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T Oguro

Publications and source records attributed to T Oguro.

At least 37 records · Page 2Linked to original sources

Nutritionally and chemically induced impairment of sulfate activation and sulfation of xenobiotics in vivo.

Sulfation requires 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as the sulfate donor. In the search for methods to inhibit sulfation reactions via impairment of PAPS synthesis, two experimental conditions have been tested in rats. A low-sulfur diet, which does not deplete hepatic glutathione, reduced inorganic sulfate but not PAPS levels in the liver and moderately decreased sulfation of acetaminophen. Administration of molybdate, which is an alternative substrate for intestinal and renal sulfate transport as well as for ATP-sulfurylase, depleted both sulfate and PAPS in liver and markedly inhibited sulfation of acetaminophen. Therefore, administration of molybdate may be used as an experimental tool to study the role of sulfation in the fate and effect of xenobiotics.

Acetaminophen↗

Effects of the reduction of cytoplasm of mouse 2-cell embryos on blastocele formation timing and developmental ability in vitro and in vivo.

Experiments were conducted to test the hypothesis that the nucleo/cytoplasmic ratio of mouse embryos determines the time of blastocele formation. Half the volume of 2-cell stage embryos was removed from each blastomere by micropipette to alter the nucleo/cytoplasmic ratio. Reduced embryos whose nucleo/cytoplasmic ratio increased and non-treated control embryos were cultured in vitro to compare the timing of division to the 4-cell stage and blastocele formation. Reduced 2-cell embryos formed blastoceles significantly earlier than the controls (49.0 +/-2.9 vs 52.2 +/-6 h) and with fewer cells, although division into the 4-cell stage was significantly delayed (11.4 +/-4.4 vs 9.0+/-2.4 h). The cell number of blastocysts 70 h after treatment and developmental ability of blastocysts after transfer to pseudopregnant recipients were the same for the reduced and control groups. The present study indicates that the nucleo/cytoplasmic ratio of embryos may possibly be an important factor that determines the time of blastocele formation.

Journal Article↗

Molybdate depletes hepatic 3-phosphoadenosine 5-phosphosulfate and impairs the sulfation of acetaminophen in rats.

Molybdate (15 mmol/kg p.o.) decreased serum sulfate concentrations of rats 70% within 6 hr after administration. Parallel to this depletion, there was a dramatic decrease in hepatic sulfate and 3-phosphoadenosine 5-phosphosulfate (PAPS) concentrations (about 40 and 65%, respectively). However, renal PAPS concentrations did not change significantly. Molybdate reduced serum, hepatic and renal sulfate as well as hepatic PAPS concentration in a dose-dependent manner up to the dose of 10 mmol/kg. However, renal PAPS did not change. The results indicate that molybdate reduced not only sulfate concentrations in serum and tissue, but also PAPS concentrations in liver. The effect of molybdate on the pharmacokinetics of acetaminophen (AA, 150 mg/kg i.v.) was also investigated in order to determine whether molybdate-induced depletion of PAPS might be a useful tool for examining the importance of sulfation in the detoxication and toxication of xenobiotics. AA-sulfate concentration in blood decreased 40 and 80% after administration of molybdate at doses of 2.5 and 15 mmol/kg, respectively. Molybdate also decreased the excretion of AA-sulfate into bile and urine by about 60 and 80%, respectively. However, molybdate did not alter the excretion of AA-glucuronide and AA-glutathione/cysteine. The excretion of the parent AA increased 2-fold after molybdate administration (15 mmol/kg). In conclusion, molybdate effectively lowers inorganic sulfate in serum and tissues, and PAPS in the liver. Reduction of hepatic PAPS markedly decreases the sulfation of AA, suggesting that molybdate treatment could be used to study the importance of sulfation in pharmacology and toxicology.

Acetaminophen↗

Ultrastructural effects of hydrogen peroxide on the sarcolemma of rat heart.

Ultrastructural effects of hydrogen peroxide (H2O2) on the sarcolemma of the isolated rat heart were investigated with transmission electron microscopy combined with biochemical, enzyme histochemical, and freeze fracture techniques. Three hundred microM H2O2 were continuously administered to the Langendorff perfused isolated rat hearts. A significant amount of lipid peroxidation associated with depressed Na-K-ATPase activity was observed after 15 minutes of H2O2 perfusion (Group I), and consequently the cell membrane permeability was greatly increased. When 2.5 mM,N'-diphenyl-1,4-phenylenediamine (DPPD), a potent antioxidant, was added to the perfusate, the lipid peroxidation was totally inhibited (Group II). DPPD prevented an increase in the cell membrane permeability. However, Na-K-ATPase activity was not restored by DPPD. Decreased cytochemical staining of Na-K-ATPase was associated with an increase in cell membrane permeability. H2O2 appears to affect, not only lipids but also, intramembranous proteins embedded in the cell membrane. The combined effects of H2O2 on the membrane lipid and proteins result in the formation of membranous blebs.

Animals↗

Effect of exogenous hydrogen peroxide on myocardial function and structure in isolated rat heart.

A time- and dose-dependent effect of exogenous hydrogen peroxide was determined on myocardial function, structure, high energy phosphate and lipid peroxidation in the isolated perfused rat heart. Hydrogen peroxide induced a dose-dependent decrease in cardiac function whereas 200 microM hydrogen peroxide reduced +dP/dt to 50% of control value after 10 mins. The effect of 300 microM hydrogen peroxide was more severe after 15 mins; changes observed with this dose were reversible within 10 mins of perfusion, becoming irreversible after 15 mins. Lipid peroxidation and severe morphological damage were observed after 10 mins of perfusion with 300 microM hydrogen peroxide. When 16 mEq potassium ions were added in the perfusion buffer during hydrogen peroxide perfusion, the degree of tissue damage and loss of ATP were attenuated. However, lipid peroxidation was not inhibited by high potassium ions. When 0.25 microM N,N'-diphenyl-1,4-phenylenediamine, a potent antioxidant, was added to the perfusate, lipid peroxidation was totally inhibited and the degree of tissue damage was decreased. However, depletion of tissue ATP and functional deterioration were not influenced. These results suggest that hydrogen peroxide-mediated ATP loss was independent of lipid peroxidation.

Adenosine Triphosphate↗

Comparative studies of the effects of stilbene compounds on hepatic ornithine decarboxylase and S-adenosylmethionine decarboxylase induction in rats.

Trans-Stilbene oxide (TSO, 2 mmol/kg, ip.) induced ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) to 60-fold and 5-fold of the controls, respectively, in the liver of rats. Parallel to ODC induction, there was a marked increase in putrescine content to 50-fold of the control levels. Cis-Stilbene oxide (CSO), a stereoisomer of TSO, also produced the induction of ODC and SAMDC and the increase in putrescine content. There was no difference in the ability to induce ODC and SAMDC between TSO and CSO with respect to the extents of induction and the time needed to reach maximal levels. Trans-Stilbene (TS), a mother compound of TSO, did not show such an effect on ODC, while cis-stilbene (CS) induced both ODC and SAMDC. Treatment with glutathione inhibited TSO- and CSO-mediated induction of ODC and SAMDC. These findings add new information concerning the abilities of TSO, CSO and CS on hepatic polyamine metabolism.

Acetylcysteine↗

Silver staining of nucleolar organizer regions in prostatic lesions.

Variations in the number of silver-stained nucleolar organizer region-associated proteins (AgNORs) were studied in paraffin sections of 42 benign prostatic lesions, comprising four cases of granulomatous prostatitis, five of squamous or transitional metaplasia, eight of atypical and 25 of regular hyperplasia, and 37 of prostatic adenocarcinoma, with their metastases. There was a significant difference between the mean AgNOR counts of the benign and malignant prostatic lesions (1.58 +/- 0.26 v. 4.34 +/- 1.53; P less than 0.01). The mean AgNOR counts significantly increased with increasing Gleason's grade (P less than 0.01) and clinical stage (P less than 0.05) of the tumours. AgNOR counting may contribute to the conventional diagnostic and prognostic indices of cancer of the prostate.

Adenocarcinoma↗

Immunocytochemical localization of xanthine oxidase in rat myocardium.

Monoclonal antibodies (MAb's) to xanthine oxidase (XO) (from bovine milk) were produced by hybridoma technique. Culture supernatants were initially screened using enzyme-linked immunoabsorbant assay (ELISA). Forty four positive clones were subcloned and further characterized by ELISA and immunoblot analysis. Out of fifteen clones, which were positive in immunoblot analysis, one clone N2-26 was also positive in immunocytochemical studies. Indirect immunoperoxidase and enzyme histochemistry staining showed that XO activity is present in endothelial cells of capillaries, small blood vessels and also in interstitial cells. Electron microscopy revealed that diaminobenzidine reaction product was distributed in the cytoplasm of interstitial cells and endothelial cells of capillaries and small blood vessels. This is the first report of the presence of XO in interstitial cells and endothelial cells of small blood vessels. Allopurinol, which inhibits the xanthine oxidase activity, did not have any effect on the immunocytochemical staining. Our results in normal rat heart suggest that XO activity is confined to interstitial cells, endothelial cells of capillaries and small blood vessels.

Animals↗

Immunohistochemical and ultrastructural localization of T antigen in ovarian tumors.

Thomsen-Friedenreich (T) antigen, the immediate precursor antigen of the human blood group MN system, has been found in many carcinomas, but it is suppressed in normal tissues and nonmalignant diseases. Using a monoclonal antibody specific for the T epitope and an indirect immunoperoxidase technique at light and electron microscopic levels, the authors studied the expression of T antigen and its potential diagnostic value in ovarian tumors. Among 30 serous and mucinous ovarian cystadenocarcinomas, 20 (67%) were positive and 10 (33%) were negative for T antigen. In carcinomas, positive rates increased in parallel with the tumor grade and were 37%, 75% and 80% for grade 1, 2, and 3 tumors, respectively. Of the nine patients with metastasis, seven (78%) had positive and two had negative reactions in their primary and metastatic tumors. T antigen staining was observed at the intraluminal cell surfaces and peripheral cell membranes. The ultrastructural localization of T antigen revealed electron-dense reaction products at the cell surface and microvillous surfaces. Of the ten benign ovarian tumors, three (30%) were weakly positive and seven (70%) were negative for T antigen. These findings indicate a positive correlation between the presence of immunoreactive T antigen and conventional unfavorable prognostic indicators in ovarian carcinoma. The surface location of T antigen suggests that it may have a functional role at the cell membrane and the membrane may be involved in secretion (shedding) of T antigen. Detection of T antigen may be a useful marker of prognosis in ovarian carcinoma.

Antibodies, Monoclonal↗

Combined immunohistochemical study of tissue polypeptide antigen and cancer antigen 125 in human ovarian tumours.

An indirect immunoperoxidase method was used to study the expression of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA 125) in 47 benign and malignant ovarian tumours. Tissue polypeptide antigen and CA 125 antigen were expressed respectively in 22 (73%) and 16 (53%) of the 30 adenocarcinomas and in five (29%) and four (23%) of the 17 benign tumours. Co-expression of TPA and CA 125 antigen occurred in 12 (40%) malignant and four (23%) benign tumours. Ultrastructurally, TPA and CA 125 antigens were located at the cell surface and microvillous surfaces. Evaluation of combined TPA and CA 125 antigen results revealed a remarkable improvement in the positivity rate and a significant decrease (P less than 0.05) in the negativity rate of ovarian carcinomas as compared with the result of each one separately. These findings provide complementary evidence for the previous results on the plasma levels of TPA and CA 125 antigen and suggest that specific combinations of tumour markers may be more effective for the diagnosis and monitoring of ovarian carcinomas, than the use of any single marker.

Antigens, Neoplasm↗

Possible role of glutathione depletion in the induction of rate-limiting enzymes involved in heme degradation and polyamine biosynthesis in the liver of rats.

Ten compounds with a wide variety of structures, which decreased hepatic glutachione (GSH) content at an early time period after their administration, simultaneously increased hepatic heme oxygenase, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activities in rats. The compounds examined were four alpha, beta-unsaturated carbonyl compounds, two prototype substrates for GSH transferase(s), one epoxide, two isothiocyanates, and an indicator of hepatic function test. Time course studies with 1-chloro-2,4-dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzene (DCNB), which are prototype substrates for GSH transferases, showed that there was an inverse relationship between the early depletion of hepatic GSH content and induction of heme oxygenase, ODC and SAMDC together with a decrease in cytochrome P-450 content and an increase in putrescine content. Buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, also increased heme oxygenase and SAMDC activities, but not ODC, and it tended to enhance the induction of the enzymes evoked by diethyl maleate (DEM), phorone and CDNB with the sustained depletion of GSH content. In contrast, GSH treatment inhibited DEM-, phorone-, and CDNB-mediated induction of these enzymes and the early depletion of GSH content. N-Acetylcysteine failed to inhibit DEM- and phorone-mediated induction of these enzymes and the early depletion of GSH content, while it inhibited somewhat these changes produced by CDNB. The findings suggest that the early depletion of hepatic GSH content is prerequisite for and plays a role in the induction of heme oxygenase, ODC and SAMDC.

Adenosylmethionine Decarboxylase↗

[Development of the computed electroradiography. Trial manufacture of digital imaging system].

The fundamental element of a latent image on a selenium plate of Electroradiography is a electrical charge. Therefore, the spatial resolution which can be expected from Electroradiography is extremely high. Here, the author developed the Pulse Electron Beam Scanner (PEBS) as the technique to obtain digital pictorial information from the latent image and obtained following results; 1. We succeeded in converting the latent image into digital signal with high accuracy by using secondary emitted electron through the apparatus that features pulsed electron beam, summing function for secondary emitted electron and plurally arranged detectors and extraction field applied grid. 2. The spatial resolution which we can enjoy to obtain through this apparatus is greater than 500 Lp/mm and the dynamic range at the time when we obtained 500 Lp/mm in terms of the voltage applied to the electrode was +60V to +110V. 3. We succeed in obtaining the digital X ray picture of the bone trabecular structure of human spongy bone with 50 power magnification without using any enlargement picture taking method. The above results indicate that converting the latent image on the selenium plate into digital signal with very high spatial resolution by using PEBS system was achieved. Therefore, we can conclude that we succeeded in obtaining the high spatial resolution digital image from the electroradiographic latent image which has the spatial resolution as high as electrical charge distribution.

Bone and Bones↗

[Identification and susceptibility of clinically isolated yeast-like fungi].

We studied the identification and susceptibility of clinically isolated yeast-like fungi at Showa University Hospital from April 1988 to March 1989. Clinically significant of yeast-like fungi were observed in 7.1% of specimens from outpatients, 13.0% of inpatients. In both outpatients and inpatients, yeast-like fungi were isolated mainly from sputum and urine. But, one third of them were considered as non-pathogenic and not identified. The species of isolates were, Candida albicans 57%, Candida tropicalis 14% and Candida glabrata 8% in both inpatients and outpatients, and these species shared most part. The isolation frequency of Candida parapsilosis was higher in blood and cerebrospinal fluid (CSF) specimen than the others. The susceptibility test by agar dilution method indicated most of the isolates were susceptible to Amphotericin B and Miconazole (MIC less than or equal to 25 micrograms/ml). There was no difference in MIC between predominantly isolated fungi and commonly isolated fungi. Notably, isolates from blood and CSF showed a significant high tolerance against Amphotericin B and Miconazole than from the other specimens. The MICs of Fluconazole were shown to be very high (greater than 100 micrograms/ml) in normal Sabouraud agar, were decreased dose-dependently by human sera in the medium. These findings indicated the component(s) of sera enhanced the anti-fungal activity of Fluconazole.

Amphotericin B↗

Tissue polypeptide antigen expression in human prostate tumors.

Thirty-seven specimens of benign and malignant prostatic tumors were studied for the localization of tissue polypeptide antigen (TPA) by an avidin-biotin-peroxidase complex technique. In addition, 23 metastases of prostatic carcinoma in other organs and 12 nonepithelial tumors of prostate also were studied. All benign and malignant tumors of epithelial origin, including their metastasis, stained positively. Nonepithelial tumors were uniformly negative. In the metastatic lesions, small foci of tumor cells and even single tumor cells could be identified by TPA staining. Immunohistochemical localization of TPA appeared to be a useful tool for assessing the micrometastases of prostatic carcinoma in other organs, especially lymph nodes, or elucidating the epithelial origin of an otherwise undifferentiated prostatic cancer.

