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Biomedical subjects

H Narita

Publications and source records attributed to H Narita.

At least 19 recordsLinked to original sources

Toxicity assessment of treated wastewater using cultured human cell lines.

Bioassay using cultured human cell lines was applied to an effluent of a wastewater treatment plant (WWTP) in Sapporo to assess their toxicity, and in order to investigate the fate of toxicity in the WWTP, bioassay of the water samples from several points in WWTP (influent, effluent, return flow from thickener, from dewatering process and from incineration process) was performed. We also applied bioassay to the mixture of the activated sludge from the investigated plant and artificial sewage. These results showed that the toxicity of the effluent was more intensive than the influent, and organic matter released from activated sludge bacteria during their decay process contributed to the increase of toxicity in the effluent.

Biological Assay↗

Finasteride 1 mg has no inhibitory effect on omeprazole metabolism in extensive and poor metabolizers for CYP2C19 in Japanese.

OBJECTIVE: To examine the inhibitory effect of finasteride 1 mg on the metabolism of omeprazole in genetically determined extensive (EMs) and poor metabolizers (PMs) for CYP2C19 in young healthy Japanese male subjects. METHODS: Twenty-four volunteers participated in this study, among whom 12 were homozygous EMs and 12 were PMs for CYP2C19. A single center, controlled, randomized, open, crossover study with a 5 day washout between the two study periods was performed. Each of the six EMs and PMs received a single oral 20 mg dose of omeprazole on day 1 (treatment I). After a 5 day washout period, these subjects received 1 mg of finasteride once a day for three consecutive days, and a single oral 20 mg dose of omeprazole was co-administered on day 3 (treatment II). The 12 other EMs and PMs received treatments I and II in reverse. Plasma samples were collected for up to a 12 hours postdose of omeprazole, and the pharmacokinetic parameters of omeprazole were determined. RESULTS: The geometric mean ratio (GMR) for the AUC((0-12 hr)) of omeprazole when co-administered with finasteride/omeprazole alone is 1.13 (90%CI, 1.03, 1.25) and 0.96 (0.88, 1.05) in EMs and PMs, respectively. Finasteride did not significantly alter C(max), T(max) and t(1/2) in both genotypes. CONCLUSION: Finasteride 1 mg, widely used for the treatment of androgenetic alopecia in men, did not meaningfully increase omeprazole exposure (20 mg) in both EMs and PMs for CYP2C19. These results indicate that finasteride does not meaningfully inhibit CYP2C19 activity in vivo at the dose of 1 mg.

Adult↗

Organic matter released from activated sludge bacteria cells during their decay process.

Organic matter released from activated sludge bacteria is a considerable issue in the wastewater reclamation process. In this study, we focused 2-keto-3-deoxyoctulosonic acid in the Lipopolysaccharide existed in the gram-negative bacterial cell wall as an index of organic matter released from bacteria, and investigated the fate of 2-keto-3-deoxyoctulosonic acid in the aerated and ultrasonicated activated sludge samples. The results shows 1) 2-keto-3-deoxyoctulosonic acid concentration in the hydrolyzed sample was higher than non-hydrolyzed sample, and this implied that 2-keto-3-deoxyoctulosonic acid existed in the water phase as a monomer and also as a polymer such as Lipopolysaccharide form and their fragments; 2) the value of (2-keto-3-deoxyoctulosonic acid)/(dissolved organic carbon) ratio did not change in the sludge sonication process and was approximately 0.0006, on the other hand, in the bacteria decay process, the ratio varied from zero to approximately 0.0012; 3) the linear relationship was observed between the degraded heterotrophic biomass and the generated 2-keto-3-deoxyoctulosonic acid; and 4) 2-keto-3-deoxyoctulosonic acid might be considered as an index of organic matter originated from activated sludge bacteria cell.

Gram-Negative Bacteria↗

Role of hydrophilic organic matter on developing toxicity in decay process of activated sludge.

It is known that the toxicity of effluent is more intensive than that of influent in the activated sludge process. In this study, we applied bioassay using cultured human cell lines to the decay process of activated sludge to evaluate the toxicity of organic matter generated and/or released from activated sludge bacteria. We also applied this bioassay to hydrophilic fraction of samples. The bioassay results showed that: (1) the variation in the dose-response relation obtained from assay with original samples was observed during decay; (2) on the other hand, the response curves of only hydrophilic fraction at each time show the same relationship between TOC and viability of MCF7 cells; (3) this trend was confirmed by plotting the time course of EC50. These results imply that: (1) the hydrophilic organic matter controlled for developing toxicity during decay process of activated sludge; and (2) the character of hydrophilic organic matter is not changed during the experimental period.

Anion Exchange Resins↗

High-resolution record of Northern Hemisphere climate extending into the last interglacial period.

Two deep ice cores from central Greenland, drilled in the 1990s, have played a key role in climate reconstructions of the Northern Hemisphere, but the oldest sections of the cores were disturbed in chronology owing to ice folding near the bedrock. Here we present an undisturbed climate record from a North Greenland ice core, which extends back to 123,000 years before the present, within the last interglacial period. The oxygen isotopes in the ice imply that climate was stable during the last interglacial period, with temperatures 5 degrees C warmer than today. We find unexpectedly large temperature differences between our new record from northern Greenland and the undisturbed sections of the cores from central Greenland, suggesting that the extent of ice in the Northern Hemisphere modulated the latitudinal temperature gradients in Greenland. This record shows a slow decline in temperatures that marked the initiation of the last glacial period. Our record reveals a hitherto unrecognized warm period initiated by an abrupt climate warming about 115,000 years ago, before glacial conditions were fully developed. This event does not appear to have an immediate Antarctic counterpart, suggesting that the climate see-saw between the hemispheres (which dominated the last glacial period) was not operating at this time.

Journal Article↗

Striking effect of left ventricular high filling pressure with mitral regurgitation on mitral annular velocity during early diastole. A study using colour M-mode tissue Doppler imaging.

AIMS: To evaluate the effect of considerably high left ventricular filling pressure with mitral regurgitation on mitral annular velocity during early diastole. SUBJECTS: Two hundred and forty-three patients who underwent cardiac catheterization for evaluation of chest pain. METHODS: Mitral annular velocity during early diastole was measured by colour M-mode tissue Doppler imaging. Patients were divided into the following three groups according to the cardiac catheterization data. Group A (n=147): patients having left ventricular relaxation time constant tau<46 ms and left ventricular end-systolic volume index <38 ml m(-2); group B (n=88): patients having tau>or=46 ms and/or end-systolic volume index >or=38 ml m(-2); group C (n=8): patients having mean pulmonary capillary wedge pressure >or=16 mmHg in addition to tau>or=46 ms and end-systolic volume index >or=38 ml m(-2). RESULTS: Mitral annular velocity during early diastole was significantly less in group B (4.8+/-1.4 cm s(-1)) than in group A (7.7+/-1.9 cm s(-1)). However, there was no significant difference between groups A and C (8.3+/-0.8 cm s(-1)). A transmitral E/A >1.0 was observed in 12/147 patients of group A, 10/88 of group B, and 8/8 of group C. The incidence of >or=Sellers' grade II mitral regurgitation was higher in group C than the others. CONCLUSIONS: A paradoxically faster mitral annular velocity during early diastole is found in patients having left ventricular dysfunction with moderate to severe mitral regurgitation and considerably high left ventricular filling pressure. Attention should be paid to an interpretation of mitral annular velocity during early diastole regarding left ventricular early diastolic performance in patients having mitral regurgitation with an E/A >1.0 in their transmitral flow.

Blood Flow Velocity↗

In vitro and in vivo activities of anti-influenza virus compound T-705.

