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J C Foreman

Publications and source records attributed to J C Foreman.

At least 37 records · Page 2Linked to original sources
PubMed1994

IgE-receptor activated chloride uptake in relation to histamine secretion from rat mast cells.

1. Antigen-stimulated histamine secretion from rat peritoneal mast cells was inhibited when extracellular chloride was replaced by either isethionate or gluconate anions, but the histamine release still remained quite substantial. 2. Rat peritoneal mast cells take up 36Cl and the uptake reaches a steady state after 60 min incubation with the isotope. At steady state, the intracellular chloride level in the cells was calculated to be 29 +/- 11.5 mM. 3. The chloride uptake in mast cells was exponential with a rate constant of 0.036 min-1 in resting cells. When the cells were stimulated with antigen, and rate constant for chloride uptake increased to 0.90 min-1: an increase of 25 fold. Under identical experimental conditions histamine release increased 3 fold. 4. The rate of chloride uptake in either resting cells or in antigen-stimulated cells was not changed when the extracellular medium was nominally calcium-free but histamine release was almost completely inhibited in the absence of extracellular calcium. 5. The putative chloride channel blocker DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) 0.3 to 30 microM, produced a concentration-related inhibition of antigen-stimulated histamine secretion but DIDS (30 microM) did not inhibit the antigen-stimulated increase of chloride uptake. 6. The cyclic AMP analogue, dibutyryl cyclic AMP (1 mM) produced a delayed increase in chloride uptake in resting mast cells but neither dibutyryl cyclic AMP nor 8-bromo cyclic AMP per se induced any histamine secretion. 7. Ouabain (1 mM) which inhibits the Na+/K+ ATPase in rat peritoneal mast cells, failed to affect the uptake of chloride in resting mast cells. 8. The Na/K/2C1-cotransport inhibitor, furosemide (0.7 mM), slowed the unstimulated chloride uptake in resting mast cells and abolished the increased antigen-induced chloride uptake when added together with antigen. In contrast, spontaneous and antigen-induced histamine release were unaffected by the presence of furosemide. However, when furosemide was added to the cell suspension 5 min before stimulation, furosemide was without effect on the antigen-induced chloride uptake.9. In addition to the chloride uptake mediated by chloride channels which may be related to the mechanism of histamine secretion, crosslinking of the high affinity membrane receptors for IgE is followed by a fast chloride uptake that is likely to occur through a furosemide-sensitive Na/K/2C1-cotransporter.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

The effect of non-steroidal anti-inflammatory drugs on the accumulation and release of interleukin-1-like activity by peritoneal macrophages from the mouse.

1. The non-steroidal anti-inflammatory drugs (NSAIDs) indomethacin, 10 and 100 microM, piroxicam, 100 microM, and sodium meclofenamate, 1 and 100 microM, potentiated the lipopolysaccharide (LPS)-stimulated release of interleukin-1 (IL-1)-like activity from mouse peritoneal macrophages. Aspirin up to 100 microM was without effect. The drugs did not themselves stimulate the release of IL-1-like activity at the concentrations used. 2. LPS, 1 microgram ml-1, stimulated prostaglandin E2 production by mouse peritoneal macrophages and this was totally inhibited by aspirin, 100 microM, indomethacin, 1 microM, piroxicam, 10 microM and sodium meclofenamate, 0.1 microM. 3. The potentiation of LPS-stimulated release of IL-1-like activity produced by indomethacin, 100 microM, piroxicam, 100 microM, or sodium meclofenamate, 10 microM, was inhibited by prostaglandin E2, (PGE2) 10 ng ml-1. 4. Aspirin, 100 microM, indomethacin, 100 nM to 10 microM, piroxicam, 1 to 100 microM, and sodium meclofenamate, 10 nM, all potentiated cell-associated IL-1-like activity in LPS- stimulated macrophages. The drugs had no effect on cell-associated IL-1-like activity by themselves. 5. Exogenous PGE2, 2 to 30 ng ml-1, inhibited the cell-accumulation of IL-1-like activity stimulated by LPS in the presence of indomethacin, 1 microM, or sodium meclofenamate, 0.1 microM. 6. The 5-lipoxygenase inhibitors BWA4C, 0.01 to 10 microM, and L-651,392, 0.01 to 10 microM, had no effect on LPS-stimulated released or cell-associated IL-1-like activity. Over the same concentration-ranges,neither of the 5-lipoxygenase inhibitors affected released or cell-associated IL-1-like activity in LPS stimulated mouse macrophages in the presence of indomethacin, 1 JM.7. The synthetic diacylglycerol, DiC8, 10 to 200 JAM, did not itself increase released or cell-associated IL-I-like activity but in the presence of the diacylglycerol kinase inhibitor, R59022, 10 JM, DiC8increased released and cell-associated IL-i-like activity. The activity of DiC8 on released and cell associated IL-l-like activity was not increased by indomethacin, 100 micro M.8. NSAIDs increase LPS-induced cell-associated IL-i-like activity in mouse macrophages by inhibiting the formation of cyclo-oxygenase products such as PGE2 but at higher concentrations the NSAIDs potentiate LPS-induced release of IL-I-like activity by a mechanism independent of cyclo-oxygenase inhibition. The potentiation of the release of IL-i-like activity appears not to be related to an effect of NSAIDs on either 5-lipoxygenase or diacylglycerol metabolism.

Animals↗
PubMed1993

Human basophil degranulation is not triggered by very dilute antiserum against human IgE.

We have attempted to reproduce the findings of Benveniste and co-workers, who reported in 1988 that degranulation of human basophil leukocytes is triggered by very dilute (10(2)-10(120)) antiserum against IgE. The results were contrary to conventional scientific theory and were not satisfactorily explained. Following as closely as possible the methods of the original study, we can find no evidence for any periodic or polynomial change of degranulation as a function of anti-IgE dilution. Our results contain a source of variation for which we cannot account, but no aspect of the data is consistent with the previously published claims.

Analysis of Variance↗
PubMed1993

The interaction of auranofin and buthionine sulfoximine blocks activation of human peripheral T lymphocytes.

We have previously demonstrated that auranofin, at nanomolar concentrations, enhances T cell activation, as measured by IL-2 release and Tac expression. However, it is not clear how enhanced T cell activation might be related to therapeutic value, since rheumatoid arthritis is widely believed to be associated with overactivation of the immune response. In this study, we show that the action of auranofin on T cell activation is dramatically influenced by the glutathione levels of the responding cells. Under conditions of very low intracellular glutathione where the synthesis of glutathione is blocked, the action of auranofin is converted from enhancement to a profound inhibition of T cell activation. Since glutathione levels in rheumatoid arthritis are known to be abnormally low, these results may explain how auranofin can act to suppress the immunological processes leading to rheumatoid arthritis. In addition, this study further demonstrated the close link which exists between auranofin action and glutathione metabolism in lymphocytes.

Auranofin↗
PubMed1993

The effects of auranofin on activation and interleukin-2 release from human peripheral blood mononuclear cells.

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 microM, 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.

Antibodies, Monoclonal↗
PubMed1993

The effect of platelet-activating factor on the responsiveness of the human nasal airway.

1. The effects of inhaled platelet-activating factor (PAF) on responsiveness of the human nasal airway were examined in normal subjects by measuring nasal airway resistance in response to histamine and bradykinin at 2, 6, 24, 48 h and 7 d after PAF administration. Eosinophil cationic protein (ECP) in nasal secretions was also measured. 2. Intranasal aerosol administration of PAF, 30 or 60 micrograms per nostril to normal human subjects induced an increased responsiveness to inhaled histamine, 50 to 400 micrograms and bradykinin, 100 micrograms per nostril at 2, 6 and 24 h following PAF treatment. However the effect was not apparent at 48 h or 7 days after PAF administration. 3. Intranasal administration of lyso-PAF, 60 micrograms by aerosol did not increase the reactivity of the nasal airway in response to histamine, 200 micrograms. 4. There was no difference in the time course of the PAF-induced hyperresponsiveness to histamine or bradykinin. 5. PAF-induced nasal hyperresponsiveness at 2 and 6 h was associated with increases in the ECP concentration of the nasal lavage fluid. 6. Vitamin E pretreatment of subjects resulted in the attenuation of the PAF-induced hyperresponsiveness to histamine, and a decrease in ECP levels of the nasal lavage fluid. 7. The results suggest that in the human nasal airway, PAF induces a non-specific hyperresponsiveness which is accompanied by eosinophil activation in the nasal cavity. Free radical production induced by PAF may contribute to the hyperresponsiveness and the activation of eosinophils.

