Hiroyo Fushida

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.

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.

Acquired Dermal Melanocytosis of the Hand: A New Clinical Type of Dermal Melanocytosis

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.

Primary anaplastic large-cell lymphoma of the skin: A case report suggesting that regressing atypical histiocytosis and lymphomatoid papulosis are subsets

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 immunohistochemical findings. The phenotype of the tumor cells was not determined, but rearrangement of the T-cell receptor beta 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.

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.