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.
Background: Oral carcinogenesis is a molecular and histological multistage process featuring genetic and phenotypic markers for each stage, which involves enhanced function of several oncogenes and/or the deactivation of tumor suppressor genes, resulting in the loss of cell cycle checkpoints. The progression towards malignancy includes sequential histopathological alterations ranging from hyperplasia through dysplasia to carcinoma in situ and invasive carcinoma. The p16 gene produces p16 protein, which in turn inhibits phosphorylation of retinoblastoma, p16 play a significant role in early carcinogenesis. Human papillomavirus is a well established heterogeneous virus and plays an important role in oral cancers. The aims of the study were to
... Show MoreBackground: Maxillary first premolar with wide MOD cavity more susceptible to fracture. The aim of this study was to assess the influence of cavity design for cusp coverage on the fracture resistance of weakened maxillary first premolar restored with CAD/CAM hybrid ceramic versus nanohybide composite. Materials and Methods: Fifty six intact maxillary first premolars of approximately comparable sizes were divided into seven groups eight for each: Group A: Intact teeth (control group); Group B: teeth prepared for MOD inlay; Group C: teeth prepared for MOD onlay covering the lingual cusp; Group D: teeth prepared for MOD covering buccal and lingual cusps ,the previous three groups indirectly restored with nanohybrid composite (3M ESPE Z 250 X
... Show MoreBackground: Tumor associated tissue eosinophilia (TATE) has been described in a variety of neoplasms. In regard to squamous cell carcinoma, some studies worldwide done to assess stromal eosinophilia in oral and cervical squamous cell carcinoma. The objectives of this study is to evaluate the association of stromal eosinophilic infiltration of cutaneous squamous cell carcinoma and to detect the significance of this association. Aim of the study The aim of our study is to establish the relationship between the degree of stromal eosinophilia and the level of invasion and the histological grade in cutaneous squamous cell carcinoma. Methods: In this retrospective study done at the histopathology department of al Wasity teaching hospital for orth
... Show MoreBackground: Tumor associated tissue eosinophilia (TATE) has been described in a variety of neoplasms. In regard to squamous cell carcinoma, some studies worldwide done to assess stromal eosinophilia in oral and cervical squamous cell carcinoma. The objectives of this study is to evaluate the association of stromal eosinophilic infiltration of cutaneous squamous cell carcinoma and to detect the significance of this association.
Aim of the study
The aim of our study is to establish the relationship between the degree of stromal eosinophilia and the level of invasion and the histological grade in cutaneous squamous cell carcinoma.
Methods: In this retrospective study
... Show MoreIn this research, we studied the effect of concentration carriers on the efficiency of the N749-TiO2 heterogeneous solar cell based on quantum electron transfer theory using a donor-acceptor scenario. The photoelectric properties of the N749-TiO2 interfaces in dye sensitized solar cells DSSCs are calculated using the J-V curves. For the 〖(CH_3)〗_3 COH solvent, the N749-TiO2 heterogeneous solar cell shows that the concentration carrier together with the strength coupling are the main factors affecting the current density, fill factor and efficiency. The current density and current increase as the concentration increases and the strength coupling increases as the N749-TiO2 heterogeneous in solar cell. However, the efficiency is more sens
... Show MoreThis work studies the role of serum apelin-36 and Glutathione S-transferases (GST) activity in association with the hormonal, metabolic profiles and their link to the risk of cardiovascular disease (CVD) in healthy and patients' ladies with polycystic ovary syndrome (PCOS). A total of fifty-four (PCOS) patients and thirty-one healthy woman as a control have been studied. The PCOS patients were subdivided on the basis of body-mass-index (BMI), into 2-subgroups (the first group was obese-PCOS with BMI ≥ 30 and the second group was non-obese PCOS MBI<30). Fasting-insulin-levels and Lipid-profile, Homeostatic-model assessment-of-insulin-resistance (HOMA-IR), follicle-stimulating-hormone (FSH), luteinizing-hormone (LH), testosterone and
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