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.
Acromegaly is ametabolic disorder characterized by an acquired progressive somatic disfigurement, mainly involving the face, extremities and many other organs, that are associated with systemic manifestations, caused by excessive secretion of growth hormone and a resultant persistent elevation of insulin-like growth factor-I concentrations. In more than 90% of cases originates from a monoclonal benign pituitary adenoma. Aim of this study to assess the level of insulin-like growth factor-I (IGF-I) in saliva of acromegalic patients, and to compare it with the basal levels of serum IGF-I. Sixty specimens of serum and saliva collected from two groups of subjects (forty acromegalic patients and twenty healthy persons). The specimens were
... Show MoreThe aim of this study is to identify the effectiveness of a rational, emotional, behavioral program in developing self-efficacy to reduce the level of Burnout in 20 teachers of students with autism disorder in Jazan, Saudi Arabia. The proposed program included 12 training sessions. The researcher found that the proposed program has contributed significantly to the development of self-efficacy and reduce the level of Burnout for the targeted subject in this study.
Economic organizations operate in a dynamic environment, which necessitates the use of quantitative techniques to make their decisions. Here, the role of forecasting production plans emerges. So, this study aims to the analysis of the results of applying forecasting methods to production plans for the past years, in the Diyala State Company for Electrical Industries.
The Diyala State Company for Electrical Industries was chosen as a field of research for its role in providing distinguished products as well as the development and growth of its products and quality, and because it produces many products, and the study period was limited to ten years, from 2010 to 2019. This study used the descriptive approa
... Show MoreMany international studies indicated that the polymorphisms of some genes disturbed the folate homocysteine (Hcy) metabolism and increased the vulnerability to Down syndrome (DS). We aimed to measure the serum levels of folate and Hcy in DS children and compare the levels with age and sex-matched apparently normal healthy children. We also aimed to study the A80G polymorphism of the gene reduced folate carrier (RFC1) in the DS children as a risk factor. Forty children with DS (24 were boys, and 16 were girls) with the age range between 5-13 years, and 26 normal healthy children (16 boys and ten girls) were included in this study. The results show that the highest genotype in the control group was AG (53.85%) followed by AA and GG (30.
... Show MoreThe study aimed to know the degree of availability of integrated preparation criteria in the Arabic Teacher training Program in Syrian universities from the viewpoint of university students of the Educational qualification diploma, and the degree of availability of these standards in the outputs of the preparation program. To achieve the Goals of the study, a list of integrated preparation criteria was prepare comprising (110) indicators, distributed to (11) criteria. The list was applied to a randomly chosen sample of (45) educational qualification diploma students. The results of the study showed that the Standards for integrated preparation are provided in a medium degree overall in the program for preparing teachers of Arabic languag
... Show MorePopulation density represents an important indicator for determining the growth of the size of urban areas. Population density has a direct impact on the quality of life, and its excessive rise may lead to the deterioration of basic service facilities. The problem of the research is that the increase in the total population densities of the residential neighborhood may reflect negatively on the nature of the services provided to the residents in these shops, and thus the failure to achieve sustainability in the residential locality. The research assumes that the increase in population densities negatively affects the achievement of sustainability in the residential neighborhood.
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Background: Thyroid cancer (TC) is an increasingly prevalent malignancy throughout the world. It has long been recognized that the incidence of TC is higher in women which increases with age. However, the association of gender disparity and age with TC aggressiveness and outcomes are still controversial. The aim of this study was focused on the association of age and gender with histopathological characteristics in TC. Methods: 153 patients who met the criteria, were selected. The included cases were divided into four age groups (≤24 years, 25-44 years, 45-64 years, and ≥65 years). Demographic, age and pathological parameters were compared among them. The association of gender and age with
... Show MorePraise be to God, Lord of the worlds, and peace and blessings be upon our master Muhammad, and upon his family and companions as a whole. Now, the research deals with the grammatical issues mentioned in the Book of Al-Zahir in the meanings of people's words to Abu Bakr Al-Anbari (d. 328 AH). Two parts of the book have more than one edition, it was printed by the Iraqi Ministry of Culture and Information Beirut in 1979 AD, and the Al-Resala Foundation issued the second edition in 1992 AD The third edition was printed in Dar Al-Bashaer in Damascus in the year 2003 AD and it was the reliance on the research and the grammatical issues were arranged on topics that are: interrogation - Deletion, exclusion, marbling, call and Wallace Relief and
... Show MoreThe goal of current research is marked "student services for the university student at the Faculty of Education for Girls at Baghdad University in light of the overall quality indicators)" to identify the relative importance of the availability of student services offered by the College of Education at the University of Baghdad, from the viewpoint of the students. The research was Aaguetdy followers researcher Find descriptive approach to suitability research topic and in order to achieve the purposes of research, the researcher designed questionnaire examined consisted of (18) items and has been questionnaire on arbitrators and experts to verify the validity and reliability that's been applied to the questionnaire on a group of students
... Show MoreThe present study evaluates the effects of Ginkgo biloba extract as monotherapy on the glycemic status, insulin resistance (IR), body mass index (BMI), and visceral adiposity index (VAI), in addition to the inflammatory markers, oxidative status and leptin level in patients with metabolic syndrome in comparison with metformin.
The study is a randomized, double-blind pilot study conducted during the period May to September, 2020. Fifty patients were recruited in the study and they were allocated into two groups (25 per each group): Ginkgo biloba and Metformin groups, they received (120 mg Ginkgo biloba extract/ capsule) and (500 mg Metformin/ capsule) respectively; orally as a single dose for 90 days. Blood samples were taken at z
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