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We report the case of a Japanese female infant with Chédiak-Higashi syndrome born to consanguineous parents. At birth she had fair skin but, when she was three months old, marked hyperpigmentation of the sun-exposed skin areas developed. Microscopic examination of blood and electron microscopic examination confirmed the diagnosis. She enjoyed good health until she was two years old when she had pneumonia with marked hepatosplenomegaly. It is important for dermatologists and pediatricians to be aware of the skin manifestations of this disease because hyperpigmentation after sun exposure may be a characteristic, initial feature of this condition.

A patient with diabetes mellitus who developed the typical classic lesions of Kaposi's sarcoma is described. Our patient presented with a reddish-purple papulonodular lesion on the right foot of five months' duration. A skin biopsy specimen showed a proliferation of spindle cells forming numerous vascular slits and a diffuse extravasation of erythrocytes. The patient's sera was negative for human immunodeficiency virus (HIV) antibodies and cytomegalovirus (CMV) antibodies. Ultrastructural examination demonstrated fibroblast-like spindle cells phagocytosing and digesting red blood cells to form vascular spaces. The patient died, due to gastrointestinal hemorrhage, and the autopsy revealed an extensive visceral involvement of Kaposi's sarcoma.

Four types of fibroblastic cell lines at various stage of differentiation, which had been derived from syngeneic mice, were cultured in collagen lattices (reconstituted dermis model). Lattice contraction, growth in the lattice, and cell morphology were compared. The following cell lines were used: [I] precrisis cells within several subcultures derived from the skin of Balb/c mice, [II] an established normal cell line derived from syngeneic mice (Balb/3T3 clone A31), and [III] two transformed lines (Balb/3T12-3, 3T3-B-SV40) originating from [II]. The cells adopted a bipolar spindle form in the collagen lattice. Lattice contraction was the most marked with cell type [I] followed in order by [II] and [III]. Relative growth in the lattice occurred in the reverse order (III greater than II greater than I). These findings suggested a correlation between lattice contraction and growth in the lattice and also between the extent of differentiation and lattice contraction.

Human dermal fibroblasts were cultured in a hydrated type I collagen lattice. When collagen fibers were arranged in one direction, fibroblasts were arranged in the same direction. Cell proliferation was markedly suppressed in the collagen lattice as compared with that on plastic, with growth being arrested after day 5. No differences in proliferation were observed between aligned cells and randomly oriented cells. Flow cytometry with DNA staining was performed to analyze each phase of the cell cycle of fibroblasts. Among the 10,000 cell population, S phase cells on day 2 of culture accounted for 43% on plastic but were markedly inhibited to 25% in the lattice. On day 4, S phase cells accounted for 33% on plastic but only for 10% in the lattice. These findings suggest that cell advancement to the S phase is markedly inhibited in the collagen lattice, resulting in accumulation of most of cells in the G0G1 phase. The present study clearly showed that culture in the collagen lattice allowed alignment of fibroblasts with a definite orientation as observed in vivo and produced a status resembling that in vivo in terms of proliferation and cell cycle phase composition.

S-carboxymethylated (SCM) fibrous proteins (FPs) from the scalp hairs of the three different hereditary hair abnormalities (trichorrhexis invaginata in Netherton's syndrome, pili trianguli et canaliculi in uncombable hair syndrome, and fine hair in anhidrotic ectodermal dysplasia) were analyzed by two-dimensional polyacrylamide gel electrophoresis. Comparison of the SCM FP compositions of the three hair abnormalities with that of the normal revealed that the SCM FP compositions of these three abnormal hairs were all electrophoretically different from each other and that of the normal.

We report a 22-year-old man with acquired dermal melanocytosis on the hand which developed without any history of previous inflammation. He had no history of contact with or oral administration of any drugs or metals which might have caused pigmentation. Histopathologically, spindle-shaped dermal melanocytes were observed running parallel to the collagen bundles and scattered in all portions of the dermis. The dopa reaction of these cells was positive. Ultrastructurally, dermal melanocytes containing numerous melanosomes (stages II to IV) which were surrounded by the extracellular sheath were observed. Differential diagnosis of other dermal melanocytosis was discussed.

Ultraviolet-B and PUVA share several biological events with phorbol ester tumor promoters. The effects of ultraviolet-B irradiation and topical PUVA treatment on ornithine decarboxylase activity, DNA synthesis, and protein kinase C activity, which are known to be induced or activated by phorbol ester tumor promoter, were investigated in hairless mouse skin. Ornithine decarboxylase activity was remarkably enhanced by ultraviolet-B and PUVA. Although PUVA did not affect DNA synthesis significantly, ultraviolet-B stimulated epidermal DNA synthesis approximately 5-fold over control values at 48 h. However, unexpectedly, neither cytosolic nor membrane-bound protein kinase C activity showed any change during the 2 h after either treatment. These results suggest that the protein kinase C system is not involved in the initial signal transduction system of ultraviolet-B or PUVA, unlike the case with phorbol ester tumor promoter.

Melanoma cells were cultured on type I collagen gel, and the infiltration of of those cells into the gel was observed. B16 murine melanoma cells initially adopted a spherical form on the gel, but they assumed a dendritic form after infiltration into the interior. The degree of infiltration increased very rapidly and was time-dependent. No correlations between the growth rate or melanogenic activity and infiltrative potential were observed. When Syrian hamster and human melanoma cell lines were cultured, the degrees of infiltration varied. This culture system using collagen gel is considered to be a useful in vitro model of tumor cell invasion.

The effects of human recombinant tumor necrosis factor-alpha (TNF-alpha) on human keratinocytes cultured in a serum-free medium were investigated. TNF-alpha markedly suppressed cell growth. The growth-inhibitory effect was reversible and cytostatic at a concentration of 1-5 U/ml, but appeared to be irreversible and cytocidal at 10 U/ml. The growth suppressive effect was more marked when TNF-alpha was added in the late growth phase or preconfluent phase than when it was added in early or mid-growth phases. No effects of TNF-alpha on cell adhesion to the substrate were observed. These results indicate that TNF-alpha is a very potent anti-proliferative agent for human keratinocytes.

As the first step in developing an in vitro model of melanoma cells infiltrating the dermis, B16 murine melanoma cells were cultured on and in type I collagen gels. Under these conditions, the melanoma cell adopted an elongated or dendritic form. Cell proliferation was suppressed in the culture system using the collagen gel as compared with the conventional monolayer culture on plastic. Microcinematographically, this suppression was found to be due to an extension of the cell cycle time of each individual cell. On the other hand, there were no appreciable differences in proliferation pattern between the cells cultured on type I and IV collagen film and those cultured on plastic. These results suggest that there are interactions between type I collagen in the gel form and melanoma cells, especially with respect to cell growth.

An allergic drug eruption due to nitrazepam was reported in a patient who had been administered methotrexate and etretinate as concurrent therapies for severe pustular psoriasis. The clinical manifestation included a moon face-like appearance with edema, a diffuse erythematous rash over almost the entire body the day after taking nitrazepam and, two days later, eroded lesions developing on the cheeks, axillae and genitocrural regions. It was proved by provocation that this drug eruption had an allergic nature.

Unusual skin manifestations of a dermatophyte infection in a 30-year-old female were reported. These included a remarkable peripheral hyperkeratosis with central yellowish pus. The pinkish papillomatous lesions were covered with thick crusts. They gave off a foul smell. Abundant fungus elements were present in the crusts and keratotic layer. The trichophytin skin test was positive. Immunologic test results revealed that the patient had hypergammaglobulinemia with hypoalbuminemia. However, she had no edema or immunologic abnormalities. The skin lesions were successfully treated with topical miconazole cream, oral griseofulvin, and topical sulconazole cream. The etiologic agent was identified as Microsporum ferrugineum Ota 1922. It seemed to us that the unusual skin manifestation were induced by her immunological response to fungal and bacterial infection due to a long history of Candida granuloma.

Samples of normal human skin were obtained from 48 sites in 26 subjects ranging in age from 2 to 85 years. The samples were examined by indirect immunofluorescence and immunoelectron microscopy using anti-human type IV collagen antibodies produced by immunizing rabbits with type IV collagen extracted from human placenta. Fluorescence was observed as granular or fine fibrous patterns, not only in the basement membrane at the dermo-epidermal junction, around the vessels, and the accessory organs of the skin, but also in the dermal regions in the vicinity of the basement membranes. This suggests the presence of type IV collagen in the dermis deep to the basement membrane. Ultrastructurally, the extrabasal lamina distribution of type IV collagen was noted as a partial distribution around the fibroblasts that existed close to the basal lamina. These findings are considered to be important in examining the function of this collagen in the dermis and the dynamics and metabolism of the basement membrane under normal and abnormal conditions.

When cafe au lait spots or pigmented nevi were combined with Mongolian spot lesions, whitish haloes were observed in the areas surrounding these cafe au lait spots and pigmented nevi. The pathogenesis of this halo-like phenomenon was investigated. The materials were two Japanese girls who had Mongolian spots present at birth over the sacrum and buttocks. In case 1, an eight-month-old, cafe au lait spots and in case 2, a six-month-old, brownish black pigmented spots appeared about one month after birth and gradually increased in size and number on the trunk and extremities. In the cafe au lait spot and pigmented nevus (histologically compound type) lesions and their boundary areas, a whitish halo-like zone, dermal melanocytes were small and round, as compared with those of surrounding Mongolian spots, although only slightly decreased in number. The characteristic bipolar dendrites were almost imperceptible. The dopa reaction of dermal melanocytes was also decreased. In the boundary halo-like areas in both cases, epidermal melanin granules and dopa-positive melanocytes were almost identical to those of the surrounding Mongolian spot. Mongolian spots were already present at birth in both cases, but the cafe au lait spots and pigmented nevi definitely appeared to arise on these Mongolian spot after birth. The Mongolian spots seemed to disappear at the sites of cafe au lait spots, pigmented nevi and boundary areas, perhaps a kind of Sutton's phenomenon.

Ultrastructural studies of vitiligo with inflammatory raised borders were performed. A 41-year-old Japanese female had developed vitiligo on the back and cervical region about six months previously and it gradually increased. Slightly elevated red borders were observed on the periphery of some of the vitiligo lesions. Electron microscopic findings showed a few melanocytes with decreased and irregular melanosomes in the basal layer and dissociation of keratinocytes in the spinous layers. Melanosomes in keratinocytes were markedly decreased. Lymphocytes were frequently observed intraepidermally, and the process by which lymphocytes passed to the basal lamina from the dermis was also observed. Lymphocytes were seen in apposition to some melanocytes in the basal layer. These melanocytes, as a result, may degenerate. The formation of many vacuoles in the cytoplasm was observed. Many typical Langerhans cells with many racket bodies were observed in the upper spinous layers. On the other hand, in the basal layer, Langerhans cells with only a few racket bodies were generally observed. These Langerhans cells were also frequently in contact with lymphocytes. The cause of this inflammatory reaction with a raised border is not known. However, these ultrastructural findings firmly suggested a relationship to some type of immunological mechanism for this occurrence of vitiligo.

Five cases of apocrine hidrocystoma are reported. One is multiple and the others are solitary lesions. There are more than 60 cases reported in the Japanese literature. Apocrine hidrocystomas usually occur as a solitary lesion. Only two cases of multiple apocrine hidrocystoma have been described so far in Japan. We reviewed the literature and discussed the clinicopathologic nature of this tumor. Apocrine hidrocystomas are usually composed of a cystic cavity lined by columnar epithelium, showing apocrine type secretion. Peripheral to this, myoepithelial cells are usually seen; however, they were absent from all of the present cases. Change in hue of the tumor is another characteristic feature. About half of the reported Japanese cases exhibited distinctive coloration, variously light brown, red-brown, or bluish. In contrast, non-Japanese cases tended to have darker coloration.

When vitiligo occurred on lesions of the pigmented nevus, the behavior of pigment cells in this nevus was investigated. Three cases of giant hairy nevi, seven cases of moles, three cases of Mongolian spots and eleven specimens in nine cases of halo nevi were used. Giant hairy nevi combining with vitiligo showed intensive decreases in nevus cells, particularly superficial A and B-type nevus cells. The epidermal dopa-positive melanocytes and melanin granules in the epidermis decreased, but still remained. On the other hand, moles in vitiligo showed an almost complete disappearance of epidermal dopa-positive melanocytes and melanin granules in the epidermis; nevus cells in the dermis decreased only slightly. Mongolian spots with vitiligo showed an epidermis similar to vitiligo, but the dermal melanocytes were hardly changed. Halo nevi exhibited an intensive decrease and degeneration of nevus cells and marked lymphocytic infiltration. Some of them showed disappearance of epidermal dopa-positive melanocytes and melanin granules in the epidermis. The characteristic findings of vitiliginous skin are mostly restricted to epidermis. In contrast, however, it is interesting to note that, on the lesions of nevocellular nevi with vitiligo, the dermis also exhibited some decrease and degeneration of nevus cells and lymphocytic infiltration.