刑部 恵介

INTRODUCTION: High-frequency oscillation (HFO) in scalp electroencephalography is a promising new noninvasive prognostic epilepsy biomarker, but further data are needed to ascertain the utility of this parameter. The present work investigated the association between epileptic activity and scalp HFO in pediatric patients with various types of epilepsy, using multivariable regression models to correct for possible confounding factors. METHODS: The authors analyzed 97 subjects who were divided into groups with active epilepsy (within 1 year of seizure), seizure-free epilepsy (>1 year without seizure), and nonepilepsy. Regarding the frequency of seizure occurrence as an indicator of epileptic activity, we categorized subjects into four groups (Daily/Weekly, Monthly, Yearly, and Rarely). RESULTS: Multiple linear regression analysis showed that the scalp HFO detection rate was significantly higher in patients with active epilepsy than in those with nonepilepsy (β [95% confidence interval] = 2.77 [1.79-4.29]; P < 0.001). The association between scalp HFO detection rate and frequency of seizure occurrence was highest in the Daily/Weekly group (β [95% confidence interval] = 3.38 [1.57-7.27]; P = 0.002), followed by Monthly and Yearly groups (β [95% confidence interval] = 2.42 [1.02-5.73]; P = 0.046 and 0.36 [0.16-0.83]; P = 0.017). In addition, HFO duration, number of peaks, and number of channels detected were significantly higher in patients with active epilepsy. CONCLUSIONS: Pediatric patients with active epilepsy and high frequency of seizure occurrence exhibited a higher scalp HFO detection rate. These results may help to establish HFO detectable by noninvasive scalp electroencephalography as a biomarker of active epilepsy in pediatric patients.

Background: The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) has become a global health problem. NAFLD has few initial symptoms and may be difficult to detect early, so there is need for a minimally invasive early detection marker. We hypothesized that miR-122 and miR-20a levels combined, as the miR-122/miR-20a ratio might detect NAFLD more sensitively. Methods: This study involved 167 participants with low alcohol intake. Those who had an increase in echogenicity of the liver parenchyma and hepato-renal contrast on ultrasonography were classified as the NAFLD group (n = 44), which was further classified into mild (n = 26) and severe (n = 18) groups based on echogenic intensity and hepatic vessel and diaphragm visualization. Participants without fatty liver were included in the normal group, except for those with an abnormal body mass index, glycated hemoglobin, and systolic blood pressure (n = 123) values. Serum miR-122 and miR-20a expression levels in participants were measured by real-time polymerase chain reaction, and the miR-122/miR-20a was calculated. Results: In the NAFLD group, miR-122 expression was significantly higher and the miR-20a was significantly lower than in the normal group, in agreement with previous studies. miR-122/miR-20a was also significantly higher in the NAFLD group. Receiver operating characteristic curve analysis was performed with miR-122/miR-20a as an NAFLD detection marker, and the area under the curve of miR-122/miR-20a was significantly larger than that of miR-122 or miR-20a alone. Conclusions: The miR-122/miR-20a ratio, combined with miR-122 and miR-20a levels, is a useful biomarker to detect NAFLD with high sensitivity.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global health problem. In recent years, the inhibitory effect of brain-derived neurotrophic factor (BDNF) on diabetes mellitus and fatty liver has been clarified. The purpose of this study was to analyze the relationship between serum BDNF and NAFLD which caused by abnormal metabolism of glucose and lipids. This cross-sectional study involved 429 participants (mean age, 63.5 years: men, 38.5%) with low alcohol intake. Of the participants, those who had an increase in echogenicity of the liver parenchyma and hepato-renal contrast on ultrasonography were classified as the NAFLD group (n = 88), and the others were classified as the normal (n = 341) group. The NAFLD group was further classified into a mild group (n = 60) and a severe group (n = 28) based on the intensity of echogenicity and visualization of the hepatic vessels and diaphragm. Median BDNF levels were higher in the NAFLD group than the normal group (35.5 vs. 42.3 ng/mL, p < 0.01). Furthermore, BDNF levels tended to be associated with the severity of NAFLD (p < 0.01). In addition to the univariate analysis, in the sex- and age-adjusted model, there was a significant association between the BDNF levels and NAFLD severity (p < 0.01). The fully adjusted regression analysis also showed a positive association between the serum BDNF level and NAFLD (p < 0.01). These results suggest that NAFLD patients have a compensatory increase in circulating BDNF levels.

