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 present study was designed to select a suitable isolate of Lactobacillus sp. in order to use it as a probiotic formula for treating diabetic foot ulcer disease in diabetic mellitus patients. In order to determine the inhibitory action, 240 isolates of Lactobacillus from different sources, were taken and exposed for screening tests to evaluate the (antagonism-activities) toward 4 multi-drug resistant foot ulcer pathogens which were chosen from 120 pathogenic isolates: Staphylococcus aureus, Klebsiella pneumonia, Proteus mirabilis, and P. aeruginosa. Twenty Lactobacillus isolates were selected from primary screening according to the capacity to restrain its expansion of f
... Show MoreAbstract:
The aim of the present research is to evaluate the child’s nutritional
method (2-5 years old) which is based on his resistance of the food highly rich
with nutritional elements and his acceptance of the food of a low nutritional
value in addition to his having forbidden food with other mates and making
use of all mates when having food, in establishing the sound social values and
affection since child hood. The required statistical equation have been used
by the researcher namely (Z test).
The sample of the present study consists of (26) children who were selected
intentionally and randomly from the kindergartens of Al-Bayaa region and the
college of Education for women. The questionnaires were d
Abstract: E2F6 is a member of the E2F family of transcription factors involved in regulation of a wide variety of genes through both activation and repression. E2F6 has been reported as overexpressed in breast cancers but whether or not this is important for tumor development is unclear. We first checked E2F6 expression in tumor cDNAs and the protein level in a range of breast cancer cell lines. RNA interference-mediated depletion was then used to assess the importance of E2F6 expression in cell lines with regard to cell cycle profile using fluorescence-activated cell sorting and a cell survival assay using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The overexpression of E2F6 was confirmed in breast tumor cDNA samp
... Show MoreTwenty-seven S. aureus isolates were obtained from patients referring various hospitals in Baghdad. Only 17 isolates produced DNase. SNase was extracted and purified from Saphylococcus aureus 3 isolate since it produces the largest zone of clearance on DNase agar. Nevertheless, only those phenotypically-producer of DNase harboured nuc gene. Present study revealed that the crude enzyme had a specific activity of 50.66 unit/mg; while it reached 241 unit/mg after ion exchange chromatography using carboxymethyl cellulose column. SDS-PAGE showed a single sharp band with an approximately 16.8 kDa molecular weight. A matter indicates that the enzyme is consistently pure. Results proved that SNase was able to significantly (P< 0.05) reduce th
... Show MoreCopper Phthalocyanine (CuPc) thin film with and without multi-walled carbon nanotubes (MWCNTs) is prepared using the solution based method and used in gas sensor and solar cell applications. The structural characteristics of the CuPc thin films showed a single peak around 7o with the preferred orientation for charge transportation. Using atomic force microscopy (AFM), morphological properties show a rough surface with some aggregates and ribbons. The optical absorption properties were determined using UV-Visible absorption spectroscopy; the optical band gap has varied after adding MWCNTs to CuPc. Electrical conductivity of CuPc:MWCNTs composite is higher than that of the pure CuPc. The CuPc thin film sensr have sh
... Show MoreThe application of physiological oxygen (physoxia) concentrations is becoming increasingly commonplace within a mammalian stem cell culture. Human mesenchymal stem cells (hMSCs) attract widespread interest for clinical application due to their unique immunomodulatory, multi-lineage potential, and regenerative capacities. Descriptions of the impact of physoxia on global DNA methylation patterns in hMSCs and the activity of enzymatic machinery responsible for its regulation remain limited. Human bone marrow-derived mesenchymal stem cells (BM-hMSCs, passage 1) isolated in reduced oxygen conditions displayed an upregulation of SOX2 in reduced oxygen conditions vs. air oxygen (21% O2, AO), while no change was noted for either OCT-4 or NA
... Show MoreChronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy.
Epigenome-wide analysis of DNA methylation was performed for 20 patients at two timepoints during treatment. The prognostic significance of differentially methylated regions (DMRs) was assessed in independent cohorts of 139 and 1
A new series of Sulfamethoxazole derivatives was prepared and examined for antifibrinolytic and antimicrobial activities. Sulfamethoxazole derivatives bear heterocyclic moieties such as 1,3,4-thiadiazine {3}, pyrazolidine-3,5-diol {4} 6-hydroxy-1,3,4-thiadiazinane-2-thione {5} and [(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)diazenyl] {8}. Their structures were elucidated by spectral methods (FT-IR, H1-NMR). Physical properties are also determined for all compound derivatives. Recently prepared compounds were tested for their antimicrobial activity in the laboratory. Each screened compound showed good tendency to moderate antimicrobial activity.