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T Morimura

Publications and source records attributed to T Morimura.

At least 19 recordsLinked to original sources
PubMed2000

Cell cycle arrest and apoptosis induced by Notch1 in B cells.

Notch receptors play various roles for cell fate decisions in developing organs, although their functions at the cell level are poorly understood. Recently, we found that Notch1 and its ligand are each expressed in juxtaposed cell compartments in the follicles of the bursa of Fabricius, the central organ for chicken B cell development. To examine the function of Notch1 in B cells, a constitutively active form of chicken Notch1 was expressed in a chicken B cell line, DT40, by a Cre/loxP-mediated inducible expression system. Remarkably, the active Notch1 caused growth suppression of the cells, accompanied by a cell cycle inhibition at the G(1) phase and apoptosis. The expression of Hairy1, a gene product up-regulated by the Notch1 signaling, also induced the apoptosis, but no cell cycle inhibition. Thus, Notch1 signaling induces apoptosis of the B cells through Hairy1, and the G(1) cell cycle arrest through other pathways. This novel function of Notch1 may account for the recent observations indicating the selective inhibition of early B cell development in mice by Notch1.

Animals↗
PubMed1999

Re-isolation of Marek's disease virus from T cell subsets of vaccinated and non-vaccinated chickens.

To know the effect of Marek's disease (MD) vaccines, we analyzed the distribution of MD virus (MDV) among T cell subsets from chickens vaccinated or non-vaccinated with MD vaccine and subsequently challenged with a virulent MDV. The challenged MDV was reisolated preferentially from CD4+ T cells, and the average titers of challenged MDV rescued were significantly lower in vaccinated chickens compared to that of non-vaccinated chickens. In addition, it was also shown that different serotypes of MDV, CVI988 and SB-1, have remarkable difference in recovery rates of viruses from CD4+ and CD8+ T cells, though both CVI988 and SB-1 can reduce the infection rates of virulent MDV to splenocytes.

Animals↗
PubMed1999

Anti-viral and anti-tumor effects induced by an attenuated Marek's disease virus in CD4- or CD8-deficient chickens.

By vaccination with an attenuated Marek's disease virus (MDV), strain CVI988, chickens are protected from the development of T cell lymphoma caused by an oncogenic MDV. To clarify the role of T lymphocyte subsets in the protection mechanisms of this vaccine, vaccinated chickens were depleted of T cell subsets by neonatal thymectomy and injections of monoclonal antibodies specific to chicken CD4 and CD8 molecules, and then challenged with an oncogenic MDV, strain Md5. The MDV titers rescued from CD8(+) T cells, which are the main targets for latent infection and subsequent transformation by MDV, was much higher in the CD8-deficient vaccinated chickens than in untreated vaccinated chickens at the early stage of the latent phase. However, the neonatal vaccination prevented lymphoma formation by strain Md5 even in either CD4(+) or CD8(+) T cell-depleted chickens. These results suggest that specific CD8(+) T cell responses induced by the MD vaccine play a crucial role in the prevention of MDV infection during the latent phase, but may not be essential for the prevention of lymphoma formation by an oncogenic MDV.

Animals↗
PubMed1999

Lateralized memory deficits on the Wada test correlate with the side of lobectomy only for patients with unilateral medial temporal lobe epilepsy.

The aim of this study was to determine whether the predictive value of the intracarotid amobarbital test (IAT) for the side to be resected is applicable only to medial temporal lobe epilepsy and to investigate whether there are different patterns of memory performances on the IAT between patients with unilateral mesial temporal sclerosis (UMT group) and those without (non-UMT group). We studied 30 patients in the UMT group and 10 in the non-UMT group, who underwent pre-surgical evaluation for intractable temporal lobe epilepsy. Memory performances on the IAT was defined as the percentage of memory items presented during unilateral hemispheric anesthesia that was recognized after recovery. More than a 20% decline of the memory performance on the IAT compared with the memory performance on the pre-test was regarded as a memory deficit. Age at onset of epilepsy was significantly younger in the UMT than in the non-UMT group. Surgical outcome was significantly better in the UMT than in the non-UMT group. The lateralizing value of unilateral memory deficits on the IAT was statistically confirmed. There was a significant association between falsely lateralizing memory performances and the non-UMT group. Excluding the exceptional cases with right-sided language dominance in spite of right-sided lesions, the high incidence of the unilateral right-sided memory deficits in the non-UMT group was statistically significant. This study suggested that the excellent lateralizing value of the memory performances on the IAT is limited to patients with mesial temporal lobe epilepsy. IAT memory performances in patients without such lesions can be misleading, even if lateralized, because their memory status presumably reflects a natural lateralization of the memory organization which is independent of the epileptogenic focus.

Adult↗
PubMed1998

BASH, a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius.

The bursa of Fabricius is a gut-associated lymphoid organ that is essential for the generation of a diversified B cell repertoire in the chicken. We describe here a novel gene preferentially expressed in bursal B cells. The gene encodes an 85-kDa protein, designated BASH (B cell adaptor containing SH2 domain), that contains N-terminal acidic domains with SH2 domain-binding phosphotyrosine-based motifs, a proline-rich domain, and a C-terminal SH2 domain. BASH shows a substantial sequence similarity to SLP-76, an adaptor protein functioning in TCR-signal transduction. BASH becomes tyrosine-phosphorylated with the B cell Ag receptor (BCR) cross-link or by coexpression with Syk and Lyn and associates with signaling molecules including Syk and a putative chicken Shc homologue. Overexpression of BASH results in suppression of the NF-AT activation induced by BCR-cross-linking. These findings suggest that BASH is involved in BCR-mediated signal transduction and could play a critical role in B cell development in the bursa.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Pathogenesis of Marek's disease (MD) and possible mechanisms of immunity induced by MD vaccine.

Marek's disease (MD) is a lymphoproliferative disease of chicken, which is characterized by malignant T cell-lymphoma formation. This disease can be effectively prevented by vaccination with attenuated MD virus (MDV), apathogenic MDV or herpesvirus of turkey. MD vaccines are ones of a few vaccines which can prevent virus-induced tumor among mammalian and avian species. To determine the roles of T cell subsets in the protection mechanism, chickens vaccinated with an attenuated MDV (CVI988) were depleted of either CD4+ or CD8+ T cells by neonatal thymectomy and injections of monoclonal antibodies against chicken CD4 or CD8 molecules and then challenged with an oncogenic MDV. These birds were effectively protected from MDV-induced tumors. However, virus titers in CD4+ T cells, which are the main target cells for MDV-latent infection and subsequent transformation, were much higher in CD8-deficient vaccinated chickens than in untreated vaccinated chickens at the early stage of the latent phase. These results suggested that CD8+ T cell responses induced by the MD vaccine are essential for anti-virus but not anti-tumor effects. Here, we will discuss how the attenuated vaccine prevents chickens from lymphoma-formation by an oncogenic MDV.

Animals↗
PubMed1998

Retroviral sequence located in border region of short unique region and short terminal repeat of Md5 strain of Marek's disease virus type 1.

A 246-base pair (bp) retroviral sequence, which was homologous to a long terminal repeat of avian erythroblastosis virus (AEV), was detected and cloned from Md5 strain (Md5) of Marek's disease virus type 1 (MDV1) by representational difference analysis (RDA). The retroviral sequence was thought to be located in the border region of short unique region (U(s) and short terminal repeat (TRs), but did not exist in the border region of U(s) and the inverted short repeat (IRs) of the Md5 genome. A cloned fragment of the US/TRs border region of the Md5 genome showed a construction of U-E'-R-U'-E-TRs with the regions designated as follows: E, expanded TRs reported by Jones et al. [Proc. Natl. Acad. Sci. U.S.A. 90, 3855, 1993]; E', a partial copy of the expanded TRs; R, the retroviral sequence detected in Md5 genome; U, TRs-end sequence of U(s); U', a partial copy of TRs-end sequence of U(s). The sequence unit indicated as E'-R-U' was thought to be heterogeneously repeated in the Md5 genome. Since this retroviral sequence reportedly did not exist in the original stock of Md5, the retroviral sequence is thought to be inserted in the Md5 genome without experimental co-infection of avian cells with retrovirus and MDV1. These results suggest that RDA could be useful for the detection of retroviral sequences in the herpesvirus genome.

