研究者業績

小谷 和彦

コタニ カズヒコ  (Kazuhiko Kotani)

基本情報

所属
自治医科大学 地域医療学センター地域医療学部門  教授
学位
博士(医学)(自治医科大学(JMU))

J-GLOBAL ID
200901036312266574
researchmap会員ID
1000361605

外部リンク

論文

 505
  • Izumi Chihara, Ritei Uehara, Kazuhiko Kotani, Atsuko Sadakane, Yasuko Aoyama, Satoshi Tsuboi, Ryusuke Ae, Tsogzolbaatar Enkh-Oyun, Yosikazu Nakamura
    ARCHIVES OF GYNECOLOGY AND OBSTETRICS 284(5) 1117-1122 2011年11月  査読有り
    Purpose Overweight or obesity is a known risk factor for cesarean delivery although there is minimal data among Japanese women. The aim of the study was to examine the effect of prepregnancy body mass index (BMI) on singleton cesarean delivery among term nulliparous women using a national sample from the Human Milk Survey. Methods Data from the Human Milk Survey between 1998 and 2008 were used for the secondary analysis. Women were categorized as underweight (BMI < 18.5 kg/m(2)), normal weight (18.5 a parts per thousand currency sign BMI < 25.0), or overweight (BMI a parts per thousand yen 25.0) based on their prepregnancy BMI. The association between maternal prepregnancy BMI and cesarean delivery was assessed using logistic regression models. Results A total of 915 women were included in the analysis. The proportion of cesarean section was 10.1%. Overall, 17.1% of the women were underweight while 6.0% were overweight. After adjusting for maternal age, smoking status, pregnancy complications, and infant birthweight, overweight women were 2.7 times more likely to have a cesarean delivery compared to normal weight women (adjusted odds ratio [adjusted OR] = 2.7, 95% confidence interval [CI] = 1.4-5.4), and underweight women were half as likely to have a cesarean delivery compared to normal weight women (adjusted OR = 0.5, 95% CI = 0.2-1.1). Conclusions Being overweight before pregnancy more than doubled the risk of cesarean delivery independent of age, smoking, pregnancy complications, and infant birthweight among term nulliparous women. Overweight Japanese women should be advised to achieve normal prepregnancy BMI in their preconception period to prevent cesarean delivery.
  • Kenta Okada, Michiaki Miyamoto, Kazuhiko Kotani, Hiroaki Yagyu, Junichi Osuga, Shoichiro Nagasaka, Shun Ishibashi
    Hospital practice (1995) 39(4) 70-75 2011年10月  査読有り
    Increased blood pressure (BP) and urinary protein (UP)/microalbuminuria are risk factors for cardiovascular disease in patients with diabetes. Although the management of BP in patients with diabetes should involve a multidisciplinary therapy, there are no reports in which modulators have been identified in an in-hospital diabetes education program. The aim of the present study was to investigate the change in BP levels in patients with type 2 diabetes mellitus (T2DM) during a short-term (2-week) in-hospital education program on lifestyle modifications. A total of 167 patients with T2DM (101 men, 66 women; mean age, 61.1 years; glycated hemoglobin, 9.2%) were divided into 2 groups on the basis of their urinary albumin levels: 1 group without UP (urinary albumin level < 30 mg/day) and 1 group with UP (urinary albumin level ≥ 30 mg/day). We defined efficacy in reducing BP as a 20-mm Hg reduction in systolic BP (SBP) and a 10-mm Hg reduction in diastolic BP, and compared the changes between the 2 groups. Although the group with UP had higher SBP levels than the group without UP at baseline, this difference disappeared at the end of the program. Adjusted multivariate logistic regression analysis showed that UP at baseline was associated with a reduction in SBP (odds ratio, 3.361; 95% confidence interval, 1.29-8.79; P = 0.013). The data suggest that UP may be a marker related to the management of SBP through lifestyle modifications in patients with T2DM.
  • Kazuhiko Kotani, Nobuyuki Taniguchi
    Journal of Clinical Medicine Research 3(5) 247-251 2011年10月  査読有り筆頭著者責任著者
    BACKGROUND: The association between the oxidative status and metabolic syndrome (MetS) should be studied in various populations with various oxidative stress-related markers. The aim of this cross-sectional study was to investigate the association between oxidative status, as assessed by the reactive oxygen metabolites (d-ROMs) test, and MetS in asymptomatic Japanese men, in relation to age. METHODS: The serum d-ROMs levels were measured in cardiovascular disease-free, non-smoking, non-medicated males (n = 140), who were divided into groups as follows: Group 1, < 60 years (n = 75, mean age 46 ± 9 [SD] years), and Group 2, ≥ 60 years (n = 65, mean 68 ± 6 years). The MetS was determined by the NCEP-ATP recommendations with minor modifications for a Japanese population. RESULTS: There was no significant difference in the d-ROMs levels between the subjects with and without MetS in Group 2 (≥ 60 years), but the subjects with MetS (n = 38, 324 ± 59 U. Curr.) exhibited significantly higher d-ROMs levels than those without MetS (n = 37, 290 ± 49 U. Curr., P < 0.01) in Group 1 (< 60 years). These differences did not change even after adjustments for basic confounders. CONCLUSIONS: These results suggest that oxidative status, as assessed by the d-ROMs, can be enhanced among asymptomatic younger, but not older, Japanese males with MetS. Further studies are required to establish the observed associations. KEYWORDS: Oxidative stress; Reactive oxygen species; D-ROMs; Obesity; Metabolic syndrome.
  • Kazuhiko Kotani, Russell Caccavello, Naoki Sakane, Toshiyuki Yamada, Nobuyuki Taniguchi, Alejandro Gugliucci
    Journal of Clinical Medicine Research 3(5) 252-257 2011年10月  査読有り筆頭著者責任著者
    BACKGROUND: Inflammation, often accompanied by oxidation, caused by advanced glycation end products (AGEs) may be quenched by the soluble receptor for AGEs (sRAGE). The present study aimed to investigate the influence of physical activity on circulating sRAGE, and the association between changes of circulating sRAGE and paraoxonase1 (PON1) activity (as an antioxidative enzyme) in a physical activity intervention study on an elderly subject cohort. METHODS: Serum sRAGE, PON1 activity and cardiometabolic variables were measured in 30 community-dwelling asymptomatic Japanese volunteers (15 men/15 women, mean age 65 years) in the pre- and post-phase of a 6-month interventional program designed to increase physical activity. RESULTS: The body mass index and sRAGE levels (1103 ± 496 to 1030 ± 437 ng/L, P < 0.05) were significantly reduced during the intervention period. In addition, the change of sRAGE was significantly and inversely correlated with that of PON1 activity, independent of the other cardiometabolic variables (β = - 0.511, P < 0.01). CONCLUSIONS: This study showed a reduction of sRAGE levels, and an inverse correlation between sRAGE and PON1 activity, after the intervention study increasing physical activity on an elderly population. These findings represent a modest but significant modulation of sRAGE by this type of exercise intervention, which warranