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Biomedical subjects

M Izawa

Publications and source records attributed to M Izawa.

At least 127 records · Page 7Linked to original sources
PubMed1984

Properties and functions of a nucleolus-specific phosphoprotein of mouse ascites sarcoma cells.

A 110K-dalton phosphoprotein previously was isolated from the nucleoli of mouse ascites sarcoma cells. The localization of this phosphoprotein in the nucleoli was confirmed by an indirect immunofluorescence assay with rabbit antisera to the phosphoprotein. This phosphoprotein formed a complex of 280K daltons with a nonphosphoprotein of 32K daltons in a molar ratio of 1 to 1. The protein complex dissociated in the presence of 6 M guanidine hydrochloride or 1% sodium dodecylsulphate. The nucleolus-specific phosphoprotein complex bound preferentially to nucleolar DNAs other than the ribosomal RNA gene in vitro and located in nucleosomes prepared from the nucleoli. The major phosphoamino acid in the phosphoprotein was phosphoserine, and slight though significant amounts of phosphotyrosine and phosphothreonine also were detected. These phosphorylated amino acids were concentrated in a specific polypeptide fragment of about 30K daltons obtained by partial digestion with V8 protease. The phosphoprotein was phosphorylated in vitro by the protein kinase activity presented in the complex itself.

Amino Acids↗
PubMed1984

Cytoplasmic inhibiting factors for 3H-dexamethasone binding to glucocorticoid receptors in rat tissues.

Factors which specifically inhibit 3H-dexamethasone binding to unoccupied glucocorticoid receptors were examined in cytosols of the seminal vesicle and ventral prostate of rats. The inhibiting factors are mostly precipitated at 40-50% saturation of (NH4)2SO4 and eluted from a Sephacryl S-200 column immediately after the elution volume of bovine serum albumin. The inhibitory activity was relatively heat-stable and decreased to approximately 35% of the initial activity by trypsin digestion. These results suggest that the inhibiting factors are of a polypeptide-like nature. The inhibitory activity of the factors seems to be blocked by treatment with dithiothreitol and molybdate. The inhibiting factors act to decrease the binding affinity of glucocorticoid receptors to 3H-dexamethasone without altering the number of the available binding sites in cytosols. These results indicate that the binding of glucocorticoid receptors to ligands in vitro is influenced by a number of factors.

Adrenalectomy↗
PubMed1984

Glucocorticoid receptor in the rat uterus.

3H-Dexamethasone binding sites with a Kd of approximately 0.7 nM and a maximum number of binding sites of approximately 0.3 pmoles/mg protein were demonstrated in the uterine cytosol of adrenalectomized rats only if dithiothreitol was present in the incubation mixture and the simultaneous presence of molybdate further enhanced the binding in the cytosol. The binding sites exhibited a high specificity for glucocorticoids and were depleted in a dose-dependent manner from cytosol after administration of dexamethasone to animals. The depletion was not due to the occupation of the binding sites by the dexamethasone administered and the rate of depletion was correlated with the inhibition of uterine growth induced by estrogen administration. The cytosol labeled with 3H-dexamethasone in the presence of dithiothreitol bound to DNA-cellulose efficiently after heating at 25 degrees C for 30 min and the binding was inhibited by pyridoxal 5'-phosphate added to the reaction mixture. The effect of heating on the DNA-cellulose binding was abolished by molybdate in the incubation mixture. From these observations, it was concluded that 3H-dexamethasone binding sites in the rat uterus were physiologically active glucocorticoid receptors.

Adrenalectomy↗
PubMed1984

Stability of receptor complexes in the rat liver bound to glucocorticoids of different biopotencies.

To examine the behavior in the receptor-acceptor system of glucocorticoids of different biopotencies, the stability of receptor complexes of dexamethasone (Dex), prednisolone (Pred) and corticosterone (Cort) in cytosols, nuclei and nuclear extracts from the rat liver was compared. Receptor complexes bound to these ligands were relatively stable at 0 degrees C, but at 25 degrees C a rapid liberation of ligands was observed. However, differences in the rate of temperature-dependent decay of these receptor complexes were obvious; the Dex receptor complex was the most stable, the receptor complex bound to Cort liberated the ligand most rapidly and the stability of the Pred-receptor complex was the intermediate of these two. The addition of molybdate and dithiothreitol stabilized the receptor complexes in cytosols but these agents accelerated the liberation of ligands from the complexes in nuclei and nuclear extracts. Among the factors examined, only bovine serum albumin decreased the rate of decay in the nuclear-bound receptor complexes. From these observations, it appears likely that different mechanisms may contribute to the dissociation of ligand from receptor complexes in cytosols, nuclei and nuclear extracts.

Animals↗
PubMed1984

[Toxicological studies on a new cephamycin, MT-141. VII. Its locally-irritating activity in rabbits].

The local irritation of MT-141 was compared with that of cefmetazole (CMZ) in rabbits to obtain following results. Microscopic observations revealed that the irritative activity of 10% solution of MT-141 in blood vessels was not so much different from that of saline and 10% solution of CMZ when they were injected twice a day into vein retroauricularis of rabbits for 7 days. The histopathological changes induced by 10% solution of MT-141 were similar to those by 10% solution of CMZ but somewhat different from those by saline, because both compounds caused slight necrosis in the tissue around vessels. Histopathological observations suggested that the occurrence of necrosis was due to the leakage of them during injections. The local irritation of MT-141 by an injection of 1 ml of its solution into muscle vastus lateralis was compared with that of CMZ in rabbits. The potencies of irritative activity of the test solutions were summarized in the following order; saline less than 5% MT-141 less than 10% MT-141 not equal to 10% CMZ much less than 0.75% acetic acid less than 6.0% acetic acid. The above-mentioned results suggest that MT-141 has low irritating activity when injected through intravenous or intramuscular route for clinical practice as 5% or 10% solution.

Animals↗
PubMed1984

[Toxicological studies on a new cephamycin, MT-141 IX. Its teratogenicity test in rats and rabbits].

A teratogenicity study of MT-141 was performed in SD rats and Japanese white rabbits. The pregnant rats were administered intramuscularly (i.m.) with MT-141 at the dose levels of 200, 400, 800 and 1,600 mg/kg/day from the day 7 up to the day 17 of gestation. The pregnant rabbits were administered intravenously (i.v.) with the drug at the dose levels of 10, 20 and 40 mg/kg/day from the day 6 up to the day 18 of gestation. The results are summarized as follows. Rats: Though the administrations with MT-141 at all dose levels did not change body weight gain and water intake of treated dams, a slight suppression in the food consumption was produced by MT-141 at the dose of 1,600 mg/kg/day. The examinations on cesarean section revealed no effect of MT-141 on teratological parameters such as external malformation and frequency of visceral and skeletal anomalies in the fetuses. MT-141 at all dose levels exerted no toxic effect on developmental, functional and behavioral parameters in F1 rats and on mating, fertility and pregnancy of F1 rats. Furthermore, there was no effect of MT-141 on the findings in cesarean section of F1 rats. The fetuses from F1 rats had no malformation of external appearance, viscera and skeleton. Rabbits: MT-141 had no significant effect on body weight gain and food consumption of dams at the all dose levels, but caused a slight suppression in the water intake at the doses more than 20 mg/kg/day. One rabbit aborted in each group given 20 or 40 mg/kg/day. One rabbit died in the group given 20 mg/kg/day. Examinations on cesarean section showed that MT-141 at the dose of 40 mg/kg/day produced a decrease in body weights of females and an increase in dead or resorbed fetuses followed by a decrease in live fetuses. MT-141 is no effect malformation of external appearance, viscera and skeleton in the fetuses of all treated groups. The above-mentioned results suggest that MT-141 has no teratogenic effect on pregnant rats and rabbits. It is concluded from these results that the maximal "no effective" dose of MT-141 on fetal toxicity is above 1,600 mg/kg/day i.m. for pregnant rats and 10 mg/kg/day i.v. for pregnant rabbits.

Abnormalities, Drug-Induced↗
PubMed1984

[Toxicological studies on a new cephamycin, MT-141. X. Its perinatal and postnatal test in rats].

A perinatal and postnatal study of MT-141 was performed in SD rats. The dams were administered intramuscularly (i.m.) with MT-141 at the dose levels of 400, 800 and 1,600 mg/kg/day from the day 17 of gestation until the day 21 post delivery. The results are summarized as follows. No significant adverse effects of MT-141 were observed on the body weight gain, food consumption and water intake in dams of all groups treated with the drug during the perinatal and postnatal period. MT-141 did not change parameters of reproductive study in birth, development, physiological function and behavior of F1 rat. This compound had no effect on the fertility in F1 rats and also did not caused significant defects in the external appearance, viscera and skeleton of fetuses from dams (F1). It is concluded from these results that the maximal "no effective" dose of MT-141 is above 1,600 mg/kg/day i.m. for dams and the offsprings.

