Biomedical subjects
Publications and source records attributed to T Fukuda.
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The chronic administration of ethionine, an analogue of methionine and alkylating hepatocarcinogen, to rats resulted in the decrease of hepatic drug metabolizing enzyme activities and cytochrome P-450 content. In contrast, the activity of hepatic heme oxygenase, a first enzyme of heme degradative pathway, was increased following ethionine administration. delta-Aminolevulinic acid (ALA) synthetase, a key enzyme of heme biosynthesis pathway, was also increased except during 9 to 15 weeks of the experimental period. Changes of cytochrome P-450 content and heme oxygenase activity were proportional to the carcinogen provided period. Further, ethionine induced neoplastic nodules showed more profound changes in heme oxygenase, ALA synthetase and drug metabolizing enzyme activities than the surrounding liver. Similar changes in the enzyme activities were also obtained by a single administration of ethionine to rats and these effects were dependent upon dose levels of the carcinogen except ALA synthetase activity. These results revealed that ethionine is a mild inducer of hepatic heme oxygenase. It is thus likely that induction of heme oxygenase produced by ethionine could lead to the decrease of cytochrome P-450 and drug metabolizing enzyme activities in the liver. The decrease of heme availability due to induction of heme oxygenase by ethionine may be one of the explanations for the decrease of cytochrome P-450 content under the experimental conditions.
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Six cases of congenital subscalp nodule associated with underlying cranium bifidum are reported. A plain skull roentgenogram showed a midline bone defect in the parieto-occipital region near the lambda. CT scan demonstrated neither brain malformation nor ventricular deformity except for the high position of the straight sinus. Cerebral angiography revealed an elongation of the vein of Galen and anomalous upward course of the straight sinus. At surgery, the tumor was solid and connected to a cord which extended intracranially via the cranium bifidum and blended with thickened arachnoid membrane either on the dorsal aspect of the midbrain or at the surface of the anterior vermis. Histologically, the tumor consisted in all cases of arachnoid cells and fibrous tissue with immature glial cells in one case. Possible pathogenesis of these tumors could be a result of the fetal nuchal bleb.
The effects on adriamycin cardiotoxicity of an immunoadjuvant, 2-[2-acetamido-2-deoxy-6-0-[10-(2,3-dimethoxy-5-methyl-1, 4-benzo-quinon-6-yl) decanoyl]-D-glucopyranos-3-0-yl]-D-propionyl-L-valyl D-isoglutamine methyl ester (QMDP-66), and a reference compound, ubiquinone-10, were studied in Wistar Kyoto (WKY) rats. Adriamycin, 1 mg/kg/day intra-peritoneally (i.p.) for 23 days, elicited cardiotoxicity, as judged by widening of the QRS complexes in ECGs. Electron microscopic examination of myocytes from the treated rats revealed many cytoplasmic vacuoles possibly originating from deranged endoplasmic reticula or mitochondria. In addition, the treatment significantly inhibited body weight gain, and decreased ventricular weight. QMDP-66 alone, 1 mg/kg/day i.p. for 23 days, had no effect on the parameters described above. When QMDP-66 (1 mg/kg/day, i.p.) or ubiquinone-10 (3 mg/kg/day, i.p.) was administered together with adriamycin, the widening of the QRS complexes was significantly depressed, and cytoplasmic vacuoles in myocytes were rarely observed. The QMDP-66 or ubiquinone-10 treatment, however, did not alleviate the decrease in body weight gain or ventricular weight due to adriamycin. Heart rate was not significantly changed by any of the treatments. These findings suggest that QMDP-66 is an effective antidote against adriamycin cardiotoxicity.
Decreased response of beta-adrenergic receptor has been considered to be one of the causes of increased responsiveness of the bronchi in asthma. Since beta-adrenergic receptor has two subtypes, beta 1 and beta 2, and the bronchodilating effect of beta stimulants is mediated by beta 2-receptor, responsiveness of the bronchi is expected to correlate to the cyclic AMP response of lymphocytes to a beta 2-stimulant. Responsiveness of the bronchi was expressed as respiratory threshold to acetylcholine (RT-Ach), which was the minimal concentration of acetylcholine solution to cause an initial decrease of FEV1 of more than 20% of the baseline value. Beta 1- and beta 2-responses were expressed as the increments of cyclic AMP content of 10(6) lymphocytes incubated with norepinephrine (beta 1-stimulant) and salbutamol (beta 2-stimulant). RT-Ach showed a significant correlation with the beta 2-cyclic AMP response of lymphocytes, but not with the beta 1-response among patients with asthma. Sixteen symptomatic patients on continuous beta-stimulants showed lower RT-Ach value and diminished beta 2-receptor activity of lymphocytes compared with 14 patients in remission. These results suggest that selective beta 2-adrenergic blockade may be one of the causes of bronchial hypersensitivity in asthma, though it should be noted that in this study beta-adrenergic responses were examined in lymphocytes and were compared with the responsiveness of the bronchi. Possible beta-receptor subsensitivity induced by administration of beta-stimulants is discussed.
The numbers of beta-adrenergic receptors on lymphocytes in normal subjects and asthmatic patients were measured by the use of [125I]hydroxybenzylpindolol. The numbers of beta-adrenergic receptors per lymphocyte in normal subjects, drug-free asthmatics and patients taking beta-stimulants were 1146 +/- 98, 845 +/- 114 and 582 +/- 47 sites/cell (mean +/- SE), respectively. The differences were statistically significant (P less than 0.05) among these groups, while no statistically significant differences were found in dissociation constants. A 42% decrease in the number of beta-adrenergic receptors per lymphocyte after administration of 6 mg/day of terbutaline for 7 days was noted in four volunteers. There was significant correlation (r = 0.68, P less than 0.01) between the number of beta-adrenergic receptors per lymphocyte and the percentage increase in blood sugar 20 min after subcutaneous injection of 4 micrograms/kg epinephrine. There was also significant correlation (r = 0.78, P less than 0.005) between the number of beta-adrenergic receptors per lymphocyte and the respiratory threshold for acetylcholine. These results suggest that beta-blockade and bronchial hypersensitivity in asthmatic patients may in part be due to a decreased number of beta-adrenergic receptors.
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Thioacetamide and one of its metabolite, thioacetamide-S-oxide, were shown to increase heme oxygenase and to inhibit delta-aminolevulinic acid (ALA) synthetase when administered in vivo to male rats. Concomitant with the increase of heme oxygenase and the decrease of ALA synthetase, concentration of cytochrome P-450 and drug metabolizing enzyme activities were decreased by in vivo administration of thioacetamide and thioacetamide-S-oxide to rats. The results of these studies indicate that thioacetamide and thioacetamide-S-oxide are not only inhibitor of ALA synthetase, but also inducer of heme oxygenase in rats. Further, thioacetamide-S-oxide is generally more effective than thioacetamide with respect to the effects on cytochrome P-450, ALA synthetase and heme oxygenase.
Effects of psychotropic drugs on the rage responses induced by electrical stimulation were investigated in cats with electrodes chronically implanted in the medial hypothalamus. Diazepam produced marked elevation in the threshold for directed attack and slight elevation in that for hissing. The inhibitory effect of etizolam on hissing was about 6 times as potent as that of diazepam. Anti-anxiety drugs such as diazepam, nitrazepam, lorazepam, clotiazepam and etizolam produced marked elevation in the directed attack threshold dose-dependently. The effect of chlorpromazine on directed attack was far less potent than that of anti-anxiety drugs. The anti-anxiety drugs used in this experiment had anti-pentetrazol activity in mice as well as muscle relaxant activity in cats. There were close correlations between the directed attack inhibition produced by the anti-anxiety drugs and both anti-pentetrazol activity and muscle relaxant activity. These results indicate that the above anti-anxiety drugs have a more potent inhibitory effect on the function of the medial hypothalamus than neuroleptic drugs. The inhibitory effect of anti-anxiety drugs on directed attack may be considered to correlate with clinical anti-anxiety effects.
An effective method for removing leukocytes and platelets from red blood cell concentrates (RBC) reconstituted with phosphate buffer solution was investigated in vitro. Reconstituted RBC were warmed at 37 degrees C for 1 hr. Neither leukocyte count nor platelet count was decreased by the treatment. When compared with whole blood, leukocytes present in the fractions below the buffy coat layer were significantly less than those of whole blood, while the distribution of platelets in reconstituted RBC was unchanged. It is suggested that the reduction of leukocytes in red blood cells below the buffy coat layer may contribute to the preparation of RBC with a poor leukocyte.
The M-mode scanning images of urethra, detrusor pressure and urine flow rate during voiding were recorded together on the line scan recorder, and allowed for plotting and calculation of some valuable urodynamic parameters by computer evaluation. This procedure will permit first application of M-mode scanning and new direction on urodynamics.
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Twelve patients with recurrent breast cancer were treated with Peplomycin monotherapy. Peplomycin was given intermittently with a dose of 10 mg intramuscularly twice a week. As side effects of Peplomycin, fever elevation in 75% (9/12), malaise in 67%, nausea and vomiting in 42%, anorexia in 42%, pulmonary toxicity in 8%, and loss of hair in 8%, were observed. Out of 8 evaluable cases, CR was obtained in 1, PR in 1, NC in 3, and PD in 3 cases, respectively.