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Notes: Two cases of Werner's syndrome are reported. Fibroblasts derived from both patients revealedreduced population doubling numbers. Chromosomal analyses for fibroblasts from both patients and lymphocytes from one patient revealed that chromosomal aberrations occur frequently and randomly. Although some of the chromosomal aberrations involved sites where tumour suppressor genes have been mapped, neither of our patients demonstrated malignancy. Chromosomal aberration at one critical site may not be sufficient to induce cancer or additional factors may be necessary.

Notes: E-cadherin is a major homophilic cell-cell adhesion molecule of the skin. There are two forms of E-cadherin—membrane and soluble types. Although various abnormalities of the former type have been identified in some cutaneous diseases, information relating to the latter is sparse. We measured the concentrations of soluble E-cadherin in several cutaneous diseases, and found higher levels in sera from patients with bullous pemphigoid, pemphigus vulgaris, psoriasis vulgaris and inflammatory skin diseases, compared with controls. In psoriasis vulgaris the levels of soluble E-cadherin in sera correlated with the PASI score. In normal individuals, levels in suction blister fluid were double those in sera. These findings suggest that changes occur in circulating levels of soluble E-cadherin in skin disease, possibly reflecting increased turnover and/or proteolysis of cell-surface molecules in the epidermis.

Notes: [Auszug] Exfoliative toxin A, produced by Staphylococcus aureus, causes blisters in bullous impetigo and its more generalized form, staphylococcal scalded-skin syndrome. The toxin shows exquisite specificity in causing loss of cell adhesion only in the superficial epidermis. Although exfoliative toxin A ...

Notes: Summary A 59-year-old male showed acquired. mechanically induced, scarring blisters on the fingers, toes, scalp and abdomen, as well as in the oral cavity. Ultrastructural and immunohistochemical examination of the bullae revealed junctional epidermal-dermal separation and lgG deposits in the lamina lucida of the basement membrane zone (BMZ). where the reactivity of the 19-DKJ-1 monoclonal antibody was decreased. Anti-BMZ autoantibodies detected in his serum were reactive to the lower lamina lacida region of normal human skin. SDS-PAGE of affinity purified antigens from human keratinocytes with IgG from the patient's serum revealed three polypeptide bands at 165, 135 and 1OO kDa. in reduced condition. The indirect immunofluorescence test of his serum was negative on skin cryosections from patients with lethal junctional epidermolysis bullosa. Pretreatment of normal human skin sections with the patient's serum, blocked the binding of 19-DEJ-1 monoclonal antibody but not that of the GB3 monoclonal antibody. This case is considered to be an acquired autoimmune bullous dermatosis due to an autoantibody reaction against uncein (19-DEJ-1 antigen). a component of anchoring filaments.

Notes: Summary  Background The most characteristic change in psoriasis vulgaris is markedly increased, persistent keratinocyte proliferation. The underlying mechanism of excessive epidermal growth is controversial. We previously found and reported that T-cadherin was expressed in keratinocytes and confined to the basal layer of mouse and human skin. Invasive cutaneous squamous cell carcinoma showed a loss of T-cadherin expression. Another study showed that T-cadherin was a negative growth regulator of epidermal growth factor in T-cadherin transfectant neuroblastoma cells.Objectives  To obtain insight into the role of T-cadherin in keratinocyte proliferation and to investigate further the pathogenesis of psoriasis vulgaris, we examined the expression of T-cadherin, as well as E- and P-cadherin, in psoriasis vulgaris.Methods  Four untreated active psoriatic skin samples from psoriasis vulgaris patients and four normal human skin samples from plastic surgery were collected, cryosectioned and immunohistochemically stained by antihuman T-, P- and E-cadherin antibodies. Further, the immunofluorescence intensities of T- and P-cadherin on the basal layer of the epidermis were quantitatively measured by the histogram function of LSM 510 software installed in a Zeiss laser scanning confocal microscope. The data were statistically analysed by Student's t-test.Results  It was observed that T-cadherin was weakly and discontinuously expressed on the basal layer of psoriatic skin, while it was intensively expressed on all basal keratinocytes in normal human skin. In contrast, P-cadherin was strongly expressed throughout the entire epidermal layer in psoriatic skin samples, although its expression is restricted to the basal cell layer in normal human skin. There were no obvious differences in E-cadherin expression between normal human skin and psoriatic skin. Statistical analyses showed that the immunofluorescence intensity of T-cadherin in the basal cell layer of psoriatic skin (35 ± 9·08) was significantly decreased compared with that in normal human skin (131·75 ± 3·49, P = 2·46 × 10−6). There was a significant increase (P = 0·00139) in the immunofluorescence intensity of P-cadherin in the basal layer of psoriatic skin (68·25 ± 12·13) compared with normal human skin (26 ± 4·90).Conclusions  The present study demonstrates that there is downregulation of T-cadherin expression and upregulation of P-cadherin expression in psoriatic skin, which are considered to be involved in the hyperproliferation of keratinocytes in psoriasis vulgaris.

Notes: Ultrastrutual, immunohistochemical and gene analytical studies were carried out on a 39-year-old patient with lymphomatoid papulosis. Two different cell groups were demonstrated in the papulonodular eruptions: large atypical cells with multiple nuclei that were well stained with anti-Tac, but not with Leu 3a, and other cells that possessed prominent hyperchromatic nuclei and which stained well with Leu 1 and Leu 3a but not with anti-Tac. Gene analytical studies using EcoRI, BamHI and HindIII revealed no rearrangement, indicating a non-clonal T-cell proliferation unlike malignant T-cell lymphoma. These results suggest that the present case was benign.

Notes: Summary Background A novel cell–cell adhesion system that consists of nectin and afadin has been identified at cadherin-based cell–cell adherens junctions. Nectin is a Ca2+-independent homophilic and heterophilic cell adhesion molecule that belongs to the immunoglobulin superfamily. Nectin has recently been shown to serve as an α-herpesvirus entry and cell–cell spread mediator. In spite of the ubiquitous expression of nectin-1α, its detailed localization in human skin has not been examined so far. Objectives To investigate the localization of nectin-1α in normal human skin and the alteration of its expression in malignant skin tumours. Methods Immunohistochemistry was employed to determine the expression of nectin-1α and other adhesion molecules. Results We detected nectin-1α in normal human epidermis, follicles and eccrine ducts. Nectin-1α was colocalized with E-cadherin at cell–cell adherens junctions of the epidermis. The concentration of the nectin–afadin system at cell–cell adherens junctions was reduced in the early stage of malignant transformation of keratinocytes, such as in basal cell carcinomas and squamous cell carcinomas, where the cadherin–catenin system was preserved. Nectin-1α at cell–cell adherens junctions was reduced in human epithelial cancer cells located at the advancing border of the tumour. Conclusions Our results showed that nectin-1α is located at cell–cell adherens junctions in human skin and that reduction of nectin-1α at cell–cell adherens junctions may be involved in the invasion of squamous cell tumours.