Administration, Inhalation↗
PubMed1992

Cutaneous responses to vasoactive intestinal polypeptide in chronic idiopathic urticaria.

Cutaneous wheal and flare responses to increasing concentrations of calcitonin gene-related peptide, substance P, neurokinin A, vasoactive intestinal polypeptide (VIP), compound 48/80, and phosphate-buffered saline were measured in 10 patients with chronic idiopathic urticaria and 10 healthy controls. A significant increase in VIP-induced wheal, but not flare or cutaneous blood flow, was seen in urticarial patients compared with controls (p less than 0.001). No significant differences in responses to other tested compounds were found between these groups. These data point to an increased sensitivity of microvasculature to VIP in patients with chronic idiopathic urticaria.

Adult↗
PubMed1992

Further studies on the actions of endothelin-1 on blood flow in human skin.

When injected into human skin, endothelin-1 produces intense vasoconstriction localized to the site of the injection, but this area of vasoconstriction is surrounded by vasodilatation which spreads several centimetres from the injection site. The vasodilatation induced by intradermal injection of endothelin-1 (63 pmol) into human skin is prevented by local anaesthetic. Pretreatment of human skin with capsaicin also inhibits this response. Pretreatment of subjects with the selective histamine H1-receptor antagonist cetirizine, 10 mg orally 4 h before intradermal injections, inhibited vasodilatation caused by the intradermal injection of histamine (750 pmol), endothelin-1 (63 pmol), and carbachol (750 pmol). Endothelin-1 (0.3-10 microM) and carbachol (1-30 microM) failed to induce histamine release from rat peritoneal mast cells. We conclude that the vasodilatation caused by intradermal injection of endothelin-1 into human skin is neurogenic and is probably mediated by neuropeptide-containing primary afferent neurones. Because neither carbachol nor endothelin-1 cause histamine release from mast cells, our data suggest that histamine release from mast cells at the effector end of the axon reflex is responsible for the carbachol- and endothelin-induced vasodilatation in human skin.

Adult↗
PubMed1992

Comparison of infrared and helium-neon lasers in the measurement of blood flow in human skin by the laser-Doppler technique.

Histamine-induced changes in blood flow in normal human skin were assessed by laser-Doppler velocimetry using 2 lasers of different wavelengths: 780 nm infrared and 633 nm helium-neon. The visible flare response in skin was also measured by planimetry. Laser-Doppler velocimetry was shown to detect both the magnitude of the change in blood flow caused by histamine and also the extent of the changes in the skin. Both parameters were related to the dose of histamine, which ranged between 25 and 750 pmol/site. There was good correlation between the magnitude of the histamine-induced blood flow change and the extent of the response. The flare induced by histamine and measured by planimetry was similar in extent to the blood flow change recorded by laser-Doppler velocimetry. No difference in either the magnitude or the extent of blood flow changes in response to histamine, as measured by laser-Doppler velocimetry, were found when lasers of different wavelengths were used.

Adult↗
PubMed1991

The effect of capsaicin application on mast cells in normal human skin.

Peptides released from sensory nerves during an axon reflex are thought to cause mast cell degranulation, histamine (Hi) release and Hi-induced vasodilatation leading to the flare of the triple response. Capsaicin stimulates peptide release from sensory neurones and causes flare in vivo but does not cause Hi release from mast cells in vitro. The effects of capsaicin on mast cell degranulation in human skin in vivo has been studied by histological examination of skin biopsies after topical capsicin (1%) treatment of stratum corneum-denuded forearm in four volunteers. The results show a significant reduction in the visible numbers of mast cells and the appearance of degranulated mast cells ghosts in the skin six hours after capsaicin application. Since capsaicin itself does not release Hi from mast cells, these data suggest that capsaicin-induced release of peptides from neurones could cause mast cell degranulation.

