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Biomedical subjects

C Yamamoto

Publications and source records attributed to C Yamamoto.

At least 145 records · Page 8Linked to original sources
PubMed1994

Cadmium stimulation of glycosaminoglycan synthesis by cultured vascular endothelial cells: comparison of various cell types.

We investigated the effect of cadmium on the synthesis of glycosaminoglycans (GAGs) in confluent cultures of vascular endothelial cells derived from bovine aorta. Cadmium markedly increased the incorporation of [3H]glucosamine into GAGs in both the cell layer and the conditioned medium but decreased [35S]sulfate in the cell layer. This suggested that cadmium induced the GAG synthesis by endothelial cells accompanied by a reduction of the sulfation of cell-associated GAGs. Of the tested heavy metals, the [35S]sulfate incorporation in the cell layer was significantly decreased by lead; zinc slightly but significantly increased the [35S]sulfate incorporation; manganese and copper failed to change the [3H]glucosamine and [35S]sulfate incorporation; and the incorporation of [3H]glucosamine was increased only by cadmium. On the other hand, vascular smooth-muscle cells and fibroblastic Balb/3T3 cells responded to cadmium in a way similar to vascular endothelial cells, while fibroblastic IMR-90 cells, Chang liver cells and epithelial LLC-PK1 cells altered the [3H]glucosamine and [35S]sulfate incorporation after exposure to cadmium in different manners. The alteration of GAGs induced by cadmium may be involved in the pathogenesis of the metal.

Animals↗
PubMed1994

[Fluctuation of HCV quasi-species population during interferon therapy; analysis by single strand conformation polymorphism].

We investigated the fluctuation of hepatitis C virus (HCV) quasispecies during interferon therapy by single strand conformation polymorphism (SSCP) analysis. In 13 of 16 interferon ineffective patients, the predominant HCV population was replaced with other quasispecies during the treatment. Especially, in 9 patients, a part of the HCV quasispecies, pre-existing before interferon therapy, became predominant after the therapy. These results indicate that sensitivity to interferon differs among HCV quasispecies and that interferon selects resistant HCV strains. Existence of such HCV quasispecies seems to be associated with interferon treatment failure.

Base Sequence↗
PubMed1994

Induction of metallothionein synthesis by bismuth in cultured vascular endothelial cells.

Metallothionein synthesis induced by bismuth nitrate was characterized using a cell culture system. It was found that bismuth (1-10 microM) significantly increased the intracellular accumulation of metallothionein in bovine aortic endothelial cells without an exhibition of cytotoxicity and a change of either general protein synthesis or proliferative DNA synthesis after a 24-h incubation. A low increase in the metallothionein accumulation was observed in bovine aortic smooth muscle cells; however, porcine kidney epithelial LLC-PK1 cells, human Chang liver cells and two human hepatoma cell lines (HLF cells and Hep-G2 cells) did not respond to bismuth. Other cations including cobalt, lead and zinc at 10 microM failed to induce metallothionein in endothelial cells, although cadmium at 1 microM was a strong inducer. Bismuth accumulated highly in endothelial cells but very slightly in LLC-PK1 cells and Chang liver cells. The present data suggest that bismuth is a selective inducer of metallothionein of vascular endothelial cells and this cell type particularly responds to the cation.

Adenine↗
PubMed1994

Circulating endothelin-1 levels in patients with bronchial asthma.

We attempted to clarify the relationship between circulating endothelin-1 levels and bronchial hyperreactivity in asthmatic patients. Sixty-two asthmatic patients were studied for plasma endothelin-1 levels during acute asthma. The relationship between plasma endothelin-1 levels and pulmonary function (FEV1/FVC) was examined in 17 patients. Twelve patients were studied for changes in plasma endothelin-1 levels during methacholine inhalation tests. Plasma endothelin-1 levels during acute asthma correlated with the severity of acute asthma defined with the Clinical Asthma Evaluation Score, and those during the methacholine challenge test correlated with the grade of bronchoconstriction (P < .01). A significant negative correlation was observed between plasma endothelin-1 levels and FEV1/FVC ratio (P < .01). These results suggest that circulating endothelin-1 levels may reflect the severity of acute asthma.

Acute Disease↗
PubMed1994

[A case of advanced gastric cancer with multiple liver metastases showing marked response to new combination chemotherapy using 5-FU, THP and MMC (FTM)].

A 67-year-old man with advanced gastric cancer with multiple liver metastases was treated by a new combination chemotherapy using 5-FU, THP and MMC (FTM). After the first course of FTM, both abnormal liver function and the elevated level of serum CA 19-9 were restored. After the second course of FTM, the primary lesion became a small ulcer around cardia. A partial response was recognized both in the primary lesion and in the liver metastases. No serious side effect was observed except for leukocytopenia, which was controlled by G-CSFS. This new combination chemotherapy (FTM) was suggested to be useful even for far advanced gastric cancer.

Adenocarcinoma↗
PubMed1993

Cadmium stimulation of plasminogen activator inhibitor-1 release from human vascular endothelial cells in culture.

We investigated the effect of cadmium (0.5, 1.0 or 2.0 microM) on the release of plasminogen activator inhibitor-1 antigen (PAI-1:Ag) from cultured human vascular endothelial cells. It was found that cadmium at 1.0 and 2.0 microM significantly increased the PAI-1:Ag release from the cells after a 24-h incubation. However, the tissue plasminogen activator antigen (t-PA:Ag) release was not changed by the metal. Although nickel as well as cadmium increased the PAI-1:Ag release, the other heavy metals including cobalt, zinc and copper did not exhibit such a stimulatory effect. The incorporation of [3H]leucine into the acid-insoluble fraction of the cell layer was unchanged by cadmium, suggesting that the metal may stimulate the synthesis of PAI-1 without association with generalized increase in protein synthesis. Cadmium at 1.0 and 2.0 microM significantly decreased the t-PA activity in the medium. The present study showed that cadmium increases the release of PAI-I:Ag from cultured endothelial cells without non-specific stimulation of protein synthesis. The decrease in the t-PA activity suggests an implication of cadmium in vascular lesion which is mediated by anti-fibrinolytic activity.

Cadmium↗
PubMed1993

ATP-sensitive K+ channel activators suppress the GABAergic inhibitory transmission by acting on both presynaptic and postsynaptic sites in rat cultured hippocampal neurons.

Effects of ATP-sensitive K+ (KATP) channel activators on the inhibitory transmission were explored by applying the patch-clamp technique to both presynaptic and postsynaptic hippocampal neurons prepared from neonatal rats. Diazoxide (0.5 mM) and cromakalim (0.5 mM) reduced GABAergic synaptic currents to 57 and 81% of control, respectively, and reduced the currents induced by exogenously applied GABA (10 microM) to 74 and 95% of control, respectively. These results suggest that KATP channel activators suppress the GABAergic transmission partly by reducing the GABA release and partly by affecting the postsynaptic GABA response.

Action Potentials↗
PubMed1993

Electrophysiological features of habenular neurons of the guinea pig: high efficacy of synaptic transmission and variable configuration of unitary spikes.

Properties of single cell discharges recorded extracellularly in the medial habenular nucleus (MHN) were examined in guinea pig MHN slices. MHN neurons fired spontaneously as well as in response to stimulation of the stria medullaris. Positive deflections representing excitatory postsynaptic potentials (EPSPs) were recorded in isolation from a neuron. In most neurons, however, EPSPs differentiable from the base-line triggered action potentials consistently, and were recorded in isolation only during administration of 6-cyano-7-nitroquinoxaline-2.3-dione. Increases in spontaneous discharge rate during administration of nicotinic agonists were not accompanied by expected decreases in latency of synaptically-evoked spikes. Action potentials were recorded as biphasic potential changes consisting of a smaller positive phase and a subsequent negative phase. The amplitude of the negative phase in synaptically-evoked spikes fluctuated from trace to trace and was larger than in spontaneous spikes. The above observations suggest high efficacy of synaptic transmission from the stria medullaris to MHN neurons and variable areas of the soma-dentritic region invaded by action potentials generated in the initial segment.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1993

Tumor necrosis factor alpha-induced alteration of glycosaminoglycans in cultured vascular smooth-muscle cells.

We studied alteration of glycosaminoglycans (GAGs) induced by recombinant human tumor necrosis factor alpha (rhTNF alpha) in vascular smooth-muscle cells from bovine aorta in a culture system. It was found that rhTNF alpha at 10 ng/ml and below significantly increased the incorporation of [35S]sulfate (35S) but conversely decreased that of [3H]glucosamine (3H) into GAGs in the trypsinate fraction of the cell layer after a 24-h incubation. These results suggested that rhTNF alpha reduced the formation and/or the anchorage of sugar chains in the cell layer but enhanced their sulfation in whole GAG synthesis by the cells. In results, the ratio of 35S to 3H in the GAGs was markedly increased. This increase occurred after 24 h and longer when the cells were treated with 1.0 ng/ml rhTNF alpha. The TNF alpha-induced alteration of the incorporation of both 35S and 3H was completely blocked by anti-rhTNF alpha antibody. Other cytokines including recombinant human interleukin-1 beta and -6, and platelet-derived growth factor failed to alter the ratio of 35S to 3H in the GAGs of the trypsinate fraction of the cell layer. In cultured vascular endothelial cells from bovine aorta, however, rhTNF alpha at 1.0 ng/ml significantly decreased the incorporation of both 35S and 3H into GAGs of both the trypsinate fraction and the medium; the ratio of 35S to 3H was not changed. Characterization of GAGs in vascular smooth muscle cell trypsinate fraction revealed that rhTNF alpha at 10 ng/ml induced (i) no change of the incorporation of 3H in the hyaluronate fraction, (ii) a marked increase in the incorporation of 35S and no change of that of 3H in chondroitin sulfates (A plus C) fraction, (iii) a significant decrease in the incorporation of both 35S and 3H in the heparan sulfate fraction, and (iv) no change of the incorporation of 35S and a marked decrease in that of 3H in the dermatan sulfate fraction. In the medium, rhTNF alpha also induced various changes of GAGs. It was therefore concluded that TNF alpha may have a capacity of inducing a qualitative change of vascular smooth-muscle cell GAGs, which may be involved in the vascular pathology such as atherosclerosis.

Animals↗
PubMed1993

Quantal analysis of modulating action of adenosine on the mossy fiber synapse in hippocampal slices.

Although adenosine has been considered to depress release of neurotransmitter in central synapses, evidence for this notion is circumstantial. To obtain more direct and quantitative evidence, the suppressing action of adenosine on transmission through the mossy fiber synapse was examined by a quantal analysis in thin transverse sections of the guinea pig hippocampus. Adenosine suppressed excitatory postsynaptic potentials (EPSPs) induced in CA3 neurons by activation of single mossy fibers to 57 +/- 19% at 10 microM (6 neurons). The input resistance of the postsynaptic neurons was reduced to 84 +/- 5%. The suppression of the unitary EPSPs was accompanied by a reduction of the mean quantal content (m) to 51 +/- 13% with no significant decrease in mean quantal amplitude (q). These findings indicate that adenosine at 10 microM suppresses transmission through mossy fiber synapses mainly by depressing release of transmitter. This study provides direct evidence for the presynaptic action of adenosine on central synapses for the first time.

Action Potentials↗
PubMed1993

Long-lasting potentiation of synaptic transmission in the Schaffer collateral-commissural pathway of the guinea pig hippocampus by activation of postsynaptic N-methyl-D-aspartate receptor.

The effects of short-period (2 min) perfusion of conditioning solution, which contains N-methyl-D-aspartate (NMDA), glycine, and spermine, on the synaptic transmission in the Schaffer collateral-commissural pathway were examined in hippocampal slices with the intracellular recording technique. Long-lasting potentiation of excitatory postsynaptic potentials (EPSPs) was induced (as long as the records lasted, up to 3 h in the longest observation) after membrane potentials of postsynaptic neurons were depolarized by current injection during perfusion of the conditioning solution. D-2-amino-5-phosphonovaleric acid (D-AP5), a specific antagonist of NMDA receptors, block the induction of the long-lasting potentiation by perfusion of NMDA containing solution. This potentiation was accompanied by a decrease in the relative magnitude of EPSP amplitude fluctuation (coefficient of variation, CV). The reciprocals of squared CVs (= mean2/variance) were almost proportional to the magnitude of the potentiation, and the ratios of 1/CV2 and the magnitudes of potentiation were not different from those of long-term potentiation (LTP) induced by tetanic stimulation. These findings suggest that long-lasting potentiation is induced solely by activation of postsynaptic NMDA receptors, and transmitter release from presynaptic terminals may be modified by the activation of postsynaptic receptors.

2-Amino-5-phosphonovalerate↗
PubMed1993

Metallothionein induction by cadmium, cytokines, thrombin and endothelin-1 in cultured vascular endothelial cells.

Metallothionein induction was investigated using vascular endothelial cells derived from bovine aorta in a culture system. The induction occurred by cadmium (2 and 5 microM) but not by zinc (10 and 300 microM) after a 24-h incubation of the confluent cultures. It was revealed that cytokines including interleukin-1 beta, interleukin-6, tumor necrosis factor alpha and transforming growth factor beta (1 ng/ml each) have a capacity of metallothionein induction. In these inducers, only cadmium and tumor necrosis factor alpha exhibited significant cytotoxicity, suggesting that metallothionein is not induced simply in response to cytotoxicity. It was found that either thrombin or endothelin-1 which are coagulation factor or anti-fibrinolytic factor, respectively, also induced metallothionein synthesis. It was therefore suggested that metallothionein in endothelial cells may be involved in the regulation of the functions of these cells as well as the protection against cytotoxic agents.

Animals↗
PubMed1993

Zinc protection against cadmium-induced destruction of the monolayer of cultured vascular endothelial cells.

The effect of zinc on the destruction of vascular endothelial cell monolayer caused by cadmium was investigated using bovine aortic endothelial cells in a culture system. It was histologically revealed that cadmium-induced de-endothelialized area formation was markedly prevented by zinc. Zinc prevented cadmium-induced detachment of [3H]thymidine-labeled endothelial cells from the monolayer. Although cadmium increased the activity of lactate dehydrogenase in the medium, a marker of nonspecific cell damage, zinc markedly suppressed it. On the other hand, zinc significantly prevented cadmium-induced decrease in the incorporation of [3H]thymidine into the acid-insoluble fraction of the growing cells. From these results, it was suggested that impairment of the endothelial cell monolayer caused by cadmium is protected by zinc; this protection was postulated to be due to both a reduction of the cell detachment caused by cadmium-induced nonspecific cell damage and a decrease in cadmium inhibition of the cell proliferation which would help the repair of de-endothelialized areas.

Analysis of Variance↗
PubMed1993

Lipopolysaccharide and granulocyte colony-stimulating factor delay neutrophil apoptosis and ingestion by guinea pig macrophages.

In previous studies, neutrophil-ingesting macrophages were clearly and easily observed in the peritoneal cavity of guinea pigs after intraperitoneal injection of thioglycolate medium, and phagocytosis of neutrophils by macrophages could be detected in in vitro cultures of peritoneal exudate cells. Using an in vitro system, we examined the effect of bacterial lipopolysaccharide and recombinant human granulocyte colony-stimulating factor on the apoptosis (programmed cell death) of neutrophils and their subsequent ingestion by macrophages. Lipopolysaccharide delayed karyopyknosis and apoptosis of neutrophils, as shown by endogenous endonuclease activity and a high proportion of trypan blue-excluding cells, and subsequent ingestion by autologous macrophages. Granulocyte colony-stimulating factor also delayed neutrophil karyopyknosis and ingestion by macrophages. When a thioglycolate medium was coinjected intraperitoneally with lipopolysaccharide into guinea pigs in the in vivo system, delays in neutrophil disappearance and ingestion by macrophages in the peritoneal cavity were also observed. We suggest that bacterial products and cytokines regulate neutrophil apoptosis and subsequent ingestion by macrophages at inflamed sites.

Animals↗
PubMed1993

Modulation by endothelin-1 of tissue plasminogen activator and plasminogen activator inhibitor-1 release from cultured human vascular endothelial cells: interaction of endothelin-1 with cytokines.

The interaction of endothelin-1 (ET-1) with either interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha) on the release of tissue plasminogen activator antigen (t-PA:Ag) and plasminogen activator inhibitor-1 antigen (PAI-1:Ag) was investigated in a culture system of vascular endothelial cells derived from human umbilical vein. The t-PA:Ag release was significantly decreased by either IL-1 beta or TNF alpha; ET-1 intensified the suppressive effect of the cytokines. In contrast, PAI-1:Ag release was significantly increased by either IL-1 beta or TNF alpha; ET-1 significantly reduced the stimulatory effect of the cytokines. The data suggest that endothelial cell-mediated fibrinolysis may be modulated by ET-1.

Cells, Cultured↗