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Notes: 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.

Notes: Serum levels of squamous cell carcinoma-related antigen (SCC-RAG) were measured in five cases of pemphigus, five cases of bullous pemphigoid and 18 cases of benign and malignant dermatoses other than SCC. The SCC-RAG titres were significantly raised in four of five patients with pemphigus, while they remained within the normal range in the other dermatoses except in one case. In three pemphigus cases in whom serial measurements were made, SCC- RAG levels seemed to be related to disease activity. The SCC-RAG levels in blister fluids were much higher than those in serum, suggesting that the skin is a major source of serum SCC- RAG.These results show that SCC-RAG is increased not only in SCC, but also in some cases of pemphigus, and suggest that pemphigus antibodies may cause the production or release of SCC-RAG.

Notes: We describe a patient in whom a suppressor/cytotoxic T cell lymphoma was suspected on the basis of histology and immunohistochemistry. DNA analysis of specimens from three different lesions, using restriction enzymes Eco RI and Bam HI, showed the same rearrangement of the T cell receptor β-chain genes. We consider this technique to be of value in the early diagnosis of malignant lymphoma when differential diagnosis from other lymphoproliferative disorders is difficult with conventional methods.

Notes: The anti-oxidant efficacy, in vitro, of the gold compounds auranofin (AF) and gold sodium thiomalate (GST) was examined by studying their effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leukocytes (PMNs) and a cell-free, xanthine-xanthine oxidase system. The oxygen species investigated were the superoxide radical anion (O2−) hydrogen peroxide (H2O2) and the hydroxyl radical (OH·).AF had an inhibitory effect on ROS production by PMNs. In particular, OH· generation was significantly suppressed in a dose-dependent fashion. AF did not inhibit ROS production in the cell-free system. GST produced only a small degree of inhibition at higher concentrations.These findings suggest that AF may play an important role in the inhibition of respiratory bursts and the generation of inflammatory reaction products. Since the products of the respiratory burst, especially potent oxidants such as OH· and H2O2, are thought to be important inflammatory mediators, it is postulated that the blockade of toxic ROS generation by AF affects rheumatoid as well as dermatological inflammation and tissue damage.

Notes: To elucidate the mechanism of action of metronidazole in the treatment of rosacea, the effect of metronidazole on the generation of reactive oxygen species was examined both in neutrophil and xanthine-xanthine oxidase systems. Metronidazole had anti-oxidant action which was not exerted by the scavenging of reactive oxygen species, but by having an effect on neutrophil cell functions. Beneficial effects of metronidazole in the treatment of papulopustular rosacea can in part be attributable to this anti-inflammatory effect.

Notes: The effects of potassium iodide, colchicine and dapsone on the in vitro generation of polymorphonudear leukocyte (PMN)-derived oxygen intermediates were investigated. These three drugs have beneficial effects on those conditions in which PMNs play an important pathogenetic role. Three oxygen intermediates, superoxide anion (O2−), hydrogen peroxide (H2 O2), hydroxyl radical (OH·) and chemiluminescence were included in assay studies. Dose response studies were performed with therapeutic doses of the drugs (10 μM–1 mM). We found that both potassium iodide and dapsone significantly suppressed the generation of oxygen intermediates, except for O2−. Colchicine decreased OH · production.Our results show that these agents to some extent exert their anti-inflammatory effects by interfering with the PMN-dependent production of oxygen intermediates, thus conferring protection from auto-oxidative tissue injury. This may account for their clinical efficacy in many PMN-mediated dermatological diseases.

Notes: Background  The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by tumorigenesis such as multiple basal cell carcinomas, odontogenic keratocysts and developmental abnormalities such as calcified dural folds and rib-anomalies. Recently, it has been shown that ultraviolet (UV) B exposure produced more BCCs in ptch knockout mice than wild mice.Objectives  To Investigate the role of UV in development of BCCs in NBCCS, cellular sensitivity to killing by UVB and removal of UVB-induced oxidative DNA damage were examined using fibroblasts derived from patients with NBCCS under physiologically relevant doses of UVB exposure.Patients and methods  Three patients with NBCCS, a 59-year-old male patient, an 18-year-old boy and a 13-year-old boy were examined by photobiological analysis. Cellular sensitivity to killing by UVB and UVC and removal of oxidative DNA damage caused by UVB were tested using fibroblasts derived from these patients. We measured cellular 8-hydroxydeoxyguanosine (8-OHdG) after UVB exposure up to 24 h after UVB exposure using high-performance liquid chromatography.Results  All three cell strains derived from the patients with NBCCS were hypersensitive to killing by UVB (D10: 50–70% of normal) but not by UVC. After UVB exposure, the production of 8-OHdG increased dose dependently up to 3200 J m−2 in both NBCCS cells and normal cells. In normal cells, 8-OHdG after UVB exposure returned to its basal level during 24 h, whereas in NBCCS cells the amount of 8-OHdG after 800 J m−2 of UVB exposure did not return to its basal level even after 24 h. The result indicates the removal of 8-OHdG could be impaired in NBCCS cells. Ability in removal of thymine dimers of NBCCS cells was similar to that of normal cells.Conclusions  Hypersensitivity to UVB can be one of the diagnostic tools of NBCCS for those whose clinical features have not yet completed. Hypersensitivity to cell killing and the impairment of removal of 8-OHdG after UVB exposure may play some role in developing BCCs and other tumours in NBCCS.

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: 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).