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: Complete seal of the root canal system following its chemo-mechanical debridement plays a pivotal role for achieving successful endodontic treatment. This can be established by reducing the gaps between the core filling material and root canal wall. Aim: To assess and compare the dislocation resistance of root canals obturated with GuttaFusion® and TotalFill BC sealer versus single cone obturation technique and TotalFill BC sealer after instrumentation of the canals with WaveOne, ProTaper Next and ProTaper Universal system. Material and Method: Sixty extracted human permanent mandibular premolars were conducted in the current study. The teeth were decorated and left the root with 15mm length; the roots were divided randoml
... Show MoreBackground: Thermocycling simulates the temperature dynamics in the oral environment. This in vitro study done to measure and compare the effect of thermocycling on the shear bond strength of stainless steel and sapphire brackets bonded to human enamel teeth using light cured orthodontic adhesive and debonded at various time, and to measure adhesive remnant index after debonding. Materials and Methods: one-hundred-twenty extracted upper first premolars for orthodontic reason were used in this study; depending on weather thermocycled or not, the sample was divided into two main groups, then within each group 30 teeth were used for stainless-steel brackets (Bionic®) and for sapphire brackets (Pure®). Both groups were subdivided into three
... Show MoreCadmium oxide (CdO) thin films were deposited using the sequencing ion layer adsorption and reaction (SILAR) method. In this study, the effect of the pH value of an aqueous solution of cadmium acetate at a concentration of 0.2 mol of the cadmium oxide film was determined. The solution source for the cadmium oxide film was cadmium ions and an aqueous ammonia solution. The CdO films were deposited on glass substrates at a temperature of 90 ℃. The cadmium oxide film thickness was determined by the weight difference method at pH values (7.2, 8.2). X-ray diffraction (XRD) and scanning electron microscopy (SEM) showed that the size of the crystals increased with the increase in the solution (pH). While the UV-visible spectra of the fil
... Show MoreThe studies on unbonded post-tensioned concrete members strengthened with Carbon Fiber Reinforced Polymers (CFRPs) are limited and the effect of strengthening on the strain of unbonded pre-stressed steel is not well characterized. Estimating the flexural capacity of unbound post-tensioned members using the design methodology specified in the design guidelines for FRP strengthening techniques of bonded post-tensioned members does not provide a reliable evaluation. This study investigates the behavior of unbonded post-tensioned concrete members with partial strand damage (14.3% and 28.6% damage) and strengthened with CFRP laminates using a near-surface mounted technique with and without U-wrap anchorages. The experimental results show
... Show MoreTwenty five samples out of sixty wound swabs taken from burn patients were identified as P. aeruginosabacteria by conventional methods. Antibiotics susceptibility tests were performed against thirteen antibiotics. P. aeruginosa samples were treated with 0.5 mg/ml of Safranin O solution then irradiated with 532nm Q-switched Nd:YAG laser at four energy densities (0.324, 0.704, 1.380, and 1.831 J/cm2) for different times of 5, 8 and 11 minutes with 5Hz repetition rate. The viability, susceptibility to antibiotic and production of pyocyanin were determined before and after irradiation. The results showed that the number of CFU/ml of P. aeruginosa decreased with increasing the dose of irradiation. Complete killing of cells was observed at 1.8
... Show MoreThis study aimed to identify the degree of frustration and guilt among addicts who hurt themselves with drug, and to know the addicts perspective who are in treatment clinics and rehabilitation centers in Palestine, in order to achieve this goal aDeterminationThe study population has been identified , this study population consisted of ' (82) addict, the researcher used the descriptive analytical method which is appropriate for this study, so the researcher questioned the addicts who are in treatment clinics and rehabilitation centers in Palestine and analyze their responses in light of some of the variables.
The study results showed that drug addicts who ar
... Show Morethis research seeks to shed light on the study of the impact of Putinism on the Russian-Ukrainian war that broke out in early 2022, by studying the contents of the speeches of Russian President Vladimir Putin before the start of the war. This research uses the structural approach in analyzing the components of the Russian political regime. The research tools used in this research include case studies, content analysis of Russian speeches, and personal meetings of researchers and specialists in Russian affairs. It sums up a number of important conclusions, most notably are : 1) Putinism is a totalitarian regime that includes the political doctrine during the era of Russian President Vladimir Putin. 2) Duginism represents the totality of t
... Show MoreThe contribution rate of tax revenues in the federal budget is very small compared to the rate of contribution of oil revenues and this leads to negative repercussions on the Iraqi economy and the budget becomes a prisoner of high and low oil prices, and this is a problem that needs to be studied to know the extent of the impact of economic and political decisions on the size of tax revenue and The research goal is determined in studying the effect of amending the Unified Law No (26) of 2019 on the size of annual tax revenues . &
... Show More