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GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Humans or Animals Humans Animals Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 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Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Results(1-25 of 631) Sort By: Publication Date Relevance Took: 0.638 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 26 1 2 3 4 > Last >> (631 articles found) Regulation of prorenin secretion in cultured human transfected juxtaglomerular cells. Sep 1987 F Pinet,J Mizrahi,I Laboulandine,J Menard,P Corvol The regulation of renin secretion was studied in continuous culture of human juxtaglomerular cells (JGC), which provided a permanent source of human renin production (Pinet, F., M. T. Corvol, F. Dench, J. Bourguignon, J. Feunteun, J. Ménard, and P. Corvol, 1985, Proc. Natl. Acad. Sci. USA, 82:8503-... ( view more )8507). 95% of the renin species secreted was prorenin, and therefore this study concerned primarily prorenin secretion. Renin production was stable, since the cells had been maintained in culture for more than two years. In culture, these human cells formed colonies of smooth musclelike cells, and electron microscopy showed the presence of cytoskeleton structures including myofibrils and attachment bodies. This human model was used to investigate the control of prorenin secretion in vitro at cellular level. Various pharmacological agents known to stimulate or inhibit renin secretion were tested in the cell cultures. The variations in prorenin secretion were measured in the supernatant. Forskolin, an independent receptor activator of adenylate cyclase, stimulated prorenin secretion in a dose-dependent manner and this stimulation was mediated by 3',5' cyclic-AMP (cAMP). Angiotensin II (AII) was found to inhibit prorenin secretion directly in a dose-dependent manner and atrial natriuretic factor (ANF), whose effects on human JGC were characterized for the first time, was also shown to exert such inhibition. When the effects of this inhibition by AII and ANF were tested on forskolin-mediated stimulation of prorenin secretion, the latter was inhibited and no change occurred in cAMP release. When JGC were treated with histamine, bradykinin, or one or two bradykinin analogues, the responses suggested that in these cells, H2-histamine receptors and kinin receptors are dependent on adenylate cyclase. One peptide, substance P, had an inhibitory effect on prorenin secretion but it was less important than AII and ANF. The present results demonstrate that the adenylate cyclase system of human JGC remains intact during culture and supports the hypothesis that cAMP is the second messenger and Cai2+, the final messenger involved in renin secretion. The cell system used here permits the evaluation of cellular responses and intracellular events in granulated cells in a human model. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Posttranscriptional effect of insulin-like growth factor-I on interleukin-1beta-induced type II-secreted phospholipase A2 gene expression in rabbit articular chondrocytes. Apr 15, 1997 C Jacques,G Béréziat,L Humbert,J L Olivier,M T Corvol,J Masliah,F Berenbaum Large amounts of type II-secreted phospholipase A2 (type II sPLA2) are secreted into inflammatory synovial fluid and they are believed to induce the synthesis of lipid mediators by articular chondrocytes. Preliminary experiments showed that insulin-like growth factor-I, which counteracts cartilage ... ( view more )degradation in arthritis, inhibits interleukin-1beta-induced type II sPLA2 gene expression in rabbit articular chondrocytes (Berenbaum, F., G. Thomas, S. Poiraudeau, G. Bereziat, M.T. Corvol, and J. Masliah. 1994. FEBS Lett. 340: 51-55). The present study showed that IL-1beta induced the sustained synthesis of prostaglandin E2 and a parallel increase in type II sPLA2 gene expression (assessed by enzymatic activity and Northern blot analysis), but no increase in cytosolic PLA2 gene expression (assessed by Northern and Western blot analysis) or cytosolic PLA2 activity in rabbit articular chondrocytes. IGF-I inhibited both IL-1beta-stimulated PGE2 synthesis and type II sPLA2 gene expression, but had no effect on cytosolic PLA2 gene expression. Nuclear run-on experiments revealed that IL-1beta stimulated the transcription rate of type II sPLA2 gene, giving rise to long-lived mRNA in cells treated with actinomycin D. IGF-I did not affect transcription rate, suggesting that it acts as a post-transcriptional step. Sucrose density gradient analysis of the translation step showed no effect of IGF-I on the entry of type II sPLA2 mRNA into the polysomal pool or on its distribution into the various polysomal complexes, suggesting that IGF-I does not act on the translation of the mRNA. Lastly, IGF-I strongly decreased the half-life of IL-1beta-induced type II sPLA2 mRNA (from 92 to 12 h), suggesting that IGF-I destabilizes mRNA. These data demonstrate that IL-1beta stimulates the transcription rate of the type II sPLA2 gene and gives rise to a very stable mRNA. In contrast, IGF-I decreases the half-life of the type II sPLA2 message. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Isolation and characterization of renin-producing human chorionic cells in culture. Dec 1988 F Pinet,M T Corvol,J Bourguignon,P Corvol Chorionic tissue is one of the major extrarenal sites of renin production, and as such, cultured chorionic cells are a potential model for in vitro studies of renin biosynthesis and regulation. Human chorionic cells were isolated from four chorions and maintained in tissue culture for a total of ei... ( view more )ght subcultures. Total renin production was considerable in the primary cultures, but fell gradually with successive passages. The cells could be frozen and thawed without losing their ability to divide or produce renin. Both the primary cultures and the subcultures contained a single type of elongated cell containing abundant rough endoplasmic reticulum and myofibrils, but no renin granules, suggesting that the cells had smooth muscle-like features. Immunocytochemistry indicated that they contained both renin and prorenin. The renin produced by the chorionic cells was not stored within the cells, but was released rapidly into the medium. More than 95% of the renin produced was prorenin, which, after activation, had biochemical and immunological properties similar to those of pure human renin. The cells contained a renin mRNA that had the same size as that for renal renin (1.6 kilobases), confirming the synthesis of renin by these cells. The cells were also examined for the presence of other components of the renin-angiotensin system. Angiotensinogen and angiotensin I were not detected, but angiotensin-converting enzyme was present in extracts of primary and secondary cultured cells. beta hCG and progesterone were also found in the medium of primary culture. However, the production of beta hCG and progesterone fell after the primary culture, and beta hCG and progesterone were indetectable in secondary and tertiary cultures, respectively. These experiments suggest that these two hormones do not influence renin synthesis or vice versa. Thus, these cultures of human chorionic cells synthesized considerable quantities of prorenin and can provide a permanent source of nonrenal prorenin-producing cells. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Isolation of renin-producing human cells by transfection with three simian virus 40 mutants. Dec 1985 F Pinet,M T Corvol,F Dench,J Bourguignon,J Feunteun,J Menard,P Corvol A human juxtaglomerular cell (JGC) tumor was used for the immortalization of renin-secreting cells. The transfection of primary JGC with three different simian virus 40 (SV40) mutants resulted in the continuous production of renin-secreting cells. The most efficient renin-producing cells (producing... ( view more ) about 400 pg of renin per 24 hr per ml of culture medium) were those transfected with the PAS SV40 mutant. The renin production was stable and the cell cultures have been maintained for greater than 1 year. Two types of cells were cultured together and could not be separated: round and birefringent cells, which exhibited features of mast cells, and elongated cells containing myofilaments and secretory granules. Immunocytochemical staining showed the presence of renin in this latter cell type. The renin produced by the transfected cells was not stored within the cells but was released rapidly into the medium. More than 95% of the renin produced was prorenin, which, after activation, had characteristics similar to those of pure human standard renin as to its enzymatic, immunologic, and biochemical properties, except that it was less glycosylated. These stable JGC tumoral cell lines provide a unique system for studying human renin biosynthesis and its regulation in vitro. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Renin biosynthesis by human tumoral juxtaglomerular cells. Evidences for a renin precursor. Apr 1984 F X Galen,C Devaux,A M Houot,J Menard,P Corvol,M T Corvol,M C Gubler,F Mounier,J P Camilleri Renin biosynthesis was studied in a juxtaglomerular cell tumor. The tumoral tissue had a high renin content (180 Goldblatt Units/g of tissue), was heavily stained by immunofluorescence using human renin antiserum, and exhibited numerous characteristic secretory granules by electron microscopy. In o... ( view more )ne series of experiments, renin biosynthesis was studied in tissue slices, by following the incorporation of radiolabeled amino acids into specific immunoprecipitable renin. Time course studies showed that renin was first synthesized in a high molecular weight form, 55,000 mol wt, i.e., 10,000 mol wt higher than that of active renin, and was then converted into a 44,000-mol wt form. In a second series of experiments renin tumoral cells were cultured. Small, round, birefringent cells obtained after collagenase digestion produced renin in both primary culture and subculture media. After 5 d most of the renin found in the culture medium was inactive, but could be activated by trypsin treatment. The tumoral tissue exhibited a strong renin immunofluorescence and numerous secretory granules were observed by electron microscopy. In contrast, the renin-producing cells isolated from this tumor and grown in culture showed little renin immunofluorescence and no secretory granule could be observed. The renin-producing cells in primary culture and subculture were pulsed with radiolabeled amino acids, and immunoprecipitable radiolabeled renin was found in the culture media, thus demonstrating the actual biosynthesis of the enzyme. This renin was not stored inside cultured cells but was rapidly released into the medium and had a molecular weight of 55,000. No conversion of this inactive high molecular weight renin into the active, 44,000 mol wt form of renin was observed. We postulate the existence of two pathways for the processing, packaging, and secretion of renin in the tumoral cells: in juxtaglomerular cells of tumoral tissue renin is synthesized as a preprorenin and rapidly converted into prorenin (55,000 mol wt), which is in turn packaged in secretory granules where it is processed into active renin (44,000 mol wt) and finally secreted; in the cultured tumoral cells renin is still biosynthesized as a preprorenin molecule and then converted into prorenin, but is neither stored as granules nor processed into active renin. In this case the renin is released in an inactive form. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Angiotensin-converting enzyme 2 (ACE2) expression and activity in human carotid atherosclerotic lesions. Jul 2008 Jc Sluimer,Jm Gasc,I Hamming,H van Goor,A Michaud,Lh van den Akker,B Jütten,J Cleutjens,Apjj Bijnens,P Corvol,Mjap Daemen,S Heeneman Angiotensin-converting enzyme (ACE)2 is a recently identified homologue of ACE. As ACE2 inactivates the pro-atherogenic angiotensin II, we hypothesize that ACE2 may play a protective role in atherogenesis. The spatiotemporal localization of ACE2 mRNA and protein in human vasculature and a possible ... ( view more )association with atherogenesis were investigated using molecular histology (in situ hybridization, immunohistochemistry). Also, the ACE : ACE2 balance was investigated using enzymatic assays. ACE2 mRNA was expressed in early and advanced human carotid atherosclerotic lesions. In addition, ACE2 protein was present in human veins, non-diseased mammary arteries and atherosclerotic carotid arteries and expressed in endothelial cells, smooth muscle cells and macrophages. Quantitative analysis of immunoreactivity showed that total vessel wall expression of ACE and ACE2 was similar during all stages of atherosclerosis. The observed ACE2 protein was enzymatically active and activity was lower in the stable advanced atherosclerotic lesions, compared to early and ruptured atherosclerotic lesions. These results suggest a differential regulation of ACE2 activity during the progression of atherosclerosis and suggest that this novel molecule of the renin-angiotensin system may play a role in the pathogenesis of atherosclerosis. Copyright (c) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Natural chondroitin sulphates increase aggregation of proteoglycan complexes and decrease ADAMTS-5 expression in interleukin 1 beta-treated chondrocytes. May 2008 K Tahiri,C Korwin-Zmijowska,P Richette,F Héraud,X Chevalier,J-F Savouret,M-T Corvol OBJECTIVE: To assess the effect of natural chondroitin sulphate (CS) on the ability of neosynthesized sulphated proteoglycans (PGs) to aggregate in cultured chondrocytes treated with interleukin (IL)1 beta. METHODS: Primary cultured rabbit articular chondrocytes were treated or not with IL1 beta al... ( view more )one or with concentrations of CS for 20 h. Neosynthesized PGs were labelled by incorporation of [35SO(4)]-sulphate and analysed by chromatography on Sepharose 2B columns. Gelatinolytic activity was measured by zymography, and matrix metalloproteinase (MMP)1 mRNA level in chondrocytes underwent real-time PCR. Expression of ADAMTS (for "a disintegrin and metalloproteinase with thrombospondin motifs") -4 and -5 was analysed by real-time PCR and western blotting. RESULTS: The production of [35SO(4)]-labelled PGs was significantly increased with 10 microg/ml CS in the cellular pool rather than in the incubation medium. The addition of CS to IL1 beta-treated cells inhibited in part the disaggregation of sulphated PGs induced by IL1 beta. This inhibitory effect of CS is associated with a significant decrease in ADAMTS-5 expression at the mRNA and protein levels. No effect of CS was observed on IL1 beta-induced gelatinolytic activity, MMP1 mRNA expression or ADAMTS-4 expression. CONCLUSION: CS increases the production of functional sulphated PGs in the direct environment of chondrocytes in vitro. This beneficial effect of CS in IL1 beta-treated cells is associated with decreased expression of ADAMTS-5. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Pharmacogenetic response to albuterol among asthmatics. May 2008 Harriet Corvol,Esteban González Burchard Pharmacogenetics offers to individualize asthma treatment by identifying genetic variants associated with drug efficacy or adverse events. Several studies have focused on pharmacogenetic associations with albuterol, the most commonly prescribed medication for asthma worldwide. However, pharmacogene... ( view more )tic associations have varied within and between studies and across populations. Herein, we focus on pharmacogenetic associations between genetic variants in the beta(2)-adrenergic receptor gene and bronchodilator response to albuterol among subjects with asthma. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Hypoxia, hypoxia-inducible transcription factor, and macrophages in human atherosclerotic plaques are correlated with intraplaque angiogenesis. Apr 1, 2008 Judith C Sluimer,Jean-Marie Gasc,Job L van Wanroij,Natasja Kisters,Mathijs Groeneweg,Maarten D Sollewijn Gelpke,Jack P Cleutjens,Luc H van den Akker,Pierre Corvol,Bradly G Wouters,Mat J Daemen,Ann-Pascale J Bijnens OBJECTIVES: We sought to examine the presence of hypoxia in human carotid atherosclerosis and its association with hypoxia-inducible transcription factor (HIF) and intraplaque angiogenesis. BACKGROUND: Atherosclerotic plaques develop intraplaque angiogenesis, which is a typical feature of hypoxic t... ( view more )issue and expression of HIF. METHODS: To examine the presence of hypoxia in atherosclerotic plaques, the hypoxia marker pimonidazole was infused before carotid endarterectomy in 7 symptomatic patients. Also, the messenger ribonucleic acid (mRNA) and protein expression of HIF1 alpha, HIF2 alpha, HIF-responsive genes (vascular endothelial growth factor [VEGF], glucose transporter [GLUT]1, GLUT3, hexokinase [HK]1, and HK2), and microvessel density were determined in a larger series of nondiseased and atherosclerotic carotid arteries with microarray, quantitative reverse transcription polymerase chain reaction, in situ hybridization, and immunohistochemistry. RESULTS: Pimonidazole immunohistochemistry demonstrated the presence of hypoxia, especially within the macrophage-rich center of the lesions. Hypoxia correlated with the presence of a thrombus, angiogenesis, and expression of CD68, HIF, and VEGF. The mRNA and protein expression of HIF, its target genes, and microvessel density increased from early to stable lesions, but no changes were observed between stable and ruptured lesions. CONCLUSION: This is the first study directly demonstrating hypoxia in advanced human atherosclerosis and its correlation with the presence of macrophages and the expression of HIF and VEGF. Also, the HIF pathway was associated with lesion progression and angiogenesis, suggesting its involvement in the response to hypoxia and the regulation of human intraplaque angiogenesis. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Can we live without a functional renin-angiotensin system? Apr 2008 Pierre Corvol,Annie Michaud,Olivier Gribouval,Jean-Marie Gasc,Marie-Claire Gubler 1. In mice, inactivation of any of the components of the renin-angiotensin system (i.e. renin, angiotensin-converting enzyme, angiotensinogen and AT1 receptor) is dispensable for survival at birth. Animals can survive although they are more sensitive to salt depletion than the wild type mice. 2. Re... ( view more )nal tubular dysgenesis (RTD) is a human disease consisting of severe abnormalities of renal tubular development and resulting in profound anuria and perinatal death. 3. Familial RTD is an autosomal recessive disease due to genetic defects in any of the constituents of the renin system. 4. Complete gene inactivation of the renin system in RTD leads to neonatal anuria and death. Proximal tubules are almost absent; renal artery hyperplasia is found in all cases of RTD. An intense stimulation of renin gene expression is noted in the kidney of patients with mutations affecting angiotensinogen, angiotensin-converting enzyme and AT1 receptor. 5. The more severe phenotype in humans than in mice devoid of a functional renin system may be attributable to the difference in nephrogenesis between mice and humans. In mice, nephrogenesis is completed 2 weeks after birth, whereas in humans it is completed before birth, at 38 weeks of gestation. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Inherited renal tubular dysgenesis: the first patients surviving the neonatal period. Mar 2008 Andrea Zingg-Schenk,Justine Bacchetta,Pierre Corvol,Annie Michaud,Thomas Stallmach,Pierre Cochat,Olivier Gribouval,Marie-Claire Gubler,Thomas J Neuhaus Renal tubular dysgenesis (RTD) is a clinical disorder either acquired during fetal development or inherited as an autosomal recessive condition. Inherited RTD is caused by mutations in the genes encoding the components of the renin-angiotensin system angiotensinogen, renin, angiotensin-converting e... ( view more )nzyme and angiotensin II receptor type 1. Inherited RTD is characterized by early onset oligohydramnios, skull ossification defects, preterm birth and neonatal pulmonary and renal failure. The histological hallmark is the absence or poor development of proximal tubules. So far, all patients died either in utero or shortly after birth. We report the first patients with inherited RTD surviving the neonatal period and still being alive. Genetic and functional analysis of the renin-angiotensin system contributes to the diagnosis of RTD. In conclusion, the clinical diagnosis of inherited RTD is easily missed after birth without renal biopsy or information on affected family members. Genetic and functional analysis of the renin-angiotensin system contributes to correct diagnosis. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Angiotensin-converting enzyme C-terminal catalytic domain is the main site of angiotensin I cleavage in vivo. Feb 2008 Sebastien Fuchs,Hong D Xiao,Christine Hubert,Annie Michaud,Duncan J Campbell,Jonathan W Adams,Mario R Capecchi,Pierre Corvol,Kenneth E Bernstein Angiotensin-converting enzyme (ACE) plays a central role in the production of the vasoconstrictor angiotensin II. ACE is a single polypeptide, but it contains 2 homologous and independent catalytic domains, each of which binds zinc. To understand the in vivo role of these 2 domains, we used gene ta... ( view more )rgeting to create mice with point mutations in the ACE C-domain zinc-binding motif. Such mice, termed ACE13/13, produce a full-length ACE protein with tissue expression identical to wild-type mice. Analysis of ACE13/13 mice showed that they produce ACE having only N-domain catalytic activity, as determined by the hydrolysis of domain specific substrates and by chloride sensitivity. ACE13/13 mice have blood pressure and blood angiotensin II levels similar to wild-type mice. However, plasma renin concentration is increased 2.6-fold and blood angiotensin I levels are increased 7.5-fold. Bradykinin peptide levels are not different from wild-type levels. ACE13/13 mice have a reduced increase of blood pressure after intravenous infusion of angiotensin I. ACE13/13 mice have a normal renal structure, but they are not able to concentrate urine after dehydration as effectively as wild-type mice. This study shows that the C-domain of ACE is the predominant site of angiotensin I cleavage in vivo. Although mice lacking C-domain activity have normal physiology under laboratory conditions, they respond less well to the stress of dehydration. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Circulating and airway neutrophils in cystic fibrosis display different TLR expression and responsiveness to interleukin-10. Jan 2008 Anne-France Petit-Bertron,Olivier Tabary,Harriet Corvol,Jacky Jacquot,Annick Clément,Jean-Marc Cavaillon,Minou Adib-Conquy We compared blood neutrophils (PMNs) collected from healthy subjects with PMNs derived from either blood or airways collected from the same cystic fibrosis (CF) patients. When compared to healthy blood PMNs, CF blood PMNs expressed enhanced level of CD64, a marker of neutrophil activation, and lowe... ( view more )r level of Toll-like receptor-2 (TLR2). CF airway PMNs expressed enhanced level of TLR4. Interleukin-8 (IL-8) production by CF blood PMNs could be enhanced upon addition of lipopolysaccharide or peptidoglycan, and this production was inhibited by recombinant human IL-10. In contrast, CF airway PMNs released spontaneously high level of IL-8 that was neither further enhanced by microbial activators nor inhibited by recombinant human IL-10. The levels of IL-10 receptors were similar in all types of neutrophils. These data further demonstrate that circulating PMNs from CF patients display a distinct pattern of surface markers, including TLRs, as compared to PMNs from healthy donors, and that airways PMNs from CF patients are primed and resistant to anti-inflammatory signals delivered by IL-10. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Self-measurement and self-titration in hypertension: a pilot telemedicine study. Dec 2007 Guillaume Bobrie,Nicolas Postel-Vinay,Jean Delonca,Pierre Corvol,SETHI Investigators BACKGROUND: Because of poor patient compliance and clinical inertia, hypertension control rates remain poor. Home blood-pressure measurements (HBPM) improve compliance of patients and achievement of blood pressure (BP) targets. However, few studies have evaluated self-BP management by patients. MET... ( view more )HODS: In a multicenter, prospective, single-group, open-label pilot study of 111 patients whose hypertension was uncontrolled despite monotherapy, we studied satisfaction with, and feasibility of, HBPM and self-titration of antihypertensive treatment using telemedicine for compliance, efficacy, and safety. After education (protocol, action plan, and use of the HBPM device), patients performed a sequence of HBPM every 2 weeks for 8 weeks. Following a stepwise approach, treatment was increased by the patient at weeks 4 and 6 if average HBPM values exceeded predefined limits. For each titration, the patient informed the Core Center by telemedicine, but BP values were transferred automatically. RESULTS: Overall, 80% of patients were satisfied (58%) or very satisfied (23%) with the program (95% confidence interval, 73% to 87%). Regarding compliance, 78% of patients fully complied with self-measurement, and just over 71% titrated their treatment adequately. Physicians were satisfied (52%) or very satisfied (22%) with the program. Between the first and final visits (at week 8), office systolic/diastolic BP (mean +/- SD) decreased significantly from 151 +/- 9/91 +/- 6 to 143 +/- 13/84 +/- 11 mmHg. During the trial, HBPM (mean +/- SD) decreased significantly from 149 +/- 13/86 +/- 12 to 138 +/- 16/81 +/- 10 mmHg. No significant safety issues were reported. CONCLUSIONS: This innovative approach to the management of hypertension, combining self-measurement and self-titration, is feasible, well-accepted by both patients and physicians, and safe. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Heart valve regurgitation, pergolide use, and parkinson disease: an observational study and meta-analysis. Dec 2007 Jean-Christophe Corvol,Jean-Baptiste Anzouan-Kacou,Elodie Fauveau,Anne-Marie Bonnet,Bénédicte Lebrun-Vignes,Camille Girault,Yves Agid,Philippe Lechat,Richard Isnard,Lucette Lacomblez OBJECTIVE: To investigate the prevalence and risk factors of heart valve disease in patients having PD treated with pergolide. DESIGN: Prospective observational study. SETTING: Patients were recruited at the Hôpital de la Pitié-Salpêtrière, Paris, France. Patients Ninety-six patients having PD trea... ( view more )ted with pergolide for longer than 3 months vs 50 control subjects. Intervention Standardized echocardiography performed by an investigator blinded to treatment status. Main Outcome Measure Moderate to severe regurgitation in at least 1 heart valve. RESULTS: One hundred thirty-three echocardiograms (86 in the pergolide-treated group and 47 in the control group) were analyzed in the study. Moderate to severe regurgitation was found in 15 patients treated with pergolide (17.4%) and in 2 control subjects (4.3%) (odds ratio [OR], 4.75; 95% confidence interval [CI], 1.02-22.1; P = .03). Moderate to severe regurgitation was associated with the cumulative dose of pergolide (OR, 1.37; 95% CI, 1.04-1.81 per 10-mg/kg increase; P =.03). Including the present study, the meta-analysis comprised 7 trials (394 patients treated with pergolide and 280 controls). The overall OR for moderate to severe regurgitation was 3.1 (95% CI, 1.7-5.6; P < .001) in the pergolide-treated group. Risk differences were correlated with the mean cumulative dose of pergolide (r = 0.90, P < .001). DATA SOURCES: Using an end point of moderate to severe heart valve regurgitation, we performed a meta-analysis of patients having Parkinson disease (PD) treated with pergolide mesylate vs control subjects by searching PubMed (January 1, 1966, to April 1, 2007) and the Cochrane databases to identify English-language prospective observational studies that reported echocardiographic data. CONCLUSION: Heart valve disease is independently associated with the use of pergolide treatment in patients having PD and correlates with its cumulative dose. Trial Registration clinicaltrials.gov Identifier: NCT00202657. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Multiple-locus variable-number tandem-repeat analysis for longitudinal survey of sources of Pseudomonas aeruginosa infection in cystic fibrosis patients. Oct 2007 Hoang Vu-Thien,Gaëlle Corbineau,Katia Hormigos,Brigitte Fauroux,Harriet Corvol,Annick Clément,Gilles Vergnaud,Christine Pourcel In order to identify the source of infection by Pseudomonas aeruginosa in patients with cystic fibrosis (CF), systematic genotyping of isolates is necessary. Multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) was used to survey the sources of P. aeruginosa infections in a French (P... ( view more )aris, France) pediatric CF center. Between January 2004 and December 2006, 108 patients ages 2 to 21 years who were regularly monitored at the center provided sputum for culture. P. aeruginosa was detected in 46 children, 17 of whom had primary colonization. A total of 163 isolates were recovered. MLVA was improved from a previously published method by the addition of new, informative, and easily typeable markers. Upon genotyping with 15 VNTRs, a total of 39 lineages composed of indistinguishable or closely related isolates, were observed. One of them corresponds to "clone C," which is widely distributed in Europe, and another corresponds to reference strain PA14. Six patients were colonized with two different strains, and the remaining 40 patients were colonized with a single strain. Strains from seven lineages were shared by at least two and up to four patients among a total of 20 patients. The study demonstrates that MLVA is an efficient, easy, and rapid molecular method for epidemiological surveillance for P. aeruginosa infection. The resulting data and strain genetic profiles can be queried on http://bacterial-genotyping.igmors.u-psud.fr. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Calcineurin is essential for depolarization-induced nuclear translocation and tyrosine phosphorylation of PYK2 in neurons. Sep 1, 2007 Camille Faure,Jean-Christophe Corvol,Madeleine Toutant,Emmanuel Valjent,Oivind Hvalby,Vidar Jensen,Said El Messari,Jean-Marc Corsi,Gress Kadaré,Jean-Antoine Girault Proline-rich tyrosine kinase 2 (PYK2) is a non-receptor tyrosine kinase expressed in many cell types and enriched in neurons. PYK2 is a cytoplasmic enzyme activated by increases in cytosolic free Ca(2+) through an unknown mechanism. We report that depolarization or electrical stimulation of hippoca... ( view more )mpal slices induced a rapid and transient nuclear accumulation of PYK2. Depolarization of cultured neurons or PC12 cells also triggered a Ca(2+)-dependent nuclear accumulation of PYK2, much more pronounced than that induced by blockade of nuclear export with leptomycin B. Src-family kinase activity, PYK2 autophosphorylation and kinase activity were not required for its nuclear translocation. Depolarization induced a slight decrease in PYK2 apparent molecular mass, compatible with a Ca(2+)-activated dephosphorylation. Pretreatment of PC12 cells with inhibitors of calcineurin (protein phosphatase 2B), cyclosporin A and FK506, prevented depolarization-induced nuclear translocation and tyrosine phosphorylation of PYK2. Transfection with dominant-negative and constitutively active calcineurin-A confirmed the role of calcineurin in the regulation of PYK2 tyrosine phosphorylation and nuclear accumulation. Our results show that depolarization independently induces nuclear translocation and tyrosine phosphorylation of PYK2, and that both responses require calcineurin activation. We suggest that PYK2 exerts some of its actions in the nucleus and that the effects of calcineurin inhibitors may involve PYK2 inhibition. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Characterization of the first angiotensin-converting like enzyme in bacteria: Ancestor ACE is already active. Sep 1, 2007 Guillaume Rivière,Annie Michaud,Hazel R Corradi,Edward D Sturrock,K Ravi Acharya,Virginie Cogez,Jean-Pierre Bohin,Didier Vieau,Pierre Corvol Angiotensin-converting enzyme (ACE) is a metallopeptidase that converts angiotensin I into angiotensin II. ACE is crucial in the control of cardiovascular and renal homeostasis and fertility in mammals. In vertebrates, both transmembrane and soluble ACE, containing one or two active sites, have bee... ( view more )n characterized. So far, only soluble, single domain ACEs from invertebrates have been cloned, and these have been implicated in reproduction in insects. Furthermore, an ACE-related carboxypeptidase was recently characterized in Leishmania, a unicellular eukaryote, suggesting the existence of ACE in more distant organisms. Interestingly, in silico databank analysis revealed that bacterial DNA sequences could encode putative ACE-like proteins, strikingly similar to vertebrates' enzymes. To gain more insight into the bacterial enzymes, we cloned the putative ACE from the phytopathogenic bacterium, Xanthomonas axonopodis pv. citri, named XcACE. The 2 kb open reading frame encodes a 672-amino-acid soluble protein containing a single active site. In vitro expression and biochemical characterization revealed that XcACE is a functional 72 kDa dipeptidyl-carboxypeptidase. As in mammals, this metalloprotease hydrolyses angiotensin I into angiotensin II. XcACE is sensitive to ACE inhibitors and chloride ions concentration. Variations in the active site residues, highlighted by structural modelling, can account for the different substrate selectivity and inhibition profile compared to human ACE. XcACE characterization demonstrates that ACE is an ancestral enzyme, provoking questions about its appearance and structure/activity specialisation during the course of evolution. ( view less ) View Full Abstract View Article Details   Related Articles Pharmacologic induction of heme oxygenase 1 reduces acute inflammatory arthritis in mice. Aug 2007 Mourad Benallaoua,Mathias François,Frédéric Batteux,Natacha Thelier,John Y-J Shyy,Catherine Fitting,Lydia Tsagris,Jorge Boczkowski,Jean-François Savouret,Marie-Thérèse Corvol,Serge Poiraudeau,François Rannou OBJECTIVE: To determine the consequences of pharmacologic up-regulation of heme oxygenase 1 (HO-1), and inhibition of HO-1 by injection of an anti-HO-1 small interfering RNA (siRNA), in vivo in the acute phase of a mouse model of nonautoimmune arthritis. METHODS: In the K/BxN mouse serum transfer m... ( view more )odel, which mimics human inflammatory arthritis without lymphocyte influence, HO-1 was up-regulated by intraperitoneal injection of cobalt protoporphyrin IX (CoPP), a potent pharmacologic inducer, and was inhibited using a specific siRNA. The clinical progress of arthritis was monitored by measurement of paw thickness. Interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNFalpha), serum antioxidant, and nitric oxide (NO) levels, prostaglandin E(2) (PGE(2)) production, and matrix metalloproteinase 9 (MMP-9) activity were measured in serum. At the end of the experiments, joints were examined for immunohistopathologic changes. RESULTS: Intraperitoneal injection of CoPP alleviated disease symptoms, such as joint swelling, cartilage degradation, and proliferation of inflammatory tissue in joints, in the acute phase of inflammatory arthritis. The CoPP-induced expression of HO-1 in the joints and liver was associated