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Biomedical subjects

Noboru Kaneko

Publications and source records attributed to Noboru Kaneko.

At least 19 recordsLinked to original sources

K201, a multi-channel blocker, inhibits clofilium-induced torsades de pointes and attenuates an increase in repolarization.

K201 (JTV519) is a 1,4-benzothiazepine derivative that exhibits a strong cardioprotective action and acts as a multiple-channel blocker, including as a K+ channel blocker. An experimental model of prolongation of the QT interval and torsades de pointes can be induced in rabbits by treatment with clofilium in the presence of the alpha1-adrenoreceptor agonist methoxamine. In this study we examined the effects of K201 with and without methoxamine on the QT and QTc intervals, and determined whether K201 inhibits clofilium-induced torsades de pointes in the presence of methoxamine (15 microg/kg/min) in rabbits (n=74). Administration of K201 (0, 40, 100, 200 and 400 microg/kg/min) with and without methoxamine prolonged the QT interval in a dose-dependent manner, and torsades de pointes did not occur in any animals. However, clofilium (50 microg/kg/min) with methoxamine induced torsades de pointes in all animals (6/6). Torsades de pointes occurred at rates of 100%, 67%, 40% and 0% at K201 concentrations of 0, 50, 200 and 400 microg/kg/min, respectively, in the clofilium-infused torsades de pointes model. Therefore, 400 microg/kg/min of K201 completely inhibited clofilium-induced torsades de pointes and attenuated the increase of repolarization caused by clofilium; the inhibitory effects of K201 may be related to its pharmacological properties as an alpha1-adrenoceptor blocker. Overall, our results show that K201 causes prolongation of the QT and QTc intervals, but does not induce torsades de pointes, with and without alpha1-adrenoceptor stimulation. Furthermore, K201 inhibits clofilium-induced torsades de pointes, despite QT prolongation, suggesting that QT prolongation alone is not a proarrhythmic signal.

Adrenergic alpha-1 Receptor Agonists↗

Influence of a fluoride mouthrinse on mutans streptococci in schoolchildren.

This study aimed to determine whether the long-term use of a fluoride mouthrinse affects the salivary levels of mutans streptococci. Two hundred and fifteen schoolchildren (aged 9-10 years) participated. One hundred and forty-nine of these children had used a fluoride mouthrinse since 5 years of age at nursery school, and the remaining 66 children had not. DFT (decayed and filled teeth) was recorded, and the salivary levels of Streptococcus mutans and Streptococcus sobrinus were measured using mitis salivarius bacitracin agar. The group that had used a fluoride mouthrinse had a significantly lower prevalence of both S. mutans and S. sobrinus (p = 0.038) and a significantly lower DFT score (p < 0.001) than the other group. Using logistic regression analysis including caries experience at baseline as a dependent variable, the odds ratio of carrying S. mutans alone was 8.0 (p = 0.066) and that of carrying both S. mutans and S. sobrinus was 16.5 (p = 0.022) in the group that had not used the fluoride mouthrinse. Children carrying both S. mutans and S. sobrinus had a higher caries incidence in 1 year than the others, with odds ratios of 5.73 (p = 0.067) in the group with a fluoride mouthrinse and 3.47 (p = 0.035) in the group without it. These results show that the long-term use of a fluoride mouthrinse is associated with reduced salivary levels of mutans streptococci and this bacterial reduction may partly contribute to the suppression of dental caries in children using a long-term fluoride mouthrinse.

Cariostatic Agents↗

Effects of olmesartan medoxomil as an angiotensin II-receptor blocker in chronic hypoxic rats.

We established a rat chronic alveolar hypoxia in vivo model to evaluate the efficacy against hypoxic pulmonary hypertension of a new angiotensin II-receptor I blocker, olmesartan medoxomil. Three groups of rats were established: rats exposed for 2-6 weeks to 10% oxygen atmosphere in a normobaric chamber; hypoxic rats treated with olmesartan medoxomil oral administration (5 mg/day) every day; and control rats fed in a normoxic condition. After hypoxia treatment, the presence, etiology and severity of pulmonary hypertension, was echocardiographically evaluated, and expressions of brain natriuretic peptide (BNP), transforming growth factor (TGF-beta) and endothelin-1 genes measured by both immunohistochemical assay and real-time polymerase chain reaction. Olmesartan medoxomil significantly reduced the induction of hypoxic cor pulmonale not only on echocardiographical observations but also in BNP, TGF-beta and endothelin gene expressions in molecular studies. However, systolic blood pressure was independent of olmesartan medoxomil. The present study clearly indicates that the angiotensin II-type I-receptor blocker olmesartan medoxomil has significant efficacy for hypoxic cor pulmonale.

Administration, Oral↗

Comparison of the effects of a distal embolic protection device and an aspiration catheter during percutaneous coronary intervention in patients with acute myocardial infarction.

BACKGROUND: The beneficial effect of percutaneous coronary intervention (PCI) using stents for acute myocardial infarction (AMI) has already been demonstrated, but there is the problem that mechanical microvascular occlusion can occur because of thrombus/atheroma embolization when the PCI was performed. The aim of the present study was to retrospectively test and compare the effects of an aspiration catheter or distal embolic protection with a distal occlusion balloon catheter to prevent peripheral vascular embolization. METHODS AND RESULTS: The subjects consisted of 135 patients who underwent PCI with stenting within 12 h of the onset of chest pain caused by their first AMI. They were divided into 2 groups; the aspiration group, consisted of 81 consecutively seen patients who underwent aspiration catheter treatment between January 2001 and May 2002, and the distal protection group was the next group of 54 consecutively seen patients treated with a distal protection device between June 2002 and February 2003. The results were as follows. Thrombolysis in Myocardial Infarction (TIMI) score of 3 was obtained significantly more frequently in the distal protection group (94.4%) than in the aspiration group (79.0%). Additionally, the intensity of the cardiac muscle stain (blush score) was evaluated on coronary angiography and the rate of cases showing a blush score of 3, which indicates favorable blood perfusion at the tissue level, in the distal protection group (56.6%) was significantly greater than in the aspiration group (33.3%, p<0.01). The time to peak blood concentration of creatinine kinase was also significantly shorter in the distal protection group. CONCLUSIONS: The distal embolism protection method is superior to the aspiration method for prevention of embolization after PCI with stenting for AMI, in terms of tissue level reperfusion in myocardial recanalization therapy.

Cardiac Catheterization↗

Feasibility of eradication of mutans streptococci from oral cavities.

OBJECTIVES: Dental caries prevention programs using chlorhexidine (CHX) have been proposed, but CHX's effect in reducing levels of mutans streptococci (S. mutans and S. sobrinus) appears to last for only a few months. The aim of this study was to attempt to eradicate mutans streptococci from the oral cavity using intensive professional mechanical tooth cleaning (PMTC) and topical application of CHX in custom-made trays. METHODS: Seven adult dentate subjects participated in this study (mean age 53.7+/-5.6, age range 46 to 62, mean DMFT, 9.1+/-4.2). For each subject, PMTC was carried out eight times within ten days. After each PMTC, 1% CHX was applied twice to the tooth surface using custom-made trays. In addition, as home treatment, subjects were required to carry out tooth brushing three times a day, and apply 0.2% CHX in custom trays after brushing in the morning and evening. In addition, subjects rinsed with 0.2% CHX solution after lunch. Salivary levels of mutans streptococci were evaluated using Dentocult-SM at baseline and on days 9, 20, 70, 120. RESULTS: Mutans streptococci were eradicated by day 120 from 4 of the 7 seven subjects participating in this study. Those 3 subjects still harboring mutans streptococci exhibited deep periodontal pocketing. CONCLUSIONS: Eradication of mutans streptococci from the oral cavity is feasible using a combination of CHX application in custom-made trays and intensive PMTC.

Aged↗

Clinical significance of measurement of plasma annexin V concentration of patients in the emergency room.

Annexin V, a calcium-binding protein, is widely present in various organs and tissues. In the present study, plasma annexin V concentration was measured in 158 patients who were brought to the emergency room, including 25 patients suffering from acute myocardial infarction (AMI), 14 with cerebrovascular disease, 11 with trauma of the extremities, 11 with severe trauma associated with visceral damage, and 35 with witnessed cardiac arrest. Annexin V concentration in normal healthy individuals (n=110) was 1.9+/-0.7 ng/ml. Annexin V concentration in AMI and cardiac arrest patients was 11.0+/-4.9 and 15.3+/-7.9 ng/ml, respectively, being significantly higher than that in patients with cerebrovascular disease (5.4+/-2.7 ng/ml). The value in severe trauma patients was 15.9+/-9.4 ng/ml, being significantly higher than that in patients with trauma of the extremities (5.6+/-1.2 ng/ml). Annexin V concentrations in the cardiac arrest and AMI patients who survived more than 24 h after admission were lower than those in patients who died within 24 h after the onset of symptoms. Annexin V content in the lungs and myocardium in normal rats was extremely high in comparison to that in brain and skeletal muscle. These results suggest that the high levels of plasma annexin V in patients with AMI, cardiac arrest and severe trauma reflect the severity of damage of the myocardium and/or other visceral organs, and measurement of plasma annexin V concentration may help to assess the prognosis of patients brought to the emergency room.