T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has been found to have potent and selective inhibitory activity against influenza virus. In an in vitro plaque reduction assay, T-705 showed potent inhibitory activity against influenza A, B, and C viruses, with 50% inhibitory concentrations (IC(50)s) of 0.013 to 0.48 microg/ml, while it showed no cytotoxicity at concentrations up to 1,000 microg/ml in Madin-Darby canine kidney cells. The selectivity index for influenza virus was more than 2,000. It was also active against a neuraminidase inhibitor-resistant virus and some amantadine-resistant viruses. T-705 showed weak activity against non-influenza virus RNA viruses, with the IC(50)s being higher for non-influenza virus RNA viruses than for influenza virus, and it had no activity against DNA viruses. Orally administered T-705 at 100 mg/kg of body weight/day (four times a day) for 5 days significantly reduced the mean pulmonary virus yields and the rate of mortality in mice infected with influenza virus A/PR/8/34 (3 x 10(2) PFU). These results suggest that T-705 may be a compound that is useful and highly selective against influenza virus infections and that has a mode of action different from those of commercially available drugs, such as amantadine, rimantadine, and neuraminidase inhibitors.

Amides↗

A Drosophila haemocyte-specific protein, hemolectin, similar to human von Willebrand factor.

We identified a novel Drosophila protein of approximately 400 kDa, hemolectin (d-Hml), secreted from haemocyte-derived Kc167 cells. Its 11.7 kbp cDNA contains an open reading frame of 3843 amino acid residues, with conserved domains in von Willebrand factor (VWF), coagulation factor V/VIII and complement factors. The d-hml gene is located on the third chromosome (position 70C1-5) and consists of 26 exons. The major part of d-Hml consists of well-known motifs with the organization: CP1-EG1-CP2-EG2-CP3-VD1-VD2-VD'-VD3-VC1-VD"-VD"'-FC1-FC2-VC2-LA1-VD4-VD5-VC3-VB1-VB2-VC4-VC5-CK1 (CP, complement-control protein domain; EG, epidermal-growth-factor-like domain; VB, VC, VD, VWF type B-, C- and D-like domains; VD', VD", VD"', truncated C-terminal VDs; FC, coagulation factor V/VIII type C domain; LA, low-density-lipoprotein-receptor class A domain; CK, cysteine knot domain). The organization of VD1-VD2-VD'-VD3, essential for VWF to be processed by furin, to bind to coagulation factor VIII and to form interchain disulphide linkages, is conserved. The 400 kDa form of d-Hml was sensitive to acidic cleavage near the boundary between VD2 and VD', where the cleavage site of pro-VWF is located. Agarose-gel electrophoresis of metabolically radiolabelled d-Hml suggested that it is secreted from Kc167 cells mainly as dimers. Resembling VWF, 7.9% (305 residues) of cysteine residues on the d-Hml sequence had well-conserved positions in each motif. Coinciding with the development of phagocytic haemocytes, d-hml transcript was detected in late embryos and larvae. Its low-level expression in adult flies was induced by injury at any position on the body.

Amino Acid Sequence↗

Structural studies of lanthanide (III) complexes with oxydiacetic acid and iminodiacetic acid in aqueous solution by EXAFS.

The local structure of the trivalent lanthanide (Ln(III)) complexes with oxydiacetic acid (ODA) and iminodiacetic acid (IDA) in aqueous solution was investigated by EXAFS spectroscopy. The coordination number and the bond distance were obtained by the detailed EXAFS analysis. The coordination number of Ln(III) in both the Ln-ODA and -IDA systems decreases from nine for lighter Ln(III) to eight for heavier Ln(III). The bond distances of ether O atoms from Ln(III) in the Ln(ODA)(3)3- complexes are shorter than those of N atoms in the Ln(IDA)(3)3- ones.

Journal Article↗

Primary malignant fibrous histiocytoma of the ileum: report of a case.

We report herein a case of primary malignant fibrous histiocytoma (MFH) of the ileum. A 71-year-old Japanese man was admitted to our hospital with symptoms of abdominal pain and anorexia. Computed tomography, magnetic resonance imaging, a follow-through study of the small intestine, and angiography all demonstrated a tumor of the ileum suggestive of a primary malignancy. A partial resection of the ileum was performed. It was histopathologically and immunohistochemically diagnosed to be a storiform-type primary MFH of the ileum with peritoneal dissemination. There have been a total of 25 cases of primary small bowel MFH documented in the Japanese or Western literature including our case. The malignant potential of such tumors is high, and the prognosis tends to be very poor. Unfortunately, we could not conclude whether the poor outcome was due to a delayed diagnosis or instead to its biological malignant behavior, since the number of such reported cases is still too small to make any definitive conclusions.

Aged↗

Hemodynamic and sympathetic effects of fenoldopam and sodium nitroprusside.

BACKGROUND: Fenoldopam is a novel dopamine-1 receptor selective agonist that can be used as a vasodilator perioperatively to treat hypertension and to produce induced hypotension. We were interested to find out whether there were any differences between fenoldopam (FM) and sodium nitroprusside (SNP), one of the most popular vasodilators, in their effects on hemodynamics and sympathetic outflow using not only neuraxis intact but also baro-denervated animal models. METHODS: A total of 60 New Zealand white rabbits were divided into two groups of 30 each: the neuraxis-intact group and the totally baro-denervated group. Each group was further divided into three groups of 10 each to receive SNP 10 microg x kg(-1), FM 10 microg x kg(-1) or FM 20 microg x kg(-1), respectively. Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded before and after intravenous (i.v.) administration of each agent. In addition, cardiac and sympathetic baroreflex sensitivity were assessed in the neuraxis-intact animals. RESULTS: In the neuraxis-intact groups, although RSNA was increased to a similar extent in all three groups (P<0.01), the reduction of MAP with FM groups was significantly greater than with SNP (P<0.05). HR was increased only in the SNP group. Cardiac (HR) and sympathetic barosensitivity were significantly attenuated with FM 20 microg x kg(-1) as compared to the SNP group. In the baro-denervated groups, there were significant and similar degrees of reduction of MAP in all three group up to 1 min (P<0.01). MAP remained significantly decreased in the FM groups for 10 min (only 2 min with SNP) in both animal models. CONCLUSIONS: Unlike sodium nitroprusside, fenoldopam attenuates both cardiac (heart rate) and sympathetic baroreflex sensitivity, which may explain the lack of rebound hypertension with fenoldopam. The offset of hypotensive effects of fenoldopam is a significantly slower process as compared to nitroprusside, and this may be an unfavorable feature of fenoldopam should overshoot of hypotension occur.

Animals↗

Striking effect of left ventricular systolic performance on propagation velocity of left ventricular early diastolic filling flow.

Propagation velocity of left ventricular (LV) early diastolic filling flow (PVE) has been acknowledged as a useful parameter for LV early diastolic performance; however, the effect of LV systolic performance on PVE is not fully understood. Thus the purpose of this study was to investigate such an effect. Propagation of LV early diastolic filling flow was visualized by M-mode color Doppler imaging, and the slopes of the peak velocity tracings were measured as PVE in 150 patients who underwent coronary angiography. In cardiac catheterization, mean pulmonary capillary wedge pressure, time constant tau of LV pressure decay, LV end-systolic volume index, and LV ejection fraction were obtained. In univariate regression analysis, PVE significantly correlated with LV end-systolic volume index (r = -0.68, P <.001), LV ejection fraction (r = 0.66, P <.001), and time constant tau (r = -0.52, P <.001). In multivariate regression analysis, PVE was regressed by the LV end-systolic volume index, tau, and mean pulmonary capillary wedge pressure. The contribution of each parameter to the variance of the PVE was 46%, 3%, and 2%, respectively. A break-point linear regression analysis showed that the relation between the LV end-systolic volume index and PVE was much better characterized by a broken line than a straight line. The broken line had a steeper slope in patients with LV end-systolic volume index < or =41 mL/m(2) than in those with >41 mL/m(2). These findings suggest that PVE is determined mainly by LV systolic performance and partly by both LV relaxation and LV filling pressure. Left ventricular systolic performance may play a key role in generating a much faster PVE, especially in patients with relatively better LV systolic performance.