with marked decreases in IL-1beta, IL-6, and TNFalpha levels, PGE(2) secretion, and MMP-9 activity in serum, and with a marked increase in systemic antioxidant activity. In contrast, NO production in serum and inducible NO synthase expression in chondrocytes were not affected by HO-1 induction. Specific inhibition of HO-1 by in vivo delivery of anti-HO-1 siRNA repressed the protective effects. CONCLUSION: Our data provide the first evidence that pharmacologically induced up-regulation of HO-1 triggers a robust protective antiinflammatory response in a model of nonautoimmune arthritis in mice. This suggests that exogenously induced HO-1 may have potential as therapy in the acute phase of inflammatory arthritis in humans. ( view less ) View Full Abstract View Article Details   Related Articles Gain-of-function mutant of angiotensin II receptor, type 1A, causes hypertension and cardiovascular fibrosis in mice. Jul 2007 Sandrine Billet,Sabine Bardin,Sonia Verp,Véronique Baudrie,Annie Michaud,Sophie Conchon,Martine Muffat-Joly,Brigitte Escoubet,Evelyne Souil,Ghislaine Hamard,Kenneth E Bernstein,Jean Marie Gasc,Jean-Luc Elghozi,Pierre Corvol,Eric Clauser The role of the renin-angiotensin system has been investigated by overexpression or inactivation of its different genes in animals. However, there is no data concerning the effect of the constitutive activation of any component of the system. A knockin mouse model has been constructed with a gain-o... ( view more )f-function mutant of the Ang II receptor, type 1A (AT(1A)), associating a constitutively activating mutation (N111S) with a C-terminal deletion, which impairs receptor internalization and desensitization. In vivo consequences of this mutant receptor expression in homozygous mice recapitulate its in vitro characteristics: the pressor response is more sensitive to Ang II and longer lasting. These mice present with a moderate (~20 mmHg) and stable increase in BP. They also develop early and progressive renal fibrosis and cardiac fibrosis and diastolic dysfunction. However, there was no overt cardiac hypertrophy. The hormonal parameters (low-renin and inappropriately normal aldosterone productions) mimic those of low-renin human hypertension. This new model reveals that a constitutive activation of AT(1A) leads to cardiac and renal fibrosis in spite of a modest effect on BP and will be useful for investigating the role of Ang II in target organs in a model similar to some forms of human hypertension. ( view less ) View Full Abstract View Article Details   Related Articles Quantitative changes in Galphaolf protein levels, but not D1 receptor, alter specifically acute responses to psychostimulants. May 2007 Jean-Christophe Corvol,Emmanuel Valjent,Vincent Pascoli,Aurélie Robin,Alexandre Stipanovich,Robert R Luedtke,Leonardo Belluscio,Jean-Antoine Girault,Denis Hervé Striatal dopamine D1 receptors (D1R) are coupled to adenylyl cyclase through Galphaolf. Although this pathway is involved in important brain functions, the consequences of quantitative alterations of its components are not known. We explored the biochemical and behavioral responses to cocaine and D... ( view more )-amphetamine (D-amph) in mice with heterozygous mutations of genes encoding D1R and Galphaolf (Drd1a+/- and Gnal+/-), which express decreased levels of the corresponding proteins in the striatum. Dopamine-stimulated cAMP production in vitro and phosphorylation of AMPA receptor GluR1 subunit in response to D-amph in vivo were decreased in Gnal+/-, but not Drd1a+/- mice. Acute locomotor responses to D1 agonist SKF81259, D-amph and cocaine were altered in Gnal+/- mice, and not in Drd1a+/- mice. This haploinsufficiency showed that Galphaolf but not D1R protein levels are limiting for D1R-mediated biochemical and behavioral responses. Gnal+/- mice developed pronounced locomotor sensitization and conditioned locomotor responses after repeated injections of D-amph (2 mg/kg) or cocaine (20 mg/kg). They also developed normal D-amph-conditioned place preference. The D1R/cAMP pathway remained blunted in repeatedly treated Gnal+/- mice. In contrast, D-amph-induced ERK activation was normal in the striatum of these mice, possibly accounting for the normal development of long-lasting behavioral responses to psychostimulants. Our results clearly dissociate biochemical mechanisms involved in acute and delayed behavioral effects of psychostimulants. They identify striatal levels of Galphaolf as a key factor for acute responses to psychostimulants and suggest that quantitative alterations of its expression may alter specific responses to drugs of abuse, or possibly other behavioral responses linked to dopamine function. ( view less ) View Full Abstract View Article Details   Related Articles Angiotensinogen impairs angiogenesis in the chick chorioallantoic membrane. May 2007 Marcus Brand,Noël Lamandé,Etienne Larger,Pierre Corvol,Jean-Marie Gasc Angiotensinogen shares with other members of the serine protease inhibitor (serpin) family antiangiogenic properties. Angiotensinogen inhibits in vitro endothelial cell proliferation, and is antiangiogenic in ovo in the chick chorioallantoic membrane assay. The cellular mode of action of angiotensi... ( view more )nogen has been studied by applying purified human angiotensinogen or Chinese hamster ovary cells producing recombinant angiotensinogen onto the developing chorioallantoic membrane. Vessel density of the control and angiotensinogen-treated areas was quantitated by using Sambucus nigra lectin, a specific endothelial cell marker. After 48 h of angiotensinogen treatment by either applying purified angiotensinogen or angiotensinogen-producing Chinese hamster ovary cells, there was a 70% decrease in mesodermic vessel density in comparison to the control sections. Angiotensinogen treatment induced a strong decrease in endothelial cell proliferation of the chorioallantoic membrane vasculature, as shown by incorporation of