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Biomedical subjects

Hiroyuki Watanabe

Publications and source records attributed to Hiroyuki Watanabe.

At least 37 records · Page 2Linked to original sources
PubMed2006

Aberrant methylation of secreted apoptosis-related protein 2 (SARP2) in pure pancreatic juice in diagnosis of pancreatic neoplasms.

OBJECTIVE: Secreted apoptosis-related protein (SARP) families are considered to counteract the oncogenic Wnt signaling pathway, and inactivation of this gene may aid cancer development and progression. Recently, the aberrant methylation of SARP2 was detected frequently in pancreatic carcinoma (PCa) tissue, but not in normal pancreatic tissue. We evaluated the hypermethylation of SARP2 in pure pancreatic juices (PPJ) aspirated endoscopically from patients with PCa, intraductal papillary mucinous neoplasm of the pancreas (IPMN), chronic pancreatitis (CP), and a control group who were consequently free of pancreatic diseases according to the differential diagnosis of PCa. METHODS: We investigated the aberrant methylation of SARP2 in 9 human PCa cell lines and in the PPJ samples from 33 patients with PCa, 20 with IPMN, 19 with CP, and 10 control patients. DNAs extracted from not only sediment, but also the supernatant of the PPJ and PCa cell lines were treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction (PCR) (MSP). Moreover, real-time MSP was also performed for the melting curve analysis and the quantitative analysis of SARP2 in the PPJ. RESULTS: The incidence of the aberrant methylation of SARP2 using MSP was 8/9 (89%) in PCa cell lines, 26/33 (79%) in the PPJ with PCa, and 17/20 (85%) with IPMN. However, it was only 1/19 (5%) in the PPJ with CP, and 0/10 (0%) in the PPJ of the control patients, respectively. The incidences of aberrant methylation of SARP2 in the PPJ with PCa and IPMN were significantly higher than that in the PPJ with CP (P < 0.001, P < 0.001). Melting curve analysis by real-time MSP revealed that the incidences of aberrant methylation of SARP2 in PPJ was 28/33 (85%) with PCa, 9/11 (82%) with the malignant group of IPMN, 5/9 (56%) with the benign group of IPMN and 5/19 (26%) with CP. In this analysis, there were significant differences between PCa and CP (P < 0.001), and between the malignant group of IPMN and CP (P < 0.005). In the quantitative analysis by real-time MSP with a suitable cut-off value, the incidences of aberrant methylation of SARP2 in the PPJ with PCa, the malignant group of IPMN, the benign group of IPMN, and CP were 19/33 (58%), 6/11 (55%), 3/9 (33%), and 2/19 (11%), respectively. The incidence of the aberrant methylation of SARP2 in the PPJ was significantly different between PCa and CP and between the malignant group of IPMN and CP (P < 0.005 and P < 0.05, respectively). CONCLUSIONS: Hypermethylation of SARP2 in the PPJ may be a highly sensitive and useful marker for the detection of pancreatic neoplasms, including PCa and the malignant group of IPMN.

Adult↗
PubMed2006

Coronary flow velocity reserve measurement in three major coronary arteries using transthoracic Doppler echocardiography.

BACKGROUND: Measurement of the coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE) has been reported to be useful for the noninvasive assessment of significant coronary artery stenosis or myocardial ischemia. The purpose of this study was to evaluate the value of this method in three major coronary arteries for detecting myocardial ischemia in the clinical setting. METHODS: We studied 89 consecutive patients who were referred to our outpatient clinic because of chest pain. We measured CFVR using TTDE in three major coronary arteries. We defined CFVR<2.0 in at least one vessel as being positive for myocardial ischemia. The accuracy of CFVR measurements for detecting myocardial ischemia was determined in comparison with exercise thallium-201 (Tl-201) single photon emission computed tomography (SPECT) as a reference standard. RESULTS: CFVR in at least one vessel was successfully measured in 87 of 89 patients (98%). The sensitivity and specificity of CFVR<2.0 in at least one coronary vessel, in any of the coronary territories, was 86% and 89%, respectively. In terms of assessing myocardial ischemia in each coronary artery territory, the agreement between CFVR<2.0 and Tl-201 SPECT for the left anterior descending coronary artery, the posterior descending coronary artery, and the left circumflex coronary artery territories was 95%, 81%, and 73%, respectively. CONCLUSION: Noninvasive CFVR measurement by TTDE may be useful for detecting myocardial ischemia, as well as for identifying ischemic territories in the clinical setting.

Adenosine Triphosphate↗
PubMed2006

Automated three-dimensional analysis of mitral annular dynamics in patients with myocardial infarction using automated mitral annular tracking method.

BACKGROUND: A newly developed automated mitral annular tracking method (AMAT) has recently become available and enables us to perform automated analysis of mitral annular dynamics. PURPOSE: To evaluate mitral annular dynamics using AMAT. METHODS: AMAT was performed using a Toshiba Aplio SSA-770 ultrasound system in 15 normal healthy volunteers (group N), 16 patients with anterior MI (group A), and 12 inferior MI (group B). The distance between an annular point at end-diastole and at end-systole (distance D) was automatically measured using AMAT at the basal portion of the anterior, lateral, posterior, inferior, and inferoseptal wall. The angle between the mitral annular plane at end-diastole and the direction of movement of each mitral annular point from end-diastole to end-systole (angle A) was also automatically measured at all five mitral annular points. The coefficients of variation (CV) of both distance D and of angle A were calculated as indices of asynchrony of mitral annular dynamics. RESULTS: CV of distance D in group A (22 +/- 9% (P < 0.01 vs group N)) and group B (22 +/- 10% (P < 0.01 vs group N)) were both significantly larger than in group N (13 +/- 4%). CV of angle A in group A (15 +/- 10% (P < 0.05 vs group N)) and group B (15 +/- 10% (P < 0.05 vs group N)) were also significantly larger than that in group N (8 +/- 3%). CONCLUSION: Automated analysis using AMAT showed that mitral annular dynamics of patients with MI were less symmetrical than in normal healthy volunteers.

Adult↗
PubMed2006

Acute hyperglycemia induced by oral glucose loading suppresses coronary microcirculation on transthoracic Doppler echocardiography in healthy young adults.

OBJECTIVES: We sought to evaluate the effect of acute hyperglycemia on coronary microcirculation by noninvasive measurement of coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). RESEARCH DESIGN AND METHODS: Measurements of CFVR using TTDE and levels of plasma glucose and serum insulin and lipids were determined before and 1 hour after loading with oral glucose (75-g glucose) in 10 young healthy males (mean age, 30 +/- 2 years) or an artificial sweetener in five of the 10 subjects without coronary risk factors. RESULTS: In all subjects, the levels of plasma glucose and serum insulin significantly increased after glucose loading compared with baseline (5.1 +/- 0.6 vs 7.6 +/- 1.2 mM/l, 6 +/- 3 vs 49 +/- 13 microU/ml, respectively; P < 0.0001). CFVR was significantly decreased 1 hour after acute oral glucose loading (4.4 +/- 0.7-3.8 +/- 0.7, respectively; P < 0.01). There was no significant change in CFVR after loading with an artificial sweetener (4.4 +/- 0.6-4.4 +/- 0.5 cm/sec). CONCLUSIONS: TTDE revealed that acute hyperglycemia induced by oral glucose loading suppresses CFVR in healthy young male subjects. This result suggests that acute hyperglycemia may have adverse effects on coronary microcirculation.

Acute Disease↗
PubMed2006

Effects of diacylglycerol oil on adiposity in obese children: initial communication.

Several studies have shown that diacylglycerol (DAG) oil may suppress accumulation of body fat in adults compared to triacylglycerol (TAG) oil. In this study, we investigated the effect of DAG oil as part of dietetic therapy in obese children. The participants were 11 male and female obese children who were under treatment at the outpatient clinic (four boys, seven girls, age: 7-17 years old). Daily-use cooking oil was changed to DAG oil, and the effects on abdominal fat areas, adipocytokines, and serum lipids were investigated. The total and subcutaneous fat areas significantly decreased in the 5th month after ingestion of DAG oil. Leptin was significantly lower than the initial level after ingestion of DAG oil. The ingestion of DAG oil decreased both the abdominal fat area and leptin in obese children, suggesting that DAG oil prevents obesity in children as well as in adults.

Abdominal Fat↗
PubMed2005

Involvement of aquaporin-4 in astroglial cell migration and glial scar formation.

Aquaporin-4, the major water-selective channel in astroglia throughout the central nervous system, facilitates water movement into and out of the brain. Here, we identify a novel role for aquaporin-4 in astroglial cell migration, as occurs during glial scar formation. Astroglia cultured from the neocortex of aquaporin-4-null mice had similar morphology, proliferation and adhesion, but markedly impaired migration determined by Transwell migration efficiency (18+/-2 vs 58+/-4% of cells migrated towards 10% serum in 8 hours; P<0.001) and wound healing rate (4.6 vs 7.0 microm/hour speed of wound edge; P<0.001) compared with wild-type mice. Transwell migration was similarly impaired (25+/-4% migrated cells) in wild-type astroglia after approximately 90% reduction in aquaporin-4 protein expression by RNA inhibition. Aquaporin-4 was polarized to the leading edge of the plasma membrane in migrating wild-type astroglia, where rapid shape changes were seen by video microscopy. Astroglial cell migration was enhanced by a small extracellular osmotic gradient, suggesting that aquaporin-4 facilitates water influx across the leading edge of a migrating cell. In an in vivo model of reactive gliosis and astroglial cell migration produced by cortical stab injury, glial scar formation was remarkably impaired in aquaporin-4-null mice, with reduced migration of reactive astroglia towards the site of injury. Our findings provide evidence for the involvement of aquaporin-4 in astroglial cell migration, which occurs during glial scar formation in brain injury, stroke, tumor and focal abscess.

Animals↗
PubMed2005

A new approach to correct the QT interval for changes in heart rate using a nonparametric regression model in beagle dogs.

INTRODUCTION: Over- and/or under-correction of QT intervals for changes in heart rate may lead to misleading conclusions and/or masking the potential of a drug to prolong the QT interval. This study examines a nonparametric regression model (Loess Smoother) to adjust the QT interval for differences in heart rate, with an improved fitness over a wide range of heart rates. METHODS: 240 sets of (QT, RR) observations collected from each of 8 conscious and non-treated beagle dogs were used as the materials for investigation. The fitness of the nonparametric regression model to the QT-RR relationship was compared with four models (individual linear regression, common linear regression, and Bazett's and Fridericia's correlation models) with reference to Akaike's Information Criterion (AIC). Residuals were visually assessed. RESULTS: The bias-corrected AIC of the nonparametric regression model was the best of the models examined in this study. Although the parametric models did not fit, the nonparametric regression model improved the fitting at both fast and slow heart rates. DISCUSSION: The nonparametric regression model is the more flexible method compared with the parametric method. The mathematical fit for linear regression models was unsatisfactory at both fast and slow heart rates, while the nonparametric regression model showed significant improvement at all heart rates in beagle dogs.

Administration, Oral↗
PubMed2005

Diacylglycerol oil ingestion in type 2 diabetic patients with hypertriglyceridemia.

