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Lysyl oxidase initiates cross-linkage of collagen and elastin by catalysing the formation of a lysine-derived aldehyde. In order to study cross-linking in scleroderma, we used monoclonal antibodies to lysyl oxidase to determine the localization of this enzyme in systemic and localized scleroderma, and compared the distributions obtained with that in normal skin. Using an indirect immunofluorescent antibody method and an avidin-biotinylated enzyme complex method, 11 cases of diffuse type of systemic scleroderma and seven cases of localized scleroderma were studied. In the oedematous stage of systemic scleroderma, intracellular and extracellular lysyl oxidase were remarkably increased in the dermis, particularly in groups around blood vessels. In the sclerotic stage of systemic scleroderma, lysyl oxidase was detected intracellularly in fibroblasts and extracellularly among collagen bundles between the lower dermis and the subcutaneous fat tissue. In localized scleroderma, a marked increase in lysyl oxidase was observed in mononuclear cells and fibroblasts near blood vessels in the lower dermis and in the subcutaneous fat tissue, in addition to the extracellular deposits between collagen bundles. The increase in lysyl oxidase in localized scleroderma was much more common than in the oedematous stage of systemic scleroderma. These findings indicated that intracellular and extracellular expression of lysyl oxidase expression was greater in sclerodermatous skin than in normal skin.

We diagnosed phakomatosis pigmentovascularis type IIIb in an 11-month-old baby who had a giant nevus spilus, a nevus flammeus, and moyamoya disease. Development of the patient was normal until 6 months of age when he developed a sudden onset of focal seizures and left hemiparesis. This patient represents the sixth case of phakomatosis pigmentovascularis type IIIb, including three cases in the Japanese literature, reported thus far. However, to our knowledge, this is the first case with an association to moyamoya disease.

Langerhans cells (LCs) are activated in the epidermis by external and internal stimuli, such as antigens and cytokines, respectively. To reveal the morphologic and functional properties of in vivo-activated LCs during inflammation, we injected the streptococcal preparation OK-432 intradermally into the earskin of mice and performed time-course analyses by immunofluorescence and electron microscopy. Cellular infiltrate appeared in the dermis at 6 h after OK-432 injection and had progressively extended to the dermoepidermal junction at 12 and 24 h. Immunostaining for class II antigen revealed that LCs were enlarged and extended long dendrites during inflammation. Acidic compartments such as lysosomes and multivesicular bodies also increased in number and Golgi apparatuses developed as demonstrated by electron microscopy and morphometric analysis. Birbeck granules, although not showing numerical changes, were translocated from the Golgi area to the subplasmalemmal area. After epicutaneous application of cationic ferritin, LCs often contained endosomes as the result of engulfment by the cytoplasmic projections. The present results indicate that nonspecifically induced dermal inflammation is capable of inducing activation of LCs in vivo, and that in vivo-activated LCs have the capacity for active endocytosis and intracellular digestion or processing.

We diagnosed a unique case of Merkel cell carcinoma (MCC) coexisting with Bowen's disease on the sole of the foot of a 72-year-old man who had worked for about 4 years in a factory handling inorganic arsenic. He had a past history of arsenical keratosis and multiple Bowen's disease. The tumour first appeared as a reddish macule and then showed marked growth over the next month. The tumour was excised and the specimen was examined histopathologically. The tumour consisted of two components: a group of atypical cells representing Bowen's disease in the epidermis and another group of atypical cells with a trabecular pattern characteristic of MCC in the dermis. Neither group of cells showed transitional findings, and the tumour elements were divided by a clear basement membrane. The tumour cells in the dermis were positive for neurone-specific enolase, and on electron microscopy had dense core granules in the cytoplasm. Inorganic arsenic can cause various cutaneous neoplasms, but to our knowledge, this is the first report of a case of MCC associated with Bowen's disease.

Cutaneous metastases from pancreatic carcinoma are uncommon. Eight cases have been described in the literature. The metastases display some common features such as umbilical nodules and the histologic pattern of adenocarcinoma. Our patient had erythematous infiltrated plaques in the left axilla and on the upper portion of the chest. A skin biopsy specimen disclosed many poorly differentiated atypical cells throughout the dermis. The diagnosis was confirmed by positive immunohistochemical staining for carbohydrate antigen 19-9.

A patient with primary anaplastic large-cell lymphoma of the skin with characteristic clinical findings is described. The diagnosis was made on the basis of histologic and immunohis-tochemical findings. Thephenotypeof the tumor cells was not determined, but rearrangement of the T-cell receptor β gene indicated that the tumor was of T-cell lineage. Despite high-grade malignancy of the tumor cells, the patient unexpectedly had a benign clinical course. The findings in this case suggest that regressing atypical histiocytosis and lymphomatoid papulosis type A are subsets of anaplastic large-cell lymphoma.

We report a case of adult T-cell leukaemia/lymphoma (ATLL), in whom the polymerase chain reaction (PCR) on genomic DNA from saliva demonstrated the monoclonal integration of human T-cell lymphotropic virus type-1 (HTLV-1) proviral DNA in lymphocytes in the saliva. These results provided evidence of the possibility of saliva-borne transmission of HTLV-1.

We report a Japanese patient with congenital hypomelanosis with a segmental pattern on the lett abdomen, whorl-like pattern on the back; mosaic pattern on the chest, right abdomen, and proximal extremitiea; and with yellow hair on a portion of the scalp. Chemical analysis of the yallow hair revealed decreased eumetanin content, whereas the pheometanin content was normal.

Summary The activity and gene expression of ornithine decarboxylase (ODC, an indicator of tumour promotion) were induced by the phorbol ester tumour promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), in mouse skin. In the present study, the effect of colchicine, a microtu-bule-disrupting agent, on ODC activity and its gene expression were investigated. On administration of colchicine (100 μg) intraperitoneally 1·5 h before TPA treatment, ODC activity and ODC mRNA levels stimulated by TPA were suppressed to about 52 and 64%, respectively. These results suggest the involvement of a microtubule or colchicine-sensitive substrate in the signal transduction system for gene expression.

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.

Vogt-Koyanagi-Harada disease is a rare disease characterized by uveitis, meningitis, dysacusis, alopecia, poliosis, and vitiligo. We describe a 48-year-old patient with Vogt-Koyanagi-Harada disease associated with thin inflammatory raised erythema and plaque-type inflammatory erythema superimposed on vitiligo. Interestingly, inflammatory raised erythema was separated from the perfect vitiligo, and the incomplete vitiligo lay between them initially. Thereafter, incomplete vitiligo became completely depigmented with diminution of inflammatory raised erythema. This is the second case of vitiligo with inflammatory raised borders associated with Vogt-Koyanagi-Harada disease. Our results of immunohistochemical and electron microscopic studies suggested the involvement of T-cell-mediated cytotoxicity and apoptosis in the development of skin lesions.

Chemotherapy-induced acral erythema (CAE) is an uncommon and distinct reaction seen in patients receiving high-dose chemotherapy. The exact pathogenic mechanisms of this disorder are still unknown. We report a 27-year-old woman who presented with red, swollen and painful macules on both palms, clinically consistent with this disease. Histological examination demonstrated vacuolar degeneration of the basal cell layer and spongiotic blisters in the epidermis, especially in the atrophied eccrine ducts and papillary oedema with mild perivascular infiltration of mononuclear and hypersegmented neutrophils. Immunohistochemistry showed that the infiltrating mononuclear cells were CD3-CD16+CD56+ leucocyte function antigen-1+, possibly natural killer cells. The eccrine ducts expressed HLA-DR and intracellular adhesion molecule-1 (ICAM-1). Our findings suggest that cell-to-cell interaction between NK cells and keratinocytes in the eccrine apparatus may induce CAE and may be involved in the pathogenesis of the skin reaction in our patient and possibly in this disease.

We describe a combined cutaneous hamartoma in a 57-year-old man, which comprised a vellus hair cyst, an epidermoid cyst and an intradermal melanocytic naevus in a single facial tumour. The vellus hair cyst was filled with keratinous material with unusual slit-like lacunae. While numerous cases of epidermoid cyst have been reported in association with an intradermal melanocytic naevus, our case is a rare example of a lesion combining several hamartomatous elements.

Two patients with epidermolysis bullosa dystrophica recessiva who had squamous cell carcinoma are presented. Case 1 is a 40–year-old woman who had ulcers on her left lower leg. Case 2 is a 42–year-old man who had a tumor on his left first toe. Wide surgical excision with skin coverage by autograft was performed in case 1. Amputation of the toe in case 2 was performed. A review of the cases of epidermolysis bullosa dystrophica associated with cancer reported in Japan is also presented.

By using antibodies to type I, III, IV, V, and VI collagens and laminin, we examined the localization of interstitial collagens and basement membrane components with indirect immunofluorescence and immunoelectron microscopy (IEM). Furthermore, the morphological changes of these collagens in malignant transformation were investigated. In neurofibroma, IEM showed type I, III, and V collagens to be present diffusely on cross-striated collagen fibrils, whereas type VI collagen was present between the fibrils. Type IV collagen and laminin were observed to surround tumor cells. In neurofibrosarcoma, tumor collagen bundles that reacted with antibodies to type I, III, V, and VI collagens were irregularly arranged. Immunofluorescent deposits that reacted with anti-type IV collagen and anti-laminin antibodies were decreased in number, showing a thin and sparse arrangement.

糖尿病患者にみられたカポシ肉腫を報告した。患者は69歳男子。1982年頃に右足踵から足底にかけて, 紅色∼暗赤色の丘疹, 小結節が出現し, 徐々に増数増大, 疼痛を伴うようになってきた。組織学的にカポシ肉腫と診断され, 5年後には左足, 両手にも皮疹が出現した。糖尿病に対して, インスリン, 経口血糖降下剤投与を行い, さらにアクチノマイシンD, ビンクリスチンによる化学療法を行ったが, 発病約5年後に消化管出血のために死亡した。剖検では, 消化管, 副腎, 横隔膜, リンパ節など多臓器にカポシ肉腫が認められた。

Balb 3T3 fibroblasts were cultured in type I collagen gel and the effects of tretinoin (all-trans-retinoic acid) were examined on cell growth and the gel contraction produced by cells. Cell proliferation was suppressed and the degree of gel contraction was enhanced by the addition of 10−7 and 10−6 M tretinoin. Growth and gel contractility of transformed cells derived from the Balb 3T3 cells were not influenced by this agent. Addition of 12-O-tetradecanoylphorbol ester, which is known to antagonize tretinoin in several biological processes, enhanced gel contraction synergistically with tretinoin. These results suggest that tretinoin influences cell-to-collagen interactions.

A primary adenoid cystic carcinoma of the skin is reported. Light microscopy revealed pseudocysts. PAS-positive basement membrane and true glandular lumen, which in aggregates are specific for adenoid cystic carcinoma. Perineural invasion was also observed. Ultrastructural examinations revealed three types of cystic spaces; pseudocysts, true glandular lumens and intercellular spaces. Enzyme histochemical examinations showed positive reactions for eccrine enzymes, including phosphorylase and succinic dehydrogenase and negative for apocrine enzymes. Immunolocalization of collagens and laminin revealed that basement membranes of the pseudocysts involve Type V collagen as well as Type IV collagen and laminin.

Three patients with subungual exostoses, two involving the great toe and one the fourth toe, are presented. Local excision was performed, and the specimens were processed for light and electron microscopy. Light-microscopic study revealed that the tumours consisted of a proliferative fibrocartilaginous cap that merged into mature trabecular bone at its base. Electron-microscopic examination revealed that the tumour was composed of two types of cells: one was rich in cell organelles including rough endoplasmic reticulum, well-developed Golgi apparatus, and glycogen granules; the other cell had few such cell organelles. The former cells seemed to be osteoblasts actively engaged in bone formation, and the latter to be osteocytes related to those situated deeper in bone matrix in normal bone. However, ossification or calcification in subungual exostosis is rather casual, and osteocytes in this disorder may lack the capacity to elaborate compact bone.

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.

The proliferation and cell cycle phase composition of human dermal fibroblasts cultured on or in type I collagen lattices (reconstituted dermis model) were examined. On collagen lattices, as compared with conventional cultures on plastic dishes, the proliferation of human dermal fibroblasts was suppressed, being arrested at about one-half the saturation density after 10 days of culture. In collagen lattices, proliferation was further suppressed, being nearly arrested within 4-7 days of culture. Cells were analyzed for cell cycle phases by two-color flow cytometry using DNA staining and S phase cell staining with FITC-conjugated antibromodeoxyuridine antibody. After 5 days of culture, the number of S phase cells on collagen lattices was 49.3% of that on plastic dishes, with an increase in G0G1 phase cells of 79.8%. In collagen lattices, the number of S phase cells was very small (4.3% of all cells), and most of the cells accumulated in G0G1 phase. These findings suggest that the cell cycle of fibroblasts is arrested at G0G1 phase by their interaction with collagen. On the basis of these results, the reconstituted dermis model using collagen lattice is considered to be analogous to the dermis in vivo with respect to cell growth and cell cycle phase composition.

To elucidate the interaction between melanoma and its matrix, we cultured B16 murine melanoma cells on and in type I collagen gel and evaluated specified functions of melanoma cells; tyrosinase activity and melanin-synthesizing capacity. Proliferation of cells cultured in these environments was markedly suppressed compared with that of cells cultured conventionally on plastic. On the other hand, the tyrosinase activity of cells cultured in or on collagen gel was two to three times higher than that of cells cultured on the plastics, while their melanin production was approximately double that achieved during conventional culture of cells. In conclusion, collagen gel influenced the growth and cell-specific functions of the melanoma cell. The culture system using collagen gel as substrate may be useful for the investigation of the interaction between melanoma and its matrix.

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.

The influence of topical PUVA on the activity of ornithine decarboxylase (ODC) and its gene expression was investigated in the skin of hairless mouse. After 1 h of application of 0.3% 8-methoxypsoralen, irradiation of 3 J/cm2 of ultraviolet A (UV-A) was administered. The ODC activity markedly increased and peaked at 24 h following UV-A irradiation. The ODC raRNA level analyzed in dot-blot analysis elevated to about 5 times that of control at 24 h after treatment. These results show that the PUVA-induced ODC activity is due in part to an increase in ODC gene expression.

腫瘍間質と腫瘍細胞との相互作用をin vitroで研究する目的の第一歩として, B16メラノーマ細胞をI型コラーゲン·ゲル上およびゲル内で培養し, その形態, 増殖, チロジナーゼ活性, メラニン産生量について検討し, 通常のプラスチック上で培養した場合と比較した。ゲル内での細胞の形態は, プラスチック上に比べて, より細長く樹枝状となつた。増殖は, ゲル上およびゲル内ともに著明に抑制され, 培養7日後の細胞数は, プラスチック上と比較して, それぞれ約15%と10%となつた。チロジナーゼ活性は, ゲル上およびゲル内では促進され, プラスチック上での場合に比べて約3倍に増加した。それにともなつて, メラニン合成量もゲル上およびゲル内では, 約2倍にまで増加した。したがつて, 今回の結果よりコラーゲンとメラノーマ細胞との相互作用の存在が示唆された。

I型コラーゲン·ゲル上およびゲル内でヒト真皮線維芽細胞を培養し(再構成真皮モデル), その増殖を検討するとともに, propidium iodideによるDNA染色と, S期細胞に取り込ませたbromodeoxyuridineに対するFITC標識モノクローナル抗体を使つたtwo color flow cytometryを用いて, 線維芽細胞の細胞周期上の位相分布分析を行つた。通常のプラスチック上での培養に比べて, ゲル上では線維芽細胞の増殖は抑制され, 10日目に約50%の飽和密度で増殖を停止した。ゲル内では, さらに抑制され, 4∼7日以内にほぼ増殖を停止した。培養後5日目では, プラスチック上での培養に比べて, ゲル上においてはS期細胞は49.3%に減少し, G0G1期細胞は79.8%の増加を見た。一方, ゲル内では, S期細胞は非常に少数で(総細胞数の4.3%), 大多数はG0G1期に蓄積した。したがつて, コラーゲンとの相互作用により大多数の線維芽細胞は, G0G1期で停止することが示された。以上より, コラーゲン·ゲルを用いた再構成真皮モデルは, 増殖度と細胞周期位相分布の面からも生体真皮に近いことが示された。

ポリアミン合成の律速酵素であるオルニチン脱炭酸酵素(ODC)は, マウス実験的皮膚発癌におけるプロモーション過程のマーカー酵素として知られている。アルビノ·ヘアレスマウスに中波長紫外線を照射すると, この酵素活性は著明に上昇した。このメカニズムを分子生物学的に検索する目的で, マウス皮膚よりmRNAを抽出し, ODC cDNAをプローブとしてノーザン·ブロット分析を行つた。その結果, 90 mJ/cm2の中波長紫外線照射により, コントロールに比べて, 4時間後で2.0倍, 24時間後では2.6倍のODC mRNAレベルの増加を認めた。酵素活性の上昇とmRNAレベルの増加度とは並行せず, 転写後の調節の可能性も示唆されたが, 中波長紫外線照射によるODC活性の促進には, ODC mRNAレベルの増加が関与することが示された。

A 7-year-old girl with alopecia universalis had dystrophy of all 20 nails. A nail biopsy specimen disclosed features of lichen planus. The patient also had ichthyosis vulgaris and hypogammaglobulinemia. We are not aware of any previous reports of these associations, which we believe to be noncoincidental.

A case of subcorneal pustular dermatosis (SPD) is reported in a 48-year-old man with a 2-year history of hyperthyroidism (Graves' disease). SPD has been reported in association with IgA monoclonal gammopathy, but to our knowledge it has not been associated with hyperthyroidism. The coexistence of hyperthyroidism and SPD suggests that immunologic factors may play a role in the pathogenesis of SPD.

A 14-year-old boy with linear localized scleroderma had a dramatic improvement in contractures after treatment with N-(3',4'-dimethoxycinnamoyl) anthranilic acid (tranilast, Rizaben). The observation that this anti-allergic drug was effective in localized scleroderma lends further support to the concept that mast cells play a role in increased collagen synthesis in this disease.

Summary Four cases of solitary glomus tumour are reported, three of the angiomatous type, and one of the epitheliomatous type. In all cases, mucinous degeneration was seen, the extent of which correlated with the number of glomus cells.

Background. Rhinophyma is an end stage of acne rosacea. It results in a large nose due to a proliferation of sebaceous glands and fibrous tissue. Many cases of rhinophyma have been reported in the Western world; however, in Japan, rhinophyma has been an uncommon disease. Methods. We present two patients associated with rhinophyma who were treated by cross-shaped full-thickness excision followed by direct closure and compare the rhinophyma in Japan with that in the West. Results. To date, only 20 rhinophyma cases including our 2 cases have been reported in Japan. Epidemiologic factors of rhinophyma between the West and Japan do not differ except for location, malignancy and surgical treatment. Conclusions. In Japan, almost all cases are located on the lower half of the nose, treated by full-thickness excision followed by application of either skin grafts or direct closure. None have been malignant.

Summary Secondary cutaneous T-cell lymphoma may present with various types of skin lesions, hut rarely produces ulceration in contrast to primary cutaneous T-cell lymphoma. We report a case of malignant lymphoma of the tonsil that recurred as a giant cutaneous ulcer on the back of a 45-year-old man, Biopsy of the ulcer revealed a malignant lymphoma of diffuse, mixed-cell type. Surface marker analysis of the tumour cells showed suppressor/cytotoxic T-cell characteristics. The skin lesions were treated by electron beam therapy.

Summary Articular tissue was obtained at surgery for a femoral neck fracture in a patient with psoriasis without arthritis. The proteoglycan of the cartilage of the sample was analysed biochemically. Normal cartilage is known to produce two types of proteoglycan monomers (fast- and slow-sedimenting groups), which are distinguishable by density-gradient ultracentrifugation. In the psoriatic cartilage analysed in the present study, it was shown that the former group was absent and only the latter group remained.

Summary A case of a solitary pigmented neurofibrosarcoma involving the lateral side of the face in a 19-year-old female is described. Clinically it resembled a haemangioma, and angiography showed hypervascularity of the tumour. Light-microscopic study revealed that the major cellular element of the tumour was composed of bizarre neoplastic cells with large pleomorphic, hyperchromatic nuclei, conspicuous nucleoli and moderate to abundant amounts of conspicuous cytoplasm. Mitotic figures and multi-nucleate cells were present in most fields. Neurofibrosarcoma is one of the most highly malignant tumours; however, in the present case, there was no evidence of recurrence during a follow-up period of 5 years.

Cutaneous inflammation induced by electrophilic compounds involves irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). Reduced glutathione (GSH) and related thiols have been postulated to play important roles in detoxification of electrophilic xenobiotics, protection of tissues against reactive oxygen species, and modulation of immunologic functions in normal and diseased subjects. The dynamic aspects of GSH metabolism, however, and its significance in patients with ICD and ACD remain to be clarified. The current study was carried out to elucidate the pathogenesis and possible involvement of GSH in both types of inflammation. Normal mice and mice sensitized with dinitrochlorobenzene (DNCB) were challenged by cutaneous administration of DNCB, and changes in GSH metabolism in skin and liver were determined. Kinetic analysis revealed that 24 h after challenge with DNCB, levels of hepatic glutathione and its secretion increased more markedly in the sensitized mice than in the unsensitized animals. Administration of buthionine-L-sulfoximine (BSO), a specific inhibitor of GSH synthesis, inhibited the increase in glutathione levels in the liver and the skin of both groups. Histologic examination revealed that cutaneous inflammation was enhanced by BSO more significantly in mice with ACD than with ICD. These results suggest that GSH might play an important role in the suppression of the immune reaction in mice with ACD.

A 21-year-old male patient had localized papules on the chest and arms. Biopsy of a lesion showed it to be a malignant lymphoid neoplasm, and immunohistochemical studies confirmed a lymphoblastoma origin. Aberrant lymphoid cells were noted in the cutaneous blood vessels, but simultaneous examination of the peripheral blood showed no evidence of leukemia. One month elapsed before observable leukemic cells were found in the blood and sternal marrow, confirming the diagnosis of acute lymphocytic leukemia. Examination of a cutaneous biopsy specimen led to early diagnosis of the disease.

Tumor necrosis factor-alpha (TNF-alpha) has been demonstrated to selectively decrease the production of type I and type III collagens in human dermal fibroblasts. The effects of the commonly used food antioxidants, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), alpha-tocopherol, propyl gallate, superoxide dismutase (SOD), and catalase on TNF-alpha-induced growth enhancement and collagen metabolism were evaluated in the present study. BHA at concentrations of both 5 x 10(-5) and 10(-4) M inhibited cell proliferation and DNA synthesis induced by 10 ng/ml TNF-alpha in human dermal fibroblasts, while other antioxidants had minimal effects. Further, BHA (5 x 10(-5) M and 10(-4) M) significantly blocked TNF-alpha-induced decreases in collagen synthesis. These results suggest that antioxidants such as BHA may be involved in the modulation of collagen synthesis by TNF-alpha in human dermal fibroblasts.

Lysyl oxidase (LOX) initiates the crosslinking of the lysine-derived aldehyde and plays an essential role in maturation of collagen, for example in wound healing. Although the activity of this enzyme has been examined in various disorders, and a further intriguing aspect of the relationship between LOX and tumorigenesis has recently emerged, its gene expression pattern in tissues is still unknown. We examined LOX gene expression during wound healing in rat skin. In addition, type III collagen gene expression was studied to determine the formation of fibrils. The LOX mRNA level reached a peak by day 3 after injury, which was earlier than that of type III collagen, and continued at a high level until day 22. The type III collagen mRNA level began to rise from day 3 and had increased intensely by day 22. In situ hybridization revealed grains corresponding to LOX mRNA in the fibroblasts of the granulomatous tissue. These results suggest that LOX is produced before collagen synthesis in preparation for crosslinking in the early phase of wound healing.

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.