摘要:

SummaryDermal effects of KH 1060, a novel, highly potent 20‐epi analogue of 1α,25‐dihyroxyvitamin D3, were investigated in a hairless mouse model. During daily topical applications of a 0.4 μm solution of KH 1060 for 4 weeks, epidermal hyperplasia and an increase of dermal thickness and mass were observed. KH 1060 upregulated glycosaminoglycan and collagen synthesis in the skin, and increased glycosaminoglycan deposition in the subepidermal region. Reverse transcription‐polymerase chain reaction amplification of the transforming growth factor (TGF) β1‐specific mRNA revealed that KH 1060 stimulated expression of this growth factor in the epidermis, but not in the dermis. Changes observed after application of 1α, 25‐dihydroxyvitamin D3were much less pronounced but qualitatively similar to the effects of KH 1060, whereas structurally related but receptor inactive compounds, vitamin D3and 1β,25‐dihydroxyvitamin D3, did not produce any effects. Furthermore, we were unable to demonstrate the involvement of the non‐genomic, receptor‐independent vitamin D signalling in the skin, using a specific stimulator (Ro 24–2090) and a blocker (1β, 25‐dihydroxyvitamin D3) of this pathway. Our findings provide the first evidence that a strong vitamin D3analogue triggers synthesis of skin connective tissue, possibly via vitamin D receptor activation and the paracrine action of

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb16939.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThe interactions between three liposomal formulations and human stratum corneum were visualized using freeze fracture electron microscopy. A new replica cleaning method was introduced. Human stratum corneum was submerged for 48 h in liposome suspensions prepared from commercially available phospholipid mixtures. The size, lamellarity and lipid moieties of the liposomes were similar. The main difference between the three phospholipid formulations was the hydrophilicity of the headgroups. The composition dependence of the interactions between these vesicles and human stratum corneum was investigated.In essence, two types of interaction were observed: adsorption of the liposomes on to the outer surface of the stratum corneum, and ultrastructural changes in deeper layers of the stratum corneum caused by mixing of the liposomal constituents and the stratum corneum lipids. The electron microscopic observations were verified with small‐angle X‐ray scattering. It was found that liposomes composed of phospholipids containing relatively small hydrophilic headgroups showed a marked interaction with the skin lipids of human stratum corneum in vitro. The complexity of the phospholipid mixtures, however, made it very difficult to determine the exact effect each of these headgroups has on the interactions between these vesicles and human stratum corn

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb16940.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryProteases are known to enhance the spread of tumour cells. Possible sources of these proteases are the tumour cells themselves or fibroblasts in the tumour tissue. Immunological staining with anticathepsin B antibody indicates that the subcellular distribution of cathepsin B in tumour cell lines differs from that in normal liver.The aims of this study were: (i) to show whether different types of melanoma differ in their production of cathepsin B; (ii) to identify the cathepsin B‐producing cells; and (iii) to determine the subcellular distribution of cathepsin B in melanoma cells.All types of melanomas contained cell regions stained with anticathepsin B antibody. The intensity of the stain and the number of cells reacting with anticathepsin B antibody depended on the size of the tumour but not on the type of melanoma. Epithelioid cells stained more intensely with anticathepsin B antibody than spindle‐shaped cells. Cells staining with anticathepsin B antibody were almost exclusively tumour cells. Anticathepsin B stain was located mainly in vesicular structures which did not contain a filamentous matrix. Additional anticathepsin B stain was detected at the extracellular spaces.Hypomelanotic melanoma cells, mainly of the epithelioid type, produced most of the cathepsin B. Cathepsin B may be involved in both the degradation of possibly abnormal melanosomes and the focal degradation of the extracellular mat

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb16941.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThe effects of pregnancy on the pathophysiology of melanoma remain unclear. Although a gender‐specific advantage for women vs. men is seen for characteristics such as stage at presentation, site of primary tumour, and survival time, an adverse effect of pregnancy on melanoma development and progression has been reported.In a retrospective study, we investigated the tumour characteristics of women who developed pregnancy‐associated melanoma, and compared them with melanomas arising in non‐pregnant women of child‐bearing age. The patient records of the Massachusetts General Hospital Pigmented Lesion Clinic were reviewed, and 465 women of reproductive age (16–45 years) who developed melanoma were identified. Of these, in 45 women (age 21–42 years) there was a close temporal relationship between diagnosis of the tumour and pregnancy. Clinical and histological characteristics of the primary tumours were recorded. Differences in tumour thickness, site and histological type were analysed.The mean thickness of pregnancy‐associated melanomas was significantly greater than that of non‐pregnancy‐associated tumours (2.28 vs. 1.22 mm, respectively:P<0.007). No differences in histological type (P= 0.64) or site (P= 0.74) of the primary tumours were found between the two patient groups. Not surprisingly, multivariate analysis revealed that tumour thickness was a statistically significant variable in determining prognosis (P= 0001). An unexpected finding, on multivariate analysis, was a possible pregnancy‐associated prognostic advantage (P= 008).Melanomas arising during pregnancy are thicker, but are not necessarily associated with a less favourable prognosis than tumours arising in non‐pregnant women of child‐bearing age. The mechanisms by which pregnancy may lead to increased thickness of melanoma have yet to be elucidated,

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb16942.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryUltraviolet (UV) irradiation oftrans‐urocanic acid (UCA), a major UV absorbing component of the epidermis, leads to the formation ofcis‐UCA, which mediates immunosuppressive effects. In this study, the net yield ofcis‐UCA was measured after the photoisomerization of urocanic acid by narrow UV wavebands (spectral range 295–405 nm), with the irradiation doses related to solar irradiance at sea level. The formation ofcis‐UCA in Caucasian skin (in vivo), as well as in aqueous solution (in vitro), was determined by HPLC analysis. The same irradiation conditions were met in both components of the study. Thein vivoexperiments showed high efficiency ofcis‐UCA formation in the spectral region of 305–341 nm, whereas high efficiencyin vitrowas found at 305 and 326 nm. At 350 and 363 nm,cis‐UCA was formedin vivo, but notin vitro.At longer test wavelengths up to 405 nm. no significant formation ofcis‐UCA was detectable. The established partition between UVB and UVA at 320 nm is not relevant for the isomerization pattern of UCA. Additional studies revealed substantialcis‐UCA formation in human skin by UVA phototherapy lamps. Furthermore, raised levels of 295 nm irradiation doses, a possible effect of stratospheric ozone depletion, were found to increase thecis‐UCA yield. Our results demonstrate that the formation ofcis‐UCA in the skin with common exposures takes place over a broad spectrum range of UVB and UVA, up to at least 363 nm. These findings emphasize the potency of UVA to isomerize UCA, and they may contribute to further elucidation of the effects of phot

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb16943.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThe mitogenic effect of the neuropeptide substance P and bombesin was investigated in normal human keratinocytes in serum‐free culture, both with and without the presence of epidermal growth factor (EGF). Although both neuropeptides induced a small Increase in cell numbers in the presence of EGF. the response was much greater in its absence, and cell numbers Increased to 200% of controls at 5 days. Changes in intracellular free calcium are frequently seen following mitogenic stimulation of cells, and this phenomenon was studied in individual keratinocytes. Epidermal growth factor (10 ng/ml) induced calcium transients in 57% (n= 21) of cells. The mean Intracellular free calcium was 97 ± 11 nM (mean ± SEM) in quiescent cells, and the calcium transients reached approximately 250 nM for 3–4 min. In the presence of EGF. calcium transients were never observed with the addition of either substance P or bombesin. For EGF‐deprived cultures. 20% of keratinocytes (n= 10) showed a large calcium transient following the addition of 500 nM bombesin, and ft 63% (n= 12) of cells gave calcium transients following the addition of 700 nM of substance P. Studies in calcium‐free medium, and following depletion of intracellular calcium stores with thapsigargin. showed that all of the calcium transients were dependent on the presence of intracellular stores, but also partially mediated by an influx of extracellular calcium. These studies demonstrate the mitogenic effect of substance P and bombesin on human keratinocytes in the absence of EGF. The ability of the neuropeptides to increase keratinocyte growth In culture suggests a possible role in woun

