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141.
Dequeker E Stuhrmann M Morris MA Casals T Castellani C Claustres M Cuppens H des Georges M Ferec C Macek M Pignatti PF Scheffer H Schwartz M Witt M Schwarz M Girodon E 《European journal of human genetics : EJHG》2009,17(1):51-65
The increasing number of laboratories offering molecular genetic analysis of the CFTR gene and the growing use of commercial kits strengthen the need for an update of previous best practice guidelines (published in 2000). The importance of organizing regional or national laboratory networks, to provide both primary and comprehensive CFTR mutation screening, is stressed. Current guidelines focus on strategies for dealing with increasingly complex situations of CFTR testing. Diagnostic flow charts now include testing in CFTR-related disorders and in fetal bowel anomalies. Emphasis is also placed on the need to consider ethnic or geographic origins of patients and individuals, on basic principles of risk calculation and on the importance of providing accurate laboratory reports. Finally, classification of CFTR mutations is reviewed, with regard to their relevance to pathogenicity and to genetic counselling. 相似文献
142.
Frédéric MY Monino C Marschall C Hamroun D Faivre L Jondeau G Klein HG Neumann L Gautier E Binquet C Maslen C Godfrey M Gupta P Milewicz D Boileau C Claustres M Béroud C Collod-Béroud G 《Human mutation》2009,30(2):181-190
Congenital contractural arachnodactyly (CCA) is an extremely rare disease, due to mutations in the FBN2 gene encoding fibrillin-2. Another member of the fibrillin family, the FBN1 gene, is involved in a broad phenotypic continuum of connective-tissue disorders including Marfan syndrome. Identifying not only what is in common but also what differentiates these two proteins should enable us to better comprehend their respective functions and better understand the multitude of diseases in which these two genes are involved. In 1995 we created a locus-specific database (LSDB) for FBN1 mutations with the Universal Mutation Database (UMD) tool. To facilitate comparison of identified mutations in these two genes and search for specific functional areas, we created an LSDB for the FBN2 gene: the UMD-FBN2 database. This database lists 26 published and six newly identified mutations that mainly comprise missense and splice-site mutations. Although the number of described FBN2 mutations was low, the frequency of joint dislocation was significantly higher with missense mutations when compared to splice site mutations. 相似文献
143.
Lidia Ghisdal Christophe Baron Yannick Le Meur Arnaud Lionet Jean-Michel Halimi Jean-Philippe Rerolle Fran?ois Glowacki Yvon Lebranchu Mireille Drouet Christian No?l Hakim El Housni Pascale Cochaux Karl Martin Wissing Daniel Abramowicz Marc Abramowicz 《Journal of the American Society of Nephrology : JASN》2009,20(11):2459-2467
144.
145.
Al Awwadi NA Borrot-Bouttefroy A Umar A Saucier C Segur MC Garreau C Canal M Glories Y Moore N 《Thrombosis research》2007,119(4):407-413
Previous studies showed that alcohol-free extracts of Armagnac, an oak cask aged spirit rich in polyphenols, inhibit human platelet function in vitro and in vivo, in an experimental rat arteriovenous shunt thrombosis model and in human healthy volunteers. To identify active compounds, we fractionated a freeze-dried extract of a 10-year-old Armagnac using successively chloroform, diethyl ether and ethyl acetate. The 4 resulting fractions were tested on in vitro human platelet aggregation induced by ADP and in vivo on arteriovenous shunt thrombosis after 10 days oral treatment in rats. Active components were found mainly in fractions 1 and 3: at the highest concentration (2.4 10(-2) g/l), in vitro ADP-induced aggregation was inhibited by 62.7+/-2.1% and 51.2+/-3.8% for F1 and F3, respectively, vs 18.9+/-2.4% and 13.9+/-0.4% for fractions 2 and 4 and 33.6+/-1.5% for the crude extract. There was a significant decrease in thrombus weight with the crude extract and all fractions tested after 10 days treatment with 2.5 mg/kg/day orally, greatest with fraction 1. Characterisation of phenol content showed that fraction 1, the most biologically active, was essentially devoid of ellagic acid and ellagitannins, the polyphenols initially thought responsible for the effect, whereas fraction 2 which was mostly inactive, was the richest in polyphenols. CONCLUSION: The antiplatelet and antithrombotic activity of Armagnac seems mostly unrelated to polyphenols. 相似文献
146.
