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Biomedical subjects

O Inoue

Publications and source records attributed to O Inoue.

At least 199 records · Page 11Linked to original sources

Morphological studies on the mechanism of hepatocellular injury during acute phase of infection in marmosets inoculated with hepatitis A virus.

The histological changes during the acute phase of infection in the livers of marmosets inoculated with hepatitis A virus were examined. The acute phase was divided into four stages according to the liver enzyme changes and serological markers for the viral infection (Stage I, II, III, IV). Round cell infiltration in the portal tracts was first recognized in Stage I. Localization of parenchymal changes was predominantly periportal in Stage I, II, and IV, whereas the lesion was diffuse in Stage III. Hepatitis A virus antigen (HAVA) was widely distributed but spotty and the largest amount of HAVA was found in Stage II by immunofluorescent and immunoperoxidase study. By electron microscopy the endoplasmic reticulum was altered in the liver cells and in some area there was interaction between the hepatocytes and lymphocytes. These findings suggest that hepatocellular damages seen in this model are the result of immune response rather than cytotoxic effect.

Acute Disease↗

Radioactive N,N-dimethylphenylethylamine: a selective radiotracer for in vivo measurement of monoamine oxidase-B activity in the brain.

N-[methyl-14C]N,N-dimethylphenylethylamine (DMPEA) was synthesized and its availability as a selective radiotracer for in vivo measurement of mouse brain monoamine oxidase (MAO) activity was examined. Relatively high incorporation of labelled DMPEA into brain (about 10% of the injected dose/per gram of brain) was observed just after its injection; however, radioactive dimethylamine, a metabolite produced from labelled DMPEA in the brain 1 h after DMPEA injection, was reduced in a dose-dependent manner by pretreatment with various doses of a specific MAO-B inhibitor, 1-deprenyl, but was not reduced appreciably by pretreatment with a specific MAO-A inhibitor, clorgyline. Pretreatment with 1-deprenyl did not affect significantly the rate of incorporation of the radiotracer DMPEA into the brain, suggesting that reduction of the radioactivity in brain by this compound might be due to a decrease in the rate of production of the radioactive metabolite dimethylamine by brain MAO-B. The amount of the radioactive metabolite trapped in the brain was found to be proportional to the brain MAO-B activity remaining after pretreatment with 1-deprenyl. In vitro deamination of DMPEA by mouse brain MAO showed a higher sensitivity to inhibition by 1-deprenyl than that by clorgyline. These results indicate that DMPEA is a selective substrate for mouse brain MAO-B both in vivo and in vitro and that the positron emitter [11C]DMPEA might be used instead of [14C]DMPEA as a radiotracer for in vivo measurement of MAO-B activity in human brain.

Animals↗

Synthesis of N-methyl and N-11C-methyl spiperone by phase transfer catalysis in anhydrous solvent.

Spiperone, a butyrophenone neuroleptic drug, has been used in binding studies of dopamine receptors. Långström et al. developed N-11C-methyl spiperone, and, in cooperate with Wagner et al., made it possible to visualize the distribution of dopamine receptors in the human brain in vivo. In this paper, we independently developed another synthetic method of N-11C-methyl spiperone using the phase transfer catalyst in an anhydrous solvent. Separation of the product is feasible only by passing the reactant solution through a Millipore filter and injecting it onto high pressure liquid chromatography (HPLC). The time required for the synthesis and purification of N-11C-methyl spiperone from 11C-methyl iodide and spiperone was 20 min. Radiochemical yield exceeded 35% against 11C-methyl iodide without correcting decay of the radioactivity.

Anhydrides↗

Alterations in biodistribution of [3H]Ro 15-1788 in mice by acute stress: possible changes in in vivo binding availability of brain benzodiazepine receptor.

The biodistribution of [3H]Ro 15-1788 in control and stress-loaded mice (forced swimming) was compared. In control mice, carrier-free [3H]Ro 15-1788 was selectively and highly distributed in Bz receptor rich brain regions, while radioactivity in the brain was very low following administration of carrier-added tracer, which suggested that in vivo non-specific binding of this tracer was very low. Significant changes in biodistribution of carrier-free [3H]Ro 15-1788 were observed in stress-loaded mice, which strongly indicated that in vivo binding availability of Bz receptor in the brain was rapidly and reversibly reduced by acute stress. The degree of these changes was very dependent upon the stressful conditions, such as swimming duration and water temperature, and a significant alteration in biodistribution of [3H]Ro 15-1788 was particularly observed in the cerebral cortex. Simplified Scatchard analysis of in vivo binding of this tracer was performed, and results suggested that these alterations were mainly caused by changes in the Kd value rather than the Bmax value.

Animals↗

[Intracoronary thrombolytic therapy in Kawasaki disease and the usefulness of two-dimensional echocardiography in detecting intracoronary thrombi].

The main cause of death in patients with Kawasaki disease is myocardial infarction due to thrombotic occlusion of a coronary aneurysm. Intracoronary thrombolytic therapy was administered to dissolve the intracoronary thrombi of one infarcted patient and five non-infarcted patients who had massive intracoronary thrombus formations which were detected by two-dimensional echocardiography (2-D echo). Intracoronary injections of Urokinase ranged in dose from 2000 to 240000 IU. Systemic Urokinase infusions were performed for two patients in addition to intracoronary injections. Coronary angiography revealed complete obstruction of coronary aneurysms in two patients and partial obstruction in one patient. Although coronary angiography failed to visualize the intracoronary thrombi in three patients, 2-D echocardiography imaged massive thrombus formations in coronary aneurysms. Partial but significant coronary arterial recanalization was achieved after injecting Urokinase in a patient with myocardial infarction. Complete resolution of massive intracoronary thrombi was observed in three of five patients using 2-D echocardiography. A decrease in size of the intracoronary thrombus in one patient was observed after thrombolytic therapy. In another patient, the size of a thrombus did not change after thrombolytic therapy. Recurrence of thrombus formation in coronary aneurysms was observed in three patients using serial 2-D echocardiography. Urokinase was readministered to them and one showed significant reduction in the thrombus size. We conclude that 1) 2-D echocardiography is more sensitive and reproducible than coronary angiography. Therefore, serial 2-D echocardiography should be performed for patients with Kawasaki disease to detect intracoronary thrombus formation and to evaluate serial changes in thrombi. 2) Intracoronary thrombolytic therapy is useful for patients who have intracoronary thrombi to treat or prevent myocardial infarction.

Aneurysm↗

Increased o- and p-cresol/hippuric acid ratios in the urine of four strains of rat exposed to toluene at thousands-ppm levels.

Rats (Fisher, Wistar, Donryu and Sprague-Dawley strains) were exposed to 5 approximately 3500 ppm toluene for 8 h, and urine samples were analyzed for hippuric acid and cresols. While hippuric acid increased in proportion to the exposure concentration, a sharp increase in o-cresol excretion was observed at high toluene concentrations so that the o-cresol/hippuric acid ratio was elevated after 500 approximately 3500 ppm exposures. Changes in the p-cresol: hippuric acid ratio were less marked. There were strain differences in toluene metabolism. Fisher rats were highest and Sprague-Dawley rats lowest in o-cresol excretion and in the o-cresol: hippuric acid ratio, whereas Wistar rats excreted p-cresol most abundantly.

Animals↗

A new method for in vivo measurement of brain monoamine oxidase activity.

The radiotracers, C-14-N-methylphenylethylamine (MPEA) and N-methylphenylethanolamine (MPEOA) both rapidly entered mouse brain after their intravenous injection and were metabolized by brain monoamine oxidase (MAO) to C-14-methylamine and corresponding aldehydes. The labelled metabolite was trapped in the brain. Measurement of radioactivity showed that the amount of the metabolite produced in the brain from C-14-MPEA was proportional to the MAO activity remaining after combined treatment with a specific MAO-A inhibitor, clorgyline and a MAO-B inhibitor, 1-deprenyl, but not by treatment with either inhibitor alone. The rate of production of the labelled metabolite produced from C-14-MPEOA was highly sensitive to the extent of inhibition of MAO-B activity (with phenylethylamine as substrate) by pretreatment with 1-deprenyl, but was relatively insensitive to inhibitor clorgyline. This selectivity suggests that MPEOA is a specific substrate of MAO-B in mouse brain in vivo. The above results indicate that C-14-labelled N-methylphenylethylamine and N-methylphenylethanolamine derivatives can be used for measurement of brain MAO activity and that C-14-MPEOA is a specific substrate for mouse brain MAO-B. The value and possible applications of this method for measurement of MAO-B in brain under different physiological conditions are discussed.

2-Hydroxyphenethylamine↗

Variant strain of Propionibacterium acnes: a clue to the aetiology of Kawasaki disease.

By means of anaerobic culture for 3-4 weeks a variant strain of Propionibacterium acnes was isolated from one lymph-node biopsy specimen, and from blood samples of five of twenty-three patients with early Kawasaki disease, but from only one of fifteen blood samples from patients after 8 days' illness. No anaerobe was isolated from sixty age-matched controls with various disorders, but the same bacillus with the same serotype was isolated from house-dust mites from six patients' homes. Patients had significantly higher serum agglutination titres to these strains than controls. The antigen moiety of P acnes was found in the patients' circulating immune complexes. Inoculation of animals caused various inflammatory lesions, particularly in the reticuloendothelial system, and coronary arteritis, myocarditis, and endocarditis in one of them, suggesting that the bacillus is pathogenic. The culture filtrate of this strain showed toxicity in tissue culture. This variant strain of P acnes may have a causative role in Kawasaki disease and house-dust mites a role as vectors.

Acute Disease↗

Production system for 18F-2-deoxy-2-fluoro-D-glucose--a trial for automatic production.

We have developed a production system for 18F-2-deoxy-2-fluoro-D-glucose (18F-2FDG), which assures reliable production with easy handling and reduces radiation exposures to the operator. Chemical procedures in this system are the same as manual method developed in NIRS. This system has 2 operation modes; one is remote controlled manual operation mode and the other is microcomputer controlled automatic operation mode. In remote controlled mode, we tested this system 5 times and 18F-2FDG synthesized was supplied for clinical use once. The mean radiochemical yield of 18F-2FDG from the target gas recovery with decay time correction was 8%, that is the same as in the manual synthesis. It took about 2 hours from end of bombardment (EOB) to end of synthesis (EOS). Since this time is shorter than in manual synthesis, the available activity at EOS is increased.

Deoxy Sugars↗