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.
We report herein an innovative approach to prostate tumor therapy using tumor specific radioactive gold nanoparticles (198Au) functionalized with Mangiferin (MGF). Production and full characterization of MGF-198AuNPs are described. In vivo therapeutic efficacy of MGF-198AuNPs, through intratumoral delivery, in SCID mice bearing prostate tumor xenografts are described. Singular doses of the nano-radiopharmaceutical (MGF-198AuNPs) resulted in over 85% reduction of tumor volume as compared to untreated control groups. The excellent anti-tumor efficacy of MGF-198AuNPs are attributed to the retention of over 90% of the injected dose within tumors for long periods of time. The retention of MGF-198AuNPs is also rationalized in terms of the higher
... Show MoreIn this work, a comparative analysis for the behavior and pattern of the variations of the IF2 and T Ionospheric indices was conducted for the minimum and maximum years of solar cycles 23 and 24. Also, the correlative relationship between the two ionospheric indices was examined for the seasonal periods spanning from August 1996 to November 2008 for solar cycle 23 and from December 2008 to November 2019 for solar cycle 24. Statistical calculations were performed to compare predicted values with observed values for the selected indices during the tested timeframes. The study's findings revealed that the behavior of the examined indices exhibited almost similar variations throughout the studied timeframe. The seasonal variations were
... Show MoreThe world is keeping pace with evolution in all its fields as a result of scientists' pursuit of continuous scientific and technological development. This evolution included the sports field, which had a large space in the aspect of development and for all disciplines, Therefore, it's reflected today in what we see of records and advanced achievements in sporting events and activities. The development in the field of sports was the result of scientific research (Hussein and Jawad., 2022), where the interest in the training process has become one of the most important pillars of the development of achievement (Neamah and Altay., 2020). The shooting sport has also witnessed a remarkable development due to the diversity and development of its
... Show More15 local isolates of Pseudomonas were obtained from 35 samples from several sources such as soil, water and some high-fat foods. The ability of isolates to produce lipase was measured by the size of the clarification zone formed around the colonies on the lipase production medium and by measuring the enzymatic activity and specific enzymatic activity, the isolate M3 was found to be the most efficient for production of the enzyme, This isolate was identified by microscopic, morphological, some biochemical tests and genetic diagnosis of 16S gene sequences by using the (PCR) technique, and then comparing the results obtained with the National Center for Biotechnology Inform
... Show MoreThis research studying the phenomenon of Doppler (frequency Doppler) as a method through which the direction and speed of the blood cells flows in blood vessels wear measured. This Doppler frequency is relied upon in medicine for measuring the speed of blood flow, because the blood flow is an important concept from the concepts of medicine. It represents the function and efficient of the heart and blood vessels in the body so any defect in this function will appear as a change in the speed of blood flow from the normal value assumed. As this speed changes alot in cases of disease and morbidity of the heart, so in order to identify the effect of changing the Doppler frequency on the speed of blood flow and the relationship of
... Show MoreThe crystalline zeolite, namely faujasite type Y with SiO2/Al2O3 mole ratio of 5 was used as raw material for preparation of isomerization catalysts. A 0.5 wt % Pt/HY-zeolite catalyst was prepared by impregnation of the decationized HY-zeolite with chloroplatinic acid. The dectionized HY-zeolite was treated with HCl, HNO3 and HI promoters using different normalities and with different concentrations of Sn, Ni and Ti promoters by impregnation method to obtain acidic and metallic promoters' catalysts, respectively. A 0.5 wt% of Pt was added to above catalysts using impregnation method. Isomerization of n-hexane was carried out at different prepared catalysts. The isomerization temperature varied from 250–325° C over weight hourly space
... Show MoreTwilight is that light appear on the horizon before sunrise and after sunset, Astronomically it is known that sunrise and sunset are effected by high above sea level, but the effect of high above sea level on the time of astronomical twilight still not decided and controversy among astronomers, in This research we studies the effect of high above sea level on the time of astronomical twilight, through adding the equation correct high above sea level to equation computation of twilight and then calculate of changing in the time of twilight for different highest (0-10000) meters above sea level , and the ratio of increase for time with high between (15.45-20.5) minutes. It was found that there was an increase in the time of the twilight along
... Show MoreThe purpose of this paper is to depict the effect of adding a hydraulic accumulator to a hydraulic system. The experimental work includes using measuring devices with interface to measure the pressure and the vibration of the system directly by computer so as to show the effect of accumulator graphically for real conditions, also the effects of hydraulic accumulator for different applications
have been tested. A simulation analysis of the hydraulic control system using MATLAB.R2010b to study was made to study the stability of the system depending on the transfer function, to estimate the effect of adding the accumulator on stability of the system. A physical simulation test was made for the hydraulic system using MATLAB to show the ef