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Biomedical subjects

A Miyazaki

Publications and source records attributed to A Miyazaki.

At least 37 records · Page 2Linked to original sources

Glibenclamide acts as an inhibitor of acyl-CoA:cholesterol acyltransferase enzyme.

Sulfonylureas are used in the treatment of non-insulin-dependent diabetes mellitus. Little is known, however, about their effects on cholesterol metabolism. We tested in the present study the effects of glibenclamide (GB) on cholesterol esterification (CE) in macrophage-derived cells. GB inhibited intracellular accumulation of CE induced by acetylated LDL or oxidized LDL in J774 cells, but no such effect on total cholesterol, suggesting that the target of GB was acyl-CoA:cholesterol acyltransferase (ACAT). In the cell-free reconstitution ACAT assay, GB inhibited the ACAT activity with an IC(50) value of 20 microM. Furthermore, GB effectively inhibited the ACAT activity of PMA-stimulated THP-1 cells to the undifferentiated level of THP-1. In the whole-cell ACAT assay using CHO cells overexpressed with ACAT-1 or ACAT-2, GB inhibited the activity of both isozymes with similar potency. Our in vitro data suggest that sulfonylurea could be a potential seed for a new generation of ACAT inhibitors.

Anilides↗

Sites of action of protein kinase C and phosphatidylinositol 3-kinase are distinct in oxidized low density lipoprotein-induced macrophage proliferation.

Oxidized low density lipoprotein (Ox-LDL) can induce macrophage proliferation in vitro. To explore the mechanisms involved in this process, we reported that activation of protein kinase C (PKC) is involved in its signaling pathway (Matsumura, T., Sakai, M., Kobori, S., Biwa, T., Takemura, T., Matsuda, H., Hakamata, H., Horiuchi, S., and Shichiri, M. (1997) Arterioscler. Thromb. Vasc. Biol. 17, 3013-3020) and that expression of granulocyte/macrophage colony-stimulating factor (GM-CSF) and its subsequent release in the culture medium are important (Biwa, T., Hakamata, H., Sakai, M., Miyazaki, A., Suzuki, H., Kodama, T., Shichiri, M., and Horiuchi, S. (1998) J. Biol. Chem. 273, 28305-28313). However, a recent study also demonstrated the involvement of phosphatidylinositol 3-kinase (PI3K) in this process. In the present study, we investigated the role of PKC and PI3K in Ox-LDL-induced macrophage proliferation. Ox-LDL-induced macrophage proliferation was inhibited by 90% by a PKC inhibitor, calphostin C, and 50% by a PI3K inhibitor, wortmannin. Ox-LDL-induced expression of GM-CSF and its subsequent release were inhibited by calphostin C but not by wortmannin, whereas recombinant GM-CSF-induced macrophage proliferation was inhibited by wortmannin by 50% but not by calphostin C. Ox-LDL activated PI3K at two time points (10 min and 4 h), and the activation at the second but not first point was significantly inhibited by calphostin C and anti-GM-CSF antibody. Our results suggest that PKC plays a role upstream in the signaling pathway to GM-CSF induction, whereas PI3K is involved, at least in part, downstream in the signaling pathway after GM-CSF induction.

Androstadienes↗

Premeiotic aster as a device to anchor the germinal vesicle to the cell surface of the presumptive animal pole in starfish oocytes.

The germinal vesicle (GV) of starfish oocytes stays just beneath the oocyte cortex at the presumptive animal pole during the long period of oogenesis. We subjected oocytes to a centrifugal force field to detach the GV from the cortex. The association between the cortex and the GV persisted and withstood a small amount of centrifugal acceleration at 200 g. The GV was eventually separated from the cortex at 700 g. The amount of acceleration sufficient for the GV separation was lowered when the oocytes were pretreated with Nocodazole and was increased by Taxol pretreatment. Observation of microtubular structures with an anti-alpha-tubulin antibody revealed the presence of a complex of spots and radiating arrays as was described by J. J. Otto and T. E. Schroeder (1984, Dev. Biol. 101, 274-281) and called the premeiotic aster. Nocodazole shortened the astral arrays, and Taxol enhanced them. These observations indicate that the premeiotic aster works as a device to hold the GV in an eccentric position just beneath the oocyte cortex.

Animals↗

A case report of intravenous leiomyomatosis extending into the heart.

The patient was a 47-year-old woman who underwent total hysterectomy for uterine leiomyoma in 1994. Two years later, intracaval and intravenous tumors were found by ultrasonic cardiography, magnetic resonance imaging, enhanced chest computed tomography, and venography. The patient underwent total removal of these tumors. Pathological findings indicated that these tumors were leiomyomas. After comparing the present findings with those of similar cases in the literature, we concluded that our patient had intravenous leiomyomatosis extending into the heart.

Female↗

Localization of human acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) in macrophages and in various tissues.

To investigate the distribution of acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) in various human tissues, we examined tissues of autopsy cases immunohistochemically. ACAT-1 was demonstrated in macrophages, antigen-presenting cells, steroid hormone-producing cells, neurons, cardiomyocytes, smooth muscle cells, mesothelial cells, epithelial cells of the urinary tracts, thyroid follicles, renal tubules, pituitary, prostatic, and bronchial glands, alveolar and intestinal epithelial cells, pancreatic acinar cells, and hepatocytes. These findings showed that ACAT-1 is present in a variety of human tissues examined. The immunoreactivities are particularly prominent in the macrophages, steroid hormone-producing cells, followed by hepatocytes, and intestinal epithelia. In cultured human macrophages, immunoelectron microscopy revealed that ACAT-1 was located mainly in the tubular rough endoplasmic reticulum; immunoblot analysis showed that the ACAT-1 protein content did not change with or without cholesterol loading; however, on cholesterol loading, about 30 to 40% of the total immunoreactivity appeared in small-sized vesicles. These vesicles were also enriched in 78-kd glucose-regulated protein (GRP 78), a specific marker for the endoplasmic reticulum. Immunofluorescent microscopy demonstrated extensive colocalization of ACAT-1 and GRP 78 signals in both the tubular and vesicular endoplasmic reticulum before and after cholesterol loading. These results raise the possibility that foam cell formation may activate an endoplasmic reticulum vesiculation process, producing vesicles enriched in the ACAT-1 protein.

Adult↗

Polymorphism of linoleic acid (cis-9, cis-12-octadecadienoic acid) and alpha-linolenic acid (cis-9, cis-12, cis-15-octadecatrienoic acid).

Crystallization and polymorphic properties of linoleic acid (cis-9, cis-12-Octadecadienoic acid) (LA) and alpha-linolenic acid (cis-9, cis-12, cis-15-Octadecatrienoic acid) (alpha-LNA) have been studied by optical microscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The DSC analyses presented three polymorphs in LA, and two polymorphs in alpha-LNA. The XRD patterns of the higher- and lower-temperature forms in LA and alpha-LNA showed orthorhombic O'(//)+O-like and O'(//) subcell, which were similar to those of alpha- and gamma-forms of mono-unsaturated fatty acids, respectively. From the solvent crystallization of LA and alpha-LNA in acetonitrile, single crystals of the higher temperature polymorphs have been obtained. The crystal habits of truncated rhombic shape were also similar to those of alpha-forms of the mono-unsaturated fatty acids. The enthalpy and entropy values of fusion and dissolution of the alpha-forms of LA, alpha-LNA and oleic acid showed that the two values decreased with increasing number of the cis-double bond.

Calorimetry, Differential Scanning↗

A quantitative extraction method for the determination of trace amounts of both butyl- and phenyltin compounds in sediments by gas chromatography-inductively coupled plasma mass spectrometry.

A simple and reliable extraction method was developed for quantitative determination of both butyl- and phenyltin compounds in sediments by capillary gas chromatography combined with inductively coupled plasma mass spectrometry (GC-ICP-MS). Both types of organotin compounds were extracted quantitatively from sediment by mechanical shaking into tropolone-toluene and HCl-methanol. After phase separation and pH adjustment, these organotins were ethylated with sodium tetraethylborate. The method was evaluated by analyzing PACS-2 and NIES No. 12 sediment certified reference materials. The dibutyltin (DBT; 1.14 +/- 0.02 micrograms g-1) and tributyltin (TBT; 1.01 +/- 0.04 micrograms g-1) values observed in PACS-2 sediment closely matched the certified values (DBT, 1.09 +/- 0.15; TBT, 0.98 +/- 0.13 microgram g-1 as tin). The monobutyltin (MBT) value was higher (0.62 +/- 0.02 microgram g-1) by more than two fold over the reference value (0.3 microgram g-1 as tin). The concentrations of TBT (0.18 +/- 0.04 microgram g-1) and triphenyltin (TPhT; 0.0099 +/- 0.002 microgram g-1) in the NIES No. 12 sediment were also in good agreement with the certified and reference values of TBT (0.19 +/- 0.03 microgram g-1 as compound) and TPhT (0.008 microgram g-1 as compound), respectively. Recoveries of TBT, tripentyltin (TPeT) and TPhT from spiked sediments were satisfactory (TBT, 102 +/- 3.4%; TPrT, 96 +/- 3.4%; TPhT, 99 +/- 8.5%). The detection limits as tin were in the range 0.23-0.48 ng g-1 for a 0.5 g sample size. It is also noteworthy that clean-up of the extract is not necessary because of the superior selectivity of ICP-MS detection. The present method was successfully applied to marine sediment samples.

Environmental Pollutants↗

The incidence of reflux oesophagitis after cure of Helicobacter pylori in a Japanese population.

AIM: To investigate the incidence of reflux oesophagitis after antibacterial therapy for Helicobacter pylori infection in our patient population. METHODS: Subjects were 451 H. pylori-infected patients (primary symptom: peptic ulcer disease in 347, nonulcer dyspepsia in 100, and reflux oesophagitis in four): 11 of these patients had reflux oesophagitis on study entry. H. pylori infection was treated by a proton pump inhibitor/amoxycillin-clarithromycin regimen for either 7 or 14 days. Each patient was examined by endoscopy before treatment and more than 6 months after treatment to compare oesophageal findings. In addition, 227 patients were interviewed regarding reflux symptoms, using symptom questionnaires, before and more than 6 months after treatment. RESULTS: Among 440 patients who did not have reflux oesophagitis prior to antibacterial treatment (340 peptic ulcer patients and 100 nonulcer dyspepsia patients), 23 patients whose infection was eradicated developed reflux oesophagitis (5.4%). The 11 patients who had reflux oesophagitis prior to treatment were all successfully cured of infection. Six of these patients showed no change in their oesophagitis, while the condition improved in three and worsened in two. Symptom scores improved in 34 of the 36 patients who reported reflux symptoms. Among 19 patients who showed persistent infection, only one developed reflux oesophagitis (5.2%), while none complained of newly developed symptoms following treatment. CONCLUSIONS: Development of reflux oesophagitis after treatment of H. pylori infection was observed in a Japanese population. However, the incidence of this condition was comparable between those with persistent H. pylori infection and those in whom the infection was eradicated.

Adult↗

Effects of growth factors on aspirin-induced inhibition of wound repair in a rabbit gastric epithelial cell model.

BACKGROUND: Aspirin is known to cause adverse effects, including gastric mucosal injury, and to retard gastric wound healing. Growth factors including hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) have been shown to play an important role in the repair of gastric mucosal injury. AIM: To employ the cultured gastric epithelial cell model to elucidate the effects of aspirin, as well as several growth factors (HGF, EGF and IGF-I), on gastric wound repair. METHODS: Isolated rabbit gastric epithelial cells (92% mucous cells) were cultured in F-12 medium and formed a complete monolayer cell sheet in 48 h. A wound with a cell-free area of constant size (2 mm2) was then created and the wound repair process was monitored by measuring wound size every 12 h. Proliferating cells were detected by BrdU staining. Effects of aspirin (8 mM), HGF (10 ng/mL), EGF (10 ng/mL) and IGF-I (30 ng/mL) were assessed. RESULTS: Aspirin significantly retarded wound healing, but simultaneous addition of growth factors significantly accelerated wound repair compared with aspirin alone. Growth factors reversed the aspirin-induced inhibition of cell proliferation. CONCLUSION: Growth factors, including HGF, EGF and IGF-I, reversed the aspirin-induced inhibition of wound repair through their cytoprotective effects on gastric epithelial cells.

Animals↗

Role of Kupffer cells and gut-derived endotoxins in alcoholic liver injury.

The hepatotoxic effects of alcohol have been described in detail, but factors responsible for its hepatotoxicity have only partially been characterized. For example, it is known that chronic ethanol ingestion increases hepatotoxicity and produces fatty liver, hepatitis and cirrhosis. However, acute ethanol consumption reduces endotoxin hepatotoxicity. It now appears that Kupffer cells participate in several aspects of these phenomena. Previously, most studies on the effects of alcohol on liver function have focused chiefly on the hepatocyte. Recently, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut-derived endotoxins (lipopolysaccharides) via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cells and alcohol-induced liver injury. Here we will review new evidence for the proposal that Kupffer cells and endotoxins play a pivotal role in hepatotoxicity following alcohol exposure, based on studies using the continuous intragastric enteral feeding model developed by Tsukamoto and French and an acute model developed by us.

Ethanol↗

Macrophage proliferation in atherosclerosis.

Oxidized LDL can induce an increase in intracellular calcium concentration and the activation of protein kinase C in mouse peritoneal macrophages. The activation of protein kinase C leads to the release into the culture medium of granulocyte-macrophage colony-stimulating factor, which plays a priming role in oxidized LDL-induced macrophage proliferation. The expression of granulocyte-macrophage colony-stimulating factor in macrophages by oxidized LDL is positively regulated in the 5'-flanking region of granulocyte-macrophage colony-stimulating factor gene from sequence -169 to -160, but negatively regulated from -91 to -82. Granulocyte-macrophage colony-stimulating factor released by oxidized LDL from macrophages induces proliferation in autocrine or paracrine fashion via the activation of phosphatidylinositol 3-kinase. The capacity of oxidized LDL to induce macrophage proliferation in vitro may be involved in the enhanced progression of atherosclerosis in vivo.

Animals↗

Topographic mapping of P300 and frontal cognitive function in Parkinson's disease.

The purpose of this study was to evaluate the relationship between P300 that is one of the event-related potentials and frontal cognitive functions in Parkinson's disease (PD) without clinically apparent dementia. Subjects were 20 PD cases 48 to 79 years of age, all of whom were within normal limits on the Mini-Mental State examination, and 55 age-matched healthy adults. P300 was elicited with an auditory oddball paradigm and recorded at 15 sites on the scalp. Cognitive functioning of the frontal lobe was evaluated using the New Modified Wisconsin Card Sorting Test (WCST) and the Letter Pick-Out Test (LPOT) which reflects selective attention and semantic categorization. P300 latency was delayed in 30.0% of P300 demonstrated abnormal distribution in 20.0%. the WCST and the LPOT were abnormal in 15.0%, P300 latency significantly correlated with number of subcategories achieved on the WCST. P300 amplitude correlated with scores on the LPOT. These results suggest that cognitive dysfunction which linked partly to the frontal lobe might begin in PD even without clinically apparent dementia.

Journal Article↗

Cost analysis between stent and conventional balloon angioplasty.

The present study evaluated the cost of coronary stenting compared with conventional balloon angioplasty in Japan. Procedural cost was estimated as the sum of the procedural fee and the cost of devices such as angioplasty balloon and stent. The data such as the number of balloon catheters and stents used, and the rate of crossovers that was shown by the Stent Restenosis Study (STRESS) were applied to calculate the costs of stenting and conventional balloon angioplasty. For the estimation of hospital room and nursing costs, the length of the in-hospital stay was estimated at 7 days. The costs of procedures such as laboratory and radiological tests were determined based on routine coronary intervention at Chiba University Hospital. The rates of target lesion revascularization in the STRESS trial (conventional balloon angioplasty: 21%, stenting: 15%) were used to calculate the cost during follow up. The in-hospital costs of conventional balloon angioplasty and stenting were estimated to be Yens 982,300 and Yens 1,416,893, respectively. The overall costs, including follow-up cost, of conventional balloon angioplasty and stenting were estimated to be Yens 1,188,583 and Yens 1,564,238, respectively. The in-hospital cost of stenting is higher compared with conventional balloon angioplasty because of greater balloon use and direct stent cost. Lower target lesion revascularization reduces the cost difference between conventional balloon angioplasty and stenting, but the higher initial cost of stenting is not fully offset.

Angioplasty, Balloon↗

Transcatheter occlusion of patent ductus arteriosus using a 0.052-inch coil--immediate results.

Coil occlusion of a patent ductus arteriosus (PDA) was attempted with a 0.052-inch Gianturco coil. The patients' ages and body weights at occlusion ranged from 5.8 to 19.7 (12.3+/-5.0, mean+/-SD) years and 18.9-99.1 (44.8+/-23.7) kg, respectively. Three types of 0.052-inch Gianturco coils with loop diameters (mm) and coil lengths (cm) of 6x8 (diameter x length), 8x8, or 8x10 were used. The delivery system was prepared as reported by Hays et al with slight modification. The minimal diameter and the Qp/Qs of the PDA ranged from 2.3 to 4.7 (3.4+/-0.7) mm, and 1.1-1.8 (1.5+/-0.3), respectively. There were 7 cases with type A PDA and 3 with type B, and coils were successfully deployed in all. Complete occlusion in the catheter laboratory was achieved in 4 cases. A minor leak disappeared within 24 h in 3 cases and at 3 months follow-up in 1 case. A tiny leak without a heart murmur persisted in 2 cases at 3 months' follow-up. No procedure-related complications occurred. This technique has significant advantages over previously reported techniques using a 0.038-inch coil for type B, or A PDA with a minimal diameter of 3-4 mm or more.

Adolescent↗

Control of Pythium root rot on hydroponically grown cucumbers with silver-coated cloth.

Silver-coated cloth (SCC) effectively controlled root rot that was caused by Pythium aphanidermatum in hydroponically grown cucumber plants. The presence of SCC in the hydroponic solution reduced the root rot from 100% to 10% 20 days after inoculation with zoospores of P. aphanidermatum. It was suggested that the inhibition of SCC was caused not only by the silver ion dissolved from SCC, but also by the metallic silver and silver compounds formed on the surface of the root.

Cucumis sativus↗