PubMed HealthSearch

Biomedical subjects

S Shuster

Publications and source records attributed to S Shuster.

At least 73 records · Page 4Linked to original sources

Role of protein kinase C in the pigment cell of the lizard (Anolis carolinensis).

The role of protein kinase C in melanosome dispersion was examined using the melanophores of the lizard Anolis carolinensis and an in-vitro rate method of bioassay. The phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which directly activates protein kinase C, was able to potentiate the melanophore response to alpha-MSH in a dose-dependent manner. Similarly, the stimulatory response to forskolin, which activates the adenylate cyclase catalytic subunit, was also potentiated by TPA. The response of the melanophore to cyclic AMP, however, remained unaltered by any dose of TPA. We thus propose that the potentiation of alpha-MSH potency by TPA is through an interaction of protein kinase C with adenylate cyclase and, more specifically, that this interaction may be at the level of the linkage of the nucleotide regulatory subunit Ns with the catalytic moiety C of adenylate cyclase.

Animals

Effect of aspirin on pruritus.

The effect of 900 mg aspirin on persistent itch from chronic dermatoses other than urticaria (eight patients) and other causes (five patients) was measured subjectively using a 10 cm line and objectively as nocturnal scratch using limb meters. There was no change in itch or scratch and it is concluded that aspirin neither affects itch centrally by a pain related mechanism nor affects itch physiologically by cyclo-oxygenase inhibition in the skin.

Adolescent

Site variation in anthralin inflammation on forearm skin.

The effect of application site on anthralin inflammation was measured at 10 clinically normal volar skin sites on each forearm of 31 subjects as the increase in skin thickness at 48 h using Harpenden calipers. Pre-treatment and increase in skin thickness were significantly related to application site. Pre-treatment thickness increased distally and laterally by an amount depending on sex, and to a lesser extent other factors, whilst the increase in skin thickness values was greater proximally, laterally and on the right arm but was not affected by age, sex or skin type. When increases in skin thickness values were adjusted for pre-treatment thickness, the difference between proximal and distal sites was lost but there was still a significant difference between the medial and lateral aspect and the right and left arms. The absolute differences were small but demonstrate the need to use symmetrical forearm skin sites and randomized treatment sides when comparing the effects of topical agents on anthralin inflammation.

Adolescent

Measurement of lipogenesis in isolated preputial gland cells of the rat and the effect of oestrogen.

Lipogenesis was measured in isolated preputial gland cells of female rats after ovariectomy and after the administration of oestradiol benzoate. Ovariectomy decreased preputial gland cell lipogenesis and also altered the pattern of lipid synthesis, producing a relative decrease in the proportion of polar lipids and an increase in the proportion of 'triglycerides'. Although daily administration of 2 or 10 micrograms oestradiol benzoate for 7 days produced slight increases in preputial gland cell lipogenesis in ovariectomized rats, the effects were not significant. A single injection of 10 micrograms oestradiol benzoate, however, produced significant increases in preputial gland cell lipogenesis of ovariectomized rats at both 2 and 24 h and, moreover, at 24 h the pattern of polar lipid and triglyceride labelling was restored to normal. Prior administration of actinomycin D reduced the lipogenic effect of oestradiol benzoate. Oestradiol benzoate had little or no effect on preputial gland cell lipogenesis in male rats. These results confirm that oestrogen is able to stimulate preputial lipogenesis in female rats. Whether this action of oestrogen is related to its pheromone-producing effect on the preputial glands is not yet known.

Animals

The nature of mycosis fungoides.

Thirty-four patients with a clinical diagnosis of plaque stage mycosis fungoides, poikiloderma atrophicans vasculare (poikiloderma) and parapsoriasis en plaques (parapsoriasis) were investigated for evidence of extracutaneous disease using a biochemical screen, blood films, bone marrow examination, chest radiograph, abdominal ultrasound, isotope liver scan, liver biopsy and lymphangiography. Skin biopsies were also taken from these patients and, in order to rule out non-specific histological change, from 29 controls with inflammatory skin disease; the slides were examined blind by two independent observers for evidence of mycosis fungoides or poikiloderma and graded accordingly. Both observers were able to differentiate significantly histological grades of mycosis fungoides corresponding to the clinical diagnosis although exact histological grades only corresponded on 35 per cent of slides. Features graded as classical or probable mycosis fungoides were found in between 22 and 67 per cent of patients with parapsoriasis and between 67 and 100 per cent of those with poikiloderma. We found no evidence of extracutaneous disease in any of our patients. Lymphangiograms were abnormal in 30 of 31 examinations but the changes were non-specific and did not correspond to disease type, duration or extent. Four patients had apparently unrelated co-existing disease including chronic lymphatic leukaemia in two, a monoclonal gammopathy and autoimmune haemolytic anaemia. This study shows that in its early stages mycosis fungoides is predominantly if not primarily a cutaneous disease. The findings also suggest that parapsoriasis and poikiloderma are part of the same disorder as mycosis fungoides or evolve into it. Aggressive treatment to prevent progression to mycosis fungoides plaque and tumour stage should therefore be tried. The findings support the idea that mycosis fungoides is a reactive rather than a neoplastic disorder.

