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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report quantitative data on epidermal melanogenesis by established and new furocoumarins. The ears and dorsal skin of pigmented hairless mice were treated for 12 d with compounds in ethanol, at equi-optical concentrations, and exposed to subphototoxic doses of ultraviolet A. Increased pigmentation was observed with 6,4,4'-trimethylangelicin > psoralen > 8-methoxypsoralen > 5-methoxypsoralen > 4,4',5'-trimethylazapsoralen = bergamot oil. Assessment of melanocyte numbers and morphology in epidermal sheet dihydroxyphenylalanine preparations showed that 6,4,4'-trimethylangelicin was the best compound with 536 ear melanocytes/mm2 +/- 15 SEM compared with 46 +/- 4 in controls. Psoralen induced 297/mm2 +/- 33, compared with its methoxy derivatives with ranges between 200 and 240/mm2.6,4,4'-trimethylangelicin had a striking effect on dorsal skin with 462 +/- 18 melanocytes/mm2 compared to less than 80/mm2 in all other ultraviolet A treatment groups. Khellin, 5-GOP and ultraviolet A only and all non-ultraviolet A controls had no effect. Melanogenesis was associated with increased dendricity, melanocyte size, especially with 5-methoxypsoralen, and giant melanocytes were noted with some treatments. The potency of 6,4,4'-trimethylangelicin, which does not form DNA interstrand crosslinks, may be related to its high DNA binding constant. Our data may be useful in the selection of compounds to treat vitiligo.
J Invest Dermatol 1994 Jul
PMID:Quantitative assessment of epidermal melanogenesis in C3H/Tif hr/hr mice treated with topical furocoumarins and UVA radiation. 802 88

Ultraviolet radiation (UVR)-induced erythema may be mediated in part by free radical-generated tissue damage, including lipid peroxidation. We have examined the effect of dietary fish oil rich in omega-3 fatty acids upon susceptibility to UVB-induced erythema and epidermal lipid peroxidation. Fifteen volunteers took 10 g fish oil, containing 18% eicosapentaenoic acid and 12% docosahexaenoic acid, daily for 3 or 6 months. Sensitivity to UVB was assessed at intervals on fish oil, and 2.5 months after stopping treatment. Paired skin shave biopsies were taken from six subjects, at baseline and 3 months, from both irradiated and control skin. Fatty acid composition was analyzed and thiobarbituric acid-reactive substances measured as an index of lipid peroxidation. With increasing time on fish oil the minimal erythema dose rose progressively, from 18.9 +/- 13.9 mJ/cm2 (mean +/- SD) at baseline to 41.1 +/- 16.6 mJ/cm2 at 6 months, p < 0.01. Ten weeks after stopping fish oil the minimal erythema dose fell to 23.1 +/- 4.9 mJ/cm2, p < 0.05. Epidermal total omega-3 fatty acids rose from 1.8 +/- 0.4% total fatty acids (mean +/- SEM) to 24.2 +/- 3.9% at 3 months, p < 0.01. This was accompanied by a rise in thiobarbituric acid-reactive substances in irradiated skin from 6 +/- 0.3 (mean +/- SEM) to 18.5 +/- 2.6 A532/g skin, p < 0.01. Hence dietary omega-3 fatty acids produce a pronounced reduction in UVB-erythemal sensitivity, although susceptibility of skin to lipid peroxidation is increased. Thus, omega-3 fatty acids may act as an oxidizable buffer, protecting more vital structures from free radical damage.
J Invest Dermatol 1994 Aug
PMID:Dietary fish-oil supplementation in humans reduces UVB-erythemal sensitivity but increases epidermal lipid peroxidation. 804 Jun 3

Antigen-dependent activation of T cells occurs through the T-cell antigen-receptor complex (TCR/CD3). Antigen-independent T-cell activation may occur through the surface molecules CDw60, CD2, and CD28. We wished to determine whether these antigen-independent T-cell-activation pathways could be involved in proliferation of leukemic T cells from patients with cutaneous T-cell lymphoma (CTCL). Whereas CDw60 was only expressed on 28% +/- 7% (mean +/- SEM) of blood T cells obtained from healthy control subjects (n = 4), CDw60 was expressed on 94% +/- 3% of blood T cells obtained from patients with CTCL (n = 4). Dual color immunofluorescence microscopy of the T-cell infiltrate in involved skin of these patients demonstrated that almost 100% of the T cells expressed CDw60. Not only did T cells in the patients with CTCL express CDw60, but triggering of the T cells with anti-CDw60 resulted in enhanced proliferation relative to anti-TCR/CD3 and mitogenic lectins. Other antigen-independent pathways also appeared highly active in the T cells from patients with CTCL because enhanced proliferation relative to anti-TCR/CD3 or mitogenic lectins was found when anti-CD2 or anti-CD28 plus phorbol ester was used as stimulant. Despite the brisk proliferation induced by anti-CDw60, anti-CD2, or anti-CD28, T cells from the patients did not produce detectable amounts of gamma-interferon. The inability to produce gamma-interferon correlates with our finding of absent (n = 3) or weak (n = 1) intercellular adhesion molecule-1 expression in the lesional keratinocytes in these patients. In conclusion, T cells of patients with CTCL demonstrate elevated expression of a T-cell-independent signaling molecule CDw60 and respond to antigen-independent activating signals.
J Invest Dermatol 1993 May
PMID:Leukemic T cells from patients with cutaneous T-cell lymphoma demonstrate enhanced activation through CDw60, CD2, and CD28 relative to activation through the T-cell antigen receptor complex. 809 45

Vitamin D, 1,25(OH)2D3, decreases proliferation and promotes differentiation of keratinocytes, and other keratinocyte differentiation stimuli have been associated with an early rise in intracellular free calcium, [Ca2+]i. We therefore investigated the effect of 1,25(OH)2D3, its precursor D3 and five 20-epi-analogues (EB1089, KH1060, KH1139, MC1288, MC1301) on growth and [Ca2+]i levels of normal human keratinocytes. Cells were cultured in medium MCDB153 with an extracellular calcium concentration of 70 microM or 1 mM. All the analogues were more potent than 1,25(OH)2D3 at inducing the morphological changes of differentiation, but D3 was inactive. At concentrations down to 10(-8) M 1,25(OH)2D3, caused significant inhibition of growth, as assessed by counting cells and measurement of thymidine labelling. At 5 days 50% inhibition of growth occurred with 64 nM 1,25(OH)2D3 and 3330 nM D3. All the analogues were more potent than 1,25(OH)2D3, and KH1060 inhibited growth at 10(-10) M. In single keratinocytes [Ca2+]i was measured by microspectrofluorimetric techniques using the dye fura-2. No immediate rise in [Ca2+]i was observed following addition of 1,25(OH)2D3 or the analogues up to 10(-6) M. However 10(-7) M 1,25(OH)2D3 or the analogues induced a gradual increase in [Ca2+]i, significant at 4 h (P < 0.001), which increased further over 2-3 days. D3 had no effect on [Ca2+]i. Increases in [Ca2+]i following the differentiation stimuli of either 2 mM extracellular calcium or 1,25(OH)2D3 were similar at 48 h, increasing from 100 +/- 3 nM (mean +/- SEM) in control cells to 150 +/- 3 nM with 2 mM calcium and 144 +/- 6 nM with 10(-7) M 1,25(OH)2D3. The effect of extracellular calcium in raising [Ca2+]i within minutes was more rapid than 1,25(OH)2D3, but in combination the two were not additive.
Arch Dermatol Res 1994
PMID:Intracellular free calcium and growth changes in single human keratinocytes in response to vitamin D and five 20-epi-analogues. 815 25

Two studies of the additional effect of an H2 receptor antagonist when given in combination with an H1 antagonist were undertaken in dermographic urticaria. Using a randomized, double-blind, crossover design in 19 patients, a combination of cetirizine (10 mg at night) and ranitidine (150 mg twice daily) was compared with a combination of cetirizine (10 mg at night) and placebo. The addition of ranitidine did not produce any significant difference in linear analogue scores for weal, itch or sleep disturbance. There was a significant depression of the frictional force/wealing response curve with an increase in wealing threshold (P < 0.0001) following the addition of H2 blockade. The wealing threshold was 54.7 +/- 4.4 (mean +/- SEM) g/mm2 for the H1 antagonist alone, and 73.2 +/- 5.7 for the combination of H1 and H2 antagonists. In a second similar study involving nine different patients, comparing terfenadine (120 mg twice daily) with a combination of terfenadine and ranitidine (150 mg twice daily), the weal threshold was 59.8 +/- 6.6 for the H1 antagonist alone, and 73.0 +/- 6.4 for the combination of H1 and H2 antagonists. Thus, in dermographic urticaria, adding an H2 antagonist to treatment with a potent H1 antagonist gives a small, significant reduction in wealing response, but no symptomatic benefit. We conclude that involvement of the H2 receptor in this urticarial disease is minimal, and does not justify the use of H2 receptor antagonists.
Br J Dermatol 1993 Nov
PMID:In dermographic urticaria H2 receptor antagonists have a small but therapeutically irrelevant additional effect compared with H1 antagonists alone. 825 54

The effect of cetirizine, 10 mg at night, on dermographic urticaria, was studied in 19 patients. The study design was a randomized, double-blind, crossover comparison with placebo, each treatment being given for 7 days. Patients kept a daily diary of itch and weal severity (100-mm linear analogue scale), and recorded sleep disturbance. The dermographic weal response was measured objectively with a spring-loaded stylus, and the weal threshold calculated from the force/response curve. There was a small, insignificant subjective response to placebo, but no objective response. On cetirizine, the subjective assessment of wealing was reduced from 34.3 +/- 6.7 (mean +/- SEM, 0-100 scale) to 16.8 +/- 4.1 (P = 0.02), itch was reduced from 43.2 +/- 6.6 to 19.4 +/- 4.1 (P = 0.001), and nights disturbed from 46.2 to 8.8% (P = 0.03). There was a shift to the right in the position of the force/response curve, and the wealing threshold increased from 24.6 +/- 3.2 to 54.7 +/- 4.4 g/mm2 (P = 0.00001), but there was no correlation between change in itch scores and wealing threshold. Cetirizine 10 mg daily is an effective treatment in dermographic urticaria, and its usefulness will depend on the prevalence of unwanted effects.
Br J Dermatol 1993 Nov
PMID:The effect of cetirizine on symptoms and wealing in dermographic urticaria. 825 55

Wound closure with cultured skin substitutes results in epithelium that is consistently hypopigmented. Hypothetically, addition of human melanocytes to cultured skin grafts may result in normal pigmentation of healed skin. Skin substitutes were composed of human epidermal keratinocytes and melanocytes, dermal fibroblasts, and collagen-glycosaminoglycan substrates, and were incubated for 12 d in media for keratinocyte growth (KG, n = 4), for keratinocyte differentiation containing four fatty acids and vitamin E with basic fibroblast growth factor (KDF, n = 6) or epidermal growth factor (KDE, n = 6), or for melanocyte growth (MG, n = 6) with phorbol ester and 5% fetal bovine serum. Skin substitutes were grafted orthotopically to full-thickness skin wounds (2 x 2 cm) on athymic mice, and scored for percent original wound size (+/- SEM), visible pigmentation (number pigmented/n), and positive staining for human leukocyte antigens (HLA)-ABC after 6 weeks on the mice. The data show that cultured skin grafts containing human melanocytes that are incubated in KDE or MG media have statistically significant reduction in wound contraction, 1:1 correlation of expression of pigment and HLA-ABC, and increased frequency of pigmentation after healing compared to incubation in KG or KDF media. Transmission electron microscopy confirmed the presence of melanocytes, melanosomes, and pigment transfer to keratinocytes in pigmented skin. These results suggest that survival and differentiated function of cultured epithelium can support melanization of skin, and that skin analogues exposed to phorbol ester in vitro can support skin pigmentation after wound healing.
J Invest Dermatol 1993 Apr
PMID:Pigmentation and inhibition of wound contraction by cultured skin substitutes with adult melanocytes after transplantation to athymic mice. 845 98

