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Biomedical subjects

M W Greaves

Publications and source records attributed to M W Greaves.

At least 253 records · Page 14Linked to original sources
PubMed1981

Nevus oligemicus. A variant of nevus anemicus.

A man had a long history of a persistent, fixed area of livid erythema on the trunk. The distribution of hair, sweat, and sensation were normal as were the histologic findings in the affected skin. The involved area had a decreased total skin blood flow and a lower surface temperature compared with surrounding uninvolved skin, but showed normal responses to vasoconstrictor and vasodilator stimuli. Incomplete sympathetic blockade partially abolished the erythema. We suggest that the appearance of the nevus is caused by increased vasoconstrictor tone in the thermoregulatory vessels of the involved skin, leading to relative stasis in the superficial "nutritional" vasculature. This would seem to be a new example of a "pharmacological nevus" showing similarities to and differences from nevus anemicus.

Hemangioma↗
PubMed1980

The kinetic properties and reaction mechanism of histamine methyltransferase from human skin.

The substrate kinetic properties of histamine methyltransferase from human skin were studied at limiting concentrations of both histamine and S-adenosylmethionine. Substrate inhibition by histamine was observed at concentrations above 10 microM. Primary plots showed evidence of a sequential reaction mechanism. The Michaelis constants were derived from secondary plots of slopes from the primary plots ([S]/v versus [S]) versus reciprocal of the second substrate concentration. The mean Km values for histamine and S-adenosylmethionine were 4.2 and 1.8 microM respectively. Histamine in concentrations of 25-100 microM inhibited enzyme activity uncompetitively with respect to S-adenosylmethionine. No substrate inhibition was observed with S-adenosylmethionine. To elucidate the reaction mechanism further, inhibition by the two products, S-adenosylhomocysteine and 1-methylhistamine, was studied. S-Adenosylhomocysteine inhibited non-competitively with respect to histamine and competitively with respect to S-adenosylmethionine. 1-Methylhistamine inhibited non-competitively with respect to histamine and to S-adenosylmethionine. These results are interpreted as providing evidence for an ordered sequential Bi Bi reaction mechanism, with the methyl-group donor S-adenosylmethionine as the first substrate that adds to the enzyme and histamine as the second substrate. 1-Methylhistamine is the first product to leave the enzyme and S-adenosylhomocysteine is the second. The results are discussed in terms of the possible role that this enzyme could play in the modulation of histamine-mediated reactions in skin.

Histamine↗
PubMed1980

The catabolism of prostaglandins by rat skin.

The activities of NAD+-dependent 15-hydroxy prostaglandin dehydrogenase in soluble fractions of rat skin and lung were compared by using a radiochemical assay method. Tritiated prostaglandin F2 alpha was incubated with NAD+ and 120,000 g supernatant of tissue homogenate. Extracted prostaglandin substrate and reaction products were separated by t.l.c. and quantitatively determined by liquid-scintillation counting. With skin 120,000 g supernatant, 10 mM-NAD+ and an incubation time of 15 min, the mean Vmax. was 5.5 nmol of prostaglandin F2 alpha converted/s per litre of reaction mixture. With lung 120,000 g supernatant, 60 mM-NAD+ and an incubation time of 5 min, the mean Vmax. was 26.9 nmol/s per litre, demonstrating 5-fold greater dehydrogenase activity in lung per unit wet weight of tissue. However, the total wet weight of skin was about 23 times that of lung, on dissection of individual rats, indicating that the entire skin may contain 4.5 times the total 15-hydroxy prostaglandin dehydrogenase activity of the lungs. Skin may thus be an important organ of prostaglandin catabolism.

Animals↗
PubMed1980

Cold urticaria. Dissociation of cold-evoked histamine release and urticara following cold challenge.

Nine patients with acquired cold urticaria were studied to assess the effects of beta-adrenergic agents, xanthines, and corticosteroids on cold-evoked histamine release from skin in vivo. The patients, in all of whom an immediate urticarial response developed after cooling of the forearm, demonstrated release of histamine into the venous blood draining that forearm. Following treatment with aminophylline and albuterol in combination or prednisone alone, suppression of histamine release occurred in all but one patient. In some patients, this was accompanied by a subjective diminution in pruritus or buring, but there was no significant improvement in the ensuing edema or erythema. In one patient, total suppression of histamine release was achieved without any effect on whealing and erythema in response to cold challenge. Our results suggest that histamine is not central to the pathogenesis of vascular changes in acquired cold urticaria.

Adolescent↗
PubMed1980

The anti-inflammatory and pharmacological effects of topically applied flurbiprofen on human skin 24 hours after ultraviolet B irradiation.

