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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 65 (1987), S. 424-427 
    ISSN: 1432-1440
    Keywords: Valproate intoxication ; Cerebral edema
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 29-year-old man, who had been treated with sodium valproate for 3 years because of generalized cerebral seizures, ingested a large amount of this drug in an attempt to suicide. The exact amount he had swallowed could not be determined. The patient arrived in the intensive care unit in a deep coma, was intubated, and artificially ventilated. He developed a massive cerebral edema, as proved by computerized tomography (CT). This was supported by electroencephalography (EEG). The measured value for the concentration of valproate in serum was markedly elevated on the day of admission (2300 µmol/l; therapeutic range 350–700 µmol/l). Treatment with sodium thiopental, glycerol, and glucocorticoids was initiated. A second CT scan performed 9 days after admission showed a complete normalization and the EEG yielded a markedly improved pattern. At this point the patient slowly regained consciousness. We conclude that in patients with an acute sodium-valproate intoxication, care should be taken with regard to the development of a severe cerebral edema, which in the reported case could be treated successfully.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: Posttransfusion purpura ; Thrombocytopenia ; Blood transfusion ; Platelet antibodies ; HLA antigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirteen cases of posttransfusion purpura (PTP) which were diagnosed in Germany and Austria from 1977–1985 are described. All patients were women with a mean age of 58.6 years (range, 36–77 years). All but one had been pregnant and received blood transfusions 2 to 12 days prior to the onset of PTP. The thrombocytopenic purpura was always severe with a nadir of platelet counts below 10×109/l and lasted between 3 and 60 days. All patients recovered from PTP. Optimal therapy consisted of administration of high-dose IgG. Twelve of the 13 patients had developed platelet-specific Zwa antibodies (eight of them together with HLA antibodies), in one Zwa positive individual only HLA antibodies were detectable. Five of six HLA-DR typed patients carried DR3 which is considered an immunogenetic risk factor in PTP. Clinical awareness of this rare, but serious iatrogenic transfusion complication is prerequisite for prompt diagnosis and improved therapy.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Archives of microbiology 152 (1989), S. 215-217 
    ISSN: 1432-072X
    Keywords: Cyanobacterium ; Oscillatoria limnetica ; Anacrobic unsaturated fatty acid synthesis ; Positional isomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The mechanism for synthesis of monounsaturated fatty acids under aerobic and anaerobic conditions was studied in the facultative anaerobic cyanobacterium, Oscillatoria limnetica. The hexadecenoic acid (C16∶1) of aerobically grown O. limnetica was shown to contain both the Δ7 (79%) and Δ9 (21%) isomers, while the octadecenoic (C18∶1) acid was entirely the Δ9 acid. Incorporation of [2-14C] acetate into the fatty acids under aerobic conditions resulted in synthesis of the Δ7 and Δ9 C16∶1 and the Δ9 C18∶1. Synthesis of unsaturated fatty acids in the presence of DCMU required sulfide. Anaerobic incubations in the presence of DCMU and sulfide (less than 0.003% atmospheric oxygen) resulted in a two-fold increase in monounsaturated fatty acids of both Δ7 and Δ9 C16∶1 and Δ9 and Δ11 C18∶1. The synthesis of these isomers is characteristic of a bacterialtype, anaerobic pathway.
    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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    Berlin : Periodicals Archive Online (PAO)
    Deutsche Zeitschrift für Philosophie. 35:10 (1987) 913 
    ISSN: 0012-1045
    Topics: Philosophy
    Notes: Zum 70. Jahrestag der Grossen Sozialistischen Oktoberrevolution
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  • 8
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    Unknown
    Berlin : Periodicals Archive Online (PAO)
    Deutsche Zeitschrift für Philosophie. 37:9 (1989) 853 
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  • 9
    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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  • 10
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Psychology 40 (1989), S. 327-351 
    ISSN: 0066-4308
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Psychology
    Type of Medium: Electronic Resource
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