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.
Lafutidine (LAF) a newly developed histamine H2-receptor antagonist with absorption window makes it a good candidate to be prepared as floating drug delivery system. The current study involves formulation and in- Vitro evaluation of lafutidine as floating microspheres. Different formulation variables that affect the physicochemical properties of the prepared microspheres besides to the drug release behavior were investigated. Fourteen formulas were prepared by emulsion (o/w) solvent evaporation method using Ethyl cellulose (EC) as the polymeric matrix and tween 80 (TW80) as an emulsifying agent. The prepared formulas were evaluated for their percentage buoyancy (%), Percentage yield (%) and Entrapment efficiency (EE %). The results obt
... Show MoreThis paper aims to study the role of a prey refuge that depends on both prey and predator species on the dynamics of a food web model. It is assumed that the food transfer among the web levels occurs according to Lotka-Volterra functional response. The solution properties, such as existence, uniqueness, and uniform boundedness, are discussed. The local, as well as the global, stabilities of the solution of the system are investigated. The persistence of the system is studied with the assistance of average Lyapunov function. The local bifurcation conditions that may occur near the equilibrium points are established. Finally, numerical simulation is used to confirm our obtained results. It is observed that the system has only one type of a
... Show MoreHeat treatment by solid solution method in the ?+? phase region was used at 970°C for Ti-5Al-2.5Fe alloy. The specimens cooled under different cooling media [water quenched (WQ), air cooled (AC) and furnace cooled (FC)], and subsequently aged at 550°C for 4 hours. Five specimens from each treatment were immersed in simulated body fluid SBF for a period of time (3 months). The dependence of corrosion rate on compositional variation in the phases resulted from various type of cooling rates are discussed based on immersion tests. The EDXA results show the precipitation of phosphate and calcium compounds on the alloy after 3 months of immersion in blood plasma solution forming a bone-like apatite, which enhanced the alloy biocompatibility ma
... Show MoreThe waste material problem in today's world has become a major topic affecting all sectors of human life. Researchers are interested in providing solutions for each kind of waste material. Waste glass is one of the waste materials whose amounts increase daily. This article deals with two types of modified cement mortar with glass granular in the masonry wall to find their effect on the wall's property (direct tensile, flexural, and compressive bond strength). Seven different mixes were prepared according to the used glass granular ratio (three mixes contained white glass with 15, 20, and 25% while three of them contained green glass granular 5, 10, and 15%, and the last mix was a controlled mix which contains no glass gr
... Show MoreThis research studied the relationship of patterns of investigator personality with the big five dimensions (Extraversion, stability, interoperability, openness, and personal benevolent), in facing the job stress with its resources(characteristics of the role, quality of work, organizational structure, work environment, organizational policies, social relations, and organizational processes) which the investigators exposed to it at the General Inspectors Offices.
The researcher derived the idea of research from the importance of the work of these offices in a confrontation of various cases of financial and administrative corruption in Iraq at the present time, since itis one of the most important in
... Show MoreThe tax revenues achieved through projects of transition to private sector are regarded as an important source for using in achieving political, economic and social objectives. Since Iraq is heading towards free market economy, new strategies should be adopted to reform the taxation system from by a qualified taxation management office and to activate the taxation policy and to reconsider legislation in relation to the aware of the legible to the importance of disclosure of their taxable real income in order to arrive at contribution of privatization in the taxation revenues for the important role effect on economic activities. In the light of the above, the research is based upon a hypothesis which stipulates that privatization contribu
... Show MoreVariation orders are an on-going phenomenon in construction and industry projects worldwide, particularly in the province of Sulaimani, where the project's damage from cost and schedule overrun because of variation orders. However, the effect on project costs and time overrun of variation order has yet to be identified. This study evaluates the impact of variation orders on the cost and time off in the Sulaimani governorate. Two hundred twenty-eight projects from various construction sectors built between 2007-2012 were adopted to calculate the contract cost and schedule overruns due to variation orders. Data analysis was applied in the study were descriptive statistics. One-way ANOVA was also applied to determine w
... Show MoreObjective : The present study is aimed to evaluate the effectiveness of short wave diathermy and
ultrasound therapy for the management of patients with knee osteoarthritis
Methodology : all patients who referred to the Medical Rehabilitation Unit in Baghdad Teaching
Hospital and Sadr A!-Qanat Center. The period of the study was from October 2004 to April 2005, total
number of patients was 24 (9 male and 15 female). Age range of patients was 42-70 years. Complete
clinical and radiological examinations were achieved on all patients and referred to the Medical
Rehabilitation Unit for physiotherapy. Short wave diathermy and ultrasound therapy were applied on
all patients.
Results : Demographic distribution revealed th