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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Auranofin, 30–300 nM causes a concentration-dependent potentiation of phytohaemagglutinin (PHA)-induced interleukin-2 (IL-2) release from human peripheral blood mononuclear cells in culture. At concentrations of auranofin between 1 and 3 μM, PHA-stimulated IL-2 release was inhibited, and the drug is cytotoxic at these concentrations. At concentrations of auranofin which potentiated PHA-induced IL-2 release, it had no effect on [3H]-thymidine incorporation. Auranofin, 3 to 300 nM caused a concentration-dependent increase in the population of peripheral blood mononuclear cells bearing the IL-2 receptor (Tac positive cells). Auranofin, 300 nM caused an increase of approximately 100% in the glutathione level within the resting cells, and also increased the glutathione level in PHA-stimulated cells. We conclude that auranofin acts early in the cell cycle, selectively to increase the release of IL-2 and the expression of Tac. The action of auranofin on cellular glutathione levels may alter the redox state of the cell which is known to be important in the control of transcription factor activation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 8 (1978), S. 400-400 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 42 (1994), S. 154-158 
    ISSN: 1420-908X
    Keywords: Interleukin-1 ; Mouse macrophages ; Tumour necrosis factor ; Calcium ionophores ; Lipopoly-saccharide ; Phorbol ester
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lipopolysaccharide (LPS) caused a concentration-dependent increase of released and cell-associated interleukin-1 (IL-1) in resident peritoneal macrophages from the mouse. LPS was about 30 times more potent at stimulating the level of cell-associated IL-1 than it was at stimulating the release of IL-1. Human recombinant tumour necrosis factor-α (TNF-α) and the calcium ionophores A23187 and ionomycin induced a concentration-dependent increase of cell-associated IL-1 but failed to cause release of IL-1 at concentrations producing maximal stimulation of cell-associated IL-1. The phorbol ester, 4β-phorbol dibutyrate, stimulated the release of IL-1 from mouse macrophages but failed to induce an increase in cell-associated IL-1. Substance P, neurokinin A, neurokinin B, calcitonin gene-related peptide and platelet-activating factor did not increase the released or cell-associated IL-1 in mouse macrophages. These agents also failed to alter released or cell-associated IL-1 stimulated by LPS, 1 μg ml−1. It appears that a calcium signal is sufficient for the transcription and translation of IL-1 mRNA but does not result in the secretion of biologically active forms of IL-1. Our data also indicate that different intracellular signals may control the release and the cell accumulation of IL-1. We conclude that inflammatory mediators may independently increase either the release of, or the cell accumulation of IL-1.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 14 (1984), S. 420-424 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract (D-Pro4 D-Trp7,9,10)SP4–11 (SPA) has been shown to be a competitive antagonist of the histamine releasing action of substance P in rat peritoneal mast cells. Antagonist activity of SPA is expressed in the concentration range 1 to 10 μM, but at higher concentrations SPA releases histamine. SPA inhibits the flare response induced by substance P in human skin but is without effect on the wheal response. Up to 12.5 pmol SPA produces neither wheal nor flare response by itself. The structurally related peptide, kassinin, does not cause histamine release from rat mast cells at concentrations up to 10 μM whereas the methyl ester of substance P was found to 1.6 times more active than substance P in this respect. The findings are discussed in terms of the classification of substance P receptors and the mechanism of wheal and flare in human skin.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 16 (1985), S. 155-159 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relationship between rat peritoneal mast cell activation and inactivation (desensitization) was studied for a variety of stimuli acting via IgE and IgG receptors on the cell surface. Anti-IgE, antigen (ovalbumin), anti-IgG1, anti-IgG2a and dimers, trimers and higher oligomers of IgE were used to induce histamine release from rat mast cells. All produced similar characteristics of cell activation, with a rapid rate of histamine release from the cells, release being 90% complete within 5 minutes and with calculated doubling times between 21.6±3.6 s (±SEM) for ovalbumin and 93.0±18.6 s (±SEM) for anti-IgG1. The characteristics of inactivation, however, varied with the releasing agent used. Of all the stimuli used only ovalbumin showed a rapid rate of desensitization (t 1/2=330±34.8 s) which correlated with the cessation of histamine release. The other stimuli showed slow rates of desensitization (t 1/2 between 1068±40.2 s for dimer and 3576±660 s for anti-IgE) even though the rate of release was rapid. Thus, although these stimuli are thought to be stimulating the cells by cross-linking of either IgE or IgG receptors, the difference in subsequent response of the cells would indicate that the transduction mechanism bringing about release can distinguish between these various stimuli. Also, it seems that the idea that duration of histamine release is determined by the rate of desensitization may need revising as with most of these stimuli, release has terminated when the cells are still in a fully activated state.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 21 (1981), S. 63-81 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 31 (1980), S. 181-190 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 134 (1996), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been argued that the digital cutaneous microvasculature is the site of the anomaly which causes Raynaud's phenomenon (RP). Both endothelin-1 (ET-1), a potent vasoconstrictor peptide present in the digital cutaneous microvasculature. and calcitonin gene-related peptide (CGRP). a powerful vasodilator present in digital cutaneous perivascular nerves, have been implicated in the pathogenesis of RP. Circulating ET-1 levels are raised, and there is a diminution of CORP-containing perivascular nerves in linger skin in RPWe undertook a pharmacological study to investigate the sensitivity of the digital cutaneous microvasculature to intradermal ET-l and CGRP. Differences were found in RP compared with normal digital skin, supporting the idea that the digital cutaneous microvasculature is actively involved in the pathogenesis of RP. In RP, the erythematous response to ET-1 was diminished at both 20 and 5°C (a low temperature at which RP classically occurs) providing pharmacological support for the morphological evidence that in RP there is a deficiency of CGRP-containing nerves in the distal digital skin.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 42 (1987), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 to 30 ng/ml) produced a dose-related inhibition of substance P (SP)-induced histamine release from rat peritoneal mast cells. TPA itself induced some histamine release over this concentration range (maximum release about 20% of total). Maximum inhibition of SP-induced release by TPA required preincubation with TPA for at least 10 min. The inhibitory action of TPA was observed in the absence as well as in the presence of extracellular calcium (0.4 mM). Inhibition of diacylglycerol kinase by R 59022 or of diacylglycerol lipase by RHC 80267 reduced SP-induced histamine release. Oleolylacetylglycerol (OAG, 50 μM) inhibited histamine release induced by SP but was less potent than TPA. It is concluded that protein kinase C activation in rat peritoneal mast cells is associated with inhibition of SP-induced histamine release.
    Type of Medium: Electronic Resource
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