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Article: Genetic variability of arrhenotokous and thelytokous Venturia canescens (Hymenoptera)

Mateo Leach, Irene / Ferber, Steven / van de Zande, Louis / Beukeboom, Leo W

Genetica. 2012 Mar., v. 140, no. 1-3

2012

Abstract: The ichneumonid wasp Venturia canescens (Hymenoptera) has been studied extensively for foraging behaviour and population dynamics of sexually (arrhenotokous) and parthenogenetically (thelytokous) reproducing individuals. Here we report the development of ...

Abstract	The ichneumonid wasp Venturia canescens (Hymenoptera) has been studied extensively for foraging behaviour and population dynamics of sexually (arrhenotokous) and parthenogenetically (thelytokous) reproducing individuals. Here we report the development of a set of microsatellite markers for V.canescens and use them to show that arrhenotokous individuals have more genetic variability than thelytokous ones, which are even homozygous for all tested loci. Crosses between arrhenotokous individuals suggested one marker, Vcan071, to be linked with the Complementary Sex Determiner (CSD) locus and one, Vcan109, with the Virus Like Protein (vlp-p40) locus. The genome size of V. canescens was estimated to be 274–279 Mb. We discuss how both reproductive modes can give rise to the observed genetic variability and how the new markers can be used for future genetic studies of V. canescens.
Keywords	Venturia canescens ; crossing ; foraging ; genetic variation ; genome ; loci ; microsatellite repeats ; population dynamics ; viruses
Language	English
Dates of publication	2012-03
Size	p. 53-63.
Publishing place	Springer-Verlag
Document type	Article
ZDB-ID	2165-9
ISSN	1573-6857 ; 0016-6707
ISSN (online)	1573-6857
ISSN	0016-6707
DOI	10.1007/s10709-012-9657-6
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Article ; Online: Genetic variability of arrhenotokous and thelytokous Venturia canescens (Hymenoptera).

Mateo Leach, Irene / Ferber, Steven / van de Zande, Louis / Beukeboom, Leo W

Genetica

2012 Volume 140, Issue 1-3, Page(s) 53–63

Abstract	The ichneumonid wasp Venturia canescens (Hymenoptera) has been studied extensively for foraging behaviour and population dynamics of sexually (arrhenotokous) and parthenogenetically (thelytokous) reproducing individuals. Here we report the development of a set of microsatellite markers for V.canescens and use them to show that arrhenotokous individuals have more genetic variability than thelytokous ones, which are even homozygous for all tested loci. Crosses between arrhenotokous individuals suggested one marker, Vcan071, to be linked with the Complementary Sex Determiner (CSD) locus and one, Vcan109, with the Virus Like Protein (vlp-p40) locus. The genome size of V. canescens was estimated to be 274-279 Mb. We discuss how both reproductive modes can give rise to the observed genetic variability and how the new markers can be used for future genetic studies of V. canescens.
MeSH term(s)	Animals ; Crosses, Genetic ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/genetics ; Female ; Genetic Variation ; Genome Size/genetics ; Genome, Insect/genetics ; Haplotypes ; Male ; Microsatellite Repeats/genetics ; Parthenogenesis/genetics ; Phylogeny ; Reproduction/genetics ; Wasps/classification ; Wasps/genetics
Chemical Substances	DNA, Mitochondrial ; Electron Transport Complex IV (EC 1.9.3.1)
Language	English
Publishing date	2012-05-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2165-9
ISSN	1573-6857 ; 0016-6707
ISSN (online)	1573-6857
ISSN	0016-6707
DOI	10.1007/s10709-012-9657-6
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Article ; Online: Pharmacoepigenetics in heart failure.

Mateo Leach, Irene / van der Harst, Pim / de Boer, Rudolf A

Current heart failure reports

2010 Volume 7, Issue 2, Page(s) 83–90

Abstract: Epigenetics studies inheritable changes of genes and gene expression that do not concern DNA nucleotide variation. Such modifications include DNA methylation, several forms of histone modification, and microRNAs. From recent studies, we know not only ... ...

Abstract	Epigenetics studies inheritable changes of genes and gene expression that do not concern DNA nucleotide variation. Such modifications include DNA methylation, several forms of histone modification, and microRNAs. From recent studies, we know not only that genetic changes account for heritable phenotypic variation, but that epigenetic changes also play an important role in the variation of predisposition to disease and to drug response. In this review, we discuss recent evidence of epigenetic changes that play an important role in the development of cardiac hypertrophy and heart failure and may dictate response to therapy.
MeSH term(s)	DNA Methylation ; Epigenesis, Genetic ; Genetic Predisposition to Disease ; Heart Failure/genetics ; Humans ; MicroRNAs/genetics ; Pharmacogenetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2010-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2151202-4
ISSN	1546-9549 ; 1546-9530
ISSN (online)	1546-9549
ISSN	1546-9530
DOI	10.1007/s11897-010-0011-y
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Article ; Online: Inhibition of Interleukin-6 Receptor in a Murine Model of Myocardial Ischemia-Reperfusion.

Hartman, Minke H T / Vreeswijk-Baudoin, Inge / Groot, Hilde E / van de Kolk, Kees W A / de Boer, Rudolf A / Mateo Leach, Irene / Vliegenthart, Rozemarijn / Sillje, Herman H W / van der Harst, Pim

PloS one

2016 Volume 11, Issue 12, Page(s) e0167195

Abstract: Background: Interleukin-6 (IL-6) levels are upregulated in myocardial infarction. Recent data suggest a causal role of the IL-6 receptor (IL-6R) in coronary heart disease. We evaluated if IL-6R blockade by a monoclonal antibody (MR16-1) prevents the ... ...

Abstract	Background: Interleukin-6 (IL-6) levels are upregulated in myocardial infarction. Recent data suggest a causal role of the IL-6 receptor (IL-6R) in coronary heart disease. We evaluated if IL-6R blockade by a monoclonal antibody (MR16-1) prevents the heart from adverse left ventricular remodeling in a mouse model of ischemia-reperfusion (I/R). Methods: CJ57/BL6 mice underwent I/R injury (left coronary artery ligation for 45 minutes) or sham surgery, and thereafter received MR16-1 (2mg/mouse) 5 minutes before reperfusion and 0.5mg/mouse weekly during four weeks, or control IgG treatment. Cardiac Magnetic Resonance Imaging (CMR) and hemodynamic measurements were performed to determine cardiac function after four weeks. Results: I/R caused left ventricular dilatation and a decrease in left ventricular ejection fraction (LVEF). However, LVEF was significantly lower in the MR16-1 treatment group compared to the IgG group (28±4% vs. 35±6%, p = 0.02; sham 45±6% vs. 43±4%, respectively; p = NS). Cardiac relaxation (assessed by dP/dT) was not significantly different between the MR16-1 and IgG groups. Also, no differences were observed in histological myocardial fibrosis, infarct size and myocyte hypertrophy between the groups. Conclusion: Blockade of the IL-6R receptor by the monoclonal MR16-1 antibody for four weeks started directly after I/R injury did not prevent the process of cardiac remodeling in mice, but rather associated with a deterioration in the process of adverse cardiac remodeling.
MeSH term(s)	Animals ; Antibodies, Monoclonal/pharmacology ; Disease Models, Animal ; Fibrosis/metabolism ; Heart/drug effects ; Heart/physiopathology ; Hemodynamics/drug effects ; Hypertrophy/metabolism ; Interleukin-6/blood ; Interleukin-6/metabolism ; Male ; Mice, Inbred C57BL ; Microscopy, Fluorescence ; Myocardial Infarction/metabolism ; Myocardial Infarction/pathology ; Myocardial Infarction/prevention & control ; Myocardial Reperfusion Injury/metabolism ; Myocardial Reperfusion Injury/physiopathology ; Myocardium/metabolism ; Myocardium/pathology ; Receptors, Interleukin-6/antagonists & inhibitors ; Receptors, Interleukin-6/metabolism ; Time Factors ; Ventricular Remodeling/drug effects
Chemical Substances	Antibodies, Monoclonal ; Interleukin-6 ; Receptors, Interleukin-6
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0167195
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Article ; Online: Leukocyte telomere length and left ventricular function after acute ST-elevation myocardial infarction: data from the glycometabolic intervention as adjunct to primary coronary intervention in ST elevation myocardial infarction (GIPS-III) trial.

Haver, Vincent G / Hartman, Minke H T / Mateo Leach, Irene / Lipsic, Erik / Lexis, Chris P / van Veldhuisen, Dirk J / van Gilst, Wiek H / van der Horst, Iwan C / van der Harst, Pim

Clinical research in cardiology : official journal of the German Cardiac Society

2015 Volume 104, Issue 10, Page(s) 812–821

Abstract: Background: Telomere length has been associated with coronary artery disease and heart failure. We studied whether leukocyte telomere length is associated with left ventricular ejection fraction (LVEF) after ST-elevation myocardial infarction (STEMI).!## ...

Abstract	Background: Telomere length has been associated with coronary artery disease and heart failure. We studied whether leukocyte telomere length is associated with left ventricular ejection fraction (LVEF) after ST-elevation myocardial infarction (STEMI). Methods and results: Leukocyte telomere length (LTL) was determined using the monochrome multiplex quantitative PCR method in 353 patients participating in the glycometabolic intervention as adjunct to primary percutaneous coronary intervention in STEMI III trial. LVEF was assessed by magnetic resonance imaging. The mean age of patients was 58.9 ± 11.6 years, 75 % were male. In age- and gender-adjusted models, LTL at baseline was significantly associated with age (beta ± standard error; -0.33 ± 0.01; P < 0.01), gender (0.15 ± 0.03; P < 0.01), TIMI flow pre-PCI (0.05 ± 0.03; P < 0.01), TIMI flow post-PCI (0.03 ± 0.04; P < 0.01), myocardial blush grade (-0.05 ± 0.07; P < 0.01), serum glucose levels (-0.11 ± 0.01; P = 0.03), and total leukocyte count (-0.11 ± 0.01; P = 0.04). At 4 months after STEMI, LVEF was well preserved (54.1 ± 8.4 %) and was not associated with baseline LTL (P = 0.95). Baseline LTL was associated with n-terminal pro-brain natriuretic peptide (NT-proBNP) at 4 months (-0.14 ± 0.01; P = 0.02), albeit not independent for age and gender. Conclusion: Our study does not support a role for LTL as a causal factor related to left ventricular ejection fraction after STEMI.
MeSH term(s)	Acute Disease ; Causality ; Combined Modality Therapy ; Comorbidity ; Double-Blind Method ; Female ; Genetic Predisposition to Disease/epidemiology ; Genetic Predisposition to Disease/genetics ; Humans ; Hypoglycemic Agents/therapeutic use ; Incidence ; Leukocytes ; Longitudinal Studies ; Male ; Metformin/therapeutic use ; Middle Aged ; Myocardial Infarction/epidemiology ; Myocardial Infarction/genetics ; Myocardial Infarction/therapy ; Netherlands/epidemiology ; Percutaneous Coronary Intervention/statistics & numerical data ; Placebo Effect ; Risk Assessment ; Telomere Shortening/genetics ; Treatment Outcome ; Ventricular Dysfunction, Left/epidemiology ; Ventricular Dysfunction, Left/genetics ; Ventricular Dysfunction, Left/therapy
Chemical Substances	Hypoglycemic Agents ; Metformin (9100L32L2N)
Language	English
Publishing date	2015-10
Publishing country	Germany
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2213295-8
ISSN	1861-0692 ; 1861-0684
ISSN (online)	1861-0692
ISSN	1861-0684
DOI	10.1007/s00392-015-0848-x
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Article ; Online: Mutations in

van den Berg, Maarten P / Almomani, Rowida / Biaggioni, Italo / van Faassen, Martijn / van der Harst, Pim / Silljé, Herman H W / Mateo Leach, Irene / Hemmelder, Marc H / Navis, Gerjan / Luijckx, Gert Jan / de Brouwer, Arjan P M / Venselaar, Hanka / Verbeek, Marcel M / van der Zwaag, Paul A / Jongbloed, Jan D H / van Tintelen, J Peter / Wevers, Ron A / Kema, Ido P

Circulation research

2018 Volume 122, Issue 6, Page(s) 846–854

Abstract: Rationale: Orthostatic hypotension is a common clinical problem, but the underlying mechanisms have not been fully delineated.: Objective: We describe 2 families, with 4 patients in total, experiencing severe life-threatening orthostatic hypotension ... ...

Abstract	Rationale: Orthostatic hypotension is a common clinical problem, but the underlying mechanisms have not been fully delineated. Objective: We describe 2 families, with 4 patients in total, experiencing severe life-threatening orthostatic hypotension because of a novel cause. Methods and results: As in dopamine β-hydroxylase deficiency, concentrations of norepinephrine and epinephrine in the patients were low. Plasma dopamine β-hydroxylase activity, however, was normal, and the Conclusions: This study is the first to implicate cytochrome b561 in disease by showing that pathogenic mutations in
MeSH term(s)	Adrenal Glands/metabolism ; Adult ; Animals ; Ascorbic Acid/metabolism ; Brain/metabolism ; Catecholamines/metabolism ; Codon, Nonsense ; Cytochrome b Group/genetics ; Female ; Humans ; Hypotension, Orthostatic/genetics ; Hypotension, Orthostatic/pathology ; Mice ; Mice, Inbred C57BL ; Norepinephrine/metabolism ; Pedigree ; Secretory Vesicles/metabolism ; Syndrome
Chemical Substances	Catecholamines ; Codon, Nonsense ; Cytochrome b Group ; Ascorbic Acid (PQ6CK8PD0R) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2018-01-17
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.117.311949
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Article ; Online: Parental vitamin D deficiency during pregnancy is associated with increased blood pressure in offspring via Panx1 hypermethylation.

Meems, Laura M G / Mahmud, Hasan / Buikema, Hendrik / Tost, Jörg / Michel, Sven / Takens, Janny / Verkaik-Schakel, Rikst N / Vreeswijk-Baudoin, Inge / Mateo-Leach, Irene V / van der Harst, Pim / Plösch, Torsten / de Boer, Rudolf A

American journal of physiology. Heart and circulatory physiology

2016 Volume 311, Issue 6, Page(s) H1459–H1469

Abstract: Vitamin D deficiency is one of the most common nutritional deficiencies worldwide. Maternal vitamin D deficiency is associated with increased susceptibility to hypertension in offspring, but the reasons for this remain unknown. The aim of this study was ... ...

Abstract	Vitamin D deficiency is one of the most common nutritional deficiencies worldwide. Maternal vitamin D deficiency is associated with increased susceptibility to hypertension in offspring, but the reasons for this remain unknown. The aim of this study was to determine if parental vitamin D deficiency leads to altered DNA methylation in offspring that may relate to hypertension. Male and female Sprague-Dawley rats were fed a standard or vitamin D-depleted diet. After 10 wk, nonsibling rats were mated. The conceived pups received standard chow. We observed an increased systolic and diastolic blood pressure in the offspring from depleted parents (F1-depl). Genome-wide methylation analyses in offspring identified hypermethylation of the promoter region of the Pannexin-1 (Panx1) gene in F1-depl rats. Panx1 encodes a hemichannel known to be involved in endothelial-dependent relaxation, and we demonstrated that in F1-depl rats the increase in blood pressure was associated with impaired endothelial relaxation of the large vessels, suggesting an underlying biological mechanism of increased blood pressure in children from parents with vitamin deficiency. Parental vitamin D deficiency is associated with epigenetic changes and increased blood pressure levels in offspring.
MeSH term(s)	Animals ; Atrial Natriuretic Factor/genetics ; Blood Pressure/genetics ; Blotting, Western ; Connexins/genetics ; DNA Methylation ; Endothelium, Vascular/physiopathology ; Epigenesis, Genetic ; Female ; Hypertension/genetics ; Hypertension/physiopathology ; Male ; Maternal Exposure ; Nerve Tissue Proteins/genetics ; Parathyroid Hormone/metabolism ; Paternal Exposure ; Pregnancy ; Pregnancy Complications/genetics ; Prenatal Exposure Delayed Effects/genetics ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Receptor, Angiotensin, Type 1/genetics ; Receptors, Calcitriol/genetics ; Renin/genetics ; Vasodilation/genetics ; Vitamin D/analogs & derivatives ; Vitamin D/metabolism ; Vitamin D Deficiency/genetics ; Vitamin D Deficiency/metabolism
Chemical Substances	Connexins ; Nerve Tissue Proteins ; Parathyroid Hormone ; RNA, Messenger ; Receptor, Angiotensin, Type 1 ; Receptors, Calcitriol ; pannexin 1, rat ; Vitamin D (1406-16-2) ; Atrial Natriuretic Factor (85637-73-6) ; 25-hydroxyvitamin D (A288AR3C9H) ; Renin (EC 3.4.23.15)
Language	English
Publishing date	2016-10-21
Publishing country	United States
Document type	Journal Article ; Video-Audio Media ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00141.2016
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Article ; Online: Genetic determinants of P wave duration and PR segment.

Verweij, Niek / Mateo Leach, Irene / van den Boogaard, Malou / van Veldhuisen, Dirk J / Christoffels, Vincent M / Hillege, Hans L / van Gilst, Wiek H / Barnett, Phil / de Boer, Rudolf A / van der Harst, Pim

Circulation. Cardiovascular genetics

2014 Volume 7, Issue 4, Page(s) 475–481

Abstract: Background: The PR interval on the ECG reflects atrial depolarization and atrioventricular nodal delay which can be partially differentiated by P wave duration and PR segment, respectively. Genome-wide association studies have identified several genetic ...

Abstract	Background: The PR interval on the ECG reflects atrial depolarization and atrioventricular nodal delay which can be partially differentiated by P wave duration and PR segment, respectively. Genome-wide association studies have identified several genetic loci for PR interval, but it remains to be determined whether this is driven by P wave duration, PR segment, or both. Methods and results: We replicated 7 of the 9 known PR interval loci in 16 468 individuals of European ancestry. Four loci were unambiguously associated with PR segment, while the others were shared for P wave duration and PR segment. Next, we performed a genome-wide analysis on P wave duration and PR segment separately and identified 5 novel loci. Single-nucleotide polymorphisms in KCND3 (P=8.3×10(-11)) and FADS2 (P=2.7×10(-8)) were associated with P wave duration, whereas single-nucleotide polymorphisms near IL17D (P=2.3×10(-8)), in EFHA1 (P=3.3×10(-10)), and in LRCH1 (P=2.1×10(-8)) were associated with PR segment. Analysis on DNA elements indicated that genome-wide significant single-nucleotide polymorphisms were enriched at genomic regions suggesting active gene transcription in the human right atrium. Quantitative polymerase chain reaction showed that genes were significantly higher expressed in the right atrium and atrioventricular node compared with left ventricle (P=5.6×10(-6)). Conclusions: Genetic associations of PR interval seem to be mainly driven by genetic determinants of the PR segment. Some of the PR interval associations are strengthened by a directional consistent effect of genetic determinants of P wave duration. Through genome-wide association we also identified genetic variants specifically associated with P wave duration which might be relevant for cardiac biology.
MeSH term(s)	Atrioventricular Node/metabolism ; Calcium-Binding Proteins/genetics ; Cohort Studies ; Electrocardiography ; Fatty Acid Desaturases/genetics ; Gene Expression Regulation ; Genetic Loci ; Genome-Wide Association Study ; Genotype ; Heart Atria/metabolism ; Heart Ventricles/metabolism ; Humans ; Interleukin-17/genetics ; Kidney Failure, Chronic/genetics ; Kidney Failure, Chronic/pathology ; Microfilament Proteins/genetics ; Polymorphism, Single Nucleotide ; Shal Potassium Channels/genetics
Chemical Substances	Calcium-Binding Proteins ; IL17D protein, human ; Interleukin-17 ; KCND3 protein, human ; LRCH1 protein, human ; Microfilament Proteins ; Shal Potassium Channels ; Fatty Acid Desaturases (EC 1.14.19.-) ; FADS2 protein, human (EC 1.14.19.3)
Language	English
Publishing date	2014-05-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2477394-3
ISSN	1942-3268 ; 1942-325X
ISSN (online)	1942-3268
ISSN	1942-325X
DOI	10.1161/CIRCGENETICS.113.000373
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Article ; Online: Telomere length and outcomes in ischaemic heart failure: data from the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA).

Haver, Vincent G / Mateo Leach, Irene / Kjekshus, John / Fox, Jayne C / Wedel, Hans / Wikstrand, John / de Boer, Rudolf A / van Gilst, Wiek H / McMurray, John J V / van Veldhuisen, Dirk J / van der Harst, Pim

European journal of heart failure

2015 Volume 17, Issue 3, Page(s) 313–319

Abstract: Aims: Leucocyte telomere length is considered a marker of biological ageing and has been suggested to be shorter in patients with CAD and heart failure compared with healthy controls. The aim of this study was to determine whether telomere length is ... ...

Abstract	Aims: Leucocyte telomere length is considered a marker of biological ageing and has been suggested to be shorter in patients with CAD and heart failure compared with healthy controls. The aim of this study was to determine whether telomere length is associated with clinical outcomes in patients with ischaemic heart failure and whether this association is superior to chronological age as defined by date of birth. Methods and results: We measured leucocyte telomere length in 3275 patients with chronic ischaemic systolic heart failure participating in the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA) study. The primary composite endpoint was cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, which occurred in 575 patients during follow-up. We observed a significant association of leucocyte telomere lengths with the primary endpoint (hazard ratio 1.10; 95% confidence interval 1.01-1.20; P=0.03). However, this observation was not superior to age as defined by date of birth. The neutral effect of rosuvastatin treatment on clinical outcomes was not modified by baseline telomere length. Conclusion: Biological age as defined by leucocyte telomere length was associated with clinical outcomes in patients with ischaemic heart failure, but this association did not add prognostic information above age as defined by date of birth.
MeSH term(s)	Aged ; Aged, 80 and over ; Aging/physiology ; Biomarkers ; Double-Blind Method ; Female ; Heart Failure/diagnosis ; Heart Failure/mortality ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Leukocytes/physiology ; Male ; Myocardial Ischemia/drug therapy ; Myocardial Ischemia/genetics ; Retrospective Studies ; Rosuvastatin Calcium/therapeutic use ; Telomere
Chemical Substances	Biomarkers ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Rosuvastatin Calcium (83MVU38M7Q)
Language	English
Publishing date	2015-03
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1483672-5
ISSN	1879-0844 ; 1388-9842
ISSN (online)	1879-0844
ISSN	1388-9842
DOI	10.1002/ejhf.237
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Article ; Online: Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study.

Vimaleswaran, Karani S / Cavadino, Alana / Verweij, Niek / Nolte, Ilja M / Mateo Leach, Irene / Auvinen, Juha / Veijola, Juha / Elliott, Paul / Penninx, Brenda W / Snieder, Harold / Järvelin, Marjo-Riitta / van der Harst, Pim / Cohen, Robert D / Boucher, Barbara J / Hyppönen, Elina

European journal of endocrinology

2015 Volume 173, Issue 6, Page(s) 863–872

Abstract: Background and objective: Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause ... ...

Abstract	Background and objective: Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause liver disease through their interactions with obesity and alcohol intake. To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations (n=20 242). Design and methods: The study populations included the Northern Finland Birth Cohort 1966 (n=4996), Netherlands Study of Depression and Anxiety (n=1883) and LifeLines Cohort Study (n=13 363). Interactions between the polymorphisms and obesity and alcohol intake on dichotomised ALT and GGT levels were assessed using logistic regression and the likelihood ratio test. Results: In the meta-analysis of the three cohorts, none of the three UCP2 polymorphisms were associated with GGT or ALT levels. There was no evidence for interaction between the polymorphisms and alcohol intake on GGT and ALT levels. In contrast, the association of WC and BMI with GGT levels varied by rs659366 genotype (Pinteraction=0.03 and 0.007, respectively; adjusted for age, gender, high alcohol intake, diabetes, hypertension and serum lipid concentrations). Conclusion: In conclusion, our findings in 20 242 individuals suggest that UCP2 gene polymorphisms may cause liver dysfunction through the interaction with body fat rather than alcohol intake.
MeSH term(s)	Adult ; Alanine Transaminase/metabolism ; Alcohol Drinking/metabolism ; Cohort Studies ; Female ; Finland ; Gene-Environment Interaction ; Humans ; Ion Channels/genetics ; Liver Diseases/genetics ; Liver Diseases/metabolism ; Liver Function Tests ; Logistic Models ; Male ; Middle Aged ; Mitochondrial Proteins/genetics ; Netherlands ; Obesity/metabolism ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Risk Factors ; Uncoupling Protein 2 ; gamma-Glutamyltransferase/metabolism
Chemical Substances	Ion Channels ; Mitochondrial Proteins ; UCP2 protein, human ; Uncoupling Protein 2 ; gamma-Glutamyltransferase (EC 2.3.2.2) ; gamma-glutamyltransferase, human (EC 2.3.2.2) ; Alanine Transaminase (EC 2.6.1.2)
Language	English
Publishing date	2015-10-29
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1183856-5
ISSN	1479-683X ; 0804-4643
ISSN (online)	1479-683X
ISSN	0804-4643
DOI	10.1530/EJE-15-0839
Database	MEDical Literature Analysis and Retrieval System OnLINE

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