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Biomedical subjects

Y Kanda

Publications and source records attributed to Y Kanda.

At least 127 records · Page 7Linked to original sources
PubMed1999

Transcriptional inhibition of p53 by the MLL/MEN chimeric protein found in myeloid leukemia.

The t(11;19)(q23;p13.1) translocation is frequently found in adult myeloid leukemia. In the MLL/MEN fusion protein generated by this translocation, most of the coding region of the MEN protein, an RNA polymerase II elongation factor, is fused to the N-terminal third of the MLL protein, a possible transcriptional regulator. However, the molecular mechanism of leukemogenesis by the fusion protein remains unclear. We investigated the effects of the fusion protein on p53 function using luciferase assays. Overexpression of the fusion protein suppressed the transactivation ability of p53. This negative effect of the fusion protein on p53 function was dependent on the region derived from MEN. Moreover, p53 coimmunoprecipitated with MLL/MEN as well as MEN, suggesting that the fusion protein binds to p53 through the MEN region. We found that MEN binding to p53 was mediated by its N-terminal region and repression of p53 transcriptional activity was mediated by its C-terminal region. We also found that these two functional regions were essential for the transformation of Rat1 cells mediated by MEN. Although we could not demonstrate a functional difference between MLL/MEN and MEN in this study, these data suggest that the MLL/MEN chimeric transcriptional regulator may exert its oncogenic activity by inhibiting the function of the p53 tumor-suppressor protein by binding to it. Our findings provide a novel insight into the leukemogenic mechanism exerted by the t(11;19)(q23;p13.1) translocation.

Adult↗
PubMed1999

Differential regulation of Na+/H+ exchange and DNA synthesis in vascular smooth muscle cells.

Na+/H+ exchange has been proposed to be involved in the regulation of cell growth. However, little is known about the regulatory pathway and relationship between Na+/H+ exchange and DNA synthesis. In vascular smooth muscle cells, platelet-derived growth factor (a tyrosine kinase-coupled receptor agonist) and thrombin (a G protein-coupled receptor agonist) stimulate both activation of Na+/H+ exchange and DNA synthesis. In this study, we compared the effect of platelet-derived growth factor (PDGF) and thrombin on the signal transduction pathway leading to the activation of these responses in A10 cells, clonal rat thoracic aortic smooth muscle cells. To investigate the role of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase as potential mediators, we examined the effect of pharmacological kinase inhibitors on these responses. The Na+/H+ exchange activity induced by thrombin was inhibited by a specific inhibitor of MAPK kinase, 2'-amino-3'-methoxyflavone (PD98059), but was not affected by a specific phosphatidylinositol-3-kinase inhibitor, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). Thrombin-induced DNA synthesis was inhibited by LY294002, but not by PD98059. In contrast, the Na+/H+ exchange activity induced by PDGF was inhibited by neither LY294002 nor PD98059, but PDGF-induced DNA synthesis was inhibited by both LY294002 and PD98059. These data suggest that, in A10 cells, Na+/H+ exchange activation and DNA synthesis are differently regulated by the two extracellular stimuli.

Animals↗
PubMed1999

TT virus in bone marrow transplant recipients.

TT virus (TTV) is a newly discovered transfusion-transmissible DNA virus, which may cause posttransfusion hepatitis. The virus was detected in 12% of Japanese blood donors. The aim of the study is to investigate the prevalence and clinical influence of TTV in bone marrow transplant (BMT) recipients. Sera from 25 BMT recipients obtained 6 to 12 weeks after the transplant were examined for TTV-DNA by the seminested polymerase chain reaction. Serial samples were additionally analyzed in patients with TTV-DNA. Fifteen of 25 recipients (60%) were positive for TTV-DNA after transplant, whereas it was detected in only two of 20 BMT donors (10%). In patients positive for TTV-DNA before BMT, the amount of TTV-DNA decreased to an undetectable level during the myelosuppressed period after BMT. We also found that there was a novel group of TTV, G3, classified by the nucleotide sequences. The median peak alanine aminotransferase (ALT) levels were 135.0 IU/L and 116.5 IU/L (normal range, 4 to 36 IU/L) in TTV-positive and TTV-negative recipients, respectively. In one of the seven TTV-positive patients who developed hepatic injury (ALT > 150 IU/L), a serial change in the serum TTV titer showed a good correlation with the ALT level. We concluded that (1) the prevalence of TTV is high in BMT recipients, (2) TTV might be replicated mainly in hematopoietic cells, (3) transfusion-transmitted TTV may cause persistent infection, (4) a novel genetic group of TTV, G3, was discovered, and (5) TTV does not seem to frequently cause hepatic injury, although one patient was strongly suggested to have TTV-induced hepatitis.

Adolescent↗
PubMed1999

N5 endometrial stromal cell line: a model system to study decidual prolactin gene expression.

Prolactin gene expression in extrapituitary tissues, such as decidua and lymphocytes, is regulated by a distinct promoter approximately 6 kb upstream of the pituitary prolactin gene transcription start site. Here we describe studies in a human endometrial stromal cell line, N5, that was immortalized by transfection with an SV40 mutant and which expresses the prolactin gene driven by the extrapituitary promoter. The N5 cells have phenotypic features of primary cultures of decidualized human endometrial stromal cells and secrete low levels of prolactin and insulin-like growth factor binding protein-1 (IGFBP-1), both of which are markers of decidualized endometrial stromal cells. As in primary cultures of endometrial stromal cells, treatment of N5 cells with progesterone and estradiol alone or in combination with prostaglandin E2 stimulated the synthesis and release of prolactin. Transient transfection of the N5 cells with an expression vector containing - 2927/ + 66 bp of the decidual prolactin promoter coupled to a luciferase reporter gene resulted in a 20 to 25-fold increase in luciferase activity, a magnitude similar to that which occurs in primary cultures of endometrial stromal cells decidualized in vitro by treatment with progesterone and estradiol. Luciferase expression levels were similar in untreated N5 cells and N5 cells treated with progesterone and estradiol. Taken together, these results indicate that the N5 human endometrial stromal cell line has phenotypic characteristics of normal decidualized stromal cells and is a useful model to study regulation of decidual prolactin gene expression.

Bucladesine↗
PubMed1999

Unilateral papilledema after bone marrow transplantation.

We describe a patient who developed unilateral papilledema after allogeneic BMT. This is a rare manifestation of pseudotumor cerebri, which results from elevated intracranial pressure caused by cyclosporin A. The papilledema usually involves the fundi bilaterally, but unilateral involvement has been described. Congenital anomalies, compression and adhesion of the optic nerve sheath are its causes. In this patient, the right optic fundus was spared although leukemic infiltration was present on this side and high-dose irradiation (72 Gy) was given. Although papilledema is a sensitive marker of elevated intracranial pressure, this sign may be masked by constriction of the optic sheath in patients who suffer from leukemic infiltration of the central nervous system and receive high doses of cranial irradiation.

Adult↗
PubMed1999

Aspergillus tracheobronchitis after allogeneic bone marrow transplantation.

We describe a patient who developed Aspergillus tracheobronchitis after BMT. She complained of progressive dyspnea on day +165 and her respiratory function deteriorated rapidly. Although neither early chest X-rays nor CT scans were negative, bronchoscopy revealed formation of a pseudomembrane around the bronchial walls. Based upon pathological and microbiological examinations, she was diagnosed as having invasive Aspergillus tracheobronchitis. Retrospectively analyzed, the Aspergillus circulating antigen detection tests became positive before clinical symptoms developed, and may be beneficial for early diagnosis of Aspergillus tracheobronchitis. This form of aspergillosis should be regarded as one of the serious complications after BMT.

Adult↗
PubMed1999

Early diagnosis of central nervous system aspergillosis using polymerase chain reaction, latex agglutination test, and enzyme-linked immunosorbent assay.

To investigate the usefulness of examination of cerebrospinal fluids (CSF) in the diagnosis of central nervous system (CNS) aspergillosis, we examined five patients with either brain abscesses or cerebral infarctions and 11 control patients. CSF samples were subjected to enzyme-linked immunosorbent assay (EIA), latex agglutination test (LA) and polymerase chain reaction (PCR). Cultures of CSF samples were negative in all the patients, but PCR, EIA and LA were positive in five, four and four patients with CNS aspergillosis, respectively. None of these tests were positive in the control patients. CSF examination may be beneficial in the diagnosis of CNS aspergillosis.

Adult↗
PubMed1999

Inhibition of phosphodiesterase/pyrophosphatase activity of PC-1 by its association with glycosaminoglycans.

PC-1 is a type II membrane-bound glycoprotein consisting of a short N-terminal cytoplasmic domain and a large C-terminal extracellular domain, which contains phosphodiesterase/pyrophosphatase activity. When Jurkat T cells were cultured with dibutyryl cAMP, the membrane-bound PC-1 and its soluble form were induced. They were purified as a homodimer of a 130 kDa peptide and a 120 kDa monomer, respectively, and the same two forms could also be obtained from COS-7 cells that had been transfected with PC-1 cDNA. The membrane-bound and soluble forms of PC-1 were indistinguishable from each other in terms of their enzyme kinetics and N-glycosylated moieties. Thus, the enzymatically active and fully glycosylated form of soluble PC-1 was utilized to search for its interacting molecules. The phosphodiesterase/pyrophosphatase activity of PC-1 was competitively inhibited by glycosaminoglycans, such as heparin and heparan sulfate, which are the major components of the extracellular matrix. PC-1 was capable of binding to heparin-Sepharose and the binding was inhibited in the presence of the enzyme substrate, ATP or its nonhydrolyzable analog. The enzyme activity of PC-1 itself, however, was not required for the binding to heparin-Sepharose. These results suggest that PC-1 might function as an adhesion molecule independent of its enzyme activity to associate with glycosaminoglycans in the extracellular matrix.

Animals↗
PubMed1999

Antitumor activity of KF22678, a novel thioester derivative of leinamycin.

