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Biomedical subjects

M W Greaves

Publications and source records attributed to M W Greaves.

At least 199 records · Page 11Linked to original sources
PubMed1984

The analysis of arachidonic acid metabolites in normal, uninvolved and lesional psoriatic skin.

Collection of exudate from suction bullae is a commonly used method for sampling human skin for mediator analysis. It is satisfactory on skin of normal structure but is unreliable on lesional psoriatic skin in which there are major structural changes and excessive scaling. Collection of exudates from abraded sites was found to be a suitable alternative method for psoriatic skin. Arachidonic acid and 12-HETE, but not PGE2, were significantly higher in exudate from abraded lesional psoriatic skin (494 +/- 88, 45.9 +/- 4.2 and 9.6 +/- 1.8 ng/ml respectively, mean +/- sem, n = 5) compared to uninvolved skin (154 + 38, 18.5 + 5.1 and 7.7 + 1.9 ng/ml) or skin of normal volunteers (119 +/- 37, 14.5 +/- 6.7 and 4.5 +/- 1.6 ng/ml, n = 7) which were similar. The coefficient of variation for exudate collection and mediator analysis was usually less than 55%. The analysis of lipoxygenase and cyclooxygenase products was simplified by the use of chlorobutane to extract preferentially arachidonic acid and HETEs from neutral aqueous solutions.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1984

The effect of etretinate on the cyclo-oxygenase and lipoxygenase products of arachidonic acid metabolism in psoriatic skin.

Eight psoriatic patients were treated with etretinate (50 mg daily) for 6 weeks. Skin chamber exudates from involved and uninvolved skin were assayed for arachidonic acid, 12-HETE, PGE2 and for neutrophil chemokinetic activity co-chromatographing with leukotriene B4, before and at weekly intervals during therapy. Pre-treatment concentrations of arachidonic acid, 12-HETE and leukotriene B4-like chemokinetic activity but not of PGE2 were elevated in involved skin when compared to uninvolved skin. The concentrations of arachidonic acid and 12-HETE declined during therapy but changes in PGE2 were minimal. LTB4-like activity was detectable in involved skin both before and after etretinate treatment. Clinically, scaling and infiltration improved but erythema was still evident.

Adult↗
PubMed1984

Levels of arachidonic acid and its metabolites in the skin in human allergic and irritant contact dermatitis.

Increased concentrations of arachidonic acid and prostaglandin E2, but not 12-hydroxy-eicosatetraenoic acid, were found in the skin in human contact dermatitis due to nickel and chromate allergens. Significant levels of neutrophil chemokinetic activity, with similar properties to leukotriene B4, were found in a high proportion of exudates from inflamed skin treated with allergen but not in exudates from untreated skin. Neither arachidonic acid nor its metabolites were increased in primary irritant dermatitis due to benzylalkonium chloride.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1984

Autonomic function in cholinergic urticaria and atopic eczema.

Autonomic function in patients with cholinergic urticaria and atopic eczema was compared with that in patients with chronic idiopathic urticaria and non-atopic allergic contact dermatitis, respectively. Forty-nine patients were studied. The following specific tests of sympathetic and parasympathetic function were used to assess the integrity of autonomic control: pupillary reflex amplitude in response to pulsed light stimulation and response to topical arecoline hydrobromide (parasympathetic); the speed of pupillary dilatation following a large light reflex (sympathetic); pupillary resting diameter (sympathetic and parasympathetic); sweat gland response to forearm intradermal injection of acetylcholine chloride; and the effect of postural change and deep breathing on blood pressure and heart rate (sinus arrhythmia indicating parasympathetic function). No significant difference in autonomic function was found between the four groups of patients.

Acetylcholine↗
PubMed1984

Increased concentrations of immunoreactive leukotrienes in cutaneous lesions of eosinophilic cellulitis.

A case of eosinophilic cellulitis is described. Tests of eosinophil function were normal. Radioimmunoassay identification of inflammatory mediators showed greatly increased concentrations of leukotrienes LTC4/D4 (components of slow-reacting substance of anaphylaxis) in the affected skin. These mediators may play a causal role in the inflammation seen with eosinophilic cellulitis.

Adult↗
PubMed1984

Leukotriene B4-like material in scale of psoriatic skin lesions.

