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  • 2000-2004  (2)
  • Keywords Insulin receptor inhibition, tyrosine kinase activity, serine phosphorylation, protein kinase C.  (1)
  • Schlüsselwörter Vorhofflimmern – Flimmerfrequenz –¶EKG-Signalverarbeitung – Elektrisches Remodeling  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Serine residues 994 and 1023/25 are important for insulin receptor kinase inhibition by protein kinase C isoforms β2 and θ (2000)
    Springer
    Diabetologia 43 (2000), S. 443-449 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin receptor inhibition, tyrosine kinase activity, serine phosphorylation, protein kinase C.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Inhibition of the signalling function of the human insulin receptor (HIR) is one of the principle mechanisms which induce cellular insulin resistance. It is speculated that serine residues in the insulin receptor β-subunit are involved in receptor inhibition either as inhibitory phosphorylation sites or as part of receptor domains which bind inhibitory proteins or tyrosine phosphatases. As reported earlier we prepared 16 serine to alanine point mutations of the HIR and found that serine to alanine mutants HIR-994 and HIR-1023/25 showed increased tyrosine autophosphorylation when expressed in human embryonic kidney (HEK) 293 cells. In this study we examined whether these mutant receptors have a different susceptibility to inhibition by serine kinases or an altered tyrosine kinase activity.¶Methods. Tyrosine kinase assay and transfection studies.¶Results. In an in vitro kinase assay using IRS-1 as a substrate we could detect a higher intrinsic tyrosine kinase activity of both receptor constructs. Additionally, a higher capacity to phosphorylate the adapter protein Shc in intact cells was seen. To test the inhibition by serine kinases, the receptor constructs were expressed in HEK 293 cells together with IRS-1 and protein kinase C isoforms β2 and θ. Phorbol ester stimulation of these cells reduced wild-type receptor autophosphorylation to 58 % or 55 % of the insulin simulated state, respectively. This inhibitory effect was not observed with HIR-994 and HIR-1023/25, although all other tested HIR mutants showed similar inhibition induced by protein kinase C.¶Conclusion/interpretation. The data suggest that the HIR-domain which contains the serine residues 994 and 1023/25 is important for the inhibitory effect of protein kinase C isoforms β2 and θ on insulin receptor autophosphorylation. [Diabetologia (2000) 43: 443–449]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051327
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  • 2
    Electronic Resource
    Electronic Resource
    Determination of fibrillatory frequency for assessment of the atrial electrophysiologic state in human atrial fibrillation – (2000)
    Springer
    Herzschrittmachertherapie & Elektrophysiologie 11 (2000), S. 77-87 
    Details
    ISSN: 1435-1544
    Keywords: Schlüsselwörter Vorhofflimmern – Flimmerfrequenz –¶EKG-Signalverarbeitung – Elektrisches Remodeling ; Key words Atrial fibrillation – fibrillatory frequency –¶ECG signal processing – electrical remodeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Atrial fibrillation (AF) being the most common arrhythmia encountered in clinical practice is based on the continuous propagation of multiple wavelets wandering throughout the atria in most cases. Neither the natural history of AF nor its response to therapy are sufficiently predictable by clinical and echocardiographic parameters.¶   In contrast, invasively determined atrial fibrillatory frequency has been shown to be related with AF complexity, AF behavior and cardioversion success. Fibrillatory frequency can also be assessed from the surface ECG using digital signal processing (filtering, subtraction of averaged QRST complexes, and Fourier transformation). This measurement correlates well with intraatrial cycle length, a parameter which appears to have primary importance in the genesis and perpetuation of AF. Low frequency fibrillation is more likely to terminate spontaneously or to respond to antiarrhythmic therapy, while high frequency fibrillation is more often persistent and drug refractory. The influence of physiological and pharmaceutical interventions can be monitored directly.¶   Thus, determination of fibrillatory frequency from the surface ECG may prove useful for non-invasive assessment of the electrophysiologic state of the atria in patients with AF. Further studies are necessary to determine the role of this test in the management of AF.
    Notes: Zusammenfassung Vorhofflimmern (VHF) ist das elektrographische Bild mehrerer simultaner Kreiserregungen in den Vorhöfen. Weder der natürliche Verlauf von VHF noch die Effektivität therapeutischer Maßnahmen sind mit klinischen oder echokardiographischen Variablen vorhersagbar.¶   Im Gegensatz dazu konnten verschiedene Untersuchungen einen Zusammenhang zwischen invasiv ermittelter atrialer Flimmerfrequenz (atriale Zykluslänge) und VHF-Komplexität, klinischem Verhalten sowie Kardioversionserfolg feststellen. Die atriale Flimmerfrequenz kann ebenfalls aus dem Oberflächen-EKG mittels digitaler Signalverarbeitung (Filterung, Subtraktion gemittelter QRST-Komplexe, Fourie-Transformation) bestimmt werden. Die so erhaltene Frequenz korreliert hoch mit der invasiv ermittelten Frequenz. VHF mit niedriger Frequenz zeigt die Tendenz zur spontanen Termination und eine hohe Ansprechrate auf akute medikamentös-antiarrhythmische Therapie. Hingegen ist VHF mit hoher Frequenz eher persistierend und medikamenten-refraktär. Physiologische und pharmakologische Einflüsse auf die atriale Flimmerfrequenz können direkt beobachtet werden.¶   Die vorgestellte Methodik könnte somit zur Einschätzung des Krankheitsstadiums von VHF und damit dem gezielten Einsatz therapeutischer Optionen dienen. Weitere Studien müssen die Wertigkeit der atrialen Frequenzbestimmung aus dem Oberflächen-EKG im Management von VHF-Patienten zeigen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003990070042
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    Paper (German National Licenses)
    Fulltext
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