摘要:

SummaryPrior studies have demonstrated a Ca2+gradient within the epidermis, with the highest concentration in the outer nucleated layers, disappearance of the Ca2+gradient when the permeability barrier is acutely disrupted, and reappearance of the Ca2+gradient in parallel with barrier repair, and disruption of the gradient in psoriasis. These observations suggest that integrity of the permeability barrier may maintain the epidermal Ca2+gradient. To determine further whether a functional barrier is crucial for maintaining the Ca2+gradient, we examined Ca2+distribution by ion‐capture cytochemistry in essential‐fatty‐acid‐deficient (EFAD) and topical‐lovastatin‐treated mice, which display a chronic barrier abnormality. In both models, loss of the Ca2+gradient occurred due to increased cytosolic Ca2+in the lower epidermis, which normally displays a paucity of Ca2+. Moreover, artificial barrier restoration for 48 h with a water vapour‐impermeable wrap normalized the Ca2+distribution pattern. Acute barrier disruption also leads to the loss of the Ca2+gradient, but in contrast with the chronic models, loss of the gradient was due to decreased Ca2+in the upper epidermis. Occlusion with a vapour‐impermeable wrap blocked restoration of the Ca2+gradient after acute barrier disruption. These results demonstrate that chronic barrier disruption increases Ca2+in the epidermis, and blockade of water flux normalizes Ca2+distribution, whereas acute barrier disruption leads to loss of Ca2+, and blockade of water flux prevents the return of Ca2+. We conclude: (i) that the epidermal Ca2+reservoir is derived from the movement of fluids and Ca2+across the basement membrane, and (ii) that the integrity of the permeability barrier maintains the epiderm

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb02892.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryAcantholysis is a feature of disorders such as Hailey‐Hailey disease and Darier's disease. Immunocytochemical studies have shown internalization of desmosomal components after acantholysis. Basal cytokeratins show suprabasal expression in lesional Darier's disease. The exact mechanisms of acantholysis are still unclear. Cantharidin induces blistering, with suprabasal keratinocyte acantholysis, possibly by protease activation. Plasmin has been implicated in the pathogenesis of acantholysis in Darier's disease and Hailey‐Hailey disease. We examined the distribution of desmosomal components, proteases and cytokeratins in cantharidin blisters, to compare them with those previously found in Darier's disease and Hailey‐Hailey disease. Two drops of cantharidin collodion were applied to the skin of five normal volunteers. A 4‐mm punch biopsy of the blister was taken, and snap frozen. Sections were stained with antibodies to desmosomal proteins (dp) 1/2, dp 3, desmosomal glycoproteins (dg) 1, 2/3, extracellular carbohydrate residues, using the lectins peanut agglutinin (PNA) and soybean agglutinin (SBA), proteases and cytokeratins. Acantholytic cells were stained diffusely with dp l/2: there was markedly reduced or absent peripheral staining for dp 3, dg l, dg 2/3, PNA and SBA. There was no clumping of stain. Plasminogen, fibrinogen and urokinase were expressed in some acantholytic cells. Basal keratin markers were expressed suprabasally in acantholytic cells. These results are similar to those previously obtained in Darier's disease, but different from the staining obtained in Hailey‐Hailey disease. Extracellular glycosylated portions of adhesion molecules may be lost after acantholysis, perhaps as a result of conformational changes, internalization of extracellular domains, or proteolysis. The changes in the expression of plasminogen, fibrinogen, urokinase and cytokeratins in acantholytic cells in cantharidin‐induced blisters are, as in Darier's disease and Hailey‐Hailey disease, probably secondary to acantholysis, and changes in the shape of cells. We conclude that cantharidin blisters may be a useful model for the study of acantholysis in Dar

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb02893.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryTwo new types of intracytoplasmic inclusion bodies (ICBs) associated with distinct clinical features, and the presence of DNA of distinct types of human papillomaviruses (HPVs) are reported. One hundred and seven cutaneous warts containing ICBs were grouped into three categories according to distinct clinicopathological features: 67 were wart lesions with well‐known granular (Gr)‐ICB. 1 3 were punctate keratotic lesions with filamentous (Fl)‐ICB and 31 were pigmented warts with homogeneous (Hg)‐ICB. Molecular biological studies were performed in order to assess a specific association of each group of warts with distinct types of HPV.HPV‐1 DNA sequences were detected in all the lesions with a Gr‐ICB. Punctate keratotic lesions with Fl‐ICB were associated with HPV‐63, which was newly cloned from such a lesion. One of the samples also contained HPV‐1 DNA. Pigmentcd warts with Hg‐ICBs contained one of the related HPVs, i.e. HPV‐4. HPV‐60 or a novel type of HPV, HPV‐65. Based on these associations, a classification of in

