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Biomedical subjects

Y Yui

Publications and source records attributed to Y Yui.

At least 37 records · Page 2Linked to original sources
PubMed1995

A novel modified tissue-type plasminogen activator (t-PA), E6010, reduces reperfusion arrhythmias induced after coronary thrombolysis--comparison of native t-PA and urokinase.

The aim of this study was to compare the effects of a novel modified tissue-type plasminogen activator (t-PA), E6010, to those of native t-PA and urokinase on reperfusion arrhythmias (premature ventricular complexes: PVC) and the mortality rate after coronary thrombolysis. The frequency of PVC and the mortality rate were evaluated in anesthetized dogs which had 1-, 3- or 6-h-old thrombi induced by a copper coil in the coronary artery. Thrombolytic treatment with a bolus intravenous (iv) injection of E6010 was compared with the continuous iv administration of native t-PA or urokinase. The frequency of PVC was significantly lower in the E6010 group than in the native t-PA and urokinase groups (P < 0.05). The mortality rate in the E6010 group (0.0%) tended to be lower than those in the native t-PA group (10.7%) and the urokinase group (7.1%). These results indicate that the bolus iv injection of E6010 reduced both PVC and the mortality rate, compared with the continuous iv administration of native t-PA or urokinase for coronary thrombolysis; Therefore, E6010 may have beneficial effects in prehospital thrombolysis.

Analysis of Variance↗
PubMed1995

Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in reversible endotoxic shock studied by a novel monoclonal antibody against rat iNOS.

An antirat monoclonal antibody (mAb) against inducible nitric oxide synthase (iNOS), ANOS11, was used for immunohistochemistry to examine the expression of iNOS in various organs and tissues of adult rats in experimental endotoxic shock induced by lipopolysaccharide (LPS) injection. The phenotype of iNOS-expressed cells was also examined immunohistochemically using various mAbs. In control rats, very few cells were positive for ANOS11 except in the thymus. After intravenous injection of LPS, the number of iNOS-positive cells increased rapidly in almost all organs, except the thymus and brain, peaked 6 h after the injection, and decreased slowly. Of the numerous inflammatory cells that infiltrated the lungs, liver, and spleen after LPS injection, many were positive for ANOS11. Besides inflammatory cells, hepatocytes and endothelial cells of the aorta were also positive for ANOS11 but only around 6 h after injection. The cellular composition of iNOS-positive infiltrated cells changed along with the progression of endotoxic shock. At 4 to 6 h after injection, most iNOS-positive cells were considered polymorphonuclear leukocytes judging by their positive reactivity to OX42 and their nuclear morphology. The population of iNOS-positive macrophages positive for ED1 or ED2 increased with time. After 24 h, many iNOS-positive macrophages were found around the focal necrosis in the liver and spleen. These results indicate that the expression of iNOS in neutrophils, endothelial cells, and hepatocytes precedes that of macrophages in experimental endotoxic shock. The expression of iNOS in various cells and organs is closely associated with the progress and pathological changes of endotoxic shock.

Amino Acid Oxidoreductases↗
PubMed1995

Expression and localization of inducible nitric oxide synthase in anti-Thy-1 glomerulonephritis.