bromo-deoxyuridine. Two days after local angiotensinogen treatment, increased apoptosis of endothelial cells of mesodermal blood vessels was detected by transferase-mediated deoxyuridine triphosphate nick end labeling assay. As assessed by in situ hybridization, the gene expression pattern of the main vascular growth factors and their receptors was not altered by angiotensinogen. Angiotensinogen, therefore, impairs angiogenesis without altering the expression level of vascular growth factors through the induction of apoptosis and decreased endothelial cell proliferation. ( view less ) View Full Abstract View Article Details   Related Articles Anti-angiogenic properties of myo-inositol trispyrophosphate in ovo and growth reduction of implanted glioma. Mar 6, 2007 Gabin Sihn,Thomas Walter,Jean-Claude Klein,Isabelle Queguiner,Hiroshi Iwao,Claude Nicolau,Jean-Marie Lehn,Pierre Corvol,Jean-Marie Gasc We investigate here the anti-angiogenic properties of the synthetic compound myo-inositol trispyrophosphate (ITPP). By increasing oxy-haemoglobin dissociation, ITPP has the potential to counteract the effects of hypoxia, a critical regulator of angiogenesis and cancer progression. ITPP inhibited an... ( view more )giogenesis of the chorioallantoic membrane (CAM), as analyzed with an original program dedicated to automated quantification of angiogenesis in this model. ITPP also markedly reduced tumor progression and angiogenesis in an experimental model of U87 glioma cell nodules grafted onto the CAM. These results point out the potential of ITPP for the development of a new class of anti-angiogenic and anti-cancer compounds. ( view less ) View Full Abstract View Article Details   Related Articles Oestrogens inhibit interleukin 1beta-mediated nitric oxide synthase expression in articular chondrocytes through nuclear factor-kappa B impairment. Mar 2007 Pascal Richette,Marie-France Dumontier,Khadija Tahiri,Magdalena Widerak,Antoine Torre,Mourad Benallaoua,Mourad Benallaloua,François Rannou,Marie-Therese Corvol,Jean-François Savouret OBJECTIVES: To investigate the presence and functionality of oestrogen receptor alpha (ERalpha) in interleukin (IL)1beta-treated rabbit articular chondrocytes in culture, and to determine the mechanisms of 17beta oestradiol (E2) effects on IL1beta-induced inducible nitric oxide synthase (iNOS) expr... ( view more )ession. METHODS: The presence and functionality of ERalpha were investigated by immunocytochemistry and transient expression of an E2-responsive reporter construct. iNOS expression and production were determined by transient expression of a chimeric iNOS promoter-luciferase construct and protein immunoblotting. Nitric oxide (NO) production was determined by the Griess reaction. DNA-binding activities of nuclear factor-kappaB (NF-kappaB) and activated protein 1 were determined by electrophoretic mobility shift assay (EMSA)-ELISA assays. Nuclear translocation of p65 was studied by immunocytochemistry. RESULTS: ERalpha was identified in the nucleus of chondrocytes. ERalpha efficiently transactivated a transiently expressed E2-responsive construct. On IL1beta treatment, ERalpha partially diffused from its nuclear localisation into the cytoplasm and its transactivation ability was impaired. Nevertheless, E2, tamoxifen and raloxifene efficiently inhibited IL1beta-induced NO production (-34%, -31% and -36%, respectively). E2 decreased IL1beta-induced iNOS protein expression (-40%). Transient expression of an iNOS promoter construct strongly suggested that iNOS expression was inhibited at the transcriptional level, and EMSA-ELISA assays showed that E2 reduced (-60%) the IL1beta-induced p65 DNA-binding capacity. Finally, the p65 nuclear translocation induced by IL1beta was also strongly decreased by E2. CONCLUSIONS: Our data support a reciprocal antagonism between oestrogens and IL1beta, ultimately resulting in the decrease of cytokine-dependent NO production through transcriptional inhibition of iNOS expression. This effect was associated with selective inhibition of p65 DNA binding and nuclear translocation. ( view less ) View Full Abstract View Article Details   Related Articles Glucocorticoid receptor gene polymorphisms associated with progression of lung disease in young patients with cystic fibrosis. 2007 Harriet Corvol,Nadia Nathan,Celine Charlier,Katarina Chadelat,Philippe Le Rouzic,Olivier Tabary,Brigitte Fauroux,Alexandra Henrion-Caude,Josue Feingold,Pierre-Yves Boelle,Annick Clement BACKGROUND: The variability in the inflammatory burden of the lung in cystic fibrosis (CF) patients together with the variable effect of glucocorticoid treatment led us to hypothesize that glucocorticoid receptor (GR) gene polymorphisms may affect glucocorticoid sensitivity in CF and, consequently,... ( view more ) may contribute to variations in the inflammatory response. METHODS: We evaluated the association between four GR gene polymorphisms, TthIII, ER22/23EK, N363S and BclI, and disease progression in a cohort of 255 young patients with CF. Genotypes were tested for association with changes in lung function tests, infection with Pseudomonas aeruginosa and nutritional status by multivariable analysis. RESULTS: A significant non-corrected for multiple tests association was found between BclI genotypes and decline in lung function measured as the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). Deterioration in FEV1 and FVC was more pronounced in patients with the BclI GG genotype compared to the group of patients with BclI CG and CC genotypes (p = 0.02 and p = 0.04 respectively for the entire cohort and p = 0.01 and p = 0.02 respectively for F508del homozygous patients). CONCLUSION: The BclI polymorphism may modulate the inflammatory burden in the CF lung and in this way influence progression of lung function. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 26 1 2 3 4 > Last >> (631 articles found)

      
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