摘要:

AbstractThis review briefly will focus on the role of selected proto‐onco‐genes and their activated forms during the regulation of cell proliferation, cell death and tumor formation in the epidermis. In addition, the multiple and complex functions of these proteins in normal as well as transformed cells will be discus

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00224.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract15‐hydroxyeicosatrienoic acid, 15‐HETrE, the 15‐lipoxygenase product of dihomogammalinolenic acid (DGLA), can inhibit the biosynthesis of the proinflammatory eicosanoids leukotriene B4(LTB4) and 12‐hydroxyeicosatctraenoic acid (12‐HETE). The purpose of the present study was to investigate the incorporation of [I4C] 15‐HETrE in specific membrane phospholipids of cultured human keratinocytesin vitro. [I4C] 15‐HETrE was rapidly incorporated into keratinocytes. When a plateau was reached after 3 hours, 15% of the added radioactivity was incorporated into lipids; 96.5% into phospholipids (PL) and 3.5%. into neutral lipids (NL). Within the phospholipid classes, [I4C]15‐HETrE showed selectivity for incorporation into phosphatidylinositol (PI). The mean proportion of [I4C] 15‐HETrE in the PI, phosphatidylcholin (PC) and phosphatidyle‐thanolamin (PE) was 83.2%, 8.5% and 8.3%, respectively. We then investigated the incorporation of 15‐HETrE in epidermal phospholipids of psoriatic skin intralesionally injected with 15‐HETrE. Four patients took part in the study. In each patient four identical plaques were injected with 0.65 ml of 2.0 µM, 6.2 µM, 18.6 µM of 15‐HETrE (0.4 µg, 1, 2 µg and 3.6 µg respectively) or 0.65 ml of 0.88% NaCl twice a week. After 3 wk keratome biopsies were obtained from the treated plaques. Phospholipids extracted from the skin biopsies were separated into major classes by two‐dimensional thin layer chromatography. 15‐HETrE was then released from specific phospholipids after treatment with phospholipase A2and identified by reverse phase and straight phase high preformance liquid chromatography. There was a dose‐dependent incorporation of 15‐HETrE into the specific phospholipids PI and PC. When expressed as ng 15‐HETrE/ug phospholipid phosphate, 15‐HETrE accumulated preferent‐ically in PI. After injection of the highest 15‐HETrE concentration, the mean amount of 15‐HETrE estcrified in PI and PC was 81.9 ng/µg PI phosphate and 19.4 ng/µg PC phosphate, respectively. This incorporation of 15‐HETrE incorporated into epidermal PLs was not accompanied by a clinical change of the treated psoriatic plaques. It remains to be determined whether higher 15‐HETrE inco

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00225.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractUsing a clonogenic assayin vitro, it has been shown that exposure to azelaic acid “1‐100 mM” for 24 hours has a dose‐dependent effect on the survival of the colony‐forming ability of murine “B16” and human “HMB2, and SK23” melanoma cells as compared with a non‐melanotic non‐tumoral Chinese hamster cell line “CHO”. Both human cell lines were more sensitive to the diacid than the murine cells, and the HMB2 cells were more sensitive than the SK23 cells. These differences may be partly correlated with differences in pigmentation and doubling times between the three melanoma cell lines. The two human lines were more pigmented than the B16, and the SK23 more than the HMB2; the human lines had a longer doub

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00226.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractTyrosine kinase inhibitors of the tyrphostin family which block EGF receptor kinase are reported to arrest the growth of psoriatic keratinocytesin vitro.Three tyrphostins with the potency ratio AG555>>AG18>>AG814 were found to arrest growth with no adverse cytotoxic effects. The potency ratio to inhibit keratinocyte proliferation follows their potency to inhibit EGF receptor kinase activityin vitro. These compounds represent novel leads for the therapy of psoriasis.

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00227.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractEffective methods exist for separating epidermis from dermis for many species; however, a simple and effective skin separation method for non‐human primates is not available. This investigation describes an easy and reliable method for separating epidermis from dermis in Rhesus monkeys. Skin was shaved and washed prior to necropsy. Skin samples were placed on cardboard and then in Whirl‐Pak bags, frozen on dry ice and stored at −70°C. Just prior to the separation procedure, Whirl‐Pak bags were returned to dry ice storage. Immediately after removal from dry ice, each closed Whirl‐Pak bag was placed into a waterbath maintained between 60 and 67°C. After 2 minutes, the Whirl‐Pak bag was removed from the waterbath, opened and the skin surface of the application site was gently scraped with a scalpel blade to remove the epidermis. Effectiveness of removal was verified by histologic examination of the remaining d

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00228.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractAn intradermal administration of histamine into human skin results in a local erythema, edema and often also the sensations of itch and/or pain. These effects have classically been attributed to the presence of histamine‐containing mast cells. However, in the present investigation, we report the observation of histamine‐immunoreactive nerves in the skin of Sprague‐Dawley rats using a new and highly sensitive immunohistochemical approach. These data suggest a more direct route of cutaneous histamine effects, mediated exclusively by the peripheral nervous system. The findings could also give a new basis for explaining histamine‐related issues, such

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00229.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractCultured human neonatal keratinocytes were used to study the mechanisms and factors involved in the regulation of CRABP II gene expression. Post‐confluent, relatively differentiated keratinocyte cultures had higher levels of CRABP II mRNA, but nuclear run‐on experiments detected no sustained increase in CRABP II gene transcription rate between pre‐confluent and post‐confluent cells. Also, our studies could detect no change in the long half‐life<32 hours of this message in pre‐ and post‐confluent cultures. Hydrocortisone was found to reduce the confluency‐related increase in CRABP II mRNA in keratinocyte cultures. Because corticosteroids are known to reduce the effect of various cytokines, a series of epidermal cytokines were examined for a modulating effect on CRABP II mRNA content in cultured keratinocytes. IL1 α produced the greatest increase and IL6 the strongest reduction in the level of this message in cells grown in serum‐free, defined medium. These data support a role for CRABP II in the proliferation and differentiation of human keratinocytes and suggest that epidermal cytokines may at least in part regulate the expression of the CRABP II gene

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00230.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractBeta‐carotene, a quencher of excited species such as singlet oxygen and free radicals, has been reported to protect against cutaneous photodamage, including sunburn acutely and photocarcinogenesis chronically. The present double blind placebo‐controlled study examines the ef‐tect of beta‐carotene supplementation on the human sunburn response and specifically on the induction of sunburn cells at the time of peak reaction intensity (24 h) after a single solar simulated light exposure 3 times the individually determined minimal erythema dose (MED). Administered orally either as a single 120 mg dose to dietarily restricted subjects or for 23 d as a daily 90 mg supplement to subjects on standard diets, beta‐carotene increased plasma and skin levels of beta‐carotene compared to both pretreatment levels and placebo‐treated controls, but provided no clinically or histologically detectable protection against a 3 MED sunburn reaction. Thus, these data suggest that oral beta‐carotene supplementation is unlikely to modify the severity of cutaneous photodamage in normal individuals to a clinically me

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00231.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractTo develop a new method to evaluate autoantibodies in various autoimmune bullous skin diseases, we examined reactivity of bullous pemphigoid (BP) and pemphigus vulgaris (PV) patients' sera with partial bacterial fusion proteins of the 230 kD BP antigen (BPAG1) and PV antigen, respectively, by an enzyme‐linked immunosorbent assay (ELISA), and compared the results with those of immunoblotting. We used two fusion proteins derived from the mouse BPAG1 and a fusion protein derived from the amino‐terminus (EC 1‐2) of PV antigen. For both BP and PV sera, the ELISA scores were well correlated with the reactivities on immunoblot assays. The present study indicates that ELISA using recombinant antigen proteins in various autoimmune bullous skin diseases will be a new useful technique to detect the autoantibodies. However, development of recombinant proteins with the entire molecule and correct conformation will be necessary to establish a perfect ELISA system in the f

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00232.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00233.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY