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.
Therapeutic contact lenses TCLs is an approach used to enhance corneal residence time and reduce frequent instillation, which is a problem with eye drops. The problem with CLs is loading of hydrophobic drugs. In this research the CLs were prepared with molecular imprinting MI to enhance the loading of itraconazole, which is used as antifungal drug for fungal keratitis. CLs using different concentration of hydroxyethyl methacrylate HEMA and methacrylic acid MAA were prepared with and without MI using PEGDA (25 μL) and AIBN (37 mg) as crosslinker and initiator respectively. All the prepared CLs were clear and have good folding endurance. MICLs had significantly higher drug loading compared to conventional CLs. The release of i
... Show Moren this work, the effect of gamma rays on blood thinning drugs was studied using the drug (Aspirin), where gamma rays were spread with the drug using a radioactive source (Co60), and 15,000 grams of Aspirin were placed in the device (gamma chamber 900). The drug was subjected to different irradiation doses (5 KGy, 10 KGy, 15 KGy) and the amount of absorption of the drug was observed in the gamma for different doses and the study of x-rays. After confirming the absorption of the drug to radiation, the effect of the drug on blood thinning was calculated using the rat model and compared with the same drug and the same dose but without exposing the drug to radiation and comparing all results with the control group. The way drugs absorbed radiati
... Show MoreThis study aimed to measure the accounting conservatism and the lemited factors which affected on it in the annual financial reports of insurance companies which listed on the Amman Stock Exchange during the period from 2005 to 2016, these factors were represented by firm age, firm debt and firm size.
Using the market value model (MV) To book value ( BV) Beaver and Ryan (2000) The level of the accounting conservatism was measured. The study found that the insurance companies which are listed on the ASE exercise the accounting conservatism when they were preparing financial reports. And when conducting a process of the test of the affected of the factors (The age of the
... Show MoreIn this research, the study effect of irradiation on structural and optical properties of thin film (CdO) by spray pyrolysis method, which deposited on glasses substrates at a thickness of (350±20)nm , The flow rate of solution was 5 ml/min and the substrate temperature was held constant at 400˚C.The investigation of (XRD) indicates that the (CdO) films are polycrystalline and type of cubic. The results of the measuring of each sample from grain size, micro strain, dislocation density and number of crystals the grain size decreasing after irradiation with gamma ray from(27.41, 26.29 ,23.63)nm . The absorbance and transmittance spectra have been recorded in the wavelength range (300-1100) nm in order to study the optical properties.
... Show MoreIn this research, the study effect of irradiation on structural and optical properties of thin film (CdO) by spray pyrolysis method, which deposited on glasses substrates at a thickness of (350±20)nm , The flow rate of solution was 5 ml/min and the substrate temperature was held constant at 400˚C.The investigation of (XRD) indicates that the (CdO) films are polycrystalline and type of cubic. The results of the measuring of each sample from grain size, micro strain, dislocation density and number of crystals the grain size decreasing after irradiation with gamma ray from(27.41, 26.29 ,23.63)nm . The absorbance and transmittance spectra have been recorded in the wavelength range (300-1100) nm in order to study the optical properties. the op
... Show MoreScleral acrylic resin is widely used to synthesize ocular prosthesis. However, the properties of this material change over time, thus requiring the prosthesis to be refabricated. Many studies were conducted to improve these properties by reinforcing this material with nanoparticles. This study aims to evaluate the effect of silver nanoparticle powder on the mechanical properties (transverse flexural strength, impact strength, shear bond strength, surface microhardness, and surface roughness) of scleral acrylic resin used for ocular prostheses. Two concentrations were selected from the pilot study and evaluated for their effects on scleral acrylic resin properties. According to the pilot study, 0.01 and 0.02wt% AgNPs powder improved
... Show MoreA thin film of SnSe were deposited by thermal evaporation technique on 400 ±20 nm thick glass substrates of these films were annealed at different temperatures (100,150,200 ⁰C), The effect of annealing on the characteristics of the nano crystalline SnSe thin films was investigated using XRD, UV-VIS absorption spectroscopy, Atomic Force Microscope (AFM), and Hall effect measurements. The results of X-ray displayed that all the thin films have polycrystalline and orthorhombic structure in nature, while UV-VIS study showed that the SnSe has direct band gap of nano crystalline and it is changed from 60.12 to 94.70 nm with increasing annealing temperature. Hall effect measurements showed that all the films have a positive Hall coeffic
... Show MoreThe aqueous extract of banana fruits peal was tested for its effect on mitosis . The root tips of Allium cepa were used as plant test system and the bone marrow cells of the albino mice Mus musculus were used as mammalians test system in vivo .Root tips of Allium cepa were treated for four hours with five concentrations of the extract (5 , 10 , 20 , 40 ,60 mg / ml.).The Metaphase was arrested in all the treatments , the highest percentage ( 100 % ) was recorded in the first concentration , the last concentration caused stickiness and clumping of the chromosomes. The treatments did not cause significant difference in the mitotic index. The peals extract (5 mg /ml) was compared with the extracts of fruits bulb, leaves and r
... Show MoreThe aqueous extract of banana fruits peal was tested for its effect on mitosis . The root tips of Allium cepa were used as plant test system and the bone marrow cells of the albino mice Mus musculus were used as mammalians test system in vivo .Root tips of Allium cepa were treated for four hours with five concentrations of the extract (5 , 10 , 20 , 40 ,60 mg / ml.).The Metaphase was arrested in all the treatments , the highest percentage ( 100 % ) was recorded in the first concentration , the last concentration caused stickiness and clumping of the chromosomes. The treatments did not cause significant difference in the mitotic index. The peals extract (5 mg /ml) was compared with the extracts of fruits bulb, leaves and roots of
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