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.
The lead-acid battery has become so dependable in its used applications of automobile starting, emergency lighting and telecommunications, which left an impression that no further investigation is necessary or desirable. While there has been slow continuous improvements in lead-acid battery performance and mainly limited to design and material engineering. This work is mainly devoted to the properties of the active mass of the positive electrode and the acid/water ratio during the manufacturing process. A field study is carried out at the State Battery Manufacturing Company located in Baghdad, to prepare batches of lead mono-oxide with predefined quantities of liquid additives (i.e. sulfuric acid and water). Quality control and laborator
... Show MoreThe effect of short range correlations on the inelastic Coulomb form factors for excited +2 states (1.982, 3.919, 5.250 and 8.210MeV) and +4 states (3.553, 7.114, 8.960 and 10.310 MeV) in O18 is analyzed. This effect (which depends on the correlation parameterβ) is inserted into the ground state charge density distribution through the Jastrow type correlation function. The single particle harmonic oscillator wave function is used with an oscillator size parameter .b The parameters β and b are adjusted for each excited state separately so as to reproduce the experimental root mean square charge radius of .18O The nucleusO18 is considered as an inert core of C12 with two protons and four neutrons distributed over 212521211sdp−− activ
... Show MoreA Laced Reinforced Concrete (LRC) structural element comprises continuously inclined shear reinforcement in the form of lacing that connects the longitudinal reinforcements on both faces of the structural element. This study conducted a theoretical investigation of LRC deep beams to predict their behavior after exposure to fire and high temperatures. Four simply supported reinforced concrete beams of 1500 mm, 200 mm, and 240 mm length, width, and depth, respectively, were considered. The specimens were identical in terms of compressive strength ( 40 MPa) and steel reinforcement details. The same laced steel reinforcement ratio of 0.0035 was used. Three specimens were burned at variable durations and steady-state temperatures (one
... Show MoreIncremental sheet metal forming process is an advanced flexible manufacturing process to produce various 3D products without using dedicated tool as in conventional metal forming. There are a lot of process parameters that have effect on this process, studying the effect of some parameters on the strain distributions of the product over the length of deformation is the aim of this study.
In order to achieve this goal, three factors (tool forming shape, feed rate and incremental step size) are examined depending on three levels on the strain distributions over the wall of the product. Strain measurement was accomplished by using image processing technique using MATALB program. The significance of the control factors are explored u
... Show MoreBackground:The demand for esthetic orthodontic appliances is increasing so that the esthetic orthodontic archwires were introduced. This in vitro study was designed to evaluate the surface roughness offiber-reinforced polymer composite (FRPC) archwires compared to coated nickel-titanium (NiTi) archwires immersed in artificial saliva. Materials and Methods:Three types of esthetic orthodontic archwires were used: FRPC (Dentaurum), Teflon coated NiTi (Dentaurum) and epoxy coated NiTi (Orthotechnology). They were round (0.018 inch) in cross section and cut into pieces of 15 mm in length.Forty pieces from each type were divided into four groups; one group was left at a dry condition and the other three groups were immersed in artificial saliva (
... Show MoreCaptopril is an angiotensin converting enzyme inhibitor (ACEI) used to treat hypertension,
congestive heart failure, and myocardial infraction.
The only dosage form available for captopril is the plain tablet in strength of 12.5,25,50 and 100mg
tablet.
This investigation is concerned with factors affecting the formulation of captopril as a plain
tablet dosage form of 50mg. Many trials were made to prepare satisfactory tablets for the drug by
using wet – granulation methods with various additives. It was found that poly vinyl pyrrolidone
(P.V.P.) as binder gave the most satisfactory tablets. At the same time a shorter disintegrantion time
and slower dissolution rate were obtained with the addition of starch
Background: Anemia of chronic disease (ACD) occurs in the presence of chronic infection, inflammatory conditions or neoplastic conditions despite of adequate iron and vitamins storage. Gingivitis is the inflammation of the gingiva, periodontitis is the inflammation in the periodontium that extend deeper with loss of connective tissue attachment and supporting bone. The main pathogenesis of periodontal diseases and ACD is immune activation. Aims of study: Determine and compare the clinical periodontal parameters (plaque index (PLI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL)). Evaluate the hematocrit (Hct) level, red blood cells (RBCs) count and white blood cells (WBCs) c
... Show MoreUrinary tract infections (UTIs) mean microbial pathogens in the urethra or bladder (lower urinary tract). Important risk factors for recurrent UTI include obstruction of the urinary tract, use of a bladder catheter or a suppressed immune system. This study aims to isolate and identify bacteria from patients with TCC-bladder cancer or patients with a negative cystoscope and estimate antibiotic susceptibility patterns and evaluate some of the virulence factors. From a total of 62 patients with TCC-BC or negative cystoscope, only 35 favorable bacterial growths were obtained, including Escherichia coli (UPEC), a significant bacterial isolate, and Stenotrophomonas maltophilia. The percentage of multi drug-resistance bacteria
... Show MoreIn this study, the response of ten composite post-tensioned concrete beams topped by a reinforced concrete deck with adequate reinforcing shear connectors is investigated. Depending on the concrete compressive strength of the deck slab (20, 30, and 40 MPa), beams are grouped into three categories. Seven of these beams are exposed to a fire attack of 700 and 800 °C temperature simultaneously with or without the presence of a uniformly distributed sustained static loading. After cooling back to ambient temperature, these composite beams are loaded up to failure, using a force control module, by monotonic static loading in a four-point-bending setup with two symmetrical concentrated loads applied in