Purpose It has been demonstrated that circulating microRNA profiles are affected by physiological conditions. Several studies have demonstrated that microRNAs play important roles in the regulation of adiposity. However, few have investigated the relationship between circulating microRNAs and obesity, which has become a major public health problem worldwide. This study investigated the association between circulating microRNAs and obesity in a Japanese population. Methods Obesity parameters, such as subcutaneous and visceral fat adipose tissue, body fat percentage, and body mass index were assessed in a cross-sectional sample of 526 participants who attended health examinations in Yakumo, Japan. In addition, five circulating microRNAs (miR-20a, -21, -27a, -103a, and -320), which are involved in adipocyte proliferation and differentiation, were quantified using real-time polymerase chain reaction amplification. Results We compared the circulating microRNA concentrations in a percentile greater than 75th (high) with below the value (low) of subcutaneous adipose tissue, visceral fat adipose tissue, body mass index, and per cent body fat. For visceral fat adipose tissue, significant decrease in miR-320 expression was observed in high group. Also, for body mass index, significant change of miR-20a, -27a, 103a, and 320 expression level was observed in high group. Multiple linear regression analysis demonstrated that circulating levels of some microRNA such as miR-27a were significantly associated with subcutaneous adipose tissue, visceral fat adipose tissue, and body mass index. Conclusions Our findings support the need for further studies to determine whether such changes are consistent across different populations and whether the identified microRNAs may represent novel biomarkers to predict the susceptibility and progression of obesity-related disorders.

Background: The effect of the redox state of human serum albumin (HSA) on the antioxidant properties of the entire body has been a focus of recent research. The usefulness of HSA redox state as a biomarker for reducing oxidative stress has been investigated in clinical settings however, evidence for its significance as a health index in non-clinical settings is yet to be established. This study aimed to examine the associations between HSA redox state and the atherosclerotic indices of carotid intima-media thickness (IMT) and plaque formation in a rural Japanese population. Methods: We conducted a cross-sectional study as part of a health check-up program in the rural area of Hokkaido, Japan, at the end of August 2013. A total of 281 residents (124 men and 157 women) were included in the final analysis. Lifestyle-related data were obtained through a self-reported questionnaire, and ultrasound examinations were performed to measure IMT and determine plaque formation. The high-performance liquid chromatography postcolumn bromocresol green method was used to separate HSA into human nonmercaptalbumin and human mercaptalbumin (HMA). Results: We found a significant negative relationship between the fraction of HMA [f(HMA)] and IMT (standardized β = - 0.132, p = 0.03). Moreover, f(HMA) was significantly associated with plaque formation (p &lt 0.01) with an odds ratio of 0.89 (95% confidence interval, 0.81-0.97) for every 10% increment in f(HMA). Conclusions: We found that the HSA redox state, as determined by f(HMA), was associated with atherosclerotic indices in Japanese subjects. These results suggest that the HSA redox state indicates the risk of developing atherosclerosis.

AimGenome-wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)-DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection. MethodsThe SNPs of HLA-DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection. ResultsIn 224 hepatitis B e antigen (HBeAg)-negative patients, those with rs2856718 genotype AG+GG had significantly lower hepatitis B core-related antigen levels (P=0.0184), less frequent treatment with nucleotide/nucleoside analogs (NAs) (P=0.0433), and less frequent HCC development (P=0.0256) than those with genotype AA. Multivariate analysis selected age (P=0.0460), platelet count (P=0.0481), -glutamyl transpeptidase (P=0.0030), and nucleotide/nucleoside analog treatment (P=0.0003) as factors independently associated with HCC development. HBeAg-negative patients with rs7453920 genotype GG had significantly lower HBsAg levels (P&lt;0.0001), a higher prevalence of HBV genotype C (P=0.0063), and a lower prevalence of the wild-type basal core promoter region (P=0.0045) than those with genotype AA + AG. Multivariate analysis selected age (P&lt;0.0001), platelet count (P=0.0021), HBV DNA levels (P=0.0314), wild type of precore region (P=0.0015), and rs7453920 (P&lt;0.0001) as factors independently associated with HBsAg levels. ConclusionThis study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.

Objectives: Circulating micro (mi)RNA profiles are influenced by various medical conditions, and miRNAs have been examined as potential biomarkers for cancer, cardiovascular disease, and diabetes. However, few studieshave investigated whether circulating miRNAs and cigarette smoking are correlated. Our aim was to determine theassociation between smoking status and expression of various miRNAs in a Japanese population sample.Methods: We conducted a cross-sectional analysis of 526 subjects (219 men and 307 women) aged 39 years and older who had undergone a health examination at a clinic in Yakumo, Hokkaido in August 2012. We used quantitative real-time polymerase chain reaction to determine serum miRNA expression. We then calculated the odds ratios for elevated serum miRNA levels according to smoking status using never-smokers as the reference group.Results: Expression of lethal (let)-7d, miRNA(miR)-150, miR-192, miR-197 and miR320 was significantly higher in current smokers than in never-smokers. Multivariate logistic regression analyses showed that while current smokers were significantly more likely to have elevated serum levels of miRNA let-7d, miR-21, miR-122, miR-146, miR-150, miR-192, miR-197, and miR320 than never-smokers, former smokers had significantly higher odds of having elevated miR-1, miR-146, miR-150, miR-195, and miR-320 levels in their sera.Conclusions: We found that cigarette smoking is associated with elevated expression of various serum miRNAs. Our results suggest that it is necessary to consider the confounding effect caused by smoking when evaluating expression of serum miRNAs for diagnosing pathological conditions.

AIM: To evaluate the changes of shear-wave velocity (Vs) by acoustic radiation force impulse after treatment in chronic hepatitis C. METHODS: Eighty-seven patients with chronic hepatitis C were consecutively treated with combinations of interferon (IFN) plus ribavirin (RBV). Vs value (m/s) was measured with acoustic radiation force impulse before treatment, at end of treatment (EOT), 1 year after EOT, and 2 years after EOT. RESULTS: In patients with a sustained virological response (SVR) (n = 41), Vs significantly decreased at EOT [1.19 (1.07-1.37), P = 0.0004], 1 year after EOT [1.10 (1.00-1.22), P = 0.0001], and 2 years after EOT [1.05 (0.95-1.16), P &lt; 0.0001] compared with baseline [1.27 (1.11-1.49)]. In patients with a relapse (n = 26), Vs did not significantly decrease at EOT [1.23 (1.12-1.55)], 1 year after EOT [1.20 (1.12-1.80)], and 2 years after EOT [1.41 (1.08-2.01)] compared with baseline [1.39 (1.15-1.57)]. In patients with a nonvirological response (n = 20), Vs did not significantly decrease at EOT [1.64 (1.43-2.06)], 1 year after EOT [1.66 (1.30-1.95)], and 2 years after EOT [1.61 (1.36-2.37)] compared with baseline [1.80 (1.54-2.01)]. Among genotype 1 patients, baseline Vs was significantly lower in SVR patients [1.28 (1.04-1.40)] than in non-SVR patients [1.56 (1.20-1.83)] (P = 0.0142). CONCLUSION: Reduction of Vs values was shown in SVR patients after IFN-plus-RBV therapy by acoustic radiation force impulse.

Aim: To investigate associations between patatin-like phospholipase domain-containing 3 (PNPLA3) genotypes and fibrosis and hepatocarcinogenesis in Japanese chronic hepatitis C (CHC) patients. Methods: Two hundred and thirty-one patients with CHC were examined for PNPLA3 genotypes, liver stiffness measurements (LSM), and hepatocellular carcinoma (HCC) from May 2010 to October 2012 at Fujita Health University Hospital. The rs738409 single nucleotide polymorphism (SNP) encoding for a functional PNPLA3 I148M protein variant was genotyped using a TaqMan predesigned SNP genotyping assay. LSM was determined as the velocity of a shear wave (Vs) with an acoustic radiation force impulse. Vs cut-off values for cirrhosis were set at 1.55 m/s. We excluded CHC patients with a sustained virological response or relapse after interferon treatment. Results: PNPLA3 genotypes were CC, CG, and GG for 118, 72, and 41 patients, respectively. Multivariable logistic regression analysis selected older age (OR = 1.06; 95% CI: 1.03-1.09; p &lt; 0.0001), higher body mass index (BMI) (OR= 1.12; 95% CI: 1.03-1.22; p = 0.0082), and PNPLA3 genotype GG (OR = 2.07; 95% CI: 0.97-4.42; p = 0.0599) as the factors independently associated with cirrhosis. When 137 patients without past history of interferon treatment were separately assessed, multivariable logistic regression analysis selected older age (OR = 1.05; 95% CI: 1.02-1.09; p = 0.0034), and PNPLA3 genotype GG (OR = 3.35; 95% CI: 1.13-9.91; p = 0.0291) as the factors independently associated with cirrhosis. Multivariable logistic regression analysis selected older age (OR = 1.12; 95% CI: 1.07-1.17; p &lt; 0.0001), PNPLA3 genotype GG (OR = 2.62; 95% CI: 1.15-5.96; p = 0.0218), and male gender (OR = 1.83; 95% CI: 0.90-3.71); p = 0.0936) as the factors independently associated with HCC. Conclusion: PNPLA3 genotype I148M is one of risk factors for developing HCC in Japanese CHC patients, and is one of risk factors for progress to cirrhosis in the patients without past history of interferon treatment.

Background: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelium nitric oxide synthase (NOS). ADMA binds to a substrate-binding site of NOS and then inhibits nitric oxide production from vascular endothelial cells. Elevated ADMA levels are a risk factor for cardiovascular disease. Recently, it was reported that plasma ADMA levels were negatively correlated with vegetable and fruit consumption. The purpose of this study was to examine the association between serum levels of carotenoids and serum ADMA levels in Japanese subjects. Methods: We conducted a cross-sectional study of 470 subjects (203 men and 267 women) who attended a health examination in August 2011. Serum levels of several carotenoids were separately measured by high-performance liquid chromatography. Serum ADMA levels were determined by using an enzyme-linked immunosorbent assay kit. Results: In women, the multivariate-adjusted odds ratios (ORs) of elevated serum ADMA levels were significantly decreased in the highest tertile for beta-cryptoxanthin (OR 0.47, 95% CI 0.23-0.95), alpha-carotene (OR 0.39, 95% CI 0.18-0.79), and beta-carotene (OR 0.36, 95% CI 0.17-0.73) compared to the lowest tertile. In men, significantly decreased ORs were observed in the highest tertiles of serum zeaxanthin/lutein (OR 0.23, 95% CI 0.06-0.69) and acarotene (OR 0.26, 95% CI 0.07-0.82), and in the middle and the highest tertiles of serum beta-carotene (OR 0.27, 95% CI 0.09-0.74 and OR 0.20, 95% CI 0.03-0.88, respectively) when the tertile cutoff points of women were extrapolated to men. Conclusions: Higher serum levels of carotenoids, such as alpha-carotene and beta- carotene, may help to prevent elevated serum ADMA levels in Japanese subjects.

AIM: To investigate the factors other than fibrosis stage correlating with acoustic radiation force impulse (ARFI) elastograpy in chronic hepatitis C. METHODS: ARFI elastograpy was performed in 108 consecutive patients with chronic hepatitis C who underwent a liver biopsy. The proportion of fibrosis area in the biopsy specimens was measured by computer-assisted morphometric image analysis. RESULTS: ARFI correlated significantly with fibrosis stage (beta = 0.1865, P &lt; 0.0001) and hyaluronic acid levels (beta = 0.0008, P = 0.0039) in all patients by multiple regression analysis. Fibrosis area correlated significantly with ARFI by Spearman's rank correlation test but not by multiple regression analysis. ARFI correlated significantly with body mass index (BMI)(beta = -0.0334, P = 0.0001) in F0 or F1, with gamma-glutamyltranspeptidase levels (beta = 0.0048, P = 0.0012) in F2, and with fibrosis stage (beta = 0.2921, P = 0.0044) and hyaluronic acid levels (beta = 0.0012, P = 0.0025) in F3 or F4. The ARFI cutoff value was 1.28 m/s for F &gt;= 2, 1.44 m/s for F &gt;= 3, and 1.73 m/s for F4. CONCLUSION: ARFI correlated with fibrosis stage and hyaluronic acid but not with inflammation. ARFI was affected by BMI, gamma-glutamyltranspeptidase, and hyaluronic acid in each fibrosis stage. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.