Adolescent↗

Pedicle or free musculocutaneous flaps for shoulder defects after oncological resection.

Management of soft-tissue defects of the shoulder is described. Extensive defects of soft tissues with or without overlying skin were created after resection of sarcomas in five patients. Reconstruction was performed using musculocutaneous flaps, which included three pedicle latissimus dorsi and two free tensor fascia lata flaps. Simultaneous functioning replacement of the defects of the trapezius and deltoid muscles were each achieved in two patients. Primary wound healing was achieved, and each patient recovered good contour of the shoulder. Functional results were satisfactory in all patients with an average score of 93.4% (range, 83%-100%) using the system of the Musculoskeletal Tumor Society. The four functioning muscles recovered active contraction in the transferred position. The shoulder elevation was normal in three patients, and was 90 degrees and 30 degrees in one patient each. All patients remained disease-free at the time of latest follow-up. Thus, shoulder defects of the soft tissues can be managed appropriately with the two representative musculocutaneous flaps.

Adolescent↗

Administration of atrial natriuretic peptide attenuates reperfusion phenomena and preserves left ventricular regional wall motion after direct coronary angioplasty for acute myocardial infarction.

To evaluate the effects of synthetic human atrial natriuretic peptide (hANP) on myocardial reperfusion injury and left ventricular remodeling, 19 patients within 12 h of a first attack of anterior myocardial infarction (AMI) underwent intracoronary injection of 25 microg of hANP immediately after coronary angioplasty, combined with intravenous infusion of 0.025 microg x kg(-1) x min(-1) of hANP initiated on admission for 1 week (hANP group); 18 similar patients had saline administered (control group). The incidences of premature ventricular contraction, ventricular tachycardia and/or fibrillation in the hANP group were significantly less than in the control group after coronary angioplasty. Left ventricular ejection fraction was significantly greater and left ventricular end-diastolic volume index was significantly smaller 6 months after coronary angioplasty. Left ventricular regional wall motion of the infarcted segments significantly increased. Thus, hANP remarkably suppressed reperfusion phenomena and preserved left ventricular function through improvement of regional wall motion of the infarcted segments after coronary angioplasty.

Angioplasty, Balloon, Coronary↗

Real-time PCR for quantification of Streptococcus mutans.

A real-time polymerase chain reaction (PCR) assay was developed for the quantification of Streptococcus mutans. Primers targeting gtf genes of S. mutans were designed and tested for their specificity using 28 oral streptococcal strains, three other bacterial strains, and human DNA. The primers could amplify specifically the target DNA fragment from a mixture of oral streptococcus genomic DNA containing about 10 fg to 10 ng of S. mutans genome DNA. The real-time PCR produced a linear quantitative detection range over concentrations spanning seven exponential values, with a detection limit of a few copies of S. mutans' genomic DNA per reaction tube. The results of the real-time PCR assay corresponded well to those of conventional culture assays for S. mutans in saliva samples. A real-time PCR assay for Streptococcus sobrinus and Streptococcus downei was also established and produced results that corresponded well to those from conventional culture assays for S. sobrinus in saliva samples. These assays will be useful as a new means to assess one of the important risk factors for caries.

Bacterial Typing Techniques↗

Clinical significance of vascular endothelial growth factor in patients with primary lung cancer.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is an angiogenesis factor closely associated with the growth and metastasis of malignant tumours. METHODOLOGY: In the present study, we measured plasma VEGF levels in 20 normal subjects (N), 35 patients with benign lung diseases (B), 28 patients with untreated advanced lung cancer (NT) and 10 patients with treated lung cancer (T). In addition, we measured the VEGF levels in pleural effusions from five patients with primary lung cancer and two patients with active infectious diseases. Vascular endothelial growth factor was measured by ELISA. RESULTS: The mean (+/-SD) plasma VEGF level in NT patients (160.8 +/- 177.4 pg/mL) was fivefold higher than that in other patient groups (T, 17.7 +/- 4.9 pg/mL; B, 28.3 +/- 17.6 pg/mL) and the N group (14.9 +/- 7.0 pg/mL; P < 0.01). Vascular endothelial growth factor from lung cancer pleural effusions (17 526.0 +/- 22 498.2 pg/mL) was 25-fold higher than that from patients with active infectious diseases (665.5 +/- 259.0 pg/mL). CONCLUSIONS: Plasma VEGF may be a good clinical indicator for the assessment of primary lung cancer and pleural effusion VEGF in primary lung cancer is higher than pleural effusion VEGF in patients with inflammatory diseases.

Adenocarcinoma↗

Suppressive effect of pulmonary hypertension and leukocyte activation by inhaled prostaglandin E1 in rats with monocrotaline-induced pulmonary hypertension.

The effect of long-term prostaglandin E(1) (PGE(1)) aerosol was investigated in rats with chronic pulmonary hypertension induced by monocrotaline (MCT). Six-week-old Sprague-Dawley rats were separated into groups of 6 and administered 1 mL of saline (group A) or 60 mg / kg of MCT. The MCT-treated mice were then administered either nothing (group B) or 5 mL of PGE(1) (4 microg/mL) via a nebulizer every day for 1 week (group C), 2 weeks (group D), 3 weeks (group E), or 4 weeks (group F) after MCT injection. The pulmonary artery medial wall thickness was measured and the weight ratio of the right ventricle to the intraventricular septum plus the left ventricle (RV ratio) was determined 1 month after saline or MCT injection. Leukocytes positive for the activation markers CD18, CD49d, CD62L were determined in each group every week for 1 month. The pulmonary artery medial wall thickness and RV ratio gradually decreased in proportion to the duration of PGE(1) inhalation. In groups E and F, the level of CD62L-positive leukocytes gradually decreased after MCT injection in proportion to the duration of PGE(1) inhalation. We conclude that long-term inhalation of PGE(1) is very useful therapy in chronic pulmonary hypertension and that the antileukocyte effect of PGE(1) is associated with the suppression of CD62L-positive leukocytes at an early stage of progression.

Administration, Inhalation↗

Clinical significance of blood brain natriuretic peptide level measurement in the detection of heart disease in untreated outpatients: comparison of electrocardiography, chest radiography and echocardiography.

The aim of present study was to compare the predictive characteristics and cost-benefit of measuring the concentration of blood brain natriuretic peptide (BNP), compared with electrocardiography (ECG), chest radiography and echocardiography, as a diagnostic test for heart disease. The study group comprised 130 untreated patients who had symptoms suggestive of heart disease. According to the results of additional examinations and follow-up checks, 86 patients were diagnosed as having heart disease and 44 patients were judged free of heart disease. Positive findings in each test suggestive of heart disease were checked in accordance with criteria, and the number of positive and negative cases for each test was calculated. The predictive characteristics, such as specificity, sensitivity, accuracy, positive and negative predictive values, of each test and the cost-benefit value were calculated and analyzed statistically. The sensitivity, specificity and accuracy of blood BNP and echocardiography were significantly greater than those of ECG and chest radiography. Echocardiography had a significantly lower cost-benefit value compared with measuring blood BNP concentration. Thus, the blood BNP concentration had significantly higher predictive characteristics than ECG and chest radiography, and a cost-benefit value significantly greater than that of echocardiography.

Aged↗

Detection of circulating prostate tumor cells: alternative spliced variant of PSM induced false-positive result.

RT-nested PCR has been introduced as a highly specific and sensitive assay method to detect the prostate-specific membrane antigen (PSM) mRNA in peripheral blood. However, appreciable percentages of false-positive cases have been reported. Additionally, primer sets reported previously could not discriminate between PSM and PSM', an alternatively spliced variant, mRNA. These isoforms can be produced from a single gene. Switches in alternative splicing patterns are often controlled with strict cell-type or developmental-stage specificity. Therefore, it is most important to discriminate between PSM mRNA and PSM' mRNA. Using our highly specific primer sets, PSM mRNA was detected in 3 of 24 peripheral blood samples of normal male volunteers (12.5%) and was not detected in peripheral blood of 11 normal female volunteers. PSM' mRNA was detected in 5 of 24 peripheral blood samples of normal male volunteers (20.8%) and in 4 of 11 of normal female volunteers (36.4%). PSM' mRNA induced false-positive results, it is important for genetic diagnosis of prostate cancer to discriminate between PSM and PSM' using our primer sets with high specificity. The advances in the uniquely designed primer sets may allow researchers to detect a real PSM mRNA without PSM' mRNA.

Adult↗

[A case of successful pulmonary embolectomy for massive acute pulmonary thromboembolism].

A 54-year-old man was admitted to our hospital complaining of sudden-onset dyspnea in shock. Chest computed tomography(CT) showed thrombi in the right main and left intermediate pulmonary arteries. The case was diagnosed as a massive acute pulmonary thromboembolism. Although his hemodynamic status was stable after catecholamine infusion, his dyspnea was still in progress. Emergency pulmonary embolectomy was performed and the life of patient was saved. It is thought that progressive dyspnea is an important sign of a deteriorating hemodynamic status and the predictive symptom indicating a surgical procedure in patients with massive acute pulmonary thromboembolism.

Acute Disease↗

Chronic pulmonary thromboembolism. Air trapping on computed tomography and correlation with pulmonary function tests.

OBJECTIVE: We evaluated lung attenuation on inspiratory/expiratory computed tomography (CT) and spiral CT angiography (CTA) from patients with chronic pulmonary embolism and correlated the CT findings with pulmonary function test (PFT) results. METHODS: We retrospectively reviewed 9 patients with chronic embolism (mean age, 62.3 years; 5 women and 4 men). Paired inspiratory, expiratory CT and matching CTA images were reviewed, and lung attenuation was evaluated in each segment. Lower attenuation on inspiratory images and air trapping on expiratory images were subjectively assessed and correlated with PFT results. The relationship between the presence of clot and lung attenuation was evaluated. Nine age-matched normal subjects served as controls. RESULTS: Lower attenuation with mosaic perfusion and air trapping were identified in 6 and 9 patients, respectively (mean scores, 8.1 and 11.3, respectively). Air trapping was identified in 19 (42.2%) of 45 segments with lower attenuation on inspiratory images, but was also noted in 31 segments with normal inspiratory attenuation. Air trapping was associated with the presence of proximal arterial stenosis (P<0.01), and the area showed less contrast enhancement than the adjacent lung (P<0.05). Extent of air trapping correlated inversely with PFT parameters of peripheral airway obstruction such as maximum mid-expiratory flow rate (r=-0.86, P=0.003). On the other hand, extent of mosaic perfusion did not correlate with PFT. CONCLUSIONS: Air trapping is commonly seen in chronic embolism and is found in areas of relative hypoperfusion. The extent of air trapping correlates with parameters of peripheral airway obstruction.

Adult↗

Changes of sequestered leukocytes and platelets by inhalation prostaglandin E(1) in the pulmonary microvasculature of rats with monocrotaline-induced pulmonary hypertension.

The role of leukocytes (WBCs) and platelets (PLTs) in the pulmonary circulation may be important in the development of monocrotaline (MCT)-induced pulmonary hypertension in rats. We investigated the suppressive effects of long-term prostaglandin E(1) (PGE(1)) aerosol on the changes in WBCs and PLTs in the peripheral blood and the pulmonary microvasculature during the development of chronic pulmonary hypertension in MCT rats by real-time confocal scanning laser microscopy. The number of WBCs and PLTs in peripheral blood did not significantly change by inhalation of PGE(1). The number of WBCs and PLTs sequestered in the pulmonary microvasculature of rats subjected PGE(1) inhalation immediately after MCT injection rats with (MCT plus PGE(1) inhalation) significantly decreased from 1 to 4 weeks compared to rats not subjected to PGE(1) inhalation (p < 0.01). The pulmonary systolic arterial pressure and the weight ratio of the right ventricle to the intraventricular septum plus the left ventricle (RV/IVS + LV weight ratio or RV weight ratio) in rats with MCT plus PGE(1) inhalation significantly decreased compared to rats not subjected to PGE(1) inhalation (p < 0.01). The levels of peripheral CD62L-positive WBCs in rats with MCT plus PGE(1) inhalation significantly decreased from 1 to 2 weeks compared to rats not subjected to PGE(1) inhalation, but the levels of peripheral CD18 and CD49d-positive WBCs did not significantly change. We conclude that long-term inhalation of PGE(1) is a very useful therapy in chronic pulmonary hypertension, and the mechanism of suppressing pulmonary hypertension is associated with suppressive effects on sequestered WBCs, especially CD62-positive WBCs and PLTs in the pulmonary microvasculature.

Administration, Inhalation↗