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S Toyama

Publications and source records attributed to S Toyama.

At least 19 recordsLinked to original sources
PubMed1992

Direct proof that the primary site of action of cytochalasin on cell motility processes is actin.

We have previously described the isolation of a mutant KB cell (Cyt 1 mutant) resistant to the cytotoxic effect of cytochalasin B (CB). The Cyt 1 mutant carries an altered form of beta-actin (beta'-actin) and lacks normal beta-actin (Toyama, S., and S. Toyama. 1984. Cell. 37:609-614). Increased resistance of the Cyt 1 mutant to CB in vivo is reflected in altered properties of beta'-actin in vitro (Toyama, S., and S. Toyama. 1988. J. Cell Biol. 107:1499-1504). Here, we show that the mutation in beta-actin is solely responsible for the cytochalasin-resistant phenotype of the Cyt mutant. We have isolated a cDNA clone encoding beta'-actin from Cyt 1 cells. Sequence analysis reveals two mutations in the coding region that substitute two amino acid residues (Val139----Met and Ala295----Asp). Expression of the beta'-actin cDNA confers cytochalasin resistance upon transformed cytochalasin-sensitive KB cells. Levels of resistance to CB in the transformed cell clones correlate well with amounts of beta'-actin polypeptide. Both of the two mutations in beta'-actin are necessary for the high level expression of cytochalasin resistance. Overall, we conclude that the primary site of action of cytochalasin on cell motility processes in vivo is actin.

Actin Cytoskeleton↗
PubMed1992

[The gastric mucosal adhesiveness of Z-103 in rats with chronic ulcer].

The gastric mucosal adhesiveness of Z-103 in rats with acetic acid ulcer was studied macroscopically, histologically, and biochemically. From macroscopical observations, when Z-103 was orally administered to an acetic acid ulcer model, there was adhesion of Zn to the normal mucosa as well as the ulcerous site under both the fasting condition and after feeding. It was also proven that the strength and duration of adhesiveness were increased dose-dependently under fasting conditions. In addition, histological localization of Zn was noted from the covering epithelial cell layer to the gastric lamina propria mucosae in the normal tissue and in the most superficial ulcerous layer and the granulous layer of the ulcerous site. Measurement of the gastric tissue Zn content after oral administration of 100 mg/kg of Zn showed that the Zn content was significantly increased for 6 hr at the normal site and for 24 hr at the ulcerous site. On the other hand, although ZnSO4 and ZnSO4+carnosine combination macroscopically produced generally the same level of adhesiveness as Z-103, when the gastric tissue Zn content for Z-103 and ZnSO4 were compared, the Zn content of ZnSO4 was lower than that for Z-103 at both the normal and ulcerous site. In summary, Z-103 shows a long-term adhesive and permeable action on the gastric mucosa in acetic acid ulcer rats, and it has a comparable high affinity at the ulcerous site.

Acetates↗
PubMed1992

[Chronic fatigue syndrome--cases in the Kanebo Memorial Hospital].

In our hospital, 134 patients (28 male, 106 female, 10-82 years of age) were diagnosed as having chronic fatigue syndrome (CFS). Some patients had mild elevation of antibodies against Epstein-Barr Virus and immunologic abnormalities (natural killer cell dysfunction and high rates of skin reactivity to house dust, pollen, drugs and common food). In the patients with immunologic abnormalities, we found decreases in serum concentrations of arachidonic acid and dihomogamma-linolenic acid. A Kampo medicine, Ren-Shen-Yang-Rong-Tang was used in the management of 134 patients and 98 patients returned to work or school.

Adolescent↗
PubMed1992

[Selection of graft materials in case of emergency coronary bypass surgery following failed angioplasty].

The clinical characteristics of selection of graft materials were analysed for patients undergoing emergency coronary artery bypass surgery (CABG) following failed coronary angioplasty (PTCA). Ten emergency CABGs were performed from January 1983 to December 1991. Perioperative variables and follow-up were compared to 18 patients undergoing elective CABG after PTCA. The emergency group had shorter operative time (p less than 0.01) and shorter bypass time (p less than 0.05). Moreover the emergency group had decreased use of the internal thoracic artery (ITA) (40% vs 94.4%, p less than 0.01). There was no use of bilateral ITAs in the emergency group. There was not significant difference in hospital mortality and medium term follow-up between two groups. In conclusion, emergency CABG carries a significantly less use of ITA graft than elective CABG although ITAs are superior to SVGs about long term patency rate. So it is desirable that arterial graft should be used under an appropriate selection at emergency operation.

Aged↗
PubMed1991

Measurement of voltage dependence of capacitance of planar bilayer lipid membrane with a patch clamp amplifier.

The voltage dependence of capacitance was measured by using the setup which was almost the same as that for the study of ion channels. The coefficient which represents the voltage dependence of capacitance itself also changes as a function of the duration of voltage application if hexadecane is contained in bilayer lipid membrane (BLM). The method of Alvarez, O., and R. Latorre (1978. Biophys. J. 21:1-17) was extended to treat BLM with hexadecane.

Alkanes↗
PubMed1991

Clinical effects of nitrendipine on variant angina pectoris.

The clinical effects of nitrendipine, a new calcium antagonist, were investigated in a single-blind test on 21 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 different treatment periods at doses of 10 mg once a day (period I) and 20 mg once a day (period II). The number of anginal attacks decreased significantly from a pretreatment level of 2.1 +/- 0.3 per day to 0.7 +/- 0.2 per day in treatment period I and 0.3 +/- 0.1 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The consumption of sublingual nitroglycerin tablets decreased significantly in both treatment periods in comparison with the observation period before treatment (p less than 0.01, p less than 0.001, respectively). In 20 patients with continuous ECG monitoring, the frequency of ST-segment elevation was 4.5 +/- 1.0 per day during the pretreatment period; it decreased significantly to 0.9 +/- 0.6 per day in treatment period I and 0.5 +/- 0.3 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The duration and the maximum magnitude of ST-segment elevation also improved significantly in both treatment periods. These results demonstrate the efficacy of nitrendipine in the treatment of variant angina at a single daily dose of 10 mg.

Angina Pectoris, Variant↗
PubMed1991

Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 1st communication: absorption, distribution, metabolism and excretion after single administration to rats.

Studies on the absorption, distribution, metabolism and excretion 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) were performed after oral administration to rats. After oral administration of 14C-Z-103 and 65Zn-Z-103, the blood concentrations of 14C-radioactivity were 30- to 40-fold higher than those of 65Zn-radioactivity. The 14C-radioactivity showed a dose-dependent increase of Cmax and AUC values in the dose range from 13.1 mg/kg to 100 mg/kg, and remained longer in the blood. In contrast, no dose-dependent increase of AUC was observed with 65Zn-radioactivity, suggesting saturation of absorption at doses more than 30 mg/kg of 65Zn-Z-103. The major route of excretion of 14C-radioactivity was by excretion into the expired air, amounting to 38.8% of the administered dose, while the urinary and fecal excretions were low values at 4.1% and 13.3%, respectively. The radioactivity remaining in the carcass accounted for 39.3% of the dose. On the other hand, in the case of 65Zn-radioactivity, 85.0% of the administered dose was excreted into the feces and 10.5% of the dose remained in the carcass. Both 14C- and 65Zn-radioactivities were distributed to the whole body, while 14C-radioactivity showed higher concentrations in the body, and was retained longer than the 65Zn-radioactivity. When the plasma and the liver and kidney homogenates, from rats received 14C-Z-103, were treated with trichloroacetic acid (TCA), the radioactivities in the TCA-insoluble fraction increased as a function of time. Following the treatment of the homogenates with protease, the radioactivities in the TCA-insoluble fraction decreased. In vitro study was showed that L-carnosine of 14C-Z-103 added to the homogenates of liver and small intestine was metabolized to L-histidine. The results suggest that the remaining radioactivities in tissues and organs caused the incorporation of the metabolites of 14C-Z-103 into endogenous high molecular substances.

Animals↗
PubMed1991

Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 2nd communication: absorption, distribution, metabolism and excretion after repeated administration to rats.

After repeated administration of 14C-Z-103 (catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) to rats for 21 days, the accumulation of radioactivity in the blood and tissues was proportional to the number of doses given. Following treatment of the terminal blood, plasma, liver and kidney samples with trichloroacetic acid (TCA) or protease, the radioactivity in these tissues was demonstrated to be TCA-insoluble and solubilized by the protease treatment. Thus, the accumulation of radioactivity after repeated administration of 14C-Z-103 was considered to be due to the utilization of the metabolites of L-carnosine, the constituent of Z-103, into a protein. The cumulative ratios of radioactivity excreted into the urine, feces and expired air and the radioactivity remaining in the carcass after repeated administration of 14C-Z-103 for 21 days were similar to those values obtained after a single administration, suggesting that repeated administration did not influence the excretion profile of Z-103. During the period of repeated administration of non-radioactive Z-103 to rats for 21 days, the fecal content of zinc was higher than that in nontreated rats, whereas it returned to the control level at 48 h after the final administration. There was no significant difference in the urinary concentration of zinc between treated and non-treated animals during the period of repeated administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
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

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

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↗
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↗