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Biomedical subjects

M W Greaves

Publications and source records attributed to M W Greaves.

At least 145 records · Page 8Linked to original sources
PubMed1988

Polymorphonuclear leukocyte random migration and chemotaxis in psoriatic and healthy adult smokers and non-smokers.

Random migration and chemotactic responsiveness of polymorphonuclear leukocytes (PMNs) from psoriatic and control smokers and non-smokers were studied in vitro and in vivo. In vivo, but not in vitro, PMNs from psoriatic smokers responded to a significantly greater degree to a standard chemotaxin than did PMNs from psoriatic non-smokers, control smokers and control non-smokers. This suggests that smoking has a selective effect on psoriatic PMNs. The possible relevance of this to the pathogenesis of psoriasis vulgaris and to palmoplantar pustulosis is discussed.

Adolescent↗
PubMed1988

The release of prostaglandin D2 from human skin in vivo and in vitro during immediate allergic reactions.

1. The release of prostaglandin D2 (PGD2) during immediate allergic reactions in human skin was investigated in vivo and in vitro. 2. Skin exudates were collected from abraded sites on the thigh of atopic subjects sensitive to D. pteronyssinus antigen and from non-atopic control subjects. Challenge with antigen caused the release of PGD2 and histamine, but not PGE2, from the skin of the atopic subjects. The molar ratio of histamine to PGD2 was about 140:1. Control subjects were unresponsive. 3. PGD2 was released from passively sensitized human skin challenged with antigen in vitro. The time course was similar in vitro and in vivo. The ratio of histamine to PGD2 in vitro was 78:1. 4. The identities of the prostaglandins were confirmed by high performance liquid chromatography and radioimmunoassay to PGD2 and PGE2. 5. PGD2 is the major arachidonic acid cyclo-oxygenase product synthesized by human mast cells. It is pro-inflammatory in human skin but its functions as a mediator in immediate hypersensitivity reactions in human skin are not clear. The results of this study suggest that, relative to histamine, PGD2 contributes little to the oedema and erythema of immediate reactions in human skin.

Adult↗
PubMed1988

Psoriatic skin lesions contain a novel lipid neutrophil chemokinetic compound which is distinct from known chemoattractant eicosanoids.

1. Lipid extracts of scale from the lesions of the skin disease psoriasis were purified by high performance liquid chromatography (h.p.l.c.). Assay of fractions by an agarose microdroplet method showed the presence of a novel neutrophil chemokinetic compound which possessed the chromatographic properties of a monohydroxy fatty acid, yet was distinct from the chemoattractant eicosanoid, 12-hydroxyeicosatetraenoic acid, previously isolated in psoriasis. 2. The novel, material, termed compound X, was also detected in fractions collected on h.p.l.c. of extracts of chamber fluid samples obtained from abraded psoriatic lesions, but was not detectable in samples from clinically normal skin. 3. Comparison of the straight and reversed phase h.p.l.c. retention times of compound X with those of a range of standard monohydroxy fatty acids, together with further analysis by gas chromatography-mass spectrometry and assay of selected standards for neutrophil chemokinetic activity, failed to reveal the structural identity of compound X. 4. The finding of a further compound in psoriatic lesions, which stimulates neutrophil movement, highlights the complexity of inflammatory mediator production in this disease.

Adult↗
PubMed1988

Human recombinant interleukin-1 alpha is proinflammatory in normal human skin.

The proinflammatory effects of recombinant human interleukin-1 alpha (HRIL-1 alpha) have been determined in the skin of normal human volunteers. Intradermal injection of 10, 50 and 100 U HRIL-1 alpha produced dose-related erythema which first appeared at 2 h, was maximal around 24 h, persisted for up to 48 h, and was associated with oedema. Histological examination revealed dermal mononuclear cell infiltrates, which were accompanied by neutrophils at 4 and 8 h. Injection of heat-treated HRIL-1 alpha (100 U) produced no erythema or oedema. These results demonstrate the potent proinflammatory properties of HRIL-1 alpha in human skin.

Adult↗
PubMed1988

Calcium antagonist in the treatment of symptomatic dermographism. Low-dose and high-dose studies with nifedipine.

The effect of nifedipine on subjective symptoms and objective dermographometer induced whealing was assessed independently in two double-blind cross-over trials in which active drug or placebo were taken for 2 weeks. The lower dose study used nifedipine 5 mg 3 times daily and gave rise to symptomatic improvement as assessed by diary card and visual analogue scale in 5 of 11 patients. This was not statistically significant and was not accompanied by a reduction in dermographometer-induced wheal and flare responses except at highest pressures. In a separate study 7 patients were treated with nifedipine 10 mg 3 times daily. No change in whealing occurred, 3 patients' symptoms became worse and only 1 showed symptomatic improvement on nifedipine. Side effects were frequent at this dose. The reasons for the unfavourable response despite in vitro evidence for inhibition of mast cell degranulation by this drug are discussed.

