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Biomedical subjects

S Toyama

Publications and source records attributed to S Toyama.

At least 55 records · Page 3Linked to original sources
PubMed1991

Study on the metabolic fate of catena-(S)-[mu-N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 3rd communication: transfer into fetus and milk in rats.

Studies on the transfer into the fetus and the milk were performed after administration of 14C-Z-103 and 65Zn-Z-103 (catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]- zinc], CAS 107667-60-7) to rats. After oral administration of 14C-Z-103 to pregnant rats, the transfer of radioactivity to the fetus was studied by means of whole body autoradiography (ARG) and measurement of radioactivity in the fetus. The concentration of radioactivity in the fetus was approximately the same as those in the blood and the placenta of the maternal animal. The transfer of radioactivity into the milk was demonstrated after administration of 14C-Z-103 to lactating rats. Radioactivity in the fetus and milk are considered to be due to metabolites of L-carnosine of Z-103, such as amino acid or protein. The distribution of radioactivity in the fetus was also observed after administration of 65Zn-Z-103 to pregnant rats. However, after administration of non-radioactive Z-103 to pregnant rats, the zinc level in the fetus was found to be almost the same level as that in the fetus of the untreated rats. The transfer of radioactivity to the milk was studied after administration of 65Zn-Z-103 to the lactating rats, and it was seen that the concentration of radioactive zinc in the milk was much lower than the endogenous level of zinc in the milk at any of the time points investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 4th communication: disposition of zinc and amino acids in rats, dogs and monkeys.

The time course of the zinc plasma concentrations in rats, dogs and monkeys and the metabolic fate of L-carnosine were investigated after oral administration of Z-103 (catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7). There was no intradiurnal variation in the plasma concentrations of endogenous zinc in rats, dogs and monkeys. The plasma concentrations of endogenous zinc in dogs and monkeys were approximately the same as that in humans, whereas the plasma concentration of zinc in rats was 2.2-fold higher than that in man. After administration of Z-103 to non-fasted dogs at 100 mg/kg, the plasma concentration of zinc reached Cmax at 0.5 h after administration (1.7-fold higher than endogenous zinc level), while the plasma concentration was the lowest in comparison with other animal species. After administration to fasting rats at 50 mg/kg, the plasma concentration of zinc reached Cmax at 1 h after administration (2.5-fold higher than endogenous zinc level) and decreased thereafter, returning to the endogenous level at 8 h after administration. After oral administration to monkeys at 10 mg/kg and 50 mg/kg, the Cmax values were 4.1-fold and 6.8-fold higher than the endogenous level, respectively. The Tmax values were achieved at 4-6 h and 8 h after each administration, respectively, showing slower absorption in comparison with other animal species.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1991

[A case of Bochdalek hernia in an adult with volvulus of the stomach and hypopotassemia].

Gastric volvulus is a rare disease. We recently encountered a gastric volvulus associated with Bochdalek hernia and severe hypopotassemia. A 32-year-old woman experienced epigastric pain and recurrent vomiting. The changes of the electrocardiogram in this patient (K1.8mEq/l) were inverted T wave and ST depression. She was diagnosed as having gastric volvulus associated with Bochdalek hernia by chest X-ray films, contrast radiography of the upper digestive tract and thoraco-abdominal CT scans. Symptoms did not disappear with the administration of conservative therapy. At laparotomy, the stomach was rotated around its mesenteric axis in the sagittal plane. After operative repair, symptoms disappeared, and serum potassium level returned to normal. Gastric volvulus is rather easily diagnosed if its existence is kept in mind.

Adult↗
PubMed1990

Monomorphic and polymorphic isozymes of arylamine N-acetyltransferases in hamster liver: purification of the isozymes and genetic basis of N-acetylation polymorphism.

Two forms of cytosolic acetyltransferases, AT-I and AT-II, have been purified from hamster livers, and a comparison made of their chemical and catalytic properties and genetically expressed difference. Homogeneous AT-I and AT-II were 31 and 30 kd respectively on SDS-PAGE and catalyzed efficiently various N- and O-acetylations in their reconstitution systems. AT-I used both acetyl CoA and arylhydroxamic acids as acetyl donors, while AT-II did not utilize arylhydroxamic acids as acetyl donors. In the reconstitution system, purified AT-I, but not AT-II, catalyzed acetyl CoA-dependent O-acetylation of 2-N-hydroxyamino-6-methyldipyrido[1,2-alpha:3', 2'-d]imidazole (N-OH-Glu-P-1) and arylhydroxamic acid-dependent N-acetylation of 4-aminoazobenzene (AAB). On the other hand purified AT-II showed high activities of acetyl CoA-dependent N-acetylation of 2-aminofluorene (AF) and p-aminobenzoic acid (PABA). Polyclonal antibodies raised against AT-I inhibited cytosolic acetylations of N-OH-Glu-P-1 and AAB, and to a lesser extent of AF, while PABA N-acetylation was only marginally inhibited. Using Western blots, both AT-I and AT-II were recognized by the antibodies. AT-I was detectable in all the livers examined, and the content did not differ among the individuals (monomorphic distribution). In contrast, AT-II was distributed polymorphically, and the trimodal distribution of AT-II (high, intermediate and low) was correlated with the phenotype identified by cytosolic N-acetylations of AF and PABA (rapid, intermediate and slow). In addition, cross-mating experiments with intra- and inter-phenotype animals confirmed that hepatic AT-II isozyme is inherited by a Mendelian co-dominant trait. These results indicate that the polymorphic appearance of an acetyltransferase, AT-II, is responsible for the N-acetylation polymorphism in individual hamsters.

4-Aminobenzoic Acid↗
PubMed1989

Pharmacokinetics of internally labeled monoclonal antibodies as a gold standard: comparison of biodistribution of 75Se-, 111In-, and 125I-labeled monoclonal antibodies in osteogenic sarcoma xenografts in nude mice.

In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with 75Se by incubating [75Se]methionine and hybridoma cells. 75Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of 125I- and 111In-labeled antibodies. 75Se-, 125I- and 111In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of 75Se- and 125I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of 111In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with 75Se- and 111In-labeled antibodies, whereas 125I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both 111In- and 125I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a "gold standard" of biodistribution of monoclonal antibody, high liver uptake of 111In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of 111In-labeled antibodies if stably coupled conjugates are administered i.v.

Animals↗
PubMed1989

Crystal structure analysis of omega-amino acid:pyruvate aminotransferase with a newly developed Weissenberg camera and an imaging plate using synchrotron radiation.

The three-dimensional structure of omega-amino acid:pyruvate aminotransferase from Pseudomonas sp. F-126, an isologous alpha 4 tetramer containing pyridoxal 5'-phosphate (PLP) as a cofactor, has been determined at 2.0 A resolution. The diffraction data were collected with a newly developed Weissenberg camera with a Fuji Imaging Plate, using synchrotron radiation. The mean figure-of-merit was 0.57. The subunit is rich in secondary structure and comprises two domains. PLP is located in the large domain. The high homology in the secondary structure between this enzyme and aspartate aminotransferase strongly indicates that these two types of enzymes have evolved from a common ancestor.

Aspartate Aminotransferases↗
PubMed1988

Purification of an antihemorrhagic factor from the serum of the non-venomous snake Dinodon semicarinatus.

An antihemorrhagic factor was purified from the serum of Dinodon semicarinatus, a non-venomous snake (Akamata), by a series of high performance liquid chromatographies with a TSK gel DEAE-5PW column. The purified antihemorrhagic factor showed a single band on polyacrylamide gel disc electrophoresis and inhibited the hemorrhagic activity of HR1 and HR2, the hemorrhagic factors of Trimeresurus flavoviridis Okinawa. The antihemorrhagic factor was stable from 0 degrees to 60 degrees and at pH values 2.0-11.0. The molecular weight of the factor was estimated to be 59,000 and 52,000 by a gel filtration and SDS-disc electrophoresis, respectively, suggesting that it consists of a single subunit, as we also found for the antihemorrhagic factors of the mongoose Herpestes edwardsii.

Animals↗
PubMed1988

Purification and crystallization of hemorrhagic factor, HR2b, from the venom of Trimeresurus flavoviridis (habu).

The hemorrhagic factor, HR2b, was purified from the venom of Trimeresurus flavoviridis (habu) by a combination of gel filtration, cation exchange column chromatography and high performance liquid chromatography. The purified HR2b was homogeneous by the criteria of ultracentrifugation and SDS-disc electrophoresis. The mol. wt of HR2b was 18,000 and 18,500 by gel filtration on Sephadex G-50 and by SDS-disc electrophoresis, respectively, indicating a monomer structure for the hemorrhagic factor. Crystals of HR2b, taking the form of thin plates, were obtained in the presence of ammonium sulfate.

Animals↗
PubMed1988

Functional alterations in beta'-actin from a KB cell mutant resistant to cytochalasin B.

We recently described the isolation of mutant KB cells (Cyt 1 cells) resistant to the cytotoxic effect of cytochalasin B (CB). This mutant carried an altered beta-actin; i.e., beta'-actin (Toyama, S., and S. Toyama. 1984. Cell. 37:609-614). In the present study, we have examined the functional properties of actin in Cyt 1 cells. Our results showed that increased resistance of Cyt 1 cells to CB was reflected in altered properties of beta'-actin itself. This was shown directly by two findings. First, the polymerization of beta'-actin was more resistant than that of beta- or gamma-actin to the multiple effects of CB. Second, beta'-actin bound less CB than beta- or gamma-actin. The functional alteration of beta'-actin in Cyt 1 cells was further supported by the observation that, although treatment of KB cells with CB increased the pool of unpolymerized actin, the same treatment did not affect the pool of unpolymerized actin in Cyt 1 cells, and that microfilaments of Cyt 1 cells were more resistant to the disrupting action of CB than those of KB cells. These results strongly suggest that the primary site of action of CB on cell motility processes is actin.

Actin Cytoskeleton↗
PubMed1988

Metabolic activation of a protein pyrolysate promutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline by rat liver microsomes and purified cytochrome P-450.

The enzymatic activation of a promutagenic pyrolysate, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), was studied using the Ames mutagenesis test system. The enzyme catalyzing the mutagenic activation of MeIQx is mainly localized in the microsomal fraction. A large number of revertants was observed in the presence of hepatic microsomes obtained from 3-methylcholanthrene (3-MC)- or polychlorinated biphenyl (PCB)-treated rats but only a minimal number with the hepatic microsomes from untreated or phenobarbital (PB)-treated rats. In addition, the microsomal activation was reduced efficiently by known inhibitors of cytochrome P-450-mediated reactions such as 7,8-benzoflavone, ellipticine and flavone. Among five forms of purified rat cytochrome P-450, the highest sp. act. (no. of revertants induced/nmol cytochrome P-450) for the activation of MeIQx was observed with a high-spin form of cytochrome P-450, P-448-H, followed by the low-spin form, P-448-L, and to a lesser extent by PB-inducible forms, P-450b and P-450e. P-450-male, which is a main constitutive form of cytochrome P-450 in male rat livers, showed considerable catalysis for the mutagenic activation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and MeIQx. These results indicate that the metabolic activation of MeIQx is catalyzed mainly by two forms of cytochrome P-450, P-448-H and P-488-L, in the livers of PCB- or 3-MC-treated rats, but also that P-450-male may play an important role in the activation in livers of intact male rats.

Animals↗
PubMed1988

Effects of ozone and peroxyacetyl nitrate on polar lipids and Fatty acids in leaves of morning glory and kidney bean.

To compare the effects of ozone and peroxyacetyl nitrate (PAN) on leaf lipids, fatty acids and malondialdehyde (MDA), morning glory (Pharbitis nil Choisy cv Scarlet O'Hara) and kidney bean (Phaseolus vulgaris L. cv Gintebo) plants were exposed to either ozone (0.15 microliter per liter for 8 hours) or PAN (0.10 microliter per liter for up to 8 hours). Ozone increased phospholipids in morning glory and decreased in kidney bean at the initial stage (2-4 hours) of exposure, while it scarcely changed glycolipids, the unsaturated fatty acids, and MDA in both plants. A large reduction of glycolipids occurred 1 day after ozone exposure in both plants. PAN caused marked drops in phospholipids and glycolipids in kidney bean at relatively late stage (6-8 hours) of exposure, while it increased phosphatidic acid and decreased the unsaturated fatty acids, an increase which was accompanied by a large increase in MDA. These results suggest that ozone may not directly oxidize unsaturated fatty acids at the initial stage of exposure, but may alter polar lipid metabolism, particularly phospholipids. On the other hand, PAN may abruptly and considerably degrade phospholipids and glycolipids by peroxidation or hydrolysis at the late stage of exposure. The present study shows that ozone and PAN affect polar lipids in different manners.

Journal Article↗
PubMed1988

Effect of a new calcium antagonist, nilvadipine, on variant angina pectoris evaluated by 24-hour Holter electrocardiography.

The clinical effect of nilvadipine, a new calcium antagonist, was investigated in a single blind trial in 19 patients with variant angina pectoris. The efficacy of the drug was evaluated on the basis of frequency of anginal attacks and Holter electrocardiographic findings during observation periods and during two treatment periods when the drug was given in doses of 4 mg twice a day or 4 mg 3 times a day. The frequency of anginal attacks and the consumption of sublingual nitroglycerin tablets decreased significantly in both treatment periods in comparison with those in the observation period before treatment, but in the observation period after treatment tended to increase in comparison with those during the second treatment period. The frequency and duration of ST-segment elevation and the maximum ST-segment elevation confirmed by Holter electrocardiography also improved significantly in both treatment periods, compared with those in the observation period before treatment. Our findings show that nilvadipine is effective for variant angina pectoris at doses of 4 mg twice a day.

Angina Pectoris, Variant↗
PubMed1987

Purification of three antihemorrhagic factors from the serum of a mongoose (Herpestes edwardsii).

Three antihemorrhagic factors (AHF-1, AHF-2 and AHF-3) were purified from the serum of H. edwardsii, a mongoose, by a combination of gel filtration on a Sephadex G-200 column and high performance liquid chromatography with a TSK gel DEAE-5PW column. Each of the purified antihemorrhagic factors showed a single band on polyacrylamide gel disc electrophoresis. The three antihemorrhagic factors inhibited the hemorrhagic activity of HR 1 and HR 2, the hemorrhagic principles from the snake venom of Trimeresurus flavoviridis Okinawa. AHF-1, AHF-2 and AHF-3 were stable at temperatures from 0 degrees to 60 degrees C and at pH values between 2.0 and 11.0. The same molecular weight (65,000) was obtained for the three antihemorrhagic factors. No precipitin lines were found for the purified antihemorrhagic factors with the venom of T. flavoviridis Okinawa and its hemorrhagic principles, HR 1 and HR 2.

Animals↗
PubMed1987

Myocardial infarction size and location: a comparative study of epicardial isopotential mapping, thallium-201 scintigraphy, electrocardiography and vectorcardiography.

Based on epicardial isopotential mapping (the Ep Map), which was calculated from body surface isopotential mapping (the Body Map) with Yamashita's method, using the finite element technique, we predicted the location and size of the abnormal depolarized area (the infarcted area) in 19 clinical cases of anterior and 18 cases of inferoposterior infarction. The prediction was done using Toyama's diagnostic method, previously reported. The accuracy of the prediction by the Ep Map was assessed by comparing it with findings from thallium-201 scintigraphy (SCG), electrocardiography (ECG) and vectorcardiography (VCG). In all cases of anterior infarction, the location of the abnormal depolarized areas determined on the Ep Map, which was localized at the anterior wall along the anterior intraventricular septum, agreed with the location of the abnormal findings obtained by SCG, ECG and VCG. For all inferoposterior infarction cases, the abnormal depolarized areas were localized at the posterior wall and the location also coincided with that of the abnormal findings obtained by SCG, ECG and VCG. Furthermore, we ranked and ordered the size of the abnormal depolarized areas, which were predicted by the Ep Map for both anterior and inferoposterior infarction cases. In the cases of anterior infarction, the order of the size of the abnormal depolarized area by the Ep Map was correlated to the size of the abnormal findings by SCG, as well as to the results from Selvester's QRS scoring system in ECG and to the angle of the maximum QRS vector in the horizontal plane in VCG.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiography↗
PubMed1986

Clinical evaluation of bisoprolol in patients with stable angina pectoris: a preliminary report.

Efficacy and safety of the new beta-adrenoceptor antagonist, bisoprolol, in treatment of stable angina pectoris were studied in 36 patients using two types of single-blind design. After 2 weeks of therapy with bisoprolol in doses of 5 mg to 10 mg a day, exercise duration and time to 1 mm of ST-segment depression were significantly prolonged in 7 out of 10 patients who had a positive treadmill exercise test before bisoprolol. Bisoprolol significantly reduced heart rate (HR), systolic blood pressure (SBP), and rate-pressure product (RPP) at peak exercise, which would account for the beneficial effect of bisoprolol on exercise tolerance. Bisoprolol also produced improvement in symptoms for 26 patients with stable effort angina, as indicated by decreased frequency of anginal attacks and nitroglycerin consumption with a once-a-day regimen. Ten patients had no attacks after 5 mg of bisoprolol, and three more did not develop angina after increasing the dose to 10 mg a day. These results suggest that bisoprolol will be a promising, efficacious, and safe drug for the treatment of stable angina pectoris.

Adrenergic beta-Antagonists↗
PubMed1986

[Mitral valve prolapse with myocardial disarrangement and familial hypertrophic cardiomyopathy: a case report].

This is a report of a patient with mitral valve prolapse (MVP) and myocardial abnormalities on endomyocardial biopsy in whose relatives hypertrophic cardiomyopathy (HCM) was identified. A 19-year-old woman was admitted to our hospital for evaluation of a heart murmur. A systolic ejection murmur was audible in the third intercostal space at the left sternal border, and a standard 12-lead electrocardiogram showed ST-T wave changes in leads II, III and aVF. Echocardiography revealed prolapse of the anterior leaflet of the mitral valve, but no left ventricular hypertrophy. Endomyocardial biopsy disclosed mild hypertrophy and disarrangement of the myocardium. The family study revealed asymmetrical septal hypertrophy in her mother, who had no history of hypertension. Her younger sister had mild hypertrophy of the interventricular septum on echocardiography, and her histopathological findings suggested a diagnosis of HCM. This case was clinically regarded as MVP, but development of left ventricular hypertrophy as noted in her mother may occur in the future.

Adolescent↗