Adenocarcinoma↗

Synergistic induction of rat hepatic ornithine decarboxylase by multiple doses of cobalt chloride.

The level of rat hepatic ornithine decarboxylase (ODC) induced by repetitive administration of Co2+ was determined by affinity labeling with [3H]difluoromethylornithine. Such a treatment with Co2+ ion induced ODC level to a 10-fold greater extent than single dose of the metal ion or well-known inducers of the enzyme, such as thioacetamide or carbon tetrachloride. The half life of ODC activity induced by repetitive treatment with Co2+ (95 min) was substantially increased to about 10-fold over the value obtained from the enzyme induced by single treatment with the metal ion (10 min). ODC activity induced by repetitive treatment with Co2+ was separated into two peaks by DEAE-Sepharose column chromatography. The two independently collected fractions of ODC peaks exhibited different affinity for pyridoxal 5'-phosphate in vitro and sensitivity to cycloheximide in vivo.

Animals↗

Induction of ornithine decarboxylase and S-adenosylmethionine decarboxylase by sulfobromophthalein in rats.

The administration of sulfobromophthalein (BSP, 0.5 mmol/kg, ip.) increased ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activities to 30-fold and 5-fold, respectively, of the controls at 12 hr in the liver of rats. Parallel to the increase in ODC, there was an increase in hepatic putrescine content. However, spermine content tended to decrease. BSP increased ODC and SAMDC activities and putrescine content, but decreased spermine content, in a dose-dependent manner. Pretreatment of rats with actinomycin D and cycloheximide almost completely blocked the BSP-mediated increase of ODC and SAMDC activities. Pretreatment with glutathione (GSH) failed to inhibit BSP-mediated increase of ODC and SAMDC activities. In addition, the administration of BSP-GSH conjugate (0.5 mmol/kg, iv.) did not produce the increase of ODC and SAMDC activities. Pretreatment with phenobarbital and 3-methylcholanthrene did not inhibit BSP-mediated increase of ODC and SAMDC. The results indicate that BSP could cause changes in hepatic polyamine content due to the induction of ODC and SAMDC.

Adenosylmethionine Decarboxylase↗

Comparative studies on the inducing effects of cobalt chloride and co-protoporphyrin on hepatic ornithine decarboxylase and heme oxygenase in rats.

Co-protoporphyrin, like Co2+, produced a significant and persistent induction of hepatic ornithine decarboxylase (ODC) as well as its known inducing effect on heme oxygenase and the decreasing effects on drug-metabolizing enzymes. The induction of ODC and heme oxygenase by Co-protoporphyrin occurred dose-dependently with the lowest effective dose of 6.25 mumol/kg. Although Co-protoporphyrin produced similar effects on ODC and heme oxygenase to Co2+, there were differences in the mode of ODC induction. In particular, pretreatment with diethyl maleate failed to augment the induction of ODC by Co-protoporphyrin. Moreover, multiple administrations of Co2+, but not Co-protoporphyrin, caused super-additive induction of ODC to about 1000-fold over the controls. This super-additive induction of ODC by Co2+ was dependent on the doses and time intervals between two administrations. In parallel with a large induction of ODC evoked by two administrations of Co2+, hepatic putrescine content was increased markedly, while spermine content was decreased as compared to the control levels. Pretreatment with Co2+ led to super-additive induction of ODC by subsequent administration of the metal ion itself or diethyl maleate, but not by other ODC inducers, such as Co-protoporphyrin and thioacetamide, and not by subsequent partial hepatectomy. Under these experimental conditions, the magnitudes of heme oxygenase induction were similar. ODC induced by two doses of Co2+ was insensitive to exogenous putrescine, but sensitive to alpha-difluoromethylornithine and 1,3-diaminopropane. These findings add new insight into the effects of Co2+ and Co-protoporphyrin on hepatic polyamine metabolism; and the results suggest that the metal ion could cause extensive derangement of the ODC regulatory system in a manner different from the metalloporphyrin.

Animals↗