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1.
    
Glucuronidation, mediated by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, is an important metabolic process during which steroids are converted to more easily excreted compounds in steroid target tissues, such as the prostate. The aim of our study was to investigate the possible correlation between UGT1A1 promoter gene polymorphism and benign prostatic hyperplasia. 421 blood samples were obtained from 138 consecutive patients diagnosed with benign prostatic hypeplasia (BPH group) and 283 healthy volunteers (control group). A(TA)6TAA promoter polymorphism of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7 and normal homozygous 6/6) were identified. No significant differences were observed between the BPH group and controls regarding the genotyping distribution of the three UGT1A1 promoter genotypes (P = 0.39). Also, no association was found between overall disease risk and the presence of the polymorphic homozygous genotype (TA(7)/TA)7) vs. TA(6)/TA(7) + TA(6)/TA(6)) (P = 0.31). Our data suggest that the TA repeat polymorphism of UGT1A1 is not associated with increased BPH risk susceptibility in Caucasian men.  相似文献   
2.
Abdominal aortic aneurysm (AAA) is a localized dilatation of the aortic wall. The lack of an accurate AAA rupture risk index remains an important problem in the clinical management of the disease. To accurately estimate AAA rupture risk, detailed information on patient-specific wall stress distribution and aortic wall tissue yield stress is required. A complete fluid structure interaction (FSI) study is currently impractical and thus of limited clinical value. On the other hand, isolated static structural stress analysis based on a uniform wall loading is a widely used approach for AAA rupture risk estimation that, however, neglects the flow-induced wall stress variation. The aim of this study was to assess the merit of a decoupled fluid structure analysis of AAA wall stress. Anatomically correct, patient specific AAA wall models were created by 3D reconstruction of computed tomography images. Flow simulations were carried out with inflow and outflow boundary conditions obtained from patient extracted data. Static structural stress analysis was performed applying both a uniform pressure wall loading and a flow induced non-uniform pressure distribution obtained during early systolic deceleration. For the structural analysis, a hyperelastic arterial wall model and an elastic intraluminal thrombus model were assumed. The results of this study demonstrate that although the isolated static structural stress analysis approach captures the gross features of the stress distribution it underestimates the magnitude of the peak wall stress by as much as 12.5% compared to the proposed decoupled fluid structure approach. Furthermore, the decoupled approach provides potentially useful information on the nature of the aneurysmal sac flow.  相似文献   
3.
Early changes in neuroendocrine pathways are essential in the development of metabolic pathologies. Thus, it is important to have a better understanding of the signals involved in their initiation. Long-term consumption of high-fat diets induces insulin resistance, obesity, diabetes. Here, we have investigated early neural and endocrine events in the hypothalamus and hippocampus induced by a short-term high fat, low carbohydrate diet in adult male Wistar rats. The release of serotonin, which is closely associated with the actions of insulin and leptin, was measured, by electrochemical detection following reverse-phase liquid chromatography (HPLC), in the extracellular space of the medial hypothalamus and the dorsal hippocampus in samples obtained from non-anesthetized animals, by microdialysis. The high-fat diet had a specific effect on the hypothalamus. Serotonin release induced by food intake was reduced after 1 week, and effectively ceased after 6 weeks of the diet. After 1 week, there was an increased gene expression of the insulin receptor and the insulin receptor substrates IRS1 and IRS2, as measured by real-time PCR. After 6 weeks of diet, insulin gene expression increased. Leptinemia increased in all cases. This new data support the concept that high-fat diets, in addition to have peripheral effects, cause a rapid alteration in specific central mechanisms involved in energy and glucose homeostasis. The changes in the gene expression of insulin and signaling elements represent possible adaptations aimed at counterbalancing the reduced responsiveness of the serotonergic system to nutritional signals and maintaining homeostasis. Sophie M. Banas and Claude Rouch have contributed equally to this work.  相似文献   
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We reported recently that internalization of the plant blue light receptor phototropin 1 (phot1) from the plasma membrane in response to irradiation is reliant on receptor autophosphorylation. Pharmacological interference and co-immunoprecipitation analyses also indicated that light-induced internalization of phot1 involves clathrin-dependent processes. Here, we describe additional pharmacological studies that impact the subcellular localization and trafficking of Arabidopsis phot1. Alterations in the microtububle cytoskeleton led to dramatic differences in phot1 localization and function. Likewise, inhibition of phosphatidic acid (PA) signaling was found to impair phot1 localization and function. However, action of PA inhibition on phot1 function may be attributed to pleiotropic effects on cell growth. While phot1 kinase activation is necessary to stimulate its internalization, autophosphorylation is not required for phot1 turnover in response to prolonged blue light irradiation. The implications of these findings in regard to phot1 localization and function are discussed.Key words: phototropin 1 (phot1), phototropism, subcellular trafficking, autophosphorylation, protein turnover  相似文献   
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Dysregulation of leptin associated with obesity is implicated in obesity-related colon cancer, but mechanisms are elusive. Increased adiposity and elevated plasma leptin are associated with perturbed metabolism in colon and leptin receptors are expressed on colon epithelium. We hypothesise that obesity increases the sensitivity of the colon to cancer by disrupting leptin-regulated gene targets within colon tissues. PCR arrays were used to firstly identify leptin responsive genes and secondly to identify responses to leptin challenge in wild-type mice, or those lacking leptin (ob/ob). Leptin-regulated genes were localised in the colon using in situ hybridisation. IL6, IL1β and CXCL1 were up-regulated by leptin and localised to discrete cells in gut epithelium, lamina propria, muscularis and at the peritoneal serosal surface. Leptin regulates pro-inflammatory genes such as IL6, IL1β and CXCL1, and might increase the risk of colon cancer among obese individuals.  相似文献   
6.
Oct4 is an essential regulator of pluripotency in vivo and in vitro in embryonic stem cells, as well as a key mediator of the reprogramming of somatic cells into induced pluripotent stem cells. It is not known whether activation and/or repression of specific genes by Oct4 is relevant to these functions. Here, we show that fusion proteins containing the coding sequence of Oct4 or Xlpou91 (the Xenopus homolog of Oct4) fused to activating regions, but not those fused to repressing regions, behave as Oct4, suppressing differentiation and promoting maintenance of undifferentiated phenotypes in vivo and in vitro. An Oct4 activation domain fusion supported embryonic stem cell self-renewal in vitro at lower concentrations than that required for Oct4 while alleviating the ordinary requirement for the cytokine LIF. At still lower levels of the fusion, LIF dependence was restored. We conclude that the necessary and sufficient function of Oct4 in promoting pluripotency is to activate specific target genes.  相似文献   
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Bacterial synergism or antagonism in a gel cassette system   总被引:1,自引:0,他引:1  
The growth and the metabolic activity of Shewanella putrfaciens, Brochothrix thermosphacta, and Pseudomonas sp., when cultured individually or in all possible combinations in gel cassettes system supplemented with 0.1% glucose at 5 degrees C, were investigated. The overall outcome was that the coexistence of the above-mentioned microorganisms affected not only each growth rate but also their type of metabolic end products compared to the control cultures. These effects were varied and depended on the selection of the combination of the tested bacteria. For example, the growth of Pseudomonas sp. strains cocultured with either B. thermosphacta or S. putrefaciens strains resulted in different effects: a promoting one for the first and an inhibitory one for the second. Moreover, the production of formic acid and two unidentified organic acids (peaks a and b) was characteristic in all cases in which S. putrefaciens was cultured.  相似文献   
10.
    

Objective:

In children and adolescents with cardiovascular risk factors, the assessment of subclinical target‐organ damage is of paramount importance. This study investigated factors associated with carotid intima‐media thickness (cIMT) in adolescents.

Design and Methods:

A cross‐sectional study was performed in 448 apparently healthy adolescents recruited from schools (mean age 14 ± 2.2 years, 211 boys), which involved cIMT measurements (common carotid artery) and assessment of lipid profile, glucose, and blood pressure (BP).

Results:

The prevalence of overweight/obesity was 28.1%/12.7% and of BP ≥95th percentile 19.6%. Left cIMT was correlated with age (r = 0.10), waist circumference (WC) (0.15), and BP (0.21/0.13, systolic/diastolic) (all P < 0.05). Right cIMT was correlated with waist to hip ratio (WHR) (0.10), whereas the mean of left and right cIMT was correlated with WC (0.12), WHR (0.12), and systolic BP (0.14) (all P < 0.05). After the age of 13 years, boys tended to have higher cIMT than girls, which was significant in the 13‐15 years subgroup (P < 0.05). In stepwise multivariate analysis (independent variables: age, gender, WC, WHR, body mass index z‐score, lipid parameters, glucose, BP), left cIMT was independently associated with systolic BP; right cIMT with WHR; mean left and right cIMT with WC. Adolescents with BP ≥90th percentile had higher left cIMT than those <90th percentile (0.63 ± 0.09 vs. 0.61 ± 0.09 mm respectively, P < 0.05).

Conclusion:

Central adiposity and systolic BP appear to be independently associated with increased cIMT values in apparently healthy adolescents. Left side cIMT appears to be superior to right side measurements in terms of association with cardiovascular risk factors.  相似文献   
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