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21.
Human CR2 is a B cell membrane glycoprotein that plays a central role in autoimmunity. Systemic lupus erythematosus (SLE) patients show reduced CR2 levels, and complete deficiency of CR2 and CR1 promotes the development of anti-DNA antibodies in mouse models of SLE. Here we show that multiple forms of DNA, including bacterial, viral and mammalian DNA, bind to human CR2 with moderately high affinity. Surface plasmon resonance studies showed that methylated DNA bound with high affinity with CR2 at a maximal K(D) of 6nM. DNA was bound to the first two domains of CR2 and this binding was blocked by using a specific inhibitory anti-CR2 mAb. DNA immunization in Cr2(-/-) mice revealed a specific defect in immune responses to bacterial DNA. CR2 can act as a receptor for DNA in the absence of complement C3 fixation to this ligand. These results suggest that CR2 plays a role in the recognition of foreign DNA during host-immune responses. This recognition function of CR2 may be a mechanism that influences the development of autoimmunity to DNA in SLE. 相似文献
22.
Objective
To explore the effect of menopause and hormone replacement therapy on pelvic organ prolapse and pelvic floor muscle function.Methods
The records of patients who attended a tertiary urogynaecological center were reviewed retrospectively. A standardised interview included menopausal age, i.e. years since last period or onset of menopausal symptoms, current or previous hormone use. The clinical examination included prolapse assessment (POP-Q) and palpation of the levator ani muscle. 4D transperineal ultrasound, supine and after voiding, was performed in all patients. Volume data sets were analysed for pelvic organ descent and measures of contractility and distensibility of the pelvic floor at a later date, blinded to all clinical data.Results
Of 311 women seen during the inclusion period, 65% were postmenopausal. Current systemic or local hormone use was reported by 7% and 6%, respectively. 163 women (52%) reported prolapse symptoms with a mean bother of 5.7/10. Significant pelvic organ prolapse was found on clinical examination (POP-Q stage ≥ 2) in 77%, and diagnosed on ultrasound in 61%. On multivariate analysis, controlling for calendaric age, parity and levator avulsion, there was no evidence for menopausal age as an independent predictor of any symptom and sign of pelvic organ prolapse and pelvic floor muscle function. Local oestrogen use and past or present hormone replacement therapy had no detectable effect on any pelvic floor parameter.Conclusions
Hormone deficiency following menopause is unlikely to play a major role in pelvic organ support and levator ani function. Hence, both do not appear to be substantially influenced by local or systemic hormone replacement therapy. 相似文献23.
Ethical challenges in nursing homes – staff's opinions and experiences with systematic ethics meetings with participation of residents’ relatives 下载免费PDF全文
24.
Klomp LW Vargas JC van Mil SW Pawlikowska L Strautnieks SS van Eijk MJ Juijn JA Pabón-Peña C Smith LB DeYoung JA Byrne JA Gombert J van der Brugge G Berger R Jankowska I Pawlowska J Villa E Knisely AS Thompson RJ Freimer NB Houwen RH Bull LN 《Hepatology (Baltimore, Md.)》2004,40(1):27-38
Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BRIC) are clinically distinct hereditary disorders. PFIC patients suffer from chronic cholestasis and develop liver fibrosis. BRIC patients experience intermittent attacks of cholestasis that resolve spontaneously. Mutations in ATP8B1 (previously FIC1) may result in PFIC or BRIC. We report the genomic organization of ATP8B1 and mutation analyses of 180 families with PFIC or BRIC that identified 54 distinct disease mutations, including 10 mutations predicted to disrupt splicing, 6 nonsense mutations, 11 small insertion or deletion mutations predicted to induce frameshifts, 1 large genomic deletion, 2 small inframe deletions, and 24 missense mutations. Most mutations are rare, occurring in 1-3 families, or are limited to specific populations. Many patients are compound heterozygous for 2 mutations. Mutation type or location correlates overall with clinical severity: missense mutations are more common in BRIC (58% vs. 38% in PFIC), while nonsense, frameshifting, and large deletion mutations are more common in PFIC (41% vs. 16% in BRIC). Some mutations, however, lead to a wide range of phenotypes, from PFIC to BRIC or even no clinical disease. ATP8B1 mutations were detected in 30% and 41%, respectively, of the PFIC and BRIC patients screened. 相似文献
25.
