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Biomedical subjects

Hiroshi Inoue

Publications and source records attributed to Hiroshi Inoue.

At least 235 records · Page 13Linked to original sources

Long-term usefulness of percutaneous intrapericardial fibrin-glue fixation therapy for oozing type of left ventricular free wall rupture: a case report.

This report describes a long-term survival case of left ventricular free wall rupture treated with percutaneous intrapericardial fibrin-glue fixation therapy. A 82-year-old woman was admitted to the emergency room because of vomiting and syncope diagnosed as acute posterolateral myocardial infarction complicated by cardiac tamponade. After her hemodynamic condition was stabilized by drawing off the bloody pericardial effusion, fibrin-glue was injected into pericardial space with the expectation that the glue would cover the oozing site of the left ventricular epicardium. After this therapy, the patient recovered and did not have any no recurrent cardiac events for 1 year. Serial echocardiographic studies revealed a preserved left ventricular function and no development of left ventricular restriction. This case suggests that percutaneous intrapericardial fibrin-glue fixation therapy is an effective treatment for the oozing type of left ventricular free wall rupture and that there is no risk of left ventricular restriction during long-term follow-up.

Administration, Cutaneous↗

Relation of circulating blood volume to left ventricular geometry in essential hypertension.

To investigate whether circulating blood volume contributes to left ventricular (LV) geometry, 60 outpatients with untreated, mild to moderate essential hypertension and 45 normotensives were studied. Based on echocardiographic LV mass index and relative wall thickness, four patterns of LV geometry, i.e., normal left ventricle, concentric remodeling, eccentric hypertrophy and concentric hypertrophy, were identified. Plasma volume and blood volume were measured by the 131I labeled human serum albumin technique. LV end-diastolic volume was greater in patients with eccentric hypertrophy than in the groups of patients with normal left ventricles, concentric remodeling, or concentric hypertrophy or in normotensive subjects. No differences were found in systolic function among the five groups. Both plasma volume and blood volume were decreased in the concentric remodeling group as compared with the other four groups. However, there were no differences in plasma volume or blood volume among the normal left ventricle, eccentric hypertrophy and concentric hypertrophy groups. These data indicate that a small LV chamber in cases of "concentric remodeling" may be related to decreased plasma and blood volumes, but an enlarged LV chamber in cases of "eccentric hypertrophy" is not likely to be related to either plasma or blood volume levels in mild to moderate untreated essential hypertension.

Adult↗

Aortic spontaneous echocardiographic contrast and hemostatic markers in patients with nonrheumatic atrial fibrillation.

OBJECTIVES: To determine the relationship between spontaneous echocardiographic contrast (SEC) in the descending thoracic aorta and plasma levels of hemostatic markers in patients with nonrheumatic atrial fibrillation (AF). DESIGN AND SETTINGS: A cross-sectional study at a university hospital. PATIENTS AND MEASUREMENTS: In 91 consecutive patients (mean +/- SE age, 70 +/- 1 years; 68 men) with nonrheumatic AF who underwent transesophageal echocardiography, plasma levels of markers for platelet activity (platelet factor 4 [PF4] and beta-thromboglobulin [beta-TG]), thrombotic status (thrombin-antithrombin III complex [TAT]), and fibrinolytic status (D-dimer and plasmin-alpha(2)-plasmin inhibitor complex [PIC]) were determined. RESULTS: Forty-three patients who had aortic SEC (AoSEC) were older (72 years vs 68 years; p < 0.05) and had a higher prevalence of chronic AF (88% vs 52%; p < 0.05) than 48 patients without AoSEC. TAT, PIC, and D-dimer levels were significantly higher in patients with AoSEC than in those without AoSEC, whereas PF4 and beta-TG levels were not different between the two groups. Although the prevalence of cerebral embolism did not differ between the two groups (23% vs 29%), the prevalence of peripheral embolism was higher in patients with AoSEC than in those without AoSEC (10% vs 0%; p < 0.05). Multivariate analysis revealed mitral regurgitation (odds ratio, 7.53; p < 0.02), SEC in the left atrium (odds ratio, 2.14; p < 0.02), and aortic atherosclerosis (odds ratio, 1.87; p < 0.04) emerged as independent predictors of AoSEC. CONCLUSIONS: Patients with nonrheumatic AF who have AoSEC appear to have enhanced coagulation activity but not platelet activity. Intensive anticoagulation treatment might be required for these patients.

Aged↗

Effects of esophageal acid perfusion on cough responsiveness in patients with bronchial asthma.

STUDY OBJECTIVES: The effect of gastroesophageal reflux (GER) on cough responsiveness in patients with bronchial asthma has yet to be studied in significant detail. The purpose of this study was to assess the effect of distal esophageal acid perfusion on cough responsiveness in patients with bronchial asthma. PATIENTS AND INTERVENTIONS: In seven patients with mild persistent bronchial asthma (mean +/- SD age, 57.7 +/- 3.7 years; four women and three men), esophageal pH was monitored by a pH meter and cough responsiveness was evaluated by single-breath aerosol inhalation of capsaicin with increasing dosage from 0.30 to 9.84 nmol. Simultaneously, esophageal perfusion was performed through an esophageal tube filled with either saline solution or 0.1 N hydrochloric acid (HCl), the order of which was selected at random, in 1-week intervals. Results were expressed as the lowest concentration of capsaicin eliciting three coughs (PD3). Spirometry was also performed during esophageal pH monitoring. RESULTS: A significant decrease in the geometric mean of log PD3 was observed during distal esophageal HCl perfusion (0.45 +/- 0.04 nmol) compared with that of the saline solution perfusion (0.04 +/- 0.06 nmol) [p < 0.01]. However, no significant changes were observed either in FVC, FEV1, or peak expiratory flow during the periods of the saline solution or HCl perfusion. CONCLUSION: The present data demonstrate that an increase in cough responsiveness may be induced when HCl stimulates the distal portion of esophagus in patients with bronchial asthma, suggesting that the GER would be one of the important factors that influence asthmatic status.

Aerosols↗

Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and beta-adrenergic desensitization in heart failure after myocardial infarction in rats.

One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of beta-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by 131I-metaiodobenzylguanidine (MIBG), beta-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to beta-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of beta-adrenergic pathway in this model of heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

Unregulated elevation of glutamate dehydrogenase activity induces glutamine-stimulated insulin secretion: identification and characterization of a GLUD1 gene mutation and insulin secretion studies with MIN6 cells overexpressing the mutant glutamate dehydrogenase.

Glutamate dehydrogenase (GDH) is important in normal glucose homeostasis. Mutations of GDH result in hyperinsulinism/hyperammonemia syndrome. Using PCR/single-strand conformation polymorphism analysis of the gene encoding GDH in 12 Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy (PHHI), we found a mutation (Y266C) in one PHHI patient. This mutation was not found in any of the control or type 2 diabetic subjects. The activity of the mutant GDH (GDH266C), expressed in COS-7 cells, was constitutively elevated, and allosteric regulations by ADP and GTP were severely impaired. The effect of the unregulated increase in GDH activity on insulin secretion was examined by overexpressing GDH266C in an insulinoma cell line, MIN6. Although glutamine alone did not stimulate insulin secretion from control MIN6-lacZ, it remarkably stimulated insulin secretion from MIN6-GDH266C. This finding suggests that constitutively activated GDH enhances oxidation of glutamate, which is intracellularly converted from glutamine to alpha-ketoglutarate, a tricarboxylic acid cycle substrate, which thereby stimulates insulin secretion. Interestingly, insulin secretion is also exaggerated significantly at low glucose concentrations (2 and 5 mmol/l) but not at higher glucose concentrations (8--25 mmol/l). Our results directly illustrate the importance of GDH in the regulation of insulin secretion from pancreatic beta-cells.

Adenosine Diphosphate↗

Role of the insulin receptor substrate 1 and phosphatidylinositol 3-kinase signaling pathway in insulin-induced expression of sterol regulatory element binding protein 1c and glucokinase genes in rat hepatocytes.