Alpharetrovirus↗
PubMed1998

Analysis of tumor suppressor gene p53 in chicken lymphoblastoid tumor cell lines and field tumors.

To determine whether there is any abnormalities of the p53 gene in chicken lymphoblastoid tumor cell lines derived from Marek's disease (MD), lymphoid leukosis, reticuloendotheliosis, and field tumors, some portions of p53 cDNA corresponding to core and C-terminal domains (nucleotide positions 277-1104 in the p53 open reading frame (ORF)) were sequenced. Several mutations were identified in both cell lines and field tumors. However, none of these mutations is localized at the "hot spot", which has been reported as the site for transformation-activating mutations. Moreover, partial cDNA clones with a 122-bp deletion in the p53 ORF were identified in two cell lines, MSB1 and MTB1 derived from MD tumors. Southern blot analysis showed that no deletion occurred in the genome of p53 in MSB1, indicating that deletion occurred at the transcriptional level. This deletion could cause a frame shift of the encoding p53 protein, possibly resulting in the generation of a functionally different p53 protein. However, we confirmed that p53 mRNA without deletion is also present in each of these cell lines. These mutations of the p53 gene and deletion in the p53 transcript may be ones of molecular changes specific to the transformation induced by MD virus.

Amino Acid Sequence↗
PubMed1998

Pineal dermoid cyst developing 18 years after gross total removal of a pineal mature teratoma.

A 21-year-old male presented with a pineal dermoid cyst manifesting as headache and diplopia. He had undergone gross total removal of a pineal mature teratoma 18 years before and had done well until recently. Diffusion-weighted magnetic resonance imaging showed a region of high signal intensity due to a round mass in the pineal region and extending into the trigone of the right lateral ventricle. Subtotal excision of the tumor was achieved. Histological examination showed an epidermoid cyst consisting of keratinized stratified squamous epithelium and connective tissue. Intraoperative observation had detected black hairs, so the diagnosis was dermoid cyst. The dermoid cyst may have arisen from a microscopic remnant of the cyst wall of the original pineal mature teratoma. The regrowth of a dermoid cyst 18 years after gross total removal of a mature cystic teratoma in the pineal region is exceptional. However, careful follow-up of patients who undergo gross total removal of a pineal teratoma is recommended for a period more than that of the patient's age at surgery plus 9 months.

Adolescent↗
PubMed1997

Induction of apoptosis in multi-drug resistant (MDR) human glioblastoma cells by SN-38, a metabolite of the camptothecin derivative CPT-11.

The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumors. Recent studies demonstrate that SN-38, a metabolite of the camptothecin (CPT) derivative CPT-11, has antitumor effects on several tumors, but the mechanisms responsible for its cytotoxicity remain unclear. We therefore determined whether SN-38 has cytotoxic effects on MDR human glioblastoma GB-1 cells and non-MDR human glioblastoma U87-MG cells. Furthermore, we determined what role SN-38 plays in the induction of cytotoxicity in these tumor cells. In this study, we demonstrated that SN-38 had significantly stronger antitumor effects on GB-1 and U-87MG cells than did CPT (P < 0.01 and P < 0.05, respectively). In addition, findings obtained using a DNA fragmentation assay, Hoechst 33258 staining, in situ end-labeling and cell cycle analysis demonstrated that SN-38 induced apoptosis in these tumors. Our results suggest that SN-38 has a stronger antitumor effect on malignant glioma cells regardless of MDR expression than does CPT, and therefore can be considered a new chemotherapeutic agent potentially effective in the treatment of human primary or recurrent malignant gliomas resistant to chemotherapy.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Photodegradation products of a new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution.

