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  • Articles: DFG German National Licenses  (29)
  • 1
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 51 (1995), S. 1099-1102 
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: Microgravity offers an environment for protein crystallization where there is an absence of convection and sedimentation. We have investigated the effect of microgravity conditions on the perfection of protein crystals. The quality of crystals for X-ray diffraction studies is characterized by a number of factors, namely size, mosaicity and the resolution limit. By using tetragonal lysozyme crystals as a test case we show, with crystal growth in two separate Space Shuttle missions, that the mosaicity is improved by a factor of three to four over earth-grown ground control values. These microgravity-grown protein crystals are then essentially perfect diffraction gratings. As a result the peak to background of individual X-ray diffraction reflections is enhanced by a similar factor to the reduction in the mosaicity. This then offers a particularly important opportunity for improving the measurement of weak reflections such as occur at high diffraction resolution. These microgravity results set a benchmark for all future microgravity and earth-based protein crystallography procedures.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 53 (1997), S. 231-239 
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: The protein apocrustacyanin C1 has been crystallized by vapour diffusion in both microgravity (the NASA space shuttle USML-2 mission) and on the ground. Rocking width measurements were made on the crystals at the ESRF Swiss-Norwegian beamline using a high-resolution ψ-circle diffractometer from the University of Karlsruhe. Crystal perfection was then evaluated, from comparison of the reflection rocking curves from a total of five crystals (three grown in microgravity and two earth controls), and by plotting mosaicity versus reflection signal/noise. Comparison was then made with previous measurements of almost `perfect' lysozyme crystals grown aboard IML-2 and Spacehab-I and reported by Snell et al. [Snell, Weisgerber, Helliwell, Weckert, Hölzer & Schroer (1995). Acta Cryst. D51, 1099–1102]. Overall, the best diffraction-quality apocrustacyanin C1 crystal was microgravity grown, but one earth-grown crystal was as good as one of the other microgravity-grown crystals. The remaining two crystals (one from microgravity and one from earth) were poorer than the other three and of fairly equal quality. Crystal movement during growth in microgravity, resulting from the use of vapour-diffusion geometry, may be the cause of not realising the `theoretical' limit of perfect protein crystal quality.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 73 (1978), S. 287-297 
    ISSN: 1435-1803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wird über Versuche an isolierten Meerschweinchenherzen berichtet, bei denen myodardiale Kontraktionskraft (MCF), koronarer Perfusionsdruck (CPP) und myokardialer Sauerstoffverbrauch (QO2) simultan und kontinuierlich gemessen wurden. Die Herzen wurden mit konstanter Frequenz (180/min) elektrisch gereizt und nachLangendorff volumenkonstant (10 ml/min) perfundiert. Alle Tiere waren mit Reserpin vorbehandelt. Zusatz von Adenosin (ADO) oder PGE2 zur Perfusionslösung führte zu einer konzentrationsabhängigen Abnahme des CPP. Die ED50 (50% der maximalen Reaktion) betrug 2.1±0.6 nM für PGE2 und 40±7 nM für ADO (P〈0.01) bei 1.8 mM Cae. Kumulative Erhöhung des Cae in 6 Stufen von 0.55 auf 9.0 mM beeinflußte die koronare Vasodilatation durch ADO oder PGE2 nicht. Die Koronardilatation kann auch nicht durch eine substanzspezifische Wirkung auf MCF oder QO2 erklärt werden, obwohl beide durch ADO bei hohem Cae vermindert waren (P〈0.05). ADO-Effekte wurden durch gleichzeitig appliziertes PGE2 nicht gehemmt. Die Ergebnisse sprechen für eine spezifische koronardilatierende Wirkung von PGE2. Die Substanz ist an diesem Modell etwa 20fach wirksamer als Adenosin.
    Notes: Summary Experiments were performed on the isolated, electrically driven guinea-pig heart, perfused at constant rate. All animals were pretreated with reserpine. Myocardial contractile force (MCF), coronary perfusion pressure (CPP) and myocardial oxygen consumption (QO2) were monitored continuously. Both adenosine (ADO) and PGE2 produced a concentration-dependent decrease in the CPP. The ED50 (50% of maximum response) was 2.1±0.6×10−9 M for PGE2 but 40±7×10−9 M for ADO (P〈0.01) at 1.8 mM Cae. This coronary vasodilation was independent of the external Ca-concentration, which was varied between 0.55–9.0 mM. PGE2 had no effect on MCF or QO2 and the effect of ADO was only slight. There was no evidence that any action of ADO could be inhibited by simultaneously applied PGE2. The results provide evidence for the specific coronary vasodilating action of PGE2 which in this system is about 20 times as effective as adenosine.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-1803
    Keywords: Key words Smooth muscle cells – proliferation – cyclooxygenase-2 – PGI2– PGE1– iloprost – prostacyclin receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Vasodilatory prostaglandins (PGI2, PGE2, PGE1) are known inhibitors of proliferation of vascular smooth muscle cells (SMC) after stimulation with mitogenic factors. However, endogenous prostaglandins do not prevent SMC proliferation subsequent to vessel injury in vivo. Since vascular cells produce large amounts of antiproliferative prostaglandins, especially subsequent to COX-2 expression, insufficient vascular PGI2 formation is not likely to explain the failure of endogenous prostaglandins to prevent excessive SMC growth. In this paper we demonstrate a rapid development of tolerance to PGI2 in SMC, resulting in diminished antiproliferative activity. These findings may not only be relevant for the control of SMC growth by endogenously synthesized prostaglandins but also for clinical use of PGI2 mimetics.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 33 (1977), S. 349-350 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Prostaglandin A2 (PGA2) in concentrations of 1.5·10−8 to 3·10−6 M was found to produce concentration-dependent increase in the coronary vascular resistance of the guinea-pig isolated heart without alterations in myocardial contractile force and oxygen consumption.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 341 (1990), S. 308-315 
