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  • 1
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The effect of transforming growth factor-type β 1(TGF-β) on the growth and differentiation of normal human skin keratinocytes cultured in serum-free medium was investigated. TGF-β markedly inhibited the growth of keratinocytes at the concentrations 〉2 ng/ml under low Ca2+ conditions (0.1 mM). Growth inhibition was accompanied by changes in cell functions related to proliferation. Remarkable inhibition of DNA synthesis was demonstrated by the decrease of [3H]thymidine incorporation. The decrease of [3H]thymidine incorporation was observed as early as 3 hr after addition of TGF-β. TGF-β also decreased c-myc messenger RNA (mRNA) expression 30 min after addition of TGF-β. This rapid reduction of c-myc mRNA expression by TGF-β treatment is possibly one of the main factors in the process of TGF-β-induced growth inhibition of human keratinocytes. Since growth inhibition and induction of differentiation are closely related in human keratinocytes, the growth-inhibitory effect of TGF-β under high Ca2+ conditions (1.8 mM Ca2+ differentiation-promoting culture environment) was examined. TGF-β inhibited the growth of keratinocytes under high Ca2+ conditions in the same manner as under low Ca2+ conditions, suggesting that it is a strong growth inhibitor in both low and high Ca2+ environments. The induction of keratinocyte differentiation was evaluated by measuring involucrin expression and cornified envelope formation: TGF-β at 20 ng/ml increased in-volucrin expression from 9.3% to 18.8% under high Ca2+ conditions, while it decreased involucrin expression from 7.0% to 3.3% under low Ca2+ conditions. Cornified envelope formation was modulated in a similar way by addition of TGF-β: TGF-β at 20 ng/ml decreased cornified envelope formation by 53% under low Ca2+ conditions, while it enhanced cornified envelope formation by 30.7% under high Ca2+ conditions. Thus, the effect of TGF-β on keratinocyte differentiation is Ca2+ dependent. It enhances differentiation of human keratinocytes under high Ca2+ conditions, but inhibits differentiation under low Ca2+ conditions. Taken together, there is a clear discrepancy between TGF-β effects on growth inhibition and induction of differentiation in human keratinocytes. These data indicate that growth inhibition of human keratinocytes by TGF-β is direct and not induced by differentiation.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 4 (1978), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 21 (1989), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Contact dermatitis 12 (1985), S. 0 
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-069X
    Keywords: Polyamine ; Psoriasis ; Putrescine-Spermine ; Spermidine ; Polyamin ; Psoriasis ; Putrescin-Spermin ; Spermidin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der Polyamingehalt des 24-h-Urins von 16 Psoriatikern und sieben Probanden wurde bestimmt. Die durchschnittlichen Werte von Putrescin und Spermien waren in der psoriatischen Gruppe etwas erhöht, während die von Spermidin unverändert blieb. Bei Unterteilung psoriatischer Patienten in drei Gruppen unter Berücksichtigung der Ausdehnung der Hautveränderungen, ist der Putrescinspiegel im Urin höher in der Gruppe der großflächiger befallenen Psoriasis.
    Notes: Summary Polyamine contents in 24 h urine of 16 psoriatic patients and seven healthy individuals are measured. The average values of putrescine and spermine showed slight increase in the psoriatic group, while those of spermidine were unchanged. When psoriatic patients are divided into three groups according to the extent of their skin lesion, the putrescine level is found to be higher in the group more serverely affected.
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  • 6
    ISSN: 1432-069X
    Keywords: Key words Serine protease ; Epidermis ; Differentiation ; Inflammation ; Wound repair
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of neuropsin mRNA in vivo in mouse skin was examined by in situ hybridization and Northern blotting under stimulated conditions. Two kinds of epidermal stimuli, a topical application of a chemical tumor promoter and incisional wounding, were used. A single topical application of 12-O-tetradecanoyl-phorbol 13-acetate induced epidermal hyperplasia and simultaneously induced an extensive increase in neuropsin mRNA in the suprabasal cells. A full-thickness skin incision also induced a profound increase in neuropsin mRNA in the suprabasal cells surrounding the wound but not in actively proliferating basal cells. The increases in neuropsin mRNA occurred rather late and were limited to the site of drug application or around the incision. Interestingly, neuropsin mRNA was not expressed in the epithelial tongue migrating toward the wound during re-epithelialization. Thus, neuropsin might participate in accelerated epidermal differentiation rather than in the proliferation or migration of keratinocytes in the wound.
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  • 7
    ISSN: 1432-069X
    Keywords: Keywords Vitamin B6 ; UVA ; Phototoxicity ; ESR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously reported that pyridoxine shows UVA-induced cytotoxicity. Four other vitamin B6 compounds (pyridoxal, pyridoxamine, pyridoxal phosphate, and pyridoxamine phosphate) are metabolically more important in vivo than pyridoxine. These compounds were examined for UVA phototoxicity to cultured human fibroblasts. The cytotoxicity was measured by post-UVA irradiation colony-forming ability. All the B6 compounds except pyridoxal phosphate showed cytotoxicity. Pyridoxamine phosphate, which is the most important form of vitamin B6 in vivo, had the strongest cytotoxic effect. To examine the involvement of reactive oxygen species in the phototoxicity, we performed an electron spin resonance study using the spin trapping agent, 5,5-dimethyl-1-pyrroline N-oxide, and diethylenetriaminepentaacetic acid. We failed to detect radicals derived from vitamin B6. The cytotoxic effect remained in UVA-irradiated solutions for at least 30 min after the end of UVA irradiation. Hydrogen peroxide was produced in the solution, but the amount was not enough to cause cytotoxicity. In addition, the cells from xeroderma pigmentosum patients who belong to group A or C showed survival curves similar to those of normal fibroblasts. This suggests that cyclobutane pyrimidine dimers or 6-4 photoproducts of DNA were not involved in this damage. These findings suggest that UVA-induced vitamin B6 cytotoxicity is caused by toxic photoproducts resulting from irradiated vitamin B6.
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 92 (1975), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Prostaglandins E1 and E2 stimulate cyclic AMP accumulation in pig epidermis and in human epidermis from patients with psoriasis. Prostaglandins A1, A2 and F2α are relatively ineffective. The fact that this stimulation is not inhibited by a β-blocker (propranolol) and that the stimulation by prostaglandin E2 and adrenaline is additive indicates that each drug acts independently on the epidermal adenyl cyclase system. In other words, prostaglandins E1 and E2 act on a site other than the β-receptor of adenyl cyclase in epidermis. The stimulation by prostaglandins E1 and E2 is not additive; hence they probably act on the same site. Concentrations of prostaglandin E above 3 × 10−7 M are effective in causing stimulation. This concentration may be within the physiological range and the contribution of endogenous prostaglandin levels in the control of intracellular cyclic AMP levels cannot be disregarded.
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  • 9
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effect of various hormones and drugs on the adenyl cyclase system of pig and human epidermal slices was studied in vitro.Adrenaline and isoproterenol in the presence of theophylline increased the epidermal cyclic AMP level 20-fold in 5 min. Noradrenaline also stimulated cyclic AMP accumulation but to a much lesser degree. The adrenaline stimulation was marked even in the absence of the phosphodiesterase inhibitor, theophylline. Theophylline potentiated the effect of adrenaline at the concentration of 2–10 mM although theophylline alone did not elevate the cyclic AMP level significantly. The Km for adrenaline stimulation of the adenyl cyclase system of pig epidermis was 77·10−7 M. A β-adrenergic antagonist, propranolol, markedly inhibited the adrenaline stimulation while α-antagonists, phentolamine or priscoline, showed little effect. These results are in accord with the view that the epidermis possesses an active adenyl cyclase system with β-adrenergic receptors.
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  • 10
    ISSN: 1468-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim This paper compares the effects of MC903 (calcipotriol) and 1,25-dihydroxyvitamin D3[1,25(OH)2D3; calcitriol] on differentiation and proliferation of normal human keratinocytes cultured in serum-free medium. In order to understand the inhibitory mechanism of MC903, we examined its effect on cell cycle kinetics and the phosphorylation of retinoblastoma gene product (pRB), a tumor suppressor gene products, in normal human keratinocytes.Background The hormonally active form of vitamin D3, 1,25-dihydroxy vitamin D3 [1,25(OH)2D3], regulates the differentiation and proliferation of epidermal keratinocytes in vitro. MC903 is a novel vitamin D3 analogue which is at least 100 times less potent than 1,25(OH)2D3 in its effects on calcium homeostasis.Methods We analyzed cell differentiation and cell cycle by flow cytometry using a FACScan, and pRB phosphorylation by Western blotting and densitometer.Results MC903 induced growth inhibition and differentiation of human keratinocytes. Cell cycle analysis demonstrated that 10-6 M of MC903 induced cell cycle arrest in both G1/G0 (62.4 ± 0.7% versus 56.5 ± 1.7% in control, p 〈 0.01) and G2 + M (19.2 ± 0.3% versus 14.0 ± 0.9% in control, p 〈 0.01) phase. 10-6 M of MC903 also increased the depnosphorylated pRB from 25% at 0 h to 84% at 48 h, as well as 1,25(OH)2D3.Conclusions Since pRB phosphorylation is supposed to be essential for the progression from G1 to S phase, the inhibition of pRB phosphorylation could be responsible for the G1/G0 growth arrest induced by MC903 in normal human keratinocytes.
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