Adolescent↗
PubMed1988

Cholinergic urticaria, passive transfer experiments from human to monkey.

Passive transfer experiments in cholinergic urticaria were carried out from 16 patients to a Macaca cymnologous monkey. Intravenous Evans blue dye was used to demonstrate vascular permeability. The animal was challenged after 24 h first by heating the serum-injected dorsal skin to 45 degrees C and secondly by superinjection of acetylcholine into serum-injected sites, and a control site. Local heat proved insufficient to evoke a response. Seven of 16 serum-injected sites showed positive reaction to acetylcholine, control injection of acetylcholine did not. These experiments suggest the presence of a serum factor in cholinergic urticaria which, with acetylcholine, causes increased vascular permeability.

Acetylcholine↗
PubMed1988

Neutrophilic urticaria.

Eight patients with neutrophilic urticaria were identified in a 5-year biopsy experience (1980-1984). All patients had a neutrophilic venulitis without fibrinoid necrosis, hemorrhage, or leukocytoclasia. Four patients had a history of angioedema, and two had a personal history of atopic disease. Results of laboratory studies, including complement and protein values and antibody serologic tests, were normal. All patients responded to antihistamine agents. Despite occasional clinical or histologic diagnoses of vasculitis for such cases in the past, the clinical, laboratory, and histologic features and the therapeutic course of these patients are compatible with a phase or type of chronic urticaria.

Diagnosis, Differential↗
PubMed1988

Prostaglandins, leukotrienes, phospholipase, platelet activating factor, and cytokines: an integrated approach to inflammation of human skin.

The purpose of this review is to underline the interactions between eicosanoids, platelet activating factor and IL-1. While the evidence for arachidonate metabolites, especially 12-HETE and the leukotrienes, as major mediators of skin inflammation is persuasive, we wish to draw attention to the potential importance of leukotrienes and prostaglandins as modulators of PAF and IL-1 activity. Phospholipase A2 emerges as a key enzyme in relation to the three above-mentioned mediator classes of human skin. Activation of phospholipase A2 leads to synthesis of both eicosanoids and PAF. Leukotriene products in addition to being pro-inflammatory per se also enhance IL-1 formation whilst cyclo-oxygenase products inhibit IL-1. Prostaglandin E2 also potentiates the actions of PAF. In this scheme it appears improbable that selective inhibition of one component (e.g. a PAF antagonist) or one enzyme (e.g. a 5-lipoxygenase inhibitor) would do more than create an imbalance in this closely integrated network of mediators which might not necessarily be beneficial. On the other hand phospholipase A2 inhibitors including lipocortin would seem to have a greater chance of clinical usefulness because of the central role this enzyme appears to play in the formation or modulation of all these classes of mediator.

Annexins↗
PubMed1987

[New pharmacologic developments in physical urticaria--therapeutic consequences].

Recent evidence suggests that mast cell derived mediators other than histamine are likely to be involved in the pathogenesis of physical urticarias. Much of the work has been performed in idiopathic cold contact urticaria where the presence of neutrophil and eosinophil chemotactic factors, and platelet activating factor-like lipid substances have been previously demonstrated. Now, an increase in prostaglandin D2 measured by GC-MS has been demonstrated in venous blood draining the cold challenged area. This appeared a few minutes later than histamine, but then both substances paralleled the onset, development and subsidence of the urticarial reaction. There appeared to be no quantitative relationship between histamine and PGD2 release. A similar rise in histamine and PGD2 occurred on heat challenge of a subject with the rare localized form of heat urticaria. This rise of both substances was considerably reduced after combined treatment with induction of tolerance and oral indomethacin. The concentrations of PGD2 measured suggested that it plays an indirect role.

Cold Temperature↗
PubMed1987

Cholinergic urticaria. A clinical and histologic study.

We studied the natural history, the prevalence of atopy, and the frequency of systemic symptoms during attacks in 35 patients with cholinergic urticaria, the histologic condition of the eruption in seven patients (20%), and the response to intradermal injections of acetylcholine, histamine, and methacholine in 18 patients (51%). In most patients symptoms began between the ages of 10 and 30 years, persisted for many years, and caused them to modify their activities to avoid the provoking factors of exercise, emotion, and heat. The condition usually improved with time, and five patients (14%) had a spontaneous remission. Atopy, present in about 12 (34%) of the patients, was more frequent than in the general population. Systemic symptoms were uncommon during attacks, and patients had no greater responses than controls to the intradermal tests. The histologic study revealed neutrophils in and around the walls of superficial subpapillary dermal vessels.

Adolescent↗
PubMed1987

Cutaneous responses to 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and 5,12-dihydroxyeicosatetraenoic acid (leukotriene B4) in psoriasis and normal human skin.

