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Biomedical subjects

H Okuda

Publications and source records attributed to H Okuda.

At least 433 records · Page 24Linked to original sources

An aberrant adenylate kinase isoenzyme from the serum of patients with Duchenne muscular dystrophy.

The sera from patients with human Duchenne (X-linked) progressive muscular dystrophy contain elevated adenylate kinase (ATP: AMP phosphotransferase, EC 2.7.4.3) activities, in addition to their characteristically high creatine kinase (ATP; creatine N-phosphotransferase, EC 2.7.3.2) activities. By agarose gel electrophoresis of human Duchenne dystrophic serum, the presence of an apparently normal human serum adenylate kinase together with a variant species of adenylate kinase was detected. The latter enzyme species appeared, in its mobility, to be similar to that of the normal human liver-type adenylate kinase. The presence of this aberrant liver-type adenylate kinase could also be demonstrated by characteristic (for the liver type) inhibition patterns with P1,P5-di-(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate. On the other hand, by inhibition titrations with an anti-muscle-type adenylate kinase, hemolysates from the erythrocytes of several Duchenne and Becker's dystrophics were found to contain approx. 96% muscle-type adenylate kinase and their serum approx. 97% muscle-type adenylate kinase. These same patients contained approx. 89% M-M type creatine kinase in their serum (by inhibition against anti-human muscle-type creatine kinase) indicative of the presence also of M-B plus B-B type active isoenzymes. All of these data can best be explained by the presence of a variant or mutant adenylate kinase isoenzyme in the dystrophic serum. This isoenzyme appears to resemble the liver type in its inhibition patterns with P1,P5-di(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate, and in its heat stability (compare also the agarose gel electrophoresis pattern); but structurally, it is a muscle type, or derived from a muscle type, as shown immunologically by inhibition reactions with anti-muscle-type adenylate kinase. Whether this is a fetal-type isoenzyme of adenylate kinase will require further investigation.

Adenine Nucleotides↗

The mechanism of the lipolytic action of theophylline in fat cells.

The lipolytic action of theophylline was examined using both intact fat cells and a fat globule system. Theophylline had similar lipolytic actions in both systems. However theophylline did not activate hormone-sensitive lipase in the fat globule system as measured with added Ediol. Pretreatment of the fat globules with phospholipase C suppressed theophylline-induced lipolysis, but phospholipase D had no effect. A theophylline-sensitive system was reconstituted from endogenous fat and a lipase fraction. Inhibitors of theophylline-induced lipolysis such as quinine and propranolol inhibited theophylline binding to artificial lipid micelles. Purine nucleosides such as adenosine, inosine and guanosine inhibited theophylline-induced lipolysis in the fat globule system. These results suggest that theophylline has a lipolytic action similar to that of adrenaline. Both share a lipolytic mechanism additional to that involving the activation of hormone sensitive lipase through the cyclic-AMP dependent protein kinase. Phospholipids play an important role in this additional mechanism.

Adipose Tissue↗

Embryotoxic effects of ethylene glycol monomethyl ether in mice.

An embryotoxicity study on ethylene glycol monomethyl ether (EGM) was carried out in ICR mice. They were given EGM daily at 6 dose levels (31.25, 62.5, 125, 250, 500 or 1000 mg/kg body wt) by gastric intubation on days 7 through 14 of gestation. On day 18 of gestation all fetuses were examined. Marked and dose-related embryotoxic effects were observed. Skeletal and gross anomalies, reduced fetal weight and fetal death were all observed at lower dosages of EGM, while marked leucopenia of the dams occurred at the highest dose.

Abnormalities, Drug-Induced↗

Effect of amino acids on insulin-stimulated glucose metabolism in fat cells.

The effect of amino acids on insulin responsiveness in epididymal adipose tissue was examined. It was found that insulin-stimulated glucose oxidation in fat cells was significantly inhibited by glycine, alanine, valine, leucine, isoleucine, cysteine, methionine, lysine, phenylalanine, and proline. The effect of insulin on glucose incorporation into triglyceride is also severely diminished by these amino acids. In addition, alanine reduced the incorporation of precursors ([U-14C]glucose or [1-14C]palmitate) into triglyceride both in vitro and in vivo. The Ki values of alanine were 0.4 and 0.5 mM toward the precursors of glucose and palmitate, respectively. The mechanism of reduction of insulin responsiveness in rat adipose tissue is discussed on the basis of these results.

Adipose Tissue↗

ATP citrate lyase in human adipose tissue.

ATP citrate lyase [EC. 4.1.3.8] activity in human adipose tissue was assayed. The activity was considerably higher in tissue from patients who had been supplied with nutrients only by intravenous injection than that from patients who had orally taken a meal and then fasted overnight. These results suggest that ATP citrate lyase activity in human adipose tissue is greatly influenced by the nutritional status.

ATP Citrate (pro-S)-Lyase↗

[Laboratory and clinical studies on cefotaxime in obstetrics and gynecology (author's transl)].

We have conducted basic and clinical examination of a new cephalosporin derivative, cefotaxime (CTX). The average level of transfer measured at various locations in uterus tissue and adnexa 15 to 105 minutes (53.4 minutes in average) after intravenous administration of this drug ranged from 1.5 mcg/g (myometrium) to 3.3 mcg/g (portio vaginalis). It was distributed in cervix uteri and portio vaginalis at highest concentration, followed by oviduct, tunica serosa and ovary, and to myometrium at lowest concentration. The same pattern of distribution was observed in transfer ratio of various location in uterus tissue to uterus arterial blood. The drug was transferred at very high level in pelvic cavity fluid after total hysterectomy throughout 3 postoperative hours. Five cases of gynecological infections receiving in total 10 to 42 g of CTX demonstrated 'excellent' results in 2 cases, and 'good' in 3 cases. Out of these, 3 cases did not respond to other antibiotic. Neither side effect nor clinical test abnormality was observed, except for one case, in which mild increase of GOT and GPT occurred. Based on the results of basic and clinical studies as described above, this drug is considered to have excellent efficacy and safety.

Adult↗

[Effects of inflammation and stimulant diets on functions of autonomic nervous system (author's transl)].

In usual medical consultation, we have been met a lot of female patients suffering from disturbances of autonomic nervous system such as headache, shoulder-ache and so on. Experiments were designed to elucidate whether or not these disturbances of autonomic nervous system were induced by inflammation and accelerated by stimulant diets. Functions of autonomic nervous system were examined by lipolysis in rat epididymal adipose tissue which was partly controlled by sympathetic nervous system. It was found that free fatty acid release from the epididymal adipose tissue was considerably elevated by inflammation which was formed in abdominal wall or in abdominal cavity or oral administration of stimulant diets such as red pepper and white pepper, and that such elevation of lipolysis was significantly reduced by resection of the autonomic nerve. These results indicated that the inflammation and the stimulant diets induced excitement of sympathetic nerve which controlled the epididymal adipose tissue. Experiments were now in progress to clarify relationship between such excitement of sympathetic nervous system induced by the inflammation or by the stimulant diet and irregular complaints due to disturbances of autonomic nervous system.

Adipose Tissue↗

Purification and characterization of a lipolytic factor (toxohormone-L) from cell-free fluid of ascites sarcoma 180.

A lipolytic substance in the ascites fluid of mice with Sarcoma 180, called toxohormone-L, was purified and characterized. The lipolytic activity of toxohormone-L was measured in vitro using rat adipose tissue slices. Toxohormone-L, purified approximately 90-fold from the ammonium sulfate fraction, gave a single band on polyacrylamide gel electrophoresis. Its molecular weight was about 75,000, and its isoelectric point was 4.7. Toxohormone-L is heat labile and nondialyzable, but, on its digestion with trypsin, an active fragment that was heat stable and dialyzable was produced. Toxohormone-L is a protein and is also present in the ascites fluid of patients with hepatoma and Grawitz's tumor.

Animals↗

A prospective study on the development of hepatocellular carcinoma from liver cirrhosis with persistent hepatitis B virus infection.

We made a prospective study on the development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis with hepatitis B virus infection from April, 1973 to December, 1977. Seven out of 30 patients (23%) with hepatitis B surface antigen (HBsAg)-positive cirrhosis developed HCC. On the other hand, only 5.9% of the patients with HBsAg-negative liver cirrhosis developed HCC. These patients were classified into three groups according to their anti-HB core (anti-HBc) titers. When the anti-HBc titer, expressed as a dilution of serum, was 2(10) or more (Group I), 20-24% of the liver cirrhosis patients developed HCC either with or without a detectable amount of HBs Ag present in the sera. When the anti-HBc titer was 2(9) or less (Group II), only 0-5.7% developed HCC. There was no significant difference between this and the anti-HBc and HBsAg-negative group (Group III), which was 4.4%. In five individual cases from group I, HBsAg was detected in serum, and in biopsies of liver cells, before HCC could be detected by angiography and/or rising levels of alphafetoprotein (AFP). In all of these cases, the anti-HBc titer was higher than 2(10) throughout the observation period, even before the development of HCC. These findings indicate that active virus proliferation in chronic hepatitis B virus infection precedes the development of HCC as indicated by a higher anti-HBc titer. Therefore we have prepared these studies to show the pathogenic role of hepatitis B virus in the development of hepatocellular carcinoma.

Biomarkers, Tumor↗

Studies on lipase and esterase in human post heparin plasma.

Lipase and esterase in post heparin plasma from patients with various diseases were well correlated, r=0.77. Lipase and esterase hydrolyzed both tri and monoacylglycerol. The chain lengths of fatty acids in esters susceptible to the enzymes became longer by conversion of the substrate from triacylglycerol to monacylglycerol.

Esterases↗

Electrical arrhythmias in gastric antrum of the dog.

Antral electrical arrhythmias were investigated in 32 unanesthetized chronic dog preparations implanted with serosal electrodes and transducers. Five of these animals underwent surgical removal of the duodenal cap and the adjacent hypomuscular segment. In the intact dogs two distinct types of arrhythmias of the basic electric rhythm (BER) were observed. During phase I (basal activity) arrhythmias were recorded in 17 of 32 dogs. In 9 of the 32 dogs, arrhythmias were present in more than 10% of recorded phase I activity. These arrhythmias included tachygastria as well as mixed gastric rhythms. A second type of arrhythmia consisting of premature and delayed BER occurred in all dogs during phase III (burst activity). In all five dogs, duodenal cap removal produced a marked increase in antral arrhythmias as well as the disruption of normal interdigestive motor and electrical patterns. The changes in terminal antral electrical rhythmicity after surgery may be due to an interaction with the higher frequency duodenal pacemaker tissue. Antral frequencies of 15-18 cycles/min in two of five dogs several days after cap removal were evidence of a duodenal influence. Antral arrhythmias may be present during both normal and pathophysiological states. Their importance is as an indicator of the functional status of the antral smooth muscle and its responsiveness to normal physiological and pharmacologic stimuli.

Action Potentials↗