Human abdominal skin was irradiated, with three minimal erythema doses of ultraviolet B (290-320 nm) radiation, producing maximal erythema at 24h, with an associated rise in PGE2 and PGF2 alpha, measured by gas chromatograph-mass spectrometry. Topical applications of 5% flurbiprofen, a prostaglandin synthetase inhibiting drug applied immediately after irradiation, partially suppressed the u.v.B. evoked erythema at 24h but totally prevented elevation of PGE2 and PGF2 alpha, without any associated significant rise in arachidonic acid. These findings support the view that erythema due to u.v.B. is only partly mediated by products of cyclo-oxygenase pathway, and should prompt a search for other mediators, including non-prostaglandin metabolites of arachidonic acid.

Adult↗
PubMed1980

Time course changes in levels of arachidonic acid and prostaglandins D2, E2, F2 alpha in human skin following ultraviolet B irradiation.

1 Clinically normal human abdominal skin was irradiated with three minimal-erythema doses of ultraviolet B irradiation, (u.v.B). 2 Erythema was assessed visually, and exudate recovered by a suction bulla technique from normal skin, and at 10 min, 2, 6, 18, 24 and 48 h after irradiation. 3 Erythema was barely visible at 2 h, but increased to maximum at 24 h, which was maintained at 48 h. 4 Increased arachidonic acid and prostaglandin E2, F2 alpha and D2 concentrations in the exudate, measured by gas chromatography-mass spectrometry, accompanied the developing erythema, with the maximal rise of arachidonic acid, prostaglandin E2 and D2 occurring at the height of the erythema at 24 h. 5 At 48 h, still at the height of the erythemal response, arachidonic acid and PGE2 levels had returned to near normal. 6 Concentrations of arachidonic acid and of its products from the cyclo-oxygenase pathway, parallel the development of i.u.B. erythema in the first 24 h.

Adolescent↗
PubMed1980

Elevated blood histamine levels and mast cell degranulation in solar urticaria.

1 Ultraviolet radiation (UVR)-induced wealing was studied in four patients with solar urticaria, whose measured action spectra were within the range 300 to 700 nm. 2 Elevated histamine levels were found in blood draining wealed skin in all four patients. 3 Histological and electron microscopial studies of the irradiated skin showed evidence of mast cell degranulation. 4 These findings demonstrate an association between histamine release from mast cells and wealing in solar urticaria, and should encourage evaluation of drugs which suppress histamine release in this disorder.

Adult↗
PubMed1980

Oxatomide: in vivo assessment of antagonistic activity, and effects on histamine release and enzymatic histamine degradation in skin.

The antagonistic activity of oxatomide, and its effects on evoked histamine release and histamine-N-methyl transferase activity in skin, have been studied. Oxatomide antagonizes H1 activity in a dose-dependent but non-competitive manner. It also shows some atropine-like activity. Oxatomide did not cause detectable inhibition of antigen-stimulated histamine release from skin slices of sensitized guinea-pigs although the possibility that oxatomide may cause weak inhibition could not be excluded. In the presence of low concentrations of histamine, oxatomide suppressed human skin histamine-N-methyl transferase, but in the presence of higher substrate concentrations it enhanced activity of this enzyme. These observations, which were limited by the poor solubility of oxatomide in aqueous media, should encourage further in vivo studies of oxatomide's histamine-suppressing properties in the human subjects.

Acetylcholine↗
PubMed1980

treatment of hereditary angio-oedema by low dose attenuated androgens: disassociation of clinical response from levels of C1 esterase inhibitor and C4.

Nine patients with hereditary angio-oedema (H.A.E.) with a deficiency of C1 esterase inhibitor (C1 INH), have been treated with low dose attenuated androgenic drugs, with complete control of their disease. The C1 esterase inhibitor and C4 levels became normal in only one patient. It is concluded that H.A.E. can be controlled in the absence of correction of the reduced levels of C1 INH and C4. The mode of action of these drugs appears to be more complex than is generally realized.

Adult↗
PubMed1980

Protease inhibitor profiles in urticaria and angio-oedema.

Plasma levels of six protease inhibitors have been measured in patients with chronic urticaria, chronic urticaria with angio-oedema, cold and cholinergic urticaria. In chronic urticaria C1 esterase inhibitor activity was increased compared with a reference control population but there was no detectable abnormality of any other protease inhibitor. Patients with chronic urticaria/angio-oedema showed a reduction in inter-alpha trypsin inhibitor. They also manifested a rise in C1 esterase inhibitor. In cold urticaria there was a significant lowering of alpha 1 antichymotrypsin. The reduction in alpha 1 antitrypsin in this group probably reflects a genetic difference compared with the control population. Patients with cholinergic urticaria also showed a reduction of alpha 1 antichymotrypsin. The elevated levels of alpha 2 macroglobulin in the three groups are probably due to differences in the mean age of these groups compared with the reference population. Comparison of levels of subgroups of patients with and without active lesions suggest that a consumptive effect may contribute to the reduced values, although it seems unlikely to account for them entirely. The results suggest that involvement of pharmacologically active products of protein digestion may be involved in the pathogenesis of urticaria and should prompt attempts to identify these agents and encourage trial of medications which lead to inhibition of proteolytic activity in urticaria.

Adolescent↗