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Biomedical subjects

F Otsuka

Publications and source records attributed to F Otsuka.

At least 199 records · Page 11Linked to original sources
PubMed1989

Porokeratosis has neoplastic clones in the epidermis: microfluorometric analysis of DNA content of epidermal cell nuclei.

Clinical evidence of malignant epithelial tumors developing on the lesions of porokeratosis has accumulated. To determine the cytologic basis for the malignant change of porokeratosis, the nuclear DNA content of epidermal cells from porokeratosis lesions was measured using microfluorometry. A total of 42% of 33 porokeratosis skin lesions in eight of the 16 patients showed DNA polyploidization in the epidermis. Most of the porokeratosis skin lesions, with or without DNA polyploidization, increased cell proportions in the S and G2/M phase range. These findings suggest that porokeratosis is undergoing the neoplastic process, and is the precursor skin manifestation of malignant tumors.

Adult↗
PubMed1989

Strong anti-tumor effect of monosialoganglioside specific monoclonal antibody 202: a clinical trial in a cancer patient with melanoma.

Mab 202, a mouse monoclonal IgM antibody which recognizes sialic acid alpha 2----3 galactosyl residue in monosialogangliosides and reacts with human melanoma cells but not with normal cells, was administered to a melanoma patient by either intralesional injection or intravenous infusion. Mab 202 induced regressions of the metastatic tumors without side effects. Histopathologic examination showed remarkable degenerative and necrotic changes in the tumor, around which lymphocytes, eosinophils, plasma cells and macrophages infiltrated. Immunoperoxidase staining revealed Mab 202 binding to melanoma cells. Clinical and pathologic evidence suggested that Mab 202 has cytotoxic effects against melanoma cells. Mab 202 may therefore be useful in the treatment of human malignant melanoma.

Antibodies, Monoclonal↗
PubMed1989

Cultured skin fibroblasts from patients with porokeratosis are hypersensitive to the lethal effects of X-radiation.

Porokeratosis is an autosomal dominant inherited skin disorder. The lesions are characterized by localized abnormal keratinization and may develop into malignant tumors. To determine the cellular basis of the cancer susceptibility associated with this skin condition, we examined the colony-forming ability of X-ray or ultraviolet (UV) light irradiated, cultured fibroblasts derived from porokeratosis patients' normal-appearing skin. Four fibroblast strains derived from four porokeratosis patients' skin were significantly hypersensitive to the lethal effects of X-radiation. However, they all showed a similar sensitivity to strains from normal donors to 254 nm UV light. The hypersensitivity to X-ray radiation in cultured skin fibroblasts from porokeratosis patients suggests an inherent instability of cellular DNA and may probably be associated with the cancer-prone nature of this skin condition.

Cell Survival↗
PubMed1989

Pemphigoid vegetans.

A Japanese case of pemphigoid vegetans is described. The clinical, histopathological and immunological features were similar to the previously reported cases. The patient also developed vesicular lesions. Indirect immunoelectronmicroscopy revealed that the autoantibody in this patient's serum reacted with basal cell hemidesmosomes. This study provides further evidence that pemphigoid vegetans is a subtype of bullous pemphigoid.

Aged↗
PubMed1989

[Two cases of infantile subungual pigmented nevi with Hutchinson's sign].

Two cases of subungual pigmented nevi with periungual melanotic freckles, namely Hutchinson's sign, are presented. They are a 4-year-old female and a 11-month-old male; in neither case did the mother notice the lesion at birth. Histologically, both cases were characterized by the presence of well-circumscribed small nests of nevus cells in the periungual melanotic areas; diagnoses of junctional nevus and compound nevus were made, respectively. However, atypical proliferations of melanocytes at the dermo-epidermal junction of the nail matrix and nail bed were observed in some areas. The measurement of the DNA content of melanocytes by means of microfluorometry revealed normal diploid pattern in the former case, but the latter case contained a few aneuploid cells, suggesting that the proliferating melanocytes might have malignant potentials. Infantile subungual pigmented nevi with Hutchinson's sign must be examined thoroughly and watched carefully.

