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 paper reports an experimental study regarding the influence of vertical oscillations on the natural convection heat transfer from a vertical channel. An experimental set-up was constructed and calibrated; the vertical channel was tested in atmosphere at 25o
C. The channel-to-ambient temperature difference was varied with the power supply to the electrical heater ranging between
15W to 70W divided into five levels. Data sets were measured under different operating condition from a test rig under six vibrating velocities (VVs) levels ranging from (5-30 m/s) in addition to the stationary state. The results show that the maximum heat transfer enhancement factor (E) occurs at Rayleigh number (Ra=2.328×103 ) and vibrational Reynol
Psoriasis is a chronic, inflammatory condition that primarily affects the skin, hair, and joints and is associated with significant humanistic and economic consequences. Psoriasis was induced in mice in this work using an imiquimod 5% cream, an immune response modifier that can cause psoriasis-like skin inflammation when given orally. Paquinimod is prepared as a suspension and has been orally given to mice before imiquimod application. The current study found that paquinimod suspension reduced psoriasis area and severity index, spleen index, skin thickness ,TNF-α,IL-23,IL17 level and gene expression of TN
... Show MoreThe research aimed to test the effect of independent variables career plateaus and workaholism on employees loyalty through the influence of the mediator variable organizational socialization. Descriptive approach with survey style on a sample of managers and executives in the Iraqi Drilling Company in Basra's (123) employees. The most important findings of the research are: the existence of a significant effect of the independent variables career plateaus and workaholism in employees loyalty by having a mediator variable organizational socialization and introduced numerical from recommendations. &nbs
... Show MoreThe effects of short-range correlation on elastic Coulomb (charge) form factors, charge density distributions as well as root mean square charge radii of various nuclei (for instance, 46, 48, 50Ti, 52, 54Cr, 56, 58Fe, and 72, 74, 76Ge nuclei) are examined. The one- and two body terms of the cluster expansion together with the single-particle harmonic oscillator wave functions are utilized. For the purpose of embedding these effects into the formulae of charge density and form factor we employ the correlation function of Jastrow-type. These formulae depend upon the short-range correlation parameter (which instigates from the Jastr
... Show MoreCharacterized Iraq, being one of the oldest countries where oil was discovered in the Middle East since 1927, and possess a vast oil reserves. In addition, the production and marketing of Iraqi oil continued since 1934 and until the present time. Over the past eight decades, the range of economic benefit of the financial Iraq’s oil resources varied according to the applicable forms of investments in the oil sector in Iraq.
This research included a study
... Show MoreThis research theme of the pressures of work , which is one of the important topics in order to recognize the reality of( influencing the pressures of work in the performance of employees in the General Company for Vegetable Oil Industry in Baghdad )through the statement of the existence of the correlation and influence whether or not the statement of the strength of this relationship and its impact in the case of its existence has been provided as part of my Search for variables and their removal in front of the Sub- scientific aspect has been the distribution of the questionnaire on a sample of( 62) people working in the company Mint distributors on several sections where.
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... Show MoreDoxorubicin (DOX) is an efficient antineoplastic agent with a broad antitumor spectrum; however, doxorubicin-associated cardiotoxic adverse effect through oxidative damage and apoptosis limits its clinical application. Cafestol (Caf) is a naturally occurring diterpene in unfiltered coffee with unique antioxidant, antimutagenic, and anti-inflammatory activities by activating the Nrf2 pathway. The present study aimed to investigate the potential chemoprotective effect of cafestol on DOX-induced cardiotoxicity in rats. Wistar albino rats of both sexes were administered cafestol (5 mg/kg/day) for 14 consecutive days by oral gavage alone or with doxorubicin which was injected as a single dose (15 mg/kg intraperitoneally at day 14) to i
... Show MoreNon-thermal or cold plasma create many reactive species and charged particles when brought into contact with plant extracts. The major constituents involve reactive oxygen species, reactive nitrogen species and plasma ultra-violets. These species can be used to synthesize biologically important nanoparticles. The current study addressed the effect of the green method-based preparation approach on the volumetric analysis of Zn nanoparticles. Under different operating conditions, the traditional thermal method and the microwave method as well as the plasma generation in dielectric barrier discharge reactor were adopted as a preparation approach in this study. The results generally show that the type of method used plays an important role in d
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