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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 42 (1999), S. 77-84 
    ISSN: 1437-1588
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Darüber hinaus soll das Lebensmittel-Monitoring längerfristig dazu dienen, zeitliche Trends in der Belastung von Lebensmitteln aufzuzeigen und eine ausreichende Datenbasis zu schaffen, um Aufnahmeberechnungen von unerwünschten Stoffen, die der Verbraucher über die Nahrung aufnimmt, durchführen zu können.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Insulin receptor kinase ; compound heterozygous insulin receptor mutations ; human muscle ; erythrocytes ; congenital fibre type disproportion myopathy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied insulin receptor kinase activation in two brothers with congenital muscle fibre type disproportion myopathy and compound heterozygous mutations of the insulin receptor gene, their parents, and their unaffected brother. In the father who has a heterozygote Arg1174→Gln mutation, in situ activation of the receptor kinase in skeletal muscle was reduced about 70 %. Selection of only those receptors that bound to anti-phosphotyrosine antibody showed that these receptors had normal kinase activity and that the reduction in overall kinase activity was due to the inability of about 70 % of the receptors to become insulin-dependently activated. The mother carries a point mutation at the last base pair in exon 17 which, due to abnormal alternative splicing, could lead to normally transcribed receptor or truncated receptor lacking the kinase region. Kinase activation was normal in the mother's skeletal muscle, suggesting that virtually no truncated receptor was expressed. Receptor kinase activity was, however, reduced by 95 and 91 % in the compound heterozygous brothers. This suggests that the mother's mutated allele contributes little to the generation of functional receptor protein and that the receptors in the mother's skeletal muscle are transcribed almost exclusively from the non-mutated allele. The mutation in exon 17 could lead to reduced transcription or rapid degradation of a predominantly transcribed truncated gene product or both. [Diabetologia (1999) 42: 245–249]
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of materials science 18 (1999), S. 1941-1943 
    ISSN: 1573-4811
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 167 (1999), S. 43-52 
    ISSN: 1432-1424
    Keywords: Key words: HeLa cells — Inward rectifier — Cloning — Kir2.1 —Xenopus oocyte — Channel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract. Previous patch-clamp studies have shown that the potassium permeability of the plasma membrane in HeLa cells, a cell line derived from an epidermoid carcinoma of the cervix, is controlled by various K+-selective pores including an IRK1 type inwardly rectifying K+ channel. We used the sequence previously reported for the human heart Kir2.1 channel to design a RT-PCR strategy for cloning the IRK1 channel in HeLa cells. A full-length clone of 1.3 kb was obtained that was identical to the human cardiac Kir2.1 inward rectifier. The nature of the cloned channel was also confirmed in a Northern blot analysis where a signal of 5.3 kb corresponding to the molecular weight expected for a Kir2.1 channel transcript was identified not only in HeLa cells, but also in WI-38, ECV304 and bovine aortic endothelial cells. The HeLa IRK1 channel cDNA was subcloned in an expression vector (pMT21) and injected into Xenopus oocytes. Cell-attached and inside-out single channel recordings obtained from injected oocytes provided evidence for a voltage-independent K+-selective channel with current/voltage characteristics typical of a strong inward rectifier. The single channel conductance for inward currents measured in 200 mm K2SO4 conditions was estimated at 40 ± 1 pS (n= 3), for applied voltages ranging from −100 to −160 mV, in agreement with the unitary conductance for the IRK1 channel identified in HeLa cells. In addition, the single channel conductance for inward currents, Γ, was found to vary as a function of αK, the external K+ ion activity, according to Γ=Γ0 [αK]δ with Γ0= 3.3 pS and δ= 0.5. Single channel recordings from injected oocytes also provided evidence of a voltage-dependent block by external Cs+ and Ba2+. The presence of 500 μm Cs+ caused a voltage-dependent flickering, typical of a fast channel blocking process which resulted in a reduction of the channel open probability at increasingly negative membrane potential values. The fractional electrical distance computed for the Cs+ blocking site was greater than 1 indicating a multiple ion channel occupation. In contrast, external Ba2+ at concentrations ranging from 25 to 100 μm caused a slow channel block, consistent with the binding of a single Ba2+ ion at a site located at half the membrane span. It is concluded on the basis of these observations that HeLa cells expressed a Kir2.1 type inwardly rectifying channel likely to be involved in maintaining and regulating the cell resting potential.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Herzschrittmachertherapie & Elektrophysiologie 10 (1999), S. 30-41 
    ISSN: 1435-1544
    Keywords: Key words Animal models ; ventricular tachycardia ; ventricular fibrillation ; myocardial infarction ; Schlüsselwörter Tiermodelle ; Kammertachykardie ; Kammerflimmern ; Myokardinfarkt
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Experimentelle Tiermodelle ventrikulärer Tachyarrhythmien wurden entwickelt, um die Mechanismen dieser Herzrhythmusstörungen beim Menschen besser zu verstehen. Solche Modelle sind notwendig, weil der lebensbedrohliche Charakter dieser Herzrhythmusstörungen und die zeitliche Unvorhersehbarkeit ihres Auftretens ein umfassendes Studium am Patienten oft unmöglich machen. Im Tierlabor stehen zusätzliche technische Möglichkeiten, wie Bestimmung des Transmembranpotentials mit Mikroelektroden oder hochauflösendes optisches und elektrisches Mapping zur Verfügung. Diese Methoden erlauben Untersuchungen, die im Rahmen klinischer Studien nicht möglich sind. Experimente an Tiermodellen haben neue Ideen und Hypothesen hervorgebracht, die in klinischen Studien getestet wurden und sich für klinische Herzrhythmusstörungen bestätigt haben. Tiermodelle haben entscheidend zu unserem Verständnis der Mechanismen von Fibrillation und Defibrillation und der Entwicklung neuer Therapiekonzepte beigetragen. Dieser Artikel wird eine kurze Übersicht über verschiedene Tiermodelle ventrikulärer Tachyarrhythmien geben und auch einige Erkenntnisse, die mit Hilfe dieser Modelle erzielt wurden, diskutieren. Aufgrund der klinischen Bedeutung der koronaren Herzkrankheit wird der Schwerpunkt auf ventrikuläre Tachyarrhythmien im Rahmen von Myokardischämie und Myokardinfarkt gelegt. Es gibt kein Tiermodell, daß den natürlichen Verlauf der koronaren Herzkrankheit beim Menschen simuliert. Den Modellen ist gemeinsam, daß eine regionale Myokardischämie durch permanente oder temporäre Okklusion einer oder mehrerer Koronargefäße erzeugt wird. Dies geschieht am offenen oder geschlossenen Thorax. Die Arrhythmien entstehen „spontan“ während akuter Ischämie oder in der Reperfusionsphase oder können durch elektrische Stimuli induziert werden. Solche Untersuchungen können bei verschiedenen Spezies durchgeführt werden. Neben Studien am intakten Tier werden auch isolierte, mit der Langendorff-Technik perfundierte Herzen verwendet. Diese Modelle haben dazu beigetragen, die Arrhythmiemechanismen während der einzelnen Phasen der Infarktentstehung und -heilung zu untersuchen.
    Notes: Summary Experimental animal models of ventricular arrhythmias have been developed to investigate the mechanisms of arrhythmogenesis in man. Ventricular arrhythmias associated with ischaemia and infarction often cannot be elucidated by clinical studies on patients because those arrhythmias are potentially lifethreatening and their occurrence is unpredictable. Because of additional experimental procedures and techniques that can be used in the animal laboratory, such as microelectrode recording of transmembrane action potentials and high-density optical and electrical activation mapping, animal models have provided information that cannot be obtained from clinical studies. Studies on animal models have provided new ideas and hypotheses that have been tested in clinical studies and that have been found to be true for clinical arrhythmias. Animal models have enabled the mechanisms of fibrillation and defibrillation to be understood and new therapeutic concepts to be developed. The purpose of this article is to briefly review some animal models of ventricular tachycardia and fibrillation. Some contributions that these animal studies have made to our understanding of ventricular tachyarrhythmias will be discussed. Because of the clinical importance of coronary artery disease this article concentrates on those arrhythmias caused by myocardial ischaemia and infarction. An animal model that resembles the clinical course of coronary artery disease in humans does not exist. In animal studies designed to reproduce arrhythmias caused by myocardial ischaemia or infarction regional ischaemia is induced by transient or permanent occlusion of one or more coronary arteries. Coronary occlusion is performed with a variety of techniques in open- or closed-chest animals of different species. Arrhythmias occur „spontaneously“ during acute ischaemia or reperfusion or can be induced by electrical stimuli. Hearts isolated and perfused by the Langendorff technique can also be used to study the arrhythmias caused by coronary occlusion or occlusion and reperfusion. These animal models of myocardial ischaemia and infarction have helped to elucidate the mechanisms of arrhythmogenesis of each stage of infarct development and healing.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Herzschrittmachertherapie & Elektrophysiologie 10 (1999), S. 1-2 
    ISSN: 1435-1544
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Herzschrittmachertherapie & Elektrophysiologie 10 (1999), S. 51-58 
    ISSN: 1435-1544
    Keywords: Key words Atrial fibrillation ; electrical remodeling ; atrial pressure ; mechanical-stretch ; Schlüsselwörter Vorhofflimmern ; Vorhofdruck ; elektrisches Remodeling ; Vorhofdehnung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Hintergrund: Hohe atriale Depolarisationsfrequenzen bei Vorhofflimmern führen über einen verstärkten zellulären Kalziumeinstrom zu einer signifikanten Verkürzung der atrialen Refraktärzeit. Dieses atriale Remodeling scheint ein bedeutender Faktor zu sein, der zur Aufrechterhaltung des Vorhofflimmerns beiträgt. Das Ziel der vorliegenden Studie war es, zu untersuchen, ob unterschiedliche atriale Druckverhältnisse einen modulierenden Effekt auf das Entstehen und das Ausmaß des atrialen Remodeling besitzen und damit auch zur Entwicklung von Vorhofflimmern im Tiermodell beitragen. Methoden: Bei 10 Hunden (25±1kg) wurde während Inhalationsnarkose mit Isofluran der rechte Vorhof über einen quadripolaren Elektrodenkatheter für 7 Stunden mit 800bpm stimuliert. Komplette autonome Blockade wurde durch intravenöse Gabe von Atropin und Propranolol induziert und über den Versuchszeitraum konstant gehalten (Atropin: Bolus: 0,04mg/kg gefolgt von 0,007mg/kg/h und Propranolol: Bolus: 0,2mg/kg gefolgt von 0,04mg/kg/h). Die atriale effektive Refraktärzeit wurde stündlich bei einer Basiszykluslänge von 350ms über eine implantierte atriale Schrittmacherelektrode im rechten Herzohr bestimmt. Die Tiere wurden nach Abschluß der Versuchsreihe entsprechend dem mittleren atrialen Druckes im rechten Vorhof in zwei Gruppen eingeteilt. Der mittlere Vorhofdruck in Gruppe1 (n=5) betrug 4±0,2mmHg und der in Gruppe2 (n=5) 7±1mmHg (p〈0,01). Ergebnisse: Bei allen Tieren kam es zu einer signifikanten Verkürzung der effektiven atrialen Refraktärzeit während hochfrequenter Stimulation. Die ERP verkürzte sich in Gruppe1 von 166±12ms auf 145±16ms (p〈0,05) und in der Gruppe2 von 164±14ms auf 126±17ms (p〈0,001). Die Verkürzung der effektiven Refraktärzeit war in Gruppe2 mit 23±5% signifikant größer als bei Tieren der Gruppe1 (13±5%; p〈0,05). Die Dauer des induzierten Vorhofflimmerns war mit 59±22s in Gruppe2 ebenfalls signifikant gegenüber Gruppe1 (19±12s; p〈0,05) verlängert. Die Zykluslänge des Vorhofflimmerns war nicht signifikant unterschiedlich (135±27ms in Gruppe1 versus 146±23ms in Gruppe2; p=ns). Während in Gruppe1 die Refraktärzeit 30 Minuten nach Beendigung der Stimulation den Ausgangswert erreicht hatte, war die effektive Refraktärzeit in der 2. Gruppe lediglich auf 91±8% des Basiswertes angestiegen (p=0,054). Zwischen den untersuchten Gruppen bestand kein Unterschied hinsichtlich der mittleren atrialen und ventrikulären Erregungsfrequenz bzw. des systemischen Blutdrucks. Schlußfolgerungen: Erhöhter Vorhofdruck scheint, auch unabhängig von einer möglichen vagalen Stimulation, ein zusätzlicher Faktor zu sein, der zu einer progressiven Verkürzung der atrialen effektiven Refraktärzeit während hochfrequenter atrialer Stimulation beiträgt. Es ist durchaus möglich, daß durch diesen Effekt das atriale elektrische Remodeling begünstigt und dadurch die Persistenz von Vorhofflimmern verlängert wird.
    Notes: Background: Electrical atrial remodeling during rapid atrial activation is known to be an important phenomenon for perpetuation of atrial fibrillation. Recent studies have demonstrated that electrical remodeling is mediated by an increase in calium currents through L-type calcium channels during atrial fibrillation. Electromechanical factors may also contribute to the observed shortening in the effective refractory period (ERP) during atrial remodeling. The purpose of our study was to examine the influence of right atrial pressure on electrical remodeling during high frequency pacing in an intact animal model. Methods: 10 closed-chest dogs (25±1kg) were studied during continuous autonomic blockade with i.v. Atropine (bolus: 0.04mg/kg followed by 0.007mg/kg/h) and i.v. Propranolol (bolus: 0.2mg/kg followed by 0.04mg/kg/h). The right atrial appendage was paced for 7 hours at a rate of 800bpm (4mA). Right atrial pressure and systemic blood pressure were continuously recorded. Atrial ERP was determined at a different right atrial site every hour at a basic cycle length of 350ms. After 7h pacing, animals were divided into two groups according to the mean right atrial pressure (group 1: 4±0.2mmHg versus group 2: 7±1mmHg; p〈0.01). Results: Despite autonomic blockade, significant electrical remodeling was observed in all animals. The decrement in ERP was significantly greater in group 2compared to group1 (group1: 166±12ms to 145±16ms versus group2: 164±14ms to 126±17ms; p〈0.05). The duration of induced atrial fibrillation was significantly longer in group 2 compared to group1 (59±22s vs. 19±12s; p〈0.05). The mean AF cycle length was not significantly different in both groups (135±27ms vs. 142±24ms; p=ns). While ERP reached baseline 30 minutes after cessation of rapid pacing in group 1 the ERP remained shorter in group2 (91±8%; p=0.054). There were no differences in blood pressure, mean atrial or ventricular rates between the two groups. Conclusions: Atrial remodeling is accentuated by elevated right atrial pressure despite complete autonomic blockade. Thus, increases mechanical stretch produced by elevated atrial pressure may be an additional factor which contributes to electrical remodeling during atrial fibrillation.
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  • 8
    ISSN: 1434-601X
    Keywords: PACS: 21.10.Pc Single-particle levels and strength function – 23.20.Lv Gamma transitions and level energies – 25.55.-e 3H-,3He-, and 4He-induced reactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: An in-beam experiment with the subcoulomb reaction 209Bi(3He, d*γγ)210Po at 20.5 MeV was performed with two Euroball Cluster detectors in Cologne. It closed the gap between the low energy levels of the level-scheme and the high energy levels found in 209Bi(3He, d)210Po and 208Pb(4He, t)210Po particle experiments. New branchings have been found and the (3He, d*γγ) reaction below the coulomb-barrier has been used successfully.
    Type of Medium: Electronic Resource
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