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Biomedical subjects

Minoru Yamakado

Publications and source records attributed to Minoru Yamakado.

At least 19 recordsLinked to original sources
PubMed2006

Urinary PGDS levels are associated with vascular injury in type 2 diabetes patients.

BACKGROUND: The presence of metabolic syndrome has been shown to be predictors of cardiovascular morbidity and mortality in patients with type 2 diabetes. In a cross-sectional clinical study, we investigated the association of metabolic syndrome with asymptomatic lacunar strokes and cardiovascular disease (CVD) and we compared its significance with urinary protein markers. METHODS: We studied Japanese type 2 diabetes patients (n=233, men=124, women=109). The diagnosis of metabolic syndrome was made according to WHO and International Diabetes Federation (IDF) criteria. Cardiovascular events were recorded and asymptomatic lacunar lesions were evaluated with magnetic resonance imaging (MRI). We also measured urinary levels of albumin, type IV collagen, beta2-microglobulin (beta2MG), N-acetyl-beta-d-glucosaminidase (NAG) and lipocalin-type prostaglandin D synthase (PGDS). RESULTS: The prevalence of metabolic syndrome is 31.3% (IDF) and 52% (WHO) in 233 patients and microalbuminuria was present in 62 subjects (26.6%). Metabolic syndrome (WHO) significantly associated with asymptomatic lacunar lesions (p=0.035, OR=2.854, CI 1.075-7.579), while metabolic syndrome (IDF) or urinary markers failed to associate with presence of asymptomatic lacunar lesions. The presence of metabolic syndrome or microalbuminuria did not show significant association with CVD; however, the elevation of beta2MG, NAG and PGDS showed significant association with CVD. By a logistic regression analysis using urinary proteins as independent variables, the presence of higher PGDS excretion independently associated with history of CVD (p=0.025, OR=3.847, CI 1.180-12.545). CONCLUSIONS: In type 2 diabetes patients, the elevation of urinary PGDS secretion closely associated with cardiovascular events and may be a supplemental or additional marker to the criteria of metabolic syndrome.

Albuminuria↗
PubMed2006

Association between serum albumin, carotid atherosclerosis, and metabolic syndrome in Japanese individuals.

Serum albumin is a maker of nutritional status and possesses antioxidative properties. Here, we have sought to investigate the mode of association between serum albumin levels, metabolic syndrome, and carotid atherosclerosis by analyzing the data of the cross-sectional data from 8143 individuals who underwent general health screening test. After adjusting for age, total cholesterol, and smoking status, the highest quartile of serum albumin (>or=4.7 g/dL) was associated with increased prevalence of metabolic syndrome with an odds ratio of 1.80 (95% CI 1.41-2.23, P<0.0001) in women, and 1.60 (95% CI 1.44-1.78, P<0.0001) in men, when compared to the lowest serum albumin quartile (<4.3g/dL). By contrast, when compared with the lowest quartile, the highest quartile of serum albumin was associated with reduced prevalence of carotid plaque with an odds ratio of 0.62 (95% CI 0.42-0.91, P<0.001) in women, and 0.76 (95% CI 0.62-0.93, P<0.01) in men, and for carotid intima-media thickening with an odds ratio of 0.57 (95% CI 0.35-0.94, P<0.05) in women, and 0.71 (95% CI 0.55-0.92, P<0.01) in men. Our data showed that higher serum albumin was inversely associated with the prevalence of early carotid atherosclerosis, although it was positively associated with the prevalence of metabolic syndrome. Whether these observations are in part explained by the antioxidative properties of albumin requires further investigation.

Aged↗
PubMed2006

Metabolic syndrome may not associate with carotid plaque in subjects with optimal, normal, or high-normal blood pressure.

Much evidence indicates that metabolic syndrome is a risk factor for the development of cardiovascular disease, but whether metabolic syndrome is an independent risk factor for early atherosclerosis in the individuals with only minor hemodynamic abnormalities, if any, is not well investigated. Here we have investigated the association between metabolic syndrome and carotid atherosclerosis in individuals with blood pressure of <140/90 mm Hg. Between 1994 and 2003, 8143 subjects underwent general health screening including carotid ultrasonography. Of 8143 individuals, 5661 individuals without antihypertensive medications who had blood pressure of <140/90 mm Hg were considered to have optimal, normal, or high-normal blood pressure. After adjustment for age, systolic blood pressure, body mass index, total and high-density lipoprotein cholesterol, triglycerides, fasting glucose, and smoking status, metabolic syndrome was not found to be an independent risk factor for carotid plaque (odds ratio: 1.65; 95% CI; 0.72 to 3.76 in women and odds ratio: 0.95; 95% CI: 0.70 to 1.28 in men) or for carotid intima-media thickening (odds ratio: 0.56; 95% CI: 0.18 to 1.72 in women and odds ratio: 0.93 95% CI: 0.62 to 1.38 in men) in these subjects. Thus, presence of metabolic syndrome may not increase the prevalence of carotid atherosclerosis independent of other cardiovascular risk factors in Japanese individuals with optimal, normal, or high-normal blood pressure.

Adult↗
PubMed2006

Higher serum uric acid is associated with increased arterial stiffness in Japanese individuals.

Hyperuricemia is postulated to be a risk factor for atherosclerotic diseases, although whether it is independent of classical atherogenic risk factors is controversial. The automatic computer-assisted measurement of brachial-ankle pulse wave velocity (baPWV) is a valid and reproducible method by which to assess arterial stiffness, a potential surrogate marker of early atherosclerosis. By analyzing cross-sectional data from 982 individuals who underwent health screening, we have investigated whether serum uric acid is associated with high baPWV, which was determined as the highest quartile of baPWV values, in a sex-specific manner. Multivariate analysis showed that the odds ratios (95% CI) of the highest baPWV quartile across the sex-specific quartiles of serum uric acid were 1.0, 2.80 (0.93-8.40), 2.13 (0.74-6.19), and 2.76 (1.01-7.55) in women, and 1.0, 1.10 (0.55-2.20), 1.97 (1.04-3.75), and 2.24 (1.10-4.56) in men after adjusting for age, total and HDL-cholesterol, BMI, systolic blood pressure, triglycerides, fasting glucose and smoking status. The association between uric acid and high baPWV was observed in both subjects with metabolic syndrome and those without. These data suggest that in both genders, serum uric acid level is associated with increased baPWV, a marker of arterial stiffness, and is in part independent of other conventional risk factors for atherosclerosis and metabolic syndrome.

Aged↗
PubMed2006

Relationship between the adiponectin-leptin ratio and parameters of insulin resistance in subjects without hyperglycemia.

We previously reported that the adiponectin-leptin (A/L) ratio was more efficacious as a parameter of insulin resistance than adiponectin or leptin alone, and a more sensitive and reliable marker of insulin resistance than homeostasis model assessment (HOMA-R) as the fasting plasma glucose (FPG) level elevated in type 2 diabetes mellitus. In this study, we examined the usefulness of the A/L ratio as compared to HOMA-R for assessing insulin resistance in Japanese subjects without hyperglycemia. A total of 411 Japanese adults without hyperglycemia (205 men, aged 49 +/- 10 years; 206 women, aged 48 +/- 10 years) were enrolled. We investigated the correlation between fasting serum insulin level, FPG, leptin or adiponectin, and body mass index (BMI), fat mass (FM), triglycerides (TGs), high-density lipoprotein (HDL) cholesterol, or preheparin serum lipoprotein lipase (LPL) as parameters of insulin resistance. Next, we examined the relationships between parameters of insulin resistance and the A/L ratio or HOMA-R. By simple regression of the correlation between serum insulin level, FPG, leptin or adiponectin, and each parameter of insulin resistance, the best correlation coefficients were seen in leptin (men, r = 0.501; women, r = 0.667) as compared with BMI, in leptin (men, r = 0.658; women, r = 0.747) as compared with FM, in adiponectin (r = -0.285) in men and leptin (r = 0.299) in women as compared with TGs, in adiponectin (men, r = 0.405; women; r = 0.442) as compared with HDL cholesterol, and in adiponectin (men, r = 0.228; women, r = 0.452) as compared with LPL. By simple regression of the correlation between A/L ratio or HOMA-R and each parameter of insulin resistance, the highest correlation coefficients were seen with the A/L ratio except HDL cholesterol in men. Next, we carried out multiple linear regression to analyze the association between A/L ratio or HOMA-R and FM, TGs, HDL cholesterol, and LPL, excluding BMI, simultaneously. In men, the A/L ratio was significantly correlated with FM and TGs, and HOMA-R was significantly correlated with FM. This model explained 34% of the variance in the A/L ratio and 17% of the variance in HOMA-R. In women, the A/L ratio was significantly correlated with FM and LPL, and HOMA-R was significantly correlated with FM and LPL. This model explained 39% of the variance in A/L ratio and 14% of the variance in HOMA-R. In conclusion, the present study suggested that the A/L ratio might be more useful than HOMA-R to accurately assess insulin resistance in subjects without hyperglycemia.

Adiponectin↗
PubMed2006

Coronary artery spasm and the polymorphisms of the endothelial nitric oxide synthase gene.

BACKGROUND: Coronary artery spasm plays an important role in the pathogenesis of vasospastic angina, and contributes to the development of several acute coronary syndromes. Endothelial nitric oxide synthase (ecNOS) catalyzes the synthesis of nitric oxide, which regulates vascular tone, and may be related to coronary vasospasm. The present study investigated whether coronary spasm is related to particular polymorphisms of the ecNOS gene. METHODS AND RESULTS: Spasm provocation by serial infusions of acetylcholine was performed on 165 patients who were clinically suspected of having angina. In both study patients and healthy controls (n=400), genomic polymorphisms of the ecNOS gene were determined by using polymerase chain reaction. Quantitative luminal diameter measurements of the 3 major coronary arteries were initially obtained before and after acetylcholine injection, and then after isosorbide dinitrate injection, by using a computer-assisted analysis system. Logistic multiple regression analysis identified the a/a or a/b genotype in intron 4 of ecNOS (NOS4a: p=0.0431, odds ratio (OR) 2.43) and diabetes mellitus (p=0.0060, OR 4.88) as significant predictors of coronary spasm. In the patients with NOS4a, both the induced and spontaneous contractions were augmented. CONCLUSION: The present study results indicated that NOS4a could be a good marker for coronary artery spasm.

Acetylcholine↗
PubMed2006

[Age specific reference ranges and clinical trial for complexed prostate specific antigen (cPSA)].

We compared the complexed PSA (cPSA) reference range of values by age against that for total PSA. The subjects were 1,210 men who underwent a complete medical checkup at our center between September and November 2003. We found an upward trend of the measured values associated with age and defined a set of expected result range by age groups. The cPSA 95th percentile upper limit value increased across all age groups: for men under 40 years, 1.38ng/ml: for men 40 to 49 years, 1.60ng/ml; for men 50 to 59 years, 2.25 ng/ml; for men 60 to 69 years, 2.50 ng/ml; and for men 70 years older, 4.31 ng/ml (The number of subjects in each group was 153, 323, 429, 220 and 77). The total PSA also increased with age: 1.85 ng/ml, 2.11 ng/ml, 2.80 ng/ml, 4.20 ng/ml, and 5.69 ng/ml, respectively. We also compared other prostatic tumor markers in urology patients.

Adult↗
PubMed2005

Association between serum uric acid, metabolic syndrome, and carotid atherosclerosis in Japanese individuals.

OBJECTIVE: There are few data available on possible independent association between uric acid and carotid atherosclerosis. Here we first sought to investigate association between uric acid levels and metabolic syndrome in Japanese; second, we assessed whether there is an independent association of uric acid with prevalence of carotid atherosclerosis in individuals subdivided according to gender and metabolic syndrome status. METHODS AND RESULTS: Cross-sectional data from 8144 individuals who underwent general health screening were analyzed. After adjusting for age, total cholesterol, and smoking status, the odds ratios (95% CI) of sex-specific quartiles of serum uric acid for metabolic syndrome were 1.0, 1.06 (0.60 to 1.87), 2.18 (1.30 to 3.64), and 4.17 (2.56 to 6.79) in women, and 1.0, 0.92 (0.74 to 1.14), 1.52 (1.25 to 1.65), and 1.97 (1.61 to 2.40) in men. After adjusting for age, serum levels, total cholesterol, and smoking status, prevalence of carotid plaque was higher in subjects in the second, third, and fourth quartiles of uric acid level with odds ratios (95% CI) of 1.24 (1.01 to 1.52), 1.37 (1.11 to 1.68), and 1.31 (1.05 to 1.63), respectively, in men without metabolic syndrome but not in men with metabolic syndrome or in women with or without metabolic syndrome. CONCLUSIONS: The prevalence of metabolic syndrome showed a graded increase according to serum uric acid values in both genders. In men who did not have metabolic syndrome, uric acid was found to be an independent risk factor for incidence of carotid plaque.

Adult↗
PubMed2005

Association between cigarette smoking, metabolic syndrome, and carotid arteriosclerosis in Japanese individuals.

Cigarette smoking is associated with increased insulin resistance and other metabolic abnormalities. Here, we investigate the prevalence of metabolic syndrome (MetS) in cigarette smokers and people who never smoked by analyzing cross-sectional data of 5033 subjects aged between 35 and 65 years who underwent general health screening. Both former and current smoking was associated with an increased incidence of metabolic syndrome defined by modified-National Cholesterol Education Program (NCEP) criteria with odds ratios of 1.77 (95% CI 1.42-2.22, P < 0.0001) and 2.38 (95% CI 1.95-2.91, P < 0.0001), respectively. In both former and current smokers, prevalence of metabolic syndrome increased when the duration of cigarette smoking was > or = 10 years. The positive association between metabolic syndrome and smoking was only partially reversed even 5 years after quitting. Multivariate logistic regression analysis showed that metabolic syndrome was an independent risk factor for carotid plaque with an odds ratio of 1.72 (95% CI 1.43-2.08, P < 0.0001). On the other hand, when limited to individuals without metabolic syndrome, former and current smoking was still found to be associated with carotid plaque with odds ratios of 1.49 (95% CI 1.15-1.92, P = 0.0023) and 1.57 (95% CI 1.22-2.03, P = 0.0005), respectively, in men. Collectively, these data suggest that the atherogenic consequences of smoking may, at least in part, be explained by its association with metabolic syndrome.

Adult↗
PubMed2005

Hypertension is the most common component of metabolic syndrome and the greatest contributor to carotid arteriosclerosis in apparently healthy Japanese individuals.

The cluster of metabolic and hemodynamic risk factors known as metabolic syndrome is known to be a risk factor for ischemic cardiovascular diseases and stroke. By analyzing the cross-sectional data from 8,144 individuals (age 19-88 years) who underwent general health screening, we have investigated the prevalence of metabolic syndrome, as diagnosed by modified-National Cholesterol Education Program (NCEP) criteria corresponding to the following five categories: triglycerides > or = 150 mg/dl; high density lipoprotein (HDL)-cholesterol < 40 mg/dl in men or < 50 mg/dl in women; fasting plasma glucose > or = 110 mg/dl; systolic/diastolic blood pressure > or = 130/85 mmHg; and body mass index > 25 kg/m2. We found that the prevalence of metabolic syndrome was 19% in men and 7% in women. After adjustment for age, metabolic syndrome was found to be significantly more prevalent in men than in women, with an odds ratio of 3.08 (95% confidence interval [CI] 2.62-3.61, p < 0.0001). Among the five metabolic/hemodynamic risk factor components, hypertension was observed most frequently in individuals with metabolic syndrome, at 85% in men and 87% in women. In addition, multivariate logistic regression analysis adjusted for age, sex, serum total cholesterol levels, and smoking status showed that hypertension possessed the greatest odds ratio (1.43, 95% CI 1.27-1.60) for carotid plaque among the metabolic/hemodynamic risk factors. These data emphasize the importance of controlling blood pressure for reducing the risk of both metabolic syndrome and carotid arteriosclerosis in apparently healthy individuals.

Aged↗
PubMed2004

Nicked beta2-glycoprotein I: a marker of cerebral infarct and a novel role in the negative feedback pathway of extrinsic fibrinolysis.

BEta(2)-glycoprotein I (beta(2)-GPI) is proteolytically cleaved by plasmin in domain V (nicked beta(2)-GPI), being unable to bind to phospholipids. This cleavage may occur in vivo and elevated plasma levels of nicked beta(2)-GPI were detected in patients with massive plasmin generation and fibrinolysis turnover. In this study, we report higher prevalence of elevated ratio of nicked beta(2)-GPI against total beta(2)-GPI in patients with ischemic stroke (63%) and healthy subjects with lacunar infarct (27%) when compared to healthy subjects with normal findings on magnetic resonance imaging (8%), suggesting that nicked beta(2)-GPI might have a physiologic role beyond that of its parent molecule in patients with thrombosis. Several inhibitors of extrinsic fibrinolysis are known, but a negative feedback regulator has not been yet documented. We demonstrate that nicked beta(2)-GPI binds to Glu-plasminogen with K(D) of 0.37 x 10(-6) M, presumably mediated by the interaction between the fifth domain of nicked beta(2)-GPI and the fifth kringle domain of Glu-plasminogen. Nicked beta(2)-GPI also suppressed plasmin generation up to 70% in the presence of tissue plasminogen activator, plasminogen, and fibrin. Intact beta(2)-GPI lacks these properties. These data suggest that beta(2)-GPI/plasmin-nicked beta(2)-GPI controls extrinsic fibrinolysis via a negative feedback pathway loop.

Aged↗
PubMed2004

Association between white blood cell count and carotid arteriosclerosis in Japanese smokers.

Recent studies have shown the relationship between general inflammatory markers and ischemic heart and cerebrovascular diseases. Here we have investigated the potential association between the circulating white blood cell count and carotid arteriosclerosis in apparently healthy individuals. Between 1994 and 1998, 3455 subjects who had undergone general health screening tests including carotid ultrasonography were enrolled in this study. The intertertile cutoff points for the white blood cell count were 5.1 x 10(3) and 6.4 x 10(3) microL(-1) in the male subjects and 4.6 x 10(3) and microL(-1) in the female subjects. The prevalence of carotid plaque in the first (lowest), the second, and the third tertiles was 19, 28, and 28% in the male subjects, respectively (P < 0.0001), and 10, 15, and 14% in the female subjects, respectively (n.s.). The multivariate analysis showed that the male subjects in the second and third tertiles had increased risk for carotid plaque with odds ratios of 1.54 (95% CI 1.18-2.01) and 1.47 (95% CI 1.11-1.95), respectively, compared to those in the first tertile. When male subjects were subdivided according to their smoking status, the association between white blood cell count and carotid plaque was significant in those who smoked, but not in those who had never smoked. These data suggested the possible association between the circulating white blood cell count and formation of carotid plaque in male smokers, but not in male never smokers or in females, in an apparently healthy Japanese population.

Arteriosclerosis↗
PubMed2004

Increased electronegative charge of serum low-density lipoprotein in patients with diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus have been reported to show increased serum levels of modified low-density lipoprotein (LDL), including glycosylated, oxidized and small, dense LDL. This change has been suggested to represent an important risk factor for diabetic macroangiopathy. A common characteristic shared by these modified LDL species is the increase in electronegative charge on particle surfaces, which can be detected by agarose gel electrophoresis as "LDL charge modified frequency" (LDL-CMF) determined from the relative mobility of LDL fraction. METHODS: LDL-CMF was measured in the sera from 129 outpatients with type 2 diabetes mellitus and compared with the data from 34 normal subjects. RESULTS: The LDL fraction from diabetics migrates more closely to the anode side as compared with that from normal subjects. The LDL-CMF measured in diabetics, 5.5+/-8.1%, was significantly (p<0.0001) higher than 0.6+/-3.4% in normal subjects. Serum LDL-CMF showed significant positive correlations with triglyceride at r=0.552 (p<0.0001) and malondialdehyde modified LDL at r=0.390 (p<0.0001), as well as systolic blood pressure, body mass index, fasting plasma glucose, hemoglobin A(1c), total cholesterol, free fatty acid (FFA) and homeostasis model assessment ratio. It showed negative correlations with high-density lipoprotein and total superoxide dismutase activity. CONCLUSION: The results indicate that LDL-CMF reflects the degree of serum LDL modification in diabetics and can be regarded as an important risk factor for diabetic macroangiopathy.

Cholesterol, HDL↗
PubMed2003

Association between insulin resistance and carotid arteriosclerosis in subjects with normal fasting glucose and normal glucose tolerance.

OBJECTIVE: We examined the possible association between insulin resistance and carotid arteriosclerosis in subjects who had both normal fasting glucose and normal glucose tolerance after intake of a glucose load. METHODS AND RESULTS: Our subjects were individuals who underwent general health screening at our institute, which included carotid ultrasound and oral glucose tolerance testing. Of the 1238 subjects enrolled in our study, 738 (60%) were classified as normal, defined as a normal fasting glucose level and normal glucose tolerance, and 334 (27%) and 166 (13%) were classified as borderline and diabetic, respectively, according to the criteria of the Japan Diabetes Society. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index to measure insulin resistance. In normal-type subjects, univariate analysis showed that insulin resistance, but not insulin secretion, was associated with the presence of carotid plaque. Multivariate analysis showed that HOMA-IR was positively associated with carotid plaque in normal-type subjects, with an odds ratio of 1.19 (95% confidence interval, 1.00 to 1.41; P<0.05). CONCLUSIONS: These data suggest the possibility that the presence of higher insulin resistance could be a risk factor for carotid arteriosclerosis in subjects with normal fasting glucose and normal glucose tolerance.

Adult↗
PubMed2003

Association between hepatitis C virus core protein and carotid atherosclerosis.

A link between certain infectious microorganisms and an increased risk of atherosclerotic disease has been suggested. By analyzing the data of subjects who had undergone general health-screening tests, a possible association between carotid atherosclerosis and seropositivity of antibody against hepatitis C virus (HCV) has been previously reported. In the present study, a possible link between carotid atherosclerosis and HCV core protein positivity was assessed, because it is postulated to be a better marker of viremia and thus persistent infection. Of the 1992 enrolled subjects, 496 (25%) had carotid artery plaque, and 25 (1.3%) were positive for HCV core protein. Carotid artery plaque was positive in 480/1967 (24%) and 16/25 (64%) of the core protein-negative and core protein-positive subjects, respectively (p<0.0001 by chi(2) test). Serum concentrations of transaminases were higher in core protein-positive subjects, but albumin concentrations were not significantly different between the 2 groups. Multivariate logistic regression analysis showed that HCV core protein positivity is an independent predictor of carotid plaque with an odds ratio of 5.61 (95% confidence interval 2.06-15.26, p<0.001). These data further support the possible link between persistent HCV infection and carotid atherosclerosis in the subjects without severe liver dysfunction.

Adult↗