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Notizen: A 73-year-old man with angiosarcoma of the scalp died about 1 year after disease onset, despite systemic and topical administration of recombinant interleukin-2. Histopathology showed typical changes of endothelial cells with very sparse lymphocytic infiltration into the tumour. An autopsy revealed that the primary site penetrated cranial bone and invaded vertically into the subarachnoid space. Multiple metastases to lung, chest wall, vertebrae and ribs were also found. On immunofluorescence staining, the expression of vascular endothelial cadherin, which is present in normal endothelium, was absent from both primary and metastatic sites. This may have promoted local invasion and metastasis.

Notizen: 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.

Notizen: Summary DNA-ploidy in primary cutaneous squamous cell carcinomas which had developed from different preceding clinical lesions was examined by flow cytometry using paraffin-embedded blocks. DNA-aneuploidy was detected in none of 15 squamous cell carcinomas arising from a burn scar. On the other hand. 12 of 26 squamous cell carcinomas arising from sun-damaged skin in the elderly, and two of four arising from chronic radiodermatitis, showed aneuploid patterns. A significantly higher incidence of DNA-aneuploidy was observed in squamous cell carcinomas arising from sun-damaged skin than those from a burn scar (P 〈 0.01): the mean diameter size of the former was significantly smaller than that of the latter (P 〈 0.0001). The mean age of patients with aneuploid tumours (74·2 ± 9·2: years ± standard deviation (SD)) was significantly higher than that with diploid tumours (64·1 ± 13·8) (P 〈 0〈01).

Notizen: Background  The epidermis, which is a typical stratified epithelium, has tight junctions (TJs) in the granular layer, as do simple epithelia. So far, abnormalities of TJs and involvement of claudin-1 have been reported in tumours of simple epithelia.Objectives  To examine the expression of TJ-associated proteins (occludin, ZO-1, claudin-1 and claudin-4) in normal human epidermis and in malignant disorders of keratinization.Methods  Expression of the proteins in normal human epidermis, five cases of squamous cell carcinoma (SCC) of the skin and five cases of Bowen's disease (BD) was examined by immunofluorescence staining.Results  In normal human epidermis, occludin, ZO-1 and claudin-4 were expressed at the cell–cell borders in the granular layer specifically or dominantly, whereas claudin-1 was expressed in the whole epithelium. In SCC, occludin, ZO-1, claudin-1 and claudin-4 were strongly expressed in tumour cells with keratinization such as cancer pearls. Claudin-1 was heterogeneously expressed in unkeratinized tumour cells, whereas expression of occludin, ZO-1 and claudin-4 was decreased or absent. In BD, aberrant expression of occludin, ZO-1, claudin-1 and claudin-4 was observed at the cell–cell borders in addition to their expression patterns observed in normal epidermis.Conclusions  Expression of occludin, ZO-1 and claudin-4 is associated with keratinization in SCC and BD. However, the heterogeneous expression of claudin-1 in SCC is not determined only by keratinization.

Notizen: Background: The symptoms of a 56-year-old man with systemic mastocytosis became worse with exposure to sunlight. We evaluated mast-cell-derived mediators and cytokines before and after exposure to ultraviolet light in the patient. Methods: The patient was irradiated with middle-wave ultraviolet light, so-called ultraviolet light B, and the levels of mediators and cytokines were measured serially. The point mutation Asp816Val in c-kit was investigated by analyzing polymerase chain reaction products from the complementary DNA of peripheral blood mononuclear cells. Results: Before irradiation, the levels of mast-cell-derived mediators and metabolites were elevated. Among various cytokines measured, including soluble c-kit and stem cell factor, only the level of nerve growth factor was elevated. After irradiation, the nerve growth factor level was further increased along with the levels of mast-cell-derived mediators and metabolites. The point mutation Asp816Val in c-kit was not detected in peripheral blood mononuclear cells. Conclusions: Middle-wave ultraviolet light may activate mast cells to release nerve growth factor and mediators in systemic mastocytosis.

Notizen: KleinJan et al, (Allergy 1996;51:614-20) reported that Carnoy's fixative reduced the number of chymase-positive mast cells in the nasal mucosa. Therefore, in the present study, we investigated whether Carnoy's fixative reduces the number of chymase-positive cells from cord-blood-derived human cultured mast cells when compared with other types of fixatives. Human mast cells were obtained by culturing cord-blood-derived CD34-positive cells in the presence of stem cell factor and interleukin-6. Staining procedures of the cells in fixation with Carnoy's fixative and with other fixatives gave no differences among the number of tryptase-positive cells, whereas fixation with Carnoy's fixative for 15 min gave a significant decrease i n the number of chymase-positive cells compared with acetone for 10 min. The number of chymase-positive cells decreased in a time-dependent manner under fixation with Carnoy's fixative, indicating that Carnoy's fixative had a negative effect on the number of chymase-positive cells from cord-blood derived human cultured mast cells.

Notizen: Rat peritoneal mast cells purified on a Percoll gradient were loaded with the fluorescent Ca2+ indicator fura-2 and were challenged with different concentrations of substance P (SP), and intracellular calcium concentrations ([Ca2+]i) were measured by a spectrofluorometric assay. SP at 5 × 10−6 mol/1 and 10−5 mol/1 caused a significant histamine release with a significant increase in [Ca2+]i in a dose-dependent manner. However, SP at 10−8-10−6 mol/1 did not induce either histamine release or increase in [Ca2+]i. Extracellular calcium at 0.9 mM inhibited the histamine release with a significant reduction of [Ca2+]i compared with that of the cells in a nominally calcium-free condition. These results indicate that the action of SP on rat mast cells relies upon [Ca2+]i to induce histamine release.

Notizen: Background The mtist cell is one of the important cells In the pathogenesis of allergic disorders. However, isolating human mast cells is a laborious procedure. Recently, cultured human mast cells raised from umbilical cord blood cells have become available. It is necessary to examine whether these cells are useful in investigating the role of mast cells in human diseases.Objective The phenotype of mast cells depends on their anatomical sites. To examine which phetiotype of mast cells these cultured mast cells most closely resemble, their ability to release was investigated.Methods The mast cells were raised from human umbilical cord blood cells in the presence of stem cell factor and interIeukin-6. To determine the mast cell subtypes, the mast cells were immunocytochemically stained for tryptase and chymase. The cultured mast cells were then stimulated with various secretagogues, and histamine release was measured by a fluorometric technique using high-performance liquid chromatography. Results The immunocytochemical staining for mast cell proteases revealed that virtually all cells contained tryptase, the definitive marker of mast cells, and that about a quarter of the cells contained chymase. Anti-TgE effectively stimulated these mast cells to release histamine in a dose-dependent, lime-dependent manner. The release was completed in about 30 min. One of the non-specific stimuli, calcium ionophore A23I87. also induced histamine release in a dose-dependent, time-dependent manner. In contrast, compound 48/80 and substance P failed to induce histamine release from these cells. Conclusion Cultured human mast cells resemble lung mast cells in their ability to release histamine. They will help in studying the functional properties of human mast cells and may contribute to clarifying the pathophysiology of human allergic diseases.