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Biomedical subjects

M Yamazaki

Publications and source records attributed to M Yamazaki.

At least 433 records · Page 24Linked to original sources
PubMed1995

Abnormal hepatic copper accumulation of spheroid composed of liver cells from LEC rats in vitro.

The LEC rat is a mutant strain displaying hereditary hepatitis, and shows abnormal accumulation of copper (Cu) similar to that occurring in Wilson's disease. We prepared a multicellular spheroid composed of LEC rat liver cells to investigate the mechanism for abnormal accumulation of Cu. These multicellular spheroids were prepared by detaching the monolayer on the collagen-conjugated thermo-responsive polymer coated culture dish at a temperature below the critical solution temperature and culturing on the non-adhesive substratum. Long-term cultured spheroids of LEC rat liver cells as well as SD rat liver cells were attempted. Non-parenchymal cells obtained by collagenase perfusion from the LEC liver were fewer than those from the SD liver. Cells from the LEC rat, over 11 weeks of age, did not form a cell sheet; however, a mixture of parenchymal cells from LEC rats over aged 11 weeks and non-parenchymal cells from SD rats of any age yielded intact spheroids. We examined the toxicity, the accumulation and distribution of Cu in spheroids. The accumulation of Cu in LEC spheroids was higher than that in SD spheroids. Results suggest that spheroids consisting of LEC liver cells are useful as an alternative model to in vivo tests to investigate the mechanism for abnormal accumulation of Cu in liver.

Animals↗
PubMed1995

Pseudoaneurysm caused by disruption of an externally supported knitted Dacron graft for femoropopliteal bypass.

Technological advances in artificial blood vessels used in arterial reconstructive surgery have contributed significantly to the development of this field. The 5-year cumulative patency rate of femoropopliteal bypass using knitted Dacron grafts at Keio University Hospital is over 80% (1). This rate is comparable with the results of femoropopliteal bypass surgery using autovein grafts (2, 3, 4). Therefore, we usually perform femoropopliteal bypass using a knitted Dacron graft. However, pseudoaneurysm formation remains one of the major complications of arterial reconstructive surgery. In most cases, a pseudoaneurysm is caused by infection or external injury, and is detected at the anastomotic site. This paper deals with an extremely rare, non-anastomotic aneurysm caused by total disruption in the middle of an externally supported knitted Dacron graft used for femoropopliteal bypass.

Aneurysm, False↗
PubMed1994

Lysophosphatidylcholine plays an essential role in the mitogenic effect of oxidized low density lipoprotein on murine macrophages.

We previously demonstrated that the growth of starch-induced murine macrophages was stimulated by modified low density lipoproteins, such as oxidized low density lipoprotein (Ox-LDL) and acetylated low density lipoprotein (acetyl-LDL), and that the mitogenic effect of Ox-LDL was much greater than that of acetyl-LDL (Yui, S., Sasaki, T., Miyazaki, A., Horiuchi, S., and Yamazaki, M. (1993) Arterioscler. Thromb. 13, 331-337). The present study was undertaken to elucidate the factor(s) that are involved in this growth-stimulating effect of Ox-LDL. The growth-stimulating effect of acetyl-LDL on murine resident macrophages was negligibly weak compared with that of Ox-LDL. However, the treatment of acetyl-LDL with phospholipase A2 led to an increase in lysophosphatidylcholine (lyso-PC) (75% of total phospholipids) and a concomitant increase in the mitogenic activity of acetyl-LDL. In contrast, cell-free incubation of Ox-LDL with high density lipoprotein resulted in a decrease in lyso-PC content and a concomitant loss of growth-stimulating activity. These results suggest that lyso-PC may play an essential role in the mitogenic activity of Ox-LDL.

Animals↗
PubMed1994

Postmortem changes in drug-metabolizing enzymes of rat liver microsome.

Postmortem changes in the drug-metabolizing enzymes in rat liver microsome were studied. Parameters investigated were: microsomal protein, NADPH-cytochrome P-450 reductase activity, NADH-cytochrome b5 reductase activity, cytochrome b5 content, cytochrome P-450 content, aminopyrine N-demethylase activity, aniline p-hydroxylase activity, p-nitroanisole O-demethylase activity, uridine diphosphate (UDP)-glucuronyl transferase activity and glutathione S-transferase activity. Nearly all the parameters based on microsomal protein decreased during autolysis and the time-dependent decrement ratios of the parameters changed by various amounts. Cytochrome b5 content decreased more rapidly than that of other components. By 36 h post mortem, levels of cytochrome b5 were not detectable. By 48 h post mortem, NADPH-cytochrome P-450 reductase activity decreased to 91%, NADH-cytochrome b5 reductase activity decreased to 94%, and cytochrome P-450 content decreased to 92% of relative activities. By 48 h post mortem, aminopyrine N-demethylase activity decreased to 87%, aniline p-hydroxylase activity decreased to 98% and p-nitroanisole O-demethylase activity decreased to 75% of relative activities. The activity of p-nitroanisole O-demethylase appeared to be more stable than that of aminopyrine N-demethylase or aniline p-hydroxylase. These results demonstrate that there are multiple forms of isozymes of the cytochrome P-450-linked monooxygenase system. Hepatic transferases showed decrease patterns different to those of monooxygenases, so UDP-glucuronyl transferase activity of approximately 32% of relative activity was detected at 48 h post mortem. Thus, UDP-glucuronyl transferase activity appeared to be more stable than the cytochrome P-450-linked monooxygenases. These results show that these activities and components would be useful as markers of postmortem time. The causes of the variety of instability of these enzyme systems are discussed.

Animals↗
PubMed1994

C-kit gene is expressed by skin mast cells in embryos but not in puppies of Wsh/Wsh mice: age-dependent abolishment of c-kit gene expression.

The Wsh is a mutant allele at the W (c-kit) locus of mice, but no significant abnormalities are found at the coding region of the Wsh allele. Since cultured mast cells derived from the spleen of Wsh/Wsh mice do not express messenger RNA (mRNA) of c-kit, we studied the interrelation between the number of mast cells and the magnitude of c-kit mRNA expression in the skin of Wsh/Wsh mice of various ages. The number of mast cells in the skin of Wsh/Wsh embryos of 18 days postcoitum (pc) was approximately 40% that of normal control (+/+) embryos, but the number of mast cells decreased exponentially after birth; the number dropped to 0.6% that of +/+ mice at day 150 after birth. A weak but apparent signal of c-kit mRNA was detectable in the skin of 18-day pc Wsh/Wsh embryos by RNase protection assay but not in the skin of 5-day-old Wsh/Wsh mice. The number of c-kit protein-containing cells was significantly greater in the skin of 18-day pc Wsh/Wsh embryos than in the skin of 5-day-old Wsh/Wsh mice. The abolishment of c-kit mRNA expression appeared to be specific, because the expression of mast cell carboxypeptidase A mRNA but not of c-kit mRNA was detectable by in situ hybridization in skin mast cells of 5-day-old Wsh/Wsh mice. Taken together, the expression of c-kit mRNA was abolished first, then the content of c-kit protein dropped to undetectable levels, and then the disappearance of Wsh/Wsh mast cells themselves followed.

Age Factors↗
PubMed1994

Signal transduction pathway in human polymorphonuclear leukocytes for chemotaxis induced by a chemotactic factor. Distinct from the pathway for superoxide anion production.

The tyrosine kinase inhibitors erbstatin and herbimycin A inhibited the chemotactic response to FMLP (2 x 10(-7) M) and the superoxide anion (O2-) production stimulated by FMLP (1 x 10(-6) M) in human polymorphonuclear leukocytes (PMN) in similar manners. These compounds also inhibited phospholipase D (PLD)-catalyzed breakdown of phosphatidyl choline, suggesting a possible link between tyrosine kinase and PLD. In the presence of propranolol (phosphatidic acid (PA) phosphohydrolase inhibitor), or ethanol, the activation of PLD results in the modulation of PA and/or diglyceride (DG) generation, producing an irregularity in O2- production. However, PMN motility was not affected in these conditions. These results suggest that PLD is a downstream effector of FMLP-induced tyrosine kinase activation that leads to activation of the PMN superoxide release but not to chemotactic migration. In contrast, the tyrosine kinase inhibitors did not inhibit inositol 1,4,5-triphosphate generation and increase of intracellular concentration of free calcium. Furthermore, a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), did not affect the migration of PMN and the activation of PLD induced by FMLP at concentrations of less than 50 microM. These results support the premise that there is a specific signaling pathway for chemoattractant-induced PMN locomotion.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

A hippocampal protein associated with paraneoplastic neurologic syndrome and small cell lung carcinoma.

A hippocampal 38 kd autoantigen recognized by an autoantibody from the serum of a patient with paraneoplastic limbic encephalitis (PLE) and small cell lung carcinoma (SCLC) was isolated by screening a human hippocampal cDNA library. The 1,991-nucleotide ple21 clone was obtained and the deduced 350-residue protein encoded by the ple21 cDNA clone was found to be highly homologous to the neuron-specific RNA recognition motifs (RRMs)-containing proteins. The homologies were confined to the RRMs and the RRM connecting region. The presence of RRM in the antigenic protein may be important in the pathogenesis of SCLC-associated paraneoplastic neurologic syndrome.

Amino Acid Sequence↗
PubMed1994

Induction of macrophage growth by advanced glycation end products of the Maillard reaction.

We previously showed that negatively-charged phospholipids, acetylated low density lipoprotein (LDL) and oxidized LDL, which are known to be taken up by macrophages via the scavenger receptor for modified LDLs, were able to induce the growth of peripheral macrophages in vitro. The present study demonstrated the macrophage growth-stimulating activity of the ligands for another macrophage receptor for advanced glycation end products (AGE) of the Maillard reaction. Experiments with murine macrophages showed that significant cell growth was induced by AGE-modified proteins such as bovine serum albumin (AGE-BSA) and AGE-human hemoglobin. The capacity of AGE-BSA to induce macrophage growth was completely blocked when cells were cultured with the mAb against granulocyte/macrophage CSF (GM-CSF). Moreover, PCR analysis revealed that AGE-BSA induced the expression of mRNA of GM-CSF. These data suggest that the macrophage AGE receptor may play an active role not only in phagocytic elimination of AGE-proteins but also induction of the growth of macrophages.

Animals↗
PubMed1994

Astrocytic straight tubules in the brain of a patient with Pick's disease.

This report concerns an immunohistochemical and ultrastructural study of cerebral astrocytes in a patient with Pick's disease of 20 years' duration. The autopsied brain was prominently small (710 g) with marked fronto-temporal lobar atrophy. Histological examination demonstrated profound neuronal loss and spongy changes with tau-positive Pick bodies in the frontal and temporal cortex. In addition, many glial cells in the temporal lobe white matter contained round to oval, argentophilic and slightly hematoxinophilic cytoplasmic inclusions that were also immunolabeled with the anti-tau antibody. On electron microscopy, the glial inclusions were observed in the perikarya of astrocytes that were recognized as such from intracytoplasmic glial filaments and the presence of gap junctions. The inclusions were free in the cytoplasm, without a limiting membrane, and mainly comprised irregular aggregations of bundles of about 15-nm straight tubules, which were indistinguishable from those of intraneuronal Pick bodies. Furthermore, various patterns of accumulation of the same straight tubules were frequently noted in perivascular astrocytic processes carrying a basal lamina. These findings indicate that in Pick's disease astrocytes are also affected by a similar insult to that which affects neurons.

Aged↗
PubMed1994

Ethylene vinylacetate copolymer particles dissolved in polyvinyl alcohol (2,000-mer) solution as an embolic material for vascular anomalies. A preliminary study.

We have prepared a new material for embolisation: ethylene vinylacetate copolymer dissolved in polyvinyl alcohol. When in contact with blood, polyvinyl alcohol rapidly becomes a soft gel, which is accompanied by wedging of the ethylene vinylacetate copolymer. We analysed the histopathology of intra-arterial microemboli in rats, after intracarotid injection of this material. We confirmed that it was applicable to embolisation for neurosurgical treatment.

Animals↗
PubMed1994

Activation of tumor-infiltrating macrophages by a synthetic lipid A analog (ONO-4007) and its implication in antitumor effects.

ONO-4007 is a novel synthetic analog of lipid A subunit and has been shown to exert antitumor activities on various experimental tumors with less toxicity than lipopolysaccharide. It remains unclear, however, what biological activities of this compound are relevant to its antitumor effects. We therefore investigated the activation of macrophages by ONO-4007 in vitro and in vivo and its implication in antitumor effects, using mouse MM46 mammary tumor as an experimental model. Intravenous injection of ONO-4007 produced significant therapeutic effects on this solid tumor. ONO-4007 could stimulate glycogen-elicited peritoneal macrophages in vitro, not only to produce tumor necrosis factor (TNF), but also to exert cytocidal activities against MM46 cells in vitro. Substantial TNF production was induced in tumor tissue by i. v. injection of ONO-4007, and its successive administration to tumor-bearing mice gave tumor-infiltrating macrophages a prominent in vitro tumoricidal activity and primed them for in vitro TNF secretion. These results suggest that activation of tumor-infiltrating macrophages to a direct tumoricidal state as well as to TNF secretion in tumor tissues may be at least some of the antitumor effects of this novel lipid A analog.

Animals↗
PubMed1994

Direct evidence of induction of interdigitated gel structure in large unilamellar vesicles of dipalmitoylphosphatidylcholine by ethanol: studies by excimer method and high-resolution electron cryomicroscopy.

Interaction of large unilamellar vesicle (LUV) of dipalmitoylphosphatidylcholine (DPPC) with ethanol was investigated by the excimer method developed by Yamazaki et al. (Yamazaki, M., M. Miyazu, and T. Asano. 1992. Biochim. Biophys. Acta. 1106:94-98) and the high-resolution electron cryomicroscope with a new cryostage (top-entry superfluid stage) (HiRECM) developed by Fujiyoshi, Y. et al. (Fujiyoshi, Y., T. Mizusaki, K. Morikawa, H. Aoki, H. Kihara, and Y. Harada. 1991. Ultramicroscopy. 38:241-251). The excimer method is based on the fact that the ratio of excimer to monomer fluorescence intensity (E/M) of pyrene PC is lowered in the membrane in the interdigitated gel structure (L beta I), because structural restriction of L beta I structure largely decreases collisions of pyrene rings of the pyrene PCs in the membrane. E/M of pyrene PC in DPPC LUV decreased largely at high concentrations of ethanol, which indicated the induction of L beta I structures in DPPC LUV. Frozen-hydrated DPPC LUVs in a vitreous ice were observed at 4K with HiRECM, and these images were characterized by a pair of concentric circles. The membrane thickness of DPPC LUV which was estimated from the distance between the two concentric lines decreased largely at high concentration of ethanol. The mean value of membrane thickness of the LUV in the absence of ethanol was 3.8 nm, while at 15% (w/v) ethanol was 3.0 nm. These values were almost same as those obtained from the electron density profile of DPPC MLV by the x-ray diffraction analysis in each structures, L beta' and L beta I structures, respectively. These results indicated directly the induction of L beta 1 structure in DPPC LUV at high concentration of ethanol.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1994

Carrier-mediated transport of H1-antagonist at the blood-brain barrier: mepyramine uptake into bovine brain capillary endothelial cells in primary monolayer cultures.

The transport mechanism of the H1-antagonist mepyramine at the blood-brain barrier (BBB) was studied by using primary cultured monolayers of bovine brain capillary endothelial cells (BCEC). The initial uptake of [3H]mepyramine into the BCEC showed strong temperature and concentration dependency, indicating that it involves both saturable and nonsaturable processes. Transport at the luminal membrane may be the rate-limiting process in the transcellular transport, since the values of the uptake coefficient of [3H]mepyramine at the luminal membrane (609 microliters/mg protein/min) and the transcellular permeability coefficient (488 microliters/mg protein/min) are very similar. The initial uptake of [3H]mepyramine was not affected by metabolic inhibitors, but was stimulated by preloading with the drug. Mepyramine appears to be transported into the BCEC by a carrier-mediated transport system which does not require metabolic energy, probably via a facilitated diffusion mechanism.

Animals↗
PubMed1994

Carrier-mediated transport of H1-antagonist at the blood-brain barrier: a common transport system of H1-antagonists and lipophilic basic drugs.

The blood-brain barrier (BBB) transport system for H1-antagonists was studied using primary cultured bovine brain capillary endothelial cells (BCEC). The uptake of [3H]mepyramine was inhibited by various H1-antagonists. Ketotifen competitively inhibited [3H]mepyramine uptake with an inhibition constant (Ki) of 46.8 microM. Lipophilic basic drugs such as propranolol, lidocaine and imipramine significantly inhibited [3H]mepyramine uptake. In particular, propranolol inhibited [3H]mepyramine uptake competitively at an inhibition constant (Ki) of 51.1 microM. Moreover, in ATP-depleted BCEC, [3H]mepyramine uptake was stimulated by preloading with H1-antagonists and lipophilic basic drugs. These results indicated that H1-antagonists are transported across the BBB via a carrier-mediated transport system common to lipophilic basic drugs.

Animals↗
PubMed1994

Anti-tumour activity of low-toxicity lipopolysaccharide of Bordetella pertussis.

A lipopolysaccharide (BP-LPS) isolated from killed Bordetella pertussis (Tohama strain) was determined to have low toxicity based on the mortality and decrease in body weight of BP-LPS-injected mice. BP-LPS, administered intradermally or intraperitoneally, clearly inhibited the growth of an MM46 murine mammary carcinoma. When compared with a toxic Escherichia coli-derived LPS, BP-LPS displayed excellent anti-tumour activity against MH134 hepatoma and Meth A fibrosarcoma. As part of a combined chemotherapy/immunotherapy regimen, BP-LPS also seemed to prolong the lifespan of mice inoculated with Lewis lung carcinoma. BP-LPS thus appears to have valuable characteristics as an anti-tumour agent.

Animals↗
PubMed1994

Effects of halothane and diltiazem on L-type calcium currents in single smooth muscle cells from rabbit portal veins.

We have studied the effects of halothane and diltiazem on L-type voltage-dependent calcium currents (ICa) in single smooth muscle cells from rabbit portal veins using a whole cell voltage clamp technique. The threshold of ICa was -30mV and the peak current was reached at 0mV. Halothane (0.25, 0.5, 1.0, 1.5 and 2.0%) decreased ICa in a concentration-dependent manner and shifted the ICa activation threshold to the depolarizing side. Halothane 2.0% abolished ICa. Diltiazem 10(-8)-10(-6) mol litre-1, a calcium channel antagonist, also depressed ICa in a concentration-dependent manner. Administration of both 0.5% halothane and diltiazem 10(-7) mol litre-1 (concentrations lower than the clinical therapeutic range) abolished ICa; however, halothane did not exhibit use-dependent inhibition of ICa whereas diltiazem showed partial use-dependency. We conclude that the decrease in ICa produced by halothane is associated with a direct vasodilator effect of this anaesthetic, but is not explained by block of Ca2+ channels similar to the action of diltiazem. Furthermore, administration of low concentrations of both halothane and diltiazem decreased ICa and may reduce the contractility of the vascular smooth muscle cells.

Animals↗
PubMed1994

Responses to histamine and acetylcholine in isolated monkey mesenteric veins versus arteries.

OBJECTIVE: The aim was to analyse and compare mechanisms of histamine or acetylcholine action in mesenteric venous and arterial strips obtained from Japanese monkeys. METHODS: Monkey mesenteric arterial and venous strips were suspended for isometric tension recording in modified Ringer-Locke solutions, and responses of the strips precontracted with prostaglandin F2 alpha to histamine or acetylcholine were compared. RESULTS: Histamine (2 x 10(-8) M-10(-5) M) produced a concentration related relaxation in the arteries and veins. The arterial relaxation was slightly but significantly attenuated by endothelial denudation [57.1(SEM 11.2)% inhibition at 10(-7) M, n = 14, p < 0.05] and treatment with 10(-6) M chlorpheniramine [26.7(6.7)% inhibition at 10(-7) M, n = 10, p < 0.05] or 10(-5) M methylene blue [31.5(11.2)% inhibition at 10(-7) M, n = 9, p < 0.05], and markedly suppressed by 10(-5) M cimetidine [96.8(1.2)% inhibition at 10(-7) M, n = 13, p < 0.001]. Indomethacin (10(-6) M) was without effect. On the other hand, relaxant responses to histamine of the venous strips were not influenced by endothelial denudation and treatment with chlorpheniramine or indomethacin but were abolished by treatment with cimetidine. Removal of the endothelium did not alter the venous relaxation caused by acetylcholine (10(-8) M-10(-4) M) but almost abolished the response to Ca2+ ionophore A23187 (10(-7) M) and substance P (10(-7) M). The acetylcholine induced relaxation was reversed to a contraction by indomethacin. CONCLUSIONS: Histamine-induced relaxations of monkey mesenteric arteries seem to be associated mainly with activation of the H2 receptor subtype in smooth muscle and partially mediated by relaxing factor liberated by stimulation of the H1 subtype in the endothelium, whereas the mesenteric venous relaxation seems to be due exclusively to a mediation of H2 receptors. Acetylcholine-induced relaxations of venous strips appear to be caused by vasodilator prostanoids, possibly prostaglandin I2, liberated from subendocardial tissues.

Acetylcholine↗