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 paper presents the results of the research on the influence of the adjuvant concentration on the size of the drops produced by the spray nozzles of agricultural sprayers. For the tests, adjuvant Normaton with the composition of total nitrogen, amide nitrogen (N-NH2) and phosphorus pentoxide (P2O5) was used. The adjuvant was added to the water taken from the municipal water supply system of the city of Lublin. The tests were carried out for three concentrations, i.e. 75%, 100%, and 125% of the adjuvant concentration recommended by the manufacturer, and water without the adjuvant. The surface tension of water with adjuva
This paper presents an experimental and numerical study which was carried out to examine the influence of the size and the layout of the web openings on the load carrying capacity and the serviceability of reinforced concrete deep beams. Five full-scale simply supported reinforced concrete deep beams with two large web openings created in shear regions were tested up to failure. The shear span to overall depth ratio was (1.1). Square openings were located symmetrically relative to the midspan section either at the midpoint or at the interior boundaries of the shear span. Two different side dimensions for the square openings were considered, mainly, (200) mm and (230) mm. The strength results proved that the shear capacity of the dee
... Show MoreThis paper presents an experimental and numerical study which was carried out to examine the influence of the size and the layout of the web openings on the load carrying capacity and the serviceability of reinforced concrete deep beams. Five full-scale simply supported reinforced concrete deep beams with two large web openings created in shear regions were tested up to failure. The shear span to overall depth ratio was (1.1). Square openings were located symmetrically relative to the midspan section either at the midpoint or at the interior boundaries of the shear span. Two different side dimensions for the square openings were considered, mainly, (200) mm and (230) mm. The strength results proved that the shear capacity of the dee
... Show MoreIn this paper, a simulation of the electrical performance for Pentacene-based top-contact bottom-gate (TCBG) Organic Field-Effect Transistors (OFET) model with Polymethyl methacrylate (PMMA) and silicon nitride (Si3N4) as gate dielectrics was studied. The effects of gate dielectrics thickness on the device performance were investigated. The thickness of the two gate dielectric materials was in the range of 100-200nm to maintain a large current density and stable performance. MATLAB simulation demonstrated for model simulation results in terms of output and transfer characteristics for drain current and the transconductance. The layer thickness of 200nm may result in gate leakage current points to the requirement of optimizing the t
... Show More: Cervical malignancy positioned as the fourth most prevalent disease among women around the world. HPVs especially HPV16 are the causative agent of cervical cancer, responsible of about 5% of all human cancers worldwide. Some researchers found that the fibronectin is repressed by the papillomavirus (HPV) type 16 E7 oncoprotein in both HPV-positive nontumorigenic and tumorigenic cell lines, while others found that the HPV oncoprotein increase the levels of fibronectin. The aim is to study the effect of HPV infection on Fibronectin expression and their correlation onthe development of Cervicalcancinoma. The current retrospective study enrolled paraffinized blocks of two groups. The research included 30 cervical carcinomatous tissues as well
... Show MorePulsatile drug delivery systems are time-controlled dosage forms which are designed to release the active pharmaceutical ingredient after a predetermined lag time to synchronize the disease circadian rhythm. A migraine shows circadian rhythm with a marked increase in attacks between 6 a.m. and 8 a.m.
Sumatriptan is a selective agonist at serotonin (5-Hydroxy tryptamine1 (5-HT1))receptors, is an effective treatment for acute migraine attacks.
The aim of this work is to prepare time-controlled press-coated tablet with a lag time of 5.45 hrs.
Six formulas of fast dissolving core tablets and three formulas of press-coated tablets were prepared by using direct compression method using different variables to prepa
... Show MoreBackground: Relapse of previously moved teeth, is major clinical problem in orthodontics with respect to the goals of successful treatment. This study investigated the effect of orthodontic relapse on the proliferation of fibroblast and epithelial rests of Malassez cells in periodontal ligament of rat molars. Materials and Methods: Sixteen ten-week- old male Wister rats were randomly divided into four groups composed of four animals each: Group I received no orthodontic force (control). In both Group II and Group III, uniform standardized expansive springs were used for moving the maxillary first molars buccally for periods of one and three weeks respectively. The spring initially generated an average expansive force of 20 g on each side.
... Show MoreThe current study, performed during the period from February 2021 to June 2022 at the University of Thi- Qar/ College of Education for Pure Sciences, and aimed to follow the changes in external morphological features at different Embryonic developmental stages in pregnant rats treated with different doses of amlodipine. Usage In this study, 18 pregnant rats were randomly divided into three groups, each with six pregnant rats. Each group received different concentrations of amlodipine (0.3, 0.5) in oral doses until the 20th day of gestation, while the control group was injected with 0.9% normal saline. Teratomas are bizarre tumors derived from embryonic tissue that are normally found only in the gonadal and sacral regions of adults. Primary
... Show MoreAS Salman, SK Hameed…, Karbala Journal of Physical Education Sciences, 2020
Background: asthma has an influence on craniofacial development. Recently evidences show that there is an association between oral health problems and chronic lung disease. The present study was designed to estimate the changes in arch dimension measurements among asthmatic children aged 12 years old who were collected from AL- Zahra Center Advisory for Allergy and Asthma and compare them with the non-asthmatic children of the same age and gender. Material and Methods: Fifty children (25 asthmatic and 25 non- asthmatic children) were included for the odontometric measurement. For both upper and lower study models, photographs were taken using special photographic apparatus for each child, and the statistical analysis were done by using SPSS
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