The mechanism by which insulin induces the expression of the sterol regulatory element binding protein 1c (SREBP-1c) and glucokinase genes was investigated in cultured rat hepatocytes. Overexpression of an NH(2)-terminal fragment of IRS-1 that contains the pleckstrin homology and phosphotyrosine binding domains (insulin receptor substrate-1 NH(2)-terminal fragment [IRS-1N]) inhibited insulin-induced tyrosine phosphorylation of IRS-1 as well as the association of IRS-1 with phosphatidylinositol (PI) 3-kinase activity, whereas the tyrosine phosphorylation of IRS-2 and its association with PI 3-kinase activity were slightly enhanced. The equivalent fragment of IRS-2 (IRS-2N) prevented insulin-induced tyrosine phosphorylation of both IRS-1 and IRS-2, although that of IRS-1 was inhibited more efficiently. The insulin-induced increases in the abundance of SREBP-1c and glucokinase mRNAs, both of which were sensitive to a dominant-negative mutant of PI 3-kinase, were blocked in cells in which the insulin-induced tyrosine phosphorylation of IRS-1 was inhibited by IRS-1N or IRS-2N. A dominant-negative mutant of Akt enhanced insulin-induced tyrosine phosphorylation of IRS-1 (but not that of IRS-2) and its association with PI 3-kinase activity, suggesting that Akt contributes to negative feedback regulation of IRS-1. The Akt mutant also promoted the effects of insulin on the accumulation of SREBP-1c and glucokinase mRNAs. These results suggest that the IRS-1-PI 3-kinase pathway is essential for insulin-induced expression of SREBP-1c and glucokinase genes.

Animals↗

[The efficacy of intravenous theophylline injection for treatment of acute exacerbations of bronchial asthma].

The efficacy of the intravenous injection of aminophylline for treatment of acute exacerbations of bronchial asthma has been recognized since 60 years ago by many reports. It has been published on the "Asthma Prevention and Management Guidelines 1998, Japan" as one of important treatment for acute exacerbations of bronchial asthma. An intravenously Administered Theophylline (IAT) was newly developed in Japan in 2000. Different from aminophylline, the theophylline is not combined with ethylenediamine. We investigated efficacy and safety of IAT. In the present study, subjects were 16 asthmatic patients with mild acute exacerbations of bronchial asthma. They were administered IAT (200 mg theophylline with 200 ml saline) intravenously for two hours. After administration of the IAT, PEF and FEV1 were increased significantly. And severity of asthma, Borg scale, wheezing and breath sound were improved significantly. It should be emphasized that none of the patients treated in this study had any adverse symptom. The present study suggested that IAT is useful for patients with acute exacerbations of bronchial asthma.

Aged↗

[Drug-induced arrhythmias].

Drug-induced arrhythmias are commonly described as proarrhythmia, arrhythmogenesis or aggravation of arrhythmias. A variety of drugs including cardiotonic drugs (antiarrhythmics, digitalis, cathecholamines), psychiatric drugs(phenothiazines, antidepressants), and macrolide antibiotics would worsen or induce arrhythmias. Among them are bradyarrhythmias and tachyarrhythmias, especially torsade de pointes(TdP) resulting from QT prolongation. There exist some predisposing factors which could potentiate proarrhythmic effect of drugs. They include age, congestive heart failure, ischemic heart disease, renal or hepatic dysfunction, electrolyte disturbance and previous history of proarrhythmia. It should be, therefore, very cautious when drugs with potentially proarrhythmic effect are given to subjects with predisposing factors. Correction of these factors and prevention of bradycardia are important in the management of proarrhythmia and TdP can be treated by infusion of magnesium.

Anti-Bacterial Agents↗

Study of the causes of higher mortality rates from chronic liver diseases in Tokushima Prefecture.

Mortality rates from chronic liver diseases (CLD) such as liver cirrhosis and hepatocellular carcinoma have been reported to be higher in Tokushima prefecture, although its causes remain unclear. To clarify the causes of CLD in Tokushima prefecture, we evaluated the positive rates of HBs antigen and anti-HCV antibody and the mortality rates from CLD in patients with liver diseases and blood donors after dividing the entire Tokushima prefecture into 8 district boundaries of health centers. In addition, to evaluate the causes of the higher frequency of CLD and the relationship between the development of CLD and viruses, medical examinations were performed in 2 mountain villages in Tokushima prefecture where the drift of population was limited and the mortality rates from CLD differed from each other. As a result, it was found that HCV infection was the major cause of the higher mortality rates from CLD in Tokushima prefecture. Although there were marked regional differences in the mortality rates from CLD, they were mainly due to different rates of HCV infection.

Adult↗

Interferon-alpha enhances biological defense activities against oxidative stress in cultured rat hepatocytes and hepatic stellate cells.

Oxidative stress has been implicated as a cause of hepatic fibrosis, and hepatic stellate cells (HSCs), which are the most important collagen-producing cell types, have been reported to be activated by lipid peroxidation products. Antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) provide a defense system that plays a critical role in protecting the cell from free radical damage, particularly lipid peroxidation. To elucidate the antioxidant activity of interferon-alpha (IFN-alpha), the effects of IFN-alpha on rat hepatocytes undergoing oxidative stress and HSCs in primary culture as well as isolated rat liver mitochondria were examined. IFN-alpha was observed to dose-dependently increase the immunoreactive protein levels of copper, zinc-and manganese-dependent SOD as well as the enzyme activities of GPx, and decrease the lipid peroxidation product levels and oxidative burst both in stressed hepatocytes and activated HSCs; GPx activities, however, were not detected in the latter cells. IFN-alpha also inhibited HSC activation and lipid peroxidation in liver mitochondria. These findings suggest that IFN-alpha may enhance biological defense activities against oxidative stress and function as a potent fibrosuppressant by protecting hepatocytes and hepatic stellate cells from lipid peroxidation in vivo.

Actins↗

[Brugada syndrome occurring in an identical twin: a case report].

A 51-year-old man was admitted for evaluation of palpitation and syncope. Electrocardiography showed right bundle branch block with ST segment elevation. Intravenous administration of pilsicainide(50 mg) converted the saddle-back type into coved type ST elevation. Ventricular fibrillation was induced with double extrastimuli applied to the right ventricular outflow tract. His identical younger twin had neither symptoms nor abnormality by electrocardiography. Intravenous administration of pilsicainide(50 mg) induced no significant changes in the younger twin. Although SCN5A mutation is considered to be associated with Brugada syndrome, the present results suggest that the genetic factor is not the only factor responsible for the pathogenesis of Brugada syndrome.

Anti-Arrhythmia Agents↗

Prognostic score of gastric cancer determined by cDNA microarray.

PURPOSE: To estimate gastric cancer patients' prognosis more comprehensively,we tried to develop a prognostic scoring system using a cDNA microarray. EXPERIMENTAL DESIGN: RNA was extracted from tumor/normal paired samples of 43 patients with gastric cancer, and cDNA microarray hybridization was performed. RESULTS: We selected 78 genes that were differentially expressed between aggressive and nonaggressive groups with respect to five conventional pathological factors. Next, we determined a coefficient for each gene. Thereafter a prognostic score was calculated by summing-up the value for each gene. It ranged from -47 to 201 with a median of 114. There were two peaks in its distribution. Ten of 11 patients who were alive with no evidence of recurrence >5 years after the operation showed a score of <100 points, whereas all 19 patients who died of disease showed >100 points. In 13 patients who were alive but the follow-up time was <5 years, 2 of the 3 patients with >100 points revealed recurrent disease during the follow-up. CONCLUSIONS: These findings demonstrate that such a system with cDNA microarray can contribute to the comprehensive analysis of malignant behavior of the tumor and may provide accurate information on prognosis.

Blotting, Northern↗

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2000)].

From October 2000 to September 2001, we collected the specimen from 410 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various anti-bacterial agents and antibiotics and patients' characteristics. Of 499 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 493 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 73, Haemophilus infiuenzae 99, Pseudomonas aeruginosa (non-mucoid) 64, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 25, Moraxella subgenus Branhamella catarrhalis 21, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 53.8%. Vancomycin and arbekacin had the most potent activities against MRSA as observed in 1999. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 38.4% being consistent with that in 1999 (34.7%). PRSP accounted for 11.0% of the total, being more than that in 1999 (3.0%). Carbapenems had strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 73 strains at 0.125 microgram/ml. Generally, all drugs had strong activities against H. influenzae with MIC80s of 8 micrograms/ml or less. The drug that had the strongest activity against H. infiuenzae was levofloxacin, which inhibited the growth of 94 of the 99 strains at 0.063 microgram/ml. Tobramycin had a strong activity against P. aeruginosa (both mucoid and non-mucoid) with MIC80 of 1 microgram/ml. The mucoid strain was little isolated (14 strains) but the susceptibilities to all drugs were better than the non-mucoid strain. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and the MIC80S were 2 micrograms/ml or less. Particularly, cefpirome, cefozopran, and levofloxacin had strong bactericidal activities against K. pneumoniae with MIC80s of 0.125 microgram/ml, and cefotiam, second-generation cephems, also had a favorable activity being MIC80 of 0.25 microgram/ml. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or less. The drug having the strongest activity was imipenem and levofloxacin inhibiting all 21 strains at 0.063 microgram/ml. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (44.4%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 38.0% and 31.7% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (18.3%) and S. pneumoniae (16.1%). In contrast, H. infiuenzae (20.4%) and P. aeruginosa (both mucoid and non-mucoid: 16.7%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from all the patients were S. pneumoniae (24.3%) and H. infiuenzae (26.7%). The frequency of isolated S. pneumoniae tended to decrease with the increase in the number of administration days while that of isolated H. infiuenzae did not. The frequency of isolated P. aeruginosa tended to increase with the duration of administration. The isolated bacteria were comparable between the patients already treated with penicillins and cephems. In the patients treated with aminoglycosides, macrolides, and quinolones, P. aeruginosa was most frequently isolated (33.3 to 40.0%).

Anti-Bacterial Agents↗

[A possible role of anti-endothelial cell antibody in the sera of MCTD patients on pulmonary vascular damage relating to pulmonary hypertension].

OBJECTIVES: Pulmonary hypertension (PH) is one of the major fatal causes in patients with mixed connective tissue disease(MCTD), which showed remarkable angiopathy from large to small vessels in the lungs. However, the etiology of PH in MCTD is still unknown. Even the lung tissues of MCTD patients without overt clinical PH represent minor vascular damages such as microthrombus or slight intimal thickening. These findings suggest some serum factors cause endothelial cell damage especially to pulmonary micro vessels, which leads to PH in MCTD. To elucidate the mechanisms of PH in MCTD we studied the anti-endothelial cell antibodies (AECA) in the sera of MCTD patients, which are considered to correlate with activity in some collagen diseases, and compared the three kinds of endothelial cells, especially the effects on pulmonary endothelial cells. MATERIALS AND METHODS: Sera from 14 MCTD patients who satisfied the Kasukawa's criteria in Japan including 4 cases of PH, 8 cases of non-PH and 3 untreated cases, and 5 healthy controls were analyzed as follows: (1) AECA to human pulmonary arterial endothelial cells (HPAEC), pulmonary microvascular endothelial cells (HMVE-L) and human aortic endothelial cells(HAEC) were analyzed by an indirect immunofluorescence method using flow cytometry. (2) Effects of MCTD patients' and healthy controls' sera on cell proliferation and induction of apoptosis on cultured HPAEC were investigated by methods of MTS and TUNEL. (3) A cytotoxic effect of patients' sera in combination with activated NK cells on HPAEC were studied by a method of LDH concentration. RESULTS: (1) Patients' sera from MCTD have IgG type AECA, and sera from MCTD patients with PH showed a higher intensity of AECA compared with non-PH and control cases (P < 0.01). (2) Only patient's sera revealed no potency of cell proliferation and induction of apoptosis in every kinds of endothelial cells compared with controls. (3) Sera from MCTD patients with PH, and from untreatment patients were high intensity of AECA, which shows cytotoxicity by addition of activated NK cells. CONCLUSIONS: Apoptosis of pulmonary arterial endothelial cells induced by AECA in combination with activated NK cells may be the fist step of vascular damage associated with pulmonary hypertension in patients with MCTD.

Adult↗

Susceptibility-induced changes in signal intensity from spin-echo versus gradient-echo sequences.

This manuscript describes a study of the evaluation of T2 and T2* changes in a hypervascular tumor model (hemodialyzer phantom) under conditions simulating dynamic perfusion study. The measured 1/T2* was strongly dependent on the compartmentalization of contrast material within the model, whereas the observed 1/T2 was not. Gradient-echo magnetic resonance (MR) imaging may be more suitable than a spin-echo MR imaging for the evaluation of tumor vascularity.

Contrast Media↗