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.
The electronic properties and Hall effect of thin amorphous Si1-xGex:H films of thickness (350 nm) have been studied such as dc conductivity, activation energy, Hall coefficient under magnetic field (0.257 Tesla) for measuring carrier density of electrons and holes and Hall mobility as a function of germanium content (x = 0–1), deposition temperature (303-503) K and dopant concentration for Al and As in the range (0-3.5)%. The composition of the alloys and films were determined by using energy dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS).
This study showed that dc conductivity of a-Si1-xGex:H thin films is found to increase with increasing Ge content and dopant concentration, whereas conductivity activati
The development taking place on the sports field at the general level and in the game of football at the private level, being the most popular game in the world, has reached very advanced stages. The use of modern aids and technology has contributed greatly to this development from the collective and individual aspects, as the goalkeeper is the most important position in the team, the use of devices gave objective readings about the goalkeeper’s ability in terms of skill and physical aspects, as the importance of the research lies in designing an electronic device to measure the degree of bending of the knee angle because of its great importance in developing the skill of catching and dimensions of the high ball for football goalkeepers.
... Show MoreThe health care industry is witnessing an increasing trend in the use of generic medicines because of their presumed low cost compared with innovator medicines. The aim of this study was to determine and compare the performance of the copy drug Osveral®and its innovator drug deferasirox (Exjade®).
A prospective observational study including 223 patients receiving the branded medicine Exjade®and 101 patients receiving the copy Osveral®was carried out. Data were assessed for a 1-year period and included clinical symptoms, serum ferrit
A new method for construction ion-selective electrode (ISE) by heating reaction of methyl orange with ammonium reineckate using PVC as plasticizer for determination methyl orange and determination Amitriptyline Hydrochloried drug by formation ion-pair on electrode surface . The characteristics of the electrode and it response as following : internal solution 10-4M , pH (2.5-5) ,temperature (20-30) and response time 2 sec. Calibration response for methyl orange over the concentrationrange 10-3 -10-9 M with R=0.9989 , RSD%=0.1052, D.O.L=0.315X10-9 MEre%=(-0.877- -2.76) , Rec%.=(97.230 -101.711) .
Background: Inflammatory bowel disease (IBD) is a collection of chronic, recurrent inflammatory illnesses of the gastrointestinal system, including Crohn's disease (CD). Infliximab is one of the biological medications used to treat CD. Therapeutic drug monitoring has evolved as a treatment in IBD, aiming to optimize benefit while meeting more demanding, objective end criteria. Objective: To determine the achievement of target trough level (TL), develop anti-drug antibodies (ADAs) to infliximab, assess response to therapy, and study TL relations with different variables. Methods: The present study was cross-sectional and conducted from May 2022 to November 2022. It included 40 CD patients allotted into 2 groups: group 1 patients ach
... Show MoreA method is developed for the determination of iron (III) in pharmaceutical preparations by coupling cloud point extraction (CPE) and UV-Vis spectrophotometry. The method is based on the reaction of Fe(III) with excess drug ciprofloxacin (CIPRO) in dilute H2SO4, forming a hydrophobic Fe(III)- CIPRO complex which can be extracted into a non-ionic surfactant Triton X-114, and iron ions are determined spectrophotometrically at absorption maximum of 437 nm. Several variables which impact on the extraction and determination of Fe (III) are optimized in order to maximize the extraction efficiency and improve the sensitivity of the method. The interferences study is also considered to check the accuracy of the procedure. The results hav
... Show MoreAbstract
This research aims to identify the effect of measuring reinforcement (regular - irregular) in gamification upon developing computer skills among secondary education students in the Kingdom of Saudi Arabia. The research experiment was applied on two samples of (68) secondary education students in the Kingdom of Saudi Arabia in the Aurar region. The results revealed there is a significant difference between the experimental group that used (irregular) reinforcement and the control group used (regular) reinforcement in gamification through the post-application of the electronic programming test and through the programming, language skills observing card (Visual Basic Studio).