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Biomedical subjects

Y Yui

Publications and source records attributed to Y Yui.

At least 19 recordsLinked to original sources
PubMed1992

The intracoronary administration of urokinase following direct PTCA for acute myocardial infarction reduces early restenosis.

Early restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) without antecedent thrombolytic therapy in patients with acute myocardial infarction (AMI) was assessed by performing in-hospital cardiac catheterization in 62 (88%) of 70 consecutive patients. Specific attention was focused on the effectiveness of the intracoronary administration of urokinase in cases with angiographic residual thrombus after successful direct PTCA. The following two treatment regimens were used: PTCA alone (43 patients) and PTCA followed by the intracoronary infusion of urokinase (27 patients). The rate of early restenosis was higher after successful direct PTCA alone (28%) than after direct PTCA followed by intracoronary urokinase (5%). Bleeding complications were no different between the two groups. These findings suggest that intracoronary urokinase can be effective in reducing early restenosis in patients with angiographic residual thrombus after successful direct PTCA. Therefore early restenosis may be related to residual intracoronary thrombus.

Aged↗
PubMed1992

Purification of insoluble nitric oxide synthase from rat cerebellum.

Nitric oxide synthase [EC 1.14.23] from the particulate fraction of rat cerebella was purified and characterized. The homogenate of rat cerebella was centrifuged to obtain a pellet, which was washed and incubated with Triton X-100 containing buffer. The enzyme activity appeared in the 100,000 x g supernatant after incubation with the detergent. The solubilized enzyme was then purified by sequential affinity chromatography using adenosine 2',5'-diphosphate agarose and calmodulin Sepharose 4B, which gave a product that migrated as a single protein band on SDS/PAGE with a molecular mass of about 150 kDa. The purified enzyme exhibited an absolute requirement for FAD, in addition to NADPH and Ca2+/calmodulin. Thus, there is an insoluble nitric oxide synthase in rat cerebellum that has similar characteristics to the soluble type.

Amino Acid Oxidoreductases↗
PubMed1992

Percutaneous transluminal coronary angioplasty for patients with unstable angina pectoris.

Percutaneous transluminal coronary angioplasty (PTCA) was successful in 91% of 76 patients with unstable angina pectoris refractory to pharmacological treatment. However, the rate of acute occlusion and reocclusion was rather high (95). Restenosis developed in 56.5% of successful cases after initial PTCA, and 29 patients underwent 2nd, and nine 3rd PTCA. Most refractory unstable angina can be controlled by PTCA, which may require repeating in some patients.

Adult↗
PubMed1992

HA-1077 suppress both proliferation of vascular smooth muscle cells and c-fos mRNA induction.

HA1077 is a newly synthesized vasodilator with unique intracellular calcium antagonistic action. In this study, its effect on the growth of vascular smooth muscle cells (VSMC) stimulated by fetal calf serum was examined. Both the proliferation and [3H]thymidine incorporation into DNA of the growth-arrested VSMC was dose-dependently inhibited by HA1077. The expression of a proto-oncogene, c-fos, which reached the maximum 30 min after addition of serum, was similarly inhibited by this agent in a dose-dependent manner. Thus, HA1077 is expected to be a useful vasodilator agent capable of suppressing the growth of VSMC which is thought to be an important underlying mechanism of atherosclerosis or restenosis after angioplasty.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

[Regulation of nitric oxide synthase].

Nitric oxide (NO) synthase is known to be widely distributed in various cells. We characterized this enzyme using partially purified enzyme fractions from rat neutrophils, macrophages, and cerebellum. The cerebellar fraction required Ca(2+)-calmodulin, while that from macrophages required neither calmodulin nor Ca2+. The neutrophil fraction required Ca2+. The enzyme was inhibited by analogues of the substrate, L-arginine. N omega-nitro-L-arginine (NNA) was 20 times more potent than L-NG-monomethyl-arginine (NMA) in blocking the cerebellar enzyme. In contrast, NNA and NMA were about equipotent against neutrophil and macrophage enzymes. These data suggest that the enzyme is regulated by 3 different mechanisms in these cells, with differences between the cerebellar and neutrophil or macrophage enzyme in the catalytic binding site.

Amino Acid Oxidoreductases↗
PubMed1991

Purification of nitric oxide synthase from rat macrophages.

Nitric oxide (NO) synthase (EC 1.14.23) has been purified to apparent homogeneity from rat macrophages. The purification procedure involves affinity chromatography with adenosine 2',5'-diphosphate-agarose and gel filtration chromatography on a Superose 12 HR 10/30 column. The apparent molecular weight is 300,000 by gel filtration. On polyacrylamide gel electrophoresis in sodium dodecyl sulfate, the enzyme migrates as a single protein band with Mr = 150,000. The purified enzyme is colorless, and an absorption maximum is observed at 280 nm. The half-life of the enzyme activity is 6 h at pH 7.4 and 4 degrees C. The enzyme activity required the presence of NADPH, (6R)-5,6,7,8-tetrahydro-L-biopterin, and dithiothreitol. Although the cerebellar and endothelial enzyme require Ca2+ and calmodulin, these are not required by the macrophage enzyme. The macrophage nitric oxide synthase (an inducible enzyme) seems to be different from the cerebellar and endothelial enzyme (a constitutive enzyme).

Amino Acid Oxidoreductases↗
PubMed1991

Calmodulin-independent nitric oxide synthase from rat polymorphonuclear neutrophils.

Recently, the purification of nitric oxide synthase (EC 1.14.23) from rat cerebellum has been reported, and the enzyme is a calmodulin-requiring enzyme (Bredt, D. S., and Snyder, S. H. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 682-685). In this paper, nitric oxide synthase has been purified to near homogeneity from the cytosol fraction of rat polymorphonuclear neutrophils. The purification procedure involves affinity chromatography with adenosine 2',5'-diphosphate-agarose and an anion exchange column, DEAE-Bio-Gel A. On polyacrylamide gel electrophoresis in sodium dodecyl sulfate, the enzyme migrated as a single protein band with Mr = 150,000. The molecular weight was estimated to be 150,000 by gel filtration on a Superose 12 HR 10/30. The purified enzyme was unstable with a half-life of 3 h at pH 7.4 and 4 degrees C. The enzyme activity required the presence of Ca2+, NADPH, FAD, and (6R)-5,6,7,8-tetrahydro-L-biopterin. Calmodulin antagonists (W5, W7, W13, and trifluoperazine dihydrochloride) did not inhibit the enzyme activity, and the addition of calmodulin was also ineffective for the increase in the enzyme activity. The neutrophil enzyme appears to be a calmodulin-independent type of nitric oxide synthase.

Amino Acid Oxidoreductases↗
PubMed1991

U-61,431F, a stable prostacyclin analogue, inhibits the proliferation of bovine vascular smooth muscle cells with little antiproliferative effect on endothelial cells.

The effects of U-61,431F, ciprostene, a stable prostacyclin analogue, were examined on the proliferation of cultured quiescent bovine aortic endothelial cells (EC) and smooth muscle cells (SMC). After stimulation with 5% fetal calf serum, U-61,431F suppressed both the DNA synthesis and proliferation of SMC dose-dependently at the concentration of 3-100 microM, but had no effect on either of them in EC at a concentration of up to 30 microM. The inhibitory effect on DNA synthesis was greater in SMC than in EC at 3-50 microM. When SMC were stimulated with platelet-derived growth factor (PDGF) for 2 hrs followed by a 22-hr incubation with insulin, U-61,431F (1-50 microM) administered at the time of PDGF stimulation did not inhibit DNA synthesis. SMC initiated and terminated DNA synthesis at about 15-18 h and 24 h after stimulation with serum, respectively. Inhibition of DNA synthesis in serum-stimulated SMC as a function of the addition time of U-61,431F reduced at 3-12 h after the stimulation. U-61,431F raised the cyclic AMP (cAMP) content in SMC. Moreover, a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, and a more specific cAMP phosphodiesterase inhibitor, Ro 20-1724, augmented the inhibition of DNA synthesis in SMC concomitant with further elevation of cAMP level. These results suggest that U-61,431F inhibits DNA synthesis of SMC acting in the progression stage rather than in the competence stage, with little antiproliferative effect on EC. cAMP may play an important role in its antiproliferative action in SMC.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Thrombolytic properties of a novel modified human tissue-type plasminogen activator (E6010): a bolus injection of E6010 has equivalent potency of lysing young and aged canine coronary thrombi.

The thrombolytic properties of a novel modified human tissue plasminogen activator (E6010), in which cystein 84 in the epidermal growth factor domain is replaced by serine and that has a prolonged biological half-life, were examined. The thrombolytic efficacies of E6010 and recombinant human tissue plasminogen activator (rt-PA) on the duration of coronary artery thrombus were evaluated in a canine model (123 anesthetized dogs) with copper coil-induced left anterior descending coronary artery thrombus. Thrombi established for periods of 1, 3, or 6 h, as documented by coronary arteriography, were employed. A single bolus i.v. injection of E6010 or rt-PA and an i.v. infusion of rt-PA over 60 min were compared (n = 6). Thrombolytic efficacy was evaluated by three criteria: time to reperfusion (TR), reperfusion rate at 60 min (RR), and reocclusion rate at 60 min after reperfusion (OR). With a bolus i.v. injection of E6010 at a dose of 0.2 mg/kg or an i.v. infusion of rt-PA at a dose of 0.6 mg/kg/h, these parameters were as follows: TR, 30.0 +/- 15.3 and 27.5 +/- 4.8 min; RR, 100 and 100%; OR, 17 and 33% for 1-h aged thrombi; TR, 30.0 +/- 9.5 and 35.0 +/- 8.2 min; RR, 83 and 50%; OR, 20 and 67% for 6-h aged thrombi. These data indicate that a bolus injection of E6010 is almost equally efficacious in lysing thrombi aged both 1 and 6 h. On the other hand, in the case of rt-PA, the thrombi aged 6 h were lysed significantly less than the thrombi aged 1 h. Plasma half-lives of E6010 were t1/2 alpha, 4.8 +/- 0.95 (estimated by antigen level) and 3.0 +/- 0.78 min (estimated by activity), and t1/2 beta, 51 +/- 5.4 (antigen level) and 22 +/- 7.0 min (activity). The half-lives of rt-PA were t1/2 alpha, 3.6 +/- 0.23 (antigen level) and 2.1 +/- 0.61 min (activity), and t1/2 beta, 36 +/- 2.3 (antigen level) and 7.0 +/- 3.5 min (activity). We conclude that a bolus injection of E6010 may have a more potent and longer-lasting effect than i.v.-infused rt-PA in clot lysis therapy.

Aging↗
PubMed1991

A new relaxing factor in supernatant of incubated rat peritoneal neutrophils.

It was found that when rat peritoneal neutrophils were added to an organ bath, they released an unstable vasoactive substance designated as neutrophil-derived relaxing factor (NDRF), which is similar to endothelium-derived relaxing factor. Besides NDRF, a more stable (activity maintained for at least 7 days at -80 degrees C) relaxing factor was found to be generated in the supernatant after the incubation of rat peritoneal neutrophils in buffer. This supernatant relaxing factor (SRF) induced an increase in the guanosine 3',5'-cyclic monophosphate content of aortic strips. Its relaxing activity was potentiated by superoxide dismutase. It was inhibited by hemoglobin, hydroquinone, or methylene blue but not by catalase or mannitol. Preincubation of polymorphonuclear neutrophils with aspirin, quinacrine, metyrapone, or AA-861 had no effect on the relaxing activity of SRF. L-Arginine dose dependently increased the relaxing activity of SRF, whereas NG-monomethyl-L-arginine (L-NMMA) decreased it, and this decrease was reversed by L-arginine. In contrast, neither L-arginine nor L-NMMA affected the relaxing activity of NDRF. These data suggest that SRF may represent a relaxing factor that is synthesized de novo from L-arginine.

Animals↗
PubMed1991

Intravenous recombinant tissue-type plasminogen activator (rt-PA) and urokinase (UK) in patients with evolving myocardial infarction--a multicenter double-blind, randomized trial in Japan.

Intravenous administrations of 2000 x 10(4)IU (33 mg) (rt-PA2) and 3000 x 10(4)IU (50 mg) (rt-PA3) of a new recombinant tissue plasminogen activator (rt-PA:TD-2061) derived from uterine endothelial cells and urokinase (UK) 96 x 10(4)IU were compared in a double blind, randomized trial of 198 patients with evolving myocardial infarction. All patients entered the trial within 6 h of the onset of symptoms and underwent baseline coronary angiography of the infarct-related coronary artery before thrombolytic therapy was instituted. Sixty minutes following thrombolytic therapy occluded infarct-related arteries were successfully reperfused in 41.5% of 66 patients in the UK, 76.4% of 72 patients in the rt-PA2, and 74.6% of 59 patients in the rt-PA3 group. Statistically significant differences were observed between the UK and rt-PA groups (p less than 0.01). Serum fibrinogen levels declined in all 3 groups at 60 min post-therapy by averages of 35.9 +/- 3.1% in the UK, 16.8 +/- 4.8% in the rt-PA2 and 17.5 +/- 4.5% in the rt-PA3 group. The difference between the UK and the rt-PA groups was statistically significant (p less than 0.01). Plasma plasminogen and alpha 2-plasmin inhibitor levels showed the same tendencies. Bleeding was the most commonly observed complication and was most commonly seen at the catheterization site. There was no difference in the incidence among the 3 groups. Hospital deaths occurred in 5.3%, 6.3%, and 4.7% of the cases in the UK, rt-PA2 and rt-PA3 groups, respectively. We conclude, therefore, that rt-PA achieves a significantly higher rate of recanalization with less extensive systemic fibrinogenolysis at the dose employed than does UK. The optimum intravenous dose of rt-PA for Japanese patients is considered to be 2000 x 10(4)IU (33 mg).

Blood Coagulation↗
PubMed1991

Randomized trial of a selective inhibitor of thromboxane A2 synthetase, (E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid (CV-4151), for prevention of restenosis after coronary angioplasty.

