[Evaluation of the FAB classification of acute leukemia].
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Acute Disease↗
Biomedical subjects
M Okamoto
Publications and source records attributed to M Okamoto.
Physical dependence produced by long duration, low dose chronic barbital treatment.
Barbiturate physical dependence was produced by twice-daily administration of Na barbital to cats according to the "low" dose barbiturate protocol (Okamoto et al., J. Pharmacol. Exp. Ther. 207: 906, 1978). The duration of treatment was 1, 2, 3, 5, 9 or 14 weeks. Pharmacodynamic tolerance was assessed by relating the degree of neurofunctional impairment to the blood barbital concentration at the time when the functional test was performed. Evaluation of withdrawal was based on whole-animal observation and subjective assessment of overt withdrawal signs. Motor activity and withdrawal convulsions were monitored continuously by an activity recording device. It was found that the pharmacodynamic tolerance and physical dependence continued to develop throughout the treatment period and no apparent ceiling on these phenomena was observed. The "low" level chronic dosing merely prolonged the time required to develop physical dependence of severity comparable to that produced by shorter durations of "high" level chronic dosing.
Animals↗
[Analysis of left ventricular blood flow in cases of myocardial infarction: a preliminary report].
Analysis of left ventricular blood flow in cases of myocardial infarction was attempted by two-dimensional Doppler echocardiography. Subjects consisted of 25 cases of myocardial infarction with and without ventricular aneurysm, and 15 healthy persons as controls. The Doppler recordings were made in nine areas within the left ventricular cavity from the apical approach. For healthy subjects, ejection flows were recorded in the main cavity and directed towards the aortic orifice in systole, and diastolic flows in the left ventricular inflow were recorded from the mitral orifice to the apex. However, diastolic flows toward the aortic orifice were also recorded along the interventricular septum, and interpreted as eddy currents from the apical cavity. There were no high velocity flows in the phases of isometric contraction and relaxation. In seven of 25 cases of myocardial infarction, abnormally high velocity flows of more than 30 cm/sec were recorded in the isometric relaxation phase, which were directed away from the asynergic part. In eight of the 25 patients examined, high velocity flows toward the cardiac apex were recorded at the posteroapical area in systole. Such flows have never been observed in healthy subjects. Inertia of the diastolic mitral inflow is considered to continue during systole due to impairment of contractions of the apicoinferior wall.
Adolescent↗
[Aortic flow patterns in heart diseases with left-to-right shunts from the aorta, and their clinical significance: a Doppler echocardiographic study].
Aortic flow patterns were analyzed using two-dimensional Doppler echocardiography for 15 patients with patent ductus arteriosus, seven with ruptured aneurysms of the sinus of Valsalva, two with coronary artery fistulae and for 22 healthy persons, with special reference to diastolic flow patterns. The conclusions were as follows: In healthy subjects, there was a tiny and transient reversed flow signal in early diastole followed by a slow and sustained diastolic forward flow signal. The velocity of the diastolic forward flow was slower and the duration was shorter in the lower abdominal aorta than in the upper portion. In patients with shunts from the aorta to the right-sided chambers, the early diastolic reverse flow was enhanced, and another reversed flow developed in mid- and late diastole, which was the most evident in the lower portion of the abdominal aorta. The extent of the reversed flow correlated significantly with Qp/Qs by catheterization (r = 0.73). Thus, the abdominal flow patterns in cases with left to right shunts from the aorta to the right-sided chambers of the heart provided information for estimating the size of the shunt volume. In patients with bi-directional shunts, the dominant direction of the shunt during diastole can apparently be determined by analyzing the aortic flow patterns.
Adolescent↗
Characterization of the activity of growth factor from AH-130 tumor cells.
The activation of DNA synthesis induced by growth factor from the cytosol of AH-130 tumor cells (AH-130GF) was inhibited by alkylamines (methylamine, ethylamine, and dansylcadaverine), which inhibit the intracellular processing of hormone-receptor complexes. Calmodulin inhibitors (trifluoperazine and W-7) also inhibited the mitogenic action of AH-130GF, suggesting that the Ca-calmodulin system and proteolytic processing in lysosomes are necessary for stimulation of DNA synthesis by AH-130GF after its binding to the cell surface. Membrane phosphorylation induced by AH-130GF or epidermal growth factor (EGF) was investigated by using rat liver plasma membranes and 3T3 cell membranes in vitro. EGF increased the phosphorylation of two protein components with molecular weights of 160K and 130K in rat plasma membranes, but AH-130GF increased the phosphorylation of only the 130K protein. No specific phosphorylation induced by AH-130GF was detected in 3T3 cell membranes, but EGF induced phosphorylation of the 160K receptor protein.
Animals↗
[Ferritin levels of ascites and the contents of cystic ovarian tumors--possibilities of ferritin production and secretion by malignant tumor cells].
In this paper, we presented an interesting case with a cystic ovarian tumor, which consisted of the mucinous cystadenoma and the mucinous cystadenocarcinoma separated by a partition. The determination of ferritin concentrations in the both displayed ferritin levels of 87.5 ng/ml in the former and 14,812.0 ng/ml in latter respectively. This fact suggested the production of ferritin by the malignant tumor cells. To clarify this possibility, measurement of ferritin levels in the content of cystic ovarian tumors in fifteen cases and in the ascites of various origin in sixty-five cases was done. This study also supported a possibility that malignant tumor cells produce and/or secrete much more ferritin into the body fluid than benign tumor cells.
Ascitic Fluid↗
[Successful management of ruptured dermoid cyst and 12 similar cases].
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Adult↗
Hepatic microsomal cytochrome p-450-dependent N-demethylation of methylguanidine.
Cytochrome P-450-dependent N-demethylation of methylguanidine, a uremia toxin, was investigated. Methylguanidine was stoichiometrically converted into equal amounts of guanidine and formaldehyde by aerobic incubation with phenobarbital-induced microsomes and NADPH. The guanidine formation in the incubation mixture followed Michaelis-Menten kinetics and required the presence of molecular oxygen and NADPH. Methimazole, a non-formaldehyde-producing substrate specific for FAD-containing monooxygenase, did not inhibit significantly formaldehyde formation, suggesting that microsomal FAD-containing monooxygenase does not play a significant role in N-demethylation of methylguanidine. The direct involvement of cytochrome P-450 in the N-demethylation is supported by the observations that addition of methylguanidine to purified cytochrome P-450 preparation caused a type I spectral change and that inhibitors of cytochrome P-450, such as carbon monoxide and metyrapone, markedly decreased the rate of demethylation. Neither superoxide anion nor hydrogen peroxide was directly involved in the demethylation reaction. In addition, guanidine formation was observed in the reconstituted system containing purified cytochrome P-450. Thus, these findings indicate that the hepatic microsomal mixed function oxidase system catalyzes N-demethylation of methylguanidine to guanidine.
Animals↗
Dynamic behavior of cyclic enzyme systems.
The dynamic behavior of cyclic enzyme systems where two enzymes share a substrate or cofactor in a cyclic manner is investigated by computer simulation. The dynamic characteristics of cyclic enzyme systems display catastrophic behavior in response to specific changes in external input without assuming allosteric regulation.
Enzymes↗
A histopathologic study of benign and malignant lymphoepithelial lesions of the parotid gland.
Twenty-three cases of benign and malignant lymphoepithelial lesions without Sjögren's syndrome were examined: 21 were classical benign lymphoepithelial lesions, and were mostly found in males older than 50 years of age. The other two cases were identified as undifferentiated carcinoma arising from benign lymphoepithelial lesion (8.7%; 2/23). Histologically, this carcinoma is characterized by the formation of cell nests of variable size and by marked lymphoplasmacytic infiltrations into the stromal tissue. In immunofluorescence, an increase of plasma cells containing IgA and IgG was noted in the marginal areas of carcinoma cell clusters. Electron microscopy disclosed that the carcinoma was composed of poorly differentiated cells with occasional squamous differentiation. No dysplastic characteristics were found in the infiltrating lymphocytic components. These two cases of carcinoma were found in middle-aged females.
Adult↗
19-Hydroxylation of 18-hydroxy-11-deoxycorticosterone catalyzed by cytochrome P-45011 beta of bovine adrenocortex.
When 18-hydroxy-11-deoxycorticosterone was incubated with adrenocortical mitochondria fortified by adding exogenously adrenodoxin reductase and adrenodoxin in the presence of an NADPH-generating system, the steroid was converted to two products which were separated by high performance liquid chromatography. The retention time of one product was identical with that of 18-hydroxycorticosterone, an expected product of 11 beta-hydroxylation, whereas the retention time of the other was not coincident with those of any other corticosteroids examined. Production of the unidentified substance was also shown when 18-hydroxy-11-deoxycorticosterone was incubated with purified cytochrome P-45011 beta and its electron transport system. The ratio of the two products was always constant, even when various incubation conditions were employed with regard to reaction time, the substrate concentration, and the cytochrome concentration. Structural determination of the unidentified product was conducted by mass spectrometry and 1H NMR spectrometry. The results of these analyses indicated that the substance was 18,19-dihydroxy-11-deoxycorticosterone, a hitherto unreported corticosteroid.
18-Hydroxydesoxycorticosterone↗
Isolation of mouse mammary tumor cells showing spontaneous regression.
The tumor cells, TMT-3, was isolated from TMT-2 tumor cells by way of repeated selections of large colonies in soft agar. The cells can grow either in mice or in suspension culture. TD50 of the ascites tumor cells was 1.5 +/- 1.0. Plating efficiencies in soft agar were 40-70% for cells of ascites tumors and 25-30% for cells of solid tumors. The cells showed 4 marker chromosomes common to the parent cells and 6 new marker chromosomes. They also shared MM-antigen, but its quantity was about half of the parent cells. The growth curves of the solid tumors were characterized by temporary decrease in tumor volume followed by regrowth or regression.
Animals↗
[Case of acute myocarditis with hepatitis].
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Acute Disease↗
Effects of insulin secretagogues and inhibitors on phospholipid metabolism in Langerhans' islets of rat pancreas.
Glucose stimulation of [32P]-prelabelled pancreatic islets induced an increased incorporation of radioactivity into phosphatidylinositol. Glucagon and agents that increases cAMP in the islet did not affect phosphatidylinositol turnover, in spite of increased release of insulin. Furthermore, the potent inhibitor of insulin release, somatostatin did not alter phospholipid metabolism. Colchicine inhibited glucose-stimulated turnover of phosphatidylinositol as well as insulin release. These results may suggest that: (1) cAMP and phosphatidylinositol turnover are involved in different transmembrane control system for regulating insulin release; and (2) the function of microtubules modulate phospholipid metabolism.
Animals↗
Effect of an exogenous energy source and amino acids on DNA synthesis in regenerating rat liver.
Rats on a protein-free diet synthesized less DNA after partial hepatectomy than rats on a normal diet. In regenerating livers of animals on the protein-free diet, induction of several enzymes involved in the DNA precursor synthetic pathway, and especially ribonucleotide reductase, were depressed. When young rats were maintained solely by parenteral nutrition after partial hepatectomy, exogenous amino acids were more important than the exogenous energy source for induction of enzymes involved in synthesis of DNA and its pyrimidine nucleotide precursors. In particular, induction of ribonucleotide reductase appeared to be controlled by exogenous amino acids. Tryptophan, methionine, phenylalanine, leucine, valine, isoleucine and threonine seemed to stimulate the induction of this enzyme most after partial hepatectomy.
Amino Acids↗
Regulation of 18-hydroxycorticosterone formation in bovine adrenocortical mitochondria.
The conversion of deoxycorticosterone to 18-hydroxycorticosterone was examined by using sonicated mitochondrial suspension of bovine adrenocortex. The KM's of deoxycorticosterone for the 11 beta- and 18-hydroxylations were in the same range (1 microM), while the turnover number for the 11 beta-hydroxylation (50 nmol/min/nmol cytochrome P-450) was 6 times as great as that for the 18-hydroxylation (7.3). The KM and turnover number for the 18-hydroxylation of corticosterone were 6 microM and 0.4, respectively. Those for the 11 beta-hydroxylation of 18-hydroxy-11-deoxycorticosterone were 120 microM and 5. When products were analysed in the incubation of deoxycorticosterone with the mitochondrial suspension containing a larger amount of cytochrome P-450, the formation of 18-hydroxycorticosterone was observed in addition to the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone. The kinetic interrelation between the two pathways was further examined together with consideration of the cytochrome P-450-linked hydroxylation system. The result suggests that the pathway via 18-hydroxy-11-deoxycorticosterone substantially participates in the formation of 18-hydroxycorticosterone from deoxycorticosterone. The perturbation of this network by an artificial means, such as the addition of Triton X-100, revealed that the detergent (0.02%) facilitated the production of 18-hydroxycorticosterone from deoxycorticosterone, regardless of its inhibitory effect on the production of corticosterone and 18-hydroxy-11-deoxycorticosterone from deoxycorticosterone. These studies provide an important insight into the regulation mechanism of 18-hydroxycorticosterone formation from the precursors on the mitochondrial level.
11-Hydroxycorticosteroids↗
Zonal distribution of cytochrome P-450s (P-450(11) beta and P-450scc) and their relation to steroidogenesis in bovine adrenal cortex.
Zona glomerulosa and zonae fasciculata-reticularis of bovine adrenal cortex were separated by our improved method using a remodeled microtome. A considerable amount of fresh mitochondria and microsomes was quickly obtained. Specific content of cytochrome P-450 in the mitochondria was higher in zonae fasciculata-reticularis than in zona glomerulosa. When metyrapone was added to the mitochondria and the drug-induced difference spectra were measured, there appeared two phases in the titration curve; the first phase was saturated at a concentration of 3 microM and the second phase appeared at concentrations higher than 10 microM. The first phase seemed to be due to the substrate-free P-450(11) beta and the second phase to the cholesterol-bound P-450scc. From these spectral studies contents of cytochrome P-450scc and P-450(11) beta were estimated, and those were found to be equal for each zone. From similar studies on substrate-induced difference spectra, there seemed to be no difference between two zones in the affinity of cytochrome P-450(11) beta for deoxycorticosterone and 11-deoxycortisol. This was also the case with 11 beta-hydroxylase activity and substrate specificity for deoxycorticosterone and 11-deoxycortisol.
Adrenal Cortex↗
Purification and some properties of rat spleen phospholipase A2.
Intracellular phospholipase A2 was purified to homogeneity from rat spleen. The enzyme was efficiently concentrated by precipitation with trichloroacetic acid and purified by sequential use of column chromatographies on DEAE-Sepharose, octyl-Sepharose and Bio-Gel P-30. The positional specificity of the enzyme for an acylester bond at the sn-2-position of phospholipids was established. The purified enzyme has a pH optimum ranging from 8.0 to 10.5 and the molecular weight of the enzyme was estimated to be 14,700-14,800 by sodium dodecyl sulfate polyacrylamide gel electrophoresis and by gel filtration with a TSK-GEL G 2000 SW column. The purified enzyme requires Ca2+ for activity. The activity was not enhanced by the presence of purified calmodulin.
Animals↗