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Biomedical subjects

H Yasue

Publications and source records attributed to H Yasue.

At least 163 records · Page 9Linked to original sources
PubMed1998

Biphasic regulation of transcription factor nuclear factor-kappaB activity in human endothelial cells by lysophosphatidylcholine through protein kinase C-mediated pathway.

Lysophosphatidylcholine (lysoPC), which is generated in oxidized LDL (Ox-LDL) and abundantly exists in atherosclerotic arterial walls, has been shown to alter various endothelial functions and induces several endothelial genes expressed in atherosclerotic arterial walls. Nuclear factor-kappa B (NF-kappaB), a pleiotropic transcription factor, plays an important role in regulation of expression of various genes implicated in atherosclerosis. We have previously reported that lysoPC transferred from Ox-LDL to endothelial surface membrane activates endothelial protein kinase C (PKC), leading to modulated endothelial functions. This study was aimed at determining whether lysoPC could modulate activity of transcription factors in cultured human umbilical vein endothelial cells (HUVECs) by using electrophoretic mobility shift assay. LysoPC was found to increase DNA-binding activity of NF-kappaB in HUVECs within 15 minutes, which peaked at 1 to 2 hours and subsequently declined to the baseline level at 6 hours. Lower concentrations (5 to 15 micromol/L) of lysoPC markedly increased NF-kappaB activity, but higher concentration (50 micromol/L) of lysoPC inhibited the activity. Phorbol 12-myristate 13-acetate, a potent activator of PKC, also augmented NF-kappaB activity in HUVECs, mimicking the effects of lysoPC; furthermore, calphostin C and chelerythrine chloride, specific PKC inhibitors, and alpha-tocopherol, a clinically potent PKC inhibitor, suppressed the lysoPC-induced NF-kappaB activation. These results indicate that lysoPC regulates NF-kappaB activity in a biphasic manner dependent on its concentrations and incubation time in human endothelial cells and the endothelial PKC activation may in part be involved in the lysoPC-induced NF-kappaB activation. Thus, the time course and the positive and negative biphasic regulatory actions of lysoPC on NF-kappaB activity in endothelial cells might exhibit a unique effect of lysoPC in arterial walls on the different stages of atherosclerosis.

Cells, Cultured↗
PubMed1998

Endothelial nitric oxide synthase gene is positively associated with essential hypertension.

Essential hypertension has a genetic basis. Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no reports indicating that polymorphism in the eNOS gene is associated with essential hypertension. We have identified a missense variant, Glu298Asp, in exon 7 of the eNOS gene and demonstrated that it is associated with both coronary spastic angina and myocardial infarction. To explore the genetic involvement of the eNOS gene in essential hypertension, we examined the possible association between essential hypertension and several polymorphisms including the Glu298Asp variant, variable number tandem repeats in intron 4 (eNOS4b/4a), and two polymorphisms in introns 18 and 23. We performed a large-scale study of genetic association using two independent populations from Kyoto (n=458; 240 normotensive versus 218 hypertensive subjects) and Kumamoto (n=421; 223 normotensive versus 187 hypertensive subjects), Japan. In both groups, a new coding variant, Glu298Asp, showed a strong association with essential hypertension (Kyoto: odds ratio, 2.3 [95% confidence interval, 1.4 to 3.9]; Kumamoto: odds ratio, 2.4 [95% confidence interval, 1.4 to 4.0]). The allele frequencies of 298Asp in hypertensive subjects were significantly higher than those in normotensive subjects in both groups (Kyoto: 0.103 versus 0.050, P<0.0017; Kumamoto: 0.120 versus 0.058, P<0.0013, respectively). No such disequilibrium between genotypes was significantly associated with any other polymorphisms we examined; the Glu298Asp variant was also not linked to any other polymorphisms. In conclusion, the Glu298Asp missense variant was significantly associated with essential hypertension, which suggests that it is a genetic susceptibility factor for essential hypertension.

Adult↗
PubMed1998

Comparison of coronary hemodynamics during infusions of dobutamine and adenosine in patients with angina pectoris.

Pharmacologic stress tests are used to evaluate the significance of coronary arterial stenosis, and adenosine and dobutamine are often used for this purpose. The aim of this study was to examine coronary hemodynamics in 16 patients with stable exertional angina who had organic stenosis (> 90%) in the left anterior descending coronary arteries and in 13 control subjects at baseline and during separate intravenous infusions of dobutamine (20 micrograms/kg per min [corrected]) and adenosine (140 micrograms/kg per min [corrected]). Measurements of great cardiac vein blood flow and lactate and oxygen contents in the blood from the aortic root and great cardiac vein were analyzed in patients with ischemic signs of myocardial ischemia (ST-segment depression in the precordial ECG leads and/or myocardial lactate production) during the infusions (in 11 patients during adenosine infusion and in 12 patients during dobutamine infusion) and in control subjects. Myocardial oxygen consumption during adenosine infusion did not change compared with the baseline in both groups, whereas it increased during dobutamine infusion in both groups (p < 0.01 compared with the baseline in each case). However, great cardiac vein blood flow was significantly increased compared with the baseline during both infusions in both groups (p < 0.01 compared with baseline in each case), and the oxygen contents of great cardiac vein blood, which contains effluent from the ischemic region, showed no decrease but increased significantly during both infusions in the patients in comparison with control subjects. Although the global oxygen supply was excessive, myocardial ischemia occurred during dobutamine and adenosine infusions in the patients. As myocardial oxygen consumption remained unchanged during adenosine infusion, regional myocardial flow reduction, possibly as a result of flow maldistribution, may contribute, at least partly, to adenosine-induced myocardial ischemia. An increase in myocardial oxygen consumption may be the principal cause of myocardial ischemia during dobutamine infusion, but an inappropriate flow increase in normal myocardium may occur during dobutamine-induced ischemia.

Adenosine↗
PubMed1998

Angiographic evaluation of culprit lesions in acute coronary syndrome: relation to the original site on previous coronary angiography.

Culprit lesions in acute coronary syndrome [acute myocardial infarction (AMI) and unstable angina pectoris (UAP)] were examined angiographically in 222 patients who had previously undergone coronary angiography (CAG). The observation period lasted 5 years after primary CAG in medically treated patients (group M, 127 cases) and after final follow-up CAG in patients treated by percutaneous transluminal coronary angioplasty (PTCA) (group B, 95 cases). There were 33 AMIs, including 5 deaths (22/127, 17.3%, in group M vs 11/95, 11.6%, in group B; p<0.01) and 189 UAPs (105/127, 82.7%, in group M vs 84/95, 88.4%, in group B; NS). High-grade stenoses (>75%) were found in 76 (59.8%) patients in group M, of which 41 lesions (54%) resulted in acute coronary syndromes (ACSs). In group M, ACSs resulted from insignificant stenosis (< or =50%) in 67 (53%) patients and from significant stenosis (>50%) in 60 (47%) patients. In group B, ACSs resulted from insignificant stenosis in 78 (82%) patients and from significant stenosis in 17 (18%) patients. Out of 95 PTCA sites, high-grade restenosis occurred in 3 lesions and ACSs (2 AMI, 14 UAP) in 16 (16.8%). We conclude that ACSs are more likely to develop from insignificant lesions than from significant lesions. High-grade stenoses are prone to become occlusive lesions and PTCA reduces this potential risk. Most target sites of PTCA that escaped restenosis were stable in the long term.

Aged↗
PubMed1998

Influence of chronic nitric oxide inhibition of coronary blood flow regulation: a study of the role of endogenous adenosine in anesthetized, open-chested dogs.

The effect of chronic inhibition of endothelium-derived nitric oxide (NO) synthesis on the regulation of coronary blood flow (CBF) is yet to be elucidated. A chronic canine model of inhibited NO synthesis was created and the role of adenosine in the regulation of coronary blood flow in this model was examined. Dogs were fed a diet supplemented with 40 mg/kg per day N(G)-nitro-L-arginine methyl ester (L-NAME group, n=8) or a regular diet without L-NAME supplementation (control group, n=8) for 4 weeks. The experiments were performed in an anesthetized, open-chest state and the results were compared in the L-NAME and control groups. Chronic L-NAME treatment significantly increased arterial pressure. Neither basal CBF in the left anterior descending artery nor heart rate differed between the L-NAME and control groups. In the L-NAME group, the response of CBF to intracoronary acetylcholine and adenosine was blunted, but that to glyceryl trinitrate was not. In addition, myocardial reactive hyperemia following 20 sec coronary occlusion was blunted in the L-NAME group. During atrial pacing at a rate 60 beats/min faster than the sinus rate, CBF increased to a similar degree in the L-NAME and control groups, and systolic wall thickening (SWT) changed similarly in both groups. Intracoronary 8-phenyltheophylline (8-PT), an adenosine receptor blocker, decreased basal CBF in the L-NAME group but not in the control group. In the L-NAME group, pacing-induced increase in CBF was abolished and SWT deteriorated after 8-PT administration. Basal myocardial adenosine release was significantly increased in the L-NAME group compared with the control group. It is concluded that in anesthetized, open-chest dogs with chronic inhibition of NO synthesis, adenosine may play a compensatory role in the regulation of coronary blood flow, as concomitant blockade of adenosine causes deterioration of coronary circulation and cardiac function.

Acetylcholine↗
PubMed1998

Circadian variation in plasma levels of free-form tissue factor pathway inhibitor antigen in patients with coronary spastic angina.

Tissue factor pathway inhibitor (TFPI) is known to inhibit the initial reaction in the tissue factor-mediated coagulation pathway. We measured plasma free-form TFPI antigen levels and monitored 24-h Holter recordings at 06.00, 14.00 and 22.00 h in 15 patients with coronary spastic angina, 13 patients with stable exertional angina, and 11 control subjects. There was a significant circadian variation in plasma free-form TFPI antigen levels in patients with coronary spastic angina (25.8+/-2.0 ng/ml at 06.00 h, 21.1+/-1.6 ng/ml at 14.00 h, and 20.2+/-1.4 ng/ml at 22.00 h; p<0.01). Furthermore, free-form TFPI antigen levels at 06.00 h were significantly higher in coronary spastic angina patients than in patients with stable exertional angina or control subjects (p<0.01). Free-form TFPI antigen levels increased after the ischemic attacks in coronary spastic angina (p<0.01). This circadian variation correlated with the frequency of attacks, with the peak level occurring between midnight to early morning in patients with coronary spastic angina.

Adult↗
PubMed1998

Simultaneous elevation of the levels of circulating monocyte chemoattractant protein-1 and tissue factor in acute coronary syndromes.

The levels of circulating monocyte chemoattractant protein-1 (MCP-1) and tissue factor (TF) were examined on admission in 46 consecutive patients with acute coronary syndromes (ACS) and 30 patients with stable exertional angina (SEA). The plasma levels of both MCP-1 and TF were higher in the ACS patients than in the SEA patients (MCP-1: p<0.001; TF: p<0.001). Only the circulating TF level related to the number of diseased vessels. A positive correlation between plasma MCP-1 and TF levels was found (r=0.476, p<0.001). These results suggest that circulating MCP-1 plays an important role in the pathogenesis and/or development of ACS.

Acute Disease↗
PubMed1998

Comparison of thrombolytic therapies with mutant tPA (lanoteplase/SUN9216) and recombinant tPA (alteplase) for acute myocardial infarction.

The fibrinolytic capacity of patients with acute myocardial infarction (AMI) is known to be impaired. The primary regulatory element of the fibrinolytic system is plasminogen activator inhibitor (PAI). It has been previously observed that there are 2 peaks in the plasma PAI level of AMI patients at 4h and 16h after thrombolytic therapy with recombinant tissue plasminogen activator (rtPA). Lanoteplase/SUN9216 is a mutant tPA with a biological half-life longer than that of rtPA. Thrombolytic therapy with mutant tPA or rtPA was carried out consecutively in 21 patients with AMI (8 patients as the mutant tPA group, and 13 patients as the rtPA group). The recanalization time of the mutant tPA group was significantly faster than that of the rtPA group (16.1 +/- 3.9 min vs 39.6 +/- 4.8 min, p<0.01). The PAI activity at 4h after the initiation of thrombolysis was significantly lower in the mutant tPA group than in the rtPA group (8.74 +/- 5.46IU/L vs 26.74 +/- 3.35 IU/L, p<0.01). There was a one mild peak in serial plasma PAI activity levels 24h after the initiation of thrombolysis. The results suggest that thrombolytic therapy with mutant tPA reduced the impairment of fibrinolytic capacity. The mutant tPA gives faster recanalization and lower PAI activity after successful thrombolysis, compared with rtPA.

Aged↗
PubMed1998

Immunoradiometric assay for the N-terminal fragment of proatrial natriuretic peptide in human plasma.

Recently, the N-terminal fragment of proatrial natriuretic peptide (N-terminal proANP) has been proposed as a marker of chronic congestive heart failure. In this study, we established a two-step immunoradiometric assay using monoclonal antibodies and synthetic N-terminal proANP (1-67) as a standard. It allows us to measure plasma N-terminal proANP in only 4 h without prior extraction. The detection limit of this assay was 15 pmol/L for a 100 microL sample of plasma. Within-run CVs ranged from 1.7% to 2.9% and between-run CVs ranged from 4.2% to 5.1%. The dilution curves of plasma samples showed good linearity and analytical recovery was 89-104%. The mean (+/-SD) N-terminal proANP in plasma of 33 healthy subjects was 188 (+/-71) pmol/L and 1030 (+/-411) pmol/L in 25 patients with heart failure. Our immunoradiometric assay is rapid and precise enough for routine determination of N-terminal proANP in human plasma.

Antibodies, Monoclonal↗
PubMed1998

[Pathophysiology of coronary spasm].

There is a deficiency in both basal and stimulated NO release in the spasm arteries of patients with coronary spastic angina. The deficient NO release may lead to the supersensitivity of the artery to the vasodilator effect of nitroglycerin and to the vasoconstrictor effect of acetylcholine in patients with coronary spastic angina. Flow-dependent coronary dilation of proximal LAD was found to be less in spasm arteries than in control arteries. The infusion of L-NMMA in the proximal site of LAD suppressed the flow-dependent dilation in control arteries, while L-NMMA did not have significant effect in spasm arteries. The results indicate that flow-dependent coronary dialtion is impaired in spasm arteries partly due to deficiency in endothelial NO bioactivity, which in turn may possibly contribute to increase in coronary tone during the physiological stress in patients with coronary spastic angina.

Acetylcholine↗
PubMed1998

Relationship between serum angiotensin-converting enzyme activity and plasma plasminogen activator inhibitor activity in patients with recent myocardial infarction.

BACKGROUND: An elevated level of angiotensin-converting enzyme (ACE) has been demonstrated to increase the risk of myocardial infarction. Plasminogen activator inhibitor (PAI) is the most important physiological inhibitor of tissue plasminogen activator in plasma. An elevated level of PAI has been reported to be associated with decreased fibrinolytic capacity and to constitute a marker of the risk for recurrent coronary thrombosis. METHODS: We measured the serum ACE activity and plasma PAI activity in 34 patients with recent myocardial infarction, and evaluated the correlation between these two values by linear regression analysis. We also administered captopril (37.5 mg/day) to 17 of these patients and placebo to the other 17 patients at random, and compared the changes in PAI activity and ACE activity in these two groups over a 1-month period. RESULTS: There was a significant correlation between the serum ACE activity and the plasma PAI activity at baseline in the patients (r = 0.498, P < 0.01). The captopril-treated patients showed significantly reduced PAI activity (P < 0.01), and a concomitant decrease in ACE activity. CONCLUSION: These results suggest that elevated ACE activity is associated with impaired fibrinolysis and that treatment with an ACE inhibitor improves the fibrinolytic function in patients with recent myocardial infarction. The results also suggest that the renin-angiotensin system plays a role in the increased risk of ischemic cardiovascular events when it is activated, and in the reduction of risk of recurrent myocardial infarction by ACE inhibition.

Adult↗
PubMed1997

Hyperventilation as a specific test for diagnosis of coronary artery spasm.

The hyperventilation test has been used as a clinical tool to induce coronary spasm. However, its diagnostic and prognostic values have not been fully elucidated. This study was designed to establish the sensitivity and specificity of the hyperventilation test and to clarify the characteristics of hyperventilation test-positive patients. We examined 206 patients in whom coronary spasm was documented by angiography (spasm group), and 183 patients without angina at rest in whom acetylcholine failed to induce spasm (nonspasm group). All patients performed vigorous hyperventilation for 6 minutes in the early morning. Of the spasm group patients, 127 showed positive responses to the test, including ST elevation (n = 111), ST depression (n = 15) and negative U wave (n = 1). None in the nonspasm group showed any ischemic electrocardiographic change. Thus, the sensitivity and specificity of this test for diagnosis of coronary spasm were 62% and 100%, respectively. In the spasm group, there were no significant differences between hyperventilation test-positive and test-negative patients in age, sex, the prevalence of hypertension, diabetes mellitus, obesity, smoking, and the number of diseased vessels. When clinical characteristics were compared, the proportions of the patients with high disease activity (> or =5 attacks a week), with severe arrhythmias (second- or third-degree atrioventricular block and/or ventricular tachycardia) during attacks, and with multivessel spasm were significantly higher in the hyperventilation test-positive patients than in the negative patients (69% vs 20%, p <0.0001; 31% vs 11%, p <0.005; and 58% vs 34%, p <0.01, respectively). These findings imply that hyperventilation is a highly specific test for the diagnosis of coronary artery spasm, and that hyperventilation test-positive patients are likely to have life-threatening arrhythmias during attacks and multivessel spasm.

Adult↗
PubMed1997

Molecular evidence from retroposons that whales form a clade within even-toed ungulates.

The origin of whales and their transition from terrestrial life to a fully aquatic existence has been studied in depth. Palaeontological, morphological and molecular studies suggest that the order Cetacea (whales, dolphins and porpoises) is more closely related to the order Artiodactyla (even-toed ungulates, including cows, camels and pigs) than to other ungulate orders. The traditional view that the order Artiodactyla is monophyletic has been challenged by molecular analyses of variations in mitochondrial and nuclear DNA. We have characterized two families of short interspersed elements (SINEs) that were present exclusively in the genomes of whales, ruminants and hippopotamuses, but not in those of camels and pigs. We made an extensive survey of retropositional events that might have occurred during the divergence of whales and even-toed ungulates. We have characterized nine retropositional events of a SINE unit, each of which provides phylogenetic resolution of the relationships among whales, ruminants, hippopotamuses and pigs. Our data provide evidence that whales, ruminants and hippopotamuses form a monophyletic group.

Animals↗
PubMed1997

Targeting of endopeptidase 24.16 to different subcellular compartments by alternative promoter usage.

