摘要:

SummaryActive vitamin D3modulates epidermal growth, keratinization and inflammation, and various vitamin D3analogues have been shown to be effective in the treatment of psoriasis. These analogues now provide a useful addition to the therapeutic modalities available for the treatment of psoriasis. Epidermal hyperproliferation, abnormal keratinization and inflammation are the well‐established hallmarks of the psoriatic plaque. The aim of this review is to provide an update of information on the cell biological effects of vitamin D3, and the influence of vitamin D analogues on the pathomechanisms of psoriasi

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb00710.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThis review summarizes the efficacy and tolerability of terbinafine (Lamisil®) in the treatment of dermatophytoses in children. In six clinical studies, 152 children who received terbinafine were evaluable for efficacy and 196 were evaluable for tolerability. In these studies, terbinaline was used for between 1 and 28 weeks. The median treatment was 4 weeks, the duration of treatment in the tinea capitis studies.As a result of extensive experience in adults at doses of 10 mg/kg and less, and the overall pharmacokinetic profile in children, including the lower volume of distribution of terbinafine into lipophilic tissue, the use of a dose of 125 mg/day for children weighing 20–40 kg, and 62.5 mg/day in children weighing less than 20 kg, has been proposed. This dose was shown to be well tolerated and effective. For children weighing>40kg, the adult dose of 250mg is appropriate.Terbinafine was shown to be very effective (93% cured), in the treatment of children with tinea capitis, using a shorter treatment duration (4 weeks) than that usually employed with presently available antifungal drugs. It is also effective in children with various dermatophyte infections of the skin, with a cure rate of more than 90%. Terbinafine was shown to be well tolerated in children aged between 2 and 17 years.The recommended duration of treatment for tinea capitis is 4 weeks. The recommended duration of treatment for other skin or nail dermatophyte infections, based on extensive studies in adults, and confirmed in children, is 2 weeks for tinea corporis and tinea pedis, 6 weeks for finger‐nail onychomycosis and 12 weeks for toe‐nail onychom

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb00711.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryIn full‐thickness skin wounds dermal regeneration usually fails, resulting in scar formation and wound contraction. We studied dermal regeneration by implantation of collagenous matrices in a human punch biopsy wound model.Matrices were made of native bovine collagen 1 fibres, and either hyaluronic acid, fibronectin, or elastin was added. Matrices were placed in 6‐mm punch biopsy holes in seven patients (biopsies were used for the grafting of leg ulcers), and covered with a protective semi‐permeable polyether urethane membrane. Histology, wound contraction and dermal architecture were studied. Dermal architecture was evaluated using a recently developed laser scatter technique.All collagen matrices showed a tendency to reduce wound contraction, compared with control wounds; elastin‐ and fibronectin‐treated matrices showed significantly less contraction than control wounds. Only the addition of elastin had a clear beneficial effect on dermal architecture; collagen bundles were more randomly organized, compared with control wounds, and wounds treated with collagen matrices coated with fibronectin or hyaluronic acid, or without coating.We conclude that the punch biopsy wound model provides important information on dermal regeneration in humans. Native collagen matrices with elastin contributed to dermal regeneration and reduced wound contraction, in contrast with matrices coated with fibronectin or hyaluronic acid, or without coating. Future clinical studies of large‐area, full‐thickness wounds will be required to establish their clinical relevance for leg ulcer and b

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb00712.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryDermatitis herpetiformis (DH) is characterized by a rash and a gluten‐sensitive enteropathy (GSE) indistinguishable from that of coeliac disease. T‐cell‐mediated mechanisms have been implicated in the pathogenesis of GSE. It seems feasible that intradermal injection of gluten, in patients known to have GSE, could lead to an influx of T cells sensitized to gluten, with subsequent development of a delayed hypersensitivity‐type reaction.Six patients with DH and three normal subjects had intradermal injections of‘Frazer's fraction III’ (FFIII; the partial peptic tryptic digest of gluten which is known to be antigenic) and phosphate‐buffered saline (PBS) as a control. Skin biopsies were taken at PBS and FFIII injection sites at 48 h. In addition, two of the patients with DH had biopsies taken of FFIII injection sites at 6 h. Monoclonal antibodies and the avidin‐biotin‐peroxidase technique were used to stain for T cells in the skin biopsies. A monoclonal antibody to a neoepitope exposed in the terminal complement complex and an immunofluorescent method were used to detect the presence of terminal complement component in biopsies taken from two of the control subjects and two of the patients.Both patients and control subjects developed a weal and flare within a few minutes of injecting the FFIII, and this persisted for up to 6 h. No skin reaction was present in either the patients or the control subjects at 48 h. No skin reaction was visible at any time following injection of PBS. There was no increase in T cells in biopsies taken at 6 or 48 h from the FFIII injection sites compared with the PBS injection sites. Terminal complement component was present in the biopsies taken from DH patients at both the PBS and FFIII injection sites (6 and 48 h), but was absent from the biopsies taken from the control subjects. Normal delayed hypersensitivity responses to a battery of common recall antigens showed that the lack of response to FFIII was antigen specific.Thus, this study suggests that the T cells sensitized to gluten in patients with GSE are unable to mi

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb00713.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBoth cyclosporin (CyA) and ultraviolet radiation are effective in the treatment of psoriasis, but their precise mechanisms of action are uncertain. We investigated their effects on ornithine decarboxylase (ODC) activity, ODC gene expression, and cellular proliferation stimulated by epidermal growth factor (EGF), in cultured normal human epidermal keratinocytes. CyA (5 μg/ml) inhibited ODC activity, ODC mRNA level, and cell growth induced by 50ng/ml EGF. Ultraviolet B (10 mJ/cm2) irradiation suppressed the induction of ODC, ODC mRNA, and cell proliferation stimulated by EGF, but ultraviolet A (0‐15 J/cm2) irradiation inhibited neither EGF‐stimulated ODC activity nor cell proliferation. These findings indicate that reduction of ODC activity in CyA‐ or ultraviolet B‐treated human keratinocytes may contribute to the antiproliferative mechanism of these agents. These results also suggest that the regulation of ODC activity by ultraviolet B and A irradiation may be mediated by different signal transduction

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb00714.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryCell surface anionic charge is known to be related to various cellular functions. Therefore, we ultrastructurally localized anionic sites in normal and psoriatic human epidermis, using poly‐l‐lysine‐gold complex (cationic gold), to assess their possible participation in the differentiation of keratinocytes and the pathogenesis of psoriasis. In normal and psoriatic epidermis, the cell membrane of keratinocytes showed positive staining at pH 2.0. At pH 7.4 the cytoplasm and nucleus were diffusely stained, in addition to the cell membrane. In normal epidermis, the intensity of labelling on the cell membrane at pH 2.0 was strong in the basal layer and lower stratum spinosum, and decreased in parallel with differentiation of keratinocytes. In psoriatic epidermis, the intensity of labelling on the cell membrane at pH 2.0 was stronger than in normal epidermis. In normal epidermis, heparitinase digested 63% and chondroitinase ABC digested 80% of cationic labelling. This suggests that heparan sulphate and chondroitin sulphate (and/or dermatan sulphate) constitute anionic sites in normal epidermis. In psoriatic epidermis, chondroitinase ABC‐sensitive anionic sites were greatly increased, whereas heparitinase‐sensitive anionic sites were the same, when compared with normal epidermis. This suggests that chondroitin sulphate and/or dermatan sulphate constitute anionic sites which are increased in psoriatic

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb00715.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThe non‐invasive electrical impedance technique used in this study reflects structural changes in a tissue, and provides an estimate of the level of oedema by a simple impedance index.Sodium lauryl sulphate (SLS), dissolved in water at concentrations of 0.1, 0.5 and 2.0%, was applied for 24 h in 12 mm Finn chambers® on both volar forearms of 12 healthy volunteers. An unoccluded area was used as a reference site. Readings from all sites were taken before the application of the irritant, and 24 h after its removal. After the last reading, a 3‐mm punch biopsy was taken from each test site for histological examination.The results obtained from electrical impedance measurements at five different skin depths were correlated with those obtained from histological examination, visual scoring and transepidermal water loss (TEWL).For all of the methods used the responses were proportional to the concentration of the irritant. Statistically significant changes of electrical impedance were found for all depths and concentrations, except for 0.1% SLS at the most superficial depth. The histological changes were focused in the epidermis, and mainly consisted of oedema. Alterations in the thickness of the epidermis due to oedema were used as a quantitative parameter for correlation with the assessment of irritation using the electrical impedance technique.For the detection of irritant reactions, TEWL and electrical impedance are more sensitive than visual scoring, and selection of the optimum depth penetration further increases the sensitivity of the electrical impedance measure

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb00716.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryWe have previously identified a novel 105‐kDa lower lamina lucida protein detected by the autoantibodies from a group of patients who developed a unique immune‐mediated subepidermal bullous dermatosis. We sought to determine if this novel basement membrane zone (BMZ) protein is normally expressed in the skin of patients with various subsets of epidermolysis bullosa (EB). Indirect immunofluorescence microscopy performed on non‐lesional skin sections from patients with three major EB subsets revealed absence or significantly reduced expression of this novel BMZ protein in 20 out of 23 skin sections from patients with generalized dominant and recessive dystrophic EB. However, immunoblot analyses with the autoantibodies on Western‐blotted proteins revealed that a comigrating 105‐kDa protein is present in both cytosol extracts (n=6) and conditioned media (n=3) of cultured dermal fibroblasts derived from patients with dystrophic EB, as well as those cultured from two healthy individuals. Although the reason for such disparate findings is not known, the defectivein vivoexpression of this novel 105‐kDa protein in dystrophic EB is presumably not due to a failure of fibroblasts to synthesize or secrete the protein. It is possible, however, that the 105‐kDa protein may be unable to incorporate into the BMZ because it is produced in a dysfunctional form, or its BMZ binding site is missing. It is also possible that other structural alterations in skin BMZ, which occur in dystrophic EB, result in masking of the antigenic binding by the autoantibody when intact BMZ is probed. In any case, the reducedin vivoexpression of the 105‐kDa protein represents additional evidence for a defect in BMZ composition in dystrophic EB which extends to a number of molec

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb00717.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThe detection of cytokeratins in neoplastic tissues by immunohistochemical methods has numerous diagnostic and investigative applications, because cytokeratins are usually conserved in tumour cells during malignant transformation. Recently, however, it has been reported that progression to malignancy is associated with commencement of expression of low‐molecular‐weight cytokeratins. In the present study, 42 specimens from 35 cases of squamous cell carcinoma (SCC) of the skin were analysed by immunohistochemical techniques, using polyclonal anti‐involucrin antibody and a panel of monoclonal antikeratin antibodies, in order to investigate the nature and differentiation of SCCs. The expression of cytokeratins and involucrin in well‐differentiated SCCs was similar to that in normal epidermis. In contrast with well‐differentiated SCCs, the expression of differentiation‐specific cytokeratins and involucrin was diminished in the immature tumour cells in proportion to the malignancy of the SCCs. Some antibodies, however, stained all tumour cells, irrespective of the degree of malignancy. Furthermore, expression of simple epithelial and non‐cornifying stratified squamous epithelial cytokeratins was observed in atypical tumour cells of poorly differentiated SCCs. It is of interest that similar expression was noted in many tumour cells in the lymph node metastases and in some tumour cells in the primary cutaneous lesions. Cytokeratin expression similar to that in normal epidermal keratinocytes was conserved in well‐differentiated SCCs, but the expression of cytokeratins changed during progression to malignant transformation. The expression of simple epithelial or non‐cornifying stratified squamous epithelial cytokeratins in cutaneous SCCs may be a marker for their capability of invasion and met

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb00718.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBasal cell carcinoma (BCC) is typically a slow‐growing malignant tumour, composed of cells similar to those in the basal area of the epidermis. We investigated the expression ofbcl‐2(B‐cell leukaemia/lymphoma‐2) in BCC, and also in squamous cell carcinoma (SCC) of the skin. The proto‐oncogenebcl‐2 encodes a protein which inhibits programmed cell death (apoptosis). The protein is expressed in basal cells in normal human epithelium, but not in the suprabasal cell layers. Immunohistochemical localization using a monoclonal anti‐Bcl‐2 antibody revealedbcl‐2 expression in all the BCCs (15 patients). SCCs did not expressbcl‐2 (five patients). The positive Bcl‐2 staining of BCC tumour cells supports the hypothesis that BCCs originate from the basal layer of the epidermis. Thebcl‐2 expression of BCC tumour cells also suggests a neoplastic transformation caused by extended cell survival rather than increased cell proliferation. This type of neoplastic growth is possibly associated with less aggr

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb00719.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY