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.
The integration of nanomaterials in asphalt modification has emerged as a promising approach to enhance the performance of asphalt pavements, particularly under high-temperature conditions. Nanomaterials, due to their unique properties such as high surface area, exceptional mechanical strength, and thermal stability, offer significant improvements in the rheological properties, durability, and resistance to deformation of asphalt binders. This research reviewed the application of various nanomaterials, including nano silica, nano alumina, nano titanium, nano zinc, and carbon nanotubes in asphalt modification. The incorporation of these nanomaterials into asphalt mixtures has shown potential to increase the stiffness and high-tempera
... Show MoreIn the present study, silver nanoparticles (AgNPs) were prepared using an eco-friendly method synthesized in a single step biosynthetic using leaves aqueous extract of Piper nigrum, Ziziphus spina-christi, and Eucalyptus globulus act as a reducing and capping agents, as a function of volume ratio of aqueous extract(100ppm) to AgNO3 (0.001M), (1: 10, 2: 10, 3: 10). The nanoparticles were characterized using UV-Visible spectra, X-ray diffraction (XRD). The prepared AgNPs showed surface Plasmon resonance centered at 443, 440, and 441 nm for sample prepared using extract Piper nigrum, Ziziphus spina-christi, and Eucalyptus respectively. The XRD pattern showed that the strong intense peaks
Background: Fetal macrosomia is usually distressing to obstetricians and neonatologists. In the current study, involved mothers had poor social and medical circumstances, as they were migrated forcefully within the country borders due to war, from their original homeland to safer camps which had miserable situations. Objectives: To study rate, risk factors, and complications of macrosomia in people with low socio-economic living conditions and missed medical follow up. Methods: All internally displaced pregnant women who gave birth to neonates weighed ≥4000 g were involved in the study. All required history, examination, care, and investigations were practiced by the attending obstetrician and neonatologist. Cases of normal birth weight n
... Show MoreThis effort is related to describe and assess the performance of the Iraqi cement sample planned for oil well-cementing jobs in Iraq. In this paper, major cementing properties which are thickening time, compressive strength, and free water in addition to the rheological properties and filtration of cement slurry underneath definite circumstances are experimentally tested. The consequences point to that the Iraqi cement after special additives encounter the requests of the API standards and can consequently is used in cementing jobs for oil wells. At this research, there is a comparative investigation established on experimental work on the effectiveness of some additives that considered as waste materials which are silica fume, bauxite,
... Show MoreKE Sharquie, AA Noaimi, MN Almallah, Journal of Cosmetics, Dermatological Sciences and Applications, 2014 - Cited by 2
In the present study, five derivatives have been designed to be synthesized as possible mutual prodrugs for 5-Fluorouracil (5-FU) and non steroidal anti-inflammatory drugs (NSAIDs) to selectively deliver the drugs into the cancer cells. The synthesis of the target compounds were accomplished following multistep reaction procedures, the chemical reaction followed up and the purity of the products were checked by TLC. The structure of the final compounds and their intermediates were confirmed by their melting points, infrared spectroscopy and elemental microanalysis, the hydrolysis of compound III was studied using HPLC technique. According to the results mentioned above, compounds (I−V) can be good candidates as possible mutual prod
... Show MoreThis search include the synthesis of some new 1,3-oxazepine derivatives have been prepared, starting from reaction of L-ascorbic acid with dry acetone in presence of dry hydrogen chloride afforded the acetal (I). Treatment of the latter with p-nitrobenzoyl chloride in dry pyridine yielded the ester (II) which was dissolved in (65%) acetic acid in absolute ethanol yielded the glycol (III). The reaction of the glycol (III) with sodium periodate in distilled water at room temperature produced the aldehyde (IV). The compound (V) [2-amino-5-mercapato-1,3,4-thiadiazole] was prepared through the reaction of thiosemicarbazide with carbon disulphide (CS2) in entity of anhydrous (Na2CO3) in (abs. ethanol ). Compound (VI) [2-(5-mercapto-1,3,4-thiadiaz
... Show MoreConcurrently with the technological development that the world is witnessing the crime of money laundering to evolve faster and with multiple methods and its economic, political and social impacts raised increasingly. And for phenomenon dangerous the international community in recent years is keen to be considered combating money laundering as a general indication whereby verification of the international response the stats and its banks and financial institutions with international requirements mandated in this aspect, so the increasing interest the governments of countries in the laws and procedures that contribute to the reduction of the phenomenon of money laundering and avoid legislation economy and the banking and financial sectors
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