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K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 73 records · Page 4Linked to original sources
PubMed2002

Protection against dextran sulfate sodium-induced colitis by microspheres of ellagic acid in rats.

Ellagic acid (EA), a naturally occurring plant phenol, has the antioxidant and anti-inflammatory activities. In the present study, we examined the effect of EA contained in microspheres on the ulcerative colitis induced experimentally in rats by dextran sulfate sodium (DSS). Experimental colitis was induced in male Fisher 344 rats by daily treatment with 3% DSS solution in drinking water for 7 days. EA of microspheres (mcEA: 1 approximately 10 mg/kg as EA contents) was administered p.o. twice daily for 6 days. In a preliminary study, we found that these microsphere capsules, when administered p.o., are effectively dissolved in the proximal to the ileo-cecal junction and distributed to the terminal ileum and the colon. The ulceration area, colon length, and mucosal myeloperoxidase (MPO) activity as well as thiobarbituric acid-reactive substances (TBARS) were measured on 7th day after the onset of DSS treatment. The DSS treatment for 7 days caused severe mucosal lesions in the colon, accompanied with the increases of MPO activity and TBARS as well as the decreases of body weight gain and colon length. Administration of mcEA reduced the severity of DSS-induced colitis in a dose-dependent manner, and a significant effect was observed at 10 mg/kg, the ED50 being 2.3 mg/kg. This mcEA treatment also significantly mitigated changes in various biochemical parameters in the colonic mucosa induced by DSS. Although plain EA (without using microspheres) was also effective in reducing the severity of DSS-induced colitis, this effect was much less potent as compared with that of mcEA; the ED50 was about 15 times higher than that of mcEA. In addition, a significant effect on DSS-induced colitis was also obtained by intra-rectal administration of superoxide dismutase, an anti-oxidative agent. These results suggest that EA prevents the ulcerative colitis induced by DSS, probably by radical scavenging and/or anti-oxidative actions. The microspheres used in this study may be useful for delivering an orally administered drug specifically to the colon.

Animals↗
PubMed2002

Room temperature phosphorescence of 6-bromo-2-naphthol in micelles of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers and in their mixed aggregates with sodium dodecyl sulfate.

Room temperature phosphorescence (RTP) of 6-bromo-2-naphthol has been investigated in aqueous micellar solutions of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers as well as in their mixed aggregates with sodium dodecyl sulfate. RTP of the phosphorophor was enhanced to some extent in the micelles of the block copolymers. However, marked enhancement of RTP was observed in the mixed aggregates. The enhancement of RTP is attributed to effective incorporation of the phosphorophor into the micelles and the aggregates, resulting in suppression of nonradiative deactivation of the phosphorescent state.

Micelles↗
PubMed2002

Prophylactic effect of JTE-607 on LPS-induced acute lung injury in rats with CINC-1 inhibition.

OBJECTIVE AND DESIGN: JTE-607, a multiple cytokine inhibitor, was evaluated in lipopolysaccharide (LPS)-induced acute lung injury in rats in vivo and in vitro. MATERIALS AND METHODS: LPS instillation into airways of rats was performed. JTE-607 at 3-30 mg/kg and dexamethasone at 3 mg/kg were administered intravenously at 10 min and 0 min for JTE-607, and 60 min for dexamethasone prior to the LPS instillation (n = 8). Cytokine-induced neutrophil chemoattractant (CINC)-1 level and myeloperoxidase (MPO) activity in lung were measured at 4 h after LPS instillation, and at 24 h for lung wet weight measurement and histological study. LPS-induced CINC-1 production by rat alveolar macrophages were also measured in vitro. RESULTS: JTE-607 and dexamethasone showed a significant reduction of increased CINC-1 level and MPO activity in lung after LPS treatment in vivo. Increased wet weight was also significantly inhibited. Histological studies revealed that JTE-607 and dexamethasone significantly inhibited LPS-induced accumulation of peribronchial neutrophils and eosinophils, and perivascular edema. JTE-607 and dexamethasone suppressed CfNC-1 synthesis by rat alveolar macrophages in vitro with IC50 values of 12.4 microM and 2.3 nM, respectively. CONCLUSIONS: These results indicate that JTE-607 has an inhibitory effect on LPS-induced rat lung inflammation in parallel with CINC-1 reduction. The effect of JTE-607 was suggested to be through direct inhibition of CINC-1 production from rat alveolar macrophages. JTE-607 may thus be efficacious in cytokine-mediated lung inflammation such as acute respiratory distress syndrome.

