Tomoyuki Hisa

Allelic variants of human calcitonin receptor in the Japanese population

Abstract Evidence from cDNA cloning has shown that calcitonin receptors (CTRs) have seven potential transmembrane domains. In this study, structural analysis of CTRs from ten cultured human tumor cell lines and 117 human blood samples demonstrated allelic variants at the 1377th nucleotide in intracellular domain 4, expressing either proline or leucine as the 463rd amino acid. It was found that the variant with proline at this site was the more prevalent type of CTR among the Japanese population.

Purification of an angiogenesis inhibitor from culture medium conditioned by a human chondrosarcoma-derived chondrocytic cell line, HCS-2/8

We previously reported that a novel human chondrosarcoma-derived chondrocytic cell line, HCS-2/8, produced an anti-tumor angiogenesis factor and secreted it into the culture medium [Takigawa et al.: Anticancer Res., 10, 311-316, 1990]. In the present study, we purified the inhibitor by monitoring gelatinase inhibitory activity from the conditioned medium (CM) of HCS-2/8 cells. By a simple three-step procedure, gel filtration chromatography, ion-exchange chromtography, and reverse-phase HPLC, 200 micrograms of the inhibitor was obtained from 6 liters of CM with 239-fold enrichment. Purified inhibitor, named hCHIAMP (human chondrocyte-derived inhibitor of angiogenesis and metalloproteinase activity), showed a single protein band with a molecular mass (M(r)) of 24,000 (24K) under reducing conditions and M(r) 22K under nonreducing conditions on SDS-PAGE. On reverse-zymography, purified hCHIAMP showed a single band of 22K M(r) under nonreducing conditions. Its NH2-terminal amino acid sequence determined up to the 11th amino acid residue was identical with that of the tissue inhibitor of metalloproteinases-2 (TIMP-2). On Western blotting, anti-human TIMP-2 antibody cross-reacted with hCHIAMP, hCHIAMP at a dose of as little as 0.45 microgram significantly inhibited angiogenesis in the yolk sac of chick embryos induced by 0.25 mumol of spermine. Because HCS-2/8 is a clonal cell line, these findings clearly showed for the first time that chondrocytes themselves produce a potent inhibitor of angiogenesis, which is also an inhibitor of gelatinase. The findings also indicate that hCHIAMP is a TIMP-2-like molecule. Because the HCS-2/8 cells are an immortal cell line and of human origin, hCHIAMP could be useful for therapy of angiogenic diseases including solid tumors.

Shampoo dermatitis due to cocamidopropyl betaine

A 22-year-old male hairdresser, with no family or personal history of atopy, presented with erythematous swelling lesions on his hands, fingers and forearms. Complete blood and urine hematochemical values, including serum IgE (RIST), were within the normal range. Patch testing with the European standard series (Trolab®, Henna! Chemie Kurt Hermann, Germany), hairdressing series (Chemotechnique Diagnostics AB, Sweden), and shampoos the patient brought (1% aq.) was performed using Finn Chambers® (Epitest, Ltd., Helsinki, Finland) on Scanpor® tape (Norgesplaster A/S, Oslo, Norway). Positive ( + +, ICDRG) reactions at 3 days were seen to 2 shampoos (oil-based shampoo and Rera® styling shampoo) and cocamidopropyl betaine (Tegobetaine L7) 1% aq., which was a component of the oil-based shampoo. A second test revealed + + reactions to both I% aq. and 0.5% aq. cocamidopropyl betaine. 15 control subjects patch tested with cocamidopropyl betaine (1% aq.) showed no positive reactions.

Cutaneous metastases of pancreatic carcinoma with unusual clinical features

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.

Solitary glomus tumour with mucinous degeneration

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.

Butylated hydroxyanisole blocks the inhibitory effects of tumor necrosis factor-α on collagen production in human dermal fibroblasts

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.

Contact allergies to topical corticosteroids

The patient, a 34‐year‐old Japanese woman who noticed worsening of her rash after using topical corticosteroid preparations on her neck, was patch tested for both commercial preparations and corticosteroids themselves. The patch lest results revealed that she had a contact allergy to gold, oxytetracycline, and 2 types of corticosteroid (acetonides and esters) in 7 compounds (betamethasone valerate and dipropionate, hydrocortisone butyrate and hydrocortisone butyrate propionate, ameinonide, budesonide, and fluocinonide).

Effects of Butylated Hydroxyanisole on Ornithine Decarboxylase Activity Induced by Ultraviolet‐B and PUVA in Mouse Skin

The effects of butylated hydroxyanisole (BHA), a representative phenolic antioxidant, on the activity of ornithine decarboxylase (ODC, an indicator of tumor promotion and epidermal hyperproliferation) induced by ultraviolet‐B (UVB) or PUVA in mouse skin were investigated. By topical application of BHA (55 μmol), PUVA‐induced ODC activity was suppressed by about 60% at both 12 h and 24 h after treatment. In contrast, BHA failed to suppress UVB‐induced ODC activity in mouse skin. These results suggest that the induction of ODC activity by UVB or PUVA is mediated by different pathways.

Effects of Ultraviolet‐B and PUVA on Ornithine Decarboxylase Activity, DNA Synthesis, and Protein Kinase C Activity in Mouse Skin

Ultraviolet‐B and PUVA share several biological events with phorbol ester tumor promoters. The effects of ultraviolet‐B irradiation and topical PUVA treatment on ornithine decarboxylase activity, DNA synthesis, and protein kinase C activity, which are known to be induced or activated by phorbol ester tumor promoter, were investigated in hairless mouse skin. Ornithine decarboxylase activity was remarkably enhanced by ultraviolet‐B and PUVA. Although PUVA did not affect DNA synthesis significantly, ultraviolet‐B stimulated epidermal DNA synthesis approximately 5‐fold over control values at 48 h. However, unexpectedly, neither cytosolic nor membrane‐bound protein kinase C activity showed any change during the 2 h after either treatment. These results suggest that the protein kinase C system is not involved in the initial signal transduction system of ultraviolet‐B or PUVA, unlike the case with phorbol ester tumor promoter.

A case of acanthosis nigricans in obese siblings with a pedigree of familial polyposis coli.

Acanthosis nigricans (AN) is generally classified into the malignant, benign and pseudo-types. The malignant type is the most frequently reported and 65% of the benign type are associated with diabetes mellitus (218 of 337 reports, 1969-1995, our investigation). Moreover, familial reports are not frequent, and previous reports have suggested that AN is endocrinological or hereditary in origin, but the cause remains unclear. Familial polyposis coli (FPC), on the other hand, is a rare autosomal dominant intestinal disease that progresses to cancer in many cases. Both AN and FPC are autosomal dominant, but no common human leukocyte antigen (HLA) typing between these diseases has been reported previously.