OBJECTIVE: Coronary arteriosclerotic heart disease frequently develops in patients with diabetes. Decreases in [corrected] serum high-density lipoprotein cholesterol (HDL-C) [corrected] concentration and low-density lipoprotein (LDL) particle size, accompanied by hypertriglyceridemia, are associated with the onset of atherosclerosis. We recently reported that hypertriglyceridemia was significantly improved in patients with type 2 diabetes who ingested diacylglycerol (DAG) oil. The effect on variables, including LDL particle size related to lipid metabolism, however, was not examined. The present study investigated the effects on these variables in more detail. METHODS: Patients with type 2 diabetes (n = 24) were assigned to receive DAG oil or triacylglycerol oil, and a 3-mo, single-blind, controlled study was performed. Patients replaced cooking oil in their daily diet with DAG or triacylglycerol oil, and anthropometry and blood sampling were performed at monthly intervals. RESULTS: There were no significant differences in calorie intake or amount of test oil ingested between groups. Waist circumference and serum triacylglycerol concentrations were significantly lower and serum concentrations of high-density lipoprotein cholesterol and apolipoprotein-AI were significantly higher in the DAG oil group than in the triacylglycerol oil group. Plasma plasminogen activator inhibitor-1 concentrations were significantly lower in the DAG oil group. LDL particle size tended to increase in the DAG oil group and was significantly larger in patients who had a small initial LDL particle size (<25.5 nm). There were no significant differences in variables related to glucose metabolism or in serum concentration of free fatty acids or total ketone bodies. CONCLUSIONS: These results indicate that DAG oil may be useful for patients who have type 2 diabetes in the management of obesity and lipid abnormalities.

Adult↗
PubMed2005

Differential inhibitory effects of mu-opioids on substance P- and capsaicin-induced nociceptive behavior in mice.

The antinociceptive mechanisms of the selective mu-opioid receptor agonists [D-Ala2,NMePhe4,Gly(ol)5]enkephalin (DAMGO), H-Tyr-D-Arg-Phe-beta-Ala-OH (TAPA) or H-Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA-NH2) against substance P (SP)- or capsaicin-elicited nociceptive behaviors was investigated in mice. DAMGO, TAPA or TAPA-NH2 given intrathecally inhibited the nociceptive behaviors elicited by intrathecally administered SP or capsaicin, and these antinociceptive effects were completely eliminated by intrathecal co-administration with D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective mu-opioid receptor antagonist. Pretreatment subcutaneously with naloxonazine, a selective mu1-opioid receptor antagonist, partially attenuated the antinociceptive effect of TAPA-NH2, but not DAMGO and TAPA, against SP. However, the antinociception induced by TAPA, but not DAMGO and TAPA-NH2, against capsaicin was significantly inhibited by naloxonazine. On the other hand, co-administration intrathecally with Tyr-D-Pro-Trp-Gly-NH2 (D-Pro2-Tyr-W-MIF-1), a selective mu2-opioid receptor antagonist, significantly attenuated the antinociceptive effects of DAMGO, but not TAPA and TAPA-NH2, against capsaicin, while the antinociceptions induced by three opioid peptides against SP were significantly inhibited by D-Pro2-Tyr-W-MIF-1. These results suggest that differential inhibitory mechanisms on pre- and postsynaptic sites in the spinal cord contribute to the antinociceptive effects of the three mu-opioid peptides.

Analgesics, Opioid↗
PubMed2005

Enhanced antinociception by intracerebroventricularly administered orexin A in histamine H1 or H2 receptor gene knockout mice.

Orexins are neuropeptides that are mostly expressed in the posterior and lateral hypothalamus, and related to the central control of appetite, arousal, and antinociception. Orexin neurons projected to the tuberomammillary nucleus and orexins may release histamine from the histamine neurons in this nucleus. Histamine is known to cause hypernociception. The roles of histamine H1 and H2 receptors in the orexin A-induced antinociception, however, have not been clarified yet. Here we studied the effects of histamine H1 and H2 receptors on orexin A-produced antinociception using histamine receptor knockout mice in four assays of nociception; the hot-plate, the tail-flick, the tail-pressure and the capsaicin tests. Furthermore we studied effects of histamine H1 and H2 receptor antagonists on orexin A-produced antinociception in C57BL/6 mice. The antinociceptive effects of i.c.v. orexin A were greater in histamine H1 receptor or H2 receptor knockout mice than in the wild-type mice in all four assays of pain. Furthermore, treatment of C57BL/6 mice with a combination of i.c.v. orexin A and d-chlorpheniramine (a histamine H1 receptor antagonist) or cimetidine (a histamine H2 receptor antagonist) showed a greater antinociception than i.c.v. orexin A alone in all four assays. These findings suggest the possibility that orexin A may activate H1 and H2 receptors in the supraspinal levels through the release of histamine from neurons, which might attenuate the antinociceptive effects of orexin A. Thus, the blocking of the histamine H1 or H2 receptor may produce antinociception and enhance the orexin A-induced antinociception.

Animals↗
PubMed2005

Stat3 in resident macrophages as a repressor protein of inflammatory response.

Inflammation is counterbalanced by anti-inflammatory cytokines such as IL-10, in which Stat3 mediates the signaling pathway. In this study, we demonstrate that resident macrophages, but not other cell types, are important targets of IL-10 in a murine model of acute peritonitis. Injection of thioglycollate i.p. induced a considerable number of neutrophils and macrophages in the peritoneum, which was significantly augmented in mice with a cell-type specific disruption of the Stat3 gene in macrophages and neutrophils (LysMcre/Stat3flox/- mice). The augmented leukocyte infiltration was accompanied by increased peritoneal levels of TNF-alpha, MIP-2, KC chemokine (KC), and MCP-1/CCL2. Stat3 was tyrosine phosphorylated in peritoneal resident macrophages as well as infiltrating leukocytes in the littermate controls, suggesting that Stat3 in either or both of these cells might play a regulatory role in inflammation. The peritoneal levels of TNF-alpha, MIP-2, KC, and MCP-1 were similarly elevated in LysMcre/Stat3flox/- mice rendered leukopenic by cyclophosphamide treatment as compared with the controls. Adoptive transfer of resident macrophages from LysMcre/Stat3flox/- mice into the control littermates resulted in increases in the peritoneal level of TNF-alpha, MIP-2, KC, and MCP-1 after i.p. injection of thioglycollate. Under these conditions, control littermates harboring LysMcre/Stat3flox/- macrophages exhibited an augmented leukocyte infiltration relative to those received control macrophages. Taken together, these data provide evidence that resident macrophages, but not other cell types, play a regulatory role in inflammation through a Stat3 signaling pathway. Stat3 in resident macrophages appears to function as a repressor protein in this model of acute inflammation.

Adoptive Transfer↗
PubMed2005

Herbal medicine Ninjinyoeito ameliorates ribavirin-induced anemia in chronic hepatitis C: a randomized controlled trial.

AIM: Ribavirin (RBV) shows a strong antiviral effect on hepatitis C virus when used in combination with interferon. However, RBV-induced anemia is a major problem in this therapy. It would be of great clinical importance to ameliorate the anemia without reducing the RBV dose. We report here that, Ninjinyoeito (NYT), a herbal medicine can reduce the RBV-induced anemia. METHODS: Twenty-three patients with chronic hepatitis C were treated with interferon alpha 2b plus RBV with (NYT group) or without (control group) NYT by a randomized selection. Eighteen patients completed the treatment schedule, and hemato-biochemical and virological effects were evaluated. RESULTS: There was no significant difference in biochemical and virological responses between the two groups. However, anemia was significantly reduced in the NYT group compared with the control group. The maximal decrease of Hb in the NYT group (2.59+/-1.10 g/dL) was significantly (P = 0.026) smaller than that in the control group (3.71+/-0.97 g/dL). There was no significant difference in serum glutathione peroxidase activity, serum RBV concentration, and Th1/Th2 balance between the two groups. There was no specific adverse effect in NYT administration. CONCLUSION: These results suggest that NYT could be used as a supportive remedy to reduce the RBV-induced anemia in the treatment of chronic hepatitis C.

Anemia↗
PubMed2005

Effects of dithiothreitol and boar on pronuclear formation and embryonic development following intracytoplasmic sperm injection in pigs.

The objective of this study was to improve normal fertilization, male pronuclear formation and embryonic development following intracytoplasmic injection of dithiothreitol (DTT)-treated boar spermatozoa. To determine the effect of DTT treatment, frozen-thawed boar spermatozoa were treated with DTT for 0, 10, 30, and 60 min, and injected into porcine oocytes. The effects of DTT and male difference on normal fertilization and embryonic development were investigated. The mean normal fertilization rate in the groups treated with DTT for 30 min (73.8%) and 60 min (74.9%) was higher (P < 0.05) than that in the control group (49.3%). The mean blastocyst formation rate in the group treated with DTT for 30 min (23.2%) was higher (P < 0.05) than that in the other groups (8.7-10.9%). Among boars there was no difference in normal fertilization, but there was a significant difference between the non-treated and the DTT-treated groups. The mean rate of blastocyst formation was different (P < 0.05) among boars, and between the non-treated and DTT-treated groups. The mean number of cells in blastocysts was similar among the boars and between the non-treated and the DTT-treated groups. In conclusion, DTT treatment for 30 min increased the rate of normal fertilization and embryonic development to the blastocyst stage. Furthermore, the rate of blastocyst formation of oocytes injected with spermatozoa differed among boars.

Analysis of Variance↗
PubMed2005

Effect of mental stress on coronary flow velocity reserve in healthy men.

The effect of mental stress on coronary flow velocity reserve (CFVR) was examined in healthy men using transthoracic Doppler echocardiography. In the mental stress group (n = 31), CFVR was significantly reduced at 15 (to 3.3 +/- 0.8, p <0.001) and 30 (to 3.7 +/- 0.8, p <0.01) minutes after mental stress testing, compared with before mental stress (4.3 +/- 0.9), whereas it did not change in each of 3 measurements in control subjects (n = 10). Mental stress impaired coronary circulation even after a certain interval after the stress.

Adult↗
PubMed2005

Posterior cingulate gyrus metabolic changes in chronic schizophrenia with generalized cognitive deficits.

N-Methyl-d-aspartate (NMDA) receptor antagonists are known to induce schizophrenia-like psychotic symptoms and cognitive deficits in humans, and have been shown to cause neuronal damage in the posterior cingulate gyrus (PCG) of rodents. Patients with chronic schizophrenia exhibit generalized cognitive deficits, but it remains unclear whether or not the PCG is related to their cognitive dysfunction. To determine what biochemical changes may occur in the PCG of patients with chronic schizophrenia, and to ascertain whether or not such abnormalities may be related to the incidence of cognitive deficits, we obtained cognitive scores and proton magnetic resonance spectra (MRS) from the PCG and the left and right medial temporal lobes (MTL) of 19 patients with schizophrenia and 18 age- and sex-matched normal healthy controls. Compared to the normal controls, the patients with chronic schizophrenia showed significantly worse cognitive performance on verbal and visual memory tests, verbal fluency tests, and the Trail Making Test. The ratio of N-acetylaspartate to creatine and phosphocreatine (NAA/Cr) in the PCG of the patients was significantly lower than that of the controls. Moreover, the NAA/Cr in the PCG of the healthy controls exhibited age-related decline, whereas in the patients with schizophrenia, the corresponding values were consistently low, regardless of age. These findings are thus in accord with current speculation about neuronal dysfunction in the PCG based on the NMDA hypofunction hypothesis regarding the pathophysiology of chronic schizophrenia.

Adult↗