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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
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 29 (1951), S. 548-549 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 28 (1950), S. 179-184 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung In funktionellen und morphologischen Untersuchungen der Nebenniere des Meerschweinchens unter langdauernder 3%iger CO2-Einwirkung ergeben sich abgesehen von der unmittelbaren Bedeutung der CO2-Wirkung für Funktion und Morphologie der Nebenniere wichtige Zusammenhänge zwischen Rinde und Mark. Die funktionelle Untersuchung ergab, daß nach langdauernder CO2-Wirkung 1. der Adrenalingehalt quantitativ abnimmt; 2. Ferrosalzgaben, die bei kurzfristiger CO2-Einwirkung eine Adrenalinentleerung hervorrufen, keine Wirkung mehr haben; 3. Adrenalininjektionen nur noch eine geringe Blutzuckersteigerung auslösen; 4. der Blutzucker absinkt; 5. die Blutzuckerkurve nach Glucoseinjektion flach verläuft. Die morphologische Untersuchung ergab, daß nach langdauernder CO2-Wirkung 1. die Chromierbarkeit der Markzellen abnimmt; 2. die großvacuoligen Markzellen mit den großvacuoligen Rindenzellen zusammengehen: 3. die Z. reticularis mit anhaltender CO2-Wirkung zunimmt; 4. der Zustand, wie er nach 17 Tagen CO2-Einwirkung vorliegt, zunächst über eine Phase gesteigerter Tätigkeit geht, die nach 5 Tagen CO2-Wirkung langsam abnimmt. Die Zweiphasigkeit der CO2-Wirkung kommt sowohl funktionell wie morphologisch zum Ausdruck.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    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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  • 7
    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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  • 8
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Applied crystallography online 33 (2000), S. 1162-1174 
    ISSN: 1600-5767
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Geosciences , Physics
    Notes: The instrumental transparency functions of five commercially available texture goniometers were measured experimentally with six monocrystalline samples cut in different orientations from a large highly perfect silicon crystal with a rocking curve of less than 0.01°. Transparency functions were measured in steps of 0.02 to 0.2° in the pole-figure angles α, β. The window size Δα depends on the Bragg angle θ in the form 1/sinθ; the window size Δω is constant for each goniometer. The dominant instrumental parameter determining the long axis Δα of the pole-figure window is the axial width of the detector entrance slit. This parameter is smallest for area detectors (smaller by more than an order of magnitude compared with conventional scintillation detectors as well as one-dimensional position-sensitive detectors). The main features of the pole-figure window and their dependence on the instrumental parameters can be deduced fairly well from a simple geometrical model. The particular shapes of the transparency functions of the studied goniometers are markedly different. Particularly, they are not very well represented by Gauss functions. The two-dimensional transparency function can be fairly well characterized by its α and β profiles. The normalized profiles are virtually independent of the goniometer angles 2θ and α. The increasing size of the pole-figure window with decreasing θ puts a lower limit on the Bragg angle below which pole-figure measurement ceases to be meaningful.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Lung 109 (1953), S. 478-481 
    ISSN: 1432-1750
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung 1. Bei Untersuchungen über die Aktivität der Hyaluronidasen bei der Magen-und Darmpassage fand sich, daß die Wirksamkeit der Fermente weder durch Magen- noch durch Duodenalsaft herabgesetzt wird, im Gegenteil findet eine geringe Aktivierung bei Kontakt mit Magen- und Duodenalsaft nach optimaler Kontaktzeit von 2–3 Std statt. 2. Durch Zusatz von Hyaluronidasen zu peroral verabreichter PAS wird eine um etwa 50% erhöhte Konzentration im Blut und eine wahrscheinliche Erhöhung der PAS-Konzentration im Gewebe erreicht. 3. Die Ausscheidung von PAS im Urin wird bei gleichzeitiger Verabreichung von Hyaluronidasen ebenfalls vermehrt, was jedoch wahrscheinlich nicht durch den Einfluß der Hyaluronidasen selbst, sondern durch ein erhöhtes Angebot von PAS an den Filtrationsmechanismus des Ausscheidungsorganes bedingt ist. 4. Durch Verwendung der Hyaluronidasen wird in einer bestimmten Zeit ein vermehrter Durchlauf und damit zeitlich erhöhte Konzentration im Organismus durch das Medikament erzielt.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 320 (1951), S. 93-137 
    ISSN: 1432-2307
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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