Platel JC Dupuis A Boisseau S Villaz M Albrieux M Brocard J 《The European journal of neuroscience》2007,25(4):920-928
Spontaneous calcium activity can be detected in embryonic mouse cortical slices as fluorescence intensity variations, in the presence of a fluorescent calcium indicator. Current methods to detect and quantify these variations depend heavily on experimenters whose judgement may interfere with measurement. In the present work, we developed new software called CalSignal for automatic detection and tracking of cellular bodies and quantification of spontaneous calcium activity on time-series of confocal fluorescence images. Analysis of 28 neocortical slices revealed that 21.0% of detected cells displayed peaks of fluorescence corresponding to spontaneous activity, with a mean frequency of one peak per 4 min. This activity was blocked in the absence of extracellular calcium but was not modified after depletion of calcium stores with thapsigargin or blockade of voltage-gated calcium channels with Ni2+. Further, statistical analysis of calcium activity revealed concomitant activation of distant cells in 24 slices, and the existence of a significant network of synchrony based on such coactivations in 17 slices out of 28. These networks enclosed 84.3% of active cells, scattered throughout the neocortical wall (mean distance between cellular bodies, 111.7 microm). Finally, it was possible to identify specific cells which were synchronously active with more neighbouring cells than others. The identity of these nodal cells remains to be investigated to fully comprehend the role of spontaneous calcium activity, before synaptogenesis, in shaping cortical neurogenesis. 相似文献
147.
148.
Gender-related differences in the metabolic response to fasting 总被引:2,自引:0,他引:2
Soeters MR Sauerwein HP Groener JE Aerts JM Ackermans MT Glatz JF Fliers E Serlie MJ 《The Journal of clinical endocrinology and metabolism》2007,92(9):3646-3652
CONTEXT: Free fatty acids (FFA) may induce insulin resistance via synthesis of intramyocellular ceramide. During fasting, women have lower plasma glucose levels than men despite higher plasma FFA, suggesting protection from FFA-induced insulin resistance. OBJECTIVE: We studied whether the relative protection from FFA-induced insulin resistance during fasting in women is associated with lower muscle ceramide concentrations compared with men. MAIN OUTCOME MEASURES AND DESIGN: After a 38-h fast, measurements of glucose and lipid fluxes and muscle ceramide and fatty acid translocase/CD36 were performed before and after a hyperinsulinemic euglycemic clamp. RESULTS: Plasma glucose levels were significantly lower in women than men with a trend for a lower endogenous glucose production in women, whereas FFA and lipolysis were significantly higher. Insulin-mediated peripheral glucose uptake was not different between sexes. There was no gender difference in muscle ceramide in the basal state, and ceramide did not correlate with peripheral glucose uptake. Muscle fatty acid translocase/CD36 was not different between sexes in the basal state and during the clamp. CONCLUSION: After 38 h of fasting, plasma FFA were higher and plasma glucose was lower in women compared with men. The higher plasma FFA did not result in differences in peripheral insulin sensitivity, possibly because of similar muscle ceramide and fatty acid translocase/CD36 levels in men and women. We suggest that during fasting, women are relatively protected from FFA-induced insulin resistance by preventing myocellular accumulation of ceramide. 相似文献
149.
150.
Quantification of myocardial blood flow with <Superscript>82</Superscript>Rb dynamic PET imaging 总被引:1,自引:0,他引:1
Lortie M Beanlands RS Yoshinaga K Klein R Dasilva JN DeKemp RA 《European journal of nuclear medicine and molecular imaging》2007,34(11):1765-1774
Purpose The PET tracer 82Rb is commonly used to evaluate regional perfusion defects for the diagnosis of coronary artery disease. There is limited
information on the quantification of myocardial blood flow and flow reserve with this tracer. The goal of this study was to
investigate the use of a one-compartment model of 82Rb kinetics for the quantification of myocardial blood flow.
Methods Fourteen healthy volunteers underwent rest and dipyridamole stress imaging with both 13N-ammonia and 82Rb within a 2-week interval. Myocardial blood flow was estimated from the time-activity curves measured with 13N-ammonia using a standard two-compartment model. The uptake parameter of the one-compartment model was estimated from the
time-activity curves measured with 82Rb. To describe the relationship between myocardial blood flow and the uptake parameter, a nonlinear extraction function was
fitted to the data. This function was then used to convert estimates of the uptake parameter to flow estimates. The extraction
function was validated with an independent data set obtained from 13 subjects with documented evidence of coronary artery
disease (CAD).
Results The one-compartment model described 82Rb kinetics very well (median R-square = 0.98). The flow estimates obtained with 82Rb were well correlated with those obtained with 13N-ammonia (r = 0.85), and the best-fit line did not differ significantly from the identity line. Data obtained from the subjects with
CAD confirmed the validity of the estimated extraction function.
Conclusion It is possible to obtain accurate estimates of myocardial blood flow and flow reserve with a one-compartment model of 82Rb kinetics and a nonlinear extraction function. 相似文献