6,205 research outputs found

    The clinicopathological features and importance of p53, Rb, and mdm2 expression in phaeochromocytomas and paragangliomas

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    Aims - Phaeochromocytomas and paragangliomas are uncommon. The aims of this study were to analyse the characteristics and the possible roles of p53, Rb, and mdm2 alterations in these tumours. Methods - The clinicopathological features of 65 patients (31 men, 34 women) with phaeochromocytomas or paragangliomas were analysed. The tumours were studied for the expression of p53, Rb, and mdm2 by immunohistochemical methods. Results - Thirty nine of the patients had phaeochromocytomas and 26 had paragangliomas. Bilateral tumours were noted in eight of the patients and malignant tumours were seen in 13. Paragangliomas were often small, non-functional, and presented incidentally, whereas phaeochromocytomas were usually large, functional, and symptomatic, p53 overexpression, loss of Rb expression, and mdm2 overexpression were seen in four, 43, and 37 of the patients, respectively. Three of the four patients with p53 overexpression had bilateral tumours. Loss of Rb expression was often found in phaeochromocytomas, whereas mdm2 overexpression was more frequently seen in paragangliomas. The 10 year survival rate of patients with malignant tumours was 45%. Two patients died of tumour metastases more than 10 years after resection of the primary tumours. Conclusions - Phaeochromocytomas and paragangliomas had distinctive clinical features and genetic alterations. The prognosis of patients with these tumours was related to the malignant potential, p53 overexpression, more common in bilateral phaeochromocytomas and paragangliomas, could be a marker for this tumour subgroup.published_or_final_versio

    Assessment and Localization of Active Discontinuities Using Energy Distribution Between Intrinsic Modes

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    A method for localization and severity assessment of structural damages is proposed. The algorithm works based on nonlinear behavior of certain type of damages such as breathing cracks which are called active discontinuities in this paper. Generally, nonlinear features are more sensitive to such damages although their extraction is sometimes controversial. A major controversy is the imposition of spurious modes on the expansion of the signal which needs to be addressed for an effective application and robustness of the method. The energy content of Intrinsic Mode Functions (IMFs), which are the resultants of Empirical Mode Decomposition (EMD), and also the shape of energy distribution between these modes before and after damage, are used for localization and severity assessment of the damages. By using EMD, we preserve the nonlinear aspects of the signal while avoiding imposition of spurious harmonics on its expansion without any assumption of stationarity. The developed algorithms are used to localize and assess the damage in a steel cantilever beam. The results show that the method can be used effectively for detecting active structural discontinuities due to damage

    Health disparities and inequalities: a study of migrant workers in Shenzhen, China

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    Internal migration has induced a profound shift on social structure across China, but the effects on health for migrants remain scarcely reported. In this study we set out to investigate the disparities in health and the potential healthcare inequalities for migrant workers in Shenzhen.published_or_final_versio

    Smoking cessation and carotid atherosclerosis: The guangzhou biobank cohort studydCVD

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    Introduction Smoking has been shown to be associated with carotid atherosclerosis in cross-sectional and prospective studies in Western populations. However, few studies have examined the reversal of risk resulting from quitting smoking, and the results are conflicting. Methods 959 men aged 50e85 years were randomly selected from phase III (2006e2007) of the Guangzhou Biobank Cohort Study into this cross-sectional study. Common carotid artery intima-media thickness (CCAIMT) was measured by B-mode ultrasonography, and carotid artery plaques were identified. Major cardiovascular risk factors, including fasting triglyceride, low-density and high-density lipoprotein (LDL and HDL) cholesterol and glucose, and systolic and diastolic blood pressure, were assessed. Results CCA-IMT and the number of carotid plaque increased from never to former to current smokers (both p≤0.001). Among former smokers compared to current smokers, after adjustment for cigarette pack-years and other potential confounders, the adjusted ORs (95% CI) for quitting for 1-9, 10-19 and 20+ years were 0.77 (0.47 to 1.26), 0.45 (0.26 to 0.79) and 0.37 (0.17 to 0.77) for the presence of CCA atherosclerosis, and 0.69 (0.43 to 1.12), 0.47 (0.27 to 0.82) and 0.45 (0.23 to 0.96) for the presence of carotid plaques, respectively. Longer duration of quitting smoking was also significantly associated with decreasing risk of the severity of CCA atherosclerosis and carotid plaques (all p≤0.001). Conclusion Smoking cessation was beneficial in attenuating the risk of carotid atherosclerosis associated with cigarette smoking. The short duration of cessation in earlier studies is a likely explanation for the inconsistent results.published_or_final_versio

    Hubble Frontier Field Free-form Mass Mapping of the Massive Multiple-merging Cluster MACSJ0717.5+3745

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    Hubble Frontier Field Free-form Mass Mapping of the Massive Multiple-merging Cluster MACSJ0717.5+3745

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    A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

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    © 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network

    Экономико-социальные аспекты развития предприятия

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    The goal of dry cow therapy (DCT) is to reduce the prevalence of intramammary infections (IMI) by eliminating existing IMI at drying off and preventing new IMI from occurring during the dry period. Due to public health concerns, however, preventive use of antibiotics has become questionable. This study evaluated selective DCT in 1,657 cows with low somatic cell count (SCC) at the last milk recording before drying off in 97 Dutch dairy herds. Low SCC was defined as <150,000 cells/mL for primiparous and <250,000 cells/mL for multiparous cows. A split-udder design was used in which 2 quarters of each cow were treated with dry cow antibiotics and the other 2 quarters remained as untreated controls. The effect of DCT on clinical mastitis (CM), bacteriological status, SCC, and antibiotic use were determined at the quarter level using logistic regression and chi-squared tests. The incidence rate of CM was found to be 1.7 times (95% confidence interval = 1.4-2.1) higher in quarters dried off without antibiotics as compared with quarters dried off with antibiotics. Streptococcus uberis was the predominant organism causing CM in both groups. Somatic cell count at calving and 14 d in milk was significantly higher in quarters dried off without antibiotics (772,000 and 46,000 cells/mL, respectively) as compared with the quarters dried off with antibiotics (578,000 and 30,000 cells/mL, respectively). Quarters with an elevated SCC at drying off and quarters with a positive culture for major pathogens at drying off had a higher risk for an SCC above 200,000 cells/mL at 14 d in milk as compared with quarters with a low SCC at drying off and quarters with a negative culture for major pathogens at drying off. For quarters that were culture-positive for major pathogens at drying off, a trend for a higher risk on CM was also found. Selective DCT, not using DCT in cows that had a low SCC at the last milk recording before drying off, significantly increased the incidence rate of CM and SCC. The decrease in antibiotic use by drying off quarters without DCT was not compensated by an increase in antibiotic use for treating CM. Total antibiotic use related to mastitis was reduced by 85% in these quarters
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