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.
Background: ?-L-Fucose is a methyl pentose sugar similar to L-galactose except for the loss of alcohol group on carbon number 6. The objective of this study is to evaluate the biochemical and antioxidant effect of intracrevicular injection of fucose into rabbits periodontium, throughout measuring the levels of total protein (TP), total fucose (TF), protein bound fucose PBF) , Malondialdehyde (MDA) , and vitamin C in sera of fucose injected rabbit groups. ) Materials and Methods: The existing study was carried out on 55 male rabbits and were divided randomly into three groups ; first group was injected with 50µl of 150mM fucose solution into gingival sulcus ; second group was injected with 50 µl of normal saline ; while the third group was
... Show MoreThe research aims to find ways to minimize the use of quantities of chemical fertilizers in agriculture in order to get to an environment that is free of contaminants. Magnetized water technology used in the experience of planting seeds of tomatoes Thomson type to obtain a higher efficiency to absorb fertilizer NRK in the protected environment of the period from February to June. Magnetized water system used locally made levels Gaues (4800,2500,1500) concentrations of 50 to 100% for each level and the rate of (4) replicates, and results indicated that the severity of the magnet (4800 Gaues) and a concentration of 50% gave the highest percentage of tomato fruit size and intensity ( 1500 Gaues) and a concentration of 100% did not give any inc
... Show MoreThe Historical effect of Conflict between North and South
he planning process is generally aimed at developing the city and making it meet the needs of different citizens. The green areas constitute one of the basic needs of the city and with the rapid and unusual growth in the size of cities, especially in the third world countries, which is often embodied in capitals. Which was achieved as a result of many reasons, including political, economic and social and even enshrined through some of the decisions that were issued and the city of Baghdad, but a clear example of these cities. The city and the environment are inseparable terms. The city is where people spend their lives and their daily experiences, and the environment is the center in w
... Show MoreOver the course of six decades, Iraq exposed to many events that have affected the Iraqi people from the social, physical and mental aspects. In this study, two groups of people (2369), from Iraq (G1) and the Michigan, United States (U.S) of America (G2) selected to compare the prevalence rate and effects of trauma factors such as mental illness (anxiety, depression and PTS), somatic diseases (heart disease, hypertension, and diabetes), substances abuse (illicit drugs, alcohol and tobacco), and chemicals pollution), and self-rated health among the two groups. The study results reveals a significant different between the two groups in the all indicators for trauma. The study conclude that Iraqi in U.S. (G2) suffer from factors completely dif
... Show MoreThiazoles are heterocyclic nitrogenous compounds, which were given a great attention due to their antibacterial effect, antihypertensive, stimulating glucose absorption (like antibiotics), acts as cytoprotective agent. The present work is conducted to evaluate the degree of antibacterial activity on the growth activity of Escherichia Coli (E.Coli) and Pseudomonas aeruginosa (P. aeruginosa) by incubation with 2-methyl-4-(3,4 dihydroxy phenyl)-Thiazole compound (MDHPT). Optical density (O.B) was measured by turbidmetric method, any increase in O.D would represent the increase in the bacterial growth .The results showed that there was a 75.7 % inhibition when using 190.4 ïg/ml (MDHPT) solution and 64.3% was obtained when using concentr
... Show MoreThe present work aims to study the combustion characteristics related to syngas-diesel dual-fuel engine operates at lambda value of 1.6 operated by five different replacement ratios (RR) of syngas with diesel, which are (10%, 20%, 30 %, 40 % and 50%). ANSYS Workbench (CFD) was used for simulating the combustion of the syngas-diesel dual-fuel engine. The numerical simulations were carried out on the Ricardo-Hydra diesel engine. The simulation results revealed that the diesel engine’s combustion efficiency was enhanced by increasing the diesel replacement with Syngas fuel. The diesel engine’s combustion efficiency The peak in-cylinder temperature was enhanced from 915.9K to 2790.5K
Objective: The present study was aimed to develop a pH-triggered in situ gel for local release of lidocaine hydrochloride (lidocaine HCL) in the buccal cavity to improve the anesthetic effect of this amino amide drug which has very high water solubility. The formulations were introduced to the oral cavity as a spray to improve compliance and for easier administration.Methods: In this work, two grades of carbopol (934 and 940)-based in situ gel spray were designed. The formulations containing lidocaine HCl 5% were prepared by mixing different concentrations of carbopol with xanthan gum. Eight formulations were investigated and evaluated for gelation capacity, spray angle, volume of solution delivered per each actuation, rheological p
... Show MoreThe effect of the aqueous extract of fenugreek seeds (Trigonella Foenum Graecum L.), Rhodium complex (?) with formula [RhL2CLH2O].1 1/2 ETOH and palladium (?) [pdl2].2ETOH,where L=2-hydroxy phenyl piperonalidine was studied on two cancer cell lines. The first cell line was intestine cancer of female albino mice (L20B), the second one was Rhabdomysarcomas (RD)cell line in human. The activity of the new complexes and the aqueous extract was compared to the well-known anticancer drug (cis-platin) by utilizing the in vitro system. The cell lines were treated with four concentrations of cis-platin 31.25,62.5,125 and 250 ?g/ml for 72 hour exposure time. The same concentrations were used with extract and the new complexes. This study showed that t
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