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  • Autonomes Nervensystem  (1)
  • BINDING
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  • 1
    Keywords: CELLS ; EXPRESSION ; CELL ; COMBINATION ; Germany ; human ; COHORT ; POPULATION ; RISK ; GENE ; PROTEIN ; SAMPLE ; SAMPLES ; DNA ; BINDING ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; VARIANTS ; HUMANS ; ASSAY ; PROMOTER ; SNP ; OBESITY ; SINGLE ; VARIANT ; SINGLE NUCLEOTIDE POLYMORPHISMS ; FUNCTIONAL-CHARACTERIZATION ; HAPLOTYPES ; INSULIN-RESISTANCE ; metabolic syndrome ; USA ; REPLACEMENT ; Adiponectin ; STATE ; Luciferase reporter ; PLASMA ADIPONECTIN ; TYPE-2 DIABETIC-PATIENTS ; APM1 GENE ; HYPOADIPONECTINEMIA
    Abstract: OBJECTIVE-Adiponectin (APM1, ACDC) is an adipocyte-derived protein with downregulated expression in obesity and insulin-resistant states. Several potentially regulatory single nucleotide polymorphisms (SNPs) within the APM1 gene promoter region have been associated with circulating adiponectin levels. None of them have been functionally characterized in adiponectin-expressing cells. Hence, we investigated three SNPs (rs16861194, rs17300539, and rs266729) for their influence on adiponectin promoter activity and their association with circulating adiponectin levels. RESEARCH DESIGN AND METHODS-Basal and rosiglitazone-induced promoter activity of different SNP combinations (haplotypes) was analyzed in 3T3-L1 adipocytes using luciferase reporter gene assays and DNA binding studies comparing all possible APM1 haplotypes. This functional approach was complemented with analysis of epidemiological population-based data of 1,692 participants of the MONICA/KORA S123 cohort and 696 participants from the KORA S4 cohort for SNP and haplotype association with circulating adiponectin levels. RESULTS-Major to minor allele replacements of the three SNPs revealed significant effects on promoter activity in luciferase assays. Particularly, a minor variant in rs16861194 resulted in reduced basal and rosiglitazone-induced promoter activity and hypoadiponectinemia in the epidemiological datasets. The haplotype with the minor allele in all three SNPs showed a complete loss of promoter activity, and no subject carried this haplotype in either of the epidemiological samples (combined P value for statistically significant difference from a random sample was 0.006). CONCLUSIONS-Our results clearly demonstrate that promoter variants associated with hypoadiponectinemia in humans substantially affect adiponectin promoter activity in adipocytes. Our combination of functional experiments with epidemiological data overcomes the drawback of each approach alone. Diabetes 58-984-991, 2009
    Type of Publication: Journal article published
    PubMed ID: 19074982
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  • 2
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Herzfrequenz ; Arrhythmie ; Sinusarrhythmie ; Autonomes Nervensystem ; Anästhesie ; Key words Heart rate ; Arrhythmia ; sinus ; Autonomic nervous system ; Anaesthesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background and methods. Small, periodic fluctuations in heart rate are well known to physicians, the respiratory sinus arrhythmia (RSA) being the most easily detectable form of this heart rate variability (HRV). Since it is caused by changing activity of the autonomic nervous system (ANS) controlling heart rate, HRV is investigated to gain information on the functional states of the ANS. Recent developments have led to computer-aided processing of EKG signals based on time and frequency domain methods – the latter using power spectral analysis by fast Fourier or autoregressive algorithms – to exactly describe and quantify HRV. Three major regions in the frequency spectrum between 0.03 and 0.5 Hz (the suitable range for short-term recordings) have been established: (1) a region around the respiratory rate, usually between 0.2 and 0.35 Hz, called high frequency (HF), (2) a region around 0.1 Hz attributed to vasomotor activity feedback, called low (or mid-) frequency (LF), (3) a peak around 0.04–0.05 Hz correlated to thermoregulation, called very low (or low)frequency (VLF). Power spectral density of HRV is now commonly accetped as a measure of autonomic cardiovascular control activity. By studies on vagal or sympathetic blockade, the HF (or RSA) region has been attributed solely to vagal activity, while both parts of the ANS may contribute to the other two, with, however, the vagal part predominating the resting, healthy individuals. Clinical applications/anaesthesia. Thus, spectral analysis of HRV provides a measure for quantifying sympatho-vagal balance in its physiological range. Additionally, reduction of HRV along with cardiovascular disease, including hypertension, myocardial infarction, heart failure and sudden cardiac death, as well as with autonomic dysregulation, has been reported. Since is also a striking reduction produced by most anaesthetic agents, RSA and HRV are investigated as measures of anaesthetic depth. There are contradictory data on the influence of ventilation, medication, and co-existing disease on the spectrum, and thus validation of the method is still to be achieved. It has, however, been proven useful in some studies as a parameter for risk assessment of perioperative or post-infarction cardiovascular complications.
    Notes: Zusammenfassung Periodische Schwankungen der Herzfrequenz, speziell die respiratorische Sinusarrhythmie (RSA) als Teil dieser Herzfrequenzvariabilität (HRV), sind der Medizin lange bekannt. Da sie ihre Ursache in der Aktivität des autonomen Nervensystems (ANS) haben, wird die HRV als Maß für dessen Funktionszustand untersucht. Die Möglichkeit der computergestützten EKG-Auswertung im Zeit- und Frequenzbereich (Spektralanalyse) erlaubt eine genaue Analyse der HRV. Drei Bereiche im Frequenzspektrum zwischen 0,03 und 0,5 Hz werden beschrieben: 1. um die Atemfrequenz, meist zwischen 0,2 und 0,35 Hz, 2. um 0,1 Hz, vasomotorischer Aktivität zugeschrieben, 3. zwischen 0,04 und 0,05 Hz, als Zeichen thermoregulatorischer Prozesse. Die Spektralenergie der HRV ist als Maß für den vegetativen Einfluß auf das Herz-Kreislauf-System akzeptiert. Durch vagale und sympathische Blockade konnte die RSA allein parasympathischer Aktivität zugeordnet werden, während an den anderen Bereichen beide Teile des ANS beteiligt sind. Daher bietet die Spektralanalyse der HRV ein Maß für die autonome Balance im physiologischen Bereich. Verminderungen der HRV im Zusammenhang mit Hypertonus, Herzinfarkt, Herzinsuffizienz ebenso wie mit autonomer Dysregulation sind beschrieben. Da Narkosemittel ebenfalls einen deutlichen Abfall der HRV bewirken, sind RSA und HRV zur Überwachung der Narkose im Gespräch. Bisher existieren widersprüchliche Daten über den Einfluß von Beatmung, Medikamenten und Grunderkrankungen, so daß die Methode besserer Standardisierung bedarf. Dennoch hat sich eine erniedrigte HRV als brauchbarer Risikoparameter für perioperative oder postinfarzielle Komplikationen erwiesen.
    Type of Medium: Electronic Resource
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