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Biomedical subjects

Y Sakamoto

Publications and source records attributed to Y Sakamoto.

At least 523 records · Page 29Linked to original sources

Prognostic significance of bone morphogenetic activity in osteosarcoma tissue.

The bone morphogenetic activities of the primary tumors of 30 patients with osteosarcoma were assayed. This activity was demonstrated as ectopic new bone formation on implantation of freeze-dried fractions of 12 of 30 tumors into athymic nude mice. Pulmonary metastases developed in ten (83%) of the 12 patients with osteosarcomas that produced bone morphogenetic protein (BMP), and bone metastases developed in six (50%) of the patients. The mean period from diagnosis to metastasis was 4.2 months in these patients. In contrast, pulmonary metastases developed in only eight (44%) of the patients with osteosarcomas that did not produce BMP, and bone metastases developed in only two (11%) of these patients. The mean period to metastasis was 12.3 months in these patients. The incidence of metastases in the patients with osteosarcomas producing BMP was significantly higher, and the mean period to metastasis was also significantly shorter than in the other group. The five year survival rates of patients with osteosarcomas that did and did not produce BMP were 33.3% and 54.6%, respectively (P = 0.015, log-rank test). Thus the bone morphogenetic activity of primary osteosarcoma tissue seems to be closely correlated with the prognosis of the patients.

Adolescent↗

Pressure of papillary sphincter zone and pancreatic main duct in patients with alcoholic and idiopathic chronic pancreatitis.

To determine the significance of manometric pressure of the pancreatic duct in patients with alcoholic and idiopathic chronic pancreatitis, we used a microtransducer inserted through a duodenoscope to measure pressures in the papillary sphincter zone and pancreatic main duct in 20 control subjects and 31 patients with chronic pancreatitis without papillary stenosis including 10 cases of alcoholic chronic pancreatitis (ALCP) and 21 cases of idiopathic chronic pancreatitis (ICP). The pancreatic main ductal pressure was significantly higher in the patients with ALCP (55.7 +/- 28.9 mm Hg) or ICP (44.5 +/- 25.8 mm Hg) than in the controls (16.2 +/- 8.7 mm Hg), but there was no significant difference between ALCP and ICP. There was no significant difference between control subjects and ICP in the motility of the sphincter of Oddi. In ICP there were no correlationships between pancreatic ductal pressure and the motility of papillary sphincter zone. In ALCP, the frequency of the papillary sphincter waves was significantly higher than in normal subjects and there was a correlation between the pancreatic ductal pressure and the motility of the papillary sphincter zone. These data suggest that increased pancreatic ductal pressure in ALCP may be in part due to papillary dysfunction, but not in ICP.

Alcoholism↗

Inhibiting effects of nicotinamide on urethane-induced malformations and tumors in mice.

The antipellagratic vitamin, nicotinamide, significantly suppressed urethane-induced malformations, when it was given intraperitoneally to pregnant JCL:ICR mice immediately after a single subcutaneous injection of urethane (1.0 mg/g) on the 9th day of gestation. The level of inhibition increased with the doses of nicotinamide: 33.0, 55.8, and 70.0% at doses of 0.1, 0.3, and 0.5 mg/g, respectively. Polydactyly and tail anomalies were markedly suppressed by the post-treatment with nicotinamide, while cleft palates were less effectively suppressed. Nicotinamide was still effective, when it was given during the period of 24-48 h after urethane treatment. Furthermore, dietary administration of nicotinamide also reduced urethane-induced malformations. The level of inhibition was 39.4 and 61.1% at 0.5 and 1.0% of nicotinamide in the diet, respectively. Higher doses of nicotinamide (3 and 5% in diet) also inhibited urethane-induced malformations, but not so effectively as lower doses. The inhibiting effects of nicotinamide on the spontaneous incidence of cleft lips and palates in CL/Fr mice were significant at a low dose (0.5% in diet), but not at a higher dose (1.0%). When [carbonyl-14C]nicotinamide was given to pregnant mice, nicotinamide and small amounts of nicotinamide adenine dinucleotide (NAD+), but not nicotinic acid, were detected chromatographically in the fetus and placenta, indicating that nicotinamide or NAD+ acts directly on the fetus to suppress urethane-induced malformations. A preliminary study revealed that urethane-induced lung tumorigenesis in JCL:ICR mice was also inhibited by post-treatment with nicotinamide in the diet. The level of inhibition was proportional to the dose of nicotinamide, that is, 35.0 and 62.8% at 1.0 and 2.5% of nicotinamide in the diet, respectively.

Abnormalities, Drug-Induced↗

Computer graphic analysis of antigenic sites on the insulin molecule.

Antigenic sites on a protein have been predicted by the measurement of hydrophilicity values. We have compared this approach to the use of atomic temp factors to predict the antigenic sites on insulin. These predictions were based upon computer assisted analysis of X-ray crystallography data. The results demonstrate that the hydrophilic sites A6, B19, B23, B24, and B26 are not on the surface of the molecule and therefore are not potential antigenic determinants. Thus, hydrophilicity values alone are not sufficient to predict antigenic sites. In contrast, atomic temp factors were more predictive of antigenicity. These findings may explain why anti-insulin antibodies are less likely to develop against certain hydrophilic sites.

Animals↗

Reactions of ultimate carcinogens with cell membranes: importance of carbamoylation of phosphatidylethanolamine by the carcinogens.

The strong carcinogens, N-methyl-N-nitrosourea (MNU), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) react with phosphatidylethanolamine (PE) in chicken erythrocyte ghosts or rat kidney cells, whereas a weak carcinogen, methyl methanesulphonate (MMS), does not. The reactions of these agents with commercial PE were also carried out and their reactivities were compared with their carcinogenic potencies. When compared with the amount of PE of the blank, 64%, 18% and 0% of PE were reacted with MNNG, MNU and MMS respectively. This indicated that MNNG is approximately 4 times more reactive than MNU, while MMS does not react with PE, correlating with their tumorigenic potencies on mouse skin. A positive correlation was also observed between the reactivity of a series of N-methyl-N'-aryl-N-nitrosoureas (I-X) to PE and their tumorigenicity. In the case of the nitrosoureas, the reactions proceeded through carbamoylation of the amino group in PE by the isocyanates generated from the agents. Furthermore, many isocyanates also reacted with PE just as the strong carcinogens did. Our present results suggest that both alkylation of DNA and reaction with cell membranes would be required for the formation of transformed benign cells. For progression of the benign to malignant cells, further alkylation of DNA would be required, and the carcinogenic potency of the agents may result from a combination of both reactions.

Animals↗

Acetyl-CoA hydrolase: relation between activity and cholesterol metabolism in rat.

To examine whether cytosolic acetyl-CoA hydrolase in rat liver is involved in regulation of cholesterol biosynthesis, we investigated the alteration of the enzyme activity under conditions of stimulation (cholestyramine treatment) and suppression [cholesterol feeding, a potent competitive inhibitor of microsomal 3-hydroxy-3-methylglutaryl-CoA reductase (CS 514) treatment, and a hypolipidemic drug [alpha-(p-chlorophenoxy)isobutyric acid, CPIB] injection) of cholesterol biosynthesis. The enzyme activity in rat liver increased significantly in the early diabetic, cholesterol-fed, CS 514-, and CPIB-treated groups, but no change in its activity was observed in chronic diabetic groups. Cholestyramine treatment to cholesterol-fed rats made the enzyme activity return to the initial level. When chronic diabetic rats were given a cholesterol diet or treated with CS 514 or CPIB, the activity increased significantly. Inhibition of cholesterol biosynthesis caused by these treatments induced increase in the enzyme activity with increase in the enzyme protein, judging from results obtained by enzyme-linked immunosorbent assay. These results suggest that this enzyme has a physiological role in maintenance of the equilibrium between the cytosolic acetyl-CoA concentration and CoA-SH pool for cholesterol metabolism.

Acetyl-CoA Hydrolase↗

Purification and characterization of an adenosine triphosphate-stimulated factor that enhances the nuclear binding of activated glucocorticoid-receptor complex from rat liver.

The ATP-stimulated translocation promoter (ASTP), a protein that increases the nuclear binding of partially purified activated glucocorticoid-receptor complexes (GRC) in the presence of ATP, was purified from the liver of adrenalectomized rats to apparent homogeneity, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purification procedure consisted of DEAE-cellulose chromatography, heat treatment (60 C; 3.5 min), and sequential chromatographies on agarose gel filtration, hydroxylapatite, Mono Q, and S-Sepharose. ASTP had a mol wt of 93,000, as determined by gel filtration on Bio-Gel A-0.5 m, and was composed of two apparently identical subunits with mol wt of 48,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The sedimentation coefficient of ASTP was 6.5s, and its isoelectric point was 4.5. ASTP activity was dependent on the physiological concentration of ATP, although ASTP did not bind to ATP-agarose. Neither ADP nor AMP affected its activity. An analysis of the nuclear binding behavior of GRC suggested that the affinity of GRC for nuclei in the presence of ASTP is much greater than that in the absence of ASTP. In the presence of ATP, ASTP increased the binding of GRC to chromatin, but not to DNA-cellulose, suggesting that ASTP acts as a regulatory component, altering the chromosomal binding of GRC in rat liver.

Adenosine Triphosphate↗

Pressure of papillary sphincter zone and pancreatic main duct in patients with chronic pancreatitis in the early stage.

We measured pressures of the papillary sphincter zone and pancreatic main duct endoscopically in 20 control subjects and in 38 patients with chronic pancreatitis without papillary stenosis, including 19 cases believed to be in the early stages of chronic pancreatitis. There was no significant difference between control subjects and patients with chronic pancreatitis without papillary stenosis in the motility of the sphincter of Oddi. The pancreatic main ductal pressure was significantly higher in the patients in the early stage of chronic pancreatitis (35.7 +/- 9.1 mm Hg (mean +/- SD) in patients suspected of having chronic pancreatitis and 44.9 +/- 20.4 mm Hg in minimal-change chronic pancreatitis) than in the controls (16.2 +/- 8.7 mm Hg). The viscosity of pure pancreatic juice of patients with chronic pancreatitis (5.0 centi-Poise (cP] in the basal secretory phase was significantly higher than that of the controls (1.32 cP). These data suggest that endoscopic measurement of pancreatic ductal pressure is useful for diagnosis of the early stages of chronic pancreatitis.

Adult↗

[Diagnosis of cancer with magnetic resonance imaging (MRI)].

Following a brief review of the history of magnetic resonance imaging (MRI), advantages and disadvantages of MRI are discussed in the diagnosis of malignant tumors of the various parts of the body. The advantages include high contrast resolution, no artifacts from the bones, and arbitrary imaging planes obtainable in multiple slices, whereas disadvantages include no signals from calcifications and prolonged imaging time. The roles of MRI were discussed in relation to detection of early cancers, extent of the lesions, histologic diagnosis and monitoring of treatments. Early diagnosis of tumors is successful in the central nervous system, whereas it is not accomplished in other parts of the body. Extent of the tumors or staging of the tumors can be accomplished to excellent advantage, but signal intensity is often not useful for differential diagnosis.

Bone Neoplasms↗

Motility of the sphincter of Oddi and pancreatic main ductal pressure in patients with alcoholic, gallstone-associated, and idiopathic chronic pancreatitis.

We endoscopically measured pressures of the pancreatic duct (PP) and the sphincter of Oddi (SO) in patients with alcoholic (ALCP, n = 10), gallstone-associated (GSCP, n = 7), and idiopathic chronic pancreatitis (ICP, n = 21), and in 20 controls. The PP was significantly higher in the patients with ALCP (55.7 +/- 28.9 mm Hg), GSCP (33.6 +/- 16.2 mm Hg), or ICP (44.5 +/- 25.8 mm Hg) than in the controls (16.2 +/- 8.7 mm Hg), but there was no significant difference between ALCP, GSCP, and ICP. There was no significant difference between control subjects and ICP in the motility of SO. In ICP, there was no correlation between the PP and the motility of SO. In ALCP and GSCP, the frequencies of the papillary sphincter waves were significantly higher than in normal subjects, and there were correlations between the PP and the motility of SO. These data suggest that increased pancreatic ductal pressure in GSCP with papillitis or ALCP may be due in part to papillary dysfunction, but not in ICP.

Alcoholism↗