Porokeratosis and malignant skin tumors.
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Adult↗
Biomedical subjects
F Otsuka
Publications and source records attributed to F Otsuka.
Differential susceptibility of T- and B-lymphocyte proliferation to cadmium: relevance to zinc requirement in T-lymphocyte proliferation.
Effect of zinc on an inhibitory action of cadmium to mitogen-induced lymphocyte proliferation was investigated. Cadmium at concentrations below 10 microM selectively inhibited concanavalin A-induced T-cell proliferation as compared with bacterial lipopolysaccharide-induced B-cell proliferation. Such differential susceptibility of T- and B-cell proliferation was not observed in the cases of other cations such as mercury, lead, nickel, molybdenum, chromium(VI) and arsenic (V). The inhibitory effect of 10 microM cadmium on T-cell proliferation was almost completely prevented by addition of 30 microM zinc to the culture medium, but was not by ferrous iron, nickel and copper. Further, cadmium exerted the same extent of inhibition even when it was added at 16 h after concanavalin A stimulation, and thereafter the inhibition gradually decreased. Correlated well with this observation, the protective effect of zinc was seen as far as it existed during the first 16 h of the mitogen stimulation. As intracellular cadmium content and a cadmium-induced metallothionein level were not changed by zinc addition, these observations strongly suggest that cadmium inhibits some zinc-dependent processes required for T-cell proliferation.
Animals↗
A nuclear factor that interacts with metal responsive elements of a human metallothionein gene.
Metallothioneins (MTs) are low molecular weight heavy metal-binding proteins which are known to play a major role in heavy metal detoxification and understanding of their regulatory mechanism is toxicologically important. Expression of MT genes is induced by heavy metals and metal responsive elements (MREs) upstream of MT genes are essential for the transcriptional activation. By several types of mobility shift assay with 32P-labeled oligonucleotide probes, we detected HeLa cell nuclear as well as cytoplasmic factors that bind to MRE sequences of human MTIIA (hMTIIA) gene. One of the nuclear factors, which gives stronger signal than others, was further characterized. Competition experiments showed that the nuclear factor (named MREBP) specifically recognizes MREs of hMTIIA gene. EDTA abolished the binding of MREBP to MRE, suggesting that a divalent cation(s) is required for the complex formation. Also in blotting experiments with HeLa nuclear extract and the [32P]MRE probes an EDTA-sensitive 95k protein band, which possibly represents MREBP, was detected.
Base Sequence↗
Detection of carboxymethylmetallothionein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
A sensitive method for detecting metallothioneins (MTs) by using silver staining and autoradiography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of carboxymethylated MTs is described. Carboxymethylation of MTs is indispensable because it prevents their aggregation, thereby allowing each of them to appear as a single band using SDS-PAGE. Metallothioneins can be detected with a limit of nanogram levels per lane. This method can be applied to MTs induced in in vitro cultured cells and in in vivo tissues.
Animals↗
A case of neurofibrosarcoma associated with neurofibromatosis--ganglioside analysis.
A patient with neurofibromatosis developed neurofibrosarcoma (NFS). The tumour was composed of spindle-shaped cells with atypical nuclei arranged in a fascicular or sheet-like fashion. The tumour cells had discontinuous basement membrane-like structures and were positively stained with the monoclonal antibody against S100 protein alpha chain. Both the primary tumour and its cultured cells contained GM3 and GD3 as major gangliosides. The ganglioside pattern of the primary tumour corresponds to that of NFS in our previous study. In the cultured NFS cells, the relative amount ratio of GM3 to GD3 is almost reversed compared to that of the primary tumour. This reversion may reflect some environmental influence on the ganglioside metabolism of NFS.
Adolescent↗
Kyrle disease associated with sarcoidosis and renal failure.
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Female↗
Porokeratosis with large skin lesions. Histologic, cytologic and cytogenetic study of three cases.
Three porokeratosis patients with large skin lesion(s) are reported. The histopathology of the large lesions revealed that the epidermis 1) frequently presented slight or marked acanthosis and/or elongation of the rete ridge, and 2) contained abnormal cells, e.g. hyperchromatic, large, multinucleated, and/or irregular shaped nuclei. The DAPI-DNA microfluorometric study revealed DNA polyploidy and/or an increased population of epidermal cells with hyperdiploid and/or tetraploid DNA content. These results indicate the proliferating potential of the epidermis and the existence of a neoplastic clone or clones therein. This finding may explain the enlargement of skin lesions and possibly the development of malignancy, as sometimes occurs in large skin lesions. Furthermore, cultured skin fibroblasts from a patient's skin lesion or its surrounding skin revealed various kinds of chromosomal structural abnormalities, which may serve as a basis for the development of abnormal neoplastic clones in the porokeratotic epidermis.
Aged↗
[A case of Farber's disease--histochemical, electron microscopic and biochemical studies].
A case of Farber's disease (disseminated lipogranulomatosis) is reported. A Japanese boy presented with progressive joint deformity, a hoarse voice, mental retardation and skin granulomatous lesions. He died of bronchopneumonia at the age of 2 years. Biopsied specimen from the perianal granulomatous lesion showed many macrophage contained lipids, and acidic oligo-, or polysaccharides, or, glycoconjugates. Electron microscopic study revealed, in addition to curvilinear tubular bodies (Farber's bodies), numerous granular structures accumulated in the cytoplasm of the macrophage. Biochemical analysis demonstrated a storage of free ceramide in the patient's liver, and confirmed the patient's diagnosis. This is the 5th case reported in Japan.
Amidohydrolases↗
Sphingoglycolipids in human cultured keratinocytes.
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Cells, Cultured↗
Chromosomal instability and cellular hypersensitivity to X-radiation of cultured fibroblasts derived from porokeratosis patients' skin.
Porokeratosis is a rare genetic skin disorder known to be associated with a propensity to develop skin cancer. To further elucidate the previously reported cytogenetic and cellular abnormalities, we studied karyotypic changes and the sensitivity to X-ray irradiation of cultured fibroblasts derived from skin lesions and normal-appearing skin of 3 patients with porokeratosis. Cultured fibroblasts from normal-appearing skin of 9 controls were similarly examined. Porokeratosis subjects had a greater number of cells with chromosomal abnormalities than controls. Two porokeratosis strains which were derived from the normal-appearing skin of a patient had a noticeable clone of abnormal cells. Porokeratosis fibroblasts were hypersensitive to the lethal effects of X-radiation. This hypersensitivity was common to both the lesion-derived strains and the ones derived from normal-appearing skin. The 2 strains with clonal abnormal cells were also similarly hypersensitive to X-radiation. These results suggest that chromosomal instability is strongly related to porokeratosis and that X-ray hypersensitivity is an inherent abnormality in cultured fibroblasts of porokeratosis patients.
Cell Survival↗
Neutrophilic dermatosis with myelodysplastic syndrome: nuclear segmentation anomalies of neutrophils in the skin lesion and in peripheral blood.
Neutrophilic dermatosis developed in two patients with myelodysplastic syndrome. Biopsy specimens of their skin lesions showed marked infiltration by neutrophils with nuclear anomalies, that is, hyposegmentation (pseudo-Pelger-Huët anomaly) or hypersegmentation. Peripheral blood and bone marrow neutrophils had similar anomalies. To our knowledge, this is the first report of nuclear segmentation anomalies of neutrophils in neutrophilic dermatosis skin lesions of patients with myelodysplastic syndrome.
Female↗
Disseminated porokeratosis accompanying multicentric Bowen's disease. Characterization of porokeratotic lesions progressing to Bowen's disease.
Multicentric Bowen's disease developed in a 73-year-old man in areas involved with disseminated porokeratosis. The porokeratotic lesions were brownish; some were small and solitary, and others were coalesced and of variable size. Some lesions were erythematous. The histologic findings of the small, solitary or brownish, coalesced lesions were those of porokeratosis without apparent dysplasia; however, the erythematous coalesced lesions revealed epidermal dysplasia. Study revealed DNA ploidy abnormalities in the epidermal cells of these porokeratotic skin lesions. The skin lesions progressed in their degree of DNA ploidy abnormality from small solitary lesions to brownish coalesced ones and further to erythematous, coalesced ones. These observations suggest the direct and sequential growth of potentially malignant neoplastic clones in the patient's porokeratotic skin lesions and explain the multicentric development of Bowen's disease.
Aged↗
Clitoral and labial involvement of neurofibromatosis.
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Child↗
Use of DAPI cytofluorometric analysis of cellular DNA content to differentiate Spitz nevus from malignant melanoma.
Cellular DNA content was measured for the purpose of differentiating Spitz nevus from malignant melanoma using the cytofluorometric technique. DNA was stained by 4',6-diamidino-2-phenylindole, and measured by microfluorometer. Among 20 Spitz nevi examined, 18 of them showed a diploid DNA distribution histographic pattern similar to that of acquired pigmented nevi. The other two Spitz nevi had a few polyploid cells with the major population of cells containing diploid DNA content. In contrast, all malignant melanomas showed an aneuploid DNA distribution histographic pattern. The DNA index values of cells from Spitz nevi distributed in the similar range to that of acquired pigmented nevi and separated from those of malignant melanomas distributed in a much higher range. Our results suggest that cytofluorometric analysis of cellular DNA content reflects the biologic behavior more sensitively than do conventional clinical or histologic criteria, and that it serves as a useful aid for the differentiation of Spitz nevus from malignant melanoma.
Adult↗
Antiproliferative effect of hyperthermia and ACNU on cultured human malignant melanoma cells.
Human malignant melanoma cultured cells were treated either with ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chlorethyl)-3-nitro sourea hydrochloride), hyperthermia, or the combination of ACNU and hyperthermia. The combination treatment inhibited the cell growth to a slightly synergistic degree compared to the respective single treatments. The present in vitro experimental results support in part the finding of our previous report that the combination treatment with ACNU and hyperthermia have a significantly synergistic antitumor effect to human melanoma transplanted to nude mice. However, the synergistic effect was much less intense in the present in vitro experiment. The difference may have resulted from the environmental differences between in vitro and in vivo experimental systems.
Cell Count↗
A case of neurofibrosarcoma associated with neurofibromatosis: light microscopic, ultrastructural, immunohistochemical and biochemical investigations.
A case of neurofibrosarcoma (NFS) with neurofibromatosis was studied by light microscopic, ultrastructural, immunohistochemical and biochemical methods. Histologically, spindle-shaped tumor cells with atypical hyperchromatic nuclei were arranged in a fascicular or sheet-like fashion. Electron microscopic examination revealed discontinuous basement membrane-like structures. Immunohistochemical study revealed S100 protein alpha chains in tumor cells. A biochemical analysis showed large amounts of gangliosides (sialic acid 13.5 micrograms/g wet tissue weight) in tumors. GM3 and GD3 were the major components; these results were compatible with the NFS ganglioside patterns found in our previous study. Results confirmed the diagnosis of NFS and indicate that NFS clearly has some neuroectodermal characteristics and that Schwann cells may possibly be related to its origin.
Adolescent↗
Nerve sheath myxoma. An immunohistochemical study of a case.
An 18-year-old Japanese male presented with a normal-skin-colored, dome-shaped, slightly tender tumor on his left palm. Histopathologically, the tumor consisted of distinct lobules, which were separated by fibrous connective tissue. Each lobule was composed of spindle or round cells within a myxoid matrix, pathognomonic of nerve sheath myxoma. The mucinous material was positively stained by Alcian blue (pH 2.5) and toluidine blue (pH 4.0). Immunohistochemically, the majority of spindle cells were positive for S-100 protein (beta-subunit) and neuron-specific enolase. Our findings lend further support to the hypothesis that nerve sheath myxoma is derived from Schwann cells.
Adolescent↗
Porokeratosis as a premalignant condition of the skin. Cytologic demonstration of abnormal DNA ploidy in cells of the epidermis.
Clinical evidence has accumulated of malignant epithelial tumors developing on the lesions of porokeratosis. To determine the cytologic basis for the malignant change of porokeratosis, the nuclear DNA content of epidermal cells from porokeratotic lesions was measured using microfluorometry. A total of 42% of 33 porokeratotic skin lesions in eight of the 16 patients showed DNA polyploidization in the epidermis. Most of the porokeratotic skin lesions, with or without DNA polyploidization, increase cell proportions in the S and G2/M phase range. DNA indices of cells from these porokeratotic lesions distributed widely from the level of normal control epidermis to that of malignant epidermal conditions. These findings suggest that porokeratosis is undergoing the neoplastic process, and is a precursor of malignant tumors.
Adult↗