Acidic lipid extracts of scale from the lesions of the skin disease, psoriasis, were purified by straight phase high performance liquid chromatography (h.p.l.c.). Assay of fractions by an agarose microdroplet chemokinesis method showed the presence of biologically active material that coeluted with standard leukotriene B4 (LTB4). LTB4-like chemokinetic activity was also detected in fractions collected on reversed phase h.p.l.c. of psoriatic scale extracts that were initially purified by straight phase h.p.l.c. No LTB4-like activity was detected after similar purification of scale obtained by abrasion of large areas of normal skin. The LTB4-like material found in extracts of psoriatic scale may play a role in the pathogenesis of the neutrophil infiltrate which characterizes psoriasis.

Cell Movement↗
PubMed1984

Toxicologic study of anthralin in an aqueous cream formulation.

A group of forty-eight patients with psoriasis who were being treated with anthralin cream were examined for side effects. Based on the variables investigated, there was no evidence of any systemic toxicity or excretion of anthraquinones (detection limit 20 micrograms/ml), while clinically, patients were seen to respond satisfactorily.

Administration, Topical↗
PubMed1983

Vascular responses of human skin to injection of substance P and mechanism of action.

The mechanism of cutaneous inflammation caused by substance P in human skin was assessed in five subjects receiving i.d. injections (5-405 pmol) at pH 7.2 as compared to histamine (0.08-1.6 nmol), compound 48/80 (100 ng) and solvent control. Both substance P and histamine produced sigmoid dose-response curves for the following parameters: 1 min and 5 min planimetrically measured areas of erythema, and mean diameter of weal. Substance P pretreatment induced tachyphylaxis, as assessed by standard methods with adequate controls, to both histamine and to substance P and vice versa. Erythema following substance P i.d. was not blocked by a constricting band. Diphenhydramine, and to a lesser extent doxantrazole, (but not cimetidine or indomethacin) when assessed as inhibitors after oral pretreatment, did shift dose response curves for histamine and substance P to the right. Light and electron microscopic assessment of mast cells was compared in substance P and solvent control injected human skin. These results support a possible role for substance P in cutaneous inflammation acting either directly or via histamine release from mast cells.

Cimetidine↗
PubMed1983

The identification of hydroxy fatty acids in psoriatic skin.

Psoriasis is a common chronic inflammatory and proliferative skin disease characterised by epidermal neutrophil infiltration which may be induced by chemotactic substances in the involved epidermis. Superficial psoriatic scale was shown to contain biologically active amounts of leukotriene B4 and monohydroxy-eicosatetraenoic acid (HETE)-like material as determined by assay for chemokinetic activity in high performance liquid chromatography (HPLC) fractions of scale extracts. Extracts of scale and chamber fluid from abraded lesional and uninvolved psoriatic skin were purified by HPLC and appropriate fractions were analysed by gas chromatography - mass spectrometry (GC-MS). The following monohydroxy metabolites of arachidonic, linoleic and 11,14-eicosadienoic acids were identified: 15-HETE, 12-HETE, 11-HETE, 9-HETE, 8-HETE, 5-HETE, 13-hydroxy-octadecadienoic acid (13-HODD), 9-HODD and 15-hydroxy-eicosadienoic acid (15-HEDE). The results suggested that 12-HETE, 13-HODD and 9-HODD are the most abundant monohydroxy fatty acids in the psoriatic skin extracts described above. Assays of 13-HODD, 9-HODD and 15-HEDE for chemokinetic activity were negative with concentrations up to 10(-4)M. The biological significance of these three compounds in not known, but some of the hydroxylated metabolites of arachidonic acid may, by virtue of their chemotactic properties, be relevant to the pathogenesis of the psoriatic neutrophil infiltrate.

Chromatography, High Pressure Liquid↗
PubMed1983

Histologic changes associated with ultraviolet A--induced erythema in normal human skin.

We have examined the effects of a standardized, moderately erythemogenic dose of long-wave ultraviolet (UVA) radiation on normal human skin, with the use of an appropriately filtered solar simulator and sequential biopsy specimens processed as 1-micron Epon-embedded sections. Histologic changes were present immediately after irradiation and evolved slowly during the 48-hour study. The epidermis manifested slight intracellular and intercellular edema and progressive loss of Langerhans cells to approximately one-fifth control values. A dermal infiltrate of neutrophilic polymorphonuclear leukocytes was present in all postirradiation specimens and peaked at 3 hours. A perivascular lymphocytic infiltrate, moderate endothelial cell enlargement, mast cell hypogranulation, occasional massive venular dilation, and sparse red blood cell extravasation were also noted. Overall, our findings expand and quantify earlier impressions that, compared to UVB, UVA has a relatively greater histologic effect on the dermis than on the epidermis, depletes epidermal Langerhans cells, and recruits neutrophils into irradiated human skin.

Adult↗