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T Morimura

Publications and source records attributed to T Morimura.

At least 37 records · Page 2Linked to original sources
PubMed1996

Apoptosis and CD8-down-regulation in the thymus of chickens infected with Marek's disease virus.

Marek's disease virus (MDV)-infected chickens show thymic atrophy during the acute phase of infection. We examined whether the thymic atrophy by MDV-infection was mediated by apoptosis. Apoptosis-specific DNA ladderings were clearly observed in thymocytes one week after MDV-infection. Histological and flow cytometry studies revealed that immature CD4+ CD8+ thymocytes underwent apototic cell death. In addition, the expression level of CD8 molecules on both CD4(-)CD8+ and CD4+ CD8+ thymocyte populations was down-regulated in the infected chickens. These thymic changes might be involved in the pathogenesis of Marek's disease.

Animals↗
PubMed1996

mdm2 gene mediates the expression of mdr1 gene and P-glycoprotein in a human glioblastoma cell line.

The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumours. The mechanism by which mdr1 gene and P-gp are overexpressed in human tumours, however, is not yet clear. In this report, we show that the mdm2 (murine double minute 2) gene induced the expression of the mdr1 gene and P-gp in human glioblastoma U87-MG cells, which did not express the MDM2 protein or P-gp. The mdm2 gene, in addition, conferred the resistance of U87-MG cells to the apoptotic cell death induced by etoposide (VP-16) or doxorubicin. Furthermore, treatment with mdm2 antisense oligonucleotides inhibited the expression of P-gp in MDM2-expressing U87-MG cells. These findings suggest that the mdm2 gene may play an important role in the development of MDR phenotype in human tumours.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Involvement of interleukin-1 beta-converting enzyme in apoptosis of bFGF-deprived murine aortic endothelial cells.

Apoptosis (programmed cell death) is an essential physiological process that is genetically regulated and contributes to the balance between cell growth, differentiation, and the maintenance of normal cells. Recent studies show that deprivation of growth factor induces apoptosis in endothelial cells. However, the molecular mechanisms regulating apoptosis remain unclear. In this study, we demonstrate that deprivation of basic fibroblast growth factor (bFGF) increased the expression of interleukin-1 beta-converting enzyme (ICE) protein, and subsequently induced apoptosis in murine aortic endothelial (MAE) cells. In contrast, the proteins of the tumor suppressor p53 and c-myc were undetected during apoptosis. This apoptosis was suppressed by the tetrapeptide ICE inhibitor, Ac-YVAD-CMK. Overexpression of murine ICE, in addition, induced apoptosis in MAE cells using gene transfer techniques. These results strongly suggest that ICE may mediate apoptosis in bFGF-deprived endothelial cells, and the suppression of ICE function could represent a novel approach for the protection of endothelial cells from damages.-Kondo, S., Kondo, Y., Yin, D., Barnett, G. H., Kaakaji, R., Peterson, J. W., Morimura, T., Kubo, H., Takeuchi, J., Barna, B. P. Involvement of interleukin-1 beta converting enzyme in apoptosis of bFGF-deprived murine aortic endothelial cells.

Animals↗
PubMed1996

Detection of transcripts of Marek's disease virus serotype 1 iCP4 homologue (MDV1 ICP4) by in situ hybridization.

Homologues of herpes simplex virus ICP4 are important genes for the activation of many herpesviruses. We detected transcripts of the Marek's disease virus serotype 1 homologue of ICP4 (MDV1 ICP4) by in situ hybridization (ISH). Using a digoxigenin-labeled-RNA (DIG-RNA) probe, MDV1 ICP4 transcripts were detected in c.a. 90% of MDV1-infected chicken embryo fibroblasts (CEF) cells when cytopathic effect was reached to 90% of the CEF cells and in 0.35% of MDCC-MSB-1 (MSB-1) cells, at a frequency similar to that for MD antigen-positive MSB-1 cells. Using the same in situ procedure, we detected abundant MDV1 ICP4 transcripts in the feather follicle epithelium (FFE) and some lymphoid cells in the liver, kidney and peripheral nerve of infected chickens. The subcellular localization of the transcripts appeared to vary: MSB-1 cells had them in the nucleus, infected CEF cells and FFE had them in the nucleus and cytoplasm, and lymphoid cells contained them in the cytoplasm. The MDV1 ICP4 transcripts were also detected in the FFE and lymphoid cells in the liver by reverse-transcriptase polymerase chain reaction (RT-PCR). Detection of MDV1 ICP4 transcripts by RT-PCR indicated the existance of MDV1 ICP4 transcripts-positive cells in these tissues. And these data suggested that DIG-RNA-ISH can detect MDV transcripts on paraffin sections and provide information about their subcellular localization.

Animals↗
PubMed1995

Interleukin-1 beta-converting enzyme mediates cisplatin-induced apoptosis in malignant glioma cells.

Increasing the susceptibility of tumor cells to apoptotic cell death following chemotherapy is of importance to the outcome of cancer treatment. Although the tumor suppressor gene p53 is required for efficient induction of apoptosis by chemotherapeutic agents, it is not the only apoptosis mediator gene. The molecular mechanisms mediating apoptosis following chemotherapy via p53-dependent or p53-independent pathways remain unclear. We show here that cis-diamminedichloroplatinum (cisplatin) induces the expression of interleukin-1 beta-converting enzyme (ICE), a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, in murine and human malignant glioma cells during apoptosis regardless of their p53 status. Furthermore, overexpression of the murine ICE gene induces apoptosis in these tumor cells. The apoptosis induced by cisplatin treatment or murine ICE overexpression can be suppressed by the tetrapeptide ICE inhibitor Ac-YVAD-CMK or the apoptosis inhibitors bcl-2 or bcl-2-related bcl-XL gene. These findings suggest that ICE may mediate apoptosis induced by chemotherapy, and its induction could represent a novel approach for the effective treatment of malignant glioma.

Amino Acid Sequence↗
PubMed1995

MDM2 protein confers the resistance of a human glioblastoma cell line to cisplatin-induced apoptosis.

Induction of apoptosis in tumor cells is an important mechanism of chemotherapy-induced cell death. The tumor-suppressor gene p53 is required for the efficient activation of apoptosis following chemotherapy. However, the molecular mechanism regulating p53-associated apoptosis remains controversial. In this study, we show that the expression of both wild-type p53 and MDM2 (murine double minute 2) proteins was induced when cis-diamminedichloroplatinum (cisplatin) caused apoptosis in human glioblastoma U87-MG cells, which expressed neither wild-type p53 nor MDM2 protein prior to treatment. Overexpression of MDM2 in U87-MG cells transfected with human mdm2 expression vector conferred the resistance of tumor cell to cisplatin-induced apoptosis. In contrast, the treatment with mdm2 antisense oligonucleotide targeted against mdm2 mRNA increased the susceptibility of tumor cells to apoptosis. Changes in expression level of MDM2 protein, however, did not affect the expression of wild-type p53 protein. These findings suggest that MDM2 protein may act as a negative regulator of cisplatin-induced apoptosis, and moreover, may play an important role in the development of resistance to cisplatin in human tumors.

Apoptosis↗
PubMed1995

Combination therapy with cisplatin and nifedipine induces apoptosis in cisplatin-sensitive and cisplatin-resistant human glioblastoma cells.

We attempted to determine whether calcium channel blockers (CCBs) enhance the anti-tumour activity of cis-diamminedichloroplatinum (cisplatin) against both cisplatin-sensitive human glioblastoma U87 MG cells and cisplatin-resistant U87-MG-CR cells, the latter of which we developed for resistance to cisplatin. Nifedipine, a dihydropyridine class CCB, significantly enhanced the anti-tumour effect of cisplatin on these two cell types in vitro and in vivo. Our findings also indicated that, in the absence of normal extracellular Ca2+ nifedipine was capable of enhancing the cytotoxicity of cisplatin. In addition, this anti-tumour activity was partially inhibited by actinomycin D and cycloheximide, suggesting that it is possibly dependent upon new RNA and protein synthesis. Interestingly, ultrastructural analysis, DNA fragmentation assay and cell cycle analysis demonstrated that synergism between cisplatin and nifedipine results in apoptosis (programmed cell death) at a relatively low concentration of cisplatin, which when tested alone did not induce apoptosis. Furthermore, we demonstrated that nuclei from these cells lack a Ca(2+)-dependent endonuclease that degrade chromatin in the linker region between nucleosomes. In conclusion, our studies suggest that the non-cytotoxic agent nifedipine is able to synergistically enhance the anti-tumour effects of cisplatin on U87-MG and U87-MG-CR cells lacking a Ca(2+)-dependent endonuclease and subsequently to induce apoptosis via interaction of nifedipine with an as yet uncharacterised functional site other than a calcium channel on target cells.

Animals↗
PubMed1995

Immunomodulation of peripheral T cells in chickens infected with Marek's disease virus: involvement in immunosuppression.

Marek's disease virus (MDV) causes T cell immunosuppression in chickens during latent infection. Morphological changes specific to apoptosis were demonstrated in peripheral blood mononuclear cells (PBMC) of MDV-infected chickens at 2-3 weeks post-inoculation (p.i.). Analysis of DNA fragmentation in T cell subsets in the peripheral blood revealed that CD4+ T cells but not CD8+ T cells underwent apoptosis after MDV infection. The proportion of CD4+ T cells, but not that of CD8+ T cells, in the peripheral blood expanded transiently at 16 days p.i., and rapidly decreased 1 week later. The decrease in CD4+ T cells might be mediated by apoptosis, because a rapid reduction in CD4+ T cells was observed when these cells underwent apoptosis. Analysis of the T cell-receptor (TCR) repertoire of the peripheral blood showed that V beta 1 but not V beta 2-alpha beta TCR-bearing cells expanded at 16 days p.i., when the transient expansion of the CD4+ T cell population was observed in these chickens. Flow cytometric profiles also showed that the expression of CD8 was down-regulated after infection with MDV, but there was no difference in the expression level of CD4 molecules between normal and infected chickens. Northern blot analysis indicated that the down-regulation of CD8 occurred at the transcriptional level. These results suggest that both apoptosis of CD4+ T cells and down-regulation of CD8 molecules could contribute to the immunosuppression caused by MDV.

Animals↗
PubMed1995

Fibro-osseous pseudotumor of the digits arising in the subungual region: a rare benign lesion simulating extraskeletal osteosarcoma.

A rare case of subungual fibro-osseous pseudotumor of the digits in a 59 year old woman is reported. A painful polypoid mass with ulcerative changes was noted in the subungual portion of the right first toe. Macroscopically, the tumor arose chiefly in the subcutaneous region and was unrelated to the underlying bone tissue. Histologically, the lesion contained fibroblast-like tumor cells producing an extensive osteoid substance in a granulation-like background. Although it was necessary to distinguish the lesion from extraskeletal osteosarcoma, the tumor cells lacked prominent atypical features. It is considered that pathologists and clinicians should add fibro-osseous pseudotumor of the digits to the differential diagnosis of subungual tumor.

Diagnosis, Differential↗
PubMed1995

Tumor necrosis factor-alpha induces p53-dependent apoptosis in rat glioma cells.

In this study, we demonstrated that tumor necrosis factor (TNF)-alpha inhibited the viability of rat glioma (C6) cells and induced apoptosis but did not affect the viability of rat newborn brain, mainly astroglial cells. The antitumor activity of TNF-alpha against C6 cells was partially inhibited by actinomycin D and cycloheximide, suggesting that it is possibly dependent upon new ribonucleic acid and protein synthesis. The results of immunoblotting assay demonstrated that TNF-alpha decreased the expression of mutant p53 protein but induced the expression of wild-type p53 in C6 cells during apoptosis. We suggest that TNF-alpha may activate the function of wild-type p53 protein by the suppression of mutant p53, at least indirectly, and induce p53-dependent apoptosis in glioma cells.

Animals↗
PubMed1995

Photodegradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution.

The photodegradation kinetics of orbifloxacin (1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-pipe raz inyl)-4-oxoquinoline-3-carboxylic acid) was investigated in aqueous solution at various pH values (1.2-12.5) and at an ionic strength of 0.5. The photodegradation experiments were performed using a fluorescent or a chemical lamp as a light source and the cumulative number of photons during exposure was determined by a ferrioxalate actinometer. It was found that the photodegradation of orbifloxacin followed apparent first-order kinetics under both types of artificial light. The photodegradation rates of orbifloxacin in a neutral medium were higher than those in acidic and alkaline media. Orbifloxacin was most unstable in solution at pH 7.4, and its degradation half-life was 0.9 h. Also, the log k-pH profile indicated that the photodegradation rate of orbifloxacin was related to the dissociation of the carboxylic and dimethylpiperazinyl groups and the main photo-labile species was the zwitterionic form. In addition, the photodegradation kinetics of the decarboxylated derivative of orbifloxacin in aqueous solution was investigated to determine the effect of the functional groups on the photodegradation of orbifloxacin.

Anti-Infective Agents↗
PubMed1995

Degradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution.

The degradation kinetics of orbifloxacin [1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1-pipe raz inyl)-4-oxoquinoline-3-carboxylic acid] was investigated as a function of pH (1.5-10.5), temperature (100-120 degrees C) and buffer concentration (0.05-0.2 M) by means of high-performance liquid chromatography. The degradation of orbifloxacin in aqueous solution followed apparent first-order kinetics under all experimental conditions. No appreciable effect of buffer on the degradation of orbifloxacin was observed for any of the buffer species used in this study. The log k-pH profiles indicated specific-acid and specific-base catalyses and there were inflection points near pH 6 and 9 corresponding to the pKa1 and pKa2 values. From the Arrhenius plots, the activation energies for k'H, k'H2O, kH2O, k"H2O and k"OH were found to be 31.9, 36.9, 23.5, 26.5 and 19.0 kcal/mol, respectively. Arrhenius data obtained from this study showed that the degradation of orbifloxacin at room temperature was negligible at all pH values studied conditions (pH 1.5-10.5).

Anti-Infective Agents↗
PubMed1995

Combination therapy with cisplatin and nifedipine inducing apoptosis in multidrug-resistant human glioblastoma cells.

The authors found that multidrug-resistant human glioblastoma GB-1 cells demonstrated significantly more resistance to cisplatin than did nondrug-resistant human glioblastoma U87-MG cells (p < 0.1). They therefore attempted to determine whether calcium channel blockers enhance the antitumor activity of cisplatin against GB-1 cells. Nifedipine, a dihydropyridine calcium channel blocker, significantly enhanced the antitumor effect of cisplatin on GB-1 cells (p < 0.05). In the absence of normal extracellular Ca++, nifedipine enhanced the cytotoxicity of cisplatin. In addition, the antitumor activity of combined cisplatin and nifedipine was inhibited both by actinomycin D and cycloheximide, suggesting that such activity is dependent upon new RNA and protein synthesis. Surprisingly, DNA fragmentation assay demonstrated that synergism between cisplatin and nifedipine resulted in apoptosis (programmed cell death) at a relatively low concentration of cisplatin, which when tested alone did not induce apoptosis. In addition, it was demonstrated that nuclei from GB-1 cells lacked a Ca(++)-dependent endonuclease that degrades chromatin into nucleosomes and that calcium ionophore A 23187 did not decrease the viability of GB-1 cells. The above findings suggest the hypothesis that the noncytotoxic agent nifedipine synergistically enhances the antitumor effect of cisplatin on multidrug-resistant GB-1 cells lacking Ca(++)-dependent endonuclease, and subsequently induces apoptosis via its interaction with an as yet uncharacterized functional site other than the calcium channel on GB-1 cells.

Apoptosis↗
PubMed1994

Transfection with a bcl-2 expression vector protects transplanted bone marrow from chemotherapy-induced myelosuppression.

The use of cytokines such as granulocyte-colony-stimulating factor (G-CSF) to ameliorate chemotherapy-induced myelosuppression may not only stimulate the recovery of normal hematopoietic cells but may also enhance the proliferation of the tumor cells with functional receptors for these cytokines. In this study, we show that administration of recombinant human (rh) G-CSF decreased the in vitro and in vivo cytotoxic effects of Adriamycin or etoposide on L1210 murine leukemic cells with receptors for rhG-CSF. Transplantation of bone marrow cells expressing high levels of bcl-2 from a retroviral construct [MPZenNeo(bcl-2)] (bcl-2-BMT) did not decrease the in vivo cytotoxic effect of etoposide on L1210 cells, but enabled recovery of myelopoiesis following etoposide-induced myelosuppression to almost the same extent as did the administration of rhG-CSF. These findings suggest the possibility that bcl-2 transfection could be used to protect transplanted bone marrow from chemotherapy-induced myelosuppression on behalf of administration of rhG-CSF, in case of treatment of tumors with functional receptors for rhG-CSF.

Animals↗
PubMed1994

Induction of apoptosis in murine ACTH-secreting pituitary adenoma cells by bromocriptine.

Bromocriptine, a dopamine agonist, is now an accepted primary therapeutic agent for patients with prolactinomas and other pituitary adenomas. In this study, we demonstrated that bromocriptine inhibited the proliferation of murine ACTH-secreting pituitary adenoma (AtT-20) cells. In addition, the antitumor activity of bromocriptine was inhibited both by actinomycin D and cycloheximide, suggesting that it was dependent on new RNA and protein synthesis. Interestingly, the results of DNA fragmentation assays and cell cycle analysis clearly demonstrated that bromocriptine induced apoptosis in AtT-20 cells.

Adenoma↗
PubMed1994

bcl-2 gene prevents apoptosis of basic fibroblast growth factor-deprived murine aortic endothelial cells.

Growth factors such as basic fibroblast growth factor (bFGF) have been found to promote the survival and proliferation of endothelial cells. However, the mechanism by which growth factors control the regeneration and degeneration of the endothelial cells remained poorly understood. In this study, we demonstrated that apoptosis of murine aortic endothelial (MAE) cells was induced by deprivation of bFGF but required new RNA and protein synthesis. Furthermore, enforced expression of bcl-2 gene in MAE cells using gene transfer techniques decreased apoptosis induced by deprivation of bFGF. These findings suggest that bcl-2 interferes with a pathway for endothelial cell death that is induced by deprivation of bFGF.

Animals↗