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Biomedical subjects

A Miyazaki

Publications and source records attributed to A Miyazaki.

At least 19 recordsLinked to original sources
PubMed1995

Hepatocyte growth factor inhibits intercellular communication via gap junctions in rat hepatocytes.

We demonstrated that HGF reduces gap junctional intercellular communication of rat hepatocyte doublets and increases cell spreading. Intercellular communication via gap junctions was markedly reduced in hepatocyte doublets with HGF (20 ng/ml) 3-12 hr after inoculation. Immunocytochemistry revealed spotty localization of connexin 32 on the plasma membrane of 3-hr cultured control hepatocyte doublets, whereas HGF-treated doublets showed significantly less connexin 32 staining. Genistein maintained intercellular communication in the presence of HGF, indicating that HGF reduces intercellular communication by down regulation of connexin 32 through the c-met/HGF receptor-tyrosine-kinase-mediated pathway. Furthermore, TGF-beta 1 maintained intercellular communication in the presence of HGF. Regulation of intercellular communication in hepatocytes by HGF and TGF-beta 1 might play an important role during liver regeneration.

Analysis of Variance↗
PubMed1995

Differential effects of an acyl-coenzyme A:cholesterol acyltransferase inhibitor on HDL-induced cholesterol efflux from rat macrophage foam cells.

When rat macrophages were converted to foam cells with acetylated low density lipoprotein (acetyl-LDL) and then reacted with high density lipoprotein (HDL) and an inhibitor of acyl-coenzyme A:cholesterol acyltransferase (58-035) (sequential incubation system), 58-035 did not enhance HDL-induced cholesterol efflux. In contrast, when macrophages were exposed to acetyl-LDL in the presence of both HDL and 58-035 (simultaneous incubation system), HDL-induced cholesterol efflux was enhanced 1.6-fold by 58-035. Cholesterol efflux with HDL alone was 2-fold greater in simultaneous incubation than in sequential incubation. These results suggest the presence of an efficient cholesterol efflux pathway in simultaneous incubation which is not available in sequential incubation. This pathway, which we refer to as the neutral cholesterol ester hydrolase-independent pathway, is characterized by the efflux of lysosome-derived cholesterol without re-esterification.

Animals↗
PubMed1995

Tissue-selective inhibition of sterol synthesis in mice by pravastatin sodium after a single or repeated oral administrations.

Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, exhibits liver-selectivity in inhibiting sterol synthesis, when administered as a single oral dose to mice or rats, whereas lovastatin and simvastatin do not. This may be due to the fact that pravastatin is distributed intracellularly, to a large extent, in the liver and extracellularly in nonhepatic tissues. In the present study, we examined whether the difference in liver-selectivity among these three HMG-CoA reductase inhibitors observed in single-dose studies was preserved after repeated oral administrations of drugs to mice. De novo sterol synthesis in different tissues of mice was examined in vivo three hours after the last dose of drug by measuring incorporation of intraperitoneally injected [14C]acetate into total sterols. Pravastatin administered orally for 11 consecutive days at 5 and 10 mg/kg exhibited a greater liver-selectivity than lovastatin and simvastatin: sterol synthesis was inhibited more than 60% in the liver by all three drugs, whereas that in nonhepatic tissues was inhibited less than 10% by pravastatin and more than 30% by lovastatin and simvastatinin in most of the nonhepatic tissues examined. Pravastatin administered orally for 11 consecutive days at 10 mg/kg caused more selective inhibition of sterol synthesis in liver ex vivo than two other inhibitors at the same dose. Pravastatin inhibited de novo sterol synthesis from [14C]acetate into sterol fraction in the liver slices in vitro, but minimally in those of the spleen and testis, whereas lovastatin and simvastatin inhibited in those of all three tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Massive fetomaternal hemorrhage.

We evaluated the potential prognostic factors for fetomaternal hemorrhage (FMH). Sinusoidal heart rate pattern and decrease in fetal movement are considered important signs of FMH. However these findings were detected in only two of six cases of FMH and were thought to be late signs of FMH. Fetal hemoglobin levels in the maternal circulation for infants born alive following FMH were less than 5%. Our findings suggest that this amount of blood loss could cause fetal death.

Adult↗
PubMed1995

Bronchial hyper-responsiveness to inhaled histamine in children with congenital heart disease.

In order to assess bronchial responsiveness in patients with congestive heart failure secondary to congenital heart disease, we performed a histamine inhalation test while monitoring transcutaneous oxygen tension and compared the respiratory threshold to histamine with that obtained in patients with bronchial asthma. The inhalation test was performed by doubling concentrations of histamine solution for 2 min at 1 min intervals. The respiratory threshold of histamine was defined as the minimal concentration causing a drop in transcutaneous oxygen tension greater than 10% from baseline. Six of 10 patients with congenital heart disease and all of 12 patients with bronchial asthma had bronchial hyper-responsiveness to histamine. The mean of histamine concentration was 2750 micrograms/mL and 937 micrograms/mL, respectively. During the histamine inhalation test, respiratory resistance gradually increased in congenital heart disease patients. This was measured by the linear slope of transcutaneous oxygen pressure (-1.08 +/- 0.75 mmHg/min), whereas in the bronchial asthma patients it rapidly decreased at the infection point (-4.19 +/- 1.86 mmHg/min). We conclude that children with congestive heart failure had bronchial hyper-responsiveness. We suggest bronchial hyper-responsiveness to inhaled histamine in congestive heart failure was caused by the gradual increased respiratory resistance, which was different from that of bronchial asthma.

Blood Gas Monitoring, Transcutaneous↗
PubMed1995

Intravenous injection of rabbit apolipoprotein A-I inhibits the progression of atherosclerosis in cholesterol-fed rabbits.

The effects of intravenous injection of purified rabbit apoA-I on the progression of aortic atherosclerosis in cholesterol-fed rabbits were examined. In experiment 1, 28 rabbits were equally divided into groups A and B and fed a 0.5% cholesterol diet for 90 days. For the last 30 days, group B received 40 mg apoA-I every week. The fatty streak lesions in group B (23.9 +/- 15.6%) were significantly suppressed compared with those in group A (46.0 +/- 24.9%) (P < .05). In experiment 2, 33 rabbits were divided into four groups (8 or 9 rabbits per group) and fed a 0.5% cholesterol diet. Group A was killed on day 105, while groups B, C, and D were maintained for an additional 60 days on a normal diet, during which time groups C and D received 1 mg apoA-I every other day or 40 mg apoA-I every week, respectively. The lesions in group C (70.2 +/- 15.4%) and group D (65.7 +/- 20.0%) were significantly suppressed compared with those in group B (86.2 +/- 13.7%) (P < .05) but were not reduced to the level of group A (50.0 +/- 22.9%). Although apparent regression was not observed under these conditions, the present study provided the first evidence for the antiatherogenic effect of homologous and apoA-I on the progression of atherosclerosis in cholesterol-fed rabbits.

Animals↗
PubMed1995

Immunological study of anti-M2 in antimitochondrial antibody-negative primary biliary cirrhosis.

We investigated the specificity of various autoantibodies in antimitochondrial antibody (AMA)-negative patients with primary biliary cirrhosis (PBC). We examined sera from 144 patients with PBC, 17 of whom were AMA negative by indirect immunofluorescence. The AMA-negative group showed a significantly higher positivity for smooth muscle antibody, but not for antinuclear antibody, as compared with the AMA-positive group. IgG class anti-PDH by enzyme-linked immunosorbent assay (ELISA) were detected in 13% of the AMA-negative group. However, all PBC patients showed positive IgG, IgA, and/or IgM class anti-M2 to the four M2 proteins by immunoblotting. These results suggest that the detection of IgG and IgM class anti-PDH and that of antibodies to the four M2 proteins increases the positivity of this ELISA method, and that detection of IgG, IgA, and IgM class anti-M2 to the four M2 proteins by immunoblotting is useful in diagnosing AMA-negative patients with PBC.

Adult↗
PubMed1995

Different features of Ca2+ oscillations in differentiated and undifferentiated hepatocyte doublets.

Cytosolic free Ca2+ ([Ca2+]i) oscillations are postulated to play a critical role in cellular proliferation. By using doublets of normal rats (NR) and those 18 hours after two-thirds hepatectomy (PHR), we investigated cytosolic free Ca2+ ([Ca2+]i) responses in liver regeneration. Normal rat hepatocyte doublets that retain their bile canaliculi are polarized and well differentiated. PHR doublets, which also retain their bile canaliculi, were characterized as undifferentiated by (1) decreased canalicular secretion of fluorescein-isothiocyanate-labeled glycocholate; (2) increased labeling index of hepatocytes in BrdU staining (approximately 30%); and (3) impaired transfer of fluorescent dye injected into one cell of the pair to the other. Addition of phenylephrine to NR and PHR doublets in the presence of extracellular Ca2+ resulted in [Ca2+]i oscillations or a nonoscillatory-sustained increase in [Ca2+]i followed by a gradual return to the baseline. Extracellular Ca2+ was not required for [Ca2+]i oscillations but was necessary for a sustained increase in [Ca2+]i. Simultaneous addition of prazosin, alpha 1-receptor blocker, to doublets immediately abolished these [Ca2+]i responses. The [Ca2+]i level in each of the adjacent cells was synchronous in sustained increase in [Ca2+]i but asynchronous in [Ca2+]i oscillations. As the phenylephrine concentration was increased (1 to 100 mumol/L), oscillations were replaced by a sustained increase in [Ca2+]i in NR doublets. In contrast, in PHR doublets, oscillations remained, whereas the frequency of oscillations increased in a dose-dependent manner. These results indicate that the mechanisms of phenylephrine-evoked [Ca2+]i responses are different in differentiated and undifferentiated doublets and that the frequency modulation of [Ca2+]i oscillations may be involved in the intracellular signal transduction in the cellular proliferation process during liver regeneration.

Adrenergic alpha-Antagonists↗
PubMed1994

Antianxiety actions of Ca2+ channel antagonists with Vogel-type conflict test in rats.

We examined the effects of various derivatives of Ca2+ channel antagonists in a modified rat Vogel-type conflict model. Flunarizine (10 and 20 mg/kg), nicardipine (20 mg/kg), and verapamil (20 mg/kg), given as single i.p. injections, significantly increased punished lickings by 50-110%. Chronic administration of diltiazem, at 20 mg/kg i.p. for 8 days, a dose ineffective with a single i.p. injection, produced a significant anticonflict action. The possibility that Ca2+ channel antagonists have anxiolytic action should be considered.

Animals↗
PubMed1994

Experimental development of a chitosan-bonded beta-tricalcium phosphate bone filling paste.

Bone filling substances are needed to meet several requirements including nontoxicity, setting time, changes in pH values, and amount of dissolved elements as well as mechanical properties. In this study, the bone-generating composites were prepared by employing the in vivo absorbable beta-tricalcium phosphate as a parent matrix kneaded with CaO, MgO, and ZnO as bone mineral additives with different compositions. The setting time, pH values, compressive strength were investigated as a function of the amount of these bone mineral additives. It was found that the setting time was shortened by increasing CaO, MgO, and ZnO contents. Increasing ZnO contents resulted in the pH value lower, while the pH values increased by increasing CaO and MgO contents. Increasing ZnO contents caused the compressive strength stronger, on the other hand, the compressive strength was weakened by increasing MgO contents. Furthermore, calcium appears to be selectively released from the hardened composite sample.

Analysis of Variance↗
PubMed1993

Stimulatory effects of protein kinase C and calmodulin kinase II on N-methyl-D-aspartate receptor/channels in the postsynaptic density of rat brain.

To clarify the regulatory mechanism of the N-methyl-D-aspartate (NMDA) receptor/channel by several protein kinases, we examined the effects of purified type II of protein kinase C (PKC-II), endogenous Ca2+/calmodulin-dependent protein kinase II (CaMK-II), and purified cyclic AMP-dependent protein kinase on NMDA receptor/channel activity in the postsynaptic density (PSD) of rat brain. Purified PKC-II and endogenous CaMK-II catalyzed the phosphorylation of 80-200-kDa proteins in the PSD and L-glutamate- (or NMDA)-induced increase of (+)-5-[3H]methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate ([3H]MK-801; open channel blocker for NMDA receptor/channel) binding activity was significantly enhanced. However, the pretreatment of PKC-II- and CaMK-II-catalyzed phosphorylation did not change the binding activity of L-[3H]glutamate, cis-4-[3H](phosphonomethyl)piperidine-2-carboxylate ([3H]CGS-19755; competitive NMDA receptor antagonist), [3H]glycine, alpha-[3H]-amino-3-hydroxy-5-methyl-isoxazole-4-propionate, or [3H]-kainate in the PSD. Pretreatment with PKC-II- and CaMK-II-catalyzed phosphorylation enhanced L-glutamate-induced increase of [3H]MK-801 binding additionally, although purified cyclic AMP-dependent protein kinase did not change L-glutamate-induced [3H]MK-801 binding. From these results, it is suggested that PKC-II and/or CaMK-II appears to induce the phosphorylation of the channel domain of the NMDA receptor/channel in the PSD and then cause an enhancement of Ca2+ influx through the channel.

Animals↗
PubMed1992

Cross-linking of apolipoproteins is involved in a loss of the ligand activity of high density lipoprotein upon Cu(2+)-mediated oxidation.

A recent study demonstrated that Cu(2+)-mediated oxidation of high density lipoprotein (HDL) resulted in a loss of the capacity to reduce cholesterol from macrophage foam cells [(1991) Proc. Natl. Acad. Sci. USA 88, 6457-6461]. In the present study we characterized the physicochemical properties of oxidized HDL and correlated them with the ligand activity toward the HDL receptor. Among them, the cross-linking of apolipoproteins and an increase in lipid peroxides were characteristic and closely similar to those of tetranitromethane-treated HDL, an abortive ligand for the HDL receptor. Cellular experiments with murine peritoneal macrophages revealed that both the cellular binding activity of HDL and its capacity to enhance cholesterol efflux from macrophage foam cells were markedly reduced upon oxidation. These results suggest that cross-linking of HDL apolipoproteins is involved in the loss of the ligand activity of oxidized HDL.

Animals↗
PubMed1992

Differential effect of subspecies of lipoprotein containing apolipoprotein A-I on cholesterol efflux from cholesterol-loaded macrophages: functional correlation with lecithin: cholesterol acyltransferase.

Two species of lipoprotein containing apoA-I, one containing only apoA-I (LpA-I), and the other containing apoA-I and apoA-II (LpA-I/A-II), were tested for their effects on macrophage foam cells. Rat macrophages were converted to foam cells by incubation with radiolabeled acetylated LDL. Incubation with LpA-I or LpA-I/A-II decreased the cellular cholesteryl esters (CE) mass. However, the free cholesterol (FC) mass was only reduced by LpA-I. All the radioactivity excreted into the medium was associated with LpA-I or LpA-I/A-II; 39% of the excreted radioactivity was esterified in LpA-I and 10% in LpA-I/A-II. Upon complete inactivation of lecithin: cholesterol acyltransferase (LCAT) activity with dithiobisnitrobenzoic acid, the cholesterol reducing capacity of LpA-I was weakened significantly. However, the CE mass reducing capacity of LpA-I/A-II was not affected. When LpA-I and LpA-I/A-II were combined, the cholesterol reducing capacity of the mixture was similar to that of LpA-I alone. However, LpA-I re-isolated from the medium showed a lower esterification rate than did the re-isolated LpA-I/A-II, thereby indicating that the cholesterol esterified in LpA-I was transferred to LpA-I/A-II. These results suggest that (i) the function of LpA-I is closely linked to the LCAT activity while that of LpA-I/A-II is not, and (ii) LpA-I in concert with LpA-I/A-II induces a series of extracellular events; LCAT-mediated esterification of excreted FC by LpA-I and a subsequent CE transfer to LpA-I/A-II. These mechanisms might be important for net cholesterol efflux from macrophage foam cells in physiological states.

Adolescent↗
PubMed1992

High density lipoprotein mediates selective reduction in cholesteryl esters from macrophage foam cells.

To elucidate an anti-atherogenic nature of high density lipoprotein (HDL) at cellular level, its in vitro effect on macrophage foam cells was examined. Rat peritoneal macrophages were converted to foam cells by incubation with [3H]cholesterol-labeled acetylated LDL. HDL addition to these foam cells resulted in a reduction in cellular radioactive cholesteryl esters (CE) as well as its CE mass. The radioactive free cholesterol (FC) was similarly reduced with time, whereas its FC mass level was unaltered. Other lipoproteins such as very low density lipoprotein and low density lipoprotein also reduced the radioactive FC. However, their CE-reducing capacity was negligibly weak. These results suggest that (i) CE reduction is selective to HDL, (ii) FC transfer from plasma membrane to lipoprotein (cholesterol efflux) expressed by reduction in radioactive FC is not selective to HDL but occurs to other lipoproteins, (iii) the CE-reducing capacity of HDL became weaker when cellular binding of HDL was reduced by chemical modification with tetranitromethane or a chemical cross-linker, dithiobis-succinimidylpropionate, suggesting an importance of the specific binding in the HDL-mediated CE reduction. These in vitro results gave an experimental support to a definite role of HDL as an anti-atherogenic lipoprotein in vivo.

Animals↗
PubMed1992

Effect of the beta-adrenoceptor antagonist, propranolol, on feeding induced by noradrenaline and muscimol in rats kept at high and temperate-ambient temperatures.

Both the gamma-aminobutyric acid (GABA) receptor agonist, muscimol, and noradrenaline stimulated the feeding behavior of rats in the two environments. When noradrenaline or muscimol was administered, however, the food intake at 26 degrees C was greater than that at 33 degrees C. In addition, the stimulatory effect of noradrenaline on food intake was significantly depressed by propranolol pretreatment at both temperatures. The stimulatory effect of muscimol on food intake was significantly depressed by the propranolol pretreatment at 33 degrees C but not at 26 degrees C. Some eating-stimulatory subsystems associated with feeding behavior induced by noradrenaline or muscimol might have been depressed in the hot environment, thus the food intake increased by these drugs in rats acclimated to the hot environment was less than that in rats acclimated to the temperate environment.

Animals↗
PubMed1992

Exposure of rat peritoneal macrophages to acetylated low density lipoprotein results in release of plasma membrane cholesterol. An efficient substrate for esterification by acyl-CoA:cholesterol acyltransferase.

In J774 macrophages and murine macrophages stimulated with acetylated low density lipoprotein (acetyl-LDL), the plasma membrane free cholesterol (FC) became accessible to acyl-CoA:cholesterol acyltransferase (ACAT) as substrate, the result being an accumulation of cholesteryl esters (CE) (Tabas, I., Rosoff, W. J., and Boykow, G. C (1988) J. Biol. Chem. 263, 1266-1272). As the route of delivery of FC to ACAT was not well characterized, we examined this route in the present study. In foam cells derived from rat peritoneal macrophages by preincubation with acetyl-LDL, esterification of the exogenously labeled [3H]FC was low (1.3% of total labeled cholesterol). In contrast, when cells were first labeled with exogenous [3H]FC and then chased with acetyl-LDL, the esterification was more extensive (9.2% of the total labeled cholesterol). During this experiment a significant portion of cellular [3H]FC was released into the medium (up to 33.4% of the total labeled cholesterol). In experiments using a two-compartment chamber in which cells in the lower and upper chambers were separated by filter paper yet the cells in both compartments could communicate without direct contact, [3H]FC released into the medium was biologically active and could serve as an efficient substrate for ACAT. Thus, when acetyl-LDL is not included in culture medium, FC delivery from the macrophage plasma membrane to ACAT is not enhanced, whereas in the presence of acetyl-LDL, plasma membrane FC released and bound to acetyl-LDL may re-enter the cells, possibly through the scavenger receptor. This would provide a significant route for CE synthesis in macrophages.

Animals↗