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.
A review of comparative analytical methods for β-lactam antibiotics and heavy metals in pharmaceutical products and human biological matrices
This work investigates the use of hydrogenated amorphous silicon (a-Si:H) as a high-refractive-index material for quarter-wave distributed Bragg reflectors (DBRs) in photonic applications. In comparison to Si3N4, a-Si:H enables enhanced optical confinement, broader omnidirectional reflectance, and improved figures of merit, including higher Purcell and quality factors, while minimizing mirror complexity. To evaluate the practical impact of these advantages, a theoretical comparison is conducted between Fabry–Pérot cavities based on a-Si:H/SiO2 and Si3N4/SiO2 DBRs, examining resonance shifts as functions of cavity refractive index (1.0–3.0) and temperature (0–250 °C). The numerical results indicate that Si3N4/SiO2 planar Bragg caviti
... Show MoreBackground: This study was conducted to assess the effect of sonic activation and bulk placement of resin composite in comparison to horizontal incremental placement on the fracture resistance of weakened premolar teeth. Materials and method: Sixty sound human single-rooted maxillary premolars extracted for orthodontic purposes were used in this study. Teeth were divided into six groups of ten teeth each: Group 1 (sound unprepared teeth as a control group), Group 2 (teeth prepared with MOD cavity and left unrestored), Group 3 (restored with SonicFill™ composite), Group 4 (restored with Quixfil™ composite), Group 5 (restored with Tertic EvoCeram® Bulk Fill composite) and Group 6 (restored with Universal Tetric EvoCeram® co
... Show MoreBackground: Pemphigus vulgaris (PV) is an autoimmune vesiculobullous mucocutaneous disease with life-threatening consequences. Rituximab (RTX) has recently emerged as an effective treatment for PV. Objectives: This study aims to determine changes in neutrophil and platelet counts for PV patients treated with RTX or corticosteroids combined with Imuran (azathioprine). Materials and Methods: The present cross-sectional study was conducted in the Department of Dermatology at Baghdad Teaching Hospital, Baghdad, Iraq. Thirty PV patients received two types of treatment: 15 patients were administered RTX and 15 patients took corticosteroids with Imuran (azathioprine). Neutrophil and platelet counts were detected at the hospital laboratory. Results
... Show MoreAchieving an accurate and optimal rate of penetration (ROP) is critical for a cost-effective and safe drilling operation. While different techniques have been used to achieve this goal, each approach has limitations, prompting researchers to seek solutions. This study’s objective is to conduct the strategy of combining the Bourgoyne and Young (BYM) ROP equations with Bagging Tree regression in a southern Iraqi field. Although BYM equations are commonly used and widespread to estimate drilling rates, they need more specific drilling parameters to capture different ROP complexities. The Bagging Tree algorithm, a random forest variant, addresses these limitations by blending domain kno
Background: Beta thalassemia major is an inherited disorder that may affect general and oral health.The purpose of this study was toassess the severity of dental caries in relation to oral cleanliness, mutans streptococciamong a group of boys with beta thalassemia majorin comparison with a control group. Materials and Methods: The study involved 30 boys with BTM aged 10-12 years compared to 30 healthy boys with the same age group. d1-4mfs and D1-4 MFS indices were applied (Muhlemann, 1976), the viable counts of mutans streptococci in stimulated saliva were also determined. Results: The entire thalassemic group was caries-active. For both dentitions, a higher dmfs/DMFS values were recorded for study compared to control group, difference was
... Show MoreAdhesion (type 1 fimbriae) and host defense avoidance mechanisms (capsule or lipopolysaccharide) have been shown to be prevalent in Escherichia coli isolates associated with urinary tract infections. In this work, 50 uropathogenic Escherichia coli (UPEC) isolated from children with urinary tract infections were genotypically characterized by polymerase chain reaction (PCR) assay. We used two genes; fimH and kpsMTII, both of them previously identified in uropathogenic E.coli (UPEC) isolates. The PCR assay results identified fimH (90.0)% and kpsMTII (72.0)% isolates. In the present study, was also demonstrated that these genes may be included in both or one of them within a single isolate.