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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

[Percutaneous balloon valvuloplasty for congenital aortic valve stenosis].

We performed percutaneous balloon aortic valvuloplasty for 10 patients with congenital aortic valve stenosis aged from 2 to 17 years and a 54-day-old infant with critical stenosis. The retrograde single balloon technique was used for 6 patients including the infant; the retrograde double balloon technique was used for 3 patients; and both techniques for 2 patients. The valvuloplasty was effective for 10 patients except for the infant in terms of the peak systolic pressure gradient between the left ventricle and aorta (from 80.6 +/- 21.9 to 29.4 +/- 17.0 mmHg). Follow-up cardiac catheterizations one year after valvuloplasty in 3 patients and 3 years after valvuloplasty in one patient disclosed no re-stenosis. Aortic regurgitation newly developed in one patient and advanced Sellers' classification I in 3 patients, however, all of them were asymptomatic and did not progress further. In the infant with critical stenosis, sufficient dilatation could not be achieved and acute myocardial infarction mainly at the lateral wall of the left ventricle developed during the valvuloplasty. He died 3 days after the valvuloplasty. The double balloon technique was found to be superior to the single balloon technique with the latter being ineffective in 2 cases, because the fixation of the balloon at the annulus was very difficult. Double balloon technique has low risk of vascular trauma and is applicable to a large sized annulus, because it enables blood supply between the 2 balloons during the inflation period.

Adolescent

[Consideration of simultaneous combination chemotherapy--employing a sensitivity test in Dunn osteosarcoma and NR fibrosarcoma by intra-test tube contact of tumor cell suspension, and subcutaneous inoculation].

Fundamental concepts of combination multi-drug chemotherapy have not been well recognized from the aspects of chemo-sensitivity test upon malignant tumors. A chemo-sensitivity test by in-vitro bioassay for Dunn osteosarcoma and NR fibrosarcoma was developed by us to study the simultaneous interactions between two anticancerous agents. 0.1 ml of cell suspension of either mouse sarcoma was immersed in 0.4 ml of RPMI 1640 cell culture medium containing an anticancerous agent such as Mitomycin (MC), Cyclophosphamide (CPM), Vincristine (VC), Bleomycin (BM), 5-FU, Adriamycin (ADM), Cisplatin (CDDP) or Methotrexate (MTX) in a test-tube, and incubated at 37 degrees C for 3 or 6 hours. Then, the sedimented cell suspension of 0.1 ml was inoculated subcutaneously in the dorsum of C3H mouse which provided 4 sites for 4 different sensitivity tests. In 3 weeks, sensitivities of the anticancerous agents were evaluated as positive sensitivity if no growth of the tumor was observed, or negative sensitivity if the growth of more than 10 mm in diameter was observed. Then, the determination of antitumorous effect on 2-drug combination out of the 8 anticancerous agents, were performed on each mouse sarcoma by the same method. In Dunn osteosarcoma or NR fibrosarcoma, the combination of 2 sensitivity-positive agents revealed no apparent synergistic effects. In any combinations of one sensitivity-positive agent with the other sensitivity-negative agent, except the combinations with CPM which possessed mighty antitumorous effect, apparent reduction of antitumorous effects was observed. The combination of 2 sensitivity-negative agents never produced any antitumorous effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Biological monitoring of occupational exposure to isopropyl alcohol vapor by urinalysis for acetone.

The relationship of the intensity of occupational vapor exposure to isopropyl alcohol (IPA) with urinary excretion of acetone and unmetabolized IPA was studied in 99 printers of both sexes, who were exposed to up to 66 ppm IPA (as time-weighted average), together with toluene, xylenes, methyl ethyl ketone and/or ethyl acetate. Acetone and IPA concentrations in urine were studied also in 34 non-exposed subjects. Acetone was detectable in the urine of most of the non-exposed, and the urinary acetone concentration increased in proportion to the IPA exposure intensity (r = 0.84 for observed, non-corrected values), whereas the correction for creatinine concentration or specific gravity of urine did not give a larger correlation coefficient. IPA itself was not found in the urine of the non-exposed, and was detectable in urine of only those who were exposed to IPA above a certain level, e.g. 5 ppm. The present study results suggest that urinary acetone is a valuable index for biological monitoring of occupational exposure to IPA as low as 70 ppm.

1-Propanol

Effect of reserpine on the brain uptake of carbon 11 methamphetamine and its N-propagyl derivative, deprenyl.

The enantiomers of methamphetamine (MAMP) and its N-propagyl derivative, deprenyl, were labelled with carbon 11, and the tissue distribution of these labelled compounds in mice was studied. Both enantiomers of 11C-MAMP rapidly entered into the brain and then disappeared according to a single exponential curve. The enantiomers of 11C-deprenyl were also rapidly distributed to various organs in the same manner. With regard to elimination, however, a stereoselective, long-term retention of radioactivity in the brain, heart and lung, due to its irreversible binding with monoamine oxidase B, was observed for L-11C-deprenyl. In reserpinized mice, the initial brain uptake of both the L and D forms of 11C-MAMP was significantly decreased. On the other hand, the brain uptake of both enantiomers of 11C-deprenyl was slightly increased by pretreatment with reserpine. A significant and non-stereoselective elevation of the lung uptake of 11C-deprenyl was also seen in reserpinized mice. In addition, both the relative tissue distribution and ratios of radioactivity in the brain compared with blood or heart at 1 and 5 min after the injection of 11C-labelled methanol in mice were not changed by reserpine. These results indicate that the transport or binding processes of these amines rather than the blood flow might be altered by reserpine. There would be an important role of the pKa values of amines in both processes. The reduction of brain uptake as well as the change in ratio between brain and heart of L-11C-MAMP in reserpinized mice 1 min after injection were reversed by treatment with amphetamine in a dose-related manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Valvular heart disease in Kawasaki syndrome: incidence and natural history.

To elucidate the incidence and natural history of valvular heart disease in Kawasaki syndrome, we analyzed patients who were found to have a new heart murmur after the onset of the disease. Among 1215 patients we found 13 (1.1%) with valvular disease (12 with mitral regurgitation and one with aortic regurgitation). We compared these patients with 30 who did not have valvular lesions. The duration of fever was longer and the incidence of coronary artery lesions significantly higher than in those without valvular disease. Heart murmurs disappeared within 2 months after the onset of valvular heart disease in five patients, whereas in another six, all involving valve prolapse, they persisted for 2 years or more. We postulate that two different mechanisms may be responsible for the variation in the duration of valvular heart disease: one, which disappeared spontaneously, was attributed to pancarditis; the other, which persisted, was due to dysfunction in valve and papillary muscles as a result of ischemia.

Angiography

Effect of desipramine on dopamine receptor binding in vivo.

Effect of desipramine (given i.p. 30 min prior to the tracer injection) on the in vivo binding of 3H-SCH23390 and 3H-N-methylspiperone (3H-NMSP) in mouse striatum was studied. The ratio of radioactivity in the striatum to that in the cerebellum at 15 min after i.v. injection of 3H-SCH23390 or 45 min after injection of 3H-NMSP were used as indices of dopamine D1 or D2 receptor binding in vivo, respectively. In vivo binding of D1 and D2 receptors was decreased in a dose-dependent manner by acute treatment with desipramine (DMI). A saturation experiment suggested that the DMI-induced reduction in the binding was mainly due to the decrease in the affinity of both receptors. No direct interactions between the dopamine receptors and DMI were observed in vitro by the addition of 1 mM of DMI into striatal homogenate. Other antidepressants such as imipramine, clomipramine, maprotiline and mianserin also decreased the binding of dopamine D1 and D2 receptors. The results indicated an important role of dopamine receptors in the pharmacological effect of antidepressants.

Animals

Production of 3-N-[11C]methylspiperone with high specific activity and high radiochemical purity for PET studies: suppression of its radiolysis.

3-N-[11C]methylspiperone(11C-NMS, molecular weight = 409 for 12C-NMS) has been prepared automatically with high specific activity (37 +/- 18 GBq/mumol at EOS) for the measurement of dopamine D2 receptors in the human brain with a positron camera. It was observed that the radiochemical purity of 11C-NMS decreased from 97.8% (in HPLC eluate) to 83.5% (in saline, after the dispensing procedure, at 29 min from EOS), and to 79.9% in a further 59 min and that another 11C-labelled compound with a molecular weight of 425 (as a 12C-labelled compound) was formed. It was also observed that an aqueous solution of carrier methylspiperone (NMS) decomposed on 60Co irradiation and, using the same analytical conditions, gave the compound with the same retention time and the same molecular weight as 11C-NMS gave. The G-value of NMS decomposition by 60Co irradiation was estimated to be about two in an aqueous solution. The decomposition of 11C-NMS was suppressed remarkably by the addition of hydroxyl radical scavengers such as potassium iodide, and accelerated slightly by a hydrated electron scavenger such as sodium nitrate. Therefore, it was assumed that the hydroxyl radical generated by the radiolysis of water played an important role in the decomposition of 11C-NMS in the aqueous solution. Polysolvate-80 and ethyl alcohol were used as i.v. injectable additives to protect 11C-NMS against decomposition. In 47 routine productions, 2.7 +/- 1.7 GBq of 11C-NMS aqueous solutions ready for i.v. injection have been produced at 98.3 +/- 1.0% radiochemical purity using an automated synthesis apparatus. The products were used for clinical purposes with a positron camera and animal experiments.

Brain

A study on the optimal dose of aspirin therapy in Kawasaki disease--clinical evaluation and arachidonic acid metabolism.

Aspirin is the basic treatment for Kawasaki disease, however its optimal dose is controversial. We investigated the therapeutic efficacy of high-dose (100 mg/kg/day, n = 30) versus low-dose (30 mg/kg/day, n = 30) aspirin. Duration of fever, transaminase, plasma thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) levels were compared before enrollment and on days 4, 7 and 14. In the high-dose group, duration of fever was significantly shorter than that of low-dose group (3.2 +/- 1.8 versus 5.4 +/- 4.3 days, p less than 0.05), however, serum glutamic pyruvic transaminase levels were elevated (157.4 +/- 187.7 versus 48.0 +/- 58.2I.U./liter, p less than 0.005). No differences in the incidence of coronary artery lesions were observed (5 of 30 versus 7 of 30). Plasma TxB2 production was completely blocked in both groups, plasma 6-keto-PGF1 alpha levels in the high-dose group on day 14 was lower than that in the low-dose group (39 +/- 26 versus 160 +/- 207 pg/ml, p less than 0.05). This latter observation suggest that high-dose therapy may be disadvantageous as anti-thrombotic treatment, and supports the notion that low dose therapy is safe in the acute stage of Kawasaki disease.

Arachidonic Acid

Biliary excretion of metabolites of baicalin and baicalein in rats.

Biliary excretion of metabolites of baicalin, present in Scutellariae Radix, was investigated using rats. The bile of rats administered baicalin orally was shown to contain five major metabolites, which were identified as baicalein 6-O-beta-glucopyranuronoside (M1), 6-O-methyl-baicalein 7-O-beta-glucopyranuronoside (oroxylin A 7-O-beta-glucuronide (M2], baicalein 7-O-beta-glucopyranuronoside (M3), 6-O-beta-glucopyranuronosyl- baicalein 7-O-sulfate (M4), and baicalein 6,7-di-O-beta-glucopyranuronoside (M5) on the basis of chemical and spectroscopic evidence. The bile of rats treated with baicalein also contained the above metabolites. Slower biliary excretion of the metabolites after baicalin administration suggested that it was absorbed as baicalein after hydrolysis in the gastrointestinal tract. The total cumulative amounts of the five metabolites excreted in the bile during 30 h after oral administration of baicalin and that of baicalein were approximately 54% and 40% of the doses, respectively. In addition the bilary metabolites of both drugs were shown to be mainly composed of M5 and M4, which have high polarity and large molecular weight.

Animals

Relationship between vapor exposure and urinary metabolite excretion among workers exposed to trichloroethylene.

The exposure-excretion relationship was investigated in 140 trichloroethylene (TRI)-exposed workers and 114 nonexposed controls. The time-weighted average intensity of exposure to TRI during the shift as measured by the diffusive sampling method was compared with metabolite levels in the urine collected at the end of the shift in the second half of a working week, when the urinary metabolite levels are expected to reach a maximum. The TRI levels in breathing zone air of the exposed workers were mostly below 50 ppm. The urinary metabolite levels (i.e., total trichloro-compounds, trichloroethanol, and trichloroacetic acid) increased as a linear function of the TRI exposure. The relationship between the two exposure indicators was statistically significant in men, women, and both combined. The cross-sectional balance study at the end of the shift revealed that about 4% of TRI absorbed will be excreted at the end of the shift, in agreement with the long biological half-life of this chlorinated hydrocarbon solvent. A possible ethnic difference in the metabolism of TRI is discussed.

China

Dose-excretion relationship in tetrachloroethylene-exposed workers and the effect of tetrachloroethylene co-exposure on trichloroethylene metabolism.

Personal monitoring of 8-hour time-weighted average intensity of exposure with diffuse samplers and analysis of shift-end urine for total trichloro-compounds (TTC) and other metabolites were conducted in two groups of workers in China, one (121 subjects) exposed to tetrachloroethylene (TETRA) alone, and the other (38 subjects) exposed to a mixture of TETRA and trichloroethylene (TRI). Urinalysis was also performed on samples from 103 non-exposed controls. A linear exposure-excretion relationship could be observed in both groups of workers. Comparison of these results with those of Japanese TETRA-workers suggested the presence of ethnic difference in TETRA metabolism. Urinary metabolite levels were markedly lower in the mixed (TETRA + TRI) exposure group as compared to previous findings in a group exposed to TRI alone. The observation indicates that metabolism of TRI is suppressed by the co-exposure to TETRA in humans.

Air Pollutants, Occupational

Detection of benzodiazepine receptor occupancy in the human brain by positron emission tomography.

Benzodiazepine receptor occupancy in the brain following oral administration of clonazepam (CZP) with a dose of 30 micrograms/kg in six healthy young men and a further dose of 50 micrograms/kg in one of the subjects was estimated by carbon-11 labeled Ro15-1788 and positron emission tomography (PET). The effects of CZP on the latency of auditory event-related potentials (P300) were also studied. Overall brain 11C uptake was depressed and the % inhibition of 11C uptake in the gray matter of the brain at 30 min after [11C]Ro15-1788 injection was 15.3-23.5% (mean, n = 6) following 30 micrograms/kg CZP when compared with that in the control experiment without any previous treatment. The 11C uptake in the cerebral cortex in the subject who received both doses decreased in a dose-related manner after 30 micrograms/kg and 50 micrograms/kg CZP. The P300 latency was prolonged significantly by 30 micrograms/kg CZP [31.6 +/- 16.3 ms (mean +/- SD, n = 6), P less than 0.05]. The P300 latency in the same subject was prolonged in a dose-related manner by 30 micrograms/kg and 50 micrograms/kg CZP. The technique using [11C]Ro15-1788 and PET permits comparison of the pharmacological effects with the percentage of receptor sites which benzodiazepines occupy in the human brain. P300 also seems to be useful to investigate the pharmacological effects of benzodiazepines.

Adult