摘要:

SummaryWe have recently analysed by hislological, protein and molecular DNA techniques 23 mutations of the collagen III gene (COL3AI). most of which cause premature arterial fragility, thin skin and variants of vascular Ehlers‐Danlos syndrome. There were 14 glycinesubstitutions between residues 637 and 1021. eight exon skips between exons 7 and 45 and one small inframe deletion. The glycine substitutions produce a gradient of increasingly abnormal clinical phenotypes from exons 36 to 49 while the clinical severity of exon skips is much more variable. Each mutation is private for the affected family or individual concerned having the potential for early prenatal diagnosis and preventio

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb01143.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryIn a subgroup of patients with atopic eczema (AE), eczematous skin lesions can he induced by epicutaneous testing with aeroallergens (the atopy patch test: APT). An increased frequency of positive APT has been found in AK patients showing a predictive lesional pattern affecting air‐exposed skin areas. This study investigates the dose‐response ofthe APT in two dilTerent patient groups with AE. Petrolatum preparations of house dust mite, cat dander and grass pollen allergens in four concentrations (500–10,000) protein nitrogen imits) were tested epicutaneously in 57 patients with AE. who were prospectively divided in two groups according to whether their AE pattern was with (group I) or without (group II) a predictive distribution. Sixty‐nine per cent of patients in group I. and 39% in group II. had positive APT reactions (P = 0.02). The reactions in group I were elicitable with lower allergen concentrations (P = 0.03). A clinically recognizable subgroup of patients with AE showed increased cutaneous sensitivity to aeroal

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb01144.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryIn normal human skin, immtmoreactive thrombomodulin (TM) is expressed in a strict differentiation related pattern. solely in suprabasal spinous layer keratinocytes. To evaluate the polential application of TM as a differentiation marker for keratinocyte‐derived skin tumours, we have studied immunohistopathological, biochemical and functional TM activities in various skin tumours. Immunoreactive, full sized and enzymatically active TM was expressed in keratinocyte‐derived skin tumours (squamous cell carcinoma, seborrhoeic keratosis and partly Bowen's disease), as well as normal epidermal keratinoeytes and endothelial cells. However, no TM was detected in basal cell carcinotnas, senile keratosis or non‐squanious epithelial tumours such as malignant melanoma, naevus pigmentosus and Paget's disease. Interestingly, decreased expression was observed in verruca vulgaris. These findings suggested that differentiation‐dependent TM expression was restricted to epithelial skin tumours and undetectable on neural crest derived tumours. TM is a differentiation marker for spinous layer keratinocytes and is a useful tool in histopathological study of epithelial

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb01145.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryEpidermal Langerhans cells (LC) express several co‐stimulatory molecules such as B7/BB1. which has been Implicated as one of the important determinants for potent antigen‐presenting function of LC. Recent studies have shown that B7/BB1 antigens comprise three distinct molecules termed B7‐1, B7‐2 and B7‐3. Previous studies have revealed that the phenotypic and functional properties of murine LC are enormously affected by various cytokines including granulocyle‐macrophage colony stimulating factor (GM‐CSF), interleukin‐l (IL‐1), and tumour necrosis factor α (TNF‐α)derived from surrounding keratinocytes. We have already demonstrated that the expression of B7‐1 of murine LC is significantly enhanced by GM‐CSF, IL‐1 or TNF‐α. In this paper, we present that IL‐I, hut not TNF‐α, synergistically up‐regulates the GM‐C

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb01146.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryThe ability of antifungal azole derivatives to inhibit superoxide anion release from human leucocytes and the relevance of their documented calmodulin (CaM) antagonism was investigated with respect to anti‐inflammatory drug activity. Econazole, miconazole and clotrimazole were found to inhibit phorbol ester‐induced release of superoxide anions from human polymurphonuclear leucocytes effectively with IC50values in the range of 36–162 μmol/1. In contrast, bifonazole and ketoconazole produced minimal or no inhibition, thus suggesting that mechanisms other than inhibition of superoxide anion release may largely account for their clinical activity in inflammatory skin disorders. The selective CaM antagonist J‐8, which was used as a reference, failed to inhibit the release process, whereas W‐7 as a dual CaM/protein kinase C inhibitor induced dose‐dependent inhibition. When tested on protein kinuse C activityin vitro, econazole, miconazole and clotrimazole were inhibitory, but bifonazole and ketoconazole were without significant effect. It is thus concluded that inhibition of superoxide anion release reflects the ability of these drugs to inhibit protein kinase C, but not their potency to antagonize CaM. Given the role of reactive oxygen species in lissue damage hy neutrophils. we propose protein kinase C, rather than CaM, as another potential target of anti‐inflam

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb01147.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryAlopecia areala is a form of balding whose aetiology is uncertain. Although the dermal papilla in the hair bulb regulates the iollicie and may play a part in the pathogenesis of alopecia areata. Its ultrastructure has not been well described. As clinically normal, i.e. non‐balding, follicles from alopecia areata scalps show abnormalities at the light microscope level, it would be expected that they should exhibit the earliest pathological changes involved in the dysfunction of the follicle. This study was designed to investigate the ultrastructure of normal human scalp follicular dermal pap‐illae and to see if changes occurred in the ultrastructure of dermal papillae from either lesional or non‐balding regions of alopecia areata.Normal dermal papillae contained well formed fibroblast‐like cells with large, oval nuclei and well‐developed endoplasmic reticulum; the cells were separated from each other by extracellular matrix containing small pieces of collagen and basal lamina‐like material. Dermal papille from both clinically normal and lesional alopecia areata follicles were less well organized and the dermal papilla cells exhibited signs of cell injury and contained abnormal amounts of pigment; an increased concentration of fibrous material in the extracellular matrix and thickening of the dermal papilla‐epithelial junction were also seen. Follicles from lesional areas showed more pronounced changes than clinically normal ones.Ultrastructural abnormalities in the dermal papillae of clinically normal scalp follicles support the study of these follicles as a prime research target. The changes detected suggest that dermal papilla cells in alopecia areata would be less able to synthesize regulatory factors and that these may have more difficulty crossing into the epithelial compartment. They are consistent with an early pathological role for the dermal papilla in alopecia areata, but do not distinguish whether this is a primary aetiological role or a secondary response to an insult elsewhere in

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb01148.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryAlopecia areata (AA) is a putative autoimmune disease in which anagen hair follicles are the target of immune cell attack. While both CD4+and CD8+T lymphocytes are prominent in the infiltrate, their respective roles in the pathogenesis of AA remain unknown. Here we directly investigated the activity of CD8+cells in the inhibition of hair growth using the Dundee experimental bald rat (DEBR) model for AA. Eight lesional DEBRs were fully depleted of their CD8+cells by intraperitoneal injection of OX‐8 monoclonal antibody (MoAb) specific for these cells over a 15‐day therapy course. A control group of eight lesional rats was injected with the irrelevant MoAb OX‐21. Sequential blood samples were analysed by flow cytometry to observe changes in the CD8+cell population and macropliotography used to record changes in hair growth activity.All eight CD8+depleted rats started to regrow hair within 29 days from the start of treatment, the tinal response ranging from sparse regrowth to a near normal coal. While two rats maintained their new pelage, the remainder lost hair as the CD8+population in peripheral blood increased. Two of the control rats also showed hair regrowth over the experimental period of 156 days. These results suggest that CD8+cells play an active part in the pathogenesis of AA. As hair production did not fully recover in all animals, immune mechanisms other than CD8+cells may be involved in effecting hair loss. However, analysis of CD8+cell levels in the skin of CD8+depleted rats may help resolve their full importance

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb01149.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryAlthough a principal constituent of human skin, cutaneous water is difficull to sttidy. and litlle is known about water behaviour in physiological and pathological conditions of Ihe skin. It has heen proposed recently that changes in dermal echogenicity measured hy high‐frequency ultrasonography reflect changes in dermal water content. To validate skin ultrasonography for assessment of dermal water changes we have studied the relationship hetween dermal echogenicity and skin water content determined hy nuclear magnetic resonance technique. Twenty MHz ultrasovmd scanning of the dorsal and ventral forearm skin was performed in 59 healthy volunteers (age 18–65) and dermal echogenicity was determined by counting low echogenic pixels (LEPs) in skin images,1H magnetic resonance spectra were obtained from the same regions and the ratio of areas under the water‐ and fat‐specific peaks (W/F) were calculated to measure a relative water content. Acute dermal oedemn (histamine weal) was studied in the same way in 40 individuals. Baseline dermal echogenicily correlated significantly with W/F. both in the ventral (r=0.47l and dorsal (r = O.57) forearm, lntradennal application of histamine caused a development of intradermal oedema which could be visualized by nuclear magnetic resonance imaging. In a corresponding ultrasound image oedema was seen as a low‐echogenic area. The proportional increases in LBPs and W/F after histamine application were correlated, but the elevation in LEPs was 25–48% (95% contidence intervals) higher than that for W/F. These results suggest that high‐frequency ultrasonography is a sensitive method for assessment of changes in dermal hydration. This technique may find important applications in comparative and non‐invasive evaluations of dermal water in physiological conditions and in skin pathologies associated with o

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb01150.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryHypersensitivity to topical corticosteroids is a common cause of allergic contact dermatitis. The deveiopment of contact allergy is dependent on individual susceptibility, exposure to the potential allergen and the ability to penetrate the epidermis and react with epidermal protein. We looked at corticosteroid binding to arginine and relative usage of corticosteroids to see if these variables explain the number of allergic reactions seen to these structurally similar chemicals. A linear relationship was found between a measure of corticosteroid binding to arginine, the log of relative corticosteroid usage and the log of the relative number of corticosteroid allergies. Using multiple regression this association was significant (P = 0.01). Statistically, these two variables accounted for 73% of the variation in the results. Our results showed that the number of corticosteroid allergic reactions was dependent on usage and the intrinsic ability of the corticosteroid to degrade and bind to arginine. While total corticosteroid usage is unlikely to change, the prescription of individual corticosteroids with a reduced potential to degrade and bind to protein, but with equal efficacy, might reduce the overall prevalence of corticosteroid hypersensitivity.

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb01151.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryWe assessed the polymerase chain reaction (PCR) technique to detectMycobacterium tuberculosiscomplex DNA In 48 paraffin‐embedded specimens from 32 patients with different variants of cuttineous tuberculosis, and compared the resuts with those of culture. A 123 bp product of the 1S6110 insertion sequence specific ofM. tuberculosiscomplex was amplified and confirmed by digestion with Sall restriction endonuclease. The time required for the procedure was 3 days. Thirty‐seven samples (77.1%) were positive forM. tuberculosiscomplex DNA. No false positive results were obtained in nine negative controls, Of the 20 specimens tested by PCR and culture, the frequency of positivity was 90% for DNA amplification and 65% for culture. In seven cases of lupus vulgaris, the figures were 100% and 57% respectivety. In the 11 specimens culture negative or not microbiologically tesled and PCR negative, evidence for tuberculous infection was provided hy the correlation of various relative fmd absolute criteria. These results show that PCR amplification of the IS6110 insertion fragment is a rapid and accurate means for the detection ofM. tuberculosiscomplex DNA in paraffin‐embedded skin biopsies from patients with cutaneous tuberculosis, especially in paucibacillary le

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1996.tb01152.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY