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Biomedical subjects

Tomohiro Sakamoto

Publications and source records attributed to Tomohiro Sakamoto.

At least 37 records · Page 2Linked to original sources

Usefulness of preprocedural platelet aggregation to predict restenosis after percutaneous coronary intervention.

We investigated whether the assessment of small platelet aggregates before percutaneous coronary intervention (PCI) could predict restenosis after PCI. This was a prospective cohort study that enrolled 189 consecutive patients who had coronary artery disease. In multiple logistic regression analysis, higher levels of preprocedural small platelet aggregates were independently associated with restenosis after PCI. Measurement of small platelet aggregates may serve as a useful clinical variable for stratifying patients who present for PCI.

Aged↗

Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease.

OBJECTIVES: The purpose of this study was to examine whether CD144-EMP (endothelium-derived microparticles) is useful as a specific marker of endothelial cell (EC) dysfunction and to determine whether plasma levels of circulating CD144-EMP predicted coronary artery disease (CAD) in patients with type 2 diabetes mellitus (DM). BACKGROUND: Endothelial cell dysfunction is involved in atherogenesis; however, the quantitative assessment of EC dysfunction has yet to be established clinically. Endothelium-derived microparticles are small, membrane-shed vesicles that are generated from the EC surface in response to cellular dysfunction and/or injury. Diabetes mellitus is known to be associated with EC dysfunction and accelerated atherosclerosis. METHODS: We characterized EMP using anti-CD144 (VE-Cadherin) antibody in various atherosclerosis-related cells and investigated the association between the levels of CD144-positive microparticles and hydrogen-peroxide-induced EC injury and acetylcholine-induced coronary vasomotion. Furthermore, we evaluated plasma CD144-EMP levels in patients with and without DM. RESULTS: We demonstrated that CD144-positive microparticles were derived selectively from human EC. The levels of CD144-EMP reflected the degree of in vitro hydrogen-peroxide-induced EC injury and impairment of in vivo endothelium-dependent coronary vasodilation (p < 0.01). Plasma CD144-EMP levels were increased significantly in DM patients compared with patients without DM (p < 0.001). In DM patients, the elevated levels of CD144-EMP were the most significant risk factor for CAD relative to all other traditional risk factors (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8 to 6.9, p < 0.001). Notably, plasma CD144-EMP identified a subpopulation of established CAD patients in DM subjects without typical anginal symptoms (OR 10.6, 95% CI 3.9 to 29.5, p < 0.001). CONCLUSIONS: The CD144-positive EMP exist in human plasma, and plasma CD144-EMP levels can be a clinically specific and quantitative marker of EC dysfunction and/or injury. Measurement of CD144-EMP, by providing a quantitative assessment of EC dysfunction, may be useful for identifying DM patients with increased risk of CAD.

Aged↗

Plasma thioredoxin levels in patients with unstable angina.

Plasma levels of human thioredoxin are indicative of the responses against oxidative stress. We measured the plasma thioredoxin levels in patients with unstable angina in order to examine the relationships between subsequent clinical course and plasma thioredoxin levels before and after treatment for unstable angina. Blood was sampled both on admission and after treatment in 44 patients with unstable angina. In addition, blood samples were obtained from 41 patients with stable exertional angina and 41 patients with chest pain syndrome after admission. The plasma levels of thioredoxin were the highest in the unstable angina group among three groups (p<0.001). Treatment of unstable angina decreased the plasma thioredoxin levels (p<0.01). We divided the patients with unstable angina into two groups according to the plasma thioredoxin levels on admission and after treatment. There was a significant difference in Braunwald's classification between the high thioredoxin and the low thioredoxin group on admission, as analyzed by the chi2 test with Yates's correction (p<0.05). Moreover, there was a significant difference in incidence of recurrent anginal attacks at rest between the high thioredoxin and the low thioredoxin group after treatment, as analyzed by the chi2 test with Yates's correction (p<0.001). The present study demonstrated that plasma thioredoxin levels are significantly increased in patients with unstable angina compared to those with stable exertional angina and chest pain syndrome. Thioredoxin levels were associated with recurrent myocardial ischemia in patients with unstable angina.

Aged↗

Urinary 8-hydroxy-2'-deoxyguanosine levels increase after reperfusion in acute myocardial infarction and may predict subsequent cardiac events.

We assessed serial changes in oxidative stress in patients with acute myocardial infarction by measuring urinary 8-hydroxy-2'-deoxyguanosine excretion. The urinary 8-hydroxy-2'-deoxyguanosine creatinine levels peaked at 4 hours after reperfusion therapy and the levels were higher in the cardiac event group than in the noncardiac event group before and after reperfusion.

8-Hydroxy-2'-Deoxyguanosine↗

Acute hyperglycemia is associated with adverse outcome after acute myocardial infarction in the coronary intervention era.

PURPOSE: This study was undertaken to assess the association between acute hyperglycemia and inhospital outcome after acute myocardial infarction (AMI) in the percutaneous coronary intervention (PCI) era. We also assessed outcome of patients with a history of diabetes mellitus in the PCI era. METHODS: Between January 2001 and December 2001, 1253 patients were admitted to the hospitals within 48 hours after the onset of AMI. Plasma glucose was measured at hospital admission. Acute hyperglycemia was defined as plasma glucose of > 11 mmol/L (198 mg/dL), regardless of the diabetic status. Primary PCI was performed in 898 (72%) patients. RESULTS: The inhospital mortality rate was significantly higher in patients with acute hyperglycemia than in patients without (16% vs 6%, P < .001). However, there was no significant difference in mortality between diabetic and nondiabetic patients (8% vs 9%, P = .54). Acute hyperglycemia was associated with a higher inhospital mortality rate both in nondiabetic patients (24% vs 6%, P < .001) and in diabetic patients (10% vs 5%, P = .039). Acute hyperglycemia was associated with a higher incidence of no reflow during PCI (21% vs 12%, P < .001), but diabetes was not (14% vs 15%, P = .71). CONCLUSION: Acute hyperglycemia, but not diabetes, was a predictor for inhospital mortality after AMI in the PCI era. No reflow occurred more frequently during PCI in patients with acute hyperglycemia, suggesting that microvascular dysfunction might have contributed to adverse outcome of these patients.

Acute Disease↗

Levels of the adipocyte-derived plasma protein, adiponectin, have a close relationship with atheroma.

INTRODUCTION: Inflammation is a key process in atherosclerotic formation. Structural changes in the carotid arterial wall including detection of focal plaques are measured as the intima-media thickness (IMT) providing an index of atheroma. Coronary arterial plaques may be considered as vascular structural changes. Distensibility of the arteries can be assessed by functional changes in pulse wave velocity (PWV) providing an index of sclerosis. Adiponectin has potential antiatherosclerotic properties. We hypothesized that adiponectin was associated with atherosclerotic vascular changes involved in inflammation. MATERIALS AND METHODS: We enrolled 142 patients with coronary artery disease (CAD) and 108 control patients, matched for age, sex, and body mass index (BMI) with CAD patients. We investigated the relationship between adiponectin, C-reactive protein (CRP), and atherosclerotic vascular changes. RESULTS: CRP (p=0.0009), high-density lipoprotein cholesterol (HDL-C; p=0.02), and IMTmax (p=0.02) were determinants of adiponectin independent of glucose intolerance (p=0.0001), BMI (p=0.002), and CAD (p=0.03), all of which have been significantly associated with adiponectin (r=0.38). Adiponectin was not correlated with PWV. CRP, glucose intolerance, and HDL-C that correlated with adiponectin were inversely correlated with IMTmax and CAD. CRP was negatively correlated with HDL-C (r=-0.24, p=0.0002) and positively correlated with glucose intolerance (r=0.15, p=0.01). CONCLUSIONS: Adiponectin has a close relationship with CRP, IMTmax, CAD, HDL-C, and other established risk factors. CRP, glucose intolerance, and HDL-C are common mediators between adiponectin and atheromatous vascular changes, which are contrary to each other. The exacerbation of atherogenesis may be involved in a decrease of adiponectin through abnormal glyco- and lipid-metabolism by promoting inflammation.

Adiponectin↗

Increase in the transcriptional activity of the endothelial nitric oxide synthase gene with fluvastatin: a relation with the -786T>C polymorphism.

