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S Iwata

Publications and source records attributed to S Iwata.

At least 163 records · Page 9Linked to original sources
PubMed1995

Quantitative analysis of redox gradient within the rat liver acini by fluorescence images: effects of glucagon perfusion.

The redox gradient along the sinusoid in the rat liver was studied using a redox scanner, a device based on tissue fluorescence scanning spectroscopy measuring the fluorescence signals of oxidized flavoprotein (FP) and reduced pyridine nucleotide (PN). The FP/(FP+PN) ratio reflects the mitochondrial redox state in the liver tissue. The distribution of mitochondrial redox state on the scanned area is expressed as two-dimensional gray-scale images with a 20 micron resolution. Using this instrument, we have scanned a 2.5 x 2.5 mm area of the frozen rat liver sample to investigate the redox gradient within acini and the effects of glucagon on the changes in the redox distribution. The redox images obtained in the perfused livers showed mosaic patterns implicating a regular heterogeneity of redox state in an acinus. The analysis of gradient curve, furthermore, clarified that the redox level in an acinus decreased sigmoidally from the periportal to the pericentral region. Glucagon, which has been reported to reduce the intracellular redox state, decreased the redox potential in whole acini, especially, in the periportal region, when compared with the perfusion without glucagon. These results strongly indicate an intraacinus heterogeneity of glucagon function, with glucagon selectively operating in the upstream of the sinusoid.

Animals↗
PubMed1995

Immunoelectron microscopy and epitope mapping with monoclonal antibodies suggest the existence of an additional N-terminal transmembrane helix in the cytochrome b subunit of bacterial ubiquinol:cytochrome-c oxidoreductases.

The topology of the ubiquinol:cytochrome-c oxidoreductase (cytochrome bc1 complex) from Paracoccus denitrificans was investigated by immunoelectron microscopy with sequence-specific murine monoclonal antibodies. Epitope mapping with synthetic peptides and enzymic proteolytic cleavage of the cytochrome bc1 complex were employed to localize precisely the respective antibody epitopes on the subunits of this membrane protein complex. Localization of defined epitopes on the cytochrome bc1 complex by immunoelectron microscopy clearly demonstrates that the N-terminus of the cytochrome b subunit is exposed to the periplasmic space. This finding is in agreement with a nine-transmembrane-helices topology model (I-IX) as predicted before for cytochrome b. However, due to other published evidence we favour the existence of an additional transmembrane helix (helix 0) complementing a more recently published eight-helices model (A-C,cd, D-H), at least for prokaryotes.

Amino Acid Sequence↗
PubMed1995

Thiol-mediated redox regulation of apoptosis. Possible roles of cellular thiols other than glutathione in T cell apoptosis.

Thiol redox status modulates various aspects of cellular function. We demonstrate that oxidation of cellular sulfhydryl (SH) groups induces apoptosis. In Jurkat T cells and human PBL blasts, the fraction of apoptotic nuclei increased after treatment with an SH-specific oxidant, diamide. Analysis of DNA fragmentation and nuclear morphology also indicated that SH oxidation could induce apoptosis. In the apoptosis induced by SH oxidation, the decrease of cellular glutathione was transient and the increase of glutathione disulfide was observed only after apoptotic changes had occurred. Depletion of cellular glutathione with buthionine sulfoximine failed to induce apoptosis, despite a marked decrease of cellular glutathione, which was greater than that observed in apoptosis induced by diamide. Thus, the changes of cellular glutathione or glutathione disulfide may not be the major cause of apoptosis induced by diamide. Intracellular adult T cell leukemia-derived factor/human thioredoxin, another thiol-related antioxidant protein, was oxidized by incubation with diamide. These results suggest that thiol redox status is one of the key factors of the apoptotic pathway in which thiols other than glutathione may play even more critical roles.

Apoptosis↗
PubMed1995

Ca2+ handling mechanisms underlying neuropeptide Y-induced contraction in canine basilar artery.

The effects of neuropeptide Y on isometric tension simultaneously measured with cytosolic Ca2+ concentration ([Ca2+]cyt) and Ca2+ sensitivity of contractile elements were studied in isolated canine basilar arteries. Neuropeptide Y (1-100 nM) increased [Ca2+]cyt and tension in a concentration-dependent and parallel manner, whereas 9,11-dideoxy-11 alpha,9 alpha-epoxymethano prostaglandin F2 alpha (U46619) (10-100 nM), a thromboxane A2 mimetic, produced a large contraction with a small increase in [Ca2+]cyt. Ca2+ channel antagonists such as d-cis-diltiazem (10 mM) abolished both [Ca2+]cyt and tension augmented by neuropeptide Y. In Ca(2+)-free solution containing 0.2 mM EGTA, neuropeptide Y did not change [Ca2+]cyt and tension, whereas U46619 transiently increased both of them. Furthermore, neuropeptide Y apparently did not affect the Ca2+ sensitivity when assessed in the artery permeabilized with Staphylococcus aureus alpha-toxin, whereas U46619 augmented it. These findings suggest that neuropeptide Y-induced contraction in the canine basilar artery is produced mainly by Ca2+ influx through L-type Ca2+ channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Rational use of oral antibiotics for pediatric infections.

We carried out a survey in Japan to investigate compliance among children given oral antibiotics in an outpatient setting. The results of our survey revealed that, in Japan, approximately one-quarter of patients did not take their full course of antibiotics. Reasons for unsupervised self-discontinuation included: (1) the parent or guardian judged the infection to be cured; (2) the child refused to take the drug; and (3) the appearance of side effects. Causative organisms often involved in respiratory infections experienced in out-patient medicine include pneumococci, streptococci, staphylococci, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and Mycoplasma pneumoniae. The beta-lactams are effective against all of these bacterial species, with the exception of M. pneumoniae. We conducted a survey of beta-lactam antibiotics currently on the Japanese market and compared them to other oral antibiotics used to treat respiratory infections. Ease of administration, based on the incidence of adverse effects, particularly diarrhea, the dosage form, taste, dosage per administration and the number of doses required per day, are reported.

Administration, Oral↗
PubMed1995

Coexisting type III hyperlipoproteinemia and familial hypercholesterolemia: a case report.

A 39-year-old man presented with type III hyperlipoproteinemia in association with heterozygous familial hypercholesterolemia (FH). He had extensive tuberous xanthomas over the knees and elbows and xanthomas in the Achilles tendons. He also had palmar xanthomas. He exhibited severe hypercholesterolemia and hypertriglyceridemia. This patient was heterozygous for FH, as evidenced by low low-density lipoprotein (LDL) receptor function on lymphocytes, and had type III hyperlipoproteinemia, as determined by apolipoprotein (apo) E phenotype 2/2 in isoelectric focusing of the E isoproteins and the presence of a broad beta band on electrophoresis. Because therapy consisting of diet restrictions and lipid-lowering agents such as clinofibrate and niceritrol did not decrease serum total cholesterol ([TC] 15.26 mmol/L) and triglyceride ([TG] 10.79 mmol/L) levels effectively, the patient underwent plasmapheresis once every 2 weeks using a dextran sulfate-cellulose column. Repeated plasmapheresis markedly reduced serum TC and TG and induced complete regression of the palmar xanthoma after 6 months. The severity of tuberous xanthomas on the knees and elbows was reduced after 2.5 years. After plasmapheresis, TC decreased to 1.94 mmol/L from 10.40 mmol/L and TG decreased to 0.33 mmol/L from 7.90 mmol/L. Plasmapheresis performed with a dextran sulfate-cellulose column was highly effective in removing the lipoprotein-remnant particles in this patient, leading to generalized improvement in the lipoprotein profile.

Adult↗
PubMed1995

Fv fragment-mediated crystallization of the membrane protein bacterial cytochrome c oxidase.

Crystallization of membrane proteins, a prerequisite for their X-ray crystallographic analysis, remains difficult. Here, we demonstrate that the crystallization of the cytochrome c oxidase from Paracoccus denitrificans can be mediated by co-crystallization with an antibody Fv fragment. The crystals obtained contain all four subunits of this membrane protein complex and the Fv fragment. The approach of co-crystallizing membrane proteins with antibody fragments should be useful in obtaining well-ordered crystals of membrane proteins in general.

Antibodies, Monoclonal↗
PubMed1995

Strong anti-mutagenic activity of the novel lipophilic antioxidant 1-O-hexyl-2,3,5-trimethylhydroquinone against heterocyclic amine-induced mutagenesis in the Ames assay and its effect on metabolic activation of 2-amino-6-methyldipyrido[1,2-a:3',2'-d] imidazole (Glu-p-1).

Antimutagenic effects of a novel lipophilic antioxidant, 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), and other known antioxidants against heterocyclic amine- or other mutagen-induced mutagenesis were examined in the Ames assay using Salmonella strain TA 98 to access the chemo-preventive effects of antioxidants on heterocyclic amine-induced carcinogenesis. Further the mechanisms of inhibition by HTHQ were accessed. HTHQ was shown to potently inhibit mutagenesis induced by all of 8 different heterocyclic amines at rates between 100% and 63% in the presence of S9 mix. When the protection of HTHQ against 2-amino-6- methyldipyrido[1,2-alpha:3',2'-d]imidazole (Glu-P-1)-induced mutagenesis was compared with known antioxidants t-butylhydroquinone, propyl gallate, BHA, BHT and alpha-tocopherol, HTHQ showed the greatest effect. Among hexyl, butyl, ethyl and methyl derivatives of 1-O-alkyl-2,3,5-trimethylhydroquinone, HTHQ was the most effective in inhibiting Glu-P-1-, 3-amino-1-methyl-5-H-pyrido[4,3-b]indole (Trp-P-2)- or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced mutagenesis. On the other hand, HTHQ did not inhibit mutagenic activity induced by other mutagens such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) and benzo[a]pyrene. HTHQ weakly inhibited that due to direct mutagen 2-nitro derivative of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) only in the presence of S9 mix. No such influence on a 2-nitro derivative of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mutagenesis, was observed with or without the S9 mix. HTHQ slightly inhibited mutagenesis induced by activated Glu-P-1, a direct acting proximate metabolite of Glu-P-1, in the absence of the S9 mix. HPLC analysis revealed activated Glu-P-1 to be formed by incubating Glu-P-1 with the S9 mix, but this was considerably decreased by the addition of HTHQ. These results indicate that HTHQ is a powerful antimutagenic compound and specifically acts against heterocyclic amines. Its antimutagenic activity appeared to exert by both inhibiting metabolic activation of heterocyclic amines and action on activated N-hydroxy species.

Amines↗
PubMed1995

Suppression of adult T cell leukemia-derived factor/human thioredoxin induction by FK506 and cyclosporin A: a new mechanism of immune modulation via redox control.

Adult T cell leukemia-derived factor (ADF), which is identical to a disulfide reducing enzyme human thioredoxin (TRX), is produced and released by activated or virus-infected lymphocytes. Here we report that, in peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA), ADF/TRX mRNA was induced within 8 h after stimulation as detected by in situ hybridization study. To analyze the mechanism of ADF/TRX induction during T cell activation, the effects of immunosuppressants including FK506, rapamycin (Rap) and cyclosporin A (CsA) on ADF/TRX expression were investigated by immunoblot analysis. ADF/TRX induction in PBMC by PHA, Con A or OKT3 mAb was almost completely suppressed by FK506. Whereas CsA also inhibited ADF/TRX expression in OKT3 mAb-stimulated PBMC, Rap failed to affect it in spite of exhibiting growth inhibition. In addition, exogenous IL-2 could not increase ADF/TRX production in FK506-treated PBMC or in PHA blasts. These results indicate that ADF/TRX induction in T cell activation depends on calcineurin-dependent events in the early phase and that IL-2 production is not directly involved in ADF/TRX induction. Furthermore, when recombinant ADF (rADF) was added to a culture of PBMC 1 h before the addition of PHA and FK506, the action of FK506 was partially reversed as determined by [3H]thymidine incorporation and viable cell counts. These results suggest that ADF/TRX produced and released from PBMC may be a crucial event in lymphocyte activation, and that FK506 and CsA may exert the immune suppression partly through inhibiting the induction of the endogenous reducing factor ADF/TRX.

Adjuvants, Immunologic↗
PubMed1995

Effects of pyridoxalated hemoglobin polyoxyethylene conjugate and other hemoglobin-related substances on arterial blood pressure in anesthetized and conscious rats.

The effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and other hemoglobin-related substances on arterial blood pressure (ABP) and heart rate (HR) were examined. Infusion of PHP and other hemoglobin-related substances elevated ABP and increased HR. The degree of the increase in ABP and HR did not differ among the groups. There were species' differences in responses to PHP. Pretreatment with various blockers did not abolish the elevation of ABP. The pretreatment of NG-monomethyl-L-arginine dose-dependently reduced the elevation of ABP but did not completely abolish it. PHP also elevated ABP in conscious rats. The magnitude of the ABP elevation was significantly smaller than in the anesthetized rats. Results indicate that inhibition of nitric oxide (NO) might be responsible in part for the elevation of ABP, and the degree of the elevation would be dependent on the degree of contribution of NO to the regulation of ABP.

Adrenergic Antagonists↗
PubMed1995

Intraarterial perfusion of the hindlimb with pyridoxalated hemoglobin polyoxyethylene conjugate solution in anesthetized dogs.

To evaluate the potential clinical usefulness of a modified hemoglobin, pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), the hindlimb vascular bed was perfused with PHP solution while monitoring tissue oxygen tension (PtO2) in anesthetized dogs. The hindlimb region was perfused through the external iliac artery with a roller pump at a varying perfusion rate. PtO2 was measured using a PO2-monitoring probe inserted into the gracial muscle. After surgical preparation for perfusion, the iliac arterial flow rate was 19.9 +/- 5.6 ml/min, and baseline PtO2 was 38.4 +/- 1.3 mm Hg. Perfusion with autologous arterial blood with the pump increased PtO2 and perfusion pressure (PP) in a perfusion rate-dependent manner. Perfusion with PHP solution at 20 ml/min decreased PtO2 from the initial baseline level, but an increase in the flow rate to 40-55 ml/min restored or induced an elevation of PtO2. Results demonstrated that PHP solution can deliver oxygen to local tissue and maintain tissue oxygen tension at the same level as autologous arterial blood at a high enough flow rate.

Animals↗
PubMed1995

Effect of gabexate mesilate on thrombin and plasmin generation after hepatic resection in cirrhotic patients.

The effect of the gabexate mesilate (Gab) on thrombin and plasmin generation following liver resection in cirrhotic patients was studied. Six cirrhotic patients received an infusion of Gab after liver resection (Gab group), and another 6 patients did not receive such treatment (Con group). The parameters measured were thrombin-antithrombin complex (TAT), plasmin-antiplasmin complex (PAP) and D-dimer. The real increases of D-dimer and PAP were significantly higher in Con group after surgery while no significant difference was observed in the increase of TAT. These results show that Gab suppresses plasmin generation and following D-dimer production more effectively than thrombin generation after hepatic resection.

Aged↗