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I Yasuda

Publications and source records attributed to I Yasuda.

At least 19 recordsLinked to original sources

Involvement of a cis-acting element in the suppression of carbamoyl phosphate synthetase I gene expression in the liver of carnitine-deficient mice.

The expression of carbamoyl phosphate synthetase I (CPS) gene is suppressed in the liver of carnitine-deficient juvenile visceral steatosis (JVS) mice at weaning and under starvation at adult age. To clarify the suppression mechanism, we produced CPSL transgenic JVS mice carrying a transgene composed of the chloramphenicol acetyltransferase (CAT) gene with the upstream region (-12 kb to +138) of the rat CPS gene and CPSE transgenic JVS mice carrying a transgene composed of the luciferase gene with minimal promoter (299 bp from -161 to +138) and enhancer (469 bp around -6.3 kb) fragments of the rat gene. The expression of the CAT gene as well as the endogenous CPS was suppressed in CPSL transgenic JVS mice, but luciferase gene expression was not suppressed in CPSE transgenic JVS mice. We isolated the 5'-upstream region of the mouse CPS gene and identified an activator protein-1 (AP-1) site downstream of the minimum enhancer region of both rat and mouse CPS genes. In conjunction with the 313-bp mouse promoter region, the 714-bp mouse enhancer fragment conferred a cell-type-dependent hormone responsiveness. In rat primary cultured hepatocytes, the addition of oleic acid suppressed reporter gene expression induced by dexamethasone in the construct containing the enhancer fragment of 714 bp with the AP-1 site, but not in its AP-1 site mutants or in 519 bp without the AP-1 site. These results strongly suggest that direct protein-protein interaction between AP-1 and glucocorticoid receptor is not involved in the suppression of the CPS gene in JVS mice and that the AP-1 element is the cis-element which is responsible for the suppression.

Animals

Anti-AIDS agents. 30. Anti-HIV activity of oleanolic acid, pomolic acid, and structurally related triterpenoids.

Oleanolic acid (1) was identified as an anti-HIV principle from several plants, including Rosa woodsii (leaves), Prosopis glandulosa (leaves and twigs), Phoradendron juniperinum (whole plant), Syzygium claviflorum (leaves), Hyptis capitata (whole plant), and Ternstromia gymnanthera (aerial part). It inhibited HIV-1 replication in acutely infected H9 cells with an EC50 value of 1.7 microg/mL, and inhibited H9 cell growth with an IC50 value of 21.8 microg/mL [therapeutic index (T. I.) 12.8]. Pomolic acid, isolated from R. woodsii and H. capitata, was also identified as an anti-HIV agent (EC50 1.4 microg/mL, T. I. 16.6). Although ursolic acid did show anti-HIV activity (EC50 2.0 microg/mL), it was slightly toxic (IC50 6.5 microg/mL, T. I. 3.3). A new triterpene (11) was also isolated from the CHCl3-soluble fraction of R. woodsii, though it showed no anti-HIV activity. The structure of 11 was determined to be 1beta-hydroxy-2-oxopomolic acid by spectral examination. Based on these results, we examined the anti-HIV activity of oleanolic acid- or pomolic acid-related triterpenes isolated from several plants. In addition, we previously demonstrated that derivatives of betulinic acid, isolated from the leaves of S. claviflorum as an anti-HIV principle, exhibited extremely potent anti-HIV activity. Accordingly, we prepared derivatives of oleanolic acid and evaluated their anti-HIV activity. Among the oleanolic acid derivatives, 18 demonstrated most potent anti-HIV activity, with an EC50 value of 0. 0005 microg/mL and a T. I. value of 22 400.

Anti-HIV Agents

Endoscopic papillary balloon dilatation for common bile duct stones: efficacy of combination with extracorporeal shockwave lithotripsy for large stones.

BACKGROUND: Endoscopic papillary balloon dilatation (EPBD) is generally considered a safe and effective technique for removal of common bile duct (CBD) stones. However, some reports have prompted concern about the risk of pancreatitis following the procedure, and it seems to be more difficult and to require adjunctive procedures more frequently in patients with large stones. AIMS: To analyse the factors influencing pancreatitis after the procedure, and to examine which is the more suitable adjunct for treating large stones, mechanical lithotripsy (ML) or extracorporeal shockwave lithotripsy (ESWL). PATIENTS AND METHODS: EPBD was performed in 92 patients, including 40 with large stones (> or = 12 mm). These 40 patients were randomly assigned to two groups receiving ML or ESWL to fragment stones (20 patients each). RESULTS: Complete ductal clearance was obtained in all 92 patients. Significant elevation of the serum amylase level compared with the prior value (> 300 IU/l) was observed in 26 (28%), and eight (8.7%) developed clinical pancreatitis. To assess the influence of various factors on the amylase level, multivariate analysis was used. The number of stones and the time required for treatment had a significant influence on the incidence of increased amylase level (P < 0.05), and ML also significantly increased it (P < 0.05). On the other hand, the amylase level remained low in the ESWL group. ML caused elevation of amylase level in 11 patients (55%), while three (15%) had elevation after ESWL. CONCLUSIONS: In patients with multiple stones, elevation of the amylase level is more frequent. This seems to be because repeated cannulation and much time is required for treatment. In patients with large stones, the rate was also high if ML was used, but was low when ESWL was used. ESWL may reduce the incidence of pancreatitis.

Aged

[Aristolochic acids in herbal medicines].

Aristolochic acids are nitrophenanthrenes with a carboxylic acid fanction which have been found only among the Aristolochiaceae. In 1993, rapidly progressive interstitial renal fibrosis has been reported in women have been on a slimming regimen including Chinese herbal medicines in Belgium. In Japan, at the Kansai district, several cases of Chinese herbs nephropathy have been reported quite recently. In both cases, aristolochic acids was detected in the Chinese herbal medicines taken by the patients. We have Asiasarum Root, a species of Aristolochiaceae, in Japanese Pharmacopoeia. Therefore, we quantitatively analysed aristolochic acids in these herbal medicines and related plants.

Antineoplastic Agents

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

Deletion of serum lectin-reactive alpha-fetoprotein by acyclic retinoid: a potent biomarker in the chemoprevention of second primary hepatoma.

A goal of cancer chemoprevention is the deletion of latent premalignant or malignant clones before they expand to a clinically detectable tumor. However, such clonal deletion has not been demonstrated in clinical studies. We have evaluated serum levels of lectin-reactive alpha-fetoprotein (AFP-L3), which suggests the presence of latent hepatoma cells, in a randomized controlled trial that used acyclic retinoid to prevent second primary hepatomas in patients who had received treatments that cured initial hepatomas. The trial involved 21 patients in each acyclic retinoid (600 mg daily) and placebo group and consisted of a 12-month period of drug administration and a subsequent follow-up period. Serum AFP-L3 was determined at entry and at the end of the 12-month treatment period using lectin-affinity electrophoresis and antibody-affinity blotting. Although neither treatment affected serum levels of total AFP, acyclic retinoid significantly reduced AFP-L3 levels after a 12-month administration (P < 0.01). Acyclic retinoid not only deleted AFP-L3 from patients who had been positive for AFP-L3 at entry but also prevented the appearance of AFP-L3 in patients who had been negative at entry (P < 0.01). In contrast, placebo significantly raised the incidence of AFP-L3-positive patients after a 12-month administration from that at entry (P < 0.05). Patients positive for AFP-L3 after a 12-month treatment had a significantly higher risk of second primary hepatomas in the subsequent follow-up period (P = 0.03). Acyclic retinoid may have deleted a clone of latent hepatoma cells producing AFP-L3 and thereby inhibited second primary hepatomas. Serum AFP-L3 may be a useful intermediate biomarker in the chemoprevention of second primary hepatomas by acyclic retinoid.

Antineoplastic Agents

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].

Explore the source record for details and available documents.

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