The arachidonate lipoxygenase products 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and 5(S),12(R)-dihydroxy-6,8,10,14-eicosatetraenoic acid (leukotriene B4, LTB4) are potent leucocyte chemoattractants in vitro and in vivo. Both 12-HETE and LTB4-like material are found in increased amounts in lesional skin in psoriasis. Epicutaneous administration of 12(R,S)-HETE and LTB4 in normal skin evokes neutrophil and mononuclear dermal infiltrates accompanied by collections of neutrophils in the epidermis. Similar appearances result from the application of LTB4 to uninvolved skin in psoriasis. We have now investigated the effects of single and multiple epicutaneous applications of 12(R,S)-HETE and LTB4, both alone and in combination, in normal human skin and in clinically uninvolved skin of patients with psoriasis. As in the case of LTB4, erythematous responses to 12(R,S)-HETE were similar in normal skin and in psoriasis. Similar neutrophil polymorphonuclear responses were evoked by topical application of 50 ng LTB4 and 20 micrograms 12(R,S)-HETE. Application of the combination of 12(R,S)-HETE and LTB4 evoked only a partially additive erythematous response, and no evidence of an additive neutrophilotactic response was detected histologically. Multiple applications resulted in tolerance both clinically and histologically. Cross tolerance to 12(R,S)-HETE and LTB4 occurred in the majority of subjects. These results suggest that both 12(R,S)-HETE and LTB4 may be important in the production and control of the magnitude of the inflammatory events in psoriasis.

Dose-Response Relationship, Drug↗
PubMed1987

Extracellular deposition of eosinophil granule major basic protein in pressure urticaria.

Utilizing affinity chromatography-purified antibody to the eosinophil granule major basic protein and formalin-fixed paraffin embedded tissue, we investigated the localization of major basic protein by immunofluorescence in twenty-four skin biopsy specimens from ten patients with pressure urticaria. Fourteen of twenty-four biopsy specimens were obtained from spontaneously occurring urticarial lesions of 4 to 48 hours' duration, and ten of the twenty-four specimens were from dermographometer-induced lesions that had been present from 40 minutes to 24 hours. Twenty-one of twenty-four biopsy specimens showed extracellular fluorescence of eosinophil granule major basic protein within the dermis. The extent and intensity of extracellular staining were not related to the presence or degree of tissue eosinophilia. Serial section controls from each block were stained with protein A purified rabbit IgG and were negative. Previous immunofluorescence studies have demonstrated deposition of major basic protein in lesions of chronic idiopathic urticaria, episodic angioedema, and facial edema. Major basic protein causes release of histamine from human basophils and induces wheal-and-flare reactions on intradermal injection. The present observations add further evidence to support a role for eosinophil mediators, particularly major basic protein, in the pathogenesis of cutaneous disease characterized by edema.

Adult↗
PubMed1987

Pharmacology and significance of nonsteroidal anti-inflammatory drugs in the treatment of skin diseases.

Intensive studies of the molecular pathways involved in common inflammatory skin disorders, coupled with detailed pharmacologic evaluation of the responses of skin to the end products of these pathways, have resulted in a much clearer understanding of the mode of action of nonsteroidal anti-inflammatory drugs. In particular the development of lipoxygenase inhibitors is prompting intense interest in their possible role as anti-inflammatory agents in psoriasis and other dermatoses. Because of the potency of these and other classes of new anti-inflammatory drugs, careful monitoring of their pharmacokinetics in individual patients, especially those at risk for adverse reactions, will prove necessary, especially in the early stages of treatment. Meanwhile, currently available nonsteroidal anti-inflammatory drugs have a limited but significant place in the treatment of certain dermatoses. Current experience of the high incidence of adverse reactions to existing nonsteroidal anti-inflammatory drugs suggests that this will be no less a problem with new agents under development. The skin is frequently involved in adverse reactions to this class of drug, and past experience suggests that cutaneous reactions are among the earliest unwanted side effects reported in a new drug of this type. The dermatologist, therefore, has an important responsibility to observe, document, and report such "early warning signs" to the appropriate licensing authority and the manufacturer.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

The effect of prostaglandin D2 on the response of human skin to histamine.

The interaction of prostaglandin D2 (PGD2) and histamine in human skin was studied by intradermal injection of the compounds alone or in combination in healthy volunteers. Responses were recorded by measurement of areas of wheal and erythema, and changes in cutaneous blood flow quantified using a laser Doppler flow meter. The effect of a near-threshold dose of PGD2 on histamine dose-response relationships and on the response to a single low dose of histamine were examined. Histamine caused dose-related increases in blood flow and in areas of wheal and erythema in human skin. Prostaglandin D2 caused dose-related increases in blood flow and erythema area, but not wheal area, in the dose range used. When the compounds were injected together, PGD2 did not potentiate the increase in blood flow and areas of wheal and erythema due to histamine. The modest augmentation of histamine response in the presence of PGD2 could be attributed to summation alone. The role of PGD2 in cutaneous disorders such as the physical urticarias, in which its release has been demonstrated, is therefore uncertain. In the amounts measured in the urticarias, it is unlikely alone to cause a significant cutaneous response; nor does it appear to act by potentiation of the response to histamine.

Adult↗