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Biomedical subjects

D M MacDonald

Publications and source records attributed to D M MacDonald.

At least 127 records · Page 7Linked to original sources
PubMed1985

In situ quantification of T-lymphocyte subsets and Langerhans cells in the inflammatory infiltrate of atopic eczema.

Tissue from the acute, non-infected eruption of sixteen atopic eczema subjects was subjected to an indirect immunoperoxidase technique using monoclonal antibodies recognizing T-lymphocyte subsets, Langerhans cells and natural killer cells. Over half the cells infiltrating the dermis were T lymphocytes, including a large majority of helper T cells and relatively few suppressor T cells. Langerhans cells were present in significant proportions in the dermis and probably reflected increased antigen presentation within the affected skin. There was no evidence of increased natural killer cell presence. This study suggests that type IV hypersensitivity may be implicated in the aetiology of atopic eczema.

Adolescent↗
PubMed1985

Accumulation of inflammatory cells in response to intracutaneous platelet activating factor (Paf-acether) in man.

Platelet activating factor (Paf-acether, AGEPC) is a family of ether-linked phospholipids known to be released from a range of inflammatory cell types. In vitro and in experimental animals, it seems to be a mediator of inflammation, and intradermal injection of Paf-acether in man elicits a biphasic inflammatory response, reminiscent of the dual response to allergen in sensitized individuals. In the present study, cutaneous histology was assessed in sequential skin biopsies from six normal volunteers after intradermal injection of 200 or 800 pmol Paf-acether. Paf-acether (200 pmol) induced intravascular accumulation of neutrophils, accompanied by a perivascular mixed cellular infiltrate which was composed predominantly of neutrophils at 4 and 12 hours, and lymphocytes and histiocytes at 24 hours. Control injections of lyso-Paf and normal saline induced no noteworthy histological changes. Paf-acether (800 pmol) resulted in vessel destruction, gross endothelial swelling and a perivascular infiltrate of mononuclear cells and neutrophils, accompanied by occasional evidence of leucocytoclasis. By virtue of its ability to induce inflammatory cell accumulation in human skin, Paf-acether should be considered as a potential mediator of inflammatory disorders such as psoriasis.

Adult↗
PubMed1985

Lichen aureus: a localized persistent form of pigmented purpuric dermatitis.

Localized persistent pigmented macules and plaques due to a chronic form of pigmented purpuric dermatitis are described in forty-two patients. The designation 'lichen aureus' for this eruption can be justified because of the striking yellowish or bronze-like colour assumed by many of the lesions. The lower legs were the commonest sites but other body regions can be affected also. Histologically lichen aureus differs from other pigmented purpuric dermatoses in the density of the lichenoid tissue reaction and the marked accumulation of pigment-containing macrophages. Recently developed endothelial cell markers have been studied in selected cases.

Adolescent↗
PubMed1985

Inflammatory cell accumulation in response to intracutaneous Paf-acether: a mediator of acute and persistent inflammation?

The ether-linked phospholipid, Paf-acether (AGEPC) is released from a variety of inflammatory cell types and has properties consistent with those of a mediator of inflammation. We have examined the effects of locally administered Paf-acether on cellular accumulation in the skin of experimental animals and man by histological evaluation of sequential skin biopsies and quantification of accumulation of radiolabelled blood elements. In guinea-pig skin, immediate extravasation of plasma protein and intravascular accumulation of platelets and neutrophils was succeeded by a persistent mixed cellular infiltrate predominantly of neutrophils but also containing lymphocytes and histiocytes. Radiolabelling studies were consistent with these observations. Intradermal Paf-acether elicited persistent clinical and histopathological responses in human skin. The finding that Paf-acether is able to initiate cutaneous cellular accumulation may be important in the pathogenesis of inflammatory dermatoses.

Acute Disease↗
PubMed1985

Effects of serum albumin, indomethacin and histamine H1-antagonists on Paf-acether-induced inflammatory responses in the skin of experimental animals and man.

Cutaneous responses to synthetic platelet activating factor (Paf-acether) have been studied in guinea-pig and human skin. Intradermal injection of Paf-acether elicited an acute inflammatory response in guinea-pig skin (assessed by means of radioisotopic techniques) and acute oedema formation in human skin (assessed by means of weal volume and flare area). Acute inflammatory responses in guinea-pig and human skin are potentiated by the presence of serum albumin, a phospholipid carrier. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are not significantly affected by concomitant administration of the cyclo-oxygenase inhibitor, indomethacin. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are not significantly affected by concomitant administration of the cyclo-oxygenase inhibitor, indomethacin. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are slightly modified by the H1-receptor antagonists, mepyramine and chlorpheniramine. These results indicate that the acute inflammatory response induced by Paf-acether is independent of cyclo-oxygenase products of arachidonic acid and that histamine release has a minor contribution to the inflammatory response induced by Paf-acether.

Adult↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

Cutaneous periarteritis nodosa. Hepatitis B surface antigen-containing immunocomplexes and polymorphonuclear-leukocyte lysosomal enzyme release.

In a patient with cold-induced cutaneous periarteritis nodosa, cryoprecipitation of a circulating hepatitis B surface antigen-containing immunocomplex resulted in phagocytosis by neutrophils and monocytes with prominent vacuolation of the cells and extracellular release of lysosomal enzymes. We believe this immunocomplex attached itself to the cell membrane and induced vacuolation and degranulation in normal neutrophils.

Antigen-Antibody Complex↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

An assessment of Langerhans cell quantification in tissue sections.

In this paper we look at the regional variation of Langerhans cell (LC) numbers in tissue sections between different sites in the same individual and identical sites in different individuals. We also looked at the reproducibility of identification of LC in tissue sections by their OKT6 reactivity. In this way we could assess the validity of comparative enumeration in random tissue sections. Stepped sections were obtained and stained by the OKT6 method. The slides were projected, the cells counted, and an image analysis system used to measure the length of basement membrane. In this way we could calculate the number of LC per millimeter of basement membrane. Our subjects were six age- and sex-matched volunteers. We found that the number of LC on the trunk was significantly lower than on any of the limbs. However, each individual had significant site variation of LC that was different for each one. This makes direct comparison of individual sections invalid and suggests that the most suitable control, when counting LC in lesional skin, is adjacent normal skin.

Adult↗
PubMed1984

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↗
PubMed1984

Bullous pyoderma gangrenosum and multiple myeloma.

The previously unrecorded association of superficial bullous pyoderma and IgG-producing multiple myeloma is described. A rapid response of the cutaneous manifestations was achieved by treatment of the malignant paraproteinaemia.

Antibodies, Neoplasm↗
PubMed1984

The pathogenesis of amiodarone-induced pigmentation and photosensitivity.

A new method has been used to measure tissue levels of amiodarone and its major metabolite desethylamiodarone. Amiodarone-pigmented skin has a drug and metabolite concentration ten times that of non-pigmented skin. Iodine-rich amiodarone and its metabolite have been detected in secondary lysosomes by energy dispersive analysis of X-rays. Amiodarone induces a phototoxic reaction with an action spectrum in both the UV-B and UV-A wavelengths.

Adult↗