Search PubMed⌕ Search

Biomedical subjects

T Taniguchi

Publications and source records attributed to T Taniguchi.

At least 325 records · Page 18Linked to original sources
PubMed1997

Effects of a thromboxane A2 receptor antagonist in an animal model of inflammatory bowel disease.

BACKGROUND/AIMS: We evaluated the effects of an antagonist of the thromboxane A2 receptor (ONO-NT-126) in an animal model of inflammatory bowel disease (IBD). METHODS: Colitis was induced by intracolonic instillation of trinitrobenzenesulfonic acid/ethanol in male Wistar rats. ONO-NT-126 or vehicle alone was administered intraluminally via anus once a day. The rats were killed after 7 days for assessment of colonic damage by the colonic damage score. RESULTS AND CONCLUSION: ONO-NT-126 markedly reduced the colonic damage. Our findings suggest that the thromboxane-thromboxane receptor system plays an important role in this model of IBD and that antagonism of the thromboxane A2 receptor may prove useful for the treatment of IBD.

Animals↗
PubMed1997

Possible involvement of rapamycin-sensitive pathway in Bcl-2 expression in human neuroblastoma SH-SY5Y cells.

In human neuroblastoma SH-SY5Y cells, treatment with immunosuppressants such as FK506, cyclosporin A or rapamycin for 4 days induced the enhancement of the 27-kDa Bcl-2alpha protein level. Among immunosuppressants, rapamycin has most potency. Treatment with herbimycin A or wortmannin also enhanced Bcl-2 expression, but the BB type of platelet-derived growth factor decreased the level. These results suggest that Bcl-2 expression is probably regulated by the cascade of tyrosine kinase, phosphatidylinositol 3-kinase and rapamycin-sensitive p70 S6-kinase in human neuroblastoma SH-SY5Y cells.

Gene Expression↗
PubMed1997

Molecular cloning of bovine CD14 gene.

Genomic DNA encoding bovine CD14 was isolated from a bovine (Holstein) genomic library. Utilizing PCR fragment of mouse CD14 gene as a probe, we screened 9 x 10(5) plaques and obtained 3 clones containing the bovine CD14 gene. DNA sequencing showed that bovine CD14 gene encodes 373 amino acids, and the coding sequence was separated by a 90 nt intron. The identity of the deduced amino acid sequence of bovine CD14 was 61-73% to those of mouse, rabbit and human. Northern blot analysis revealed that CD14 mRNA (1.5 kb) was expressed in the lung. Expression of CD14 mRNA was stimulated about 2-fold in bovine peripheral blood macrophage activated with LPS in vitro.

Amino Acid Sequence↗
PubMed1997

Identification of cytochrome P450 isoforms involved in citalopram N-demethylation by human liver microsomes.

Studies to assess the enzyme kinetic behavior and to identify the cytochrome P450 (CYP) isoform(s) involved in the major metabolic pathway (N-demethylation) for citalopram (CIT), a selective serotonin reuptake inhibitor, were performed using human liver microsomes and cDNA-expressed human cytochrome P450 isoforms. The N-demethylation activities showed significant correlations with the alpha- and 4-hydroxylation activities of triazolam (r(s) = 0.818 and 0.851, respectively; P < .01) in 10 different human liver microsomes. Anti-CYP3A antibodies and ketoconazole strongly inhibited CIT N-demethylation. In addition, there was a significant correlation between CIT N-demethylation and (S)-mephenytoin 4'-hydroxylation (r(s) = 0.773, P < .05), although little inhibition was observed in the presence of anti-CYP2C antibodies or (S)-mephenytoin. cDNA-expressed CYP3A4 and CYP2C19 catalyzed CIT N-demethylation, whereas no appreciable activities were observed for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6 and CYP2E1. The percentage contributions of CYP3A4 and CYP2C19 to the overall N-demethylation of CIT in human liver microsomes were estimated using a relative activity factor; respective values of 70% and 7% were calculated for microsomes obtained from livers from putative extensive metabolizers for (S)-mephenytoin 4'-hydroxylation. These results suggest that CYP3A4 is the major isoenzyme and CYP2C19 is the minor form involved in the major metabolic pathway for CIT in human liver microsomes.

Aryl Hydrocarbon Hydroxylases↗
PubMed1997

[Changes in the extent of mitral regurgitation during hemodialysis: color Doppler echocardiographic study].

The changes in the extent of mitral regurgitation (MR) during maintenance hemodialysis patients were studied in six patients with MR by color Doppler echocardiography. M-mode, two-dimensional and color Doppler echocardiography were performed before and every hour during hemodialysis. The severity of MR was evaluated by a semiquantitative grading system and maximal MR area. Hemodialysis removed 2.1 +/- 0.9/body fluid. Blood pressure and heart rate did not change systematically by hemodialysis. Left atrial, left ventricular end-diastolic and end-systolic dimensions were significantly decreased by hemodialysis (p < 0.05). Stroke volume and left ventricular wall stress were also significantly decreased (p < 0.01). MR area was significantly smaller at the end of hemodialysis compared to pre-hemodialysis (49.0 +/- 20.5 vs 171.0 +/- 49.2 mm2, p < 0.05). During hemodialysis, the extent of MR was continuously decreased. In two out of six patients, the MR jet disappeared. The extent of MR may depend on the fluid volume removed by hemodialysis because the MR area diminished more as more fluid was removed. No major disorders of the mitral complex were detected when the MR area was decreased rapidly to less than 60 mm2 in response to the removal of a small amount of fluid. The dry weight should be determined as the body weight when MR is as small as possible by color Doppler echocardiography.

Adult↗
PubMed1997

Studies on the response of nitroglycerin oral spray compared with sublingual tablets for angina pectoris patients with dry mouth. A multicenter trial.

Nitroglycerin (glyceryl trinitrate, CAS 55-63-0, NTG) administered with an oral spray may be more effective in relieving anginal pain than sublingual tablets especially when the patient's mouth is dry. In this study, the effect of a NTG oral spray (Myocor Spray) on exercise-induced angina was compared with that of a sublingual tablet in relation to the oral dryness. In 17 patients with effort angina, graded bicycle exercise was performed twice at an interval of one week. Exercise was discontinued upon the onset of moderate anginal pain. Immediately after exercise, the oral dryness was evaluated by touching the tip of the tongue with a blotting paper for a moment. Then, 0.3 mg of NTG was administered by either a squirt of spray or a sublingual tablet in a randomized crossover fashion. Exercise results were reproducible between two exercise tests. According to the extent of the wet area of the blotting paper, the subjects were divided into two groups. In 7 patients of the wet group, the remission times of chest pain and ST segment depression were not significantly different by the formulation of NTG. In 10 patients of the dry group, however, both chest pain and ST depression more rapidly recovered with use of the oral spray (p < 0.05 and p < 0.05, respectively). These results strongly suggest that the NTG oral spray is superior to the sublingual tablet in relieving anginal attacks, when the oral wetness is decreased.

Administration, Sublingual↗
PubMed1997

Correlation between HLA-DR expression and level of poly(ADP-ribose) synthetase in human thyroid carcinoma cells.

The expression of MHC class II molecules is normally restricted to antigen presenting cells. Aberrant expression of class II molecules, however, was detected in the thyrocytes of autoimmune thyroid diseases. We attempted to regulate the expression of HLA-DR molecules in thyroid carcinoma cells by expressing the exogenous poly(ADP-ribose) synthetase gene. We transfected a metal inducible expression plasmid capable of expressing poly(ADP-ribose) synthetase gene into thyroid carcinoma 8505C cells and the transformants, treated with metal and IFN-gamma, were separated by Magnetic Cell Separation. The activity of the synthetase was increased in the HLA-DR-enriched transformants as compared with that in control or the HLA-DR+ transformants. RNA blot analysis and flow cytometric analysis revealed that the IFN-gamma-inducible expression of HLA-DR molecules was depressed by the induction of exogenous poly(ADP-ribose) synthetase gene. This result indicates that HLA-DR expression was correlated with the level of poly(ADP-ribose) synthetase in human thyroid carcinoma cells. Furthermore we examined the level of poly(ADP-ribose) synthetase in patients with autoimmune thyroid diseases. We observed a significant decrease in poly(ADP-ribose) synthetase in the patients. Taken together with the previous observation, the decrease in poly(ADP-ribose) synthetase is closely linked to the aberrant expression of HLA-DR molecules in some autoimmune thyroid diseases.

Autoimmune Diseases↗
PubMed1997

DNA damage-induced apoptosis and Ice gene induction in mitogenically activated T lymphocytes require IRF-1.

Lymphocytes are highly sensitive to DNA damage-induced apoptosis. In thymocytes, the tumor suppressor p53 has been shown to be required for this type of apoptosis. However an as yet unknown, p53-independent pathway(s) appears to mediate the same event in mitogenically activated mature T lymphocytes. By using mice with a null mutation in the IRF-1 gene, we revealed that DNA damage-induced apoptosis in the latter cell type is dependent on the anti-oncogenic transcription factor interferon regulatory factor-1 (IRF-1). Thus two different anti-oncogenic transcription factors, p53 and IRF-1, are required for distinct apoptotic pathways in T lymphocytes. Furthermore, we found that mitogen induction of the interleukin-1 beta-converting enzyme (Ice) gene, a mammalian homolog of the Caenorhabditis elegans cell death gene ced-3, is also IRF-1-dependent. An IRF-1 binding sequence was identified in the 5' flanking region of the Ice gene. In addition, ectopic overexpression of IRF-1 results in the activation of the endogenous Ice gene and enhances the sensitivity of cells to radiation-induced apoptosis. Thus, induction of Ice gene may be involved in IRF-1 dependent DNA damage-induced apoptosis in activated mature T lymphocytes.

Animals↗
PubMed1997

Liver cytosolic aldehyde dehydrogenase (ALDH1) polymorphism and its inheritance in Wistar rats.

Rats are very important experimental animal to study alcohol related problems. Liver aldehyde dehydrogenases (ALDHs) which metabolize aldehydes are reported to have several isozymes which are distributed in mitochondrial, microsomal and cytosolic fractions. However, there is discrepancy on reports concerning properties of cytosolic ALDH from normal liver. We report here the liver cytosolic ALDH (ALDH1) polymorphism and its inheritance in Wistar rats. Isoelectrophoretic focusing technique reveals the three ALDH1 phenotypes (termed AA, AC and CC) which are inherited in accordance with Mendelian fashion, indicating the existence of two alleles, ALDH1A and ALDH1C. In the range of pI 5.3 to 5.8, the AA phenotype possesses a major anodic band with pI 5.3 and CC phenotype also has a cathodic pI 5.8 band. In contrast, AC phenotype exhibits five bands with pIs of 5.3, 5.4, 5.5, 5.7 and 5.8. Intensity of these bands gradually diminishes from the main band with pI 5.5 to the both opposite ends. These findings suggest that AC phenotype as well as AA and CC types has a structure of tetramer which consist of the combination of subunit of the A and C gene products.

Aldehyde Dehydrogenase↗
PubMed1997

Failure of germinal center formation and impairment of response to endotoxin in tumor necrosis factor alpha-deficient mice.

To study the pathophysiologic roles of TNF alpha, we produced TNF alpha gene-disrupted mice by gene targeting. TNF alpha-deficient mice develop normally without any alteration in the lymphocyte populations. However, in these mice, the germinal center formation in the peripheral lymphoid organs failed in response to the T cell-dependent antigens. TNF alpha-deficient mice are resistant to lethal doses of endotoxin and D-galactosamine without hepatocyte apoptosis, yet demonstrate thymus apoptosis. Our results indicated an important role for TNF alpha in germinal center formation and in the sepsis-induced hepatocyte apoptosis that precedes liver failure.

Animals↗
PubMed1996

Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor beta c chain.

BAG-1 is a Bci-2-binding protein which functions in protection from apoptotic cell death. Here we provide evidence for interleukin-2 (IL-2)-mediated upregulation of BAG-1 expression. In hematopoietic cell line BAF-B03 F7 cells, gene transfer mediated expression of the IL-2R beta c chain is sufficient to confer proliferation and cell survival responses to IL-2. In these IL-2R beta c-expressing cells, BAG-1 mRNA was dramatically induced by IL-2. The IL-2-mediated induction of BAG-1 expression required the activation of tyrosine kinase(s) and was sensitive to rapamycin as the induction of bcl-2 expression was. Analysis of the transfectants which express mutant IL-2R beta c chains or mutant Janus family protein tyrosine kinase Jak3 lacking the kinase domain showed that the IL-2-mediated BAG-1 gene expression required the serinerich region within the IL-2R beta c chain, but Jak3 activation was dispensable. The signaling pathway for BAG-1 gene expression thus highly resembles that for bcl-2 gene expression, strongly suggesting that their induction shares the same signaling pathway. In addition, deletion of the serine-rich region led to loss of IL-2-mediated protection from apoptotic cell death. Taken together, these studies demonstrate that the serine-rich region of the IL-2R beta c chain mediates the coordinated expression of bcl-2 and BAG-1 genes, thereby contributing to suppression of apoptosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Mechanism of resistance to NO-induced neurotoxicity in cultured rat dopaminergic neurons.

We previously reported that mesencephalic dopaminergic neurons are resistant to cytotoxicity induced by nitric oxide (NO). This study investigated the intracellular mechanism that protects dopaminergic neurons against NO toxicity in rat mesencephalic cultures. Peroxynitrite anion, an active metabolite of NO, caused significant cytotoxic effects against dopaminergic and nondopaminergic neurons, but NO caused cytotoxic effects restricted to nondopaminergic neurons. In addition, we studied the effects of ascorbate, an anti-oxidant, on NO-induced neurotoxicity against dopaminergic neurons and found that coadministration of ascorbate failed to affect resistance against NO-induced neurotoxicity. These findings suggest that the protecting mechanism from NO neurotoxicity in dopaminergic neurons is based on inhibition of conversion of NO to peroxynitrite anion, is independent of the NO redox state, and is possibly due to suppression of superoxide anion production. Furthermore, we investigated NO-induced neurotoxicity with or without pretreatment with sublethal doses of methylphenylpyridium ion (MPP+). Following pretreatment with 1 microM MPP+, which did not show significant cytotoxic effects against dopaminergic neurons, NO demonstrated significant cytotoxicity. Therefore, MPP+ may inhibit the protecting systems from NO neurotoxicity in dopaminergic neurons.

1-Methyl-4-phenylpyridinium↗
PubMed1996

Autocrine loop through cholecystokinin-B/gastrin receptors involved in growth of human leukemia cells.

The cholecystokinin (CCK)-B/gastrin receptor binds two brain-gut hormones, CCK and gastrin, with high affinities. These peptides have a trophic effect on gastrointestinal cells expressing the receptor in vivo as well as in vitro. Recently, this receptor mRNA was reported to be expressed in immunocytes localized in the lamina propria of normal rat stomach mucosa. Here, we studied the receptor expression in human hematopoietic cells in order to determine whether they play a role in cell growth. The CCK-B/gastrin receptor mRNA was detectable in the polymorphonuclear (PMN) cells but not in the mononuclear cells of normal peripheral white blood cells by reverse transcription-polymerase chain reaction. The receptor transcript was, however, expressed in human leukemia cell lines (14 of 18 cell lines tested) derived from not only myeloid, but also T- and B- lymphoid lineages. The CCK-B/gastrin receptors on several leukemia cell lines were shown to be biologically active by demonstrating ligand-dependent cell proliferation in serum-deprived medium. Interestingly, a human CCK-B/gastrin receptor specific antagonist, YM022, but not its stereotype isoform, selectively inhibited the DNA synthesis of THP-1, MOLT-16, MOLT-14, and CCRF-CEM in the absence of exogenous peptide ligands. Further investigation revealed that these leukemia cell lines and normal PMN cells also expressed gastrin mRNA. These results suggest that growth of human leukemia cells is promoted by an autocrine mechanism through the CCK-B/gastrin receptors.

Cell Division↗
PubMed1996

Cooperation of the tumour suppressors IRF-1 and p53 in response to DNA damage.

