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  • 2000-2004  (9)
  • 1970-1974  (33)
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  • 1
    ISSN: 1432-0428
    Keywords: Keywords HIV protease inhibitors ; lipodystrophy syndrome ; diabetes mellitus ; insulin resistance ; insulin signalling.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Patients treated with human immunodeficiency virus-1 protease inhibitors often develop impaired glucose tolerance or diabetes, most likely due to an induction of insulin resistance. We therefore investigated whether the protease inhibitor indinavir alters insulin signalling. Methods. We incubated HepG2 cells for 48 h without or with indinavir (100 μmol/l). Subsequently 125I-insulin binding to the cells and the effects of insulin stimulation on insulin-receptor substrate-1-phosphorylation, association of phosphatidylinositol 3-kinase with insulin-receptor substrate-1 and Akt-Thr308-phosphorylation were measured. Results. In cells not exposed to indinavir, insulin (100 nmol/l) led to rapid increases of insulin-receptor substrate-1-phosphorylation, association of phosphatidylinositol 3-kinase with insulin-receptor substrate-1 and Akt-phosphorylation during the first 75 s, followed by subsequent decreases. In indinavir-treated cells, these insulin-stimulated increases during the first 75 s were reduced by 30–60 % and this was not associated with alterations in cell number or viability, insulin binding to the cells or cellular insulin-receptor substrate-1-content. Conclusion/interpretation. Effects of indinavir on initial insulin signalling could cause, or contribute to, the metabolic effects of human immunodeficiency virus-1 protease inhibitors. [Diabetologia (2000) 43: 1145–1148]
    Type of Medium: Electronic Resource
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  • 2
    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
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  • 3
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 20 normo- und hypertensiven Patienten mit normaler und verschieden stark eingeschränkter Nierenfunktion wurde das Verhalten der renalen Hämodynamik unter intravenöser Gabe von Etacrynsäure (50 mg initial mit anschließender Dauerinfusion von 50 mg/Std) im akuten Experiment unter Clearance-Bedingungen geprüft. Eine eindeutige Änderung der glomerulären Filtrationsrate (GFR) wurde dann angenommen, wenn die Abweichung von den Kontrollen, deren Schwankungsbreite ± 10% nicht überschreiten durfte, wiederholt mehr als 10% betrug. Von 19 Probanden zeigten 7 (Gruppe A) einen kontinuierlichen Abfall und 8 (Gruppe B) einen Anstieg der GFR, der allerdings auf die ersten 30–45 min beschränkt war. Dieser Unterschied zwischen beiden Gruppen ist bei doppelter Varianzanalyse fürα〈0,001 zu sichern. Der effektive renale Plasmastrom (RPF) verhielt sich nur zum Teil gleichsinnig. Die Filtrationsfraktion hatte bei Gruppe A eine leicht sinkende (α〈0,05), bei Gruppe B eine steigende Tendenz. Bei der Analyse der Ursachen dieses divergierenden Verhaltens der renalen Hämodynamik konnte ein methodischer Fehler im Sinn eines „Auswascheffektes“ ausgeschlossen werden: Das Maximum der glomerulären Filtrationsrate wurde in Gruppe B durchschnittlich erst nach 45 min erreicht. Bei Gruppe A kam in der gleichen Zeit ein Abfall zustande. Die Ausgangswerte der glomerulären Filtrationstrate lagen bei beiden Gruppen in gleicher Größenordnung. Dagegen waren Harnzeitvolumen und renale Natriumausscheidung in Gruppe A vor und in den beiden ersten Clearanceperioden nach Etacrynsäure-Gabe signifikant höher als in Gruppe B (α bis〈0,01). Diese Unterschiede kamen auch in der fraktionalen Natriumausscheidung, der tubulären Reabsorptionsfraktion von Natrium sowie der osmolalen Clearance zum Ausdruck. Sie beruhen wahrscheinlich in erster Linie darauf, daß es sich bei Gruppe A ausschließlich um Personen mit Blutdrucksteigerung handelt, deren Neigung zu beschleunigter Natrium-Elimination bekannt ist, während Gruppe B fast nur normotensive Probanden umfaßt. Das Absinken der GFR in Gruppe A erklärt sich somit am ehesten mit einer frühzeitig einsetzenden, kumulativ negativen Natrium- und Wasserbilanz mit konsekutiver Hypovolämie, die am Verhalten des peripheren Blutdrucks allerdings nicht nachweisbar war. Bei den Probanden der Gruppe B kommt diese bilanzmäßig bedingte Kontraktion des Extracellulärraums erst nach 45 min zur Auswirkung, so daß die Reaktion der renalen Hämodynamik initial von der durch Etacrynsäure an sich verursachten Dilatation der Nierengefäße geprägt wird. Die vorliegenden Ergebnisse geben jedoch keinen weiteren Aufschluß über die pharmakologischen Grundlagen dieser renalen Mehrdurchblutung.
    Notes: Summary Changes of renal hemodynamics after intravenous application of ethacrynic acid (50 mg prime injection followed by an infusion of 50 mg/h) were investigated during acute clearance conditions in 20 subjects with normal and elevated blood pressure and various degrees of impaired renal function. The change of glomerular filtration rate was only accounted as definitive when the deviation from the controls was more than 10% in different clearance periods. In 7 of 19 experiments, ethacrynic acid caused a decrease of glomerular filtration rate (group A), whereas 8 experiments showed an increase (group B) which, however, was limited to the first 30–45 min. The difference between both groups proved to be statistically significant at double variance analysis (α〈0.001). The effective renal plasma flow was only partially modified in the same direction. The filtration fraction was decreasing in group A (α〈0.05) and slightly increasing in group B. In analyzing the causes of these different effects of ethacrynic acid on renal hemodynamics, a “washout effect” could be excluded: The maximum rise of glomerular filtration rate in group B was only reached after 45 min. In contrast, the decrease in group A developed within the same time interval. In the control periods glomerular filtration rate in both groups remained within the same order of magnitude. On the other hand, urine volume and renal sodium excretion in group A (decreasing filtration rate) exceeded that of group B not only initially but also during the first two clearance periods after ethacrynic acid administration. These differences were also observed in fractional renal sodium excretion, tubular sodium reabsorption, and osmolar clearance. They are most probably the consequence of the increased arterial pressure of all patients in group A, since the tendency to exaggerated sodium elimination of hypertensive patients is well known. All subjects of group B were normotensive. The declining glomerular filtration rate in group A can best be explained by an early onset of cumulative negative sodium balance with consecutive hypovolemia which does however not affect the peripheral blood pressure. In group B, the contraction of extracellular fluid volume did not occur until 45 min after the application of ethacrynic acid. Thus, the reaction of renal hemodynamics in this group is initially influenced by the dilatation of the renal vessels caused by the drug. A further explanation of the pharmacological basis of this increase in renal blood perfusion, however, cannot be given by the experiments reported.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 50 (1972), S. 56-57 
    ISSN: 1432-1440
    Keywords: In-vitro-autoradiography ; stomach biopsies ; cell regeneration ; In vitro-Autoradiographie ; Magenschleimhautbiopsie ; Zellregeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Zur autoradiographischen Untersuchung der Zellerneuerung in der Magenschleimhaut des Menschen wurde ein früher entwickeltes in vitro-Verfahren am Biopsiematerial angewendet. Bei gleichbleibenden Versuchsbedingungen und einem Gewebsdurchmesser bis ca. 1000 µ wurden Autoradiogramme erhalten, die geeignet erscheinen, die Magenmucosa unter verschiedenen pathologischen Bedingungen zu untersuchen.
    Notes: Summary Autoradiography with bioptic specimens of human gastric mucosa. A previously tested in-vitro method was applied for an autoradiographical study of cell proliferation of the mucosa of the human stomach in biopsies under standardized conditions. From specimens of about 1000 µ in diameter autoradiographs can be obtained which show the characteristic labelling of cells in the zones of cell regeneration and permit the investigation of the normal and pathological mucosa of the human stomach.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary This paper describes the induction of partial synchronisation of diploid Ehrlich Ascites Tumor Cells by application of vincristine. The dosage of vincristine was so low that no essential tumor cell necrosis was found (1 µg/mouse). The pharmacologically induced partial synchronisation of the tumor cells was utilized for cytostatic treatment with cyclophosphamide (100 mg/kg). After the observed partial synchronisation the following application of cyclophosphamide at a moment, when a great part of tumor cells were in DNA-synthesis (32. h after vincristine) caused a marked depression of tumor growth. This depression was approximately twofold of that observed after application of cyclophosphamide without an pharmacologically induced partial synchronisation of the tumour cells.
    Notes: Zusammenfassung In der vorliegenden Arbeit wird über eine induzierte Teilsynchronisation bei diploiden Ehrlich-Ascites-Tumorzellen nach Gabe von Vincristin berichtet. Vincristin wurde in einer Dosierung verabreicht, die noch nicht zur verstärkten Tumorzellnektrose führt. Die pharmakologisch induzierte partielle Synchronisation wurde für eine zusätzliche cytostatische Tumorbehandlung mit Endoxan genutzt. Es zeigte sich, daß nach der Teilsynchronisation und der nachfolgenden Endoxan-Applikation zu einem Zeitpunkt, in dem ein großer Teil der Tumorzellen in DNS-Synthese zu erwarten ist, eine auffallend starke Wachstumshemmung erzielt wurde. Sie war etwa doppelt so stark ausgeprägt wie nach alleiniger Gabe von Endoxan, d.h. ohne vorherige Teilsynchronisation.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 263 (2000), S. 99-101 
    ISSN: 1432-0711
    Keywords: Key words Leptin ; Menstrual cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Leptin is a cytokine involved in the regulation of food intake and fertility in rodents and in humans. No data exist about serum leptin serum levels during the spontaneous menstrual cycle. In this study 16 ovulatory cycles of endocrinologically normal volunteers were analyzed. Blood samples were taken on alternate days throughout the menstrual cycle for measurement of serum estradiol, progesterone, LH, FSH and leptin serum levels. No correlation of leptin values with estradiol values (r = 0.07) or progesterone values (r = 0.14) were seen. Mean leptin values during the luteal phase were significantly higher (16.67 ± 9.45 ng/mL) compared to the follicular phase (13.50 ± 8.75 ng/mL) (P 〈 0.02). A strongly positive correlation with the progression of the menstrual cycle could be seen (r = 0.91). The physiological significance of higher luteal phase leptin levels is unknown.
    Type of Medium: Electronic Resource
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  • 7
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    Unknown
    Berlin : Periodicals Archive Online (PAO)
    Deutsche Zeitschrift für Philosophie. 22:6 (1974) 772 
    ISSN: 0012-1045
    Topics: Philosophy
    Description / Table of Contents: REZENSIONEN
    Notes: ZUM IV. PHILOSOPHIE-KONGRESS DER DDR
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  • 8
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Review of Scientific Instruments 71 (2000), S. 836-838 
    ISSN: 1089-7623
    Source: AIP Digital Archive
    Topics: Physics , Electrical Engineering, Measurement and Control Technology
    Notes: For the International Fusion Materials Irradiation Facility (IFMIF) scenario, a 140 mA deuterium beam in continuous wave (cw) mode with an atomic yield of above 85% is required. The normalized root-mean-square emittance should be less than 0.2 π mm mrad at the entrance of a RFQ. As part of a conceptual design for IFMIF, a new ion source has been developed and is tested at the Institut für Angewandte Physik in Frankfurt. The ion source is of the volume type with a tungsten cathode driving the discharge. Both cw and pulsed mode are possible and were studied. First experiments were carried out with deuterium. 80 mA deuterons with a D+ fraction of above 90% were extracted [A. Maser et al., Rev. Sci. Instrum. 67, 1054 (1996)]. In order to avoid neutron generation by the d–d reaction, hydrogen was used instead of deuterium later on. As far as the ion source and plasma production processes are concerned, the use of hydrogen instead of deuterium is equivalent because of their similar atomic shells. Recently, a 200 mA proton beam at 55 kV was extracted in cw mode (according to Child–Langmuir, 200 mA H+ corresponds to 140 mA D+) with a H+ fraction of 93%. This article will give a detailed description of the ion source and the essential experimental results. Especially, the influence of important physical parameters (such as discharge current and strength of the filter field) on the H+ fraction was studied. By using different kinds of auxiliary gases, the influence on the H+ fraction and the noise level were investigated, too. © 2000 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Review of Scientific Instruments 73 (2002), S. 1027-1029 
    ISSN: 1089-7623
    Source: AIP Digital Archive
    Topics: Physics , Electrical Engineering, Measurement and Control Technology
    Notes: For the International Fusion Materials Irradiation Facility project (IFMIF) the Institut für Angewandte Physik at the University of Frankfurt is concerned with developing a high current proton/deuteron ion source. The 1999 "Frankfurt 200 mA Proton Source" is a volume type belonging to the high-efficient ion-sources family. This type of ion source has proven its capability to produce high-current ion beams of a single mass-to-charge ratio at very low-beam emittances. The arc discharge ion source delivers a 200 mA full beam (93% protons) at 55 keV with very high-beam intensities (outlet aperture 8 mm diam). Thus, the beam requirements for the IFMIF project are fulfilled. After having done the basic plasma investigation with a 127° cylinder spectrometer, the quality of the ion beam was a point of interest. Therefore, the beam emittance was measured with a conventional slit-grid measurement device. The goal was to measure the beam emittance at high-beam currents. The article will give a detailed description of the measurement of a 56 mA beam at 26 keV with 85% protons. Theoretical considerations of the emittance value, given by ion temperature and aberrations of the extraction system, allows an estimation of the emittance of a 170 mA at 55 keV proton beam. In a second step, an estimation of a postaccelerated 140 mA at 100 keV deuteron beam was completed. © 2002 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 10
    facet.materialart.
    Unknown
    Chalfont St. Giles, U.K. : Periodicals Archive Online (PAO)
    Journal of European studies. 4:3=15 (1974:Sept.) 287 
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