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb16944.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryHLA‐A, B, Cw, DR and DQ antigens were serologically determined in 105 patients suffering from lichen planus (LP). Of these patients, 87 had idiopathic LP and 18 had secondary LP. In the first group, 43 had cutaneous LP without mucosal lesions, 17 had cutaneous LP with mucosal lesions and 27 had purely mucosal LP. No HLA antigen was found to be significantly associated with secondary LP or with mucosal idiopathic LP. In cutaneous idiopathic LP with or without mucosal lesions, the HLA‐DR1 and DQ1 antigen frequency was significantly increased, and that of HLA‐DQ3 significantly decreased. Among the HLA‐DR1 cutaneous idiopathic LP patients, 78.5% carried the DRB1*0101 allele, and 214% the DRBI*0102 allele, compared with 35.7 and 67.8%, respectively, of the HLA‐DR1 controls. Our data demonstrate that idiopathic LP is influenced by HLA‐associated genetic susceptibility and resistance factors not involved in secondary LP, and that cutaneous idiopathic LP is a genetically and therefore pathogenetically different condition from purely mucosal id

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb16945.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThe immunophenotypic characteristics of the skin pathergy reaction (SPR) at 48 h in Behçet's disease (BD) were investigated in 12 patients with BD and in five controls. The findings in 11 positive and one negative SPR lesions of patients with BD were evaluated in comparison with those of normal adjacent skin and with the negative pathergy biopsies from the controls. Positive SPR biopsies showed variable epidermal thickening and cell vacuolization, as well as subcorneal pustule formation. In the SPR dermis, a variable dense focal mononuclear cell (MNC) infiltrate was seen around vessels and skin appendages, extending into the deep dermis. The MNC infiltrate was predominantly composed of T lymphocytes and monocytes/macrophages. The majority of the T lymphocytes were CD4+, and almost all expressed CD45RO. Approximately half of the infiltrating cells strongly expressed HLA‐DR. Neutrophils constituted less than 5% of the infiltrating cells, but were present as clusters of elastase‐positive cells at the needle‐prick sites. Vessels within the lesion showed marked congestion and endothelial swelling. The endothelial cells expressed ICAM‐1 strongly, and E‐selectin moderately. VCAM‐1 was not expressed on endothelial cells. The basal and mid‐epidermal layers of keratinocytes expressed HLA‐DR and ICAM‐1 strongly, particularly so in areas close to the dermal MNC infiltrates. In negative pathergy biopsies, there were increased numbers of neutrophils and a few small clusters of macrophages and T lymphocytes only at the needle‐prick site, and the endothelial cells of vessels close to these areas expressed E‐selectin weakly. The immunohistological findings of the SPR appear to indicate an augmented antigen‐independent non‐specific induction phase of the inflammatory response. Absence of VCAM‐1 expression by endothelial cells suggests that direct epidermal injury is the cause o

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb16946.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryDithranol is established as a very successful treatment for psoriasis. Its main disadvantages are irritation and staining at sites of application. The aim of the present study was to elucidate further the mechanism of dithranol‐induced irritation, in particular to what extent this is related to an impairment of the skin barrier.Dithranol 3% in cream, paste and petrolatum was applied to the forearm skin of 20 volunteers and leftin situfor 1 h. Transepidermal water loss (TEWL) was measured during a period of 2 weeks following dithranol application. In addition, a visual scoring system and colorimetry were used to assess erythema.The study showed conclusively that TEWL was not affected by the application of dithranol, even though pronounced erythema occurre

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb16947.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThe moisture content of the epidermis was measured by magnetic resonance imaging (MRI), using transverse relaxation time. The spatial resolution was 86 μm, allowing a quantitative, accurate and localized determination of variations in epidermal hydration. The wrists of 15 volunteers were studied before and after application of a hydration cream. Results showed an increase of 15% of epidermal T2 after application of the cream. Moisture content curves varied according to different degrees of skin dryness. This study demonstrates that MRI is a useful tool in evaluation of epidermal hydration

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb16948.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY