Haruhiko Ohno

8-Methoxypsoralen plus UVA induces the 72-kDa heat shock protein in organ-cultured normal human skin

Abstract The proteins induced by heat and other stressors, called heat shock proteins (HSP) or stress proteins, are considered to play a general role in protection from cellular injury. Exposure to UVA (320400 nm) following application of 8‐methoxypsoralen (8‐MOP), termed PUVA is commonly used in the field of dermatology. In order to understand the induction of HSP in PUVA‐treated human skin, indirect immunofluorescence using a monoclonal antibody specific for the 72 kDa HSP (HSP 72) was carried out in organ‐cultured normal human skin that was treated with PUVA. When the organ‐cultured skin was treated at 37°C for 1 h with 8‐MOP at a final concentration of 10 or 100 μg/mL and exposed to UVA (51.3 kJ/m2), nuclear immunofluorcscence of HSP 72 was detected in the epidermal cells 12 h after UVA irradiation. In contrast, the induction of HSP 72 was not detected either by UVA irradiation or 8‐MOP treatment. These results suggest that PUVA treatment is one of the stressors for human skin, and DNA damage caused by PUVA induces HSP 72.

Atypical pemphigus associated with monoclonal IgA gammopathy

We describe a 60-year-old woman with atypical pemphigus and IgA-lambda monoclonal gammopathy. Histopathologic study of vesiculopustular lesions showed intraepidermal acantholytic and neutrophilic blisters. Direct immunofluorescence revealed intercellular IgG deposition with concurrent deposits of IgA and C3. Indirect immunofluorescence and immunoblotting studies revealed that the patient had circulating IgG anti-intercellular antibodies that recognized the 150 kd desmoglein (pemphigus foliaceus antigen) in bovine desmosome preparation. Immunoblot studies with human epidermal extract showed that the IgG of this patient exclusively reacted with the 140 kd protein (between the 150 kd human desmoglein and the 130 kd human pemphigus vulgaris antigen), the nature of which is currently unknown. The patient also had IgA anti-intercellular autoantibodies, which reacted with the desmoglein in the bovine desmosome sample but did not show any reactivity in human epidermal extract.

Atypical pemphigus with concomitant IgG and IgA anti-intercellular autoantibodies associated with monoclonal IgA gammopathy.

A case is reported of a 60-year-old woman with acantholytic vesiculopustular dermatosis and IgA-lambda monoclonal gammopathy. The histopathology of vesiculopustular lesions showed intraepidermal acantholytic and neutrophilic blisters. Direct immunofluorescence revealed intercellular (IC) IgD deposition with concurrent deposits of IgA and C3. Indirect immunofluorescence and immunoblotting studies revealed that the patient had circulating IgG and IgA anti-IC antibodies both of which recognized the 150-kD desmoglein that was pemphigus foliaceus antigen in a bovine desmosome preparation.

TWO CASES OF UNILATERAL AXILLARY PAGET'S DISEASE

We herein report two cases of unilateral axillary Pagets disease. Extramammary Pagets disease commonly occurs in the anogenital area. Unilateral axillary occurrence is relatively rare. One defect was reconstructed with a pedicled scapular flap, and the other was reconstructed with split‐skin graft after excision of the tumor. No recurrence was seen in either patient three years postoperatively. However, although the patient who had been reconstructed with a pedicled flap recovered uneventfully, the other patient, who had been reconstructed with a split‐skin graft, suffered from axillary contracture due to the shrinkage of the grafted skin after surgery. A skin graft requires fixation for a long period to prevent shrinkage, which causes axillary contracture. Therefore, from the viewpoint of quality of life, reconstruction using flaps is recommended for axillary lesions.

Detection of Autoantibody against 97-kD Antigen by Immunoblot, but not by Indirect Immunofluorescence, in a Patient with Linear IgA Bullous Dermatosis

A case of linear IgA bullous dermatosis in an 85‐year‐old man is reported. Direct immunofluorescence (IF) of the lesional skin showed linear deposition of IgA and weak deposition of IgG at the basement membrane zone. Although no circulating autoantibody was detected by indirect IF, immunoblotting analysis using NaCl‐separated normal human epidermal extracts revealed a circulating IgA antibody which bound to the 97‐kD antigen.

Melanin reduces ultraviolet-induced DNA damage formation and cell killing rate in cultured human melanoma cells

Epidermal melanin pigment is believed to prevent development of ultraviolet (UV)-induced skin cancer by shielding cell nuclei and reducing DNA damage formation. It has not been experimentally proved, however, whether melanin reduces UV-induced DNA damage, because published experiments have been inconclusive. The present study was carried out to determine whether intracellular melanin protected cultured cells against UV-induced DNA damage and killing. Three human melanoma cell lines containing different amounts of melanin were used. Absorption spectrum, subcellular localization of melanin, and melanin concentration were examined in the three cell lines. Two types of DNA damage, cyclobutane pyrimidine dimers and (6-4)photoproducts, were detected by an enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies specific for these photolesions. We found that melanin reduced the induction rates of both types of DNA damage in pigmented cells irradiated with low doses of UV in a melanin concentration-dependent manner. Almost no differences in repair capacity for the two types of photolesions were observed among the three melanoma cell lines. We also found that the more highly melanotic melanoma cell lines were more UV resistant than the less melanotic melanoma cell lines. These results suggest that intracellular melanin plays an important role in preventing UV-induced cell killing by reducing the formation of two types of DNA damage.