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.
ABSTRACT Background: According to Branemark’s protocol, the waiting period between tooth extraction and implant placement is 6–8 months; this is the late placement technique. Achieving and maintaining implant stability are prerequisites for a dental implant to be successful. Resonance Frequency Analysis (RFA) is a noninvasive diagnostic method that measures implant stability. The aim of this study was to investigate the influence of treatment protocol and implant dimensions on primary implant stability utilizing RFA. Materials and methods: This study included 63 Iraqi patients (37 male, 26 female; ranging 22-66 years). According to treatment protocol, the sample was divided into 2 groups; A (delayed) & B (immediate). Dental im
... Show MoreThe present study designed to determine the ethanolic extract of Cyperus rotundus on Liver in Albino Male Mice . In the present study 18 Male mice were used they divided into six groups ( 1st group consedered control group , 2nd group injected by 250 mg/ml from extract , 3th group injected by 300 mg/ml from extract , 4th group injected by 350 mg/ml from extract , 5th group injected by 400 mg/ml from extract and the 6th group injected by 450 mg/ml from extract ) . the expermint lasted for two days and the doses gived by intraperitonial injection . showed from the study results that ethanolic extract for Cyperus rotundus have negative effect on Liver tissue in 250 , 300 , 350 mg/ml concentrations when comparsion with control group . the re
... Show MoreIn the present work, the focusing was on the study of the x-ray diffraction, dielectric constant, loses dielectric coefficient, tangent angle, alter- natively conductivity and morphology of PET/BaTio3. The PET/BaTio3 composite was prepared for polyethylene terephthalate PET polymer composite containing 0, 10, 20, 30, 40, 50, and 60 wt. % from Barium titanate BaTi03 powder. The composite of two materials leads to form mixing solution and hot-pressing method. The effect of BaTio3 on the structure and dielectric properties with morphology was studied on PET matrix polymer using XRD, LCR meter and SEM.
due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeuti
... Show MoreChlorine disinfection is a globally used method to ensure the safety of drinking water. However, it has not always been successful against viruses and, therefore, it is important to find new methods to disinfect water. Seventeen different coliphages were isolated from the treated municipal wastewater. These coliphages and MS2 were treated with different dosages of chlorine in drinking water, and a combined chlorine/ultraviolet irradiation treatment for the chlorine-resistant coliphages. Chlorine disinfection with 0.3–0.5 mg/L total chlorine (free Cl-dosage 0.12–0.21 mg/L) for 10 min achieved 2.5–5.7 Log10-reductions for 11 sensitive coliphages. The six most resistant coliphages showed no reduction with these chlorine concentra
... Show MoreAbstract
Knowing the amount of residual stresses and find technological solutions to minimize and control them during the production operation are an important task because great levels of deformation which occurs in single point incremental forming (SPIF), this induce highly non-uniform residual stresses. In this papera propose of a method for multilayer single point incremental forming with change in thickness of the top plate (0.5, 0.7, 0.9) mm and lubrication or material between two plates(polymer, grease, grease with graphite, mos2) to knowing an effect of this method and parameters on residual stresses for the bottom plates. Also compare these results for the
... Show MoreThe aim of the research is to demonstrate the extent of the impact of resource consumption accounting technicality as an administrative technique that is compatible with the rapid developments and changes in the external environment, with the information it provides and scientific foundations in the allocation of indirect costs, and the identification and measurement of idle energy and its costs in a way that contributes to the rationalization of pricing decisions in economic units. In light of the intense competition and the multiplicity of alternatives, and to achieve this goal, a random sample was chosen.