During late gestation, the fetal rat exhibits marked hyperplasia of the interfollicular epidermis and accelerated cornification in preparation for birth. In this study, we utilized simple morphometric techniques to provide quantitative estimates of the rate of stratum corneum (SC) formation during the perinatal period. Cryostat sections of dorsal epidermis from rat pups between -48 and +72 h of age were expanded under alkaline conditions and the number of corneocyte interfaces counted from photomicrographs. This method yielded the following regression lines: prenatal, y = 0.19x + 13.07, r = 0.93; postnatal, y = 0.13x + 13.00, r = 0.93, where y = number of SC layers and x = age in hours. Lack of desquamation was assured by the postnatal persistence of the granular periderm. Adhesive stripping of the epidermis followed by phase-contrast microscopy revealed intact monolayer sheets of SC. Quantitation using a computerized image analysis system gave an average corneocyte surface area in the newborn rat of 1908 +/- 36 mu 2 (mean +/- SEM). Treatment of neonatal rats with epidermal growth factor (500 ng/g BW) increased the number of SC layers over the first 24 h of life (p < 0.05) and resulted in marked hyperkeratosis by one week of age. These results allow the following conclusions: 1) in the prenatal rat, SC forms at a rate of one layer every 5 h; 2) postnatally, SC formation slows to one layer every 8 h; 3) to support normal corneum synthesis at birth, dorsal keratinocytes must enter transition at a rate of approximately 3 cells/second/cm2 of body surface; and 4) treatment with exogenous EGF augments the rate of terminal differentiation of perinatal rat epidermis.
J Invest Dermatol 1993 Apr
PMID:Rate of stratum corneum formation in the perinatal rat. 845 3

The effect of growth and differentiation stimuli on intracellular free calcium ([Ca2+]i) in cultured human keratinocytes was investigated using micro-spectrofluorimetric techniques and the calcium-sensitive dye FURA-2. The mean [Ca2+]i of keratinocytes in 70 microM calcium medium was 104 +/- 3 nM (mean +/- SEM), significantly lower than the transformed keratinocyte line SVK14 (128 +/- 2 nM). When cultured in 2.0 mM calcium medium the [Ca2+]i increased in both normal and transformed keratinocytes to 135 +/- 4 nM and 180 +/- 4 nM, respectively. Keratinocytes grew more slowly in the absence of EGF, but [Ca2+]i was unaltered. Stimulation with EGF (10 ng/ml) induced, over 4 min, a large transient rise in [Ca2+]i up to 230 nm, due to an influx of extracellular calcium. Heterogeneity of keratinocytes was observed with 46% (n = 13) responding, but confluent or differentiated keratinocytes did not respond. TGF--beta (1 ng/ml) reduced cell growth without inducing differentiation and was not associated with any change in [Ca2+]i. The phorbol ester TPA (50 nM) induced irreversible growth arrest and terminal differentiation and increased the [Ca2+]i from 102 +/- 2 nM to 126 +/- 3 nM at 2 h, an effect similar to that of 2 mM extracellular calcium. Addition of 500 nM TPA was associated with a rise in [Ca2+]i, over several minutes to a plateau of 200-300 nM, due to release from internal stores and an influx of extracellular calcium. In normal human keratinocytes an increase in [Ca2+]i appears to be an early event in differentiation, whether induced by calcium or TPA, but not during growth inhibition without differentiation.
Arch Dermatol Res 1993
PMID:Growth and differentiation stimuli induce different and distinct increases in intracellular free calcium in human keratinocytes. 846 81

The metabolism of the human hair follicle was investigated in vitro under conditions that maintained glycogen and adenosine triphosphate (ATP) content and the growth rate of the follicle at values observed in vivo. We have shown that only 10% of the total glucose utilized was oxidized to CO2 and 40% of this was oxidized via the pentose phosphate shunt. Although fatty acids and ketone bodies were oxidized by the hair follicle, they are poor energetic substitutes for glucose. Nor will fatty acids or ketone bodies sustain hair growth in vitro. Glutamine, however, was shown, both biochemically and by comparing growth rates, to be an important fuel with 23% of uptake being oxidized, generating a possible 2.16 +/- 0.32 nmoles ATP/follicle/h (mean +/- SEM) (glucose metabolism generates 4.54 +/- 0.61 nmoles ATP/follicle/h). Sixty-four percent of the glutamine taken up was calculated to be metabolized to lactate, showing that the hair follicle engages in both glycolysis and glutaminolysis. The glucose-fatty acid cycle appears to be unimportant in the hair follicle but our data indicates that a glucose-glutamine cycle does operate.
J Invest Dermatol 1993 Jun
PMID:Metabolism of freshly isolated human hair follicles capable of hair elongation: a glutaminolytic, aerobic glycolytic tissue. 849 24


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