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.
A new Turbidimetric method characterized by simplicity, accuracy and speed for determination of iron(III) in drug samples by continuous flow injection analysis. The method was based on the formation of complex for iron(III) with 8-hydroxyquinoline in presence of ammonium acetate as a medium for the formation of deep green precipitate and this precipitate was determined using homemade Linear Array Ayah-5SX1-T-1D continuous flow injection analyser. The optimum parameters were 2.6 mL.min-1 flow rate using H2O as a carrier, 1.9 mL.min-1 (14 mmol.L-1) ammonium acetate, 2.4 mL.min-1 (14 mmol.L-1) 8-hydroxyquinoline, 60 L sample volume and open valve for the purge of the sample segment. Data treatment shows that linear range 0.1-8.0 mmol.L-1
... Show MoreTumor necrosis factor-alpha (TNF-α) antagonists’ therapy are expensive and has a non-responsive rate between 30% to 40% in rheumatoid arthritis patients. Genetic variation plays a vital role in the responsiveness to this type of therapy.The aim of this study is to investigate if the presence of genetic polymorphism in the TNF-α gene promoter region at locations -376 G/A (rs1800750), -806 C/T (rs4248158), and -1031 T/C (rs1799964) affects rheumatoid arthritis patient's tendency to be a non-responder to etanercept.
Eighty RA patients on etanercept (ETN) for at least six months were recruited from the Rheumatology Unit at Baghdad Teaching Hospital. Based on The European League Against Rheumatism response (EULAR) criteria, patient
... Show MoreCO2 geo-storage efficiency is strongly influenced by the wettability of the CO2-brine-mineral system. With decreasing water-wetness, both, structural and residual trapping capacities are substantially reduced. This constitutes a serious limitation for CO2 storage particularly in oil-wet formations (which are CO2-wet). To overcome this, we treated CO2-wet calcite surfaces with nanofluids (nanoparticles dispersed in base fluid) and found that the systems turned strongly water-wet state, indicating a significant wettability alteration and thus a drastic improvement in storage potential. We thus conclude that CO2 storage capacity can be significantly enhanced by nanofluid priming.
Successfully, theoretical equations were established to study the effect of solvent polarities on the electron current density, fill factor and efficiencies of Tris (8-hydroxy) quinoline aluminum (Alq3)/ ZnO solar cells. Three different solvents studied in this theoretical works, namely 1-propanol, ethanol and acetonitrile. The quantum model of transition energy in donor–acceptor system was used to derive a current formula. After that, it has been used to calculate the fill factor and the efficiency of the solar cell. The calculations indicated that the efficiency of the solar cell is influenced by the polarity of solvents. The best performance was for the solar cell based on acetonitrile as a solvent with electron current density of (5.0
... Show MoreThe present study was conducted to determine histopathological changes caused by chronic effect of Nitrofurantoin(NFT) in The albino mice Testes. The Study included 40 mice were divided on the five groups: the first group taken distilled water and become control group . the remaining group which are exposure with NFT drug in concentration (100-150-200-250) mg / kg, respectively, Doses were given orally for a period (month and two months). The results of histopathological changes included occurrence of congestion in the blood vessel and degeneration of spermatogonia and aggregation of spermatids in the lumen of semineferous tubules and inhibition of spermatogensis process and decrease of sperm inside the lumen
... Show MoreThirty- five vaginal swab samples were obtained from women vagina.All samples
were subjected to conventional morphological and cultural characteristics, isolates
distributed between Lactobacillus acidophillus(23)and Lactobacillus fermentum (12).
Antibacterial activities were done by well diffusion and blank disk method. The
Lactobacillus was used as aprobiotic treatment against bacteriaisolates from vagina
.The isolated bacteria had strong activity against indicator strains.The results showed
that Lactobacillus which was isolated from vagina by well diffusion method was
effective against pathogenic isolates more than the Lactobacillus isolated by blank
disc method , the highs inhibitory effect of Lactobacillus iso
Background: Polymorphisms in the TNF-α gene affect the development and progression of rheumatoid arthritis. Objective: To investigate the associations between (-806 T/C) and (-857 T/C) SNPs with rheumatoid arthritis severity and susceptibility in a sample of Iraqi patients. Methods: A case-control study was conducted in Baghdad, Iraq. Twenty healthy controls and 63 patients confirmed to be newly diagnosed with rheumatoid arthritis were included. Those are divided into two groups (patients and controls), and the patients were further subdivided into severe and mild-moderate groups. Samples from those participants were analyzed for clinical and inflammatory parameter measurements. Genotyping by the Sanger method was performed to stu
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