Katarzyna Walkiewicz Andres S. Benitez Cardenas Christine Sun Colin Bacorn Gerda Saxer Yousif Shamoo 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(52):21408-21413
In principle, evolutionary outcomes could be largely predicted if all of the relevant physicochemical variants of a particular protein function under selection were known and integrated into an appropriate physiological model. We have tested this principle by generating a family of variants of the tetracycline resistance protein TetX2 and identified the physicochemical properties most correlated with organismal fitness. Surprisingly, small changes in the Km(MCN), less than twofold, were sufficient to produce highly successful adaptive mutants over clinically relevant drug concentrations. We then built a quantitative model directly relating the in vitro physicochemical properties of the mutant enzymes to the growth rates of bacteria carrying a single chromosomal copy of the tet(X2) variants over a wide range of minocycline (MCN) concentrations. Importantly, this model allows the prediction of enzymatic properties directly from cellular growth rates as well as the physicochemical-fitness landscape of TetX2. Using experimental evolution and deep sequencing to monitor the allelic frequencies of the seven most biochemically efficient TetX2 mutants in 10 independently evolving populations, we showed that the model correctly predicted the success of the two most beneficial variants tet(X2)T280A and tet(X2)N371I. The structure of the most efficient variant, TetX2T280A, in complex with MCN at 2.7 Å resolution suggests an indirect effect on enzyme kinetics. Taken together, these findings support an important role for readily accessible small steps in protein evolution that can, in turn, greatly increase the fitness of an organism during natural selection. 相似文献
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29.
Sharon L. N. M. Tjin A Tsoi Anthonius de Boer Gerda Croiset Andries S. Koster Stéphanie van der Burgt Rashmi A. Kusurkar 《Advances in health sciences education : theory and practice》2018,23(3):549-566
Insufficient professional development may lead to poor performance of healthcare professionals. Therefore, continuing education (CE) and continuing professional development (CPD) are needed to secure safe and good quality healthcare. The aim of the study was to investigate the hypothesized associations and their directions between pharmacists’ basic psychological needs in CE, their academic motivation, well-being, learning outcomes. Self-determination theory was used as a theoretical framework for this study. Data were collected through four questionnaires measuring: academic motivation, basic psychological needs (BPN), vitality and lifelong learning adaptability of pharmacists in the CE/CPD learning context. Structural equation modelling was used to analyze the data. Demographic factors like gender and working environment influenced the observed scores for frustration of BPN and factors like training status and working experience influenced the observed scores for academic motivation. A good model fit could be found only for a part of the hypothesized pathway. Frustration of BPN is positively directly related to the less desirable type of academic motivation, controlled motivation (0.88) and negatively directly related to vitality (? 1.61) and negatively indirectly related to learning outcomes in CE. Fulfillment or frustration of BPN are important predictors for well-being and learning outcomes. Further research should be conducted to discover how we can prevent these needs from being frustrated in order to design a motivating, vitalizing and sustainable CE/CPD system for pharmacists and other healthcare professionals. Basic psychological needs are very important predictors for well-being and learning outcomes. Further research should be conducted to discover how we can prevent these needs from being frustrated in order to design a motivating, vitalizing and sustainable CE/CPD system for pharmacists and other healthcare professionals. 相似文献
30.
Occupational generalized urticaria and anaphylaxis after inhalation of cefuroxime in a nurse 下载免费PDF全文
Rolf Merget MD Ingrid Sander PhD Manigé Fartasch MD Vera van Kampen PhD Stefani Röseler MD Hans Merk MD Gerda Wurpts MD Monika Raulf PhD Thomas Brüning MD 《American journal of industrial medicine》2018,61(3):261-266