摘要:

SummaryErythropoietic protoporphyria (EPP) is an inherited inborn error of porphyrin metabolism caused by decreased activity of the enzyme ferrochelatase, the terminal enzyme of the haem biosynthetic pathway, which catalyses the insertion of iron into protoporphyrin to form haem. EPP is characterized clinically by photosensitivity to visible light commencing in childhood, and biochemically by elevated red cell protoporphyrin levels.Although the majority of papers and reviews have classified EPP as an autosomal dominant disorder, the inheritance has now been shown to be more complex, and both autosomal dominant and recessive patterns of inheritance have been demonstrated using ferrochelatase activity. Further molecular studies should clarify the exact mode of inheritance. It seems likely that in the majority of families a defective allele from the apparently normal parrent will be required for disease expression, but another possibility is autosomal dominant inheritance with low clinical penetrance.Exposure to bright sunlight, for as little as a few minutes in the worst affected patients, causes burning pain in exposed skin, which may be so severe and persistent that it prevents sleep for several nights. Patients usually attempt to relieve the pain by cold water or cold compresses. Apart from sun avoidance, the mainstay of prophylactic treatment has been β‐carotene. Although the published evidence for the effectiveness of β‐carotene is impressive, no controlled trials using adequate doses have been performed to unequivocally confirm its usefulness.The most serious complication of EPP is acute hepatic failure, which is due to accumulation of protoporphyrin in the liver. If jaundice develops, a rapidly fatal outcome often follows, unless liver transplantation is undertaken. Regular monitoring of liver function and red cell porphyrin levels is advisable, but this does not always identify patients before serious liver damage has occurred. Even when patients are identified at an early stage in the development of liver disease the therapeutic options available to prevent further damage are limited, and have not been fully evaluated.The gene for ferrochelatase has been cloned, sequenced and mapped to the long arm of chromosome 18. As mutations continue to be identified, phenotype/genotype correlations should become apparent, and it may eventually be possible to identify those patients at risk of developing hepatic failure. In addition, as the basic enzymatic defect in EPP is at the level of the bone marrow stem cells, which are the target cells of choice in the development of retroviral‐mediated gene transfer, definitive treatment of EPP by gene therapy is a distinct hope for the future. Furthermore, the production of a mouse model for EPP, in which the molecular defect has been identified, means that gene therapy can be attempted first in

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb08577.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryTo evaluate the role of filaggrin in keratin filament aggregation in epidermolytic ichthyosis (epidermolytic hyperkeratosis, EH), we studied EH skin by light and electron microscopic immuno‐histochemistry, and biochemical analysis using sodium dodecylsulphate‐polyacrylamide gel electrophoresis and immunoblotting. Immunohistochemical staining showed an increased number of filaggrin‐immunoreactive cell layers, but the reaction was still confined to the mid‐ and upper epidermal layers, whereas an abnormal granular pattern of staining for K10 began in the lower suprabasal cell layers. This suggests that the aggregation of kertain filaments precedes, and occurs independently of, profilaggrin synthesis during epidermal differentiation. Although keratohyalin granules were frequently associated with clumped filaments, immunoelectron microscopy showed that K10 labelling was confined to keratin filaments (including clumped filaments), and that antifilaggrin antibodies stained only keratohyalin granules, at least in the living cells. Certain keratin aggregates in the cornified cells were still devoid of filaggrin staining. However, in some cells which appeared partially cornified, filaggrin immunoreactivity occurred over the aggregated keratin filaments. Immunoblotting showed a clear increase of filaggrin/profilaggrin expression, without evidence for a qualitative abnormality. It seems unlikely, therefore, that filaggrin is primarily involved in the keratin filament clumping in EH, but that in some EH cases it interacts with keratins in a defective manner, possibly due to premature cell death and profilaggrin processing and/or altered keratin filament structure involving the interaction points of keratin with fi

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb08578.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryCD1+antigen‐presenting cells in involved epidermis of patients with cutaneous T‐cell lymphoma exhibit an enhanced functional capacity to activate autologous CD4+T cells compared with CD1+antigen‐presenting cells from uninvolved and normal epidermis. Class II major histocompatibility complex molecules are involved in antigen presentation, and their expression on CD1+Langerhans cells is known to vary. The expression of all three class II (HLA‐DR, ‐DQ, ‐DP) molecules was therefore determined on CD1+epidermal cells from both involved and uninvolved epidermis, using flow cytometry. The involved CD1+epidermal cells exhibited a 1.5–1.6‐fold, statistically significant increase in fluorescence intensity after staining of the class II molecules (HLA‐DR, ‐DQ, ‐DP) compared with CD1+epidermal cells from uninvolved epidermis. The autologous CD4+T‐cell activation was almost completely blocked by anti‐HLA‐DR, and partly by anti‐HLA‐DQ and anti‐HLA‐DP.In contrast, an antibody against class I, and an irrelevant control antibody, had no blocking effect. In a pokeweed mitogen assay it was demonstrated that autologous CD4+T cells, activated by involved epidermal cells, demonstrated suppressor activity rather than helper activity. The suppressor activity was dependent on the presence of HLA‐DR‐positive epidermal cells. Thus, in cutaneous T‐cell lymphoma, class II molecules on the individual CD1+antigen‐presenting cell are upregulated in clinically involved compared with uninvolved epidermis, and these molecules are cruc

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb08579.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryRecent research observations suggest that the keratoacanthoma (KA) is a form of resolving squamous cell carcinoma (SCC). The mechanism by which this resolution takes place has not been fully explored, although it may have an immunological basis. To investigate this, we compared 15 clinically and histologically diagnosed KAs and 15 SCCs with regard to cellular infiltrate and keratin expression. We found that KAs have significantly higher numbers of CD3+and CD4+cells invading their epidermal component than SCCs. The lymphocytes infiltrating KAs were more immunologically active, as greater numbers expressed the interleukin‐2 receptor (IL‐2R) than those in SCCs. It is of interest that CD36 was expressed by a significantly greater proportion of tumour cells within KAs than SCCs. This was also the case for the intercellular adhesion molecule ICAM‐1, and the differentiation marker keratin 10. Overall, these findings suggest that KA regression is immunologically mediated, with activated (IL‐2R+) CD4+T lymphocytes and adhesion molecules playing a pivotal role in the immune r

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb08580.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryDespite light and electron microscopic and histochemical studies, there is no consensus on the cellular differentiation of eccrine spiradenoma. In the present study, eight specimens of eccrine spiradenoma were analysed by immunohistochemical techniques, using a panel of monoclonal antibodies against cytokeratins. Two types of epithelial cells were identified in tumour nodules: large, pale epithelial cells in the centre, and small, dark epithelial cells situated at the periphery. These nodules frequently contained tubular structures lined by cuboidal, columnar or, less commonly, flattened epithelial cells. Cytokeratin expression in eccrine spiradenoma was compared with expression in normal eccrine glands. Immunohistochemistry revealed that large, pale epithelial cells expressed immunophenotypes similar to those of luminal cells in the transitional portions between the secretory portions and the coiled ducts. The small, dark cells expressed immunophenotypes similar to those of basal cells in the transitional portions. Tubular structures observed in eccrine spiradenoma showed staining patterns similar to those of the luminal cells in the transitional portions. Eccrine spiradenoma may, therefore, differentiate towards the transitional portions between the secretory portions and colled ducts of eccrine glands. Some of the large, pale epithelial cells in eccrine spiradenoma differentiate towards tubular structures, forming a lumen lined by a cuticle.

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb08581.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryWe have investigated markers of epidermal proliferation and differentiation in terms of keratin expression, the morphology of the cutaneous vasculature, and numbers of cutaneous mast cells, in patients with chronic plaque psoriasis. Using the phenomenon of the ‘active edge’, we have studied these features in the psoriatic plaque itself, and in the clinically normal active and inactive edges of the same plaque. Our results confirm the anticipated changes in keratin profiles, mast cell numbers and psoriatic morphology of the vasculature within the plaque itself. They further indicate that the vascular changes precede the epidermal and mast cell features at the active edge, and that the inactive edge is inactive for all of these variables. Mediators responsible for the vascular proliferation and elongation must be present in increased amounts at the active edge when compared with the inactive, and include locally produced and circulating fact

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb08582.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryCellular changes were immunocytochemically characterized in skin vessels of five patients with idiopathic generalized racemose livedo (Sneddon's syndrome), and one patient with localized racemose livedo associated with essential thrombocythaemia. Antibodies against α‐smooth muscle‐actin, tropomyosin, desmin, vimentin, factor VIII‐related antigen, human endothelial cells (CD31), human macrophages (CD68), and HLA‐DR positive cells (CR3/43) were used. Conventional light microscopy showed, in all cases, intimal thickening of ascending arteries and arterioles as a result of an accumulation of cells and extracellular hyalinized material. None of the specimens showed infiltration with polymorphonuclear leucocytes or macrophages. The cells in the region of the intimal hyperplasia showed intense positive immunostaining for α‐smooth muscle actin and tropomyosin. Staining for the intermediate filament desmin was localized to the resident smooth muscle cells of the media, whereas staining for vimentin was found in all types of cells in both the intima and media. Positive immunostaining for factor VIII‐related antigen and CD31 was strictly confined to the endothelial cells lining the narrowed lumina of the vessels. No positive staining with either antibody was observed in totally occluded vessels. Cells in the subintimal space did not show reactivity for CD68 in any of the specimens, but two cases showed solitary cells with positive staining for HLA‐DR in this region. There were no differences in staining pattern between Sneddon's syndrome and essential thrombocythaemia with any of the antibodies. Our results support the assumption that the ‘intimal proliferation’ in both diseases is caused by colonization of the subendothelial space with contractile cells of possibel smooth muscle origin. The similarities in histopathology and immunocytochemistry might indicate that in both diseases platelet‐derived factors

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb08583.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryTen patients with dermatitis herpetiformis had biopsies taken from involved skin.Monoclonal antibodies and the avidin‐biotin peroxidase staining technique were used to stain for T cells and Langerhans cells in skin sections. A significant increase in the number of CD3‐positive T cells was observed in the upper dermis of involved compared with uninvolved skin (P<0.0005). Most of the T cells in involved skin were CD45RO‐positive memory cells; CD4‐positive T cells exceeded the number of CD8‐positive T cells by a ratio of 4:1. In addition, CD1a‐positive dendritic cells were observed within the clumps of T cells in involved dermis in nine of the 10 patients, but were absent from the dermis of uninvolved skin. Double immunofluorescent staining demonstrated that approximately 20–40% of the CD3‐positive T cells were activated, and expressed the HLA‐DR antigen.These findings suggest that activated T cells are involved in the pathogenesis of dermatitis herpetifo

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb08584.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryCultured skin equivalents were constructed by combining keratinocytes, outer root sheath cells or isolated epidermis,in vitro, with a matrix composed of collagen and cultured fibroblasts. When equivalents were grafted on to host animals, the epidermis thickened considerably, and tongues of cells penetrated the dermis, giving the dermal/epidermal junction a deeply sculptured profile. No cutaneous appendages were found in these grafts. We explored the possibility of inducing hair follicles by incorporating ovine hair follicle dermal papillae into constructs composed of an isolated epidermal sheet and a contracted dermal equivalent.In vitro, no morphogenetic changes associated with follicle formation were observed in the recombinants, but when grafted on to nude mice, follicle‐like structures were identified. The follicles were large, and had developed adjacent to the epidermis, indicating that the matrix environment of the induced follicles may not have been compatible with the downgrowth of the epidermal plugs normally observed during follicle formation in living skin. Nevertheless, in histological sections, the induced structures displayed many of the morphological characteristics of folliclesin vivo, including the production of keratinized hairs. These results indicate that skin equivalents provide a useful model for the study of the chemical and structural features of matrices that facilitate hair follicle developmen

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb08585.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryThere is indirect evidence that both skin and hair melanocytes are regulated by the activity of adjacent cells. In hair, the specialized fibroblasts (dermal papilla cells) appear to play a role in the regulation of hair growth. Hair pigmentation may relate to hair growth. In skin, melanocytes are located adjacent to the basement membrane zone. As far as we are aware, direct interactions of fibroblasts with melanocytes have not previously been investigated. Accordingly, the objective of this study was to develop co‐culture conditions in which to investigate whether dermal fibroblasts from skin or hair could influence melanocyte differentiation. The influence of fibroblast‐conditioned media, co‐culture with fibroblasts, and fibroblast‐derived extracellular matrix (ECM) on normal human skin melanocyte tyrosinase activity was examined. Fibroblasts from both skin and hair were capable of altering melanocyte morphology and significantly increasing tyrosinase activity when melanocytes were cultured in the absence, but not the presence, of the major proliferative drives. Although stimulation of tyrosinase activity was detectable with conditioned medium and co‐culture with fibroblasts, the most striking result was obtained with the fibroblast‐produced ECM which, on average, produced a four‐fold increase in tyrosinase activity within 6 days. Thus, the study describes co‐culture conditions in which the stimulatory effect of the fibroblast on melanocyte differentiation

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb08586.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY