically by Fluent (14) software with orking conditions such as solar radiation intensity (30
... Show MoreLinguistic taboos exist in most cultures. Tabooed words are generally being culturespecific
and relating to bodily functions or aspects of a culture that are sacred. Such words are
avoided, considered inappropriate and loaded with affective meaning and failing to adhere to.
Strict rules, often, governing their use and lead to punishment or public shame. These taboo
words can be used as a way of violating social deixis represented by four types of honorifics;
addressee, referent, bystander, and finally setting honorifics. This paper shows how these
taboo words are used in Kenneth Bernard's play La Justice or The Cock that Crew from the
theatre of the Ridiculous as means of violating social deixis in its four types. Th
Patients with decompensated cirrhosis have typically prescribed a combination of therapeutic and prophylactic medications. Polypharmacy increases the probability of medication errors and drug related problems. Clinical pharmacists are highly effective at identifying, resolving, and preventing clinically important drug-related problems in their patients' care. The objectives of the study were the identification and classification of drug-related problems, as well as the discussion of these problems with health care providers (physicians, pharmacists, and nurses) and patients. Reduce their incidence as effectively as possible and educate all research participants on the significance of following their prescribed drug regimen
... Show MoreIn this research, the X-ray diffraction pattern was used, which was obtained experimentally after preparation of barium oxide powder. A program was used to analyze the X-ray diffraction lines of barium oxide nanoparticles, and then the particle size was calculated by using the Williamson-Hall method, where it was found that the value of the particle size is 25.356 nm. Also, the dislocation density was calculated, which is equal to1.555 x1015 (lines/nm2), and the value of the unit cell number was also calculated, as it is equal to 23831.
In recent decades, drug modification is no longer unusual in the pharmaceutical world as living things are evolving in response to environmental changes. A non-steroidal anti-inflammatory drug (NSAID) such as aspirin is a common over-the-counter drug that can be purchased without medical prescription. Aspirin can inhibit the synthesis of prostaglandin by blocking the cyclooxygenase (COX) which contributes to its properties such as anti-inflammatory, antipyretic, antiplatelet and etc. It is also being considered as a chemopreventive agent due to its antithrombotic actions through the COX’s inhibition. However, the prolonged use of aspirin can cause heartburn, ulceration, and gastro-toxicity in children and adults. This review article hi
... Show MoreBackground: The use of antiepileptic drugs (AEDs) during pregnancy warrants several side effects and also deleterious effects on fetal development, the antiepileptic drugs have potential to affect the fetal development throughout the pregnancy although, the majority of infants born to epileptic pregnant women are normal but more expose to the malformations. Aim: The present study aimed to investigate the effect of carbamazepine drug on the kidney development at day 7 postnatally in the Albino Rat (Rattus rattus) as a mammalian model. Material & Methods: 20 healthy pregnant female rats were divided into two groups, 10 pregnant rats in each group; group one served as control group administrated distal water while group two used as experimenta
... Show More