A protein undergoes many types of posttranslation modification. Citrullination is one of these modifications, where an arginine amino acid is converted to a citrulline amino acid. This process depends on catalytic enzymes such as peptidylarginine deiminase enzymes (PADs). This modification leads to a charge shift, which affects the protein structure, protein-protein interactions, and hydrogen bond formation, and it may cause protein denaturation. The irreversible citrullination reaction is not limited to a specific protein, cell, or tissue. It can target a wide range of proteins in the cell membrane, cytoplasm, nucleus, and mitochondria. Citrullination is a normal reaction during cell death. Apoptosis is normally accompanied with a clearance process via scavenger cells. A defect in the clearance system either in terms of efficiency or capacity may occur due to massive cell death, which may result in the accumulation and leakage of PAD enzymes and the citrullinated peptide from the necrotized cell which could be recognized by the immune system, where the immunological tolerance will be avoided and the autoimmune disorders will be subsequently triggered. The induction of autoimmune responses, autoantibody production, and cytokines involved in the major autoimmune diseases will be discussed.
Introduction Access to ionizing radiation has become widely available for diagnosis and treatment. The increased use of ionizing radiation has been associated with radiation exposure hazards for patients and radiation workers. Raising the level of radiation protection awareness is important to maintain the safety of healthcare settings. Methods Online questionnaires were distributed to 755 healthcare workers and students at King Abdulaziz Medical City and King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. The questionnaire consisted of 14 multiple-choice questions divided into two sections (questions related to radiation protection and common radiologic examination doses). Results In total, 443 participants completed the questionnaire, including 142 (32%) medical students, 107 (24%) radiology technologists, 105 (24%) radiography students, and 89 (20%) physicians. Of the participants, 245 (55%) were men. A total of 74 (84%) physicians and 51 (47%) radiology technologists had more than 5 years of experience. Eleven (12%) physicians and 44 (41%) radiology technologists had 1–4 years of experience, whereas the rest had less than 1 year of experience. Only 16% of participants attended training courses on a regular basis. However, 15% of the participants thought that they had excellent knowledge of radiation protection, whereas 18% admitted that they did not have sufficient knowledge. Sixty-two percent of the questions related to radiation protection awareness were answered correctly. Forty-five percent of the participants correctly answered questions related to doses from common radiologic examinations. Only 23% and 16% of participants were aware of the noncontrast chest CT and lumbar x-ray doses, respectively. Moreover, 35% and 24% of participants did not know that pelvic MRI and abdominal ultrasound do not contribute any radiation dose, respectively. Conclusion The results showed a knowledge gap regarding radiation protection and dose levels; therefore, periodic refresher courses are recommended for healthcare workers in order to increase the level of awareness.
Background: Asthma is a health disorder that is prevalent worldwide, and it imposes a great burden on primary health care (PHC) facilities. This work aims to study the magnitude and clinical aspects of bronchial asthma (BA) and to explore the pattern of its management at outpatient clinics (OPCs) in Jeddah, Saudi Arabia. Methods: A cross-sectional study enrolled 2,501 patients who visited the OPCs at two private hospitals in Jeddah during the study period. All patients were examined by a specialist. Data were collected using a checklist form to obtain personal characteristics, clinical assessment and management, as well as the outcome of the visits. Results: BA accounts for 4.27% of all visits, and for 19.49% of respiratory disorders visits to OPCs. Children under 6 years old were twice as likely to develop BA (OR: 1.89; 95% CI: 1.130, 3.147, p <0.015) compared to individuals older than 40 years. The common BA symptoms were cough (77.4%), dyspnea (42.5%), wheeze (29.2%), and sputum production (25.7%). CXR was the most frequent investigation performed on patients with BA (26.4%). No lung function or immunological tests were performed. Cortisol (21.7%), short-acting β2 agonist (21.7%), antibiotic (41%), paracetamol (17%), cough syrup and antihistamines (30% and 19.8%), and additionally, ketotifen (4.7%) and anti-leukotriene (7.5%) were prescribed to the patients. Counseling was neglected by physicians. The majority of cases were discharged. Conclusion: BA is a common cause for PHC visits. OPC management and use of antibiotics for BA should be revised with emphasis on adherence to the standard recommendations. PHC physicians should prioritize educating people about the prevention and control of BA.
Mx proteins are antiviral proteins that belong to the dynamin super-family of large GTPases. In a number of species Mx proteins were shown to be important components of the innate response to viral infection. Work in our laboratory showed that during early pregnancy Mx proteins are up-regulated in the ruminant uterus by conceptus-derived IFN tau. Transient oMx1 knockdown in ovine glandular epithelial cells (oGE) reduced oMx1 secretion and secretion of other unconventionally secreted proteins without affecting secretion via the classical secretory pathway. We further showed that oMx1 was present in uterine flushes from pregnant ewes. We recently characterized another Mx protein, oMx2, in sheep. The newly characterized oMx2 has higher homology with bovine Mx2 (93%) than with oMx1 (60%). The purpose of this study was to characterize cellular expression and localization of oMx2 in oGE cells and in cell lines derived from the luminal epithelium (oLE) and stroma (oSC). In addition we determined if oMx2 was secreted by oGE cells in vitro. Expressions of oMx1 and oMx2 were low to undetectable in all three lines in the absence of IFN tau and were increased by IFN tau (P < 0.01). Induction of oMx1 was greatest in oGE cells (8.4-fold increase; P < 0.01), whereas expression of oMx2 was greatest in oSC cells (19.9-fold increase; P < 0.01). Immunofluorescence analysis confirmed the high level of expression of oMx1 and oMx2 in response to IFN tau in oGE cells. Immunofluorescence analysis revealed that oMx2 co-localized with lamin A/C and nucleoporins, whereas oMx1 was distributed throughout the cytoplasm in oGE cells, suggesting that oMx2 is a nuclear membrane-associated protein. SignalP analysis indicated that oMx2 lacked a traditional leader sequence. Using an inhibitor of the classical secretory pathway, Monensin, we showed that oMx2 levels were not reduced in response to Monensin treatment. The oMx1, oMx2, and ISG15 levels in oGE-conditioned culture medium actually increased in secretions in response to Monensin (2.7-fold, 4.6-fold, and 2.9-fold increases, respectively; P < 0.1), whereas there was no effect of Monensin on �2MG levels (P > 0.1). Results show that oMx2 expression, like that of oMx1, is regulated by IFN tau. The functional significance of the different cellular localization between oMx1 and oMx2 is not clear, but may suggest that these related proteins possess distinct cellular functions. Finally, this is the first report that oMx2 is secreted, perhaps via poorly described unconventional secretory pathways. The potential intracellular and extracellular functions of oMx2 are currently being investigated. This work was supported by USDA grant 2002-02398 and NIH NCRR grant P20-RR15587-01 to T.L.O.
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