Covalent modification of protein by drugs may disrupt self-tolerance, leading to lymphocyte activation. Until now, determination of the threshold required for this process has not been possible. Therefore, we performed quantitative mass spectrometric analyses to define the epitopes formed in tolerant and hypersensitive patients taking the β-lactam antibiotic piperacillin and the threshold required for T cell activation. A hydrolyzed piperacillin hapten was detected on four lysine residues of human serum albumin (HSA) isolated from tolerant patients. The level of modified Lys541 ranged from 2.6 to 4.8%. Analysis of plasma from hypersensitive patients revealed the same pattern and levels of modification 1–10 d after the commencement of therapy. Piperacillin-responsive skin-homing CD4+ clones expressing an array of Vβ receptors were activated in a dose-, time-, and processing-dependent manner; analysis of incubation medium revealed that 2.6% of Lys541 in HSA was modified when T cells were activated. Piperacillin–HSA conjugates that had levels and epitopes identical to those detected in patients were shown to selectively stimulate additional CD4+ clones, which expressed a more restricted Vβ repertoire. To conclude, the levels of piperacillin–HSA modification that activated T cells are equivalent to the ones formed in hypersensitive and tolerant patients, which indicates that threshold levels of drug Ag are formed in all patients. Thus, the propensity to develop hypersensitivity is dependent on other factors, such as the presence of T cells within an individual’s repertoire that can be activated with the β-lactam hapten and/or an imbalance in immune regulation.
Purpose: studying and analyzing the nature of uncertainty as part of strategy formulation, through analyzing the uncertainty faced by managers in the modern business environment characterized by high complexity and dynamism, though developing of an idea about the uncertainty cases and how enable the mind to understand these cases.
Methodology: It was the use of inductive and analytical approach, in order to study the accumulation of knowledge towards development areas that could contribute to strengthening the strategy formulation.
Findings: Mentoring the future will not make the success for business organization but thought business organization ability to developing share mental
... Show MoreIslamic shrines architecture is one of the Islamic Architectural building types. It is called (Thresholds); (Atabat) in Arabic. Thoroughbred throughout the Islamic world from the east to west. In addition, it carries the style features and peculiarities of uniqueness from the rest of the types of Islamic architecture. By virtue of the particularity of its function as tomb for important person in Islamic history. Islamic shrines architecture has grown and evolved in started from the small shrines, and then taken to widen with the evolution of time in line with the value of the event and the rituals associated with it. Some of them to became centers of large cities of the largest in many parts of the Islamic world.
... Show MoreThe main purpose of this investigation is to evaluate the concentrations of six essential metals (Na+, Mg2+, K+, Ca2+, Fe2+ and Zn2+) in saffron and a farm soil using the neutron activation analysis (NAA) as a nuclear spectrometry method. The stratified random sampling method was used here. The NAA results showed the well uptake of Mg2+, K+, Ca2+, Fe2+, and Zn2+ in saffron, which is lower than the toxicity range. Based on the contamination factor and geoaccumulation index, soil contamination levels were determined uncontaminated by Zn, moderately contaminated by Na+ and Fe2+, and strongly contamin
... Show MoreRegulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers. CD177, a cell surface protein normally expressed on neutrophil, is specifically expressed on Fate-1 TI Treg cells in several solid cancer types, but not on other TI or peripheral Treg cells. Mechanistically, blocking CD
Coeliac disease is an immunologically mediated disease of the small intestinal mucosa, characterized by flattening of the small intestinal villi, increased numbers of intra-epithelial lymphocytes and inflammatory cell infiltrates in the lamina propria, resulting in gut damage and nonspecific malabsorption of nutrients. The disease is elicited by ingestion of gluten, a protein found in several cereals, principally wheat, but also barley and to a lesser extent, oats. Successful treatment is avoidance of dietary gluten. Long-standing evidence suggests a T-cell-mediated response to peptides derived from the gliadin fraction of wheat gluten, leading to immunologically mediated intestinal injury in genetically susceptible individuals. The
... Show MorePregnancy pose an additional burden on the body of the mother so as to meet their needs and the needs of the fetus and the body's need to iron increases excessively during pregnancy and iron is an essential element for the formation of hemoglobin blood Either hemoglobin is the key ingredient for red blood cells which carries oxygen to parts of the body, alas, most of the pregnant women begin their pregnancy inadequate stocks of iron in their bodies, which does not cover their need and requirement of the fetus, especially in the second and third trimesters of pregnancy When you reach the mother to the period in which they did not have the adequate amount of iron to produce hemoglobin become the mother was anemic So emerged the problem of
... Show MoreOut of 150 clinical samples, 50 isolates of Klebsiella pneumoniae were identified according to morphological and biochemical properties. These isolates were collected from different clinical samples, including 15 (30%) urine, 12 (24%) blood, 9 (18%) sputum, 9 (18%) wound, and 5 (10%) burn. The minimum inhibitory concentrations (MICs) assay revealed that 25 (50%) of isolates were resistant to gentamicin (≥16µg/ml), 22 (44%) of isolates were resistant to amikacin (≥64 µg/ml), 21 (42%) of isolates were resistant to ertapenem (≥8 µg/ml), 18 (36%) of isolates were resistant to imipenem (4- ≥16µg/ml), 43 (86%) of isolates were resistant to ceftriaxone (4- ≥64 µg/ml), 42 (84%) of isolates were resistant to ceftazidime (1
... Show MoreThis paper proposes a neuro-fuzzy system to model β-glucosidase activity based on the reaction’s pH level and temperature. The developed fuzzy inference system includes two input variables (pH level and temperature) and one output (enzyme activity). The multi-input fuzzy inference system was developed in two stages: first, developing a single input-single output fuzzy inference system for each input variable (pH, temperature) separately, using the robust adaptive network-based fuzzy inference system (ANFIS) approach. The neural network learning techniques were used to tune the membership functions based on previously published experimental data for β-glucosidase. Second, each input’s optimized membership functions from the ANF
... Show More