Adolescent

Response of scalp psoriasis to oral ketoconazole.

A randomised double-blind placebo-controlled study showed improvement of scalp psoriasis with oral ketoconazole, although the study had to be stopped before completion because of the possibility of drug toxicity. The common appearance of psoriasis in the scalp and certain other sites may be due to pityrosporal colonisation that also causes seborrhoeic dermatitis and dandruff.

Administration, Oral

Phase 1 and Phase 2 drug metabolism in isolated epidermal cells from adult hairless mice and in whole human hair follicles.

A sensitive fluorimetric assay to determine both Phase 1 (oxidation) and Phase 2 (conjugation) drug metabolism in epidermal cells isolated from hairless mice, using ethoxycoumarin as a model substrate, is described. Ethoxycoumarin was metabolized by isolated epidermal cells via dealkylation to 7-hydroxycoumarin (7-OHC) and subsequent conjugation. Phase 1 metabolites were extracted in ether from the aqueous incubation media, back extracted into sodium hydroxide and determined fluorimetrically. Conjugated metabolites remaining in the aqueous phase were hydrolysed by the action of beta-glucuronidase and extracted and determined in a similar manner. The production of free 7-OHC by isolated epidermal cells was biphasic at all substrate concentrations tested, exhibiting an initial linear increase followed by a plateau phase. The plateau phase was attributable to the conjugation of 7-OHC produced in situ. Metabolism was inhibited by SKF 525A, carbon monoxide, and alpha-naphthoflavone. Endogenous supplies of reducing equivalents in the form of NADPH were adequate to attain maximal rates of metabolism. With human hair follicles both Phase 1 and Phase 2 activity was detectable in 7 out of 11 subjects. The assay has the advantages of being sensitive, producing single defined metabolites from both Phase 1 and Phase 2 metabolism; is readily adaptable to human skin samples.

Animals

Surgery for psoriasis.

Explore the source record for details and available documents.

Dermatologic Surgical Procedures

The stimulatory effects of prostaglandins on the melanophores of the lizard, Anolis carolinensis.

The melanosome dispersing activity of prostaglandins PGE1, PGE2, PGF1 alpha, PGF2 alpha, PGI2 and 6 beta PGI, was tested on the melanophores of Anolis carolinensis. Only PGE2 and PGE1 were active and while PGE2 was the most potent and acted synergistically with alpha-MSH, PGE1 was additive with alpha-MSH. Arachidonic acid also stimulated melanosome dispersion but its effect was blocked by indomethacin suggesting an action through its conversion to PGE1 or PGE2. The effect of alpha-MSH, on the other hand, was unaltered by indomethacin which suggests that alpha-MSH stimulated melanosome dispersion does not depend upon prostaglandin synthesis. Thus, while some prostaglandins may interact with alpha-MSH to stimulate melanosome dispersion they are unlikely to mediate its action.

Animals

Drug acetylation and expression of lupus erythematosus.

Acetylator phenotype was measure in 58 patients presenting to a skin clinic with discoid lupus erythematosus (DLE) and in 51 normal healthy subjects. Twenty seven of the patients with DLE were found to have evidence of systemic lupus erythematosus (D+SLE). Frequency of slow acetylator phenotype was 58% in all DLE patients, 52% in those with D+SLE and was no different from the 57% in controls. The distribution of acetylator phenotypes within the groups with DLE and those with D+SLE was similar to controls. Severity of DLE was assessed as number of skin lesions and median lesion count was 11.5 in slow acetylators and 10 in fast acetylators but in D+SLE median lesion count was 22 in slow acetylators and 12 in fast acetylators, and there was a significant inverse relationship between lesion count and rate of acetylation; scores for systemic involvement showed no relationship. We conclude that there is no difference in the frequency or distribution of slow acetylator phenotype between normal subjects and patients with DLE with or without SLE but that actual rate of acetylation may determine severity of expression of the disease in slow acetylators.

Acetylation

Strain differences in the induction of mono-oxygenase activity in mouse skin by topical clobetasol propionate: evidence of a role for the hr locus.

The effect of the topical application of clobetasol propionate on cutaneous ethoxycoumarin O'dealkylation (EOD) has been studied in various strains of mice. Clobetasol propionate markedly increased cutaneous EOD activity in adult hairless mice only. Similar treatment of adult haired C57BL/6J mice, or adult haired DBA/2J mice had no significant effect on cutaneous EOD activity. In contrast 3 methylcholanthrene induced cutaneous EOD activity in both hairless and C57 strains to a far greater extent than in the DBA strain. EOD activity in hairless mice non-responsive to polycyclic hydrocarbons, derived by selective breeding of hairless and DBA strains was induced by clobetasol propionate to a similar extent to that observed in responsive hairless strains. Hepatic EOD activity was not induced by clobetasol propionate in any of the strains tested. Strain differences in the induction of EOD by clobetasol propionate were not related to differences in either the concentration of cytosolic glucocorticoid receptor in the skin, the dissociation constant of the cytosolic receptor, or differences in percutaneous absorption. Polycyclic hydrocarbons did not compete with triaminolone acetonide for binding to the cytosolic glucocorticoid receptor. Strain differences in the induction of EOD activity by clobetasol propionate appear therefore not to be related to strain differences in either the Ah receptor of the glucocorticoid receptor, but to be regulated by the hr locus.

7-Alkoxycoumarin O-Dealkylase

Immunofluorescent localization of intermediate filament subunits for the differential diagnosis of malignant melanoma.

Intermediate filament subunits in normal cells and in their malignant derivatives can be used as specific markers for their histogenetic origins. We have studied five neoplasms of the skin in which positive identification of vimentin containing intermediate filaments by indirect immunofluorescence microscopy helped to establish the diagnosis of malignant melanoma. All of the neoplasms included in this study posed problems in differential diagnosis by conventional light microscopy and yielded equivocal results by conventional histochemistry. Thus, definitive distinction between poorly differentiated carcinoma and poorly differentiated melanoma could not be made by conventional microscopy. In all of the neoplasms described here, immunolabeling with antibodies against different intermediate filaments demonstrated positive staining for vimentin only. This intermediate filament subunit is present in melanocytes (as well as in many mesenchymal cells) but not in epithelial cells. Our study indicates that this technique may be valuable in differential diagnosis of malignant melanoma, particularly in instances where cells lack melanin or show other atypical morphologic features.

Aged

Enhanced weal and flare response to histamine in chronic idiopathic urticaria.

Weal and flare histamine dose-responses were measured in 30 normal subjects and 15 patients with chronic idiopathic urticaria. The log dose-response curves were shifted to the left corresponding to an increase in histamine potency of 2.5 for weal and 3.1 for flare. An enhanced response to histamine may be important in chronic idiopathic urticaria and comparison of potency of antihistamines in different subjects may be unreliable where initial weal response is abnormal.

Adult

Comparison of ultrasound and caliper measurements of normal and inflamed skin thickness.

We have compared ultrasound and Harpenden calipers for the measurement of thickness of non-inflamed and anthralin-inflamed skin. In non-inflamed skin ultrasound gave consistently and significantly lower values (0.87 mm +/- 2.3% s.e.) than calipers (1.1 mm +/- 2.7% s.e.) and the ultrasound/caliper ratio was 0.89 +/- 1.3%. In anthralin-inflamed skin the ultrasound/caliper ratio was not significantly different from unity (1.02 +/- 1.3%), but ultrasound was unable to measure inflamed skin thickness in 18% of cases because the echo could not detect the dermis-subcutaneous fat interface. The proportion of unreadable ultrasound results increased linearly with increase in skin thickness and the variance of ultrasound readings increased as inflammatory skin thickness increased; by contrast caliper variance remained constant. Harpenden calipers cannot be used in all subjects or in skin sites in which skin folds cannot be raised, but if the patient and site to be studied can be selected, Harpenden calipers have a greater precision, reproducibility and reliability than ultrasound for measurement of the thickness of inflamed skin.

Anthralin