Endopeptidase 24.16 or mitochondrial oligopeptidase, abbreviated here as EP 24.16 (MOP), is a thiol- and metal-dependent oligopeptidase that is found in multiple intracellular compartments in mammalian cells. From an analysis of the corresponding gene, we found that the distribution of the enzyme to appropriate subcellular locations is achieved by the use of alternative sites for the initiation of transcription. The pig EP 24.16 (MOP) gene spans over 100 kilobases and is organized into 16 exons. The core protein sequence is encoded by exons 5-16 which match perfectly with exons 2-13 of the gene for endopeptidase 24.15, another member of the thimet oligopeptidase family. These two sets of 11 exons share the same splice sites, suggesting a common ancestor. Multiple species of mRNA for EP 24.16 (MOP) were detected by the 5'-rapid amplification of cDNA ends and they were shown to have been generated from a single gene by alternative choices of sites for the initiation of transcription and splicing. Two types of transcript were prepared, corresponding to transcription from distal and proximal sites. Their expression in vitro in COS-1 cells indicated that they encoded two isoforms (long and short) which differed only at their amino termini: the long form contained a cleavable mitochondrial targeting sequence and was directed to mitochondria; the short form, lacking such a signal sequence, remained in the cytosol. The complex structure of the EP 24.16 (MOP) gene thus allows, by alternative promoter usage, a fine transcriptional regulation of coordinate expression, in the different subcellular compartments, of the two isoforms arising from a single gene.

Amino Acid Sequence↗
PubMed1997

Supersensitive dilator response to nitroglycerin but not to atrial natriuretic peptide in spastic coronary arteries in coronary spastic angina.

It has been shown that there is the supersensitivity of the dilator effect of nitrovasodilators in the coronary arteries of patients with coronary spastic angina. This study was aimed to elucidate its mechanism(s) by examination of dilator response of spastic coronary arteries to atrial natriuretic peptide (ANP), which is known to dilate arteries by the same final common pathway through cyclic guanosine monophosphate (cGMP) as nitrovasodilators. Effects of infusion of nitroglycerin and ANP on epicardial coronary diameter of left coronary arteries were thus examined by quantitative coronary angiography in 20 patients with coronary spastic angina, who had spasm in left coronary arteries, and in 27 control subjects. Dilator response of coronary diameter to intracoronary infusion of ANP (0.5 microgram/kg) was found to be comparable between spastic coronary arteries and control arteries, whereas dilator response to nitroglycerin (250 micrograms) was enhanced in the spastic arteries compared with control arteries. The results indicate that spastic coronary arteries exhibit supersensitive dilator response to nitroglycerin but not to ANP. There is a possibility that dilator response to cGMP may be comparable between spastic and control coronary arteries and that soluble guanylate cyclase activity and/or conversion of nitric oxide bio-activity from nitroglycerin may be enhanced in spastic coronary arteries.

Adult↗
PubMed1997

Effects of imidapril therapy on endogenous fibrinolysis in patients with recent myocardial infarction.

BACKGROUND: Treatment with an angiotensin-converting enzyme (ACE) inhibitor in patients with myocardial infarction has been shown to modify endogenous fibrinolysis. HYPOTHESIS: We investigated the effects of the ACE inhibitor imidapril on endogenous fibrinolysis in association with the serum ACE activity. METHODS: In a randomized, double-blind, placebo-controlled study beginning 4 weeks after uncomplicated myocardial infarction, 15 patients received imidapril (5 mg daily) (imidapril group) and another 15 received placebo therapy (placebo group) for 4 weeks. Blood sampling was performed before the start of administration and on Days 3, 7, and 28 after the start of administration. Serum ACE activity and plasma fibrinolytic variables [plasminogen activator inhibitor (PAI) activity, plasminogen activator inhibitor type 1 (PAI-1) antigen level, and tissue type plasminogen activator (TPA) antigen level] were measured. RESULTS: There was no difference between the imidapril and placebo groups in serum ACE activity or plasma fibrinolytic variables before administration. Serum ACE activity decreased significantly on Days 3, 7, and 28 in the imidapril group. The decrease of PAI activity and PAI-1 antigen levels was significantly less on Days 7 and 28, but not on Day 3. The TPA antigen level in the imidapril group was unchanged. None of the parameters in the placebo group was changed. CONCLUSION: The ACE inhibitor imidapril modified fibrinolysis, but the effects occurred after the inhibition of serum ACE activity.

Administration, Oral↗