KF22678, a novel thioester derivative of leinamycin with the 1-oxo-1,2-dithiolane-3-one moiety, was examined for anti-tumor activity, toxicity in mice and activation mechanism. KF22678 showed a broad antitumor spectrum against human carcinoma xenografts (lung, colon, ovary and prostate). The efficacy of KF22678 was significantly higher than that of cisplatin. KF22678 exhibited low cross-resistance against various drug-resistant cell lines of MDR1 or MRP overexpressing human tumors, and, in addition, exhibited more potent antitumor activity in vivo than ADM against A2780/ADM and KB/MRP xenograft. DL-Buthionine sulfoximine (BSO) pretreatment significantly reduced intracellular glutathione (GSH) level in human lung carcinoma A549 cells, leading to decrease in the cytotoxicity of KF22678, whereas the cytotoxicity of melphalan was augmented by BSO pretreatment. DNA single-strand breaks (SSB) were observed in A549 cells treated with KF22678 and bleomycin. DNA SSB induced by KF22678 was greatly reduced in the presence of BSO in the cells, whereas DNA SSB induced by bleomycin was not. In addition, the antitumor activity of KF22678 against BSO-pretreated human lung carcinoma PC-9 tumor was significantly decreased. These results suggest that the activation of KF22678 by intracellular GSH might be important for DNA SSB and antitumor activity in vitro and in vivo.

Animals↗
PubMed1999

Interleukin-2 inhibits the synthesis and release of prolactin from human decidual cells.

PRL is synthesized and released by several extrapituitary tissues, including decidualized endometrial stromal cells. As interleukin-2 (IL-2) stimulates the synthesis and release of pituitary PRL, and decidual stromal cells have receptors for IL-2, we examined whether IL-2 also regulates the release of decidual PRL. Exposure of primary cultures of human decidual cells (10(6) cells/well) from term pregnancies to IL-2 (50 ng/mL) inhibited PRL release beginning 48 h after exposure. The inhibition by IL-2 was dose dependent, and the maximal inhibition of PRL release after 5 days of exposure to IL-2 was 71.0 +/- 0.9% (mean +/- SE). IL-2, however, had no effect on decidual cell viability. The inhibitory effect of IL-2 on PRL release was secondary to inhibition of PRL synthesis. Decidualized human endometrial stromal cells transfected with 3 kb of the extrapituitary PRL (exon 1a) promoter coupled to a luciferase expression vector responded to IL-2 (10 ng/mL) with a significant decrease in luciferase activity. These findings strongly suggest that IL-2 inhibits the synthesis and release of decidual PRL and provide further support for a critical role of cytokines in the regulation of decidual PRL gene expression.

Cells, Cultured↗
PubMed1999

Inhibitory effects of Sasa senanensis Rehder extract (SE) on calcium-ionophore A23187-induced histamine release from rat peritoneal exudate cells.

The effects of Sasa senanensis Rehder extract (SE) by alkaline hydrolysis on histamine release from rat peritoneal exudate cells (PECs) were examined. Preincubation with SE for 5 min suppressed calcium-ionophore A23187-induced histamine release in a concentration-dependent manner. A23187 evoked a quick increase in cytoplasmic free calcium ([Ca2+]i) levels in the presence of extracellular calcium. Preincubation with SE also had an inhibitory effect on calcium influx increases induced by A23187. These results indicate that SE prevents degranulation from rat PECs by inhibiting [Ca2+]i level elevation.

Animals↗
PubMed1999

Early diagnosis of central nervous system aspergillosis with combination use of cerebral diffusion-weighted echo-planar magnetic resonance image and polymerase chain reaction of cerebrospinal fluid.

We treated a patient diagnosed as central nervous system (CNS) aspergillosis with the combined use of cerebral diffusion-weighted echo-planar magnetic resonance imaging (DWI) and polymerase chain reaction of the cerebrospinal fluid (CSF-PCR). DWI, a cutting-edge imaging modality to reveal the earliest changes of cerebral infarction, detected cerebral fungal embolization when the conventional computed tomographic scan and magnetic resonance imaging failed to reveal it. CSF-PCR demonstrated the presence of Aspergillus-specific DNA in the specimen, when the conventional examination and culture of CSF were nonspecific or negative. These diagnostic methods could be useful in the early diagnosis of CNS aspergillosis.

Aspergillosis↗
PubMed1999

Increased serum soluble Fas ligand associated with recurrent B-cell non-Hodgkin's lymphoma after autologous peripheral blood stem cell transplantation.

Fas-ligand (FasL) is a member of the tumor necrosis factor family and transmits apoptotic cell death signal by binding to its receptor, Fas. FasL is expressed on the cell surface of activated T-cell and natural killer (NK) cell. It has been shown that the FasL can be released from the cell surface by metalloproteinase. The serum soluble FasL (sFasL) is increased in some patients with NK cell lymphoma/large granular lymphocytic leukemia. We have recently seen a patient with recurrent B-cell lymphoma accompanied with an increased serum sFasL level after autologous peripheral blood stem cell transplantation. The sFasL was markedly decreased with the tumor regression induced by the chemotherapy. We present here the first case of an elevated serum sFasL level associated with B-cell lineage malignancy and discuss the possible clinical value of sFasL.

Adult↗