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.
Flame thermal spray technique has been used to produce a cermets composite coating based on powders of ceramic oxides (
AhOJ) reinforced by mineral powders as bonding material ( Ni - AI ) at different rates on Inconel substrates , after preparing it by grit blasting.
After completing the best parameters of coating such as distance of spraying , surface roughness and angle of spraying , the tests of porosity , hardness , microstructure and thermal cycling have been made.
The experimental results show that all properties of coating were effected after heat treatment. The best value of heat treatmen t is at (I 000°C) for (l.Shr) in which the &
... Show MoreEmploying phase-change materials (PCM) is considered a very efficient and cost-effective option for addressing the mismatch between the energy supply and the demand. The high storage density, little temperature degradation, and ease of material processing register the PCM as a key candidate for the thermal energy storage system. However, the sluggish response rates during their melting and solidification processes limit their applications and consequently require the inclusion of heat transfer enhancers. This research aims to investigate the potential enhancement of circular fins on intensifying the PCM thermal response in a vertical triple-tube casing. Fin arrays of non-uniform dimensions and distinct distribution patterns were des
... Show Moreact : A soluble cytoplasmic antigen (Brucellin) was prepared from Brucella melitensis Rev1 and used to diagnose brucellosis in experimentally infected mice with virulent strains of Brucella melitensis and Brucella abortus two weeks after infection. The best result was obtained with the third peak of the four peaks. All four peaks were used as antigen for skin test in a group of mice two weeks after vaccinated with S19 vaccine and the best result was obtained with third peak. All four peaks were also used as antigen for skin test in a group of mice previously vaccinated with Listeria monocytogenes live attenuated vaccine. All four fractions of the extracted brucellin antigens exhibited a negative skin test result in Listeria monocytogenes ex
... Show MoreThe problem of the high peak to average ratio (PAPR) in OFDM signals is investigated with a brief presentation of the various methods used to reduce the PAPR with special attention to the clipping method. An alternative approach of clipping is presented, where the clipping is performed right after the IFFT stage unlike the conventional clipping that is performed in the power amplifier stage, which causes undesirable out of signal band spectral growth. In the proposed method, there is clipping of samples not clipping of wave, therefore, the spectral distortion is avoided. Coding is required to correct the errors introduced by the clipping and the overall system is tested for two types of modulations, the QPSK as a constant amplitude modul
... Show MoreThe role of specific amino acids namely cysteine, methionine, threonine and asparagine in the protection provided by vamin solution against B-lactam inhibition to E. coli was evaluated in vitro In minimal medium, cells were treated with 32 ug/ml of penicillin G, carbenciLlin, hostacillin, cloxacillin and cephalotin in the presence of specific amino acid supplementation. Deletion of specific amino acids from the media abolished the protection provided by vamin. Threonine was essential for the protection of cells against all tested antibiotics, while cysteine was essential for protection against carbencillin and sephalotin. Deletion of methionine or asparagine abolished the protection against carbencillin and to a less extent cephalotin.
... Show MoreABSTRACT The role of specific amino acids namely cysteine, methionine, threonine and asparagine in the protection provided by vamin solution against B-lactam inhibition to E. coli was evaluated in vitro. In minimal medium, Cells were treated with 32 ug/ml of penicillin G, carbencillin, hostacillin, cloxacillin and cephalotin in the presence of specific amino acid supplementations. Deletion of specific amino acids from the media abolished the protection provided by vamin. Threonine was essential for the protection of cells against all tested antibiotics, while cysteine was essential for protection against carbencillin and cephalotin Deletion of methionine or asparagine abolished the protec- tion against carbencillin and to a less extent ce
... Show MoreBackground: The effect of garlic extracton fungal
growth and keratinolytic activity was studied in
Trichophytonmentagrophytes as one of the major
etiologic agents of human and animal dermatophytosis
in Baghdad and other parts of the World.
Objective: To investigated an alternative
antidermatophyte with minimum side effects which is
plant based and biodegradable natural product
Methods: Culture conditions for 30 isolates of T.
mentagrophytes isolated from human dermatophytosis
from both sexes with ages of 5-63 years in Central
Medical city for the period July 2009 to October 2009
were cultured on specific solid medium.
Results: The aqueous extract of garlic at various
concentrations inhibited the
Background: Diabetes is a metabolic disorder characterized by chronic hyperglycemia due to an inability to produce insulin. Uncontrolled or poorly controlled diabetes is clinically associated with increased susceptibility to delay healing. Many recent researches have shown that stem cell therapy can be the best choice for treatment of this disease. The aims of this research were investigating regeneration of pancreatic beta cells of diabetic induced rabbits after stem cell transplantation. Materials and Methods: 64 rabbits weighting an average of (2.5 - 3 kg) were used in this experimental study, and divided into 4 groups as follows; group A ( contains 16 healthy rabbits regarded as control group ) , Group B ( contains 16 diabetic rabbits
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