    ISSN: 1432-1912
    Keywords: Prostacyclins ; PGE1 ; PGE2 ; Superoxide anion generation ; gb-Glucuronidase ; cAMP ; Ca2+ ; Human neutrophils ; Platelet activating factor (PAF) ; FMLP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The action of PGE1, PGE2, PGI2 and iloprost on superoxide anion generation, lysosomal enzyme release, and changes of Ca2+ fluxes in human polymorphonuclear leukocytes (PMN) was studied in vitro. Both PGE-type compounds were equipotent inhibitors of FMLP-and PAF-stimulated superoxide anion generation, β-glucuronidase release (IC50 3–5 μmol/l) and Ca2+ influx while PGI2 and iloprost were ineffective at concentrations up to 10 μmol/l. These inhibitory actions of PGE1 and PGE2 were paralleled by an increase in cAMP level of the PMN while no change occurred with PGI2 and iloprost. None of the prostaglandins affected the initial intracellular Ca2+ liberation after challenge with FMLP or PAF. Preincubation of PMN with PGE1 and PGE2 but not with iloprost resulted in subsequent desensitization against a second administration of these compounds. None of the compounds affected PMN activation produced by arachidonic acid or calcimycin (A 23187). These data demonstrate that PGE-type compounds are effective inhibitors of receptor-mediated (PAF, FMLP) activation of human PMN while prostacyclins are considerably less potent. This suggests that the inhibitory prostaglandin receptor on human PMN belongs to the E-type being functionally different from the inhibitory prostaglandin receptor on human platelets. These results suggest that compounds, such as PGE1 and PGE2 might be superior to prostacyclins to prevent PMN-associated generation of reactive oxygen species and lysosomal enzyme release in situations with endogenous PMN activation, i. e. inflammatory reactions.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1997), S. 10-16 
    ISSN: 1432-1912
    Keywords: Key words Thromboxane A2 receptor ; Cloning ; Expression ; Radioligand binding ; Cyclic AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study describes the molecular cloning and functional characterization of the bovine thromboxane A2 (TP) receptor. Two partial nucleotide sequences coding for the bovine TP receptor were isolated from a bovine genomic and a bovine heart cDNA library. The deduced amino acid sequence suggests a heptahelical protein of 343 amino acids. The receptor protein is homologous with that of human placenta and endothelium at 84.0% and 81.4%, respectively. COS-7 cells were transfected with the bovine TP receptor cDNA, and binding affinities were assessed by radioligand binding studies. Specific displacement of [3H]SQ 29548 was demonstrated in COS-7 cell membranes with the unlabeled TP receptor antagonist SQ 29548 (K d = 12.6 ± 1.1 nM) and the TP receptor agonist U46619 (K d = 192.1 ± 58.9 nM), but not with other prostaglandins (PGD2, PGE1, PGF2α), or the PGI2 mimetic cicaprost. Agonist-induced stimulation of adenylyl cyclase in transfected COS-7 cells indicates a linkage to the cAMP signal transduction pathway via coupling to a stimulatory G-protein. Since bovine cells, e.g. vascular smooth muscle cells, are an established model to study the role of eicosanoids in cell signaling, this report on the molecular structure of the bovine TP receptor will allow further studies on receptor regulation.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 358 (1998), S. 160-167 
    ISSN: 1432-1912
    Keywords: Key words EP3-receptor ; cAMP ; NFκB ; E-box ; SP1 ; AP2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A cDNA clone, encoding a complete porcine EP3 receptor, was isolated from a porcine heart cDNA library. The deduced amino acid sequence revealed a protein of 387 amino acid residues with an estimated molecular weight of 43 kD and strongest homology to the human EP3-II receptor (84% identity on protein level). Ligand binding studies with transfected COS-7 cells, expressing the porcine receptor, showed displacement of [3H]PGE1 with the EP3-specific agonist M & B 28.767, the EP1/EP3-agonist sulprostone but not with the EP2-specific agonist butaprost. Stimulation of transfected CHO cells with M & B 28.767 resulted in inhibition of forskolin-induced cAMP formation, suggesting coupling to an inhibitory G protein. Agonist-induced translocation of the transcription factor NFκB into the nucleus of transfected CHO cells was demonstrated by Western blot analysis, indicating that these EP3 receptors modulate NFκB-dependent cellular signal transduction. Analysis of the genomic organization identified the major transcription initiation site at about 160 bp upstream of the ATG start codon. The 800-bp 5’ flanking region contains a variety of putative cis-acting regulatory elements, including binding sites for AP2, SP1 and MyoD (E-box). The present data will now allow further studies on EP3 receptor-mediated signal transduction and its regulation.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 53 (1986), S. 61-61 
    ISSN: 1432-0584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 64 (1986), S. 545-551 
    ISSN: 1432-1440
    Keywords: Iloprost ; Antiplatelet actions ; Blood pressure ; Regional perfusion ; Peripheral arterial obliterative disease (PAOD) ; Dose-response study ; Controlled trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II–III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg×min for 4 h, with an interval of 2–3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation and secretion ex vivo at doses of 0.5–2.0 ng/kg×min iloprost, indicating that iloprost reduced platelet stimulation by 50%–70%. The antiplatelet action of iloprost remained unchanged during infusion but ceased with 2 h after administration had ended. The agent was tolerated by the patients without unacceptable side-effects at doses up to 2 ng/kg × min. It is concluded that iloprost administered i.v. at doses of 1–2 ng/kg×min in patients with stage II–III PAOD does not involve haemodynamic side-effects and might be considered an effective antiplatelet agent.
    Type of Medium: Electronic Resource
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