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.
The propaganda discourse is the most widely circulated in the media and communication studies, where the interest of scholars and researchers in this field has become clear in the analysis and interpretation of the content of this discourse, to identify the intentions, purposes and objectives of the communicator activity, which exceeded the borders of states in the heated atmosphere of rivalries and political conflicts that characterize The countries of the world as a whole and for many years.
In particular, the economically and militarily developed countries (the Nordic capitalist countries) have exerted special efforts in the production of information and ideas, using advanced methods and means in all details of communication w
... Show MoreKlebsiella pneumoniae has been found in the urinary tract of some bladder cancer patients. Bacterial presence within tumor tissue may affect the tumor-microenvironment and consequently influence cancer behavior, development, and treatment response. This study investigated mesenchymal and stemness transdifferentiation of bladder cancer cell line due to environmental stress of K. pneumoniae. Cultures of urothelial bladder cancer cell line (T24) were infected with K. pneumoniae with different multiplicity of infection (MOI) for two and four days. Transdifferentiation-associated features were morphologically assessed.
Moreover, transdifferentiation markers were estimated using Q-PCR and immunohistoc
... Show MoreA synthesis series of new heterocyclic derivatives (A2-A7) (pyrrole, pyridazine, oxazine and imidazol) derived from 4-acetyl-2,5-dichloro-1-(3,5-dinitrophenyl)-1H-pyrrole-3-carboxylate(A1) have been synthesised. Synthesis of compound (A2) by the reaction of starting material (A1) with hydroxyl amine hydrochloride in the presence of pyridine. Compound (A2) was reacted with hydrazine hydrate in dry benzene to give (A3) derivative. The compound )A3( deals with sodium nitrite to give diazonium salt, and the reaction diazonium salt with ethyl acetoacetate to produce compound (A4). To a mixture of compound (A4) and hydroxyl amine with sttired to yield (A5).Compound (A6) was prepared by reaction compound (A4) with thiosemicarbazide in presence
... Show MoreHLA genes are associated with more than 100 diseases, including infectious diseases like HIV, and some cancers. Some autoimmune conditions, including diabetes and multiple sclerosis, are also linked to specific variations in the HLA. In MS, the immune system fails to distinguish between the body's tissues and foreign proteins resulting in it attacking myelin as if it were foreign. Several HLA genes have been found to influence the risk of developing MS. Some variants make an individual more likely to develop MS, whereas others may have a protective effect and decrease the risk. Although the precise genes involved in the development of multiple sclerosis are still not fully understood, research has identified one HLA gene that is mor
... Show MoreBackground: Polymorphisms in the TNF-α gene affect the development and progression of rheumatoid arthritis. Objective: To investigate the associations between (-806 T/C) and (-857 T/C) SNPs with rheumatoid arthritis severity and susceptibility in a sample of Iraqi patients. Methods: A case-control study was conducted in Baghdad, Iraq. Twenty healthy controls and 63 patients confirmed to be newly diagnosed with rheumatoid arthritis were included. Those are divided into two groups (patients and controls), and the patients were further subdivided into severe and mild-moderate groups. Samples from those participants were analyzed for clinical and inflammatory parameter measurements. Genotyping by the Sanger method was performed to stu
... Show MoreObjective Thalassemic patients present with multiple immune abnormalities that may predispose them to oral Candida, however this has not been investigated. The aim of this study was to assess oral candidal colonization in a group of patients with β-thalassemia major both qualitatively and quantitatively. Study design The oral mycologic flora of 50 β-thalassemia major patients and 50 age- and sex-matched control subjects was assessed using the concentrated oral rinse technique. Candida species were identified using the germ tube test and the Vitek yeast identification system. Results Oral Candida was isolated from 37 patients (74%) and 28 healthy subjects (56%; P = .04). The mean candidal count was significantly higher in thalassemic patie
... Show MoreBackground: Arylesterase activity of Paraoxonase-1 (ARE-PON-1) exhibits an antioxidant role which protects lipoprotein from oxidation. It is known that ARE-PON-1 antioxidant activity associated with high density lipoprotein cholesterol (HDL-C) reduces the oxidative damage mediated by low density lipoprotein cholesterol (LDL-C). The present study was aimed to examine the level of serum ARE-PON1 in Iraqi patients with β-thalassemia minor and its relationship with lipid profile (total cholesterol (TC), HDL-C, very low density lipoprotein (VLDL-C), and LDL-C) and hematologic changes as a part of antioxidant system action. Methods: In the present study, the ARE-PON-1 activity was investigated in serum of patients with β-thalassemia minor. Resu
... Show MoreIncreased downscaling of CMOS circuits with respect to feature size and threshold voltage has a result of dramatically increasing in leakage current. So, leakage power reduction is an important design issue for active and standby modes as long as the technology scaling increased. In this paper, a simultaneous active and standby energy optimization methodology is proposed for 22 nm sub-threshold CMOS circuits. In the first phase, we investigate the dual threshold voltage design for active energy per cycle minimization. A slack based genetic algorithm is proposed to find the optimal reverse body bias assignment to set of noncritical paths gates to ensure low active energy per cycle with the maximum allowable frequency at the optimal supply vo
... Show MoreEuropean Chemical Bulletin (ISSN 2063-5346) is a peer-reviewed journal that publishes original research papers, short communications, and review articles in all areas of chemistry. European Chemical Bulletin has eight sections, namely
new Schiff base 4-chlorophenyl)methanimine (6R,7R)-3-methyl-8-oxo-7-(2-phenylpropanamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate= (HL)= C23H20 ClN3O4S) has been synthesized from β-lactam antibiotic (cephalexin mono hydrate(CephH)=(C16H19N3O5S.H2O) and 4-chlorobenzaldehyde . Figure(1) Metal mixed ligand complexes of the Schiff base were prepared from chloride salt of Fe(II),Co(II),Ni(II),Cu(II),Zn(II) and Cd (II), in 50% (v/v) ethanol –water medium (SacH ) .in aqueous ethanol(1:1) containing and Saccharin(C7H5NO3S) = sodium hydroxide. Several physical tools in particular; IR, CHN, 1H NMR, 13C NMR for ligand and melting point molar conductance, magnetic moment. and determination the percentage of the metal in the complexes by fl
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