Animals↗
PubMed2002

Transplantation for accidental acute high-dose total body neutron- and gamma-radiation exposure.

Accidental exposure to acute high-dose total body neutron radiation is rare. We report a 35-year-old man exposed to a total body dose of 5.4 Gy neutron- and 8.5-13 Gy gamma-radiation in a radiation criticality accident. He received a blood stem cell transplant from his HLA-identical sister. There was bone marrow recovery with complete donor chimerism. Random chromatid breaks were observed in donor cells suggesting a bystander effect of neutron exposure. The subject died 82 days after the accident (75 days post transplant) from multi-organ failure.

Adult↗
PubMed2002

Effect of taurine on ulcerogenic response and impaired ulcer healing induced by monochloramine in rat stomachs.

BACKGROUND: It is well known that neutrophil-derived hypochlorous acid interacts with ammonia (NH4OH) to generate monochloramine (NH2Cl) and that NH2Cl irritates the gastric mucosa and impairs ulcer healing. AIM: To examine the effect of taurine, a hypochlorous acid scavenger, on the mucosal ulcerogenic and the impaired healing response induced by NH2Cl in rat stomachs, in comparison with those of methionine and glycine. METHODS AND RESULTS: Under anaesthesia, oral administration of NH2Cl (120 mmol/L) produced severe lesions in male Sprague-Dawley rat stomachs. Taurine (10-100 mg/kg) given p.o. 30 min prior to NH2Cl dose-dependently prevented these lesions in response to NH2Cl. This action was mimicked by methionine (3-30 mg/kg) but not by glycine (10-100 mg/kg). Under urethane anaesthesia, mucosal exposure to NH4OH (120 mmol/L) caused a marked reduction of potential difference (PD) in the ex vivo chambered stomachs after induction of ischaemia, resulting in severe lesions. These ulcerogenic and PD responses by NH4OH plus ischaemia were also mitigated by taurine and methionine, but not glycine, applied to the chamber 20 min before the onset of NH4OH plus ischaemia. Moreover, oral administration of 100% ethanol produced severe haemorrhagic lesions in rat stomachs, all of which rapidly healed within 7 days after lesion induction. Daily administration of NH2Cl (20 mmol/L) significantly delayed the healing of these lesions, but recovery of this impaired healing response was obtained by concurrent administration of taurine. Both taurine and methionine showed a potent scavenging effect against NH2Cl in vitro. CONCLUSIONS: (1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa and impairs the healing response; (2) taurine exerts a prophylactic effect against the deleterious effects of NH2Cl, mainly due to its scavenging action against NH2Cl; and (3) this effect of taurine may be useful for treatment of gastritis associated with Helicobacter pylori infection.

Administration, Oral↗
PubMed2002

Gastric ulcerogenic responses following barrier disruption in knockout mice lacking prostaglandin EP1 receptors.

BACKGROUND/AIMS: Endogenous prostaglandins (PGs) are considered to play a pivotal role in maintaining the mucosal integrity of the stomach after injury. In the present study, we evaluated the mucosal ulcerogenic and mucosal blood flow (GMBF) responses in the stomach after damage by taurocholate (TC) in knockout mice lacking EP1 or EP3 receptors. METHODS: Under urethane anaesthesia, a mouse stomach was mounted in an ex vivo chamber, exposed to 20 mmol/L TC for 20 min and treated with 20 mmol/L HCl before and after TC. GMBF was measured with a laser Doppler flowmeter. RESULTS: Mucosal exposure to TC in wild-type mice caused a marked decrease in potential difference (PD), followed by an increase in H+ loss and GMBF. The decreased PD was gradually normalized after removal of TC from the chamber, with minimal damage in the mucosa 1 h after TC treatment. This hyperaemic response was inhibited by indomethacin, resulting in severe lesions in the mucosa without any change in PD or H+ loss. None of these responses induced by TC were altered in EP3-/- mice. However, in mice lacking EP1 receptors, TC treatment did not increase GMBF, despite causing PD reduction and acid loss, and resulted in severe damage in the mucosa. These responses were closely similar to those observed in animals pretreated with ONO-8711, a EP1 receptor antagonist. Mucosal PGE2 content was significantly increased after TC, similarly in all groups of mice. CONCLUSION: These results confirm a mediator role for PGE2 in gastric hyperaemic response following mucosal exposure to TC and suggest that endogenous PGs may contribute to maintaining mucosal integrity after barrier disruption, mainly through activation of the EP1 receptor subtype.

Animals↗
PubMed2002

Up-regulation of COX-2 by inhibition of COX-1 in the rat: a key to NSAID-induced gastric injury.

BACKGROUND: A recent study demonstrated that inhibition of both cyclooxygenase (COX)-1 and COX-2 is required for the development of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric lesions. However, the role of COX-1 or COX-2 inhibition in the pathogenisis of these lesions remains unclear. AIM: To examine the gastric ulcerogenic properties of selective COX-1 and COX-2 inhibitors in rats and to investigate further the relationship of COX inhibition to various events involved in the process of NSAID-induced gastric lesions. METHODS: Animals were given various COX inhibitors p.o., either alone or in combination, and killed 8 h later. Under the treatment, gastric damage, prostaglandin (PG) E2 content, mucosal permeability, myeloperoxidase (MPO) activity as well as gastric motility were examined. RESULTS: The nonselective COX inhibitor indomethacin inhibited PGE2 production, enhanced gastric motility, and provoked severe lesions in the stomach, with an increase in mucosal permeability and MPO activity. In contrast, the selective COX-2 inhibitor rofecoxib did not induce any damage in the stomach and had no effect on mucosal PGE2 content. Similarly, the selective COX-1 inhibitor SC-560 also caused no gastric damage, despite inhibiting PGE2 production. The combined administration of SC-560 and rofecoxib, however, provoked gross damage in the gastric mucosa, in a dose-dependent manner for each drug. SC-560, but not rofecoxib, caused marked gastric hypermotility and an increase in mucosal permeability, although an increase in MPO activity was observed only when rofecoxib was coadministered. The normal gastric mucosa expressed COX-1 mRNA and not COX-2 mRNA, but COX-2 mRNA was expressed in the stomach after administration of SC-560 as well as indomethacin but not rofecoxib. CONCLUSION: These results suggest that the gastric ulcerogenic properties of NSAIDs are not accounted for solely by COX-1 inhibition, but require the inhibition of both COX-1 and COX-2. The inhibition of COX-1 up- regulates COX-2 expression, and COX-2/PGs may, in turn, counteract the deleterious affects of gastric hypermotility due to COX-1 inhibition.

Amino Acid Sequence↗
PubMed2002

New applications of intracardiac echocardiography: assessment of coronary blood flow by colour and pulsed Doppler imaging in dogs.

OBJECTIVE: To explore the application of a new 10 French intracardiac echocardiography (ICE) catheter with phased array and Doppler capable transducer for the assessment of epicardial and intramyocardial coronary blood flow. METHODS: The coronary arteries were detected by cross sectional imaging in seven closed chest dogs, and coronary blood flow visualised by colour Doppler. Blood flow velocities were recorded by pulsed Doppler at baseline for reproducibility of repeated measurements, and during hyperaemia for coronary flow reserve measurements. Comparisons were made with Doppler guide wire data obtained simultaneously. Intramyocardial coronary artery blood flow was assessed by colour flow mapping, and the blood flow velocities recorded using pulsed Doppler at baseline and during hyperaemia. RESULTS: Seven left main, six left anterior descending, seven left circumflex, and five right coronary arteries were visualised in the seven animals by cross sectional or colour Doppler imaging. Repeated measurements of coronary flow velocity showed a good correlation (mean diastolic velocity, r = 0.93, n = 22, p < 0.0001; peak diastolic velocity, r = 0.96, n = 22, p < 0.0001, respectively). Intraobserver/interobserver variability was satisfactorily low. Coronary flow reserve from ICE correlated highly with the value obtained from the Doppler guide wire (r = 0.90, n = 26, p < 0.0001). Intramyocardial coronary blood flow was identified in all seven dogs, and flow velocities were recorded at baseline and during hyperaemia in four animals. CONCLUSIONS: This new ICE catheter provides high quality diagnostic resolution. It is useful for coronary blood flow assessment.

Animals↗
PubMed2002

Changes in transmural distribution of myocardial perfusion assessed by quantitative intravenous myocardial contrast echocardiography in humans.

OBJECTIVE: To clarify whether changes in transmural distribution of myocardial perfusion under significant coronary artery stenosis can be assessed by quantitative intravenous myocardial contrast echocardiography (MCE) in humans. METHODS: 31 patients underwent dipyridamole stress MCE and quantitative coronary angiography. Intravenous MCE was performed by continuous infusion of Levovist. Images were obtained from the apical four chamber view with alternating pulsing intervals both at rest and after dipyridamole infusion. Images were analysed offline by placing regions of interest over both endocardial and epicardial sides of the mid-septum. The background subtracted intensity versus pulsing interval plots were fitted to an exponential function, y = A (1 - e(-betat)), where A is plateau level and beta is rate of rise. RESULTS: Of the 31 patients, 16 had significant stenosis (> 70%) in the left anterior descending artery (group A) and 15 did not (group B). At rest, there were no differences in the A endocardial to epicardial ratio (A-EER) and beta-EER between the two groups (mean (SD) 1.2 (0.6) v 1.2 (0.8) and 1.2 (0.7) v 1.1 (0.6), respectively, NS). During hyperaemia, beta-EER in group A was significantly lower than that in group B (1.0 (0.5) v 1.4 (0.5), p < 0.05) and A-EER did not differ between the two groups (1.0 (0.5) v 1.2 (0.4), NS). CONCLUSIONS: Changes in transmural distribution of myocardial perfusion under significant coronary artery stenosis can be assessed by quantitative intravenous MCE in humans.

Contrast Media↗
PubMed2002

Myocardial protection of the pressure overload hypertrophied heart in human cardiac surgery by acceleration of anaerobic glycolysis.

BACKGROUND: Because of the decreased tolerance to ischemia and increased reperfusion injury in hypertrophied myocardium, myocardial hypertrophy is a well known risk factor for cardiac surgery. We have previously demonstrated in a left ventricular hypertrophy (LVH) model that a highly buffered cardioplegic solution (HBS) that provided glucose as a substrate and promoted anaerobic glycolysis during ischemia afforded superior myocardial protection when compared to standard formulations. And we reported the superiority of this cardioplegia in human cardiac surgery. METHODS: In this study, 16 patients with aortic stenosis (AS) and LVH receiving HBS were reviewed and compared to another patient group with AS and LVH who received either cold blood cardioplegia (CBC; n=5) or glucose insulin potassium (GIK; n=6). RESULTS: Postoperative cardiac index was better in the HBS group than the other two groups with similar or lower catecholamine. CK-MB was lower in HBS group than GIK group, but this was not significant. Only one DC cardioversion was required in the HBS group, whereas 2 DC in the CBC group and total 7 DC in the GIK group. CONCLUSIONS: We found that histidine buffered cardioplegic solution provided comparable or better pump performance after surgery with relatively lower inotropic requirement, less DC cardioversion and homologous blood requirements for left ventricular hypertrophied heart associated with aortic stenosis.

Aged↗
PubMed2001

Optical imaging of excitation propagation evoked by stimulation to the trigeminal caudalis.

The present study reports on a characteristic spatio-temporal propagation of differential fluorescent images in the rat brain stem slice by a high-speed optical imaging technique. Coronal or sagittal slices were stained with a voltage-sensitive dye RH-414, and the superficial layer of the trigeminal caudalis (Vc) was then electrically stimulated. The marginal layer and substantia gelatinosa showed larger rostrocaudal excitation than coronal, despite a lack of tract stimulation expansion in either direction. A perfusion of 0.5 micromol/l TTX, not 10 micromol/l CNQX suppressed these propagations. These findings suggest that the superficial layer of Vc has spatial differences in neuronal excitation propagation, as evidenced by morphological observations that dendrites in the superficial layers extend in the rostrocaudal direction.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

Significance of autocrine motility factor receptor gene expression as a prognostic factor in non-small-cell lung cancer.

Autocrine motility factor receptor (AMF-R) has been shown to play an important role in tumor cell migration, invasion and metastasis. We have detected AMF-R expression in tissue specimens from patients with non-small-cell lung cancer (NSCLC) and have assessed their clinical characteristics. Using RT-PCR and immunohistochemistry, we quantified the expression of AMF-R in 47 patients with NSCLC who underwent curative tumor resection, to investigate the relationship between AMF-R expression and clinicopathologic factors and prognosis. RT-PCR results agreed well with the immunohistochemic results (p < 0.0001). In 47 NSCLC patients, 34 (72.3%) samples were evaluated as having high AMF-R gene expression. AMF-R gene expression was significantly associated with lymph node metastasis and stage (p = 0.0295 for lymph node metastasis, p = 0.0152 for stage). The overall survival rate for patients with high AMF-R gene-expressing tumors was significantly worse than for those whose tumors had low AMF-R expression (p = 0.0029). Multivariate analysis also showed that AMF-R gene expression was significantly related to survival (p = 0.0165). These data indicate that AMF-R may contribute to tumor progression and that AMF-R gene expression can serve as a useful prognostic marker in NSCLC.

Adenocarcinoma↗
PubMed2001

Asynchronous development of the Benjamin-Feir unstable mode: solution of the Davey-Stewartson equation.

The long time evolution of the Benjamin-Feir unstable mode in two dimension is described by the growing-and-decaying mode solution to the Davey-Stewartson equation. The solution of the hyperbolic Davey-Stewartson (the so-called Davey-Stewartson I) equation is analyzed to show that the resonance between line soliton and growing-and-decaying mode exists. If the resonant condition is exactly satisfied, the growing-and-decaying mode exists only in the forward region of propagation of soliton and the soliton is accelerated (or decelerated). Under the quasiresonant condition, the growing-and-decaying mode grows at first in the forward region, and after the sequence of the evolution has done in the forward region the mode starts to grow in the backward region of the soliton.

Journal Article↗
PubMed2001

Identification of genes involved in epithelial-mesenchymal transition and tumor progression.

The adenovirus E1A12S gene product (WT12S) immortalizes epithelial cells and they retain their differentiated characteristics, but certain mutants cannot do the latter. Characterization of mutant immortalized epithelial cells indicated that they had undergone epithelial mesenchymal transition (EMT). Coexpression of V12ras with WT12S leads to benign tumors, but to malignant tumors with 12S mutants. Since EMT is critical for tumor progression, identification of the molecular mechanisms involved should elucidate novel therapeutic targets. To this end, representational difference analysis (RDA) was used to identify cDNAs upregulated in the mutant cell line. Thirty-five differentially expressed mRNAs were identified and classified into several functional categories, including nine novel cDNAs. Among the 26 known cDNAs, extracellular matrix and related proteins made up the largest group of differentially expressed genes, followed by growth factors and receptors and transcription factors. There was also an ion transporter, a cytoskeletal protein, glycosylation and amidinotransferase enzymes and proteins with unknown functions. Some of the known genes have previously been associated with EMT and/or tumor progression and thus served to validate the system to obtain the desired target genes, while other cDNAs are newly linked with dedifferentiation/malignancy. Array analyses indicated that the cDNAs were specifically upregulated in invasive or metastatic tumors, especially of breast, uterus and lung, suggesting their involvement in the progression of these tumors.

Adenoviridae↗
PubMed2001

First observation of clusters for solvated tropylium ions.

We have first observed clusters for solvated tropylium ions (Tr+(ROH)n) which were isolated from ROH-CH3CN (1:1 by vol.; R = Me, Et, and Prn) solutions by using a specially designed mass spectrometer and found the clear-cut essential features concerning the solvation structure around Tr+.

Journal Article↗