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.
This study was carried out in Plant Tissue Culture Labs, College of Agricultural Engineering Sciences, University of Baghdad from November 2018 to June 2019. Fresh stem cuttings, 5 cm long were selected from 6-month old C-35 Citrange rootstock. Five concentrations of BA (0, 1, 1.5, 2 and 2.5 mg.L-1) were studied and addition of meta-Topolin (mT) at four concentrations (0, 1, 5 and 10 mg.L-1) was also studied to find out its effect individually on shoot number and shoot length in multiplication stage. Rooting media supplemented with four concentrations of IBA (0, 1, 2 and 3 mg.L-1) was also studied to find out its effect on rooting percentage, root number and root length. Results showed that BA as concentration of 2.5mg.L-1 significantly gav
... Show MoreInterleukin -33 (IL)-33 is among IL-1 cytokine superfamily , which shows promise as a biomarker predictive of mortality in diabetic and several cardiovascular disorders in vivo study.The objective of this study is to investigate the differences in the levels of IL-33 between healthy controls and patients with type 2 diabetes and diabetic cardiomyopathy and to investigate the correlation of IL-33 with HbA1C (biomarkers of type 2 diabetes), hs-CRP and oxidant –antioxidant status. One hundred and fifty individuals (age 40-55) were enrolled in this study which was divided into three groups as follows: G1:50 healthy control,G2: 50 subjects with type 2 diabetes mellitus,G3: 50 patients with dia
... Show MoreLow serum total adiponectin is associated with a high incidence of type 2 diabetes or coronary artery disease in the general population. Paradoxically, serum total adiponectin is elevated in patients with chronic kidney disease (CKD), such as overt diabetic nephropathy. The current study aimed to investigate whether or not anemia to be dependently associated with serum level of total adiponectin in non-albuminuric male patients with type 2 diabetes . The study included 42 type 2 diabetic male patients. Anemia was deï¬ned as hemoglobin (Hb) below 14.0g/dL. All the patients were without microalbuminuria, to exclude diabetic nephropathy. The diabetic patients were divided into 2 groups according to the hemoglobin level in ad
... Show MoreBackground: Oral squamous cell carcinoma is the most prevalent malignant neoplasm of the oral cavity which results from accumulated genetic and epigenetic alterations. It is not always inexorable and may be reversible if early intervention in the process can occur to prevent further genetic mutation and disease progression. The FHIT gene is a tumor suppressor gene located in FRA3B region which is the most active common fragile site, where DNA damage leading to aberrant transcripts and translocations frequently occur. The WWOX is a tumor suppressor gene that plays a central role in tumor suppression through transcriptional repression and apoptosis, with its apoptotic function the more prominent of the two. This study aimed to evaluate and co
... Show MoreBackground: Oncogenesis in the oral cavity is widely believed to result from cumulative genetic alterations that cause a transformation of the mucosa from normal to dysplastic to invasive carcinoma. The p16 gene produces p16 protein, which in turn inhibits phosphorylation of retinoblastoma (Rb), p16 play a significant role in early carcinogenesis. A number of epidermal growth factor receptor (EGFR) family, HER2/neu, has received much attention because of its therapeutic implications. The aims of the study were to evaluate and compare the immunohistochemical expression of the cell cycle protein P16 INK4a and c-erbB2 (HER2/neu) in NOM, OED, and OSCC. Correlate both marker expression with each other as well as with various clinicopathological
... Show MoreNeuroendocrine differentiation has been mentioned in many cancers of non-neuroendocrinal organs, involving the gastrointestinal tract. In contrast, the correlation of focally diffused neuroendocrine differentiation in colorectal adenocarcinoma with neuroendocrine cell hyperplasia has not been somewhat reported. The objective of this research is to study the relationship between neuroendocrine cell hyperplasia and neuroendocrine differentiation in colorectal adenocarcinoma and to find the correlation of neuroendocrine differentiation and VEGF expression with clinicopathological parameters of colorectal adenocarcinoma. Methods employed in the current study were including eighty-one patients with colorectal cancer. Formalin fixed paraffin e
... Show MoreABSTRACT The present study was conducted to determine the mode of presentation of hypothyroidism in pediatric patients and the effects of timing of diagnosis and therapy on the patient’s outcome. The study involved review and evaluation of the medical records of 41 registered patients in the Endocrine clinic of Children Welfare Teaching Hospital in Baghdad during the period from January 1991 to July 2007. Forty one patients included in this study. Twenty four (58.5%) were males and17 (41.4%) were females with a male to female ratio of 1.4:1, their age range is 40 days to12.3 years. The majority of the studied patients were infants 19(47%). The most commonly observed presenting features were growth retardation and short stature. The best t
... Show MoreRecent progress in the understanding of psoriasis has shown that the regulation of local and systemic cytokines plays an important role in its pathogenesis. Different studies evaluated the association of serum levels of some proinflammatory cytokines invivo and their correlation with severity of psoriasis. Eighty cases of psoriatic patients had been studied. Patients were divided into mild psoriasis group (30) and severe psoriasis group (50) according to severity, and (30) apparently healthy individuals ware used as acontrol group. Sera samples of all groups were collected from all individuals for the estimation levels of interleukins (IL-6 and IL-8). All mean values sera levels (IL-6 32.004 pg/ml and 17.579 pg/ml for
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