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.
CdS and CdTe thin films were thermally deposited onto glass substrate. The CdCl2 layer was deposited onto CdS surface. These followed by annealing for different duration times to modify the surface and interface of the junction. The diffraction patterns showed that the intensity of the peaks increased with the CdCl2/annealed treatment, and the grain sizes are increased after CdCl2/annealed treatment
In this research the electrical conductivity and optical measurements were made on the Iron Oxide (Fe2O3) films prepared by chemical spray pyrolysis method as a function of thickness (250, 350, 450, and 550)  20 nm. The measurements of electrical conductivity (σ), activation energies (Ea1, Ea2),and optical constant such as absorption coefficient, refractive index, extinction coefficient and the dielectric constants for the wavelengths in the range (300-900) nm have been investigated on (Fe2O3) thin films as a function of thickness. All films contain two types of transport mechanisms, and the electrical conductivity (σ) increases whereas the activation energy (Ea) would decrease as the films thi
... Show MoreBackground: Ureteral stone can cause obstructive uropathy and subsequent deterioration of renal function. There are four treatment options for ureteral calculi: lithotripsy, ureteroscopy, laparoscopic ureterolithotomy, and open stone surgery. Holmium YAG laser is an excellent intracorporial lithotripter for all kinds of stones. Accordingly, there is steady increase in number of ureteroscopic laser lithotripsy operations in the managmant of Ureteral stone.
Objectives: this study was designed to demonstrate the effect of ureteric stone location on the success rate of ureteroscopic Holmium laser lithotripsy in the management of ureteric stones.
Patients and Methods: Ninety m
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The study aims to investigate the relationship between the gender diversity of board director, the accounting conservatism and firm value in Iraqi firms. The sample was represented by 30 Iraqi firms listed on the Iraqi market over the period 2017. The research was based on the main hypothesis that gender diversity has a positive relationship with conservatism and firm value, that conservatism as an intermediate variable will enhance the positive relationship between gender diversity and firm value. The study reached results that support the research hypotheses. The appointment of females to the board helps improve the provision of conservative accounting information and avoids overstate when reporting earnings. Based on these res
... Show MoreThe cyclophosphamide is commonly used for the treatment of cancer and immunosuppressive diseases in young and old age and can induce oxidative stress in reproductive organs, therefore has adverse effects on sperm quality and quantity. In this study, the effects of a single dose of cyclophosphamide on sperm parameters in adult male mice that treated with 10 mg/kg of this drug on the 11th embryonic day were investigated. Adult female pregnant NMRI mice were divided into 2 groups; the control group received saline and the cyclophosphamide group received cyclophosphamide at a dose of 10 mg / kg on day 11th of gestation (i.p). 60 days after the birth of the infants, male mice were sacrificed and the sperm collected from
... Show MoreThe experiment was conducted under shading (with the aid of Saran) condition on a nursery managed by the Baghdad Mayoralty during the season of 2014-2015 to study the effect of composed sheep manure extract on the growth and leaf nutrients content of tomato seedlings var. Wijdan. The experiment was composed of 6 treatments included the extract of sheep manure by hot (425C)and lmbient(205C) temperature water .The extract was diluted to the half by water and foliar applied to seedlings (multible application) or to the soil . Treatments also included the application of NPK chemical fertilizers as recommended and a control treatment through applying distilled water as foliar .The experiment was designed according to the randomized compl
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