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Biomedical subjects

T Aoki

Publications and source records attributed to T Aoki.

At least 73 records · Page 4Linked to original sources
PubMed2001

Cloning and expression analysis of rainbow trout Oncorhynchus mykiss tumour necrosis factor-alpha.

A rainbow trout (Oncorhynchus mykiss) gene for tumor necrosis factor (TNF) has been cloned and sequenced. The cDNA contains an open reading frame of 738 nucleotides that translate into a 246 amino-acid putative peptide, with a 5' untranslated region (UTR) of 140 bp and a 3' UTR of 506 bp. Two potential N-linked glycosylation sites exist in the translation. The genomic sequence measures 2007 bp and contains three introns that intercept four coding exons. Expression studies using RT-PCR have shown that the trout TNF gene is constitutively expressed in the gill and kidney of unstimulated fish. Trout TNF expression could be up-regulated by stimulation of isolated head kidney leucocytes with lipopolysaccharide (LPS). Similarly, stimulation of a trout macrophage cell line (RTS11) with LPS resulted in an increased transcript level, as did incubation with recombinant trout interleukin (IL)-1 beta. The optimal timing for induction of TNF expression in trout macrophages was determined using recombinant trout IL-1 beta, where a clear induction was apparent by 2 h and peaked at 4 h. Evidence that this TNF gene is equivalent to mammalian TNF-alpha is discussed.

Amino Acid Sequence↗
PubMed2001

A case of inability to belch.

A 22-year-old man was unable to belch. He could sense intraesophageal gas, but had no chest pain. An upper gastrointestinal X-ray series and endoscopic examination showed no abnormalities. Esophageal manometry showed normal relaxation of both the upper and lower esophageal sphincters with primary peristalsis during deglutition. However, bolus injection of air into the middle esophagus failed to initiate the belch reflex.

Adult↗
PubMed2001

Comparative study of self-expandable metallic stent and bypass surgery for inoperable esophageal cancer.

We evaluated the effect of two different therapies for 23 patients with inoperable esophageal cancer, of whom 13 patients underwent placement of a metallic stent and 10 received bypass surgery. We newly defined the improved level of food intake and the effective rate based on the grade of the patient's status in order to evaluate objectively. Although the effect of stent placement was significantly better than that of bypass surgery, there were no significant differences in the improved level of food intake and the effective rate between the two groups. Four out of 10 patients in the bypass group had suture insufficiency, resulting in no oral intake and a fatal outcome. In addition, the ratio of survival period of ability to ingest orally and in-hospital mortality was significantly favorable in the stent group compared with the bypass group. In conclusion, stent placement should be the first choice for inoperable malignant stenosis or esophageal fistula.

Adult↗
PubMed2001

Predictability of internal carotid artery (ICA) dissectability in cases showing ICA involvement in parasellar meningioma.

The present study identified predictors for surgical internal carotid artery (ICA) dissection in cases showing ICA involvement in parasellar meningiomas. Twelve cases encountered over the past 4 years were reviewed. Based on MRI findings, patients were divided into two groups; six patients demonstrated complete ICA involvement (encasement) and the other six showed partial ICA involvement (engulfment). The ICA was dissected in all cases in the engulfment group and in four of six cases in the encasement group. The ICA can be dissected even if it is involved at the centre of the tumour if the tumour is soft and can be aspirated. Preservation of the perforating arteries is more important and more difficult. Angiographic finding showing encasement of a long segment of the ICA is unfavourable because of the high possibility that the perforating arteries are involved. Local stenosis of ICA is another unfavourable finding for surgical dissection because tumour invasion of the arterial wall would be suspected. Thus, ICA encasement by the tumour is the less favourable finding for surgery but it is not a decisive predictor. More important findings for ICA dissection in cases showing ICA encasement are involvement of a long segment of the ICA and local ICA stenosis on angiogram.

Aged↗
PubMed2001

Hypolipidemic effect of NK-104 and other 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in guinea pigs.

Hypolipidemic effects of various HMG-CoA reductase inhibitors (statins) were examined in guinea pigs. After 2-week administration of NK-104 ((+)-monocalcium bis((3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3, 5-dihydroxy-6-heptenoate), CAS 147526-32-7), simvastatin (SV), pravastatin (PV), fluvastatin (FV), cerivastatin (CV) and atorvastatin (AV) to guinea pigs at various doses, which did not affect body weight, plasma and liver lipids were measured. Liver endoplasmic reticulum (ER) was isolated and measured for lipid content and activity of ER enzymes (NK-104: 3 mg/kg, SV: 30 mg/kg). Each statin except CV dose-dependently lowered total cholesterol (TC), with NK-104 showing the greatest effect. Only NK-104 and AV, long-acting statins, significantly lowered triglycerides (TG). A significant reduction of the liver cholesterol content was observed for NK-104 and AV. The liver TG content increased with dose for SV or PV, but not for NK-104 or AV. The TG content in ER and activity of diacylglycerol acyltransferase of ER, increased with SV and slightly with NK-104. Activity of microsomal triglyceride transfer protein, which is necessary for both apoB particle formation at rough ER and TG droplet production at smooth ER, increased by SV but not by NK-104. It is suggested that statins with prolonged action lower TG by decreasing cholesterol ester supply necessary for very low density lipoprotein formation and by attenuating an increase in TG production at ER after HMG-CoA reductase inhibition.

Acyltransferases↗
PubMed2001

Cholesterol-lowering effect of NK-104, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in guinea pig model of hyperlipidemia.

Although benefits of statins have been demonstrated even in normolipidemic patients at high risk, the main target of statin therapy is the hypercholesterolemic patient. The aim of this study was to examine the hypocholesterolemic effect of NK-104 ((+)-monocalcium bis((3R,5S,6S)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]- 3,5-dihydroxy-6-heptenoate), CAS 147526-32-7), a potent 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, and its mechanism of action in hypercholesterolemic animals. In guinea pigs fed a diet containing 15% (w/w) fat rich in laurate for 6 weeks, the liver cholesterol content was markedly increased and plasma total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and LDL-apoB were elevated 4.8, 5.2 and 1.7 times, respectively, compared with normal diet fed animals. These changes were maintained by reduced LDL clearance in the presence of markedly cholesterol-enriched LDL in the plasma. In this model, the LDL-C reduction rates by 0.1, 0.3 and 1 mg/kg of NK-104 orally administered for 2 weeks (from week 4 to week 6), were 11, 27 and 32%, respectively, from controls, being similar in normal guinea pigs previously examined. Those for 3 and 10 mg/kg of atorvastatin (CAS 134523-00-5) were 25 and 39%, respectively. Thus about 10 times higher doses of atorvastatin were required than of NK-104 to cause a similar cholesterol-lowering effect. This reduction of plasma cholesterol was accompanied by an improvement of LDL clearance (24 and 47% increase in fractional catabolic rate by 1 mg/kg of NK-104 and 10 mg/kg of atorvastatin, respectively) and LDL composition. In conclusion, in guinea pig hypercholesterolemia caused by high-laurate diet, NK-104 and atorvastatin lowered plasma cholesterol levels with an improvement of LDL composition and with an increase in LDL clearance, presumably through reduction of the liver cholesterol content, although hepatic cholesterol synthesis might have been markedly suppressed in this model.

Animals↗
PubMed2001

Protective effects of fluvastatin against reactive oxygen species induced DNA damage and mutagenesis.

Oxidative stress may be an important factor in the development of diabetic complications. Advanced glycation end-products have drown attention as potential sources of oxidative stress in diabetes. We investigated the protective effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on oxidative DNA damage from reactive oxygen species or advanced glycation end-products in vitro, as well as effects of main fluvastatin metabolites and other inhibitors of the same enzyme, pravastatin and simvastatin. Protective effects were assessed in terms of the DNA breakage rate in a single-stranded phage DNA system in vitro. DNA was exposed to either reactive oxygen species or advanced glycation end-products. Fluvastatin and its metabolites showed a strong protective effect comparable to those seen with thiourea and mannitol, though pravastatin and simvastatin did not exert clear protective effects. Furthermore, fluvastatin reduced the mutagenesis by reactive oxygen species or advanced glycation end-products in Salmonella typhimurium test strains. Both pravastatin and simvastatin still lacked protective activity. Fluvastatin and its metabolites protect against oxidative DNA damage and may reduce risk of consequent diabetic complications.

Bacteriophages↗
PubMed2001

Antioxidative effects of fluvastatin and its metabolites against oxidative DNA damage in mammalian cultured cells.

We investigated the effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on reactive oxygen species (ROS) and on oxidative DNA damage in vitro, as well as the effects of the main fluvastatin metabolites (M2, M3, and M4) and other inhibitors of the same enzyme, pravastatin and simvastatin. The hydroxyl radical and the superoxide anion scavenging activities of fluvastatin and its metabolites were evaluated using an electron spin resonance spectrometer. Fluvastatin and its metabolites showed superoxide anion scavenging activity in the hypoxanthine-xanthine oxidase system and a strong scavenging effect on the hydroxyl radical produced from Fenton's reaction. Protective effects of fluvastatin on ROS-induced DNA damage of CHL/IU cells were assessed using the single-cell gel electrophoresis assay. CHL/IU cells were exposed to either hydrogen peroxide or t-butylhydroperoxide. Fluvastatin and its metabolites showed protective effects on DNA damage as potent as the reference antioxidants, ascorbic acid, trolox, and probucol, though pravastatin and simvastatin did not exert clear protective effects. These observations suggest that fluvastatin and its metabolites may have radical scavenging activity and the potential to protect cells against oxidative DNA damage. Furthermore, ROS are thought to play a major role in the etiology of a wide variety of diseases such as cellular aging, inflammation, diabetes, and cancer development, so fluvastatin might reduce these risks.

Animals↗
PubMed2001

Is preventive resection of the extrahepatic bile duct necessary in cases of pancreaticobiliary maljunction without dilatation of the bile duct?

BACKGROUND: No consensus has been reached on whether preventive resection of the extrahepatic bile duct is necessary in cases of pancreaticobiliary maljunction (PBM) without dilatation of the extrahepatic bile duct (undilated type). METHODS: Sixty-eight patients with PBM underwent corrective surgery and several clinical characteristics and pathological findings including K-ras point mutation were evaluated. RESULTS: Unlike dilated bile duct, none of the patients with undilated type duct had clinical symptoms in early childhood. In patients with either cystic or spindle type duct, amylase levels in the bile duct were >10(4) U/l, whereas those in patients with undilated type duct were <10(4) U/l. Postoperative scintigraphy of the biliary system of undilated type revealed no evidence of cholestasis. After surgery, eight patients with undilated type duct, in whom the bile duct had been preserved, had no further clinical symptoms and no evidence of malignancy. Bile duct tissue specimens revealed no hyperplasia, dysplasia or cancerous lesions and they had no K-ras mutation in undilated type. CONCLUSION: The results showed that there was little bile stasis, injury to the mucosa was mild and less genetic changes could be seen in patients with undilated type duct. Therefore, in patients without dilatation of bile duct and advanced cancer, cholecystectomy alone is sufficient.

Adult↗
PubMed2001

Chalcone isomerase isozymes with different substrate specificities towards 6'-hydroxy- and 6'-deoxychalcones in cultured cells of Glycyrrhiza echinata, a leguminous plant producing 5-deoxyflavonoids.

Three chalcone isomerase isozymes in Glycyrrhiza echinata (Fabaceae) were separated by chromatofocusing and partially purified to examine their substrate specificities. Two isozymes, one of which was elicitor-inducible, acted on both 6'-hydroxychalcone and 6'-deoxychalcone and presumably are involved in the legume-specific 5-deoxyflavonoid pathway, while another acted on only 6'-hydroxychalcone.

Cells, Cultured↗
PubMed2001

Hyaluronan serves a novel role in airway mucosal host defense.

Enzymes secreted onto epithelial surfaces play a vital role in innate mucosal defense, but are believed to be steadily removed from the surface by mechanical actions. Thus, the amount and availability of enzymes on the surface are thought to be maintained by secretion. In contrast to this paradigm, we show here that enzymes are retained at the apical surface of the airway epithelium by binding to surface-associated hyaluronan, providing an apical enzyme pool 'ready for use' and protected from ciliary clearance. We have studied lactoperoxidase, which prevents bacterial colonization of the airway, and kallikrein, which mediates allergic bronchoconstriction that limits the inhalation of noxious substances. Binding to hyaluronan inhibits kallikrein, which is needed only in certain situations, whereas lactoperoxidase, useful at all times, does not change its activity. Hyaluronan itself interacts withthe receptor for hyaluronic acid-mediated motility (RHAMM or CD168) that is expressed at the apex of ciliated airway epithelial cells. Functionally, hyaluronan binding to RHAMM stimulates ciliary beating. Thus, hyaluronan plays a previously unrecognized pivotal role in mucosal host defense by stimulating ciliary clearance of foreign material while simultaneously retaining enzymes important for homeostasis at the apical surface so that they cannot be removed by ciliary action.

Albumins↗
PubMed2001

Role of cytokines in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty.

BACKGROUND: Inflammatory cytokines play an important role in mediating inflammatory/proliferative responses including atherosclerosis. However, their role in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty (PTCA) remains to be clarified. OBJECTIVE: To determine plasma levels of inflammatory cytokines as well as cytokine-generation capacities of monocytes before PTCA and after the follow-up period. METHODS: Plasma levels of cytokines in 34 consecutive patients before and 3-6 months after PTCA were measured by enzyme-linked immunosorbent assay. We measured the plasma levels of macrophage-colony-stimulating factor (MCSF) and transforming growth factor-beta. Cytokine-generation capacities of monocytes were also measured by a whole-blood induction method with lipopolysaccharide. The levels of cytokines measured for assessment of the capacities included those of interleukin-1alpha, interleukin-1beta, interleukin-6, granulocyte-colony-stimulating factor, tumor necrosis factor-alpha and interferon-gamma. RESULTS: Plasma levels of MCSF in patients without restenosis (n = 20) decreased significantly (from 1460+/-138 microg/ml before PTCA to 1039+/-125 microg/ml after the follow-up period, P < 0.01), whereas those in patients with restenosis (n = 14) increased significantly (from 1107+/-105 microg/ml before PTCA to 1039+/-125 microg/ml after the follow-up period, P < 0.05). We noted a positive correlation between the increase in plasma levels of MCSF and the extent of loss of lumen by restenosis. Cytokine-generation capacities of monocytes for interleukin-1alpha and interleukin-1beta of patients with restenosis significantly increased but those of patients without restenosis did not. Furthermore, plasma levels of C-reactive protein decreased significantly only in patients without restenosis after the follow-up period. CONCLUSIONS: These results suggest that inflammatory changes mediated by cytokines may be involved in the pathogenesis of restenosis after PTCA.

Aged↗
PubMed2001

Measles viruses on throat swabs from measles patients use signaling lymphocytic activation molecule (CDw150) but not CD46 as a cellular receptor.

Both CD46 and signaling lymphocytic activation molecule (SLAM) have been shown to act as cellular receptors for measles virus (MV). The viruses on throat swabs from nine patients with measles in Japan were titrated on Vero cells stably expressing human SLAM. Samples from all but two patients produced numerous plaques on SLAM-expressing Vero cells, whereas none produced any plaques on Vero cells endogenously expressing CD46. The Edmonston strain of MV, which can use either CD46 or SLAM as a receptor, produced comparable titers on these two types of cells. The results strongly suggest that the viruses in the bodies of measles patients use SLAM but probably not CD46 as a cellular receptor.

Animals↗
PubMed2001

Peripheral lung adenocarcinoma: correlation of thin-section CT findings with histologic prognostic factors and survival.

PURPOSE: To evaluate the prognostic importance of thin-section computed tomographic (CT) findings of peripheral lung adenocarcinomas. MATERIALS AND METHODS: The subjects were 127 patients with adenocarcinomas smaller than 3 cm in largest diameter who underwent at least a lobectomy with hilar and mediastinal lymphadenectomy. The margin characteristics of nodules and the extent of ground-glass opacity (GGO) within the nodules at preoperative thin-section CT were analyzed retrospectively. Regional lymph node metastasis (LNM) and vessel invasion (VI) were histologically examined in surgical specimens. Survival curves were calculated according to the Kaplan-Meier method. RESULTS: The frequencies of LNM (4% [1 of 24]) and VI (13% [three of 24]) in adenocarcinomas with GGO components of more than 50% were significantly lower than those with GGO components of less than 10% (LNM, P <.05; VI, P <.01). The patients with GGO components of more than 50% showed a significantly better prognosis than those with GGO components less than 50% (P <.05). All 17 adenocarcinomas smaller than 2 cm with GGO components of more than 50% were free of LNM and VI, and all these patients are alive without recurrence. Coarse spiculation and thickening of bronchovascular bundles around the tumors were observed more frequently in tumors with LNM or VI than in those without LNM or VI (P <.01). CONCLUSION: Thin-section CT findings of peripheral lung adenocarcinomas correlate well with histologic prognostic factors.

