Biomedical subjects

A Tsubura

Publications and source records attributed to A Tsubura.

At least 37 records · Page 2Linked to original sources

PubMed2000

Establishment of novel human esophageal cancer cell line in relation to telomere dynamics and telomerase activity.

The telomere and the telomerase in human esophageal cancer are not yet completely understood. The regulatory mechanism of telomerase activity and telomere dynamics has drawn considerable attention. It is generally assumed that when telomerase has been activated, no further telomere shortening should ensue; however, a much more complex pattern of telomere dynamics may exist in telomerase-positive cancer cells. A novel human esophageal cancer cell line (KAN-ES) was established and characterized. Using KAN-ES and its serially passaged subclones up to the 55th generation, we determined the alteration of telomere length (TRF), telomerase activity (TA), telomerase RNA expression (hTR), population doubling time, karyotype, and cytokeratin 14 expression during the process of establishing a cancer cell line. We found that the TRF was maintained between 4.0 and 5.0 kb during the serial passages, despite sustained high TA (assessed by an in vitro TRAP assay). No close relationships were found among TRF, TA, and hTR expression. TA and telomere dynamics were not associated with cellular growth ability and differentiation. However, the number of population doublings showed significant correlations with both the TA and doubling times. In conclusion, these dissociations between telomere dynamics and TA support the existence of additional controls on TRF in cancer cells. KAN-ES and its restored subclones should prove a valuable resource for esophageal cancer research.

Biomarkers, Tumor↗

PubMed2000

Immunohistochemical expression of bone morphogenetic protein-2 in pilomatricoma.

BACKGROUND: The mechanism of occurrence of calcification and ossification in pilomatricoma remains unclear. OBJECTIVES: To elucidate the pathogenesis of calcification and ossification in pilomatricoma we examined the role of bone morphogenetic protein (BMP)-2, which plays important parts in inducing ectopic bone formation both in vivo and in vitro. METHODS: Twenty cases of pilomatricoma were studied immunohistochemically using anti-BMP-2 monoclonal antibody. RESULTS: In normal skin, including hair follicles, there was no BMP-2 expression. In all pilomatricomas, BMP-2 was found exclusively in the cytoplasm of shadow cells but not in basophilic cells. In two cases of bone formation seen in pilomatricoma, osteoblasts in the periosteal area showed a strong positive reaction, while bone trabeculum (bone matrix) showed no reaction. CONCLUSIONS: Our findings indicate that shadow cells positive for BMP-2 may play an important part in generating bone formation in pilomatricoma.

Adolescent↗

PubMed2000

A pivotal role of cell-bound but not soluble CD4 molecules in full development of lupus-like manifestations in MRL-Fas(lprcg)/Fas(lprcg) mice.

The role of CD4 molecules in the autoimmune and lymphoproliferative syndrome caused by murine Fas mutations was studied using the novel systemic lupus erythematosus (SLE) model, MRL-Fas(lpr(cg))/Fas(lprcg) (MRL-lpr(cg)) mice, in combination with the novel mutant CD4 gene producing soluble CD4 (sCD4) instead of membrane-bound CD4 (mCD4). For this purpose, various autoimmune manifestations were compared among MRL-lpr(cg) mice homozygous (CD4slprcg), heterozygous (CD4s/mlpr(cg)), and wild-type (CD4mlpr(cg)) for the CD4 mutation. The mortality, glomerulonephritis, proteinuria, and lymphadenopathy were significantly ameliorated in CD4slprcg compared with CD4mlpr(cg) and CD4s/mlpr(cg) mice, both being comparable in these clinical characteristics. In parallel with the clinical improvement, the serum levels of immunoglobulin, anti-DNA antibodies, anti-nuclear antibodies and immune complexes, and the extent of glomerular immune deposition, were significantly lower in the former. The results indicate that mCD4 is important and can not be replaced by sCD4 in full development of SLE-like manifestations, and suggest that CD4+ T cells may aggravate the autoimmune disease by stimulating autoreactive B cells to produce autoantibodies through their helper activity in Fas mutant models. The sCD4 levels in the serum and spleen elevated with the increased accumulation of B220+CD4-CD8- (double-negative (DN)) T cells in CD4slpr(cg) mice. This, together with the significantly milder lymphadenopathy associated with lower DN T cell contents in CD4slpr(cg) than CD4mlpr(cg) mice, implies that some of abnormal DN T cells may be derived from cells of the CD4 lineage.

Animals↗

PubMed2000

Time-specific occurrence of alopecia in neonatal C57BL mice treated with N-methyl-N-nitrosourea and the therapeutic efficacy of tacrolimus hydrate.

Alopecia was induced in male and female neonatal C57BL mice by a single intraperitoneal injection of 60 mg/kg N-methyl-N-nitrosourea (MNU). MNU administration was most effective in the 8-day-old mice and less effective in the 5-day-old mice (at active and early anagen stages of the first hair cycle, respectively). No alopecia was seen in the day 14 MNU-treated animals (at telogen stage of the first hair cycle). MNU effectively induced hair follicular cell apoptosis at the anagen stage by up-regulation of Bax protein without down-modulation of Bcl-2 protein. In day 8 MNU-treated mice, the immunosuppressive agent 0.01% tacrolimus hydrate (FK506), when topically applied for 5 days from 1 day after MNU treatment (before the occurrence of alopecia), decreased the severity of alopecia. However, it did not stimulate hair growth when applied for 5 days from 20 days of age (after occurrence of alopecia).

Alkylating Agents↗

PubMed2000

Mucinous carcinoma of the breast with neuroendocrine differentiation.

A case of mucinous carcinoma of the breast with neuroendocrine differentiation in an 89-year-old woman is presented. The patient presented with a rapidly growing right breast mass, which she had had for 2-3 years. The tumor, 15 x 8 x 5 cm, was located mainly in the upper outer quadrant. Light microscopy revealed a pure mucinous carcinoma of type B. Neuroendocrine differentiation was demonstrated by Grimelius stain and chromogranin A, as well as the presence of neurosecretory granules. The breast cancer cells were of luminal origin and had dedifferentiated to attain neuroendocrine properties.

Adenocarcinoma, Mucinous↗

PubMed2000

Alleviation of renal disease and lymphadenopathy in MRL-Fasp(lrcg)/Fas(lprcg) (MR-lpr(cg)) mice neonatally infected with mouse mammary tumor virus encoding superantigen strongly reactive with TCR Vbeta8.2 element.

Mouse mammary tumor virus transmitted by FM mice (FM-MMTV) encodes a superantigen (SAg) characterized by strong reactivity with TCR Vbeta8.2 element and broad spectrum of Vbeta reactivity. To investigate what effects the expression in vivo of FM-MMTV SAg exhibits on the course of the disease in a lupus-prone model, MRL/MpJ-Fas(lprcg)/Fas(lprcg) (MRL-lpr9cg) mice, neonatally FM-MMTV-infected MRL-lprcg(MMTV) and uninfected MRL-lpr(cg) mice were compared for various disease parameters. In MRL-lprcg(MMTV), survival was significantly prolonged, glomerulonephritis, proteinuria, and lymphadenopathy were clearly ameliorated, and the production of serum immunoglobulin G (IgG), complement-activating IgG2a, and cryogenic IgG3 autoantibodies, which are thought to be pathogenic to kidneys, and circulating immune complexes (IC), and glomerular IC deposition were significantly suppressed. FM-MMTV infection deleted Vbeta8.2+ cells by about 90% and Vbeta14+ cells less efficiently in all of the CD4+, CD8+, and B220+ CD4- CD8- or double-negative (DN) T-cell populations, and Vbeta8.1+ cells in the CD4+ population but not in the others. Similar deletion profiles of CD8+ and DN T cells support that DN T cells are derived from the CD8 lineage. The results imply that the specific regulation of the immune system with viral SAg has a potential for development of an attractive immunomodulatory therapy of autoimmune diseases.

Animals↗

PubMed2000

[Analysis of deep mycoses in autopsy cases].

The deep mycosis in compromised patients is increasing. We examined 40 cases (3%) of the deep mycoses out of 1170 autopsy cases experienced in Saint Luke's International Hospital from 1987 to 1996. The deep mycosis was highly associated with hematologic malignancies(23%) but not with solid tumors(2%). The common mycoses were aspergillosis and candidiasis, which were observed in 27(68%) and 14 (35%) cases, respectively. Most of the patients received broad-spectrum antibiotics, anticancer agents and corticosteroids, and showed granulocytopenia. The symptoms of deep mycoses were non-specific, for example, pyrexia and/or respiratory symptoms. The clinical diagnosis was established in 8 cases and the appropriate antifungal agents were used in 12 cases(30%). Thus, empiric amphotericin-B therapy should be started early in-patients with granulocytopenia, respiratory symptoms, and pyrexia.

Adolescent↗

PubMed2000

Long-term ethanol consumption in ICR mice causes mammary tumor in females and liver fibrosis in males.

BACKGROUND: Although epidemiological studies indicate that ethanol consumption and the risk of breast cancer are positively associated in women, experimental animal models have not yet been developed that provide evidence to support this relationship. To clarify alcohol-related liver injury, it is important to reproduce, in laboratory small animals, the liver fibrosis observed in human alcoholics. However, in mice the induction of fibrosis has failed. The present study describes the first experimental models to produce mammary tumors in female ICR mice and liver fibrosis in male ICR mice treated long-term with ethanol. METHODS: The study consisted of two parts. To induce mammary tumors, female ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 25 months, with solid diet supplied ad libitum. To induce liver fibrosis, male ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 10 to 15 months. Control female and male mice were given tap water. RESULTS: In 9 (45%) of 20 ethanol-treated female mice, mammary tumors occurred at 8 to 24 months after ethanol intake began, whereas spontaneous mammary tumor was not found in the 20 control female mice. The tumors were composed histopathologically of either papillary adenocarcinoma or medullary adenocarcinoma of glandular epithelial origin. In the ethanol-treated male mice, early hepatic fibrosis at the centrilobular and pericellular areas and central-central bridging were observed at the 10th month, and marked fibrosis at the centrilobular, pericellular, and periportal areas and bridging between the neighboring vascular tissues were observed at the 15th month, which suggested that the initial fibrosis arose from the centrilobular area. No abnormalities other than mild fatty infiltration were found in livers of the control male mice. CONCLUSIONS: These murine models may be useful to study the role of ethanol in mammary tumorigenesis and the pathogenetic mechanisms of ethanol liver injury.

Animals↗

PubMed2000

Effects of genistein and synergistic action in combination with eicosapentaenoic acid on the growth of breast cancer cell lines.

Genistein, a prominent isoflavone in soy products, produced dose- and time-dependent in vitro growth inhibition at high concentrations (at least 185 microM) with an IC50 of 7.0-274.2 microM after 72 h incubation in four breast cancer cell lines (DD-762, Sm-MT, MCF-7 and MDA-MB-231) and one breast epithelial cell line (HBL- 100) of human and animal origin; it stimulated estrogen-receptor-positive MCF-7 cells at low concentrations (3.7 nM-37 microM). Genistein-exposed cells underwent apoptosis, confirmed by G2/M arrest followed by the appearance of a sub-G1 fraction in cell-cycle progression, and by a characteristic cell ultrastructure. The apoptosis cascade was due to up-regulation of Bax protein, down-regulation of Bcl-XL protein, and activation of caspase-3. Genistein acted in synergism with eicosapentaenoic acid (EPA), a fish oil component, on human breast cancer MCF-7 cells (genistein > 93.2 microM and EPA > 210.9 microM) and on MDA-MB-231 cells (genistein > 176.1 microM and EPA > 609.3 microM). Dietary intake of genistein in combination with EPA may be beneficial for breast cancer control.

Animals↗

PubMed2000

Retinal damage induced by cisplatin in neonatal rats and mice.

PURPOSE: The morphologic response of the retina at different neonatal ages to various doses of cis-platinum(II)diamminedichloride (cisplatin) was examined in rats and mice. METHODS: Cisplatin was given to rats at a dose of 1, 3 or 5 mg/kg at 0 days or 5 mg/kg at 7 or 14 days of age, and to mice at 0.5, 1.5, 3 or 6 mg/kg at 0 days or 6 mg/kg at 7 or 14 days of age, and the animals examined 12 and 24 hrs, and 3 and 7 days after the treatment. RESULTS: In both species, regardless of gender, with > or = 3 mg/kg cisplatin treatment (lethal dose) at day 0, retinal damage characterized by the appearance of aggregations of TUNEL-positive cells scattered in the undifferentiated neuroblastic layer was seen at 24 hrs, and led to rosette formation at day 3 and 7 (retinal dysplasia). At the ultrastructural level, neuroblastic cells showed condensation of chromatin and shrinkage of the cytoplasm, and rosettes encircled by an outer limiting membrane. Cell debris phagocytosed by pigment epithelial cells was seen. However, cisplatin at < 3 mg/kg in 0-day-old animals or at high dose in > or = 7-day-old animals caused no damage to the retina. CONCLUSIONS: A critical period (day 0) for the administration and a threshold dose (> or =3 mg/kg) of cisplatin in the development of retinal damage in rats and mice was seen. Although the cisplatin dose necessary to damage the retina caused a high incidence of mortality, it was below the human therapeutic dose.

Aging↗

PubMed1999

Modulations of glucocorticoid-induced apoptosis linked to the p53 deletion and to the apoptosis susceptibility gene Rapop1 (Radiation-induced apoptosis 1).

We have analysed the effects of p53 and of the apoptosis susceptibility gene Rapop1 (Radiation-induced apoptosis 1) located on chromosome 16 on glucocorticoid- and radiation-induced in vivo apoptosis of thymocytes. For those analyses, we used Rapop1 semicongenic mice heterozygous for the STS and BALB/cHeA alleles in the chromosomal segment containing Rapop1 in the BALB/cHeA background, mice bearing a p53 deficient allele in the BALB/cHeA background and the genetic crosses between these mice. The p53 wild type mice with a STS/A allele at the Rapop1 locus were less susceptible to both radiation- and glucocorticoid-induced apoptosis than those with homozygous BALB/cHeA alleles at this locus. Surprisingly, glucocorticoid-induced apoptosis was enhanced in the p53 hemizygous mice and considerably increased in the p53 nullizygous mice. In contrast, a sizable reduction of radiation-induced apoptosis was seen in the p53 hemizygous mice. The low susceptiblity to glucocortocoid-induced apoptosis linked to the STS allele of Rapop1 was less pronounced in the p53 hemizygous mice and a diminished effect of Rapop1 on radiation-induced apoptosis was seen in these mice. Although it remains to be established whether the genes modulating glucocortocoid-induced apoptosis are identical to p53 and Rapop1, our data suggest that p53 and Rapop1 may participate in glucocorticoid-induced apoptosis of thymocytes.

Animals↗

PubMed1999

Cycloprodigiosin hydrochloride, a new H(+)/Cl(-) symporter, induces apoptosis in human and rat hepatocellular cancer cell lines in vitro and inhibits the growth of hepatocellular carcinoma xenografts in nude mice.

The effects of cycloprodigiosin hydrochloride (cPrG-HCl), a new H(+)/Cl(-) symporter, were examined in liver cancer cell lines in vitro and in vivo. In the in vitro MTT assay, cPrG-HCl inhibited the growth of 6 liver cancer cell lines (Huh-7, HCC-M, HCC-T, dRLh-84, and H-35, hepatocellular carcinoma; HepG2, hepatoblastoma) in a dose- and time-dependent manner. The 50% inhibitory concentrations (IC(50)) at 72 hours' treatment for liver cancer cell lines were 276 to 592 nmol/L, while that for isolated normal rat hepatocyte was 8.4 micromol/L. The cPrG-HCl treatment of Huh-7 cells induced apoptosis as confirmed by the appearance of a subG(1) population, intranucleosomal DNA fragmentation, and chromatin condensation. cPrG-HCl raised the pH of acidic organelles and lowered pHi (below pH 6.8). In addition, the apoptosis in Huh-7 cells induced by cPrG-HCl was strongly suppressed when the cells were cultured with imidazole, a cell-permeable base. In the in vivo assay, nude mice bearing subcutaneous xenografted Huh-7 cells received 2 weeks of treatment with cPrG-HCl (1 or 10 mg/kg/d) subcutaneously. This treatment significantly inhibited tumor growth compared with the control after 8 days. The control mice were treated with 1% dimethylsulfoxide (DMSO) in saline (vehicle). A histopathological examination using the terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) method showed apoptosis in the treated tumor cells. No pathological changes were observed in any organs, and the serum alanine transaminase levels remained within normal limits. These results suggest that cPrG-HCl may be useful for the treatment of hepatocellular carcinoma.

Animals↗

PubMed1999

Biphasic effect of colchicine on acute liver injury induced by carbon tetrachloride or by dimethylnitrosamine in mice.

BACKGROUND/AIMS: The effects of colchicine on acute liver injury induced by carbon tetrachloride or by dimethylnitrosamine in mice were examined. METHODS: Nonlethal acute liver injury was induced in male BALB/c mice by a single intraperitoneal injection of 0.8 ml/kg carbon tetrachloride or 15 mg/kg dimethylnitrosamine. 0.6 mg/kg colchicine was administered 18 h or 2 h intraperitoneally before hepatotoxin treatment. RESULTS: Reversible centrilobular to mid-zone necrosis and apoptosis occupying half the liver lobular area was evoked by carbon tetrachloride, and dimethylnitrosamine, respectively. Administration of colchicine 18 h before hepatotoxins markedly suppressed liver injury, whereas colchicine administration 2 h before the hepatotoxins accelerated it. The hepatoprotective effect evoked by colchicine was due to reduction in liver cytochrome P450 content and P450 2E1 activity. In contrast, the hepatodestructive effect seen in the carbon tetrachloride model was related to the extent of lipid peroxidation promoting plasma membrane destruction, while the hepatodestructive effect in the dimethylnitrosamine model was due to suppression of Bcl-X(L) expression, leading to acceleration of apoptosis. CONCLUSIONS: A biphasic effect of colchicine on carbon tetrachloride- and dimethylnitrosamine-induced acute liver injury was seen. The time interval between colchicine administration and the hepatotoxin treatment is crucial to the subsequent development of liver lesions.

Alanine Transaminase↗

PubMed1999

Synergistic action of apoptosis induced by eicosapentaenoic acid and TNP-470 on human breast cancer cells.

The effects of eicosapentaenoic acid (EPA) and an angiogenesis inhibitor (TNP-470) on the suppression of breast cancer cell growth were examined in five human breast cancer cell lines (MDA-MB-231, T-47D, MCF-7, KPL-1, and MKL-F). In all five cell lines, EPA and TNP-470 alone both showed tumor growth inhibition in a time- and dose-dependent manner, and in combination, a synergistic effect was seen at high concentrations. EPA plus TNP-470 treatment evoked apoptosis as confirmed by the appearance of sub G1 populations, by DNA fragmentation, and by cell morphology. With the combination, the expression of Bax and Bcl-xS, the apoptosis-enhancing proteins, was more up-regulated and that of Bcl-2 and Bcl-xL, the apoptosis-suppressing proteins, was more down-regulated compared to the use of EPA or TNP-470 alone, suggesting that their synergistic effect was due to an acceleration of apoptosis.

Apoptosis↗

PubMed1999

An autopsy case of malignant mesothelioma with osseous and cartilaginous differentiation: bone morphogenetic protein-2 in mesothelial cells and its tumor.

An autopsy case of biphasic malignant mesothelioma with osseous and cartilaginous differentiation diffusely involving the peritoneal cavity was confirmed by light microscopic histochemistry, immunohistochemistry, and electron microscopy. A reverse transcription-polymerase chain reaction using specific primers for bone morphogenetic protein-2 (BMP-2) revealed weak positive transcript in normal mesothelial cells and up-regulated expression around bone-forming malignant mesothelioma tissue. However, BMP-2 protein expression was detected only in the marginal zone of bone trabeculae and spindle-shaped mesothelioma cells distributed around bone trabeculae in tumor tissue. The distribution of type IV collagen in tumor tissue was in accordance with the BMP-2 expression. Normal mesothelial cells and tumor cells expressed BMP-2 mRNA, but the BMP-2 protein expression was restricted to the bone-forming area in the malignant mesothelioma.

Abdominal Neoplasms↗

PubMed1999

Sjögren's syndrome in mice carrying the Ipr(cg) gene and the therapeutic efficacy of an immunosuppressive agent FK506.

The influence of the Ipr(cg) gene on the development of Sjögren's syndrome was followed up to 5 months of age in male and female mice of MRL, CBA and C3H strains. In MRL-Ipr(cg) mice, focal mononuclear cell infiltration started at 2 months and became conspicuous after 3 months of age in the lacrimal and submandibular glands but was minimal in the parotid and sublingual glands, even at 5 months of age, without any apparent sex effects found. In CBA and C3H mice carrying the Ipr(cg) gene, this manifestation of Sjögren's syndrome was much less prominent, indicating that the participation of some genes of the MRL strain may be indispensable for the development of Sjögren's syndrome in mice carrying this gene. In MRL-Ipr(cg) mice, an immunosuppressive agent, FK506, improved the serological abnormalities (decreased levels of anti-double-stranded DNA antibody of IgG2a and IgG3 subclasses) and proteinuria. It also reduced the manifestations of Sjögren's syndrome when it was intraperitoneally administered three times weekly at a dose of 2 mg/kg from 6 weeks (before disease onset) until 5 months of age (the termination of the experiment). Although VP8.2+ T cells have been demonstrated to be responsible for causing several autoimmune diseases, the selective deletion of Vp8.2+ T cells with the superantigen encoded by mouse mammary tumor virus did not affect the disease severity at all, suggesting that this T cell repertoire may not play a crucial role in induction of Sjögren's syndrome.

Animals↗

PubMed1999

An autopsy case of hepatoid carcinoma of the ovary with PIVKA-II production: immunohistochemical study and literature review.

A case of hepatoid carcinoma of the ovary in a 61-year-old Japanese woman, who showed high serum levels of alpha-fetoprotein and CA125, is reported. Grossly, the left ovarian tumor, which measured 12 x 9 cm, was solid and multinodular. Histologically, the tumor resembled hepatocellular carcinoma by its architectural and cytological features. Liver cell differentiation was indicated functionally by the immunohistochemical detection of alpha-fetoprotein and protein induced by vitamin K absence or antagonist II (PIVKA-II) and by positive bile production, and the hepatocellular differentiation was structurally in accord with keratin 7, 8 and 18 expression. CA125 expression, commonly present in ovarian surface epithelial carcinomas, suggested that this neoplasm originated from ovarian common epithelial cells. There are only nine such cases in the literature. A review of these cases reveals that hepatoid carcinoma of the ovary occurs exclusively in postmenopausal women (mean age, 62.7 years) and that the prognosis is poor.

Biomarkers↗

PubMed1999

Right intraventricular metastasis of squamous cell carcinoma of the uterine cervix: an autopsy case and literature review.

An autopsy case of squamous cell carcinoma of the uterine cervix, which developed cardiac intracavitary metastasis in a 28-year-old Filipina, is reported. At autopsy, the right ventricle contained a soft, red-purple, cauliflower-like mass. Histologically, this mass was made up of sheets of malignant squamous cells similar to the primary uterine foci. The metastases were extensive and associated with multiple organ involvement. Although this case was stage Ib at operation, vascular invasion at the primary site was characteristic, and the intracavitary tumor of the right ventricle developed without myocardial involvement. The carcinoma of the primary site extended along the inferior vena cava and settled as an intracardiac obstructive mass. A literature review (including the present case) disclosed only 14 uterine cervical carcinomas with right intracavitary metastasis. The mean age of these patients was 46 years of age (range, 28-77 years). The clinical stage was Ib in two cases, IIa in one case, IIb in six cases, and IIIb in two cases. The prognosis of these cases was poor; 13 of the patients died at an average of 19.1 months after diagnosis.

Adult↗