Normally growing cells promptly cease DNA synthesis when exposed to genotoxic stresses, such as radiation, and this cell-cycle arrest prevents the accumulation of mutations. The transcription factor interferon regulatory factor (IRF)-1 is essential for the regulation of the interferon system, inhibits cell growth, and manifests tumour-suppressor activities. Here we show that mouse embryonic fibroblasts (EFs) lacking IRF-1 are deficient in their ability to undergo DNA-damage-induced cell-cycle arrest. A similar phenotype has been observed in EFs lacking the tumour suppressor p53 (refs 8, 9), although the expression of IRF-1 and p53 are independent of one another. Furthermore, we show that transcriptional induction of the gene encoding p21 (WAF1, CIP1), a cell-cycle inhibitor, by gamma-irradiation is dependent on both p53 and IRF-1, and that the p21 promoter is activated, either directly or indirectly, by both in a transient cotransfection assay. These two tumour-suppressor transcription factors therefore converge functionally to regulate the cell cycle through the activation of a common target gene.

Animals↗
PubMed1996

Expression of apolipoprotein E mRNA in rat microglia.

Apolipoprotein E (apoE) is a major risk factor for Alzheimer disease (AD), which is the most common cause of progressive dementing illness. ApoE has been postulated to be synthesized by astrocytes and taken up by microglia and neuronal cells. However, it remains unknown whether apoE is also produced by microglia in the brain. We analyzed apoE mRNA expression of microglia using a rat primary culture system. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed expression of apoE mRNA in cultured rat microglia. By RT-in situ-PCR, microglia showed positive staining for the PCR product of apoE mRNA. These results indicated that apoE was biosynthesized in rat microglia. We suggest that microglia might be one of the sources of apoE in the brain, and that apoE synthesized in microglia might be closely related to the pathogenesis of AD.

Animals↗
PubMed1996

Possible involvement of Janus kinase Jak2 in interferon-gamma induction of nitric oxide synthase in rat glial cells.

To clarify the induction pathway of inducible nitric oxide (NO) synthase in the brain, we examined the effects of interferon-gamma and lipopolysaccharide on the induction of inducible NO synthase in glial cells cultured from neonatal rats, compared to those in the macrophage cell line RAW264.7 which was derived from Abelson leukemia virus-induced BALB/c lymphocytic lymphoma. NO synthase activity (NO2- accumulation) and 130 kDa protein of inducible NO synthase were induced 24 h after treatment with interferon-gamma or lipopolysaccharide in both glial cells and RAW264.7 macrophages. These induction activities were inhibited by a tyrosine kinase inhibitor, herbimycin A. Immunoprecipitation assay using antibodies against Janus kinases, and the signal transducer and activator of transcription-1 (STAT1), revealed that interferon-gamma induced tyrosine phosphorylation of the just another kinase-2 (Jak2) and STAT1 alpha but did not induced the phosphorylation of Jak1, the non-receptor tyrosine kinase-2 (Tyk2) and STAT1 beta. Tyrosine phosphorylation of Jak2 and STAT1 alpha induced by interferon-gamma was also inhibited by herbimycin A, while lipopolysaccharide did not induce any tyrosine phosphorylation of Janus kinases and STAT1 at all. These results suggest that the interferon-gamma-induced inducible NO synthase induction involves activation of Jak2-STAT1 alpha pathway in both glial cells and macrophages.

Animals↗
PubMed1996

Selective cooperation of HTLV-1-encoded p40tax-1 with cellular oncoproteins in the induction of hematopoietic cell proliferation.

Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL). The virus-encoded p40tax-1, a nuclear oncoprotein, is known to promote transcription of its own as well as a variety of cellular genes. However, the mechanism by which p40tax-1 promotes lymphocyte transformation is not fully understood. In the present study, we examined whether p40tax-1 can induce hematopoietic cell proliferation by cooperating with the products of cellular proto-oncogenes; i.e. an activated form of the src-family protein tyrosine kinase p56lck (lck F505), c-Myc or Bcl-2. These oncoproteins are critical mediators of interleukin 2 (IL-2)-induced proliferative signals. We show that p40tax-1 alone cannot render the hematopoietic cell line, BAF-B03, able to proliferate in the absence of cytokines, but it can do so in cooperation with lckF505, or c-Myc but not with Bcl-2.

Animals↗