To elucidate a possible involvement of nitric oxide in the development of a mesangial proliferative glomerulonephritis induced by anti-Thy-1 antibody administration, glomerular expression of three isoforms of NO synthase (NOS), inducible NOS (iNOS), brain NOS, and endothelial NOS, was examined at both mRNA and protein levels by ribonuclease protection assay and immunofluorescence microscopy. Light microscopy showed an accumulation of polymorphonuclear leukocytes at 1 hour, lysis of mesangial cells at 1 day, a mesangial proliferative lesion at 4 to 10 days, and minimal residual glomerular lesions by 28 days. Ribonuclease protection assay showed that the glomerular expression of iNOS mRNA peaked at 1 hour and decreased thereafter. No substantial expression of iNOS mRNA was observed in normal glomeruli or in the nephritic glomeruli obtained at different time points (1, 4, 10, or 28 days). By immunofluorescence microscopy with a specific monoclonal antibody, an intense reaction for iNOS was demonstrated in a few cells in the glomeruli at 1 hour. Most of the iNOS-positive cells were identified as polymorphonuclear leukocytes. iNOS-positive cells were found less frequently in the glomeruli on days 1 and 4. Endothelial NOS mRNA was constitutively expressed in normal glomeruli and increased biphasically with two peaks at 1 hour and at 4 days or later; however, the peak expression was much less than that of iNOS mRNA at 1 hour. Expression of brain NOS mRNA was not detectable in either normal or nephritic glomeruli. These results show that iNOS is predominantly expressed in polymorphonuclear leukocytes accumulating at 1 hour in the glomeruli of anti-Thy-1 glomerulonephritis and suggest an involvement of NO in the initiation of the disease.

Animals↗
PubMed1994

Cloning and structural characterization of the human endothelial nitric-oxide-synthase gene.

Nitric oxide accounts for the activity of endothelium-derived relaxing factor, which seems to have an important role in vasodilation and inhibition of platelet aggregation. In endothelial cells, one isoform of nitric-oxide synthase is constitutively expressed. Analysis of the cDNA encoding the human endothelial nitric-oxide synthase revealed that the mRNA is 4.1 kb in size and that the translated protein consists of 1203 amino acids. We have cloned a genomic DNA encoding the human endothelial nitric-oxide synthase and analyzed the entire nucleotide sequence of the gene. The gene consists of 26 exons with a total size of 21 kb. The 5' flanking region of the gene lacks TATA boxes, but it contains putative Sp1-binding sites in (G+C)-rich regions. Of particular interest is the fact that a shear-stress-responsive element is located at position -985, which probably regulates the nitric-oxide-synthase gene in response to fluid mechanical forces at the transcriptional level in the vascular endothelium. Two minisatellite sequences are detectable in introns 2 and 8; a 32-bp consensus sequence repeats 38 times and a 57-bp consensus sequence repeats ten times. We found polymorphisms of the BamHI fragment containing the former minisatellite sequence in genomic DNA from pedigree family members. Furthermore, five tandem repeats of a 27-bp core consensus sequence and 35 repeats of a dinucleotide (CA) are located in introns 4 and 13, respectively. These repeat sequences will probably provide genetic markers for gene mapping and linkage analysis of inherited diseases including cardiovascular diseases.

Amino Acid Oxidoreductases↗
PubMed1994

Three distinct subpopulations of GABAergic neurons in rat frontal agranular cortex.

GABAergic interneurons in the rat frontal cortex were subdivided on the basis of immunoreactivity for calcium binding proteins, neuropeptides and nitric oxide synthase, using double immunofluorescence and mirror image immunohistochemical methods. The results indicate that in this region of the neocortex there are at least three distinct subpopulations of local circuit neurons. The first subgroup consists of parvalbumin-immunoreactive cells. Those do not contain neuropeptide, calretinin or nitric oxide synthase immunoreactivity. A substantial number of parvalbumin-immunoreactive cells in layer II/III were also immunoreactive for calbindin D28k. The second subgroup consists of cells immunoreactive for calretinin. Most were usually immunoreactive for vasoactive intestinal polypeptide as well, but a few cells in layer II/III were immunoreactive for one or the other only. Calretinin-immunoreactive cells do not colocalize parvalbumin, somatostatin or nitric oxide synthase, and only a few colocalize calbindin D28k. The third subgroup consists of cells most of which contain somatostatin, and is entirely separate from the parvalbumin- and calretinin-immunoreactive populations. There was substantial colocalization of somatostatin and calbindin D28k and of somatostatin and neuropeptide Y. Some somatostatin-immunoreactive cells showed nitric oxide synthase immunoreactivity. All of the populations of immunoreactive cells examined in the present study also showed GABA immunoreactivity. About 10% of calbindin D28k-immunoreactive cells and all of those strongly stained for calbindin D28k in layer II/III showed GABA immunoreactivity. Most calbindin D28k-positive cells in deep layers also showed GABA immunoreactivity. These results support that almost all calbindin D28k-immunoreactive non-pyramidal cells are probably GABAergic.

Amino Acid Oxidoreductases↗
PubMed1994

Preferential inhibition of inducible nitric oxide synthase by ebselen.

Ebselen, 2-phenyl-1,2-benzisoselenazole-3(2H)-one can preferentially inhibit the activity of inducible nitric oxide (NO) synthase with little inhibition of endothelial constitutive NO synthase within a certain concentration range. This suggests that ebselen deserves further in vivo studies to examine its possible application to the therapy of septic shock where inducible NO synthase is responsible for vasodilation.

Amino Acid Oxidoreductases↗
PubMed1994

Nitric oxide synthase immunoreactivity colocalized with NADPH-diaphorase histochemistry in monkey cerebral cortex.

The distributions of reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and nitric oxide synthase (NOS) containing neurons and the extent of NADPH-d and NOS colocalization have been analyzed by histochemical and immunocytochemical techniques in the neocortex of Macaca fuscata monkeys. NADPH-d positive cells were consistently also NOS positive and presented a relatively uniform distribution from area to area, but area-specific differences were observed in the pattern of distribution of fiber plexuses.

Amino Acid Oxidoreductases↗
PubMed1994

Structure and function of nitric oxide synthases.

Nitric oxide (NO), which accounts for the biological activity of endothelium-derived relaxing factor, is now thought to play a variety of roles in the nervous system and in immunologic reactions. NO is synthesized from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS; type I (neuronal), type II (inducible), and type III (endothelial). The fundamental structure of the three isoforms, which contain calmodulin-, FMN-, FAD-, and NADPH-binding domains, is the same. Calmodulin is already bound to inducible NOS without requiring Ca2+, while the others are Ca2+/calmodulin-dependent. Endothelial NOS is bound to membranes by N-myristoylation, while the other isoforms are soluble. The human endothelial NOS gene has been cloned. It has several highly repetitive regions which could provide potential sites for DNA polymorphism. It might be of interest to examine the relationship between such polymorphism and cardiovascular disorders.

Amino Acid Oxidoreductases↗
PubMed1994

A novel modified tissue-type plasminogen activator (t-PA), E6010, gradually increases coronary blood flow after thrombolysis compared with native t-PA, urokinase and balloon catheter occlusion-reperfusion.

In a canine copper coil-induced coronary thrombosis model, the differences in frequency of reperfusion arrhythmias (premature ventricular complexes: PVC) and mortality rate after thrombolysis by intravenous bolus injection of a novel modified tissue-type plasminogen activator (t-PA), E6010, and by continuous intravenous infusion of native t-PA or urokinase were evaluated. Rapid coronary occlusion and reperfusion were produced with a balloon catheter in another group of dogs, and the findings were compared with those in the thrombolysis groups. Reperfusion occurred gradually after the administration of E6010, but was significantly more rapid after administration of native t-PA and urokinase (P < 0.05). PVC were observed more frequently in native t-PA, urokinase and balloon occlusion-reperfusion groups than in the E6010 group. The mortality rate due to ventricular fibrillation was 0.0% in the E6010 group, 50.0% in the native t-PA and balloon occlusion-reperfusion groups, and 33.3% in the urokinase group. These results suggest that the more gradual reperfusion of the coronary artery at an earlier period after drug administration led to the lower frequency of reperfusion arrhythmias and low mortality rate in the E6010 group than in the native t-PA, urokinase and balloon occlusion-reperfusion groups.

Animals↗
PubMed1994

[Large scale multicenter cooperative study for cardiovascular therapy (Japan Multicenter Investigation for Cardiovascular Drugs/Therapies, J-MIC)--results and perspectives].

With rapidly progressing therapeutic methods in the cardiovascular medicine, scientific evaluations for newly developed cardiovascular drugs and therapies have become mandatory. We have launched five large scale multicenter cooperative studies, namely, Japan Multicenter Investigation for Cardiovascular Drugs/Therapies, J-MIC (I), (B), (M), (S), and (K). The aims of studies include to investigate: the best therapeutic approach in patients with acute myocardial infarction who underwent thrombolytic therapy with or without any adjunctive treatment (I), the long-term comparative study (3 years) of nifedipine (extended release tablet) with ACE inhibitor in patients with essential hypertension and ischemic heart disease (B), the long-term effect (3 years) of trapidil and/or ethyl icosapentate in patients with ischemic heart disease with or without arteriosclerotic obstructive disease in terms of progression or regression of atherosclerotic changes in coronary as well as peripheral arteries (M), the efficacy and safety of pravastatin to prevent post-PTCA restenosis (S), and regression of atherosclerotic lesion of coronary arteries in patients with familial hypercholesterolemia by LDL apheresis (K).

Cardiovascular Agents↗
PubMed1993

Bending of DNA segments with Saccharomyces cerevisiae autonomously replicating sequence activity, isolated from basidiomycete mitochondrial linear plasmids.

Previous studies have indicated that DNA bending is a general structural feature of sequences (ARSs) from cellular DNAs of yeasts and nuclear and mitochondrial genomic DNAs of other eukaryotes that are capable of autonomous replication in Saccharomyces cerevisiae. Here we showed that bending activity is also tightly associated with S. cerevisiae ARS function of segments cloned from mitochondrial linear DNA plasmids of the basidiomycetes Pleurotus ostreatus and Lentinus edodes. Two plasmids, designated pLPO2-like (9.4 kb), and pLPO3 (6.6 kb) were isolated from a strain of P. ostreatus. A 1029 bp fragment with high-level ARS activity was cloned from pLPO3 and it contained one ARS consensus sequence (A/T)TTTAT(A/G)TTT(A/T) indispensable for activity and seven dispersed ARS consensus-like (10/11 match) sequences. A discrete bent DNA region was found to lie around 500 bp upstream from the ARS consensus sequence (T-rich strand). Removal of the bent DNA region impaired ARS function. DNA bending was also implicated in the ARS function associated with a 1430 bp fragment containing three consecutive ARS consensus sequences which had been cloned from the L. edodes plasmid pLLE1 (11.0 kb): the three consecutive ARSs responsible for high-level ARS function occurred in, and immediately adjacent to, a bent DNA region. A clear difference exists between the two plasmid-derived ARS fragments with respect to the distance between the bent DNA region and the ARS consensus sequence(s).

Base Sequence↗
PubMed1993

Emergency coronary angioplasty for acute myocardial infarction: predictors of early occlusion of the infarct-related artery after balloon inflation.

THE FACTORS RESPONSIBLE FOR EARLY OCCLUSION OF THE INFARCT VESSEL AFTER emergency percutaneous transluminal coronary angioplasty (PTCA) were retrospectively examined in 191 patients with acute myocardial infarction. During the 24-hour period after the initial balloon inflation, 47 patients (25%) had occlusion of the vessel (occlusion group), whereas 144 did not (nonocclusion group). The former patients immediately underwent repeat PTCA, which was successful in 37. Univariate correlates of early occlusion were a shorter time interval between the onset of symptoms and PTCA (3.5 +/- 2.2 vs 4.5 +/- 2.9 hours, p = 0.025), right coronary artery involvement (53% vs 30%, p = 0.015), prior thrombolytic therapy (49% vs 32%, p = 0.035), and undersized inflation (43% vs 17%, p < 0.001). With multivariate analysis the three independent predictors were undersized inflation (p < 0.001), right coronary artery involvement (p = 0.004), and a shorter time interval until PTCA (p = 0.011). Thus patients undergoing early PTCA and having right coronary artery involvement appear to be at greater risk of having early occlusion. Thrombolytic agents and undersized inflation may also play an important role in its development.

Aged↗
PubMed1993

Intracoronary infusion of E6010 has more potent thrombolytic activity than tissue plasminogen activator (t-PA) in dogs: a higher plasma level of E6010 than t-PA causes potent thrombolytic activity.

We examined the thrombolytic properties of a novel modified human tissue plasminogen activator (PA) (E6010), in which cysteine 84 is replaced by serine, and which has a prolonged biologic half-life (t1/2). We compared the thrombolytic efficacy of continuous intracoronary (i.c.) infusion of E6010 with that of recombinant human tissue PA (rt-PA) in a canine model with copper coil-induced 1-h-old coronary artery thrombi and also compared the relation between thrombolytic efficacy and plasma clearance represented by pharmacokinetic parameters of i.c.-infused E6010 and rt-PA. Sixty-minute E6010 and rt-PA i.c. infusions were compared. The thrombolytic effects of i.c.-infused E6010 and rt-PA, represented by time to reperfusion (TR), reperfusion rate at 60 min (RR), and reocclusion rates at 60 min after reperfusion (OR) were as follows. E6010: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 25 +/- 10, 15 +/- 10, 13 +/- 5 (min); RR 100, 100, 100 (%); and OR 0, 0, 17 (%), respectively. Recombinant t-PA: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 47 +/- 12, 18 +/- 17, 14 +/- 4 (min); RR 50, 75, 100 (%); and OR 100, 33, 33 (%), respectively. These findings indicate that E6010 has more potent thrombolytic activity than rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

A stable L-arginine-dependent relaxing factor released from cytotoxic-activated macrophages.

It has been known that cytotoxic-activated macrophages release an unstable vasorelaxing substance, nitric oxide. We have found that a more stable relaxing factor is released from those cells. This factor seems to be synthesized from L-arginine. It acts through the activation of soluble guanylate cyclase without affecting membrane potential. It has little charge at nearly neutral pH, and its molecular weight is < 500.

Animals↗
PubMed1993

Antithrombotic effect and reperfusion by low molecular weight heparin in a canine model of coronary artery thrombosis.

The lability of an intracoronary thrombus, which is common in the case of unstable angina, indicates the presence of endogenous fibrinolysis. To prove our hypothesis that suppression of coagulation facilitates the thrombolytic process, low molecular weight heparin (LMWH) was given intravenously to dogs with intracoronary thrombi induced by copper coils. LMWH caused reperfusion in this model and suppressed the formation of intracoronary thrombi, thus supporting our hypothesis.

Animals↗
PubMed1993

Thrombolysis with intracoronary administration of YM866, a novel modified tissue-type plasminogen activator, in a canine model of coronary artery thrombosis.

We compared the thrombolytic activity of YM866, a novel modified tissue-type plasminogen activator, with that of t-PA by intracoronary administration in a canine thrombosis model of copper coil-induced 6-hr-old thrombi. Either drug was administered by a single injection (10 min) or multiple injection (4 x 10 min) under heparinization (300 IU/kg, i.v.). The reperfusion rate of YM866 was 4 times higher than that of t-PA when administered by single injection. Time to reperfusion of YM866 by single injection was shorter than that of either agent by multiple injection. No group showed any decrease in plasma fibrinogen levels. No acute reocclusion was seen in animals with YM866 by single injection. The improved thrombolytic activity of YM866 by single injection correlated with the relatively higher antigen levels of this agent due to its prolonged biological half-life. These results suggest that single intracoronary administration of YM866 is a safe and effective thrombolytic method for rapid recanalization and lowered acute reocclusion without activation of systemic fibrinolysis.

Animals↗