Adult↗
PubMed1991

Vascular responses to histamine at low temperatures in normal digital skin and Raynaud's phenomenon.

A defective histaminergic dilating system in the digital vasculature has been proposed for the pathophysiology of Raynaud's phenomenon but this is not supported by studies of digital intradermal responses to histamine or agents which cause histamine release. The vascular responses (measured by planimetry and laser Doppler flowmetry) of digital skin over the middle phalanx to intradermal histamine, compound 48/80 and Substance P have now been studied at low temperatures (because it is in the cold that Raynaud's phenomenon occurs) in normal controls and patients with primary Raynaud's phenomenon. A cold-related attenuation of mast cell histamine release by compound 48/80 was observed in both normal and Raynaud's subjects. These results do not support a major histaminergic defect in the pathogenesis of Raynaud's phenomenon.

Adult↗
PubMed1991

Digital cutaneous vascular responses to histamine and neuropeptides in Raynaud's phenomenon.

The pathophysiology of Raynaud's phenomenon is not well defined, but active cutaneous microvascular vasoconstriction and emptying must occur to account for the pallor and are reasons for studying the microvasculature. It has been proposed that there may be a defect in a local histamine vasodilator mechanism. The role of the peptidergic nervous system in Raynaud's phenomenon has not been previously investigated. To study the histaminergic and peptidergic axes in Raynaud's phenomenon, we measured the cutaneous microvascular responses of patients with Raynaud's phenomenon to digital intradermal injections of saline, histamine, the histamine-releasing agent, compound 48/80, substance P, and calcitonin gene-related peptide. We compared these results with those obtained in normal subjects. Intradermal cutaneous microvascular blood flow responses were quantified by planimetry and laser Doppler flowmetry. The results show: a) that in primary Raynaud's phenomenon there is no evidence of local deficiency in histamine release or insensitivity to histamine in the cutaneous microvasculature; and b) that patients with Raynaud's phenomenon react normally to the neuropeptides calcitonin gene-related peptide and substance P, providing a rationale for treating Raynaud's phenomenon with vasoactive peptides.

Adolescent↗
PubMed1990

Effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on substance P-induced histamine release from rat peritoneal mast cells.

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 microM) 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.

Animals↗
PubMed1990

Anorexia nervosa associated with acromegaloid features, onset of acrocyanosis and Raynaud's phenomenon and worsening of chilblains.

Patients with anorexia nervosa may develop many physical and endocrinological complications. We wish to report two patients who developed soft tissue swelling of their hands and worsening of their peripheral vascular disease, evidenced by the appearance of acrocyanosis and Raynaud's phenomenon and more severe perniosis, following the onset of their anorexia nervosa.

Acromegaly↗
PubMed1989

The actions of retinal and retinoic acid on histamine release from rat peritoneal mast cells.

Histamine release from rat peritoneal mast cells induced by anti-IgE was potentiated by the retinoids: retinoic acid 2-10 microM and retinal 1-5 microM. Retinal also produced a concentration-dependent increase in anti-IgE-stimulated 45Ca uptake by these mast cells. A similar potentiating action of both retinoids was observed on histamine release induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). For both anti-IgE- and TPA-induced histamine release, the potentiating effect of the two retinoids was only observed in the presence of extracellular calcium. In contrast, histamine release induced by compound 48/80 was inhibited by retinal 1-5 microM and by retinoic acid 10-50 microM and the inhibition was the same in the presence as in the absence of extracellular calcium 1 mM. Histamine release induced by calcium and the calcium ionophore A 23187 was inhibited by retinoid acid 2-10 microM and by retinal 10 microM. Inhibitions of compounds 48/80-induced histamine release by cromoglycate and by retinal were additive. It is concluded that while the actions of retinoids on rat peritoneal mast cells are consistent with the inhibition of protein kinase C, another action of these compounds, unrelated to this enzyme, may explain the data.

Animals↗