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Biomedical subjects

T Saitoh

Publications and source records attributed to T Saitoh.

At least 415 records · Page 23Linked to original sources

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridinium ion on activities of the enzymes in the electron transport system in mouse brain.

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) on activities of enzyme complexes in the electron transport system were studied using isolated mitochondrial preparations from C57BL/6J mouse brains. Both MPTP and MPP+ dose-dependently inhibited activity of NADH-ubiquinone oxidoreductase (EC 1.6.5.3). The inhibition was reversible. Preincubation of freeze-thawed mitochondria with MPTP or MPP+ had no effect on the inhibition; however, when nonfrozen mitochondria were used, NADH-ubiquinone oxidoreductase activity was reduced to 46% of that in the nonincubated sample after a 5-min preincubation with MPTP and to 77% of that in the nonincubated sample after a 5-min preincubation with MPP+. Kinetic analyses revealed that inhibition of MPTP was noncompetitive and that of MPP+ uncompetitive with respect to NADH. On the other hand, inhibition of MPTP was uncompetitive and that of MPP+ noncompetitive with respect to ubiquinone. Succinate-ubiquinone oxidoreductase (complex II), dihydroubiquinone-cytochrome c oxidoreductase (complex III), and ferrocytochrome c-oxygen oxidoreductase (EC 1.9.3.1) activities were either slightly inhibited or not inhibited by MPTP or MPP+. The significance of these findings is discussed in relation to the mechanism of MPTP-induced neuronal degeneration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

[Clinical studies on cefuzonam in the field of obstetrics and gynecology].

Cefuzonam (CZON, L-105), a cephem type antibiotic, was clinically studied in the field of obstetrics and gynecology. The results are summarized as follows: CZON 1-2 g was administered by injection twice daily to 11 cases of infections (4 of endometritis, 2 of pyometra, 3 of adnexitis and peritonitis, 1 of abdominal abscess, and 1 of puerperal fever). Clinical efficacy was excellent in 2 cases and good in 9 cases, with a very high overall efficacy rate of 100%. Slight elevations of GOT and GPT in 1 case were noted in clinical laboratory tests. No side effects attributable to the drug were noted. CZON is considered to be a useful drug for obstetric and gynecological infections.

Adult↗

Primary saphenous venous aneurysms presenting in a child.

Venous aneurysms are dilatations of localized venous segments having no connection with varicosities. They are most often found post-traumatically in adults. The case presented here was a rare case of primary saphenous venous aneurysms in an 8-year-old child which were well demonstrated by Tc-99m human serum albumin (HSA) angiography.

Aneurysm↗

Protein kinase C in human brain and its inhibition by calmodulin.

Protein kinase C is a ubiquitous enzyme which is especially concentrated in brain tissue and which has been reported to have a key role in the regulation of neuronal activity. Substrates for this kinase were studied in frozen postmortem human cortex. Two major protein substrates with mol. wts. of 86,000 and 67,000 Da were found in the cytosol the cytosol fraction. Calmodulin was found to inhibit phosphorylation of these two proteins.

Aged↗

Increased in vitro phosphorylation of a Mr 60,000 protein in brain from patients with Alzheimer disease.

We have established in vitro conditions under which we can reliably measure kinase activity in normal postmortem human brain. Using these conditions, we detected in the brains of patients with Alzheimer disease a 2-fold increase in the level of Mr 60,000 protein phosphorylation compared to age-matched controls. The Mr 60,000 protein phosphorylation was found exclusively in the cytosol fraction. No differences were detected between phosphoproteins in 100,000 X g pellet fractions from brains of Alzheimer disease patients and from age-matched controls. Postmortem time up to 17 hr does not seem to affect the phosphorylation level of the Mr 60,000 protein. Younger Alzheimer disease patients had more prominent changes in the elevation of the Mr 60,000 protein phosphorylation level than older patients, although in the control patient, age did not affect the phosphorylation level of the Mr 60,000 protein. We conclude that in the brain cytosol of Alzheimer disease there may be an abnormality in either the degree of Mr 60,000 protein phosphorylation or in the Mr 60,000 protein concentration.

Age Factors↗

Cardiovascular effects of a new inotropic agent, denopamine (TA-064); with reference to it's effects on cardiac hemodynamics and metabolism.

A new inotropic agent, denopamine (TA-064) was shown to have a strong positive inotropic effect. Its effect on cardiac hemodynamics and metabolism was evaluated by using wall stress and direct measurement of myocardial oxygen consumption. With plasma concentration of denopamine (21-29 ng/ml on average), attainable by one single oral dose (10 mg), the positive inotropic effect was evident by the significant increase in peak (+)dp/dt (+15% increase from control), and shortening velocity of the left ventricle (+39%), when heart rate or blood pressure was not altered significantly. End diastolic stress and end systolic stress of the left ventricle, defined as indices of preload and afterload, respectively, were reduced significantly. The reduction of preload (-51%) was the result of improved left ventricular filling, and the reduction of afterload (-23%) was due to the increased contractility. Neither coronary sinus blood flow not aortocoronary AV O2 defference was changed. Consequently, myocardial oxygen consumption remained unaltered. When the dose is chosen properly, denopamine is able to exert salutary effects in patients with severe heart failure.

Administration, Oral↗

[Effect of tritoqualine (TRQ) on bile secretion in rats].

An accelerating effect by TRQ-consecutive administration perorally on bile secretion in rats was investigated in comparison with phenobarbital (PB)-administered rats. The bile secretion velocity was increased significantly by administration of TRQ (25, 50, 100 mg/kg/day) or PB (50 mg/kg/day) compared to the control group. A 24% increase in the ratio of the liver weight to body weight was observed in the PB-administered group, but in the TRQ-administered group, a slight increase (5%) was seen compared with the control group. The concentration of excreted bile acid in the bile of rats to which TRQ and PB were administered were lower than that of the control group. However, when excreted bile acid content was represented in terms of wet liver weight, no difference was seen in the TRQ-administered group, but a 17% decrease was observed in the PB-administered group compared with the control group; and also, almost the same results were obtained with regards to the cholesterol and phospholipid in the bile. Though there was no difference of Na+, K+, or Cl- concentration in bile between the TRQ or PB-administered group and the control group, more Na+, K+ or Cl-/g wet liver was excreted in TRQ-treated group than the PB-administered group. TRQ was excreted through the bile duct promptly after an i.v. injection without an increase in the bile secretion, suggesting that the excretion of TRQ and its metabolites were not accompanied by the increase in bile secretion. These results indicate that the accelerating effect of TRQ on bile secretion was presumably derived from bile acid non-dependent bile secretion such as PB; however, a different pharmacological mechanism between TRQ and PB was presumed from the discrepancy of the decomposition in the secreted bile and of drug-metabolizing enzyme induction. Thus, it was suggested that there was a possibility that the accelerating action of bile secretion by TRQ was attributed to the activating effect of TRQ on the hepatocytes.

Administration, Oral↗

[Present diagnostic status of scirrhous type gastric cancer--with special reference to the endoscopic diagnosis].

First, we presented an actual diagnostic situation in nowadays for gastric cancer of Borrmann 4, which is virtually the same as scirrhous gastric cancer. Among 12 patients treated by the author, all of whom were discovered late, only 3 underwent surgery. In fact, with inoperable cases in Borrmann 4, even those endoscopically found to show insufficient stretching of the gastric wall, thickening and tortuosity of folds, uneven gastric mucosa, redness and white coating, there may be negative in gastric biopsy. However, the significance of an endoscopic examination for diagnosis of scirrhous cancer is in obtaining proof of the carcinoma (especially when still operable) by gastric biopsy. Thus, one must strive not to overlook slight redness, white coating which means small erosions, but to go over gastric biopsy again and again. Next, with carcinoma presenting a leather bottle (linitis plastica type) of the stomach itself, the II c portion of the stomach consisted of fundic glands (undifferentiated carcinoma) shall become the primary focus supporting Nakamura's theory. One case of diffuse invasive cancer, mistakenly diagnosed as a II c case, and two cases of regional type, one similar to II c and the other a Borrmann 2 carcinoma of advanced carcinoma showing strongly fibrous scirrhous tendency toward infiltration, were jointly monitored.

Adenocarcinoma, Scirrhous↗

Formation of a leakage-type ion pathway in lipid bilayer membranes by divalent cationic cyanine dyes in cooperation with inorganic phosphate. Role of the cyanine dye in uncoupling of oxidative phosphorylation.

Divalent cationic cyanine dyes, such as 2,2'-[3-[2-(3-butyl-4-methyl-2-thiazoline-2-ylidene)-ethylidene] propenylene]bis[3-butyl-4-methylthiazolinium iodide] and platonin induced large membrane current fluctuation when an electrical potential difference was applied across a planar phosphatidylserine bilayer membrane in medium containing inorganic phosphate (Pi). Without Pi, the dyes did not induce current fluctuation at concentrations of less than 30 microM. Noise analysis of current fluctuation indicated formation of a pathway for ion leakage. From measurements of the interfacial tension between oil and aqueous phases, and of water permeability across liposomal membranes, Pi was concluded to relax the phospholipid bilayer structure, resulting in great reduction in the concentration of the cyanine dye necessary for induction of the leakage-type pathway. In the presence of Pi, cationic ions such as tetrabutyl ammonium and tetraphenyl phosphonium did not induce the leakage-type pathway, although they had electrophoretic effects at high concentrations. These facts suggest that the mechanism of the uncoupling of oxidative phosphorylation by dicationic cyanine dyes in mitochondria is different from that of cationic uncouplers such as tetrabutyl ammonium ion.

Cations, Divalent↗

Factors discriminating survivors and nonsurvivors in alcoholic heart disease.

Eighteen patients with dilated cardiomyopathy and a history of excessive ethanol intake were monitored for 3-98 months (mean 23 months). Six patients died (mean age 43.7 +/- 9.2 years) and 12 patients survived (mean age 48.8 +/- 9.5 years). Of the echocardiographic findings taken during heart failure, only the relative wall thickness to the internal dimension of the left ventricle (t/r ratio) differed significantly (survivors 0.33 +/- 0.77 vs. nonsurvivors 0.25 +/- 0.04, P less than 0.05). Of the hemodynamic data obtained after treatment of heart failure, left ventricular end-diastolic pressure differed significantly (survivors 6 +/- 2 vs. nonsurvivors 12 +/- 4 mmHg, P less than 0.001). The two groups could not be differentiated by ejection fraction, cardiac output, end-diastolic or end-systolic volumes, or semi-quantitative analysis of histologic findings obtained by right ventricular endomyocardial biopsy (light microscopy). Only two of six nonsurvivors (33%) succeeded in abstaining from alcohol, while eight of twelve survivors (67%) became teetotalers (P less than 0.05). Total abstinence from alcohol seems to be essential but was not necessarily followed by recovery in the most severe cases. Thus, the absence of adequate hypertrophy and high left ventricular filling pressure may predict the prognosis in alcoholic heart disease.

Adult↗