HMG-CoA reductase inhibitors (statins) increase endothelial nitric oxide (NO) production, although the precise mechanism of this statin induced increase in NO production remains to be elucidated. We examined endothelial nitric oxide synthase (eNOS) mRNA levels, mRNA stability and the transcriptional activities of the eNOS gene in human umbilical vein endothelial cells treated with fluvastatin and simvastatin. We further examined whether the effects of these statins differ dependent upon the -786T>C polymorphism in the eNOS gene, and whether these statins affect gene expression of replication protein A1 (RPA1), which is known to reduce the transcriptional activity of the eNOS gene with the -786C allele. Utilizing the real-time reverse transcription-polymerase chain reaction, fluvastatin significantly increased eNOS mRNA levels and mRNA stability, and decreased RPA1 mRNA levels. Luciferase reporter gene assays revealed that fluvastatin significantly increased the transcriptional activity of the eNOS gene. The effect of fluvastatin was stronger in the -786C/C genotype than in the -786T/T genotype. Simvastatin increased eNOS mRNA levels and mRNA stability, but did not affect the transcriptional activity of the eNOS gene. Fluvastatin increased eNOS mRNA levels by enhancing both the transcriptional activity and mRNA stability. The effect of fluvastatin on the transcriptional activity was augmented in the -786C/C genotype, probably because of a decrease in RPA1 gene expression. Simvastatin increased eNOS mRNA levels only by enhancing mRNA stability. The present study suggests that fluvastatin increases endothelial NO activity and thus may be more beneficial to patients with the -786C allele.

Cell Line↗

Hypoadiponectinemia is associated with coronary artery spasm in men.

BACKGROUND: The relationship between adiponectin and coronary spastic angina (CSA), both of which are closely involved in coronary endothelial dysfunction, has not been elucidated. METHODS AND RESULTS: Plasma adiponectin concentrations were examined in 55 men with CSA and 55 with chest pain syndrome (CPS). The plasma log-adiponectin levels were significantly lower in patients with CSA than with CPS (0.61+/-0.28 vs 0.80+/-0.21 microg/ml, p < 0.0001). The prevalence of smoking was significantly higher in the CSA patients than in those with CPS (50.9% vs 29.1%, p = 0.0195). In multiple logistic regression analysis, log-adiponectin (p = 0.0008) and smoking (p = 0.0210) were independent determinants of CSA. Conclusions Hypoadiponectinemia is a potential risk factor for CSA in men, independent of smoking.

Adiponectin↗

Effects of glucose abnormalities on in-hospital outcome after coronary intervention for acute myocardial infarction.

BACKGROUND: The effects of glucose abnormalities on outcomes after percutaneous coronary intervention (PCI) remain unclear. We examined the association between glucose abnormalities and in-hospital outcome in patients undergoing PCI for acute myocardial infarction (AMI). METHODS AND RESULTS: A total of 849 patients with AMI who were admitted within 12 h after symptom onset and underwent emergency PCI were classified according to the presence or absence of admission hyperglycemia, defined as a blood glucose level on admission of >11 mmol/L and whether they had a history of diabetes mellitus: group 1 (n = 504), non-diabetic patients without admission hyperglycemia; group 2 (n = 111), diabetic patients without admission hyperglycemia; group 3 (n = 87), non-diabetic patients with admission hyperglycemia; and group 4 (n = 147), diabetic patients with admission hyperglycemia. Among groups 1, 2, 3 and 4, in-hospital mortality was 2.6, 2.7, 11.5 and 8.8%, respectively (p < 0.01). Multivariate analysis showed that compared with group 1 patients, the odds ratio (95%confidence interval) for in-hospital mortality among those in groups 2, 3, and 4 were 0.80 (0.24-2.60, p = 0.708), 2.29 (1.10-5.49, p = 0.039), and 2.14 (1.14-4.69, p = 0.048), respectively. CONCLUSIONS: In-patients undergoing PCI for AMI, admission hyperglycemia, irrespective of the presence or absence of diabetes, is associated with increased in-hospital mortality, whereas diabetes without admission hyperglycemia is not.

Adult↗

Beneficial effect of preinfarction angina on in-hospital outcome is preserved in elderly patients undergoing coronary intervention for anterior acute myocardial infarction.

BACKGROUND: Preinfarction angina improves survival after acute myocardial infarction (AMI) in nonelderly but not elderly patients in the thrombolytic era. However, it remains unclear whether preinfarction angina has a beneficial effect on clinical outcome in elderly patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: The study group comprised 484 anterior AMI patients who were admitted within 24 h of onset and underwent emergency PCI. Patients were divided into 2 groups: those aged < 70 years (nonelderly patients, n = 290) and those aged > or = 70 years (elderly patients, n = 194). Angina within 24 h before AMI was present in 42% of nonelderly patients and in 37% of elderly patients. In nonelderly patients, preinfarction angina was associated with a lower in-hospital mortality rate (1% vs 7%, p = 0.02). Similarly, in elderly patients, preinfarction angina was associated with a lower in-hospital mortality rate (6% vs 16%, p = 0.03). Multivariate analysis showed that the absence of preinfarction angina was an independent predictor of in-hospital mortality in both nonelderly (odds ratio 4.20; 95% confidence interval (CI) 1.20-10.6; p = 0.04) and elderly patients (odds ratio 3.04; 95%CI 1.06-18.1; p = 0.04). CONCLUSIONS: Angina within the 24 h before AMI is associated with better in-hospital outcomes in elderly and nonelderly patients.

Aged↗

Increased plasma levels of thioredoxin in patients with glucose intolerance.

OBJECTIVE: The aim of the present study was to determine the effects of glucose intolerance on oxidative stress in patients with coronary artery disease (CAD). METHODS: The patients were divided into 3 groups, diabetes mellitus (DM), IGT or normal glucose tolerance (NGT) according to the criteria of the American Diabetes Association. PATIENTS: The present study consisted of 178 consecutive patients who underwent diagnostic coronary arteriography and a 75-g glucose tolerance test. RESULTS: The level of plasma thioredoxin, a marker of oxidative stress was measured in every patient during the fasting state. The levels of plasma thioredoxin were significantly higher in the DM and IGT groups than the NGT group. Furthermore, we found that there was a positive association between thioredoxin levels and glycosylated hemoglobin (sigma=0.225, p=0.018). In multivariate logistic regression analysis, glucose intolerance (DM or IGT) was only independently associated with the high levels of thioredoxin. The levels of plasma thioredoxin were significantly higher in the CAD group compared to the non-CAD group. In multivariate logistic regression analysis, high levels of thioredoxin, male, age and hypertension were independently associated with the presence of CAD. CONCLUSION: Glucose intolerance was associated with the high levels of thioredoxin. High levels of thioredoxin were related to the presence of CAD. The measurement of thioredoxin as the marker of oxidative stress may be useful for monitoring the development of the cardiovascular diseases.

Adult↗

Sensorineural hearing loss combined with Takayasu's arteritis.

A 49-year-old woman complained of hearing loss and diminution of left radial arterial pulsation. She had been diagnosed with sudden deafness and treated with corticosteroids. Her audibility deteriorated again after the cessation of the therapy. Angiograms showed stenosis in the bilateral carotid arteries, the left vertebral artery, the left subclavian artery, and the pulmonary arteries. She was diagnosed with Takayasu's arteritis. After steroid therapy was restarted, there were improvements in her audibility, radial arterial pulsation, and levels of inflammatory markers (erythrocyte sedimentation rate, C-reactive protein, and gamma-globulin), fibrinogen, interleukin-6, and RANTES (regulated on activation, normal T cell expressed and secreted).

Administration, Oral↗

Dynamic electrocardiographic changes due to cardiac compression by a giant hiatal hernia.

A 79-year-old woman was admitted due to chest pain with T wave inversion and anasarca. Echocardiography demonstrated a mass compressing the heart and computed tomography revealed a giant hiatal hernia within the intrathoracic stomach located just behind the heart. After drainage of the gastric contents, the T wave inversion disappeared, but subsequent ST elevation in leads V1-V6 was noted. After surgical correction of the hiatal hernia, the ST segment elevation returned to a nearly normal level. The changes in the compressed heart induced by hiatal hernia may cause pericarditis resulting in electrocardiographic changes.

Aged↗

Platypnea-orthodeoxia syndrome combined with multiple congenital heart anomalies.

A 71-year-old woman was admitted for paralysis on the left side of her body. She developed dyspnea and hypoxemia after admission. Although pulmonary embolism was suspected, hypoxemia and dyspnea occurred repeatedly in spite of anticoagulation therapy. Transesophageal echocardiography revealed a patent foramen ovale (PFO), an atrial septal aneurysm (ASA), and a right-to-left shunt that appeared in an upright position. She was diagnosed with platypnea-orthodeoxia syndrome. Moreover, cardiac catheterization showed congenital anomalies, such as unroofed coronary sinus, partial anomalous pulmonary venous return and persistent left superior vena cava. Simple surgical closure of the ASA and PFO improved all of her symptoms.

Abnormalities, Multiple↗

Successful coronary stenting of the left anterior descending artery at the branching site of the targeted septal perforator immediately after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy.

We report a case of simultaneous percutaneous treatment of hypertrophic obstructive cardiomyopathy (HOCM) and coronary artery disease. Cardiac catheterization revealed a left ventricular outflow tract pressure gradient (LVOTPG) of 130 mmHg and a significant left anterior descending artery (LAD) stenosis at the site of the 1st major septal branch. The LVOTPG was eliminated by injection of ethanol into the branch. Subsequently, a coronary stent was implanted in the LAD. A coil stent was selected due to possibility of repeat septal ablation in the future. Simultaneous treatment of HOCM and LAD stenosis is considered safe and effective using a coil stent.

Aged↗

Possible association of heart failure status with synthetic balance between aldosterone and dehydroepiandrosterone in human heart.

BACKGROUND: Aldosterone is produced not only in the adrenal gland but also in the extra-adrenal tissues, including failing human heart. This study examined the production of dehydroepiandrosterone (DHEA) in human heart and elucidated the possible physiological significance. Method and Results- Using left ventricular tissues obtained at autopsy, reverse transcription-polymerase chain reaction followed by Southern blot analysis revealed the gene expressions of CYP17. By measuring plasma aldosterone and DHEA levels at the coronary sinuses and aortic roots during cardiac catheterization, we found that DHEA but not aldosterone was secreted from control subjects (P<0.0001 and P=0.74, respectively), whereas aldosterone but not DHEA was secreted from patients with heart failure (P=0.0017 and P=0.67, respectively). To examine the significance of DHEA, we measured myocyte cell sizes and the gene expression of B-type natriuretic peptide (BNP), using a neonatal rat cardiocyte culture system. We found that DHEA (10(-8) mol/L) significantly inhibited the increase in myocyte cell sizes and BNP mRNA levels upregulated by endothelin-1 (P=0.031 and P<0.0001, respectively). CONCLUSIONS: CYP17 gene expression and production of DHEA were demonstrated in human control heart. Also, we found that cardiac production of DHEA was suppressed in failing heart. We postulated that DHEA and/or its metabolites exert a cardioprotective action through antihypertrophic effects.

Adult↗

Plasma level of B-type natriuretic peptide as a prognostic marker after acute myocardial infarction: a long-term follow-up analysis.

BACKGROUND: Circulating levels of B-type natriuretic peptide (BNP), a cardiac hormone, reflect the severity of cardiac dysfunction. Because the plasma BNP level changes dramatically during the period after the onset of acute myocardial infarction (AMI), identification of a suitable sampling time is problematic. There have been several reports indicating that the plasma BNP level obtained in the acute phase of AMI can be used as a prognostic marker. We examined whether the plasma BNP level measured 3 to 4 weeks after the onset of AMI represents a reliable prognostic marker for patients with AMI. METHODS AND RESULTS: We analyzed 145 consecutive patients with AMI. Plasma BNP levels were measured during the 3 to 4 weeks after onset of AMI. Of those patients, 23 experienced fatal cardiac events during this study. The mean follow-up period was 58.6 months. Log BNP, left ventricular end-diastolic pressure, and pulmonary vascular resistance were all significantly higher in the cardiac death group, and there were more men and more patients with a history of heart failure in the cardiac death group. A Cox proportional hazards model analysis showed that log BNP was an independent predictor of cardiac death. The survival rate was significantly higher in patients with log BNP <2.26 (180 pg/mL) than in those with log BNP > or =2.26. CONCLUSIONS: The plasma BNP level obtained 3 to 4 weeks after the onset of AMI can be used as an independent predictor of cardiac death in patients with AMI.

Adult↗