Role of tyrosinase as the determinant of pigmentation in cultured human melanocytes.

Variations in human pigmentation among different racial groups are due to differences in the production and deposition of melanin in the skin. Although melanin synthesis is known to be controlled by the rate-limiting enzyme tyrosinase, the role of this enzyme as the principal determinant of skin pigmentation is unclear. Results from studies with human melanocyte cultures derived from different racial skin types reveal an excellent correlation between the melanin content of melanocyte cultures and the in situ activity of tyrosinase. Melanocytes derived from black skin have up to 10 times more tyrosinase activity and produce up to 10 times more melanin than melanocytes derived from white skin. However, the higher level of tyrosinase activity in melanocytes derived from black skin is not due to a greater abundance of tyrosinase. Results from immunotitration experiments and Western immunoblots reveal that the number of tyrosinase molecules present in white-skin melanocytes may equal the number found in highly pigmented black skin types. Moreover, approximately equivalent levels of tyrosinase mRNA are present in white and black skin cell strains. In contrast, melanocytes derived from red-haired neonates with low tyrosinase activity contain low numbers of tyrosinase molecules and low levels of tyrosinase mRNA. These results show that tyrosinase activity and melanin production in most light-skinned people is controlled primarily by a post-translational regulation of pre-existing enzyme and not by regulating tyrosinase gene activity. In contrast, melanocytes from red-haired (type I) people have low levels of tyrosinase protein and mRNA, suggesting that transcriptional activity of the tyrosinase gene is suppressed.

The effects of scleroderma sera on endothelial cell survival in vitro.

The effects of sera and of platelet-poor plasma from patients with scleroderma on endothelial cell survival in vitro were studied. The survival ratio of rat heart endothelial cells was studied both in 10% test serum and in 10% platelet-poor plasma. Sera from patients with scleroderma decreased the survival ratio significantly when compared with sera from normal controls. In contrast, there was no significant difference between platelet-poor plasma from patients with scleroderma and that from normal controls. Our data indicate that platelets in the patients with scleroderma may cause vascular damage by affecting endothelial cell survival.

Penicillamine-induced degenerative dermatoses: report of a case and brief review of such dermatoses.

We describe a case of elastosis perforans serpiginosa with additional findings of degenerative skin changes. A 20-year-old man with hepatolenticular degeneration, under prolonged treatment with D-penicillamine, presented with a circular or serpiginous arrangement of nuchal papules. Histopathologically, transepidermal channels were accompanied by granulomatous reactions, with several giant cells engulfing elastic fibers. In addition to these findings of a typical elastosis perforans serpiginosa, we observed scar-like skin changes inside the circular arrangement of the papules. At the scar-like tissue, we found electron-microscopical evidence of randomly aggregated thin collagen fibers with no tendency toward systemic combined bundle formation, which is a characteristic feature of normal collagen fiber formation. Pseudoxanthoma-elasticum-like changes were observed on his neck. On his axillae and groin, slight skin thickening and wrinkling were detected. The diagnosis of elastosis perforans serpiginosa does not represent all of the manifestations or the pathological background described above. The skin manifestations described here represent not only an elastosis but also a total degenerative dermatosis with overhealed collagenosis. Thus, those dermatoses should be summarized as one entity, penicillamine-induced degenerative dermatosis. After considering the pathogenic background and clinical similarities, we further propose to simplify the penicillamine-induced skin manifestations to three categories: acute sensitivity reactions, bullous dermatoses, and degenerative dermatoses.

Histiocytic necrotizing lymphadenitis (Kikuchi's disease): the necrotic appearance of the lymph node cells is caused by apoptosis.

We report a case of histiocytic necrotizing lymphadenitis in a 28-year-old woman. The biopsy specimen of the enlarged lymph node showed lymphocytes, histiocytes, and a large amount of nuclear debris as well as marked eosinophilic deposits. We found DNA fragments by means of the modified TUNEL method, especially in the transitional area between intact cells and the foci of eosinophilic deposits and the cells positive for anti-Fas antibody in the biopsied lymph node. Therefore, the necrotic appearance of the lymph node was thought to be caused by apoptosis induced by the Fas-Fas ligand system. We hypothesize that the apoptosis was strongly related to the pathogenesis of this disease.

Long-term follow-up study of onychomycosis: cure rate and dropout rate with oral antifungal treatments.

The "complete cure" of onychomycosis requires long-term treatment with a systemic antifungal agent. Therefore, to properly assess the effects of an antifungal agent on onychomycosis requires a long follow-up. We have conducted a retrospective analysis of the patients treated with griseofulvin (GRF) from 1962 to 1992 and a clinical study to compare the long-term effect of GRF with that of a new oral antifungal agent, itraconazole (ITCZ), for patients who received treatment from 1992 to 1995. For the retrospective study, 281 patients who were microscopically diagnosed as having onychomycosis at the Department of Dermatology, Faculty of Medicine, University of Tokyo, and received GRF administration in 1962, 1972, 1982, and 1992, were evaluated for cure rate and dropout rate. The total cure rate was 29.2%, but the cure rate was 68.8% for the patients who continued their medication for more than one year. For the comparative study, 139 patients who received the treatment at the same institution between 1992 and 1995 were evaluated. The cure rate and the dropout rate for GRF were found to be 23.8% (23/97) and 52.6% (51/97) respectively. The cure rate and the dropout rate for ITCZ were found to be 50.0% (21/42) and 38.1% (15/42). When the two treatment protocols were compared for their long-term effects, we found that most of the patients treated with ITCZ were cured within 3 years, and about 30% of the patients treated with GRF remained uncured even after long-term administration of the agent. Furthermore, from a multiple regression analysis, the GRF/ITCZ administration required to cure onychomycosis was estimated to be 3.92 + 0.161 [Age (years)] + 0.635 [Number of infected toenails] months. The results of this study suggest that the biggest problem associated with the treatment of onychomycosis with an oral antifungal agent is compliance in long-term therapy. Notably, the final cure rate of ITCZ therapy went over 90%, suggesting that the low dose continuous therapy, the standard treatment protocol in Japan, was a key contributing factor for the higher cure rate for ITCZ.

Bilateral periorbital eccrine hidrocystoma.

We saw four patients showing identical features as cystic lesions on the bilateral external canthi. Histological examination showed cystic cavities in the dermis. Histological and enzyme histochemical findings suggest that these cystic tumors are of eccrine origin. Thus we diagnosed these cystic tumors as eccrine hidrocystoma with characteristic clinical feature. The recognition of this feature would help to correctly diagnose these eccrine hidrocystoma.

Systemic elastolytic granulomatosis with cutaneous, ocular, lymph nodal, and intestinal involvement. Spectrum of annular elastolytic giant cell granuloma and sarcoidosis.

A 15-year-old Japanese girl had widespread annular serpiginous erythematous plaques, bilateral granulomatous uveitis, bloody diarrhea, and seronegative arthralgia. She also had anemia and leukopenia. The histopathologic findings were compatible with those of annular elastolytic giant cell granuloma. Elastolytic granulomas were also found in the cervical lymph nodes, terminal ileum, parietal peritoneum, and mesentery. Bilateral hilar lymphadenopathy, hypercalcemia, and an increased level of angiotensin converting enzyme were not observed throughout the clinical course. To the best of our knowledge, systemic elastolytic granulomatosis has not been previously described in annular elastolytic giant cell granuloma or sarcoidosis. This case may represent a type of granulomatosis in the broad spectrum of annular elastolytic giant cell granuloma and sarcoidosis.

Case report. Onychomycosis due to Chaetomium globosum successfully treated with itraconazole.

We have experienced a case of toenail infection caused by Chaetomium globosum which we treated with itraconazole 100 mg day-1 for 6 months, after which time the nail lesions were almost cured. Our case is the first reported case of onychomycosis caused by Ch. globosum in Japan, and the seventh in the world.