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 research aims to investigate the role of quality management in enhancing the efficiency and effectiveness of settling accounts tax in terms of achieving satisfaction in charge of the hand and the increase of tax revenue on the other hand, by testing the main hypothesis of the study and the sub-hypotheses in the Income and Sales Tax Department in Jordan for the period 2000-20
... Show MoreThe present study discusses the semantic characteristics of the Russian newspapers journalistic headlines (The Russian newspaper "Komsomolskaya Pravda" as Example"). The study traces the characteristics of the Russian newspaper headlines, its relevance to grammar, syntax, lexical items and style. These characteristics in Russian will be investigated and compared to their Arabic correspondents in the process of translation. The study also specifies the meanings and the functions of the newspaper headlines in the light of modern linguistics stressing the grammatical, lexical and stylistic aspects of headlines translation from Russian into Arabic.
J
... Show MoreBackground: Pre-eclampsia is culmination of a multi-step process that related in part to elevated oxidative stress and associated with hyperurecimia.
Patients and methods: Thirty normotensive and hundred pre-eclamptic pregnant women attending to Al-Basra hospital of pediatrics, obstetrics and gynecology were participated in this study. The patients were randomized into six groups. They were treated with methyldopa alone, methyldopa plus vitamin C, methyldopa plus vitamin E, methyldopa plus vitamin C and E, and methyldopa plus allopurinol. The oxidative stress (MDA), renal function parameters, systolic and diastolic blood pressure were evaluated before treatment and 14 day after initiation of therapy.
R
Objective: The purpose of this study was to assess the effectiveness of Vibriophage Universiti Sains Malaysia 8 (VPUSM 8), a bacteriophage that destroys bacteria, in managing the proliferation of Vibrio cholerae, specifically the El Tor serotype, as an alternate therapeutic strategy. Methods: The study entailed subjecting water samples from Kelantan, Malaysia, to reproduce the natural circumstances that promote the growth of V. cholerae. Subsequently, the samples were contaminated with the V. cholerae O1 El Tor Inaba strain and treated using VPUSM 8. The study employed a controlled experimental design, wherein the samples were divided into three groups, each experiencing different treatment methods. Quantifying the number of colony-
... Show MoreThe study aims to follow modern methods in teaching rhythmic gymnastics skills by directing learners to develop their perceptions and absorb what the world deals with today and develop intelligence among learners, the researchers searched for the strengths of the learner by providing them with an opportunity to form their kinetic formation, hence the problem came by introducing a method of self-intelligence and social to guide the learner in the search for ways and solutions to overcome boredom and economy Time and effort in the educational process in learning and give them the freedom to express their ideas And their skills and here came the role of social and self-intelligence to teach the individual and collective kinetic formati
... Show MoreMost of the world is seeking attention to the agricultural sector, which occupies a distinguished economic center, including Iraq, it is no wonder that the focus is on this sector, especially in developing countries. Descriptive analysis of the sample tables of wheat and barley crops in Iraq showed that adherence to the principles and rules of total quality, including modern irrigation methods (irrigated) has a significant impact in increasing productivity, reducing costs and improving quality compared to traditional irrigation methods, so it became necessary to take agricultural economic units All procedures and means that will help in the application of the rules of total quality to promote the reality of wheat and barley cultivation in I
... Show MoreLiterary works include, for the most part, text thresholds, which are the first entry into reading them and understanding their connotations, and (literary works) vary according to text thresholds, some of which are limited to the title and on the cover page only, and others, in addition to these two thresholds, are based on the dedication threshold too, and others ...
This study takes the story of "Mamo Zain" of the poet Ahmed Al-Khani and his translator Sheikh Muhammad Ramadan Al-Bouti as the field of study, as it is a unique literary work, which included a number of textual thresholds which supported each other and cooperated with the content of the work.
The threshold of dedication in the story of "Mamo Zain" was a spee
... Show MoreTakbiratul Ehram "The First Takbeer to Start Prayer" means: the words that the worshiper says to start his prayers, and refrain from anything invalidates it. the findings revealed that the four school jurists agreed that the prayer is not valid without Takbiratul Ehram "The First Takbeer to Start Prayer", and they disagreed on its description, so the majority of jurists said that it is a pillar, and some of them called it an obligatory, but Hanafi made it a condition. Likewise, the four jurists agreed that the one who articulates Takbiratul Ehram "The First Takbeer to Start Prayer" with the word: “Allahu Akbar,”; his Takbeer is correct, and they disagreed about the one who adds a word, or replaced it with another, where the m
... Show More