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Biomedical subjects

E Tanaka

Publications and source records attributed to E Tanaka.

At least 541 records · Page 30Linked to original sources

Suppressive effect of interferon inducer, polyriboinosinic acid-polyribocytidylic acid on induction of uridine diphosphate-glucuronyltransferases and monooxygenases in liver microsomes of rats.

The effect of polyriboinosinic acid-polyribocytidylic acid [poly(I).poly(C)] on glucuronyltransferase activities toward 4-nitrophenol and 4-hydroxybiphenyl in liver microsomes of Wistar rats was examined by its single or co-administration with 3-methylcholanthrene and phenobarbital. The increased 4-nitrophenol glucuronyltransferase activity by treatment with 3-methylcholanthrene was significantly suppressed following the co-administration with poly(I).poly(C), although the activity was not affected by the treatment with poly(I).poly(C) alone. In addition, 4-hydroxybiphenyl glucuronyltransferase activity decreased or tended to decrease by the treatment with poly(I).poly(C) alone, and the activity induced by phenobarbital was strikingly decreased following the co-administration with poly(I).poly(C). This result suggested that poly(I).poly(C) comprehensively decrease the induction of glucuronyltransferases regardless of their multiple forms. Furthermore, contents of cytochromes P-450 and b5 were also decreased by the treatment with poly(I).poly(C) alone or the co-administration with the inducers. Concomitantly, arylhydrocarbon hydroxylase and benzphetamine N-demethylase activities were significantly decreased by the treatment alone or the co-administration with the inducers. These findings supported a view that the suppressive effect of poly(I).poly(C) may be derived from the prevention of de novo synthesis of the apoprotein of the enzymes and/or the increased degradation.

Animals↗

Hepatic trimethadione-oxidizing capacity remains normal in patients with extrahepatic cholelithiasis.

In the present study, using trimethadione (TMO) as an indicator substrate, we estimated pre- and post-operative differences in hepatic drug-oxidizing capacity in patients with extrahepatic cholelithiasis. Only total and direct bilirubin values were significantly higher in preoperative patients than in the controls. After operative procedures, those parameters did not show significant differences from corresponding control values. The serum dimethadione (DMO)/TMO ratios estimated 4 h after administration of 4 mg/kg of TMO. Neither pre- nor post-operative serum DMO/TMO ratios were significantly different from those in the controls. These results suggest that the hepatic drug-oxidizing capacity in patients with extrahepatic cholelithiasis remains unchanged even though the bilirubin level deviated from normal.

Bilirubin↗

Effect of co-administration of interferon inducer, polyriboinosinic acid-polyribocytidylic acid, with SKF 525-A on hepatic drug metabolizing enzymes of rats.

The protective effect of SKF 525-A on the suppression of cytochrome P-450 content and monooxygenase activities by treatment with CoCl2 and polyriboinosinic acid-polyribocytidylic acid [poly(I.C] was compared as a part of studies of suppression of drug metabolizing enzymes by interferon inducers. Induction of heme oxygenase activity by CoCl2 and poly (I.C) was not altered by simultaneous treatment with SKF 525-A. Depression of cytochrome P-450 content and benzphetamine N-demethylase activity by treatment with CoCl2 was prevented by co-treatment with SKF 525-A. This effect was explained by the prevention of release of heme from cytochrome P-450 by forming metabolic intermediate complexes with metabolites of SKF 525-A. On the other hand, poly(I.C) significantly suppressed P-450 content and benzphetamine N-demethylase and benzo [a] pyrene hydroxylase activities, even under simultaneous treatment with SKF 525-A. This inhibition by poly (I.C) was accompanied by weak staining of proteins corresponding to cytochrome P-450 in SDS gel electrophoresis. In addition, the activity of non-heme enzyme, 4-hydroxybiphenyl glucuronyltransferase, was suppressed by treatment with poly (I.C) but not by CoCl2-treatment. These findings strongly suggested that, unlike CoCl2, poly (I.C) suppressed cytochrome P-450 content and monooxygenase activities due to decreased synthesis or increased degradation of the apoprotein of cytochrome P-450 with slight contribution of the induced heme oxygenase.

Animals↗

Idiopathic sustained ventricular tachycardia responsive to verapamil: clinical electrocardiographic and electrophysiologic considerations.

Fifteen cases of idiopathic VT responsive to verapamil were studied to examine its clinical, electrocardiographic and electrophysiologic features. All patients were male, aged 15-49, average age 28. Initial onset of VT occurred at ages 9-48 (average 21). Time from onset of VT to first admission was 1-20 years (average 8.2 years), and patients had been followed for 17-40 months (average 27 months). 13 cases had palpitations, 5 had faintness, 1 had syncope, but no deaths were reported. ECG's at time of VT exhibited CRBBB + LAD pattern in 12 cases, CRBBB + RAD pattern in 1, and LBBB in 2. VT rate was 130-200 bpm (average 163 bpm), with QRS width of 0.11 - 0.16 sec (average 0.14 sec). ECG's during sinus rhythm revealed no ST/T abnormalities, although in 6 cases they were found post-VT. 5 cases had recognizable H waves during VT, and HV intervals were shorter than that during sinus rhythm. VT could be induced by programmed electrical stimulation in 14 cases. VT or RVR could be induced by atrial pacing in 6 of 14, single RV extra-stimuli in 12 of 14, paired pulses in 5 of 12, RV overdrive pacing in 7 of 14, and burst pacing in 6 of 14 cases. VT could be terminated by RV burst pacing in 14 of the 15 cases, while single RV stimuli were effective in 5 out of 12 cases. Among the 12 cases in which VT could be induced by single RV extra-stimuli, the relationship between changes in premature interval for the induction of VT and the echo interval of VT (extrastimulus to first VT complex) was examined. 8 showed an inverse relationship, 3 showed a concordant relationship and 1 case could not be assessed. An inverse relationship was found between changes in paced cycle length and echo interval for the 2 cases in which VT could be induced by rapid pacing. Verapamil terminated sustained VT in 12 out of 13 cases, and in another case had a pronounced decelerating effect. Prior to termination, VT rate was drastically reduced (from 163 +/- 29 bpm to 128 +/- 29 bpm). Verapamil was able to prevent the induction of VT in 6 out of 14 cases, while in 6 cases the VT zone was expanded and in 2 cases the VT zone was narrowed.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Influence of short-term water deprivation on kinetics of trimethadione and its metabolite in rats.

The effects of acute (24-, 48- or 72-hr) water deprivation on the disposition kinetics of trimethadione (TMO) and its only metabolite, dimethadione (DMO), and on the microsomal hepatic drug-oxidizing enzyme activities were investigated in male rats. The DMO/TMO ratios in the serum at 2 hr after intravenous administration of 100 mg/kg TMO were significantly decreased in 48- and 72-hr water-deprived rats, but in 24-hr water-deprived rats, the DMO/TMO ratios were not changed as compared to controls and food restrictions. In the 48- and 72-hr water-deprived rats, contents of cytochrome p-450 and activities of aminopyrine N-demethylase were significantly decreased. On the other hand, activities of aniline hydroxylase in these rats were significantly increased as compared to controls and food restrictions. These results suggest that the effects of water deprivation on drug metabolism not only depend on the time of water deprivation but also vary with the indicator substrate.

Aminopyrine N-Demethylase↗

Experimental study on the collimator for increasing the resolution of N-isopropyl-p-(123I)iodoamphetamine (IMP) SPECT imaging of the brain.

This study was carried out to design a new collimator for the present 123I-IMP SPECT imaging of the brain, which is hindered by the contamination of 124I and 126I. In this study we intended to increase spacial resolution along the transaxial direction and, at the same time, to compensate for the decrease of sensitivity by sacrificing the resolution along the axial direction to some extent. For this purpose, we developed 4 kinds of slat type units; ultrahigh resolution (UHR), high resolution (HR), high sensitivity (HS), and ultrahigh sensitivity (UHS). In practice, either UHR or HR is set to the detector together with either HS or UHS. After testing 4 kinds of combinations, we found that the combination of UHR-HS gave us far better images than those obtained with the conventional medium energy parallel hole collimator and was best suited for 123I-IMP SPECT imaging of the brain at present. We are now thinking of fusing these two units together into one collimator.

Amphetamines↗

Automated body contour detection in SPECT: effects on quantitative studies.

To perform accurate in vivo quantitation by single photon emission computed tomography, we have developed a new method for detecting body contours for the correction of tissue attenuation. Our method can rapidly derive the best fit contours throughout the body by using the measured axial length of the patient body and Fourier filtering the detected contours which are defined by a unique bit-plane algorithm. We have also evaluated the effects of the body contours on the reconstructed images by using various attenuation correction techniques including a precorrection method (Sorenson, 1974), a postcorrection method (Chang, 1978), a weighted backprojection method, and a radial post correction method (Tanaka, 1983 and 1984). Counts in the specified region-of-interest in phantom images reconstructed by the radial postcorrection, weighted backprojection, and postcorrection methods were more strongly affected by inaccurately detected contours than were counts derived from images reconstructed by the precorrection method.

Body Surface Area↗

Evolution of HBeAg/anti-HBe status and its relationship to clinical and histological outcome in chronic HBV carriers in childhood.

Fifty-five Japanese HBV carriers under 15 yr of age were followed for 12 months or longer, during which time we investigated the evolution of HBeAg/anti-HBe status and clinical and histological aspects of the liver disease. Of 45 cases positive for HBeAg at the initial examination, 34 remained positive for HBeAg during the follow-up periods, while the remaining 11 lost HBeAg and eight of these seroconverted to anti-HBe. At the final observation, HBeAg positivity in serum was found in as many as approximately 90% of the HBV carriers under 6 yr, but had fallen to 48% in carriers between 12 and 15 yr. The serum transaminase values in 11 cases who lost HBeAg were abnormally elevated for variable periods, but eventually returned to normal. In six of these 11 who had liver dysfunctions, liver biopsy was performed during the HBeAg positive phase or shortly after the disappearance of HBeAg. The histologies of liver were chronic persistent hepatitis in two cases and chronic active hepatitis in four. Repeat liver biopsies of two cases with chronic active hepatitis at the first examination showed nonspecific reactive hepatitis 2 and 4 yr after seroconversion or disappearance of HBeAg. These results indicate that HBeAg-positive HBV carriers with overt liver dysfunctions in childhood are prone to lose HBeAg or to seroconvert to anti-HBe, followed by a marked histological regression, and therefore that special antiviral therapy is probably unnecessary.

Adolescent↗

A two-site sandwich radioimmunoassay of human gamma interferon with monoclonal antibodies.

Two monoclonal antibodies (nos. 6008 and 6016) were raised against human gamma interferon (IFN-gamma) derived from E. coli harboring the recombinant cDNA for IFN-gamma, and one (3710) against a synthetic peptide representing its C-terminus amino acid sequence of 20 residues. The monoclonal antibody against the synthetic peptide (3710) reacted either with IFN-gamma or the synthetic peptide. One monoclonal anti-IFN-gamma (6008) did not react with the synthetic peptide, while the other (6016) showed a weak binding with the peptide. The binding of the monoclonal antibody against the synthetic peptide (3710) with IFN-gamma was not inhibited by 6008, but to a certain extent by 6016. A 2-site '1-step' radioimmunoassay was developed in which 6008 was fixed on a solid-phase support, and the test sample together with radiolabeled 3710 was added for the binding with it. The assay was rapid with a sensitivity capable of detecting a few ng/ml of IFN-gamma.

Antibodies, Monoclonal↗

Dose-independent pharmacokinetics of trimethadione and its metabolite in rats.

The aim of the present study was to examine the dose-independent kinetics of trimethadione (1) and its only metabolite dimethadione, 5,5-dimethyl-2,4-oxazolidinedione (2), after oral administration of 1-, 2-, and 4-mg/kg doses of 1 to rats. Pharmacokinetic parameters determined after oral administration of these doses showed that the half-life (t 1/2), metabolic clearance (CL), and apparent volume of distribution (Vd) were not significantly changed by increasing or decreasing the dose of 1, whereas there was a linear relationship between the dose of 1 and the area under the curve (AUC) (1, r = 0.912; 2, r = 0.976) or the maximum serum concentration (Cmax) (1, r = 0.990; 2, r = 0.980). The ratios of 2 to 1 at 1 and 2 h after oral administration of 1 were not significantly different. These experiments indicate that serum pharmacokinetic behavior of 1 and 2 1 or 2 h after oral administration of 1 to the rat is independent of the dose of 1 in the 1-4 mg/kg range.

Animals↗