A selective inhibitor of thromboxane A2 synthetase, CV-4151, has the unique property of increasing prostacyclin synthesis in addition to its anti-platelet aggregating effect. Prostacyclin inhibits the growth of smooth muscle cells which is considered to be an underlying mechanism of restenosis occurring after successful coronary angioplasty. A prospective randomized trial was conducted to determine whether CV-4151 could prevent restenosis. Administration was begun greater than or equal to 2 days before angioplasty, and continued until the follow-up study performed between 3 and 6 months after angioplasty. Follow-up angiography was performed in 58 patients (81 segments) taking the active drug and in 27 patients (35 segments) taking the placebo. The incidence of angiographic restenosis was 38.3% in the former group and 31.4% in the latter group. Thus, CV-4151 did not significantly reduce the incidence of restenosis, perhaps due to endothelial denudation after angioplasty preventing an increase of the subendothelial local prostacyclin level.

Angioplasty, Balloon, Coronary↗
PubMed1991

Serum from patients with restenosis after percutaneous transluminal coronary angioplasty stimulates proliferation of bovine vascular smooth muscle cells under low extracellular calcium condition.

We compared the effects on the proliferation of bovine vascular smooth muscle cells (VSMC) of serum from 36 patients without restenosis (group A), and 21 patients with restenosis (group B) after percutaneous transluminal coronary angioplasty (PTCA). Baseline characteristics were similar in both groups, except for the greater number of patients with unstable angina at the time of PTCA (52 vs 22%, p = 0.020) and the shorter interval between PTCA and repeat angiography in group B (106 +/- 30 vs 153 +/- 112 days, p = 0.022). Cultured bovine VSMC were stimulated with patient serum (5%) obtained at repeat angiography in either Ca(2+)-containing or Ca(2+)-free culture medium. DNA synthesis was assessed by [3H]thymidine incorporation. The following indices of VSMC proliferation were used: S(+) = [3H]thymidine uptake stimulated by 5% serum in Ca(2+)-containing medium/[3H]thymidine uptake stimulated by 5% fetal calf serum (FCS) in Ca(2+)-containing medium, S(-) = [3H]thymidine uptake stimulated by 5% serum in Ca(2+)-free medium/[3H]thymidine uptake stimulated by 5% FCS in Ca(2+)-free medium, and D = S(-)-S(+). D represented the preserved DNA synthesis in Ca(2+)-deprived medium. S(-) was lower than S(+) in group A (1.35 +/- 0.56 vs 1.57 +/- 0.58, p less than 0.0001), whereas it was higher than S(+) in group B (1.64 +/- 0.66 vs 1.50 +/- 0.58, p = 0.010). D was significantly higher in group B than in group A (0.14 +/- 0.23 vs -0.22 +/- 0.28, p less than 0.0001), and was not associated with any continuous variables including serum calcium level on univariate regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Human serum albumin inhibits prostacyclin production by endothelial cells: the relation of the inhibitory activity to sulfhydryl groups in albumin.

Human serum inhibited calcium ionophore-induced production of prostacyclin by cultured bovine aortic endothelial cells. The inhibitory fraction was purified from serum by anion-exchange and Blue-Sepharose affinity chromatography. The molecular weight of the purified substance was 67k dalton as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was identified as human serum albumin by N-terminal amino acid sequence analysis. Human serum albumin was separated to two forms by high-performance liquid chromatography: mercaptalbumin (SH type) and nonmercaptalbumin (SS type). Both types of albumin inhibited the conversion of arachidonic acid to prostaglandin H2 in a dose-dependent manner without affecting phospholipase A2 or prostacyclin synthetase. This inhibition was more potent in mercaptalbumin than in nonmercaptalbumin. These results suggest that the conversion between mercaptalbumin and nonmercaptalbumin may play an important role in the modulation of prostacyclin synthesis by endothelial cells.

Adenosine Diphosphate↗
PubMed1991

Decreased sulfhydryl groups of serum albumin in coronary artery disease.

We hypothesized that oxidative processes in myocardial tissues initiated by ischemia also cause the same kind of changes in blood proteins and lead to oxidation of sulfhydryl groups (SH). To test this hypothesis, the ratio (%MA) of mercaptalbumin to total albumin (= mercaptalbumin + nonmercaptalbumin) and the total SH contents of serum were measured in patients with coronary artery disease. There was a positive correlation between %MA and total SH contents and both values were reduced in proportion to the severity of the coronary artery disease. Furthermore, these values were lower early hours after the onset of acute myocardial infraction than 4 weeks later. These results support our hypothesis, and may provide a basis for the administration of agents which can counteract oxidative stress in order to protect myocardium in patients with coronary artery disease.

Adult↗