Mayumi Fujita

Roles of E- and P-cadherin in the human skin.

The Ca2+‐dependent cell‐cell adhesion molecules, termed cadherins, are subdivided into several subclasses. E (epithelial)‐ and P (placental)‐cadherins are involved in the selective adhesion of epidermal cells.

Cadherins in Cutaneous Biology

The role of cadherins in cutaneous biology has focused mainly on the classical cadherins, E‐ and P‐cadherin. In this review, roles for cadherins in skin morphogenesis, keratinocyte differentiation, and cancer metastasis are discussed.

Primary spinal intramedullary malignant melanoma: case report

A rare case of primary spinal intramedullary malignant melanoma at the T6 level in a 31-year-old man is presented. The tumor was partially removed, and neuroaxis irradiation up to 50 Gy was then administered. Subsequently, systemic interferon beta (specific activity, 2.0 X 10(8) IU/mg protein) therapy (total dose, 2.2 X 10(7) units) was begun. At the completion of these therapies, immunohistochemical analysis with monoclonal antibodies against melanoma-associated antigens confirmed the presence of melanoma cells in the cerebrospinal fluid (CSF). Chemotherapy with intrathecal administration of dacarbazine (dimethyltriazenoimidazole carboxamide, DTIC) was then initiated, to avoid the dissemination of tumor cells by the CSF. Periodic cytological examination of CSF for melanoma cells revealed a marked reduction in the number of tumor cells. Pharmacokinetic study showed that the disappearance of DTIC from the CSF was biphasic, with an initial half-life of 30 minutes and a terminal half-life of 5 hours. Follow-up examination by MRI 1 year after the operation did not disclose any significant increase in size of the residual tumor. Neither recurrence nor metastasis was observed. The pertinent literature on spinal cord melanoma is reviewed, and the usefulness of MRI and intrathecal chemotherapy with DTIC is discussed.

γδ T-cell receptor-positive cells in human skin. I: Incidence and V-region gene expression in granulomatous skin lesions

BACKGROUND There have been many reports that gamma delta T-cell receptor (TCR)+ cells respond to mycobacterial antigens in vitro, but there is little available information on human gamma delta TCR+ cells in clinical conditions. OBJECTIVE Our purpose was to investigate the distribution and involvement of human gamma delta TCR+ cells in granulomatous skin lesions. METHODS The incidence and V-region gene expression of human gamma delta TCR+ cells was examined in granulomatous skin diseases, including cutaneous tuberculosis and leprosy, by immunohistochemical procedures. RESULTS gamma delta TCR+ cells in the dermis were increased in most patients with borderline lepromatous leprosy, and they were less frequently found in lepromatous leprosy and erythema nodosum leprosum. Other granulomatous skin lesions, including sarcoidosis, contained only a few gamma delta TCR+ cells. The gamma delta TCR+ cells that were found to be increased in this study were mostly delta TCS1-, BB3+, Ti gamma A+ (V delta 1-, V delta 2+, V gamma 9+). CONCLUSION The gamma delta TCR+ cells in human granulomatous skin lesions may respond to some mycobacterial antigens, but they do not appear to be directly involved in granuloma formation.

A subpopulation of Langerhans cells (CD1a+Lag-) increased in the dermis of plaque lesions of mycosis fungoides.

The population of CD1a+ cells and the quantity of Birbeck granules were evaluated in comparison with the population of T lymphocytes in a variety of clinical lesions of mycosis fungoides. Anti-CD1a and Lag antibodies that specifically react with Birbeck granules and related structures of human Langerhans cells were used immunohistochemically. CD1a+ cells in the dermis of lesions of mycosis fungoides significantly increased in plaques of the plaque stage and in plaques of the tumor stage. They were most frequent in lesions with CD4+ cells ranging in number from 100 to 150/mm2. These lesions were suspected to be progressing from the plaque to the tumor stage. During the course of the disease, most of the dermal CD1a+ cells had few Lag antigens. These results suggest that dermal CD1a+Lag- cells may promote the progression of mycosis fungoides from the plaque to the tumor stage.

Immunohistochemical comparison of actinic reticuloid with allergic contact dermatitis

Biopsy specimens of chronic lesions and ultraviolet-induced lesions from actinic reticuloid patients were examined by immunoperoxidase techniques and compared with those of allergic contact dermatitis skin, one of the delayed-type hypersensitivity conditions. Each lesion of actinic reticuloid showed a clear predominance of suppressor/cytotoxic T cells to helper/inducer T cells and an increase of Langerhans cells in the epidermis and the dermis. These findings are generally similar to those in the late phase (on day 7 and 11) but not in the early phase (on day 2) of allergic contact dermatitis and suggest that delayed-type hypersensitivity might be involved in some parts of the pathogenesis of actinic reticuloid. CD36+DR+ epidermal cells were also observed in ultraviolet-induced lesions from actinic reticuloid patients, suggesting a possible role in the modulation of the mechanism.

Lymphomatoid papulosis: ultrastructural immunohistochemical and gene analytical studies

Ultrastrutual, immunohistochemical and gene analytical studies were carried out on a 39‐year‐old patient with lymphomatoid papulosis. Two different cell groups were demonstrated in the papulonodular eruptions: large atypical cells with multiple nuclei that were well stained with anti‐Tac, but not with Leu 3a, and other cells that possessed prominent hyperchromatic nuclei and which stained well with Leu 1 and Leu 3a but not with anti‐Tac. Gene analytical studies using EcoRI, BamHI and HindIII revealed no rearrangement, indicating a non‐clonal T‐cell proliferation unlike malignant T‐cell lymphoma. These results suggest that the present case was benign.

Erythema multiforme: pathomechanism of papular erythema and target lesion.

Skin lesions of erythema multiforme show time‐dependent changes from early papular erythema to the late target lesion which consists of a peripheral elevated erythematous area and a central depressed area. We investigated the pathomechanism of erythema multiforme, by examining the papular erythema and target lesion separately. In the early papular erythema, a small number of polymorphonuclear leukocytes and nuclear debris were seen intermingled with mononuclear cells around the slightly swollen blood vessels, on which immunoglobulin and complement components were deposited. Circulating immune complex levels were occasionally elevated. Sera from the patients generated high levels of reactive oxygen species and nitroblue tetrazolium test revealed positive reaction on the infiltrating cells around the blood vessels. These findings suggest that the papular erythema develops via incomplete type III allergic reaction, followed by damage through reactive oxygen species. In the target lesion, the activity of histamine‐N‐methyltransferase, which is the major histamine‐degrading enzyme, was markedly decreased in the peripheral elevated erythematous area and it was recovering in the central clearing area. ICAM‐1 and HLA‐DR antigens were expressed on the surfaces of the keratinocytes. An increased number of epidermal Langerhans cells and CD4 cell infiltration were observed in the peripheral elevated erythematous area, while a decreased number of epidermal Langerhans cells and CD8 cell infiltration in the central depressed area were observed. These findings suggest that impaired histamine metabolism and cellular allergic reactions play important roles in the development of the target lesion.

Immunohistochemical study of lepromin reaction in healthy adults

Lepromin reaction was studied with immunoperoxidase techniques using monoclonal antibodies. The skin reactions were induced by injecting Mitsuda antigen into healthy adults without a family history of leprosy. Both early (48 hours) and late (3 weeks and 2 months) reactions were examined. In the late reaction, focal collections of epithelioid cells had formed, and not only T- but also B-lymphocytes were observed around the granuloma. CD1a+ cells were also confirmed to have increased in the late reaction.

Analysis of Epidermal Growth Factor Receptor Gene in Psoriasis

Epidermal Growth Factor (EGF) plays an important role in cell proliferation. In psoriasis, increased histochemical expression of EGF receptor has been reported in the epidermis. In order to elucidate the mechanism of this increase, we studied the EGF receptor gene organization in psoriasis. DNAs were extracted from white blood cells of 5 patients with psoriasis and 5 normal controls and also from epidermis of 2 psoriatic patients and 1 normal control, and analyzed by Southern blot technique. There were no differences in the structural organization of EGF receptor gene in either white blood cells or epidermis between psoriatic patients and normal controls. These results suggest that the histochemical increase of EGF receptor in the epidermis of psoriatic patients is not due to a structural change in this gene.