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Biomedical subjects

J Tanaka

Publications and source records attributed to J Tanaka.

At least 199 records · Page 11Linked to original sources
PubMed1999

Enhancement of neuronal survival by 6R-tetrahydrobiopterin.

Recently, we have reported that 6R-tetrahydrobiopterin activates Ca2+ channels in neuronal cells independently of its cofactor activities. Several reports indicate that depolarization-induced activation of Ca2+ channels enhances neuronal survival. Here, we investigated the effects of 6R-tetrahydrobiopterin on survival of differentiated PC12 cells. Depletion of serum and nerve growth factor caused cell death, which was prevented by high potassium. 6R-Tetrahydrobiopterin also prevented death of PC12 cells cultured without serum and nerve growth factor in a dose-related manner at physiological concentrations (1-100 microM). However, surviving cells cultured with 6R-tetrahydrobiopterin showed undifferentiated form. 6S-Tetrahydrobiopterin, a diastereoisomer of 6R-tetrahydrobiopterin, also had a cell-surviving effect, but it was less potent as compared with that of 6R-tetrahydrobiopterin. The cell-surviving effect of 6R-tetrahydrobiopterin was eliminated by a Ca2+ channel blocker, but persisted in the presence of an inhibitor for tyrosine hydroxylase, dopamine, L-DOPA, an inhibitor for nitric oxide synthase and a nitric oxide generator. The effect of 6R-tetrahydrobiopterin was mimicked by a cyclic-AMP analogue and inhibited by an inhibitor for protein kinase A. Ca2+ channel activity was preserved but dopamine-releasing activity was disturbed in surviving cells cultured with 6R-tetrahydrobiopterin. 6R-Tetrahydrobiopterin had no effect on mitogen-activated protein kinase. These findings suggest that, independently of its cofactor activities and mitogen-activated protein kinase cascade, 6R-tetrahydrobiopterin enhances survival of PC12 cells by activating Ca2+ channels via the cyclic-AMP-protein kinase A pathway, but that 6R-tetrahydrobiopterin does not preserve neuronal character induced by nerve growth factor.

Animals↗
PubMed1999

Modulator-mediated synthesis of active lipase of Pseudomonas sp. 109 by Escherichia coli cell-free coupled transcription/translation system.

Catalytically active lipase was synthesized using Escherichia coli S30 extract from the signal-deleted lipL gene (lipL) in the presence of its N-terminal hydrophobic fragment-truncated modulator (rLimL) that was purified from the overexpressing E. coli cells. The specific activity of the lipase thus synthesized was 125 times higher than that of the purified one from Pseudomonas sp. 109. No lipase activity was detected in the absence of rLimL, even though the lipase protein itself was synthesized. Active lipase was also produced in vitro by coexpression of rlipL and the modulator gene (rlimL), although a much smaller amount of the lipase was formed. In the absence of rLimL, aggregates of the lipase were formed during its folding process. The addition of rLimL proportionally raised both lipase solubility and enzyme activity. An unstable but high activity peak of the lipase was found during its folding process.

Journal Article↗
PubMed1999

New guaianolides and xanthine oxidase inhibitory flavonols from ajania fruticulosa

Two new guaianolides (1 and 2) were isolated from the aerial parts of Ajania fruticulosa along with a triterpene (alpha-amyrin), two plant sterols (beta-sitosterol and daucosterol), four flavonols [santin (3), axillarin (4), centaureidin, and 5,7,4'-trihydroxy-3, 3'-dimethoxyflavone], and five sesquiterpenes [ketoplenolide B, 9beta-hydroxyeudesma-4,11(13)-dien-12-oic acid, 9beta-acetoxyeudesma-4,11(13)-dien-12-oic acid, 1alpha,4alpha, 10alpha-trihydroxy-9alpha-angeloyloxyguaia-2,11(13)-dien-12, 6alpha-olide, and 3beta,4alpha-dihydroxyguaia-11(13),10(14)-dien-12, 6alpha-olide]. The structures of the new guaianolides were established as 1alpha-hydroperoxy-4beta,8alpha,10alpha, 13-tetrahydroxyguaia-2-en-12,6alpha-olide (1) and 1alpha-hydroperoxy-4alpha, 10alpha-dihydroxy-9alpha-angeloyloxyguaia-2,11(13)-dien-12, 6alpha-olide (2), respectively. Xanthine oxidase assays of all isolates revealed that santin (3) and axillarin (4) inhibited the enzyme with IC(50) values of 36.5 and 36.0 &mgr;M (that of allopurinol used as a positive control in the study was 24.2 &mgr;M), respectively.

Journal Article↗
PubMed1999

Crystal growth of carbonate apatite using a CaCO3 flux.

Single crystals of carbonate apatite were grown using a CaCO3 flux under an Ar gas pressure of 55 MPa. The crystals obtained were observed by scanning electron microscopy, optical microscopy and X-ray diffraction. Electron probe microanalyses and thermal analyses were performed. CO3 ions in planar triangle form replaced both OH sites and PO4 tetrahedral sites in the apatite structure: in particular, the OH sites were perfectly substituted by CO3 ions using this method.

Journal Article↗
PubMed1999

Selective secretion of chemoattractants for haemopoietic progenitor cells by bone marrow endothelial cells: a possible role in homing of haemopoietic progenitor cells to bone marrow.

To elucidate the mechanisms by which haemopoietic progenitor cells lodge in the bone marrow, we examined the secretion of chemoattractants for haemopoietic progenitor cells by bone marrow and lung endothelial cells. The bone marrow endothelial cells, but not lung endothelial cells, secreted chemoattractants for the haemopoietic progenitor cell line, FDCP-2, and normal haemopoietic progenitor cells. Checkerboard analysis demonstrated that the conditioned medium of the bone marrow endothelial cells had chemotactic activity and random motility-stimulating activity. The bone marrow endothelial cells expressed stromal-cell-derived factor-1 (SDF-1) mRNA and produced SDF-1 protein, whereas the lung endothelial cells did not. Adhesion of FDCP-2 cells to the bone marrow endothelial cells was partially inhibited by anti-SDF-1 antibody. These findings suggest that the chemoattractants for haemopoietic progenitor cells including SDF-1 and random motility-stimulating factor(s) selectively secreted by the bone marrow endothelial cells may contribute to the homing of haemopoietic progenitor cells to bone marrow.

Animals↗
PubMed1999

Clinical experiences in Sakai City Hospital during the massive outbreak of enterohemorrhagic Escherichia coli O157 infections in Sakai City, 1996.

In the middle of July, 1996, a massive outbreak of hemorrhagic colitis (HC) occurred among elementary schoolchildren in Sakai city. This is the most widespread outbreak of O157 infection ever experienced to our knowledge. Lunch foods supplied in the elementary schools in Sakai were contaminated by Escherichia coli (E. coli) O157. One hundred and twenty-one cases developed hemolytic uremic syndrome (HUS) from 12,680 symptomatic patients, including putative secondary infections, and three girls died during this outbreak. Sakai City Hospital is one of the core medical facilities in this community; hence, 425 children with HC were treated at the hospital. Antibiotics were used extensively on all patients. Among them, 12 children developed HUS. All 425 children, including the patients with HUS, recovered without significant sequelae. In the present paper, the clinical experiences during this massive outbreak of E. coli O157 infection in Sakai City Hospital are described.

Anti-Bacterial Agents↗
PubMed1999

Effects of erythropoietin on neuronal activity.

Recently, erythropoietin (EPO) receptors and synthesis of EPO have been identified in the brain. To clarify the effects of EPO on neuronal cells, we investigated the effects of EPO on Ca2+ uptake, intracellular Ca2+ concentration, membrane potential, cell survival, release and biosynthesis of dopamine, and nitric oxide (NO) production in differentiated PC12 cells, which possess EPO receptors. EPO (10(-12)-10(-10) M) increased 45Ca2+ uptake and intracellular Ca2+ concentration in PC12 cells in a dose-related manner; these increases were inhibited by nicardipine (1 microM) or anti-EPO antibody (1:100 dilution). EPO induced membrane depolarization in PC12 cells. After a 5-day culture without serum and nerve growth factor (NGF), viable cell number decreased to 50% of that of the control cells cultured with serum and NGF. EPO (10(-13)-10(-10) M) increased the number of viable cells cultured without serum and NGF; this increase was blunted by nicardipine or anti-EPO antibody. Incubation with EPO (10(-13)-10(-10) M) stimulated mitogen-activated protein kinase activity in PC12 cells. EPO (10(-13)-10(-10) M) increased dopamine release from PC12 cells and tyrosine hydroxylase activity; these increases were sensitive to nicardipine or anti-EPO antibody. Following a 4-h incubation with EPO (10(-14)-10(-10) M), NO production was increased, which was blunted by nicardipine and anti-EPO antibody. In contrast, maximal NO synthase activity was not changed by EPO. These results suggest that EPO stimulates neuronal function and viability via activation of Ca2+ channels.

Animals↗
PubMed1999

An 18-mer peptide fragment of prosaposin ameliorates place navigation disability, cortical infarction, and retrograde thalamic degeneration in rats with focal cerebral ischemia.

It was previously reported that prosaposin possesses neurotrophic activity that is ascribed to an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain. To evaluate the effect of the 18-mer peptide on ischemic neuronal damage, the peptide was infused in the left lateral ventricle immediately after occlusion of the left middle cerebral artery (MCA) in stroke-prone spontaneously hypertensive (SP-SH) rats. The treatment ameliorated the ischemia-induced space navigation disability and cortical infarction and prevented secondary thalamic degeneration in a dose-dependent manner. In culture experiments, treatment with the 18-mer peptide attenuated free radical-induced neuronal injury at low concentrations (0.002 to 2 pg/mL), and the peptide at higher concentrations (0.2 to 20 ng/mL) protected neurons against hypoxic insult. Furthermore, a saposin C fragment comprising the 18-mer peptide bound to synaptosomal fractions of the cerebral cortex, and this binding decreased at the 1st day after MCA occlusion and recovered to the preischemic level at the 7th day after ischemia. These findings suggest that the 18-mer peptide ameliorates neuronal damage in vivo and in vitro through binding to the functional receptor, although the cDNA encoding prosaposin receptor has not been determined yet.

Amino Acid Sequence↗
PubMed1999

A low-Mr lipase activation factor cooperating with lipase modulator protein LimL in Pseudomonas sp. strain 109.

Pseudomonas sp. strain 109 produces a unique lipase (LipL) which efficiently catalyses intramolecular transesterification of omega-hydroxyesters to form macrocyclic lactones. In vivo production of enzymically active LipL requires lipase modulator protein (LimL), which functions as a molecular chaperone for the correct folding of LipL. However, previous work has shown that LipL forms a tight complex with LimL in vitro and the resulting LipL-LimL complex is only partially active, suggesting an additional mechanism that facilitates the dissociation of the complex to form enzymically active LipL. In the present work, a low-Mr compound (lipase activation factor, LAF) was found in Pseudomonas sp. strain 109 that when added to the LipL-LimL complex resulted in the activation of LipL. Ca2+ ions also enhanced lipase activity, but the instantaneous activation by Ca2+ was different from the gradual and time-dependent activation by LAF, indicating the novel nature of this compound. LAF passed through an ultrafiltration membrane with an Mr cut-off of 3000 and showed an apparent Mr of 330+/-30 on Superdex Peptide gel-filtration chromatography. Treatment of the LipL-LimL complex with LAF liberated free active LipL, indicating that LAF was necessary to dissociate the LipL-LimL complex.

Bacterial Proteins↗
PubMed1999

Epidemiology of hepatitis C virus in japan.

Blood screening for hepatitis C virus (HCV) antibodies at Japanese Red Cross blood centers has indicated an age-dependent prevalence of HCV infection in the general population of Japan: the older the age, the higher the prevalence. The same pattern was corroborated by the sentinel study conducted in an HCV-endemic area. The high prevalence of HCV in the elderly is most likely due to a spread of HCV infection during the turmoil period just after World War II: in particular by illicit intravenous amphetamine abuse. Fortunately, however, since the rate of newly acquired infection is currently too low to influence HCV prevalence in each age group, the total number of HCV carriers (estimated to be 691,852 for the age group 20-64 years) would decrease spontaneously with generation takeover to approximately 50% of the current number during the decade to come.

Adult↗
PubMed1999

Increase production of lactonizing lipase (LipL) from Pseudomonas sp. strain 109 by lipids and detergents.

LipL of Pseudomonas sp. strain 109 is a unique lipase capable of catalyzing macrocyclic lactone synthesis using omega-hydroxyfatty acid esters as substrates. Several fatty acid esters were tested as inducers of LipL production. The addition of either soybean oil or a non-ionic detergent (Noigen HC) resulted in a 44 to 45-fold increase in extracellular LipL, and the presence of both resulted in a further 56-fold increase. Among the triglycerides tested, triolein was the most effective, with a 50-fold increase in LipL production. A Northern blot hybridization analysis found that the lipL transcript increased in the presence of soybean oil or Noigen HC, indicating that the production of LipL is regulated at the transcriptional level.

Amino Acid Sequence↗
PubMed1999

Unresponsiveness to glibenclamide during chronic treatment induced by reduction of ATP-sensitive K+ channel activity.

The insulin response to the sulfonylurea glibenclamide was markedly impaired in pancreatic beta-cell line MIN6 cells with chronic glibenclamide treatment (MIN6-Glib). The intracellular calcium concentration increased only slightly in response to glibenclamide in MIN6-Glib. While the properties of the voltage-dependent calcium channels were not altered, the conductance of the K(ATP) channels, the primary target of glibenclamide, was significantly reduced in MIN6-Glib. The ATP-sensitive K+ (K(ATP)) channels in MIN6 cells comprise inwardly rectifying K+ channel member Kir6.2 subunits and sulfonylurea receptor (SUR) 1 subunits. MIN6 cells have both high- and low-affinity binding sites for glibenclamide. The binding affinities at these two sites were unchanged, but the maximum binding capacities at both sites were similarly increased by chronic glibenclamide treatment. Both SUR1 and Kir6.2 mRNA levels were not altered, but SUR1 protein was rather increased in MIN6-Glib. In addition, electron microscopic examination revealed a majority of the SUR1 to be present in a cluster near the plasma membrane in control MIN6, while it tends to be distributed in the cytoplasm in MIN6-Glib. These data suggest that chronic glibenclamide treatment causes the defect in acute glibenclamide-induced insulin secretion by reducing the number of functional K(ATP) channels on the plasma membrane of the beta-cells.

ATP-Binding Cassette Transporters↗
PubMed1999

Myelinated nerve fiber analysis of the human greater splanchnic nerve.

The purpose of the present study is to analyze the human greater splanchnic nerve in relation to aging. We adopted a new staining method which makes it possible to discriminate various structures of the nervous tissue. We examined 25 human greater splanchnic nerves from cadavers for anatomy dissection. We measured the number, area and perimeter of axons. The results reveal that: (1) there is no correlation between age and the number of axons; (2) the mean area and perimeter of axons increase with age, but not the total area and perimeter. We compared these results with those for the lesser splanchnic nerve. These morphological changes in the greater splanchnic nerve may indicate a kind of compensation through axon hypertrophy for hypofunctions in abdominal organ control.

Adult↗
PubMed1999

Possible role of granulocyte colony-stimulating factor in increased serum soluble interleukin-2 receptor-alpha levels after allogeneic bone marrow transplantation.

Serum soluble interleukin-2 receptor - alpha (sIL-2R) levels markedly increased at the engraftment period in patients who underwent allogeneic bone marrow transplantation (BMT). Since serum G-CSF levels increased during G-CSF administration and decreased after the cessation, increased sIL-2R levels appeared to be induced by G-CSF administration. There was no increase in sIL-2R levels in a patient given macrophage colony-stimulating factor (M-CSF). The sIL-2R levels at the engraftment period and the onset of acute graft-versus-host disease (GVHD) were higher in patients who developed acute GVHD during G-CSF administration than in those who developed acute GVHD after G-CSF cessation. This finding suggests that G-CSF administration may possibly augment acute GVHD. However, it appears to be unlikely, because in the entire population, 18 of 35 patients had acute GVHD while only 6 of 17 patients had acute GVHD during G-CSF administration. Further analysis is still needed in order to draw definite conclusions. Preconditioning regimens did not appear to affect the sIL-2R levels, when the variable frequencies of methotrexate (MTX) administration were compared.

Adolescent↗
PubMed1999

Correlation of dentin bond durability with water absorption of bonding layer.

In order to understand the relationship between the durability of adhesive strength in the oral cavity and water absorption, a series of O-methacryloyl-N-acyl tyrosines (MAATY)-2-hydroxyethyl methacrylate (HEMA) bond system samples was prepared and their bonding strength to unetched human dentin was measured as a function of immersion period in water. Also, bulk polymerization was carried out to measure the amount of water absorption as a function of time. All specimens absorbed water suddenly when they were immersed into water. The amount of absorbed water was large when the carbon number in the acyl group was small or the number of carboxylic groups was large. The adhesive strength of the MAATY-HEMA system to unetched dentin decreased significantly when the MAATY-HEMA absorbed a larger amount of water. We concluded, therefore, that preparation of MAATY which absorbs less water may improve durability even when immersed in water.

Absorption↗