A new antibacterial fluoroquinolone derivative, orbifloxacin (ORFX), is decomposed photochemically in aqueous solution. When ORFX solution was irradiated with a chemical lamp or sunlight, three major photodegradation products were isolated by preparative HPLC. These degradation products were identified by electron-impact mass spectrometry, liquid-secondary-ion mass spectrometry and 1-H-NMR spectroscopy. Moreover, the photodegradation pathway was investigated by a similar study using several fluoroquinolone derivatives which were presumed to be the intermediates of the photoreaction of the ORFX. Consequently, it was found that two main photochemical reactions, the decomposition of the dimethylpiperazinyl moiety and the elimination of the cyclopropyl group, take place in ORFX. The detected structures of photodegradation products and the photodegradation studies of the postulated intermediates suggested that the photodecomposition of the dimethylpiperazinyl ring at the 7-position and the elimination of the cyclopropyl group at the 1-position occurred concurrently with the release of fluorine at the 8-position.

Anti-Infective Agents↗
PubMed1997

Apoptosis in peripheral CD4+T cells and thymocytes by Marek's disease virus-infection.

Histological study revealed that Marek's disease virus (MDV) can cause apoptosis in peripheral blood lymphocytes (PBL) in latently infected chickens. Analysis of DNA fragmentation indicated that CD4+T cells but not CD8+T cells underwent apoptosis. These apoptotic changes were also observed in the thymus during the acute phase of the infection. Flow cytometry analysis showed the drastic decrease of CD4+CD8+ thymocytes, indicating that MDV can induce apoptosis in CD4+CD8+ immature thymocytes in acutely infected chickens. These changes might be involved in the immuno-suppression induced by MDV.

Animals↗
PubMed1996

The transforming activities of MDM2 in cultured neonatal rat astrocytes.

Although the molecular events regulating the pathogenesis of malignant astrocytomas remains unclear, the inactivation of tumor suppressor genes may be a key factor. The inactivation of p53 by mutation or deletion, however, is not the only obligatory step in astrocytoma genesis. The MDM2 protein has been shown to bind to and downmodulate p53 function, and to have oncogenic capacity. The MDM2 gene is also amplified and overexpressed in a subset of malignant astrocytomas without p53 mutation. Here we show that overexpression of MDM2 promoted the DNA synthesis of cultured neonatal rat astrocytes (RNB cells), abrogated the transcriptional activity of wild-type p53, conferred invasive activity, and subsequently induced the transformation from astrocytes to high-grade astrocytomas. Intriguingly, MDM2 enhanced the expression of angiogenic mitogens; basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) in RNB cells. These results indicate that MDM2 may play an important role in the progression of astrocytomas, by not only conferring invasive activity but also stimulating the expression of angiogenic growth factors.

Animals↗
PubMed1996

WAF1/CIP1 increases the susceptibility of p53 non-functional malignant glioma cells to cisplatin-induced apoptosis.

Induction of apoptosis in tumor cells is an important determinant in the outcome of therapy. Molecular details of the apoptosis pathway, however, are still poorly defined. The recently discovered WAF1/CIP1 gene is a potent inhibitor of cyclin-dependent kinases and a mediator of tumor-suppressor p53-dependent apoptosis by DNA damage. In addition, WAF1/CIP1 expression is shown to be triggered through the p53-independent pathway. The relationship between WAF1/CIP1 and p53-independent apoptosis by DNA damage, however, remains unclear. In this study, we show that WAF1/CIP1 was induced in p53-dependent apoptosis of U87-MG glioma cells by cis-diamminedichloroplatinum (cisplatin), and overexpression of WAF1/CIP1 induced apoptosis in U87-MG cells without cisplatin treatment. In contrast, the p53-independent apoptosis of GB-1 glioma cells by cisplatin did not express WAF1/CIP1. Overexpression of WAF1/CIP1 inhibited DNA synthesis in GB-1 cells, but did not induce apoptosis. Interestingly, WAF1/CIP1 increased the susceptibility of GB-1 cells to cisplatin-induced apoptosis. These results suggest that overexpression of WAF1/CIP1 may have potential for the treatment of tumors with non-functional p53.

Antineoplastic Agents↗
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↗