Aged↗

Fluvastatin depresses the enhanced lipid peroxidation in vitamin E-deficient hamsters.

Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has recently been reported to have the antioxidative activity in vitro. However, it is still unclear whether chronic treatment with this drug actually leads to amelioration of the redox status in the body. In this study, we investigated the antioxidative effect of fluvastatin in vivo, using a vitamin E-deficient hamster model, an in vivo model of enhanced oxidative stress. After pre-treatment with a vitamin E-deficient diet for 2 months, fluvastatin, pravastatin or probucol was added to the diet for 1 month. Vitamin E deficiency caused a significant increase in the levels of plasma oxidative stress markers such as 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) and hydroperoxides. Furthermore, there was a significant increase in the oxidizability of plasma lipids in the vitamin E-deficient animals, indicating that the oxidative stress was increased in the circulation. Fluvastatin markedly depressed the above oxidative stress markers in plasma, and significantly decreased the oxidizability of plasma lipids without affecting their levels. Probucol, a reference antioxidant, also showed a similar effect while pravastatin, another HMG-CoA reductase inhibitor, showed only a weak improvement. We suggest that the treatment with fluvastatin leads to a reduction of oxidative stress in vivo, which is mainly derived from its antioxidative property rather than its lipid-lowering activity.

Animals↗

In vitro and in vivo efficacies of T-3811ME (BMS-284756) against Mycoplasma pneumoniae.

T-3811, the free base of T-3811ME (BMS-284756), a new des-F(6)-quinolone, showed a potent in vitro activity (MIC at which 90% of the isolates tested are inhibited [MIC(90)], 0.0313 microg/ml) against Mycoplasma pneumoniae. The MIC(90) of T-3811 was 4-fold higher than that of clarithromycin but was 4- to 8-fold lower than those of trovafloxacin, gatifloxacin, gemifloxacin, and moxifloxacin and was 16- to 32-fold lower than those of levofloxacin, ciprofloxacin, and minocycline. In an experimental M. pneumoniae pneumonia model in hamsters, after the administration of T-3811ME (20 mg/kg of body weight as T-3811, once daily, orally) for 5 days, the reduction of viable cells of M. pneumoniae in bronchoalveolar lavage fluid was greater than those of trovafloxacin, levofloxacin, and clarithromycin (20 and 40 mg/kg, orally) (P < 0.05).

Animals↗

Regression by ACE inhibition of arteriosclerotic changes induced by chronic blockade of NO synthesis in rats.

We previously reported that chronic inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME) induces vascular inflammation at week 1 and produces subsequent arteriosclerosis at week 4 and that cotreatment with an angiotensin-converting enzyme (ACE) inhibitor prevents such changes. In the present study, we tested the hypothesis that treatment with an ACE inhibitor after development of vascular inflammation could inhibit arteriosclerosis in rats. Wistar-Kyoto rats were randomized to four groups: the control group received no drugs, the 4wL-NAME group received L-NAME (100 mg x kg(-1) x day(-1)) for 4 wk, the 1wL + 3wNT group received L-NAME for 1 wk and no treatment for the subsequent 3 wk, and the 1wL + 3wACEI group received L-NAME for 1 wk and the ACE inhibitor imidapril (20 mg x kg(-1) x day(-1)) for the subsequent 3 wk. After 4 wk, we observed significant arteriosclerosis of the coronary artery (medial thickening and fibrosis) and increased cardiac ACE activity in the 1wL + 3wNT group as well as in the 4wL-NAME group, but not in the 1wL + 3wACEI group. In a separate study, we examined apoptosis formation and found that posttreatment with imidapril (20 mg x kg(-1) x day(-1)) or an ANG II AT1-receptor antagonist, CS-866 (5 mg x kg(-1) x day(-1)), induced apoptosis (TdT-mediated nick end-labeling) in monocytes and myofibroblasts appearing in the inflammatory lesions associated with a clear degradation in the heart (DNA electrophoresis). In conclusion, treatment with the ACE inhibitor after 1 wk of L-NAME administration inhibited arteriosclerosis by inducing apoptosis in the cells with inflammatory lesions in this study, suggesting that increased ANG II activity inhibited apoptosis of the cells with inflammatory lesions and thus contributed to the development of arteriosclerosis.

Angiotensin-Converting Enzyme Inhibitors↗

Fluvastatin inhibits O2- and ICAM-1 levels in a rat model with aortic remodeling induced by pressure overload.

Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression is suggested to play an important role in the pathogenesis of vascular remodeling. The aim of the present study was to investigate the effects of the 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitor fluvastatin on superoxide anion (O2-) production and ICAM-1 expression in a rat model with vascular remodeling induced by pressure overload. Two weeks after aortic banding, marked increases in O2- production and ICAM-1 protein levels were observed in the aorta. O2- formation and ICAM-1 immunoreactivity were mainly increased in the endothelium and adventitia of the aorta in banded rats. Oral administration of fluvastatin prevented both these changes and the development of perivascular fibrosis and increased the expression of endothelial nitric oxide synthase. Cholesterol and lipid peroxide levels in serum did not change in the banded rats. Thus the beneficial effects of fluvastatin seen in this study as well as its cholesterol-lowering effect may contribute to attenuate the atherosclerotic process.

Animals↗

Characteristics of acoustic noise in echo-planar imaging.

Characteristics of the acoustic noise generated by magnetic resonance imagers of different systems and performance levels were studied when operating in echo-planar imaging (EPI) sequence. Continuous equivalent A-weighted sound pressure levels (Leq) and peak impulse sound pressure levels (Lpeak) during EPI were measured in 12 clinical super-conducting MRI systems (0.5-1.5 T). Sound pressure levels and frequency spectra of EPI were compared with those of nine different pulse sequences. EPI sound pressure levels differed among institutions (Leq = 94.2 +/- 2.7 dBA. Lpeak = 109.1 +/- 3.5 dB), but these were within permissible noise exposure levels. Sound pressure levels during EPI were not significantly different from those during other pulse sequences. However, compared to other pulse sequences. EPI had a significantly greater proportion of acoustic noise in the high octave-frequency band. Single-shot EPI had relatively higher frequency noise and greater Leq than multishot EPI, but the difference in Leq decreased when the number of slices in multishot EPI was increased.

Echo-Planar Imaging↗

Effects of fluvastatin and its major metabolites on low-density lipoprotein oxidation and cholesterol esterification in macrophages.

We investigated effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and its major metabolites, M2 and M4, on CuSO4-induced low-density lipoprotein (LDL) oxidation and cholesteryl ester accumulation in mouse peritoneal macrophages. All the test compounds inhibited LDL oxidation, and M2 had the most potent effect comparable to vitamin E. When LDL was previously incubated with the test compounds in the presence of CuSO4, the pre-treatment resulted in a marked reduction of facilitated cholesteryl ester accumulation in macrophages. Supplementation of mevalonate did not overcome the inhibitory effects of fluvastatin and its metabolites on both LDL oxidation and facilitated cholesterol esterification. Pravastatin, another HMG-CoA reductase inhibitor, did not show any inhibitory effect. Consequently, these effects of fluvastatin and its metabolites are considered to be derived from their own unique chemical structures. Moreover, fluvastatin and M2 directly inhibited cholesterol esterification induced by oxidized LDL in macrophages, but pravastatin was also found to have a weak effect. As their inhibitory effects were overcome by addition of mevalonate, the direct inhibitory effect on cholesterol esterification would be a common property of HMG-CoA reductase inhibitors. The inhibitory effects of fluvastatin and its metabolites on both LDL oxidation and cholesterol esterification in macrophages may contribute to the antiatherogenic action in vivo.

Animals↗