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.
In this paper, the fill factor of the N749/TiO2 solar cell is studied and calculated using the analysis method at standard conditions; i.e., T=300k and 100 mW/cm2 irradiation.. The current density was derived and calculated using the donor-acceptor model according to the quantum transfer theory in DSSC solar cells. We estimate the influence parameters in DSSC that's an equivalent circuit to the I-V curves for three solvents. The fill factor parameters of the N749/TiO2 device are found to be 0.137,0.146 and 0.127 with Butanol, Ethanol and Acetonitrile for carrier concentration . 1018 1/cm3 respectively. The photovoltaic characteristics ISc , Vco<
... Show MoreIn line with the advancement of hardware technology and increasing consumer demands for new functionalities and innovations, software applications grew tremendously in term of size over the last decade. This sudden increase in size has a profound impact as far as testing is concerned. Here, more and more unwanted interactions among software systems components, hardware, and operating system are to be expected, rendering increased possibility of faults. To address this issue, many useful interaction-based testing techniques (termed t-way strategies) have been developed in the literature. As an effort to promote awareness and encourage its usage, this chapter surveys the current state-of-the-art and reviews the state-of-practices in t
... Show MoreIn line with the advancement of hardware technology and increasing consumer demands for new functionalities and innovations, software applications grew tremendously in term of size over the last decade. This sudden increase in size has a profound impact as far as testing is concerned. Here, more and more unwanted interactions among software systems components, hardware, and operating system are to be expected, rendering increased possibility of faults. To address this issue, many useful interaction-based testing techniques (termed t-way strategies) have been developed in the literature. As an effort to promote awareness and encourage its usage, this chapter surveys the current state-of-the-art and reviews the state-of-practices in t
... Show MoreThroughout this paper, three concepts are introduced namely stable semisimple modules, stable t-semisimple modules and strongly stable t-semisimple. Many features co-related with these concepts are presented. Also many connections between these concepts are given. Moreover several relationships between these classes of modules and other co-related classes and other related concepts are introduced.
Thirty six bacteria were isolated from various sourcesc (soil, starch, cooked rice and other foods) and subjected to a series of primary screening tests to obtain the optimal isolation to production of amylase. The volume of producing zone by logal indicator for (Seven) isolates of the secondary screening by measuring the enzymatic activity and specific enzymatic activity. The isolate A4 was found to be the most efficient for production of amylase. Then this isolate was diagnosed through microscopic, vitek 2 system technique. in addition by gentic diagnesis through gene 16s of the genes nitrogen bases by use the polymerase chain reaction (PCR) which reached 1256 bases. In comparison to the available information at the National Center for
... Show MoreInhibition of T cell derived cytokine production could help suppress osteoclast differentiation in inflammatory skeletal disorders. Bisphosphonates are typically prescribed to prevent inflammatory bone loss but are not tolerated by all patients and are associated with an increased risk of osteonecrosis of the jaw. In light of this other anti-resorptives such as phytoestrogens are being considered. However the effect of phytoestrogens on T cell-induced osteoclast formation is unclear. The effect of genistein and coumestrol on activated T cell-induced osteoclastogenesis and cytokine production was therefore examined. Concentrations of genistein and coumestrol (10−7 M) previously shown to directly inhibit osteoclast formation also suppressed
... Show MoreCadmium has been known to be harmful to human healthy , manily Via contaminated drinking water , food supplies , tobacco and industrial pollutant . The aim of this study was to determine the toxicity of new Cadmium (II) complex ( Bis[ 5- ( P- nitrophenyl ) – ? 4 – Phenyl- 1,2,4- triazole -3- dithiocarbamatohydrazide] cadmium (II) Hydra ( 0.5) and compare it with anticancer drug cyclophosphamide ( CP) in female albino mice . This complex causes to several alterations in Enzymatic activity of Glutamate Pyruvate Transaminase (GPT) and Alkaline Phosphatase (ALP ) in three organs after the treatment of mice with different doses of a new cadmium (II) complex ( 0.09 / 0.25ml , 0.18/ 0.5ml and 0.25mg /0.7 ml /30 gm of mous
... Show MoreAccording to so many previous studies, lack of sufficient information during prescribing steps may lead to medication errors. Thus, the presence of the clinical pharmacist during routine rounding process in the ward with intervention of patient care plan may reduce the probability of adverse drug events (ADEs).This study evaluate role of the clinical pharmacists, as a member of medical team with the physician, on ADEs and report their interventions in the internal medicine unit. This study was designed to compare between two groups of patients, those receiving care from a rounding team (physician, nurse, and clinical pharmacist) (study or intervention group with 51 patient); and those receiving c
... Show MoreThis study deals with the measurement of the specific activity radiation for beryllium -7 isotope in Baghdad city for samples of surface soils, by using gamma ray spectrometer technique. Twenty one samples were collected from surface soil of Baghdad city from Risafa and Karkh sides, (7) samples from Risafa side and(14) samples from Karkh side, where the axis for locations which are fixed by using (G.P.S.) . Gamma-ray spectrometry system (DSA 2000) with high purity germanium detector was used, which has (50%) efficiency and resolution of (2.2 keV) at gamma line (1332 keV) of 60Co source. The specific activity values for beryllium -7 isotope in surface soil of R
... Show MoreThe dependence of the energy losses or the stopping power for the ion contribution in D- T hot plasma fuels upon the corresponding energies and the related penetrating factorare arrive by using by a theoretical approximation models. In this work we reach a compatible agreement between our results and the corresponding experimental results.