Animals↗
PubMed1984

[Toxicological studies on a new cephamycin, MT-141. XI. Immunological properties].

Immunogenicity, eliciting antigenicity of MT-141 and its cross-reactivity with other beta-lactam antibiotics were studied in mice, guinea pigs and rabbits. The results were as follows. Injections of MT-141 failed to produce IgE-type antibody in mice but injections of the MT-141 conjugated to rabbit serum albumin produced a trace of IgE-type antibody. No antibody was produced in the guinea pigs immunized with the MT-141 conjugated to rabbit serum albumin in alum or Freund's complete adjuvant. The conjugated MT-141 also failed to elicit anaphylactic shock in the immunized guinea pigs. The subcutaneous treatments with MT-141 in Freund's complete adjuvant produced an amount of hemagglutination antibody in rabbits. The intravenous treatments with MT-141 produced no antibody in rabbits. When rabbits were subcutaneously immunized with the MT-141 conjugated to rabbit serum albumin in Freund's complete adjuvant, production of specific antibody in the rabbits was demonstrated by observations of passive cutaneous anaphylaxis and hemagglutination. The results of hapten-induced inhibition of passive hemagglutination, passive cutaneous anaphylaxis, anaphylactic shock and hemagglutination by using conjugates of antibiotics and rabbit serum albumin as immunogens and conjugates of antibiotics and bovine gamma-globulin as eliciting antigen showed that MT-141 did not cross-react with other antibiotics. MT-141 did not cause the in vitro direct Coombs' reaction in the human blood even at a high concentration of 160 mg/ml. It is concluded from these results that immunological activity of MT-141 preparation is weak.

Anaphylaxis↗
PubMed1984

[Gangliogliomas in cerebral hemisphere].

Gangliogliomas are rare central nervous system neoplasms. The clinical features, radiological findings and surgical results in 6 histologically proven cases of gangliogliomas in the cerebral hemisphere are reviewed. The ages varied between 8 and 58 years old at the time of diagnosis. Five patients had seizure disorders without focal neurological deficit or clinical signs of increased intracranial pressure. These 5 patients had been treated as epilepsy for 6 months to 12 years. The other one patient had right sided motor weakness and left homonymous hemianopsia without seizure disorder. Plain roentgenograms of the skull revealed abnormal calcification in 3 out of 6 patients. Angiography showed an avascular mass in all 6 patients. CT scan were examined in 5 patients. In 3 patients the tumor were isodense, 2 of which demonstrated contrast enhancement. The other 2 showed low density lesion. One showed a single large cyst and another ill-defined low density containing high density calcification. In all 5 patients mass effect was slight. Three tumors were located in the temporal lobe and another 3 in the parietal lobe. At surgery total removal was accomplished in 3 patients. One patient had subtotal removal and 3 patients partial removal. Histological study revealed figures characteristic to the ganglioglioma. The predominant glial cell was astrocytic in 4 cases and oligodendroglial component was found in the other 2 cases. All patients either completely or nearly asymptomatic at the follow up for 1 to 12 years. The clinical study in 6 cases, along with a review of the literature suggest that these epileptogenic neoplasms should be aimed at surgical removal or total extirpation if possible.

Adolescent↗
PubMed1984

Stability of receptor complexes in the rat ventral prostate and seminal vesicle bound to androgens: thermodynamic study.

To examine the behaviour of the receptor-acceptor system of androgen of different biopotencies, we compared the stability of receptor complexes of dihydrotestosterone (DHT), methyltrienolone (R1881) and testosterone (Test) in cytosols, nuclei and nuclear extracts from ventral prostate and seminal vesicle of rats. Liberation of ligand from receptor complexes bound to these ligands followed the first-order kinetics. The rate constant for ligand liberation at 25 degrees C varied with the ligand. The receptor complexes bound to Test were most labile, while the receptor complexes bound to DHT were relatively stable, and intermediate stability was observed in the receptor complexes bound to R1881 under the conditions employed in the present study. Thermodynamic characteristics of the stability of the complexes were also different in these three androgens. The Arrhenius plots of the rate constant for the liberation of ligand from R1881- and DHT-receptor complexes in cytosols and nuclei showed curvilinearities, but the plots for Test-receptor complexes were almost linear. In addition, the stabilizing effect of molybdate on R1881- and DHT-receptor complexes in cytosols was observed in the range of low temperature, while the effect on Test-receptor complexes was significant at the higher temperature. The differences observed in the present study seem to be related to the difference in the biological potency of these androgens.

Animals↗
PubMed1983

Negatively charged RNase-susceptible molecules on the surface of ascites tumor cells.

RNase-susceptible ionogenic groups on the cell surface membranes of two leukemic and two nonleukemic strains of ascites tumor cells were studied by cell electrophoresis, DEAE-Sephadex A-25 column and paper chromatography, and indirect membrane immunofluorescence. RNase treatment of the nonleukemic ascites tumor cells (Ehrlich ascites tumor and Sarcoma 180) produced a significant reduction in their electrophoretic mobilities. When the cells were labeled with [3H]uridine then incubated with RNase, there was a marked increased in the radioactive nucleotides present in the incubation medium as compared to the results of the experiment with RNase-untreated controls. Indirect membrane immunofluorescence studies of nonleukemic ascites tumor cells suggest that the sites that react with anti-RNA antibody are distributed diffusely on their surfaces. RNase treatment of these cells markedly reduced their ability to react with the antibody. It thus appears that RNAs are present on the surface membrane of nonleukemic ascites tumor cells and that RNase digests these RNAs, removing negatively charged nucleotides from their electrophoretic surfaces. This results in a reduction in mobility. In contrast, leukemic ascites cells (L1210 and C1498) incubated with RNase showed no significant change in mobility or in the amount of nucleotides released into the incubation medium. Moreover, no fluorescence was found on the surface of cells examined by indirect membrane immunofluorescence. This suggests that leukemic ascites cells are devoid of RNAs on their surface.

Animals↗
PubMed1983

Receptor recycling: liberation of glucocorticoid receptors from liver nuclei in vitro.

Dynamics of the steroid receptors seems to be the consequence of receptor recycling. In the present study, as a clue to elucidate the mechanism of receptor recycling, factors which affect the rate of liberation of nuclear bound 3H-glucocorticoids were examined in vitro. Among the factors examined, NAD, NADPH, cAMP and p-nitrophenyl phosphate accelerated the liberation of radioactivity from nuclei in a temperature-dependent manner when added to the incubation mixture. The presence of a large amount of unlabeled dexamethasone (Dex) did not modify the rate of liberation. From these results, it was concluded that the metabolism of ligand bound to the receptor is not a necessary step in the liberation of receptor from nuclei. These agents did not influence the binding process of 3H-Dex-receptor complex to DNA-cellulose. Therefore the stimulation of receptor release does not seem to be mediated by reducing the binding affinity between nuclei and receptor complexes. The liberated radioactivity was eluted on a Sephadex G-100 column in the void volume and in macromolecule-unbound fractions. In both fractions, the majority of the radioactivity comigrated with authentic glucocorticoids on thin-layer chromatography.

Animals↗
PubMed1983

Binding sites for glucocorticoids in cytosols from the ventral prostate and seminal vesicle of rats.

Binding sites for 3H-dexamethasone (Dex) were demonstrated in cytosols from the ventral prostate and seminal vesicle of rats only if dithiothreitol (DTT) was present in the incubation mixture. The binding observed in the presence of DTT was high affinity (Kd=1-5 nM) and low capacity (Bmax=approx. 0.1 p mole/mg protein) and exhibited a binding specificity for glucocorticoids. The addition of molybdate (Mo) to the incubation mixture enforced the effect of DTT on the binding but the extent of the effect of Mo in cytosols of the ventral prostate differed from that in the seminal vesicle. The binding sites in the cytosols of these tissues were depleted after administration of Dex to animals. The depletion observed was not due to occupation of the binding sites by injected Dex and this was confirmed by the exchange assay. Addition of the cytosol from the seminal vesicle inhibited the 3H-Dex binding in the liver cytosol but the cytosol from the ventral prostate did not show an inhibitory effect. The binding sites in neither of these male accessory sex organs were modified markedly after the animals were castrated. Although the 3H-Dex binding sites observed in the cytoplasm of male accessory sex organs fit the definition proposed for the steroid hormone receptors, it is not clear whether these tissues are under the influence of glucocorticoid or not; the rate of incorporation of 3H-leucine and 3H-orotic acid into the acid-insoluble fraction from the ventral prostate is not influenced by the administration of Dex to animals.

Animals↗