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Biomedical subjects

I Yasuda

Publications and source records attributed to I Yasuda.

At least 19 recordsLinked to original sources

Inhibition of Na+,K(+)-ATPase by 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, a major constituent of both moutan cortex and Paeoniae radix.

The inhibition of Na+,K(+)-ATPase activity by various constituents of Moutan Cortex and Paeoniae Radix was studied. 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose (PGG), a major component of both crude drugs, strongly inhibited Na+,K(+)-ATPase activity (IC50 = 2.5 x 10(-6) M), whereas galloylpaeoniflorin, benzoic acid, and catechin were weakly inhibitory, and albiflorin, oxypaeoniflorin, paeoniflorin, paconol, and phenol were ineffective. The inhibition of Na+,K(+)-ATPase activity by PGG was decreased in the presence of BSA or phospholipids. The inhibition mode of PGG was noncompetitive with respect to ATP. The K0.5 value for Na+ was increased by the addition of PGG from 9.1 to 12.3 mM, whereas that for K+ was not altered. PGG also inhibited K(+)-dependent p-nitrophenyl phosphatase activity with an IC50 value of 5.3 x 10(-6) M, and the extent of the inhibition increased at higher concentrations of K+. The K0.5 value for K+ was decreased by the addition of PGG from 3.3 to 2.0 mM. These results suggested that the inhibition of Na+,K(+)-ATPase activity is caused by interaction of PGG with the enzyme in the E2 state. The inhibitory effect of Moutan Cortex or Paeoniae Radix is considered to be mainly attributable to PGG.

4-Nitrophenylphosphatase

Usefulness of novel imaging modalities in diagnosis of focal nodular hyperplasia of the liver.

A 17-year-old woman was admitted because of a liver tumor found incidentally by ultrasonography. Liver function was normal and there were no markers of hepatitis viruses or malignancy. Abdominal ultrasonography, computed tomography (CT), and magnetic resonance imaging revealed a mass (2 cm in diameter) in the lateral segment of the left lobe of the liver. The lesion was not detected by hepatic arteriography. However, dynamic CT with fast scanning and dynamic CO2-enhanced ultrasonography demonstrated initial central enhancement of the mass followed by centrifugal spread of enhancement to the periphery. Color Doppler flow imaging detected a central color spot, shown to be an artery by a pulsed Doppler spectrum analysis. Fine-needle biopsy confirmed a diagnosis of focal nodular hyperplasia. Dynamic CT with fast scanning, dynamic CO2-enhanced ultrasonography, and color Doppler flow imaging were useful in detecting the vascular pattern specific to focal nodular hyperplasia. Investigation of further cases with these novel imaging modalities should help to establish a comprehensive diagnostic procedure and thus avoid unnecessary surgery for focal nodular hyperplasia, which is a completely benign lesion.

Adolescent

Ester-type cephalotaxus alkaloids from Cephalotaxus harringtonia var. drupacea.

Three alkaloids, neoharringtonine, homoneoharringtonine and 3'S-hydroxyneoharringtonine, were isolated from the leaves and stems of Cephalotaxus harringtonia var. drupacea. Their structures were established by spectroscopic methods, including two-dimensional NMR and CD spectra, and their antileukaemic activity was evaluated using P-388 leukaemia cells.

Alkaloids

Inhibitory effects of shouseiryu-to on two-stage carcinogenesis. II. Anti-tumor-promoting activities of lignans from Asiasarum heterotropoides var. mandshuricum.

Two lignans, asarinin (6) and xanthoxylol (7), were isolated from the radix of Asiasarum heterotropoides var. mandshuricum, which consist of a kampo prescription, Shouseiryu-to, as inhibitors of Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). These lignans also exhibited remarkable inhibitory effects on a two-stage carcinogenesis test of mouse skin and pulmonary tumors. Furthermore, it was confirmed that these hydrophobic lignans dissolved in the water decoction of Shouseiryu-to, and these lignans might be among the active constituents of this kampo prescription in terms of its anti-tumor-promoting activity.

Animals

Extracorporeal shockwave lithotripsy of common bile duct stones without preliminary endoscopic sphincterotomy.

BACKGROUND: Endoscopic sphincterotomy (EST) is now a standard procedure for common bile duct stones. It is less invasive than surgical treatment and is well established, but complications such as bleeding and perforation occasionally occur. We have been investigating the safest and most useful method of preserving the papilla of Vater. In the present study we evaluated the effectiveness and safety of extracorporeal shock wave lithotripsy (ESWL) for common bile duct stones without preliminary EST. METHODS: From May 1992 to May 1995 ESWL was performed on 52 patients with common bile duct stones at our hospital. In all 52 patients a nasobiliary tube was inserted endoscopically, without preliminary EST, and ESWL was performed. RESULTS: Fragmentation and subsequent complete clearance of stones was achieved in 35 patients (67.3%), and no additional treatment was necessary. In 17 patients (25.0%) fragmentation was not achieved, so EST and endoscopic extraction were performed, and the stones were cleared completely. None of the patients had major complications with clinical sequelae. We compared the completely cleared group and the failed group, to assess the influence of various factors. Our findings indicated that smaller, 'floating' stones responded more favorably to ESWL. When the largest stone was < 15 mm in diameter and the stone index (diameter of common bile duct/diameter of stone) was > 1.0, the success rate was very high 25 of 27 = 92.6%). CONCLUSIONS: This treatment offers several advantages because it is less invasive, has few complications, and can preserve the papilla of Vater. This method is especially suitable for patients with smaller, floating stones.

Adult

[Pseudoaneurysm].

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Aneurysm, False

Anti-AIDS agents, 21. Triterpenoid saponins as anti-HIV principles from fruits of Gleditsia japonica and Gymnocladus chinensis, and a structure-activity correlation.

Gleditsia saponin C [1] and gymnocladus saponin G [2] were isolated from Gleditsia japonica and Gymnocladus chinensis, respectively, as anti-HIV principles. Compounds 1 and 2 demonstrated inhibitory effects against HIV replication in H-9 cells with EC50 values of 1.1 and 2.7 microM, respectively. Evaluation of the anti-HIV activities of the prosapogenins of 1 and 2 suggested that the unusual monoterpenyl moieties in 1 and 2 are essential for their anti-HIV activity. Derivatives of echinocystic acid [8], the aglycone of compound 1, were also prepared and evaluated for inhibitory activity against HIV replication. 3,16-Di-O-acetylechinocystic acid [12] was shown to be an anti-HIV agent with an EC50 value of 2.3 microM.

Acquired Immunodeficiency Syndrome

Antitumor agents, 162. Cell-based assays for identifying novel DNA topoisomerase inhibitors: studies on the constituents of Fatsia japonica.

Two pleiotropic multi-drug resistant (PDR) KB cell lines were hypersusceptible to a cytotoxic extract from Fatsia japonica. Fractionation of an active extract using a cell-based assay for DNA topoisomerase inhibitors led to the isolation of three known triterpene glycosides, FJ-1-3 [1-3]. The structures of 1-3 were identified as 3-O-alpha-L-arabinopyranosyl-oleanolic acid [1], 3-O-alpha-L-arabinopyranosyl-hederagenin [2], and 3-O-[beta-D-glucopyranosyl(1-->4)-alpha-L-arabinopyranosyl]-hed eragenin [3], respectively. However, these isolates were not DNA topoisomerase II inhibitors in vitro and nor were they active when re-tested for differential cytotoxicity. Compounds 1-3 appear to function by interfering selectively with cellular drug accumulation. Other fractions probably contained compounds active against DNA topoisomerase I; however, the enriched preparations were not cytotoxic. The present findings indicate a simple modification to improve the cell-based bioassay procedure employed to guide fractionation.

Antineoplastic Agents, Phytogenic

[Effect of 5-FU on the utilization of purine and pyrimidine by human gastric cancer cells (KATO III)].

Effect of utilization of purine and pyrimidine in the culture medium by human gastric cancer cells (KATO III) was evaluated. Nucleosides mixture solution (OG-VI), consisting of inosine, guanosine 5' monophosphate (5'GMP), cytidine, uridine and thymidine (4: 4: 4: 3: 1 in molar ratio) was used and their levels in the culture medium was measured by HPLC after 3 day culture. Purine, inosine and 5' GMP, in the medium almost decreased and purine base, xanthine and hypoxanthine levels increased, but changes in pyrimidine level were minimal. 5-FU decreased purine and increased pyrimidine consumption. Addition of nucleosides mixture did not enhance the cellular proliferation, but inhibited growth when given in higher concentrations. Nucleoside mixture solution enhanced growth inhibition by 5-FU and it is a potential biochemical modulator of 5-FU metabolism in human cancer cells.

Cell Division

Two new iridolactones and their glycosides from the roots of Patrinia scabra.

Investigation of the roots of Patrinia scabra afforded two new iridolactones, patriscabrol and isopatriscabrol. Their structures have been established by extensive analysis of their NMR spectra and an X-ray crystallographic analysis of patriscabrol. Four monoglucosides of each iridolactone were also isolated together with an apioside of glucosidic patriscabrol.

Carbohydrate Sequence

Effect of nucleosides and a nucleotide mixture on proliferation of human gastric cancer cells (KATO III).

The effect of the nucleotides and a nucleotide mixture (OG-VI), consisting of inosine, guanosine 5'-monophosphate (5'-GMP), cytidine, uridine, thymidine (TdR) (4:4:4:3:1 in molar ratio), and TdR co-administration on proliferation of KATO III human gastric cancer cells in culture was evaluated. Consumption of purine and pyrimidine by cancer cells and changes in cell number with OG-VI or TdR were compared with the control culture medium (Williams E) after 72 hour-culture. Addition of OG-VI or TdR did not enhance the cellular proliferation, but inhibited growth when given in higher concentrations (0.3-3 mM inosine, 0.3-3 mM 5'-GMP, 0.22-2.2 mM uridine, 74-740 microM TdR). Consumption rate of TdR in the medium was less in the TdR group, 33.7%, than in the OG-VI group, 72.2% (p < 0.05). This suggests that TdR metabolism is modulated by other nucleosides and nucleotide included in OG-VI. Under the coadministration of 5-fluorouracil (FUra), addition of OG-VI or TdR suppressed cellular proliferation (p < 0.05). The inhibition rate of cellular proliferation in the OG-VI group was slightly higher than the TdR group, but there was no statistically significant difference between the two groups. The combination of FUra with OG-VI or TdR enhances the antitumor effect of FUra. It is concluded that the OG-VI does not enhance the tumor cell proliferation and it is a potential biochemical modulator of FUra metabolism in human cancer cells.

Cell Division

Inhibition of Na+,K(+)-ATPase activity by beta-eudesmol, a major component of atractylodis lanceae rhizoma, due to the interaction with enzyme in the Na.E1 state.

beta-Eudesmol, a major component of the crude drug "So-jutsu" (Atractylodis Lanceae Rhizoma), inhibited Na+, K(+)-ATPase activity most strongly among the various kinds of phosphatases examined. It also inhibited Ca(2+)-ATPase and H+, K(+)-ATPase, but to a lesser extent. Its effect on Mg(2+)-ATPase was minute. No effects on H(+)-ATPase or alkaline and acid phosphatase activities were observed. The effects of beta-eudesmol on horse kidney Na+, K(+)-ATPase were studied in detail, and the following results were obtained: (1) beta-eudesmol inhibited the Na+, K(+)-ATPase activity with an I50 value of 1.6 x 10(-4) M. The mode of its inhibition was uncompetitive with respect to ATP; (2) it prevented the stimulation of enzyme activity by Na+. The inhibition gradually increased in accord with the increase of Na+ concentration, and it was constant when Na+ was higher than 6.3 mM; (3) it did not alter the K+ concentration necessary for half-maximal activation (K0.5 for K+); and (4) it inhibited the enzyme activity with a mode of action different from ouabain. Phosphorylation of enzyme with [gamma-32P]ATP was inhibited by beta-eudesmol with an I50 of 1.4 x 10(-4) M. The inhibition was greater in 1 M NaCl than in 0.1 M NaCl. It had no effects on dephosphorylation steps, i.e. none of the non-specific, the ADP-sensitive (Na.E1-P----Na.E1) and the K(+)-dependent (E2-P----K.E2) dephosphorylation processes were affected. These results suggest that beta-eudesmol, a relatively specific inhibitor of Na+, K(+)-ATPase, interacts with the enzyme in the Na.E1 form and inhibits the reaction step Na.E1----Na.E1-P.

Adenosine Triphosphatases