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Biomedical subjects

M W Greaves

Publications and source records attributed to M W Greaves.

At least 325 records · Page 18Linked to original sources

Response of skin to ammonium persulphate.

In order to investigate the histamine liberating actions of ammonium persulphate, skin slices from three species (guinea pig, rat and monkey) were incubated in vitro with concentrations of ammonium persulphate ranging from 1 to 1000 microgram/ml. None of these concentrations released significant amounts of histamine in guinea pig or monkey skin. In the rat the highest concentration (1000 microgram/ml) released 20-24% of the histamine content of the skin, but the intensitivity of this response to cooling indicates a non-specific "toxic" action on mast cells. By contrast a known chemical histamine liberator, compound 48/80, released significant amounts of histamine from skin at much lower concentrations in all three species. Ammonium persulphate is clearly not a potent histamine liberator. Ammonium persulphate dermatitis is presumably a result of increased sensitivity of skin mast cells, due to immunological or other factors, in susceptible individuals.

Ammonium Sulfate↗

Induced tolerance in cold urticaria caused by cold-evoked histamine release.

The interrelations between cold sensitivity and release of histamine and other mediators in five patients with cold urticaria undergoing cold tolerance treatment were studied. Tolerance to cold was produced in all patients by repeated cold exposure. In four patients tolerance was maintained by once daily exposures. In the fifth patient 4-hourly exposures were necessary. Cold sensitivity was associated with histamine release in venous blood draining urticated skin. No prostaglandin activity was detected, and low concentrations of kinin activity were found in blood draining the normal and exposed skin of healthy subjects as well as in patients with cold urticaria. After induction of tolerance, no histamine release occurred on challenge by cold. Relapse of sensitivity was associated with reappearance of histamine release on challenge. The conclusion that tolerance is due to depletion of histamine stores in skin after repeated cold exposure was supported by diminished wealing in response to injection of a histamine liberator (compound 48/80) in cold-tolerant skin.

Adolescent↗

Factors affecting prostaglandin synthesis by rat skin microsomes.

Prostaglandin synthesis by rat skin was measured by a radiochemical method and the adrenochrome spectrophotometric method. About 70% of the total enzyme activity was located in the microsomal fraction. Incubation with (1-14C) arachidonic acid resulted in the formation of prostaglandins F2alpha, E2 and D2. The biosynthesis of these 3 prostaglandins was stimulated by reduced glutathione and hydroquinone, and was markedly dependent on pH. A number of non-steroid anti-inflammatory drugs produced a dose related inhibition of prostaglandin biosynthesis. Five potent corticosteroid anti-inflammatory agents previously found to be inhibitory when a skin homogenate was used did not inhibit prostaglandin synthesis by the microsomal fraction.

Animals↗

Physiology of skin.

One of Montagna's greatest contributions to study of the biology of the skin has been his demolition of the artificial walls that traditionally separated the histologist from the physiologist. He has shown that only by relating function with structure can we shed light on the workings of the skin. He has stressed the fallacy of studying a single structural or functional unit in isolation from others. The skin represents an organization of many different functional units, and physiology of skin is the study of this organization. My purpose is to make a personal commentary on the achievements, failures, and prospects of understanding some aspects of the organization of the functional units. Twenty-five years ago, the importance of relating skin to internal organs and systems received much attention. We have long been aware that skin sometimes reacts to internal disease, but only recently has the impact of skin disorders on the circulatory, renal, and gastrointestinal systems been recognized. As a result, our patients are now less likely to suffer from neglect of the whole which follows narrow over-specialized attention to the part. Increased interest in endocrine effects on the skin has revealed that several important physiologic activities of the skin are either partly or wholly regulated by hormones secreted by endocrine glands. Nevertheless, some physiologic activities in skin seems to be independent, their regulation being carried out by local mediating hormones. Other activities involve both central and local regulation. The nature and roles of these two control mechanisms and their interrelation constitute by far the most promising physiologic research in skin.

Animals↗

In vitro anaphylaxis in guinea-pig skin: amplification by burimamide.

The effects of burimamide, an H2-antihistamine, on the anaphylactic reaction in the skin of ovalbumin-sensitized guinea pigs were studied in vitro. Burimamide enhanced the concentration of histamine in the supernatant fraction of antigen-challenged sensitized guinea-pig skin in a dose-related way, but did not alter the concentration of residual histamine in the skin after antigen challenge. The enhanced histamine concentration in the supernatant was not due to increased histamine synthesis by the target cells during the reaction because the increase was not inhibited by a histidine decarboxylase inhibitor, Brocresine. In further experiments it was shown that guinea-pig skin possesses potent histamine degrading enzyme activity which is inhibited by burimamide. We suggest that inhibition of these degrading enzymes leads to the increase in histamine concentration in the presence of burimamide.

Anaphylaxis↗

Anti-inflammatory action of corticosteroids.

The anti-inflammatory action of corticosteroids is complex. At a cellular level, they cause redistribution of granulocytes, resulting in increased circulating granulocytes and reduced tissue pools. They also cause lymphopenia. The significance of these phenomena in relation to the anti-inflammatory activity of steroids is unknown. The most obvious pharmacological effects of corticosteroids are seen on blood vessels. They cause adrenergically mediated vasoconstriction and non-competitive antagonism of vasodilation due to prostaglanin E and bradykinin. Prostaglandin formation is inhibited by corticosteroids but whether this is due to an effect on enzymic synthesis or release is uncertain. Corticosteroids stabilize the lysosomal membrane preventing release of lysosomal enzymes in vitro but the significance of this in vivo is debatable.

Adrenal Cortex Hormones↗

Dermatology.

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Acne Vulgaris↗

Enzymic histamine metabolism in guinea-pig skin and its role in immediate hypersensitivity reactions.

Incubation of histamine with guinea-pig skin or with a particle-free supernatant fraction of homogenized skin caused progressive temperature dependent decay of histamine activity. The loss of histamine activity was due to enzymic degradation of histamine by diamine oxidase since it was reversed by aminoguanidine. Burimamide caused a similar though less marked reversal of histamine degradation. Studies using S-adenosylmethionine, an essential cofactor of histamine-N-methyl transferase suggested the presence in a latent form in guinea-pig skin of a second pathway for enzymic degradation of histamine involving N-methylation. Pretreatment of guinea-pigs with aminoguanidine caused marked potentiation of the 72 hr homologous PCA reaction which suggests that histamine degradation is an important modulating factor in immediate allergic reaction in this species.

Amine Oxidase (Copper-Containing)↗