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Biomedical subjects

C B Archer

Publications and source records attributed to C B Archer.

72 records · Page 4Linked to original sources

Adrenoceptor function in atopic dermatitis: in vitro and in vivo observations.

Impaired beta-adrenergic and enhanced alpha-adrenergic reactivity have been implicated in the pathogenesis of atopic dermatitis. We have measured the elevation of cyclic AMP in peripheral blood leukocytes in response to isoprenaline, histamine and prostaglandin E2, in the presence and absence of a phosphodiesterase inhibitor. An impaired response to beta-adrenergic stimulation was demonstrated in subjects with atopic dermatitis but impaired responses were also observed with histamine and prostaglandin E2. In vivo, both noradrenaline and salbutamol caused significant inhibition of the histamine-induced weal response in atopic and normal subjects. However, there was no significant difference between the two groups when alpha- and beta-adrenoceptor responses were compared.

Adrenergic alpha-Agonists↗

Inflammatory characteristics of PAF-acether in the skin of experimental animals and man.

PAF-acether (AGEPC) is released from a range of inflammatory cell types and has properties consistent with those of a mediator of inflammation. Intradermal injection of PAF-acether in experimental animals causes immediate extravasation of plasma protein, accompanied by intravascular accumulation of platelets and neutrophils; this is followed by persistent extravascular accumulation of neutrophils and mononuclear cells. We have studied the inflammatory characteristics of intradermally injected PAF-acether in human skin. An early (weal and flare) response is succeeded, in 60% of subjects, by a late-onset area of erythema at the site of the resolved weal, reminiscent of the dual response to allergen in sensitized individuals. The time course and dose-response relationship of the early response was determined and a synergistic interaction between PAF-acether and prostaglandin E2 established. The weal response to PAF-acether was not inhibited by concurrent administration of chlorpheniramine. Histopathological examination of serial elliptical biopsies revealed accumulation of both neutrophils and mononuclear cells in response to intracutaneous PAF-acether. We would suggest that PAF-acether is likely to be a mediator of both acute and persistent inflammation.

Animals↗

Cutaneous and pulmonary histopathological responses to platelet activating factor (Paf-acether) in the guinea-pig.

The effect of synthetic Paf-acether has been studied in guinea-pig skin, following intradermal injection, and in guinea-pig lung, following intravenous administration. Histopathological responses to Paf-acether were assessed by both light microscopy and electron microscopy. In addition, plasma protein extravasation and platelet accumulation were quantitatively assessed using radiolabelling techniques. Intradermal injection of Paf-acether, but not lyso-Paf, elicited acute increased vascular permeability, accompanied by intravascular accumulation of platelets and neutrophils. There was evidence, 2-8 h after intradermal injection of Paf-acether, of perivascular infiltration with neutrophils. At 24 h there was a mixed cellular infiltrate comprising mononuclear cells in addition to neutrophils. Following systemic administration of Paf-acether, aggregates of platelets in close association with neutrophils were evident within the pulmonary vasculature. Intravenous injection of Paf-acether, but not lyso-Paf, caused intrathoracic accumulation of radiolabelled platelets. These results suggest that Paf-acether has properties consistent with those of a mediator of inflammation.

Animals↗

Synergistic interaction between prostaglandins and PAF-acether in experimental animals and man.

Platelet activating factor (PAF-acether) is released from a variety of inflammatory cell types and has properties appropriate to a mediator of allergy and inflammation. Here, we have examined the interaction between PAF-acether and the prostaglandins, PGE2 and ZK 36374 (a stable analogue of prostacyclin, PGI2) in the skin of guinea-pigs and human volunteers. PGE2 and ZK 36374 significantly potentiated increased plasma protein extravasation induced by PAF-acether in guinea-pigs, assessed by extravasation of I-125-HSA. In addition, PGE2 significantly potentiated the ability of PAF-acether to elicit acute wheal (volume) and flare responses in human skin. The inflammatory properties of PAF-acether should not be considered in isolation since this phospholipid interacts synergistically with prostaglandins which are recognised as modulators of inflammation.

Animals↗

Mononuclear leukocyte cyclic adenosine monophosphate responses in psoriasis are normal.

It has been proposed that immune dysfunction in psoriasis is a consequence of aberrant cyclic nucleotide metabolism. We have examined cyclic AMP responses to isoprenaline, histamine, and prostaglandin E2 in peripheral blood mononuclear leukocytes from patients with psoriasis, in the presence and absence of a potent cyclic AMP phosphodiesterase inhibitor. Stimulated and basal cyclic AMP levels in mononuclear leukocytes from psoriatics did not differ from those observed in mononuclear leukocytes from normal subjects, irrespective of the stimulant employed, either in the presence or in the absence of the phosphodiesterase inhibitor. These findings do not support the hypothesis that psoriasis is associated with either impaired beta-adrenergic reactivity or a more generalized abnormality of mononuclear leukocyte cyclic nucleotide metabolism.

Adult↗

Inflammatory characteristics of platelet activating factor (PAF-acether) in human skin.

The phospholipid PAF-acether is released from a range of inflammatory cell types and, in experimental animals, has properties appropriate to a mediator of inflammation. We have studied the inflammatory characteristics of intradermally injected PAF-acether in human skin. An early weal and flare response was succeeded, in a proportion of subjects, by an area of late-onset erythema at the site of the resolved weal, reminiscent of the dual response to allergen in sensitized individuals. The time-course and dose-response relationship of the early response has been determined and a synergistic interaction between PAF-acether and prostaglandin E2 established. PAF-acether should therefore be considered as a potential mediator of both acute and persisting inflammation in man.

Adult↗

Ultrastructural features of metastatic cutaneous carcinoid.

Tissue from the cutaneous metastases of bronchial carcinoid was examined. Fine argyrophil secretory granules were demonstrated in the cytoplasm of the abnormal cells which showed positive labelling with neuron-specific enolase. Ultrastructural studies revealed numerous electron-dense membrane bound neuro-secretory granules, 50-300 nm in diameter. Other characteristic features included inter-digitating pseudo pod-like processes (up to 2 mu in size) in the cytoplasmic membrane, perinuclear filaments, a well-defined Golgi zone and numerous large mitochondria.

Aged↗

Impaired lymphocyte cyclic adenosine monophosphate responses in atopic eczema.

Peripheral blood lymphocyte cyclic AMP responses to isoprenaline, prostaglandin E2 and histamine were examined in patients with atopic eczema, in the presence and absence of a potent phosphodiesterase inhibitor (PDEI). Basal cyclic AMP levels were not significantly different in atopic and control groups. In the presence of the PDEI, there were impaired cyclic AMP responses to both isoprenaline and prostaglandin E2 in the atopic group. Differences between atopic and control cyclic AMP responses were exaggerated by the omission of the PDEI, when impaired responses to all agonists were observed in lymphocytes from atopic subjects. These results imply that, in atopic eczema, lymphocytes exhibit impaired responses not only at the beta-adrenoceptor site but at unrelated sites of adenylate cyclase activation, and these observations are consistent with increased leukocyte phosphodiesterase activity.

Adult↗