Toshio Hamada

Hypertension Associated with Endothelin-Secreting Malignant Hemangioendothelioma

Endothelin-1, a potent vasoconstrictor peptide that has recently been isolated from the supernatant of cultured porcine aortic endothelial cells (1), is involved in some vascular disorders (2). Mal...

Light and scanning electron microscopic studies on wrinkles in aged persons' skin

Wrinkles in six aged persons (67–82 years of age) have been investigated by light microscopy (LM) and scanning electron microscopy (SEM). There are two types of wrinkles. One is a deep wrinkle which develops on the sun‐exposed skin and does not disappear on stretching (permanent wrinkle). The LM and SEM showed less elastotic change in the upper dermis in the area of wrinkle than in that of the surroundings. The other type is a shallow wrinkle which develops on sun‐protected skin and disappears on stretching (temporary wrinkle). The LM and SEM showed the decrease or loss of the elastic fibres in the papillary dermis as seen in ageing skin.

Age‐related changes in human dermal elastic fibres

Age‐related changes in the human dermal elastic fibres were studied by scanning (SEM) and transmission (TEM) electron microscopy. The SEM findings showed an increase in the complexity of shape and arrangement of the fibres including flattening and branching, an increase in the roughness of the surface, and a decrease in interfibrillar areas. The TEM findings showed a decrease in microfibrils and amorphous material, and an increase in electron dense inclusions followed by the appearance of vesicular structure.

Increased expression of lysyl oxidase in skin with scleroderma

Summary 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 mononudear cells and libroblasts 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.

Microcystic adnexal carcinoma: a light microscopic, immunohistochemical and ultrastructural study

We report a case of microcystic adnexal carcinoma (MAC) occurring on the upper lip of an 82‐year‐old woman. Microscopically the tumor showed both pilar and sweat gland differentiation, involved the entire dermis and subcutaneous tissue, and invaded perineural spaces. Immunoperoxidase studies revealed carcinoembrionic antigen to be present in the ductal lining cells and in the amorphous content in the lumen, confirming sweat gland differentiation. The S‐100 protein was positive in dendritic cells within the solid cell nests, but negative in cells lining cystic spaces. Ultrastructural study confirmed that the neoplasm was composed of two components, with pilar and eccrine differentiation. The former showed concentric layers of squamous epithelial cells with well‐developed desmosomes and cytofilaments. The latter had ductal and alveolar structures; the ultrastructural features included i) numerous villous folds of plasma membrane to interdigitate each other by focal desmosomes, ii) aggregates of cytofilaments, and iii) basally located myoepithelial cells which were separated from the surrounding stroma by rather thick basement membrane. In addition, distinct amyloid deposition was also observed on ultrastructural examination. To our knowledge, amyloid deposition has not been previously reported in MAC.

Immunohistochemical localization of lysyl oxidase in normal human skin.

Lysyl oxidase (EC 1.4.3.13), a copper‐dependent enzyme which catalyses the formation of aldehyde cross‐links, and acts primarily on collagen and elastin, is known to be increased during wound healing and in fibrotic disorders including liver cirrhosis and atherosclerosis, and to be decreased in some hereditary connective tissue diseases and in malignant cell lines. A recent study showed that lysyl oxidase might possess tumour suppressor activity as an antioncogene for ras. Little is known about the localization of this enzyme in human skin. In this study, we determined immunohistochemically the localization of lysyl oxidase in normal skin of young and elderly subjects obtained from sun‐exposed and unexposed regions of the body. All skin samples tested had similar distributions of lysyl oxidase. The enzyme was present both extracellularly and intracellularly. Extracellularly, a few granular aggregates of immunoreactants were observed along collagen and elastic fibres. These granules were more common in the adventitial portion of the dermis than in the reticular portion. Of all sun‐exposed and unexposed regions studied, the skin of the face displayed the greatest amount of extracellular immunoreactants. Immunopositive granules were observed intracellularly in fibroblasts, vascular endothelial cells, sweat glands, sebaceous glands, arrector pili muscles and some keratinocytes. These findings provide evidence that, as suggested in recent reports, lysyl oxidase may have a variety of intracellular functions.

Cell cycle analysis of human dermal fibroblasts cultured on or in hydrated type I collagen lattices

SummaryThe 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.

RHINOPHYMA IN JAPAN

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.

Treatment of linear localized scleroderma with the anti-allergic drug, tranilast.

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 antiallergic 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.

Parallel Arrangement, Growth Inhibition and Cell Cycle Phase Analysis of Human Dermal Fibroblasts Cultured in Collagen Lattice

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.