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Biomedical subjects

O Inoue

Publications and source records attributed to O Inoue.

At least 109 records · Page 6Linked to original sources

Comparison of hepatitis C virus markers in patients with NANB hepatitis.

10 different HCV-specific assays and RT-PCR of the 5' untranslated region of HCV RNA were used to analyze sixty-four patients with chronic NANB liver disease. Po, CP-9 and C22 antigens are located in the putative core; C33c in the putative NS3; C100-3 in the putative NS3/4; KCL in the putative NS4/5 and C825 is located in the putative NS5. GOR protein is not part of the HCV genome, but antibodies to it appear to be present in response to a hepatitis C infection. Positive rates were 91% for Po, 89% for CP-9, 94% for C22, 97% for C33c, 88% for C100-3 (Ortho, EIA), 86% for C100-3 (Abbott, EIA), 84% for C100-3 (Ohtsuka, RIA), 88% for KCL, 59% for C825, 58% for GOR, and 83% for RT-PCR. There were 8 cases which were negative by all anti-C100 tests. 7 of these cases were positive by other anti-HCV markers and/or PCR suggesting the need for improved blood screening assays. There is a variation in the relative reactivity for different markers with different samples. Of the tests employed, anti C33c shows the highest positivity rate.

Adult↗

Effect of sedative drugs upon receptor binding in vivo.

Acute treatment with pentobarbital (PB), ethanol and flunitrazepam significantly decreased 3H-SCH 23390 binding in mouse striatum in a dose dependent manner. In contrast, no significant alterations in 3H-SCH 23390 binding in the cerebral cortex have been observed in mice treated with these sedative and hypnotic drugs. Flumazenil Ro15-1788) reversed the effect of flunitrazepam suggesting the reduction in dopamine D1 receptor binding in the striatum was mediated via GABA-Bz-Cl channel complex. Using kinetic analysis, it was found that such changes in dopamine D1 receptor binding in vivo were mainly due to changes in rates of ligand-receptor binding in vivo. Other non-site-specific drugs such as propanol and butanol also decreased 3H-SCH 23390 binding in vivo, depending on their lipophilicities. These results indicated that micro-environmental factors surrounding receptors, including cell membranes seem to have important roles in receptor binding in vivo. Both PB and flunitrazepam decreased muscarinic acetylcholine receptor binding in mouse cortex, striatum, hippocampus and other regions. Together with the fact that PB also altered 3H-Ro15-1788 binding in vivo, this suggested global changes in microenvironmental factors may occur due to these sedative drugs. In vivo quantitative analysis of neuroreceptors with positron emission tomography (PET) seems to have some potencies to reveal the neurochemical base of benzodiazepine dependence.

Animals↗

Vasodilatory response of the coronary arteries after Kawasaki disease: evaluation by intracoronary injection of isosorbide dinitrate.

OBJECTIVE: To determine coronary artery diameter change before and after an intracoronary infusion of isosorbide dinitrate in patients who have had Kawasaki disease, we performed coronary angiography in 188 such patients. PATIENTS AND METHODS: Four patient groups were studied. Groups 1 to 3 consisted of patients with Kawasaki disease: group 1 (the "normal" group; n = 65) had no coronary artery lesions; patients in group 2 had regression to normal of a coronary artery aneurysm after Kawasaki disease and were divided, according to the time since onset, into two subgroups, group 2-a (n = 20) being at an early stage after regression to normal (followed for 1.7 +/- 0.7 years) and group 2-b (n = 34) being at a later stage after regression (followed for 8.7 +/- 2.9 years); and group 3 (the "abnormal" group; n = 25) had persistent coronary artery aneurysm or stenosis or both. Group 4, the control group (n = 44), consisted of patients without Kawasaki disease who had congenital heart disease with normal coronary arteries. The coronary artery diameter change was calculated by the following formula: Percentage of change = (Diameter after infusion - Diameter before infusion)/Diameter before infusion x 100. RESULTS: The percentages of change in the coronary artery diameter after isosorbide dinitrate infusion were 16.2% +/- 13.4% (normal group), 11.3% +/- 7.2% (early-regression group), 7.8% +/- 8.3% (late-regression group), 6.8% +/- 7.8% (abnormal group), and 15.2% +/- 11.8% (control group). In the abnormal group, there was significantly poorer dilation than in the control and normal groups. The late-regression group also had significantly less change in diameter than did the control and normal groups (p < 0.05). CONCLUSIONS: These data suggest (1) that the coronary artery after Kawasaki disease becomes stiff not only in patients with persistent abnormal lesions but also in those with regressed aneurysms and (2) that stiffness of the coronary artery may be a risk factor for atherosclerosis.

Child↗

Balloon valvuloplasty for congenital aortic valve stenosis in an infant and children.

Percutaneous balloon aortic valvuloplasty (BAV) was performed in 14 patients, including one critically ill infant with congenital valvular aortic stenosis (AS). BAV was effective in 13 patients (except the infant). The peak systolic pressure gradient between the left ventricle (LV) and the ascending aorta decreased from 76.6 +/- 21.6 to 29.5 +/- 15.3 mmHg (P less than 0.001). Follow-up cardiac catheterization was performed for eight patients between 1 and 3 years (1.6 +/- 1.1 years) after BAV. Restenosis was found in only one patient, and the efficacy of BAV continued significantly. Aortic regurgitation developed or increased in severity in 5 of 13 children immediately after BAV. Any other severe complication was not observed. Dilatation by BAV was not sufficient for the infant with critical AS, and acute myocardial infarction (AMI) in the lateral wall of the LV occurred during the BAV procedure. The infant died 3 days after the procedure due to AMI. It was concluded that the retrograde double balloon technique was superior to the retrograde single balloon technique. In two cases, the single balloon technique was ineffective because it was impossible to fix the balloon at the aortic annulus. However, the double balloon technique was effective in every patient. BAV is effective for AS in children, and an optional repeat trial may enable BAV to be the first choice for AS. Although BAV may be effective for neonates and infants with critical AS as an emergency treatment, much attention must be paid during the procedure.

Adolescent↗

The internal thoracic artery and its branches after coronary artery anastomoses in pediatric patients.

The internal thoracic artery has been favored because of its superior early and late patency for coronary artery bypass grafting (CABG) in pediatric patients. We have studied the angiographic changes of the internal thoracic artery and its side branches before and after CABG with internal thoracic artery to the left anterior descending artery. The internal thoracic artery with remaining thymic or pericardial branches was patent but showed enlargement of the branches in the early period after the operation, and a postoperative exercise test suggested a remaining ischemic lesion in the bypass. Angiogram taken 1 year after CABG demonstrated the grown internal thoracic artery with disappearance of most of the side branches, which had been enlarged 1 month after the operation. Our findings suggest the importance of ligation of the whole proximal internal thoracic artery branches to maintain good early and late patency.

Child↗

[Effects of Kamikihi-To on autonomic imbalances in SART-stressed (repeated cold-stressed) mice].

The effects of Kamikihi-To (KMK), a traditional Chinese medicine, on autonomic imbalances were evaluated in SART-stressed (repeated cold-stressed) mice. These animals exhibited decreases in pain threshold and contraction of duodenum by acetylcholine, and they showed changes in their electrocardiogram and hematological parameters. All symptoms are thought to be caused by dysautonomia. KMK in dosages of 0.5 and 1.0 g/kg were administered to mice once a day for 8 consecutive days. SART stress was induced from the second day. KMK prevented the decrease in the pain threshold and contraction of the duodenum, although it had no effect on the electrocardiographic or hematological changes. KMK had no similar effect on unstressed mice. This data suggests that KMK might be useful for the treatment of clinical autonomic imbalances.

Acetylcholine↗

Reserpine-induced reduction of in vivo binding of SCH 23390 and N-methylspiperone and its reversal by d-amphetamine.

In order to clarify the role of endogenous dopamine in the binding of [3H]SCH23390 and [3H]N-methylspiperone to the mouse striatum in vivo, the effects of reserpine and the reversal of these effects by d-amphetamine were investigated. Radioactivity was measured in the striatum and cerebellum following i.v. injection of each ligand into control and drug-treated mice. The ratio of radioactivity in the striatum to that in the cerebellum, plotted as a function of time, showed a linear correlation. Pretreatment with reserpine 24 h prior to injection of tracer significantly decreased the in vivo binding of both [3H]SCH23390 and [3H]N-methyl-spiperone in a dose-dependent manner. Saturation experiments indicated that these changes in in vivo binding were due mainly to changes in apparent affinity rather than to the number of binding sites available. Administration of d-amphetamine to reserpine-treated mice reversed the effect of reserpine in a dose-dependent manner. Blockade of dopamine D1 receptors with SCH23390 did not prevent the reversal by d-amphetamine of [3H]N-methylspiperone binding in vivo; however, treatment with haloperidol did prevent the effect of d-amphetamine on [3H]SCH23390 binding. These results suggest that dopamine D2 receptor-mediated neurotransmission might itself regulate the binding of dopamine to receptors in vivo.

Animals↗

Difference in in vivo receptor binding between [3H]N-methylspiperone and [3H]raclopride in reserpine-treated mouse brain.

The in vivo binding of [3H]N-methylspiperone (NMSP) and [3H]raclopride was compared in mice treated with reserpine (5 mg/kg, 24 hr prior to the tracer injection). With both radioligands, selective accumulation of radioactivity in the striatum following intravenous injection was observed, whereas a relatively low accumulation and a rapid decline in radioactivity in the cerebellum was seen. Reserpine significantly decreased [3H]NMSP binding in vivo, however it increased [3H]raclopride binding. By compartment model analysis, it was found that the decrease in [3H]NMSP binding was primarily due to the decrease in the association rate (K3) and the increase in [3H]raclopride was due to the decrease in the dissociation rate (K4) in vivo. As both Kd and Bmax of dopamine D2 receptors have been reported to be unaltered by reserpine, these results suggested that some unknown factors except Kd and Bmax which influence on in vivo binding of receptors might be changed by reserpine. These results revealed that it is of importance to measure kinetics of ligand-receptor binding in vivo rather than static analysis. These two different types of radioligands can be combined to reveal functional roles of dopamine receptor in vivo, especially in the study of the human brain with positron emission tomography (PET).

Animals↗

Salicylate treatment in Kawasaki disease: high dose or low dose?

Salicylate is the basic therapy for Kawasaki disease, however its optimal dose is controversial. We investigated the therapeutic efficacy of high dose (100 mg/kg per day, n = 30) versus low dose (30 mg/kg per day, n = 30) salicylate. Duration of fever, SGPT, serum salicylate, plasma thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) levels were compared before enrollment and on days 4, 7 and 14 of treatment. In the high dose group, duration of fever was significantly shorter than that of the low dose group (3.2 +/- 0.3 versus 5.4 +/- 0.8 days, P less than 0.05), however, SGPT levels were significantly elevated (157 +/- 34 versus 48 +/- 11 IU/1, P less than 0.05). No differences in the incidence of coronary artery lesions were observed (5/30 versus 7/30). Plasma TxB2 production was completely blocked in both groups, and plasma 6-keto-PGF1 alpha levels in the high dose group on day 14 was lower than that in the low dose group (39 +/- 8 versus 159 +/- 65 pg/ml, P less than 0.05). SGPT and plasma 6-keto-PGF1 alpha correlated with serum salicylate concentration. These data suggest that high dose salicylate therapy may be disadvantageous as anti-thrombotic therapy, and supports the notion that low dose therapy is safe in the acute stage of Kawasaki disease.

6-Ketoprostaglandin F1 alpha↗

Age-related changes in human D1 dopamine receptors measured by positron emission tomography.

The effects of age on the binding parameters of 11C-SCH23390, the highly selective ligand for central D1 dopamine receptors, at specific binding sites in the brain were studied. Seventeen healthy male volunteers (20-72 years old) participated. Regional radioactivity in the brain was followed for 40 min by positron emission tomography (PET). A high accumulation of radioactivity was observed in the striatum and there was a conspicuous accumulation in the neocortex. A two-compartment model was used to obtain quantitative estimates of rate constants of association (K3) and dissociation (k4). The binding potential (k3/k4) of the dopamine D1 receptors in the striatum and frontal cortex decreased by 35% and 39%, respectively, with age. The value of k3 decreased by 58% in the striatum and 83% in the frontal cortex, whereas the value of k4 decreased by 35% in the striatum and 72% in the frontal cortex with age.

Adult↗

Swim stress alters in vivo binding of [3H]N-methylspiperone.

The effect of swim stress on the in vivo binding of [3H]N-methylspiperone in the striatum of the mouse was investigated. Mice were forced to swim for 5 min at 18 degrees C and the time course of radioactivity in the striatum and cerebellum, following intravenous injection of [3H]N-methylspiperone was measured. The ratio of radioactivity in the striatum to that in the cerebellum was plotted as a function of time for the estimation of in vivo binding to dopamine D2 receptors. Immediately after the swim stress, a significant decrease in binding to D2 receptors in vivo was observed. Neither the KD nor Bmax determined by in vitro binding were altered by swim stress. The time course of the changes in binding, within a 24 hr period, following the swim stress was also studied and a rapid reversal of binding, within 1 hr after the swim stress was observed. In vivo binding of [3H]N-methylspiperone in the cerebral cortex, which appeared to involve serotonin receptors, as well as D2 receptors, was not significantly altered by the swim stress. A saturation study of in vivo binding indicated that the decreases in binding to D2 receptors, due to swim stress, were primarily caused by changes in the apparent affinity rather than in the number of binding sites available in vivo. These results support the hypothesis that micro-environmental factors, including the diffusion barrier to the synapse, might be altered by swim stress.

Animals↗

Quantitative in vivo analysis of benzodiazepine binding sites in the human brain using positron emission tomography.

Central-type benzodiazepine binding sites were characterized in a single normal human subject, using positron emission tomography (PET) and the radiolabelled benzodiazepine antagonist, carbon-11 labelled flumazenil ([11C] Ro 15-1788). The subject was scanned using tracer alone and tracer plus 4 different concentrations of unlabelled Ro 15-1788, including one concentration of unlabelled Ro 15-1788, chosen to produce maximum displacement of [11C] Ro 15-1788 from specific binding sites. Concentrations of free, unmetabolized [11C] Ro 15-1788 in plasma were estimated using a simple extraction and ultrafiltration method. Radioactivity in the regional exchangeable pool in brain was estimated under non-saturation conditions from the ratio of radioactivity in brain to plasma, under saturation conditions and the kinetics of free ligand in plasma. The specific binding was, then, estimated by the difference between the total radioactivity in brain and exchangeable pool radioactivity. Scatchard analyses were performed to yield Bmax and Kd values under pseudo-equilibrium conditions, which was observed as an increase of specific binding/free with reduction in specific binding. In cerebral cortex and cerebellum, the Bmax values were about 62-73 nmol/l and the Kd values were 3.6-6 nM in the estimation of free ligand in plasma and 12-15 nM in the estimation of exchangeable pool in brain, as free in brain.

Adult↗

Intracoronary urokinase in Kawasaki disease: treatment and prevention of myocardial infarction.

The main cause of death in Kawasaki disease is myocardial infarction due to thrombotic occlusion of a coronary aneurysm. Intracoronary thrombolytic treatment was performed in 15 patients with Kawasaki disease with giant coronary aneurysms. Three patients had acute myocardial infarction, four demonstrated silent myocardial infarction, three suffered chest pain and five did not show ischemia features but had massive thrombus in the coronary aneurysms. Urokinase was infused into the coronary aneurysms as a bolus of 8,000 to 10,000 units/kg via a catheter over 10 minutes. Partial but significant coronary recanalization was achieved after injection of urokinase in a patient with acute myocardial infarction. Complete resolution of massive intracoronary thrombi was observed in 3 of 15 patents, and partial resolution was recognized in 4 cases. In 7 patients, the size of thrombus did not change. Recurrence of the thrombus was observed in 4 patients by serial two-dimensional echocardiography. Urokinase was readministered and two showed significant reduction in the thrombus. All patients have been followed for more than 2 years with longest 8 years (mean: 3.3 yrs), and none have had a recurrence of myocardial infarction or died. These findings suggest that intracoronary urokinase is useful for the treatment and prevention of myocardial infarction in Kawasaki disease.

Child↗

Prevalence of hepatitis B virus infection markers among factory workers in Beijing, China.

Nearly 1,000 serum samples were obtained from apparently healthy workers of both sexes in various factories in Beijing during 1988-1989 and were examined for hepatitis B virus infection markers by radioimmunoassay. The overall prevalence (all ages and both sexes combined) of cases positive for HBsAg, anti-HBs and anti-HBc were 3.7%, 36.6% and 37.7%, respectively and the rate of those negative to any of the three markers studied was 56.1%. The infection rate was lower than the values reported early in the 1980s for Beijing populations or the values for populations in other parts of China.

Adolescent↗

Hepatitis B virus prevalence in industrialized cities in China.

The prevalence of HBV infection was investigated by radioimmunoassay for HBsAg, anti-HBs and anti-HBc in over 1000 workers in large scale factories located in four industrial cities (Jinxi, Shanghai, Wuxi and Xian) in 1987 to 1990. The age dependency of the prevalence was not evident. The overall prevalence rate of those positive for any of the three markers was 62.6%. The rate was significantly (p < 0.01) higher than the rates found in Beijing in a previous study but lower than the values observed in earlier studies.

Adolescent↗