Adenocarcinoma↗
PubMed2001

Effects of hypercapnia and hypocapnia on [Ca2+]i mobilization in human pulmonary artery endothelial cells.

The hydrogen ion is an important factor in the alteration of vascular tone in pulmonary circulation. Endothelial cells modulate vascular tone by producing vasoactive substances such as prostacyclin (PGI2) through a process depending on intracellular Ca2+ concentration ([Ca2+]i). We studied the influence of CO2-related pH changes on [Ca2+]i and PGI2 production in human pulmonary artery endothelial cells (HPAECs). Hypercapnic acidosis appreciably increased [Ca2+]i from 112 +/- 24 to 157 +/- 38 nmol/l. Intracellular acidification at a normal extracellular pH increased [Ca2+]i comparable to that observed during hypercapnic acidosis. The hypercapnia-induced increase in [Ca2+]i was unchanged by the removal of Ca2+ from the extracellular medium or by the depletion of thapsigargin-sensitive intracellular Ca2+ stores. Hypercapnic acidosis may thus release Ca2+ from pH-sensitive but thapsigargin-insensitive intracellular Ca2+ stores. Hypocapnic alkalosis caused a fivefold increase in [Ca2+]i compared with hypercapnic acidosis. Intracellular alkalinization at a normal extracellular pH did not affect [Ca2+]i. The hypocapnia-evoked increase in [Ca2+]i was decreased from 242 +/- 56 to 50 +/- 32 nmol/l by the removal of extracellular Ca2+. The main mechanism affecting the hypocapnia-dependent [Ca2+]i increase was thought to be the augmented influx of extracellular Ca2+ mediated by extracellular alkalosis. Hypercapnic acidosis caused little change in PGI2 production, but hypocapnic alkalosis increased it markedly. In conclusion, both hypercapnic acidosis and hypocapnic alkalosis increase [Ca2+]i in HPAECs, but the mechanisms and pathophysiological significance of these increases may differ qualitatively.

Acidosis, Respiratory↗
PubMed2001

Dye-staining stereomicroscopic examinations for fine mucosal structures of the gallbladder.

BACKGROUND: In order to diagnose an unsuspected gallbladder carcinoma and to examine whether a differential diagnosis could be made between cancer and noncancerous lesions during surgery, we evaluated the findings of fine structures of various types of gallbladder mucosa. METHODS: We used stereomicroscopy with a dye-contrast technique under water and measured the maximum blood vessel diameters of the gallbladder mucosa: normal gallbladder, chronic cholecystitis, and carcinoma. RESULTS: All normal gallbladders showed fine-reticular-type findings. In chronic cholecystitis, 5.8% of the specimens (n = 69) had fine reticular type, 87.0% had rough reticular type, and 7.2% had atrophic type. All the cases of adenomyomatosis (n = 16) showed rough reticular type. In eight specimens of pancreaticobiliary maljunction, 75% of them showed high reticular type, and the other 25% showed papillary type. The two adenoma specimens showed fine granular type. In five gallbladder carcinomas, the lattice-like pattern completely disappeared and showed rough granular type. The average of maximum vessel diameters in the gallbladder mucosa were 41.0 microm in normal gallbladders, 99.1 microm in patients with chronic cholecystitis, and 614.8 microm in patients with a carcinoma. There were significant differences among them (p < 0.05). CONCLUSION: This study showed that differential diagnosis between cancer and noncancerous lesion is possible by dye-staining mucosal pattern and measurement of maximum vessel diameters by stereoscopic examination.

Adenoma↗