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Biomedical subjects

Y Sakamoto

Publications and source records attributed to Y Sakamoto.

At least 649 records · Page 36Linked to original sources
PubMed1985

Comparison of drug-metabolizing activities in the livers of carcinogen-sensitive parent rats and carcinogen-resistant descendants.

Donryu strain albino rats were maintained on a diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) for nine successive generations. Some rats in the fourth to eighth generations showed marked resistance to the carcinogenic action of 3'-Me-DAB. In the liver where we found tumors, their size and number are smaller than in the corresponding original strain of rats fed on a diet containing 3'-Me-DAB. No significant differences were found in the total cytochrome P-450 contents or epoxide hydrolase activities of the livers of the resistant variant and the original strain, but the benzo(a)pyrene hydroxylase activity which is mainly attributed to cytochrome P-448 and glutathione S-transferase activity of the resistant variant were lower. The inductions of hepatic cytochrome P-488 and benzo(a)pyrene hydroxylase on administration of polychlorinated biphenyls or 3-methylcholanthrene were also lower in the resistant rats. In the mutagenicity test on Salmonella typhimurium TA 98 the liver 9000 X g supernatant fraction from 3'-Me-DAB-resistant F7 rats did not fully induce the mutagenicities of 3'-Me-DAB and several other carcinogens. Thus the resistance of F7 rats to the chemical carcinogen may be related to the lower activities of some drug-metabolizing enzymes and the poor inducibility of cytochrome P-448 in their liver, although selection of resistant rats should be continued for further generations before coming to a definite conclusion on biochemical basis of apparent resistance to 3'-Me-DAB.

Animals↗
PubMed1985

Undenuded invasive cervical carcinomas erroneously treated by cauterization.

Two cases of occult invasive carcinoma of the cervix have been reported with emphasis on diagnostic failure and subsequent inappropriate treatments. A prompt replacement with malignant cells simulating dysplasia or carcinoma in situ was observed at the sites of cauterization preoperatively. However, histology of postoperative specimen showed apparent invasiveness in both cases and lymphatic metastases in one of them. These findings have led us to a concept that the present cases may represent a variety of occult carcinomas, which is in between the common and verrucous types of squamous cell carcinomas.

Adult↗
PubMed1985

[Statistics of genitourinary tumors at Mito Saiseikai Hospital].

The statistics of genitourinary tumors proved by histology as benign or malignant were analyzed for a total of 7,705 patients at the Mito Saiseikai Hospital from 1974 to 1984. The prostate, the bladder, and the kidney were the organs from which the tumors originated most frequently, in that order. Among the benign tumors, benign prostatic hyperplasia (55 cases) was the most frequent. Among the malignant tumors, bladder tumor (22 cases), prostate carcinoma (20 cases), and renal tumor (9 cases) were the most frequent. The overall 5-year survival rate was 50%. The survival of patients with bladder tumor was similar to that of the patients with renal pelvic or ureteral tumors of a transitional-cell origin. The worst survival was observed in penile carcinoma. It can be concluded that the incidence and survival of genitourinary tumors in the Mito area were not significantly different from those reported in other parts in Japan.

Adult↗
PubMed1984

A cold-labile acetyl-coenzyme-A hydrolase from the supernatant fraction of rat liver. Reactivation and reconstitution of the active species from the inactive monomer.

An acetyl-coenzyme-A hydrolase from the supernatant fraction of rat liver is known to be rapidly inactivated at low temperature. Loss of catalytic activity is accompanied by apparent dissociation of tetrameric and dimeric forms of the enzyme into monomers. It was found that rewarming under appropriate conditions almost completely reversed the cold-induced inactivation and dissociation of the enzyme: At a protein concentration of 14 micrograms/ml, simple rewarming only partially restored the enzyme activity (less than 3% of the original activity), but at a higher concentration of the enzyme or in the presence of 1 mg/ml bovine serum albumin, the reactivation by warming was greater. Warming at 37 degrees C appeared to be optimal for reactivation; warming at 25 degrees C or at 43 degrees C was less effective. Longer exposure to cold did not affect reactivation on rewarming, but on repeated inactivation and reactivation the reactivation decreased to some extent, especially at lower concentrations of enzyme protein. Among various nucleotides tested, ATP greatly enhanced the restoration of the activity, while ITP, UTP and ADP were less effective and AMP, GTP, TTP and CTP had little effect. At an enzyme-protein concentration of 14 micrograms/ml, 2 mM ATP restored the enzyme activity to about 70% of that before cold treatment, while acetyl-CoA (0.5 mM) restored the activity about 50%. High concentrations of phosphate (0.92 M) and pyrophosphate (0.45 M) restored about 80% and 95%, respectively, of the original activity. Sucrose density gradient centrifugation of the active dimer at high enzyme concentration at 4 degrees C for 20 h produced a monomeric form without catalytic activity. Gel filtration showed that simple rewarming mostly converted the monomeric enzyme obtained in this way to the dimeric form, whereas on rewarming with ATP the monomer was mostly converted to a tetrameric form. The dimeric and tetrameric forms both had catalytic activity.

Acetyl Coenzyme A↗
PubMed1984

An ATP-stimulated factor that enhances the nuclear binding of "activated" receptor-glucocorticoid complex.

A macromolecular material that enhances the translocation, or binding, of already "activated" receptor-glucocorticoid complex to nuclei in the presence of 5 mM ATP was separated from the cytosol of rat liver by DEAE-cellulose column chromatography with about 0.025 M NaCl. The molecular weight of the material was about 93,000 +/- 4,900, as determined by agarose gel filtration. After incubation at 60 degrees C for 15 min, this material still had activity to increase the nuclear binding, but on boiling for 15 min it lost its activity.

Adenosine Triphosphate↗
PubMed1984

Separation and characterization of receptor-translocation inhibitors from AH 130 tumor cells.

The objective of this investigation was to study the relationship between glucocorticoid resistance and macromolecular receptor-translocation inhibitors ( MTIs ). MTIs in various cytoplasmic preparations are known to inhibit the "activated" receptor-steroid complex association with isolated nuclei, chromatin, or DNA. It was found that the MTI in the cytosol of AH 130 tumor cells (glucocorticoid resistant cells) appeared to be about 5 times more inhibitory than crude MTI from rat liver. Another difference between these MTI preparations was that ATP decreased the inhibition by crude MTI from rat liver, but had little effect on that of MTI from the tumor cells. Both preparations gave three fractions of material with inhibitory activity on DEAE-cellulose chromatography. The first fraction (Peak I), eluted with about 0.1 M NaCl, was the largest fraction separated from the tumor cytosol, but a minor fraction of that from liver. In the presence of 5 mM ATP, Peak I from rat liver enhanced nuclear binding, but that from the tumor did not, suggesting that these fractions were qualitatively different. The other two fractions (Peak II and Peak III), eluted with about 0.2 M and 0.3 M NaCl, respectively, were comparable in the two preparations.

Adenosine Triphosphate↗
PubMed1984

Activation of insulin-sensitive phosphodiesterase by lectins and insulin-dextran complex in rat fat cells.

Membrane-bound low-Km cAMP phosphodiesterase was activated by concanavalin A, wheat germ agglutinin, and insulin-dextran complex under conditions of incubation with intact rat fat cells. Concanavalin A rapidly stimulated the enzyme activities and maximum was reached at 10 to 15 minutes. As little as 10 micrograms/mL concanavalin A activated the enzyme and a maximal response was obtained at 100 to 300 micrograms/mL, but concanavalin A and wheat germ agglutinin were less potent than insulin. Specific saccharide inhibitors completely abolished activation of the enzyme by lectins, but had no effect on the activation of insulin. Digestion of fat cells with 1 mg/mL trypsin for 15 minutes completely inhibited activation of the enzyme by insulin. However, concanavalin A was less sensitive to trypsinization. The insulin-dextran complex, which did not penetrate the plasma membrane, activated the enzyme and was one tenth as effective as the native insulin. These results suggest that the insulin-like actions of these lectins are provoked through coupling with the carbohydrate moiety on the cell membrane close to insulin receptors.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

Enhancement effects of barbital on the teratogenicity of aminopyrine.

Aminopyrine and its compound with barbital have been used in humans as analgesics and antipyretics. A compound, pyrabital (2 molecules of aminopyrine and 1 molecule of barbital) given daily on Days 9, 10 and 11 of gestation produced significant yields of fetal deaths and malformations in ICR/Jcl mice. Most malformations induced were ruptured omphaloceles (eventration of the abdominal viscera), which were associated with malrotation of the intestine, cleft palates, and tail anomalies, finger and toe anomalies. Aminopyrine also induced significant yields of fetal deaths and malformations. However, the incidence of fetal deaths and malformations induced by a dose of pyrabital was significantly higher than that by an equivalent dose of aminopyrine which was contained in pyrabital. When aminopyrine (0.21 mg/g) and barbital (0.09 mg/g) were given in 2 separate injections to pregnant mice, teratogenicity was approximately equal to that by the equivalent dose of pyrabital (0.3 mg/g). Consequently, potent teratogenicity of pyrabital is not caused by the compound, but only by the coexistence of barbital and aminopyrine. Such enhancement effects of barbital may be due to the induction of enzymes responsible for transforming aminopyrine to teratogenic forms, because pretreatment with barbital and phenobarbital similarly enhanced embryotoxicity of aminopyrine.

Abnormalities, Drug-Induced↗
PubMed1984

Induction of lymphorecticular neoplasia and malformations by prenatal treatment with 1,3-di(4-sulfamoylphenyl)-triazene in mice.

1,3-Di(4- sulfamoylphenyl )-triazene ( DSPT ), synthesized from two equivalents of sulfanylamide and one equivalent of sodium nitrite, induced specific types of tumors (lymphoreticular neoplasias) in the offspring, when it was given orally to pregnant mice on Days 13-18. Tumor incidences were 6.1, 20.0, and 21.7%, when DSPT was given at 1, 4 and 10% concentration in the diet, respectively, while the control value was 0.8%. DSPT did not induce lung tumors, which are commonly induced by mutagenic carcinogens. DSPT also produced malformations (cleft palate, exencephalus , etc.), when given intraperitoneally on Days 9, 10 and 11. Incidence increased with increasing doses of DSPT , that is, 15.8, 21.1 and 36.7% at doses of 22, 36 and 44 micrograms/g, respectively, while the incidence was 0.3% in the untreated controls. DSPT was found to be non-mutagenic but weakly clastogenic in Drosophila melanogaster.

Abnormalities, Drug-Induced↗
PubMed1984

Partially purified "activated" receptor-glucocorticoid complex from rat liver: regulation of nuclear, chromatin, and DNA-cellulose binding of "activated" complex by pyrophosphate and ATP.

The effects of PP1 and ATP on nuclear binding of the "activated" receptor-[3H]-triamcinolone acetonide (TA) complex purified about 3,000-fold from adrenalectomized rat liver were investigated. ATP at up to 5 mM did not affect nuclear binding of the "activated" complex, but PP1 at 2-7 mM greatly enhanced it. However, ATP in the presence of PP1 decreased nuclear binding dose-dependently. Similar results were obtained in the case of chromatin binding, but PP1 alone did not alter DNA-cellulose binding of the "activated" complex, suggesting that the binding sites for chromatin and DNA on the "activated" complex are different. Furthermore, PP1 enhanced ATP-agarose binding of the "activated" complex, indicating that the PP1 binding site(s) on the receptor is different from the ATP binding site(s). The physicochemical properties of the "activated" receptor-glucocorticoid complex bound with ATP and/or PP1 were examined by sucrose density gradient centrifugation and Sephadex G-150 gel filtration. There was no detectable change in the sedimentation coefficient or molecular weight (about 4.2S; Mr approximately equal to 98,000) on binding with ATP and/or PP1. These results suggest that the binding of PP1 and PP1 plus ATP to the "activated" complex caused some allosteric change of the acceptor binding sites of the receptor, resulting in increase or decrease in its binding to nuclei, chromatin, or DNA.

Adenosine Triphosphate↗
PubMed1984

Histamine metabolism in patients with histidinemia: determination of urinary levels of histamine, N tau-methylhistamine, imidazole acetic acid, and its conjugate(s).

Histamine metabolism in histidinemic patients was studied by measuring the urinary levels of histamine and its metabolites. The urinary excretions of histamine, N tau-methylhistamine, imidazole acetic acid, and its conjugate(s) were higher in patients with histidinemia than in controls, and these levels of excretion were correlated with the plasma histidine level. The urinary histamine levels of patients with eczema-like dermatitis were twice that of those without dermatitis. The urinary excretion of 3-methylhistidine showed a close correlation with the urinary histidine excretion. Thus, it was concluded that histamine metabolism is higher in histidinemic patients than in normal controls.

Amino Acid Metabolism, Inborn Errors↗
PubMed1984

Circulating immune complexes in patients with house-dust-mite-sensitive bronchial asthma.

Sera from forty patients with house-dust-mite-sensitive bronchial asthma were examined for the presence of circulating immune complexes (CIC) by the sensitive and quantitative Clq solid-phase radioimmunoassay (Clq-SP) and a monoclonal rheumatoid factor solid-phase radioimmunoassay (mRF-SP). Compared to fifteen normal individuals, the asthmatic patients showed significantly higher mean values of Clq-reactive materials; however, there was no difference between the results from the patients treated by immunotherapy using Dermatophagoides farinae extract and those not so treated. Moreover, immune complexes in eight patients before and after immunotherapy showed that the amount of the complexes tend to decrease during immunotherapy. Furthermore, the presence of complexes had no relationship with the amounts of mite-specific IgG antibody. Similar results were also obtained in tests using mRF-SP. These data suggest that complexes in the sera of the house-dust-mite-sensitive asthmatic patients are not necessarily associated either with immunotherapy or with the mite-specific IgG antibodies.

Antigen-Antibody Complex↗
PubMed1984

Effects of plasma infusion on plasma lipids, apoproteins and plasma enzyme activities in familial lecithin: cholesterol acyltransferase deficiency.

The siblings presented here are the third family found in Japan with familial LCAT deficiency. Their post-heparin plasma lipoprotein lipase and hepatic triglyceride lipase activities were measured selectively by an immunochemical method. Plasma triglyceride levels were elevated, and post-heparin plasma lipoprotein lipase was decreased only in a patient with nephropathy, while hepatic triglyceride lipase activities were within reference limits in both patients. The plasma concentrations of apo A-I, apo A-II, and apo B were reduced in both patients. On the other hand, the plasma concentration of apo E was markedly increased. Enzyme replacement therapy by plasma transfusion in the propositus resulted in marked improvement of deranged compositions of triglyceride-rich lipoproteins. Also, improvement of the plasma apo E concentration was demonstrated, while the improvement of post-heparin lipase did not occur. These results suggest that LCAT may play an important physiological role in triglyceride metabolism as well as in cholesterol metabolism.

Apoproteins↗
PubMed1984

The effect of insulin-dextran complexes on the protein synthesis in the primary monolayer culture of adult rat hepatocytes.

The purpose of the present study was to investigate the mechanisms of the long-term effects of insulin on protein synthesis in rat liver parenchymal cells. Three kinds of soluble and stable insulin-dextran complexes (I: Mr 150,000; II: Mr 450,000; III: Mr 2,000,000) were prepared. The effects of insulin or insulin-dextran complexes on protein synthesis were evaluated in the primary monolayer culture of adult rat liver. To avoid the effects of serum factors, the primary monolayer culture of adult rat liver in serum free medium was established. The cultured hepatocytes well maintained the metabolic and morphological characteristics of the adult rat liver. The incorporation of [14C]-leucine into trichloroacetic acid insoluble proteins and immunoprecipitates by anti-rat albumin serum were measured in cultured hepatocytes prepared either from the control or streptozotocin-induced rats. An addition of insulin-dextran complexes to the culture medium of the hepatocytes from diabetic rats stimulated the protein synthesis as well as the native insulin. The maximal effect of insulin-dextran complex (I) on protein synthesis was comparable to native insulin. However, insulin-dextran complex (II) caused a 67% stimulation of native insulin. Insulin-dextran complexes (III) induced only a slight increase of protein synthesis. Furthermore, an addition of insulin-dextran complexes into the medium caused a more tight cellular attachment to the dish and more extensive spreading. These results favor the view that the stimulation by insulin of protein synthesis in rat hepatocytes does not require the entry of insulin into cells.

Albumins↗
PubMed1984

Clinical and histological features of sporadic non-A, non-B hepatitis.

The incidence of hepatitis A (HA), hepatitis B (HB), and non-A, non-B hepatitis (NANBH) was 27%, 30% and 43% among 73 patients with sporadic hepatitis. Epidemiological data (geographical distribution, seasonal variation, age, sex, and occupation) were not distinguishing of the type of hepatitis. Neither intrafamilial infection nor previous contact with viral hepatitis patients could be demonstrated in the NANBH cases. Fever and jaundice were less frequent in NANBH than in HA. Maximum levels of SGPT, serum bilirubin, ZTT, and gamma-globulin were significantly lower in NANBH than in HA and HB. Ten of 29 NANBH patients (35%) presented abnormal SGPT activities for more than 6 months, and four (14%) more than 12 months. In the ten patients with prolonged courses, jaundice was more frequent and maximum levels of SGPT were higher than in patients with transient courses. Histopathologic findings were not markedly different from those of HA and HB. Bile duct damage, fatty deposition, and giant multi-nucleated cells were recognized in 6, 12, and 2 NANBH patients, respectively. There were no characteristic ultrastructural changes in NANBH.

Adolescent↗