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb02894.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryClinical assessments of photodamage are based upon a subjective evaluation of characteristic features such as wrinkling and pigmentary change, and are influenced by inter‐observer differences in grading criteria. In an effort to standardize the grading of photodamage severity, we have developed a six‐point photographic scale in which each of the six grades of overall photodamage severity is depicted by three photographs. The use of three photographs to portray each grade illustrates the diversity and range of manifestations within each grade. This photographic scale was tested by two groups of dermatologists, who used it on two occasions to grade the overall photodamage severity of a single group of female Caucasian subjects. Results indicate high inter‐observer agreement, with chance‐corrected agreement ranging from 0.44 to 0.63 and from 0.54 to 0.76 on the first and second occasions, respectively. Intra‐observer repeatability was high, with chance‐corrected agreement ranging from 0.56 to 0.78. Inter‐ and intra‐observer differences were within one category in nearly all cases. Similar grades were assigned by dermatologists with and without experience in treating photodamaged patients. We conclude that application of this scale results in consistent and reproducible clinical evaluations of overall photodamage severity in Caucasian subjects. The scale may be useful in categorizing subjects for epidemiological studies, or in selecting patients for

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb02895.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryDespite the fact that several cell types residing in or travelling through the skin are targets and/or sources of nerve growth factor (NGF), little is known about the role of NGF in skin development, physiology and disease. Employing a previously defined skin organ culture assay for studying the proliferation of murine keratinocytes in their natural tissue environment, we have assessed the effect of murine NGF (7S) on keratinocyte proliferation in intact skin derived from two defined stages of the murine hair cycle. We found that 10–200 ng/ml NGF stimulated epidermal keratinocyte proliferation in organ‐cultured C57 BL‐6 mouse skin in the telogen phase of the hair cycle. Follicle keratinocyte proliferation was stimulated by 100 ng/ml NGF in telogen skin organ culture, but this concentration of NGF inhibited both epidermal and follicle keratinocyte proliferation in organ culture of anagen skin. The latter inhibitory effect of NGF was abrogated by co‐incubation with neutralizing anti‐NGF antibodies or with the protein kinase C inhibitor staurosporine. The proliferation‐modulatory effects of NGF were associated with the induction of significant mast cell degranulation, and were inhibited by cromoglycate co‐administration. This is the first report of a modulatory, hair cycle‐dependent effect of NGF on keratinocyte proliferationin situ,which may require the presence of mast cells. Our study supports the notion of auto‐ and paracrine functions of NGF in murine skin physiology, which can be further assessed in the physiologically relevant mouse mode

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb02896.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryIt is well established that cyclosporin A (CyA), a widely used immunosuppressant in human organ transplantation, is an effective drug in the treatment of psoriasis. Although it has been postulated that the effect of CyA in psoriasis is mediated through antilymphocyte activity, there is also evidence suggesting that CyA exerts a direct cytostatic effect on epidermal keratinocytes, but results of studies relating to the latter have been contradictory.Using immunohistochemical methods we investigated the influence of systemic CyA on proliferation and differentiation in the tape‐stripped uninvolved skin of psoriatic patients, a model which provides the opportunity of studying epidermal regeneration in the absence of a significant accumulation of T lymphocytes. We addressed the question of whether CyA (3–5 mg/kg/day) modulates epidermal proliferation and differentiation following standardized injury in uninvolved skin of psoriatic patients. Ten patients with severe psoriasis participated in this study. The dosages of CyA were sufficient to induce a marked and statistically significant improvement (PASI, week 0, 20.5·4.4; PASI, week 16, 4.3 ± 0.6). Before CyA treatment, and during week 16 of treatment, Sellotape stripping was carried out on a 2‐cm2area of the uninvolved skin of psoriatic patients. After 48 h punch biopsies were taken. Immunohistochemical assessment of recruitment of cycling cells (Ki‐67), filaggrin, involucrin, T lymphocytes and tenascin, was carried out. We did not find any significant alteration during the treatment period in the tape‐stripped uninvolved skin of psoriatic patients. We conclude that epidermal hyperproliferation and abnormal keratinization are not modulated directly by CyA at therapeutic dosesin vivo.Furthermore, our study provides indirect evidence that the antipsoriatic effect of CyA is mediated by the im

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb02897.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryAltered expression of α‐smooth muscle actin (α‐SMA) is known to indicate the morphological, tumorigenic and immunological changes occurring in tumour and stromal cells. The purpose of this study was to analyse the dynamics of α‐SMA expression in human basal cell epithelioma (BCE) cells and their surrounding stromal cells, in the process of differentiation towards cutaneous appendages such as hair, sebaceous, apocrine and eccrine glands. Using anti‐α‐SMA specific monoclonal antibody (MAb), 17 of 36 BCEs (47%) were shown to express α‐SMA, despite the usual absence of α‐SMA in all eukaryotic cells except muscle cells. Solid, adenoid and sclerosing types of BCE expressed α‐SMA more frequently, and in greater amount, than cystic, keratotic and superficial types. Furthermore, the expression of α‐SMA in BCE cells significantly paralleled the expression of proliferating cell nuclear antigen (PCNA) in these cells. Thus, the altered expression of α‐SMA may reflect the growing properties of BCE cells under the specific cellular regulations for differentiation.In addition, we have found anti‐α‐SMA MAb‐positive fibroblasts with smooth muscle differentiation (myofibroblasts) in desmoplastic stroma surrounding BCE nests in 13 of 36 cases (36%). Coincidental expression of α‐SMA in both BCE cells and stromal cells was found in nine of the 13 cases (69%), indicating the possibility of the induction of myofibroblastic stromal changes in surrounding tissues by cytokines secreted from BCE cells [e.g. basic fibrob

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb02898.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryThe determinants of final nail thickness and length at its point of detachment at the onychodermal band were studied in 20 normal great toe‐nails, removed after injury, by correlating measurements of nail thickness, taken at six anatomical points, with length of nail and its lunular (matrical) and ventral nail components. Final nail thickness at the onychodermal band was related to initial thickness of the proximal matrix, and independently to the lengths of the lunula and ventral nail, but not to final nail length. There was an increase in nail thickness with age, particularly in the first two decades; this appeared not to be due to a decrease in frictional loss of nai

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb02899.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryThe role of stressful life events in the progress of various skin conditions was studied retrospectively in patients who presented with either psoriasis (where there is some agreement about the importance of stress), urticaria, acne, alopecia and non‐atopic eczema (where there is some uncertainty regarding the role of stress), or malignant melanoma, fungal infection, basal cell carcinoma and melanocytic naevi (where stress is considered less relevant). When patients in the three groups were matched for age, those with psoriasis were more likely to report that the experience of stress pre‐dated the onset and exacerbations of their condition than patients with other skin diseases. For the psoriasis patients the most common types of life events were family upsets (such as bereavements), and work or school demands, but chronic difficulties were also common. There was no relationship between the severity of stress and time to onset or exacerbations. The results support the notion that stress is more likely to be associated with the onset of psoriasis than other conditions, but also that there may be considerable individual variation in the ability to cope, suggesting that psychological interventions may be helpful for particular patie

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb02900.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryIn the past 22 years, 113 patients with severe psoriasis have been treated with low‐dose methotrexate (MTX) in our department. The maximum weekly dosage was 15 mg (Weinstein schedule), the estimated mean cumulative dose was 4803 mg, and the estimated mean duration of therapy was 8 years and 11 months. In 81% of the patients, prolonged clearance or near clearance was achieved, indicating the potent and sustained potential of MTX in the treatment of both the pustular and erythematosquamous variants of psoriasis.Eighty‐three patients (73%) had side‐effects, most frequently abnormal liver function tests, nausea and gastric complaints. Apart from hair loss in seven patients, there were no mucocutaneous side‐effects, probably because of the low‐dose treatment schedule. In 71 patients MTX therapy was discontinued: in 33 patients because of side‐effects. In 55 patients one or more liver biopsies were performed. Fibrosis was seen in seven of these patients (13%) and cirrhosis in two (4%). There was no relation between liver biopsy classification and cumulative dosage or duration of MTX therapy, nor was there any relation between liver histology and abnormal liver function tests. During this 22‐year period, there were no deaths or life‐threatening side‐effects attributable to MTX treatment.We conclude that low‐dose MTX(≥15 mg/week) is a relatively safe therapy for severe psoriasis, if patients are carefully selected beforehand, and regular monitoring for side‐effects and drug interactions is performed during therapy. A liver biopsy during the first 3 months of treatment, and subsequently after each 1.5 g of MTX, should be part of the treatment protocol, until equally reliable non‐invasive screening methods for l

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb02901.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY