摘要:

SummaryA fully differentiated epithelium displaying features of human epidermis was obtained in vitro by culturing second‐passage normal human keratinocytes for 14 days in defined medium and on an inert polycarbonate filter substratum at the air‐liquid interface.Vertical sections stained for histology and indirect immunofluorescene studies showed that the‘basal’cells synthesize and secrete all major markers of hemidesmosomes and the lamina lucida. Components of the lamina densa are also expressed. Collagen VII is synthesized, but not secreted. Ultrastructural studies showed the presence of hemidesmosomes with major dense plaques and anchoring filaments, and a basement membrane‐like structure was clearly identified.These results show that epidermal cells are able to produce hemidesmosomes and to secrete the major components of the dermo‐epidermal junction in the absence of serum and dermal factors, suggesting that basement membrane synthesis and hemidesmosome assembly are not dependent on the presenc

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb11839.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryExtensive study of the p53 gene has established its role as a tumour‐suppressor gene, and the involvement of mutant p53 in a wide spectrum of human malignancy. Many mutations of p53 result in a protein product that is abnormally stable, so that it becomes readily detectable by immunocytochemistry. In contrast, under normal conditions, it has been considered that levels of wild‐type p53 were too low to be detectable. Although positive immunocytochemistry has been used as a marker of mutation, recent evidence suggests that this assumption may not always be valid. We have carried out both PCR‐sequencing of exons 5‐8 of the p53 gene in 20 basal cell carcinomas (BCC), and immunocytochemistry of these tumours with the anti‐p53 antibody Do7. Twenty cases of Bowen's disease, in which we had previously documented mutations, were also immunostained. We report a low rate of p53 mutation in the BCCs we examined (2/20), and a discrepancy between tumours with positive immunostaining and those with mutation in both Bowen's disease and BCC. Of eight tumours in which we detected mutation, only four were immunopositive; of 19 immunopositive samples, only four showed detectable mutation. We discuss the implications of our results for the use of positive immunostaining in clinical diagnosis, and the involvement of p53 in skin carci

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb11840.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryIn a retrospective follow‐up study, 36 renal transplant recipients with, and 101 without, skin cancer, who had received their first transplant before January 1981 and who were still alive with a functioning graft on 1 August 1989, were assessed to determine the risk of non‐melanoma skin cancer in relation to exposure to sunlight during childhood and adolescence. The contribution of the number of keratotic skin lesions to the skin cancer risk was also assessed.The estimated relative risks (odds ratios) of skin cancer in relation to exposure to sunlight and the presence of keratotic skin lesions were calculated by maximum likelihood estimation in a logistic model.The majority of skin cancers and keratotic skin lesions were confined to sun‐exposed skin. After adjustment for possible confounding variables, the odds ratios of skin cancer for moderate and high cumulative life‐time exposure to sunlight, respectively, compared with low exposure, were 2·4 (95% confidence interval [CI] 0·64‐9·3) and 47·6 (95% CI 5·4‐418). Exposure to sunlight before the age of 30 contributed more to the risk of developing skin cancer later in life than exposure after the age of 30.No association was found between cumulative life‐time exposure to sunlight and the number of keratotic skin lesions. Nevertheless, these lesions behaved as a strong independent risk factor in the development of skin cancer. The adjusted odds ratio of skin cancer for 50‐99 lesions compared with>50 lesions was 4·5 (95% CI 1·1‐18·2); the adjusted odds ratio for ≥100 lesions compared with>50 lesions was 20·8 (95% CI 5·3‐81·7).We conclude that exposure to sunlight before the age of 30 contributes more to the risk of skin cancer in renal transplant recipients than exposure after the age of 30. Cumulative life‐time exposure to sunlight does not appear to be associated with an increased number of keratotic skin lesions in these patients. The preferential localization of such lesions on sun‐exposed skin suggests a possible role of recently received exposure to sunlight

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb11841.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryTo investigate the hypothesis that aberrant HLA and adhesion molecule expression in alopecia areata (AA) are secondary to local release of interferon‐gamma (IFN‐γ) or other cytokines. we have studied HLA ABC. ‐DQ. ‐DR and ICAM‐1 expression by immunohistochemistry, and compared patterns of expression in lesional tissue sections with those observed in hair follicles maintained in short‐term organ culture, both from normal individuals and non‐lesional sites in AA patients. The organ cultures were supplemented with IFN‐γ, tumour necrosis factor‐alpha (TNE‐α), and granulocyte‐macrophage colony stimulating factor (GM‐CSE). in a range of doses.In lesional AA tissue sections, there was close spatial correlation of ICAM‐1 with HLA‐DR; prominent staining being noted in the pre‐cortical matrix and dermal papilla (DP) of lesional anagen follicles. In cultured follicles, dose‐dependent induction of HLA class I. DR and ICAM‐1 by IFN‐γ, and HLA class I and ICAM‐1, but not HLA‐DR. by TNE‐α was observed in follicular epithelium, mainly in the outer root sheath (ORS). The findings in these cultures were the same in follicles derived from normal individuals and AA patients.Cytokine‐induced patterns of HLA and ICAM‐1 expression observed in vitro in cultured follicles differed significantly from those observedin vivoin lesional tissue sections. In particular, IFN‐γ failed to induce HLA‐DR expression in the pre‐cortical matrix and dermal papilla (DP), sites where this is usually observed in AA. The results suggest local cytokine release is not

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb11842.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryPemphigoid gestationis (PG; herpes gestationis) is a rare autoimmune disease associated with pregnancy, currently defined by the presence of complement deposition along the cutaneous basement membrane zone. It is known to be associated with HLA‐DR 3 and DR4, and an increase in anti‐HLA antibodies in those with a history of PG has been reported. We have studied 39 patients with an immunofluorescence‐confirmed diagnosis of PG for the presence and specificity of anti‐HLA antibodies.Anti‐HLA antibodies were found in all 39 patients. Specificity was against class 1 antigens in 98% (controls 10%: P>0.001) and class II antigens in 25% (controls 8.5%: P>0.001), Almost all anti‐ HLA antibodies were cytotoxic.The universal presence of anti‐HLA antibodies in PG suggests that they may develop coincidently with anti basement membrane antibodies, and may reflect a common immuno

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb11843.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryAlthough onchocerciasis is one of the most important diseases of the skin and eye in the tropical world, to date there has been no formal consensus regarding the description and terminology of skin lesions. Furthermore, the contribution of cutaneous pathology to the morbidity and socio‐economic effects of the disease has been largely neglected. We present a clinical classification and grading system for recording the cutaneous changes of onchocerciasis, and propose that this system be used as a standard method of description to convey clinical information between workers in all endemic areas to assist local and comparative researc

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb11844.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryPatients with venous leg ulcers have a readily recognized clinical syndrome of shallow ulcers, oedema, leg pain, venous ankle blush, lipodermatosclerosis, varicose veins, hyperpigmentation, and atrophie blanche, and they are assumed to have venous abnormalities. We examined 43 patients with venous leg ulcers, and compared those with obvious venous abnormalities (defined as historical or clinical evidence of deep venous thrombosis or varicose veins) with those with presumed venous abnormalities (defined as lacking any such evidence), to see if they presented with different clinical features. We found that both groups had similar clinical features, with the exception that lipodermatosclerosis was present more frequently in those patients with obvious venous abnormalities (94 vs. 36%, P>0.001). Most patients with presumed venous abnormalities had musculoskeletal conditions which might cause calf pump dysfunction (91%). Using air plethysmography, we were unable to confirm that all patients with presumed venous abnormalities did have intrinsic venous abnormalities. We propose that ulcers occurring in this clinical syndrome be designated as calf pump dysfunction ulcers (CPD ulcers), rather than venous ulcers.

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb11845.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryDuring two tularaemia outbreaks in the Bursa region of Turkey in 1991, a total of 98 patients were diagnosed and evaluated. Thirteen of these patients had erythema nodosum, which is accepted as a secondary skin manifestation. The patients with erythema nodosum, 21 patients without any skin lesions, and 20 healthy controls were studied. Comparable elevations of levels of IgG, IgA, and IgM were detected in the two tularaemia groups. There was no difference in complement C3c and C4 levels between the groups. All of the patients with erythema nodosum had elevated circulating immune complex (CIC) levels, when compared with the patients without skin lesions and the control group. The acute phase response (C‐reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) of the erythema nodosum group was significantly higher than the patients with normal skin, and healthy controls (P>0.001). Serum transferrin levels were significantly decreased in both of the tularaemia groups (P>0.001). Serum soluble interleukin‐2 receptor levels (SIL‐2R) were significantly elevated in both tularaemia groups (P>0.001), and the elevation was more marked in the erythema nodosum group (P>0.05). Histopathologicai evaluation of biopsies from two patients with erythema nodosum showed dermal oedema, a perivascular lymphocytic infiltrate, and panniculitis. No immunoglobulin or complement deposits were detected on immunofluorescence.Erythema nodosum in the course of tularaemia is associated with many immunological changes, although it is not clear whether these findings are related to the increased tissue response, or whether they play a role in the pathogenesis of the erythema no

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb11846.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummarySignal transduction of many intracellular events is initiated by a minute influx of calcium ions into the cells, resulting in the formation of calcium‐calmodulin complex and cAMP. Because zinc appears to have an inhibitory effect on a number of tissue reactions, it is postulated that this occurs through modulation of intracellular calcium influx. To test the hypothesis that the inhibitory effects of zinc are mediated through the calcium calmodulin‐cAMP pathway, zinc was administered by various routes to five groups of nude mice (control, intragastric, intraperitoneal. intradermal and oral groups), and calmodulin and cAMP concentrations were measured in the cytosol of epidermal cells. Calmodulin levels decreased significantly in the groups given intraperitoneal zinc (P>0.025) and intradermal zinc (P>0.001) injections. Significant elevations of cAMP levels were noted with intradermal zinc (P>0.025). Overall, the relationship between calmodulin and cAMP appeared to be inversely logarithmic, with the lowest calmodulin levels associated with the highest cAMP concentrations. In addition, there was a significant trend towards a smaller calmodulin/cAMP ratio in all zinc‐treated groups, except the mice fed dietary zinc. These results appear to correlate with tissue zinc levels obtained with these various forms of zinc administration. Our results therefore indicate that there is a reciprocity between epidermal calmodulin and cAMP levels, which may be modulated by external factors such as

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb11847.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryThe influence of vehicle (two oil‐in‐water emulsions and two gels, each containing 10% or 5% ibuprofen) application time (0·5,1,2 h), applied dose (1·5,3,6. 2 mg/cm2), time (24 h after an 0·5h application time), and occlusion on the epidermal concentration of ibuprofen was investigated. The drug concentration in the epidermis was measured by HPLC. All results were expressed as μg drug/mg epidermal protein.The application time had no influence on the epidermal drug concentration, whereas the two gel formulations produced concentrations approximately twice those obtained with the emulsions. A significant positive correlation was found between the applied dose and the epidermal concentration for each formulation. After 24 h the amount of drug remaining in the epidermis was low (reduced by factors of 10‐20). Occlusion produced higher concentrations, but only with the 2‐h application time.The methods are reliable, and useful in ranking vehicles according to their ability to release ibuprofen into the epidermis. Future investigations should explore the relationship between epidermal concentration and anti‐inflammatory ef

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1993.tb11848.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY