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H Ishiyama

Publications and source records attributed to H Ishiyama.

At least 19 recordsLinked to original sources
PubMed2001

Nodulisporic acid A synthetic studies. 1. Overall strategy and construction of a western hemisphere subtarget.

In this, the first of two Letters, we outline our overall strategy for the construction of (+)-nodulisporic acid A (1), a representative member of a new class of indole diterpenes. In addition, we describe the efficient assembly of (-)-6, an advanced western hemisphere subtarget, comprising the ABC rings of (+)-nodulisporic acid A (1). The synthesis proceeded in 9% overall yield (longest linear sequence, 11 steps), exploiting a Shibasaki-Mori tandem transmetalation-cyclization to construct ring B. [reaction: see text]

Indoles↗
PubMed2001

Nodulisporic acid A synthetic studies. 2. Construction of an eastern hemisphere subtarget.

In this, the second of two Letters, we describe an effective assembly of (+)-4, an eastern hemisphere subtarget comprising the FGH rings of (+)-nodulisporic acid A (1) (17 steps, 9% overall yield). Central to the synthesis is a Koga three-component conjugate addition-alkylation sequence which secures the trans orientation of the vicinal quaternary methyl groups. [reaction: see text]

Indoles↗
PubMed2001

Development and characterization of a hybrid bioartificial liver using primary hepatocytes entrapped in a basement membrane matrix.

For the development of a bioartificial liver (BAL) support device, it is most important to establish highly differentiated liver cells cultured at high density. When rat hepatocytes were cultured on a basement membrane matrix, Engelbreth-Holm-Swarm (EHS) gel, their rates of albumin secretion were very high, as measured by ELISA, and these high rates were maintained for more than three weeks of culturing. This level of activity greatly exceeded that of hepatocytes cultured on a plastic substratum, poly-N-p-vinylbenzyl-D-lactonamide (PVLA), on a single layer of collagen, or in a collagen sandwich culture. In an in vitro perfusion experiment, rat hepatocytes rapidly and completely removed ammonia from Eagle's MEM supplemented with 0.2 mM NH4Cl, although ammonia levels of the medium serially increased in modules containing HepG2 cells. A hybrid liver support system was developed and consisted of plasma perfusion through porous hollow fiber modules inoculated with 10 billion porcine hepatocytes entrapped in EHS gel. This system was applied to pigs with ischemic liver failure 8 hr after creation of a portocaval shunt and hepatic devascularization. In animals treated with the BAL support system, blood bicarbonate levels were increased immediately after treatment, and hemodynamic stability was improved. In control pigs, on the other hand, blood bicarbonate levels and blood pressure remained low. Plasma levels of ammonia and lactate decreased in pigs treated with the BAL device, but not in control animals. These results indicate that primary hepatocytes outperform HepG2 cells as a source of biotransformation functions in a BAL system and that the use of a BAL support device in combination with a hollow fiber module and hepatocytes entrapped in EHS gel has potential advantages for clinical use in patients with fulminant hepatic failure.

Ammonia↗
PubMed2001

Determination of trace amounts of total arsenic in environmental samples by hydride generation flow injection-AAS using a mixed acid as a pretreatment agent.

A method is described for the determination of total arsenic by hydride generation-atomic absorption spectrophotometry using a mixed acid as a pretreatment. Hydride generation is done by the flow-injection method. The authors investigated in detail the temperature and time of decomposition using inorganic, organic arsenic and environmental standard samples, pretreated with nitric-perchloric-sulfuric mixed acid. By using a mixed acid as a pretreatment agent at 220 degrees C, the decomposition time could be shortened and the blank value of arsenic from the reagents used was reduced. The mixed acid of nitric-perchloric-sulfuric was also found to be effective as a pretreatment agent for organic arsenic compounds in which a dimethylated compound, sodium cacodylate or biological samples, is known to be one of the indecomposables. The present approach was proved to be satisfactory as a pretreatment for the quantitative analysis of trace amounts of total arsenic in liquid or solid environmental samples, such as geothermal water, sediments and biological samples.

Acids↗
PubMed2001

Rebamipide suppresses formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide production by inhibiting fMLP-receptor binding in human neutrophils.

The purpose of the present work was to investigate the mechanism underlying the inhibitory action of rebamipide on superoxide anion (O2) production induced by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP) in human neutrophils. Phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), a product of phosphoinositide 3-OH-kinase (PI 3-kinase) accumulated in response to fMLP and this accumulation was well correlated with O2 production in human neutrophils. Rebamipide inhibited PIP(3) production in parallel with the inhibition of fMLP-induced O2 production. PI 3-kinase activity in anti-PI 3-kinase p85 immunoprecipitates was not affected by the presence of rebamipide, therefore rebamipide did not have a direct inhibitory action on PI 3-kinase activity. Since rebamipide had no inhibitory effect on O2 production induced by NaF, a direct activator of G protein, the target of the inhibitory action of rebamipide appears to be a component of the signal transduction pathway upstream of G protein. Scatchard analysis of [3H]fMLP binding to human neutrophil membrane revealed that rebamipide increased the K(D) value of [3H]fMLP without altering the number of [3H]fMLP binding sites, suggesting that rebamipide has a competitive antagonistic action against the fMLP-receptor. The competitive antagonistic action was further confirmed by the finding that rebamipide caused a parallel shift to the right in the dose-response curve of O2 production induced by fMLP. These results provide evidence that the competitive inhibitory action of rebamipide on the fMLP-receptor plays a main role in its inhibitory action on fMLP-induced O2 production.

Alanine↗
PubMed2000

Diethyldithiocarbamate enhances production of nitric oxide and TNF-alpha by lipopolysaccharide-stimulated rat Kupffer cells.

Previous studies have shown that large doses of diethyldithiocarbamate (DDC) cause liver injury in rats and the pathogenesis of this injury involves, in part, release of superoxide anion by Kupffer cells. The purpose of this study was to evaluate if DDC was able to stimulate other potentially toxic mediators such as nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) using isolated rat Kupffer cells. DDC alone did not stimulate the release of NO and TNF-alpha by Kupffer cells. Interestingly, when Kupffer cells were stimulated by lipopolysaccharide (LPS), DDC (0-30 microM) enhanced the production of both NO and TNF-alpha in a concentration-dependent manner. Therefore, we further studied how DDC modulated the response of Kupffer cells to LPS. Immunocytochemical studies revealed that DDC increased the amount of inducible NO synthase and TNF-alpha protein in Kupffer cells after their exposure to LPS. The enhanced effects of DDC on the release of NO and TNF-alpha from Kupffer cells was inhibited by N-acetyl-L-cysteine (an inhibitor of transcription factor NF-kappaB activation). By using a specific antibody for NF-kappaBp65, it was found that DDC enhanced the LPS-activated nuclear translocation of NF-kappaB. There was no evidence of intracellular oxidative stress following either LPS alone or DDC + LPS exposure. The stimulatory effect of DDC on both NO and TNF-alpha release was inhibited by H-7 (an inhibitor of protein kinase C) but not H-8 (an inhibitor of cAMP-dependent protein kinase). These findings demonstrate that DDC enhances the production of NO and TNF-alpha by LPS-stimulated Kupffer cells and suggest that protein kinase C plays a critical role in mediating these effects of DDC.

Animals↗
PubMed1997

Histopathological changes induced by zinc hydroxide in rat lungs.

Rat lungs were histologically examined at 1, 7, 14 and 28 days following a single intratracheal instillation of zinc hydroxide (1 mM). After one day of treatment, no confirmatory findings were noted. The zinc hydroxide injections were followed by an increase in proliferating cell nuclear antigen labeling indices in both alveolar macrophages and terminal bronchioles. After 7 days, the zinc hydroxide-treated lungs showed thickening of the interstitium with infiltration by alveolar macrophages, and an increase in the grade of Masson's trichrome staining (collagen fiber) in the alveolar interstitium. Thereafter, these morphological changes disappeared. The vehicle- and zinc sulfate (1 mM)-exposed lungs had no abnormalities at any time point. Formazan deposits in alveolar macrophages, formed as a result of nitro blue tetrazolium reduction, were increased in zinc hydroxide-treated lung slices, suggesting that zinc hydroxide stimulated super oxide anion generation from alveolar macrophages. These results show that zinc hydroxide can induce morphological alterations of rat lungs.

Animals↗
PubMed1995

Structure-activity relationship of bromoeudistomin D, a powerful Ca2+ releaser in skeletal muscle sarcoplasmic reticulum.

Bromoeudistomin D and 9-methyl-7-bromoeudistomin D which have a beta-carboline skeleton are powerful Ca2+ releasers from skeletal muscle sarcoplasmic reticulum exhibiting caffeine-like properties. We examined the effects of bromoeudistomin D analogues on Ca(2+)-induced Ca2+ release from skeletal muscle sarcoplasmic reticulum. Among bromoeudistomin D analogues, the Ca(2+)-releasing activities of carboline derivatives were higher than those of carbazole derivatives, suggesting that a carboline skeleton is significantly important for the manifestation of Ca(2+)-releasing activity and Ca2+ sensitivity of Ca(2+)-induced Ca2+ release. On the contrary, the analogues which have a carbazole skeleton and bromine at C-6 inhibit both Ca(2+)- and caffeine-induced Ca2+ release. 9-Methyl-substitution of the analogue elevated its Ca(2+)-releasing activity. Moreover, there is a close correlation between the enhancement of [3H]ryanodine binding to sarcoplasmic reticulum by the analogues and the activation of Ca2+ release by them. Bromoudistomin D analogues may provide valuable information about the structure-function relationship of the ryanodine receptor/Ca2+ release channels in skeletal muscle sarcoplasmic reticulum.

Animals↗
PubMed1995

Role of Kupffer cells in rat liver injury induced by diethyldithiocarbamate.

The hepatotoxicity of diethyldithiocarbamate was examined using an in vitro rat liver slice system. Concentration- and time-dependent losses of intracellular K+ and adenosine triphosphate (ATP) levels were observed in rat liver slices incubated with diethyldithiocarbamate at concentrations between 1 and 10 mM over a 4-h period. Histological study revealed perivenous hepatocyte damage. To examine the involvement of Kupffer cells in diethyldithiocarbamate-induced cytotoxicity, rats were injected intravenously with 10 mg/kg of gadolinium chloride (GdCl3) which diminishes Kupffer cell function. Incubation of liver slice preparations from the GdCl3-treated rats with diethyldithiocarbamate showed marked inhibition of the cytotoxicity induced by diethyldithiocarbamate. Moreover, in vitro addition of manganese-superoxide dismutase, a superoxide anion scavenger, or dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, also showed potent inhibition. However, dexamethasone, an inhibitor of tumor necrosis factor, and N,N'-diphenyl-p-phenylenediamine (DPPD), an antioxidant, showed partial prevention of cytotoxicity. Formazan deposits formed as a result of nitro blue tetrazolium reduction were found in Kupffer cells at an early stage after diethyldithiocarbamate treatment, while lipid peroxidation occurred after 3 h. Both pretreatment with GdCl3 in vivo and addition of DMSO in vitro prevented the increase in lipid peroxidation within the liver slice preparations induced by diethyldithiocarbamate. These findings suggest that Kupffer cell function may be involved in the pathogenesis of diethyldithiocarbamate hepatotoxicity.

Adenosine Triphosphate↗
PubMed1995

Proliferation of hepatocytes and attenuation from carbon tetrachloride hepatotoxicity by gadolinium chloride in rats.

Intravenous injection of gadolinium chloride (GdCl3) at a dose of 10 mg/kg caused an increase in proliferating cell nuclear antigen labeling index and the grade of pyronin positivity (RNA level) in rat liver. In CCl4-exposed rats, pretreatment with GdCl3 also showed a preventive effect of the liver injury both biochemically and histologically. Moreover, the proliferative action preceded the attenuative effect of the liver injury. Results suggest that GdCl3 induces hepatocyte proliferation, and this action of GdCl3 may modify the development of CCl4-induced liver injury.

Alanine Transaminase↗
PubMed1994

Zinc hydroxide induced respiratory burst in rat neutrophils.

The effects of zinc hydroxide on the respiratory burst and phagocytosis by rat neutrophils were examined. Zinc hydroxide induced an increase in oxygen consumption and O2- production. Electronmicroscopy showed that neutrophils engulfed zinc hydroxide particles by phagocytosis. Pertussis toxin (0.25, 0.5, 1.0 micrograms/ml) and EGTA (1, 2, 5 mM) inhibited zinc hydroxide-induced O2- production in a dose-dependent manner. The inhibitors of protein kinase C, 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide inhibited zinc hydroxide-induced O2- production with IC50 values ranging between 10 microM and 25 microM. The inhibitory study using an inhibitor of myosin light chain kinase, 1-(5-iodo-naphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine, showed IC50 values ranging from 5 microM to 10 microM. These findings indicate that zinc hydroxide induces respiratory burst and phagocytosis by rat neutrophils.

Animals↗
PubMed1992

Zinc hydroxide stimulates superoxide production by rat alveolar macrophages.

The effect of zinc hydroxide on superoxide (O2-) production by rat alveolar macrophages was determined by chemiluminescence and by cytochrome c reduction. Zinc ions had no effect on the chemiluminescence of unstimulated alveolar macrophages. By contrast, zinc hydroxide (ZnOH2), a neutralized form of zinc ions, increased the chemiluminescence level and O2- release. Increased O2- release was inhibited by pertussis toxin, isoquinoline sulfonamide and pretreatment with EGTA. These findings indicate that zinc hydroxide formation from zinc compounds can stimulate the O2- production by alveolar macrophages by receptor-mediated and Ca(2+)-dependent process.

Animals↗
PubMed1992

Antiulcer mechanism of action of rebamipide, a novel antiulcer compound, on diethyldithiocarbamate-induced antral gastric ulcers in rats.

The mechanism of the inhibitory action of rebamipide, a new mucosal protective drug, was studied using rats with diethyldithiocarbamate-induced gastric antral ulcers. Rebamipide reduced ulcer formation and inhibited the elevation in lipid peroxide concentration in the gastric mucosa. Rebamipide inhibited both luminol- and lucigenin-dependent chemiluminescence of neutrophils activated by formyl-methionyl-leucyl-phenylalanine. Rebamipide did not alter the reduction of cytochrome c induced by the xanthine-xanthine oxidase system or the NADPH-dependent microsomal lipid peroxidation in the liver. These findings suggest that rebamipide prevents diethyldithiocarbamate-induced gastric ulcer formation by inhibiting neutrophil activation.

Alanine↗
PubMed1992

[Studies on the effect of combination of amphotericin B and flucytosine on Candida albicans by flow cytometry].

The antifungal effects of amphotericin B (AMPH) and flucytosine (5-FC) on three strains of Candida albicans were studied by flow cytometry (FCM). When the IFM4954 and IFM4949 were treated with AMPH or 5-FC alone, cytograms of cell distribution changed at the concentration of 1/2 MIC, respectively. Next, the effect of combination of AMPH and 5-FC were examined. Cytogram of cell distribution of IFM4954 and IFM4949 changed under the combination of 1/4 MIC of AMPH and 1/4 MIC of 5-FC, namely a synergic effect was observed. In conclusion, FCM is a useful apparatus for analysis of the effect of antifungal agents.

Amphotericin B↗