Aneuploidy↗
PubMed1989

[Topographical differences in cellular DNA content between the radial growth phase and the vertical growth phase of superficial spreading melanoma].

The nuclear DNA content of tumor cells was measured during the radial growth (RGP) and vertical growth (VGP) phases of three cases of superficial spreading melanoma. To compare these two phases, the DNA distribution histogram was analyzed and the DNA index was calculated. A aneuploid population appeared histographically in all specimens of VGP; however, no such abnormal population could be detected in RGP. VGP cells contained greater numbers of polyploid cells and had a higher DNA index value than RGP cells in all cases. These findings support Clark's postulation that the appearance of a new clonal cell population contributes to the development of VGP from RGP in malignant melanoma.

Adult↗
PubMed1988

Silver staining for carboxymethylated metallothioneins in polyacrylamide gels.

A sensitive method for detecting metallothioneins (MTs) by use of silver staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of carboxymethylated MTs was developed. Carboxymethylation of metallothioneins is indispensable because it prevents their aggregation, thereby allowing each of them to be detected as a single band by SDS-PAGE. However, when the gel was subjected to the silver-staining method of C. R. Merril, D. Goldman, S. A. Sedman, and M. H. Ebert [(1981) Science 211, 1437-1438], the image of carboxymethylated purified MTs was totally negative. Pretreatment of the gel with 1% sodium thiosulfate just prior to the silver-staining procedure successfully reversed the negative image of carboxymethylated MTs. Further, they could be detected with a limit of nanogram levels per lane. This method can be applied to MTs in cell extracts from cultured cell lines treated with cadmium or to those from liver of cadmium-intoxicated mice.

Animals↗
PubMed1988

Glutathione and metallothioneins as cellular defense against cadmium toxicity in cultured Chinese hamster cells.

To evaluate the protective role of cell glutathione (GSH) against the toxicity of cadmium, the effect of GSH depletion on the metal toxicity was investigated and the role of glutathione was compared with that of zinc-induced metallothioneins (MTs). A 6-h incubation of cultured Chinese hamster V79 cells with 0.2 mM L-buthionine-SR-sulfoximine (BSO), a selective inhibitor of gamma-glutamylcysteine synthetase, resulted in approx. 95% depletion of GSH in the cells. The depletion of GSH did not influence the rate of cell growth, the amount of cell protein or the chromosome structure during culture for at least 24 h. Cells depleted or not depleted of GSH were challenged with (1-5).10(-5) M CdCl2 for 2 h and subsequent cell growth was evaluated. The cytotoxicity of cadmium was enhanced with increasing duration of BSO pretreatment and was correlated with the decrease of cell GSH, indicating that GSH constitutes a cellular defense against toxicity by cadmium. Inducibility of MTs by zinc was investigated in cultured V79 cells. Incubation of the cells with 1.10(-4) M zinc acetate did not result in accumulation of MTs over the control values for up to 2 h. Thereafter, however, the synthesis of MTs increased with increasing duration of zinc treatment and an approx. 9-fold increase in the amount of MTs was observed 10 h after addition of zinc. Depletion of cell GSH by BSO did not much influence the increased accumulation of MTs by zinc. In contrast, zinc at the same concentration did not influence the level of cell glutathione up to 12 h. The cytotoxicity of cadmium was markedly reduced in the cells pretreated with zinc and the protective effect of zinc was dependent upon duration of pretreatment, being parallel with the increased accumulation of MTs. Protection of cells from cadmium toxicity by zinc pretreatment was as or a little more effective in the cells depleted of GSH as in those not depleted. Thus, glutathione appears to be an intrinsic protector against cadmium toxicity, while MTs serve as an induced cellular defense that is mobilized against heavy metal stress, but takes more than 2 h to accumulate in significant amounts. Accordingly, it is suggested that GSH and MTs have cooperative protective roles against cadmium toxicity, as an initial defense for the former and a second-stage defense for the latter.

Acetates↗
PubMed1988

Induction of anti-nuclear antibodies in mice orally exposed to cadmium at low concentrations.

Anti-nuclear antibodies (ANA) in serum were detected in male ICR mice fed drinking water containing 3, 30 and 300 ppm Cd as CdCl2 for 10 weeks. In response to Cd exposure, ICR mice developed ANA of the IgG class giving nuclear patterns moderately stained by immunofluorescence or immunoenzyme method. Positive immunofluorescence staining of ANA was obtained in 50, 89 and 90% of ICR mice exposed to 3, 30 and 300 ppm Cd, respectively. Their spleen cells also showed an enhancement of antibody forming response to sheep red blood cells (SRBC) without the SRBC priming. When mice were primed with SRBC after exposure to Cd, however, a significant suppression of the antibody forming response was observed in mice fed 300 ppm Cd but not in those fed 3 ppm Cd. No significant differences in delayed-type hypersensitivity reaction to SRBC were observed between Cd-fed and control animals. Inbred BALB/c mice were less susceptible to the induction of ANA by Cd, as induced only in 300 ppm Cd-fed mice. Thus environmental exposure to Cd can induce ANA in ICR mice with a high susceptibility, presumably accompanied with a non-specific stimulation of antibody formation.

Administration, Oral↗
PubMed1987

Metallothioneins of monocytes and lymphocytes.

Monocytes and lymphocytes were separated from human peripheral blood, and their capacity to synthesize metallothioneins (MTs) was examined. Both cell types can produce proteins electrophoretically similar to HeLa cell MTs. These proteins are inducible by Cd2+ and specifically precipitable by anti-MT serum. To have an insight into the capacity of T- and B-lymphocytes to produce MTs, sensitivity to Cd2+ of both cell types was estimated during mitogen-specific blastogenesis. Lymphocytes were prepared from mouse spleen and stimulated by concanavalin A (ConA) or lipopolysaccharide (LPS) in the presence of Cd2+. [3H]thymidine incorporation, as well as [3H]uridine incorporation in an earlier stage, was more severely inhibited by Cd2+ in ConA-induced mitogenesis than in LPS-induced mitogenesis, indicating T-lymphocytes are more sensitive to Cd2+ toxicity. This may reflect lower capacity of T-lymphocytes to synthesize MTs in response to Cd2+.

Animals↗
PubMed1987

Involvement of DNA polymerases in the repair of DNA damage by benzo[a]pyrene in cultured Chinese hamster cells.

Mechanisms for induction of single-strand scissions in DNA by S9-activated benzo[a]pyrene (B[a]P) and their repair in cultured Chinese hamster V79 cells were investigated with inhibitors of DNA-repair synthesis using alkaline sucrose gradient sedimentation analysis. The marked induction of single-strand scissions in DNA was observed following 3 h treatment of V79 cells with 5 micrograms/ml of B[a]P. These DNA lesions were repaired to the control level within 4 h after removal of B[a]P. The simultaneous addition of inhibitors of DNA-repair synthesis. 1-beta-D-arabinofuranosylcytosine (araC) plus hydroxyurea with B[a]P did not increase the formation of DNA single-strand scissions. When these inhibitors were added after removal of B[a]P, however, they significantly blocked the rejoining of DNA-strand scissions. On the other hand, when aphidicolin, a specific inhibitor of DNA polymerase alpha, was used instead of araC, a partial inhibition of the rejoining was observed, and further addition of 2',3'-dideoxythymidine, an inhibitor of DNA polymerase beta, augmented the inhibitory effect. These results indicate that B[a]P-induced single-strand scissions of DNA in V79 cells could be repaired mostly by excision repair which involved DNA polymerase alpha and a non-alpha polymerase, presumably polymerase beta.

Animals↗