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.
This research included the study of different factors that may effect on gatifloxacin stability (anew quinolone synthetic antibacterial agent) in its aqueous solution in order to develop and optimize the best delivary of the drug to the eye (as eye drop) with maximum local concentration and minimum systemic absorption and toxicity.Different formulas of gatifloxacin solution for ophthalmic use (0.3%)w/v were prepared in citrate, acetate,citrate/phosphate and phosphate buffers,their tonicity adjusted with suitable quantity of sodium chloride.The effect of different factors that might affectthe stability of gatifloxacin in its prepared ophthalmic solution was studied and determined spectrophotometrically at 287 nm. The results showed t
... Show MoreAbstract : This research is a field study of international cities that hosted various events of which (Sports, Exhibitions, Scientific, Cultural) and other events, these positive impacts on the city driven by such hosts were identified. The research goal was to support hosting events to improve the hostess city and to draw future plans for further developments and to invest event’s hosting to strengthen the city’s value according to a strategic vision that looks for the future the most important conclusions are Entering events hosting is a part of urban development strategies and The most important recommendations are coordination between hosting event activities and its facilities with the infrastructure structure of the host city, its
... Show MoreIn this communication, introduce the split Mersenne and Mersenne-Lucas hybrid quaternions, also obtaining generating functions and Binet formulas for these hybrid quaternions and investigating some properties among them.
الخلاصة Bahraini Parliamentary Elections and their Impact on the Popular Uprising) Bahrain has a distinguished constitutional and parliamentary experience, which distinct it from the other Gulf Cooperation Council (GCC) countries. Its experience in this area is the second after the experience of Kuwait to establish a system of government based on modern constitutional principles. As the government presented the Constitution to the Constituent Assembly elected by people and approved in 09/06/1973. After that, it witnessed the birth of the first parliament elected by the people in 1973, but the experiment did not last long and the parliament dissolved by Prince, and didn’t determine the period of the return of the working with the
... Show MoreThis research test the relationship and the effect of an explanatory variable transparency in the organizational reputation responder variable by senior management in the departments of the Ministry of Housing and Construction centrally funded, As well as come out among other recommendations contribute to the achievement of organizational reputation of the organizations surveyed. Given the importance of the research topic for the public sector and the community and the environment in which they operate researcher designed questionnaire containing (30) items, and collected data from (92) respondents, representing the research community (eight establishments) exclusively and comprehensively, relying descriptive analytic
... Show MoreTo evaluate the Interaction of Mn(II), Fe(II), Co(II), Ni(II),Cu(II), Zn(II) And Cd(II) Mixed- Ligand Complexes of cephalexin mono hydrate (antibiotics) And Furan-2-Carboxylic Acid To The Different DNA Sources. All the metal complexes were observed to cleave the DNA. A difference in the bands of complexes .The cleavage efficiency of the complexes compared with that of the control is due to their efficient DNA-binding ability and the other factors like solubility and bond length between the metal and ligand may also increase the DNA-binding ability. The ligands (Cephalexin mono hydrate (antibiotics) and Furan-2- Carboxylic acid and there newly synthesized metal complexes shows good antimicrobial activities and Binding DNA , thus, can be used
... Show MoreThe objective of this study was to investigate the drought stress and plant density possibility on water productivity and grain yield of maize (Zea mays L.) (Planting Baghdad 3 synthetic varieties), Field experiment was conducted at Abu Ghraib Research Station (Baghdad) during spring and Autumn seasons of 2016 using a randomized complete block design arranged in split plot with three replications. Three irrigation treatment included: irrigation after depletion 50% of available water (T1), irrigation after depletion 75% of available water (T2) and irrigation after depletion 90% of available water (T3) in the main plots and three plant density which were: 1 seeds hill-1 (D1) giving a uniform plant density of 66666 plants ha-1 , 2 seeds hill1
... Show MoreLead acetate as one of the environmental pollutants can threats the life of living creatures in many ways, it has a long half-life, accumulates mainly in the soft tissue and leads to adverse effects in these tissues. An experiment was conducted to study the effect of oral feeding of lead acetate on histological features of liver, kidney, testis and muscle of albino mice. Mice were treated with 0.05 mg/100 ml lead acetate (LA) for 10 days (group A) and for and for 20 days (group B) and for 30 days (group C). The histological section of liver of mice group A characterized by slightly blurred trabecular structure with foci of hepatitis which increased with cytoplasmic vacules in group B but in group C liver reveal necrosis, heamorrhage,
... Show MoreThe cytotoxic effect of different concentrations of Crude extracts of Bidens tripartita , Panex ginseng , Ceylon cinnamon and Citrullus colocynthis on mice mammary adenocarcinoma cell line were studied . The concentration used were 125 , 250, 500, 1000 Microgram/militer . The exracts were prepared by using hot water method . The preliminary chemical tests revealed acidic pH of all extracts. The time of exposure used were 24, 48 and 72 hrs.The results showed a clear toxic effect of all extracts depending on the time of exposure and the dose . The Ceylon cinnamon had the highest effect on adenocarcinoma 87.33% , followed by Bidens tripartita 86.79%, Citrullus colocynthis 74.39% and the lowes
... Show MoreThe study showed that all extracts (aqueous, ethanolic and acetonic) of the leaves of Eucalyptus and Myrtus plants had a inhibitory effect on the growth of all types of yeasts studied, acetone extract recorded the highest inhibition of yeastat 100ppm concentration,The inhibition was 35mm, 34mm, 24mm and 20mm for Candida parapsilosis, Candida glabrata, Candida tropicalis and Candida albicans respectively, The experiments above showed the least significant differences at 0.05 level.The results ofE. Cammldulensis ethanolic tincture analysis has shown the presence of 44 biologically active substances. The main Eucalyptus leaves component was: 2-Bicyclo (2-2.1) heptanol (12.37%), Ledol (8.23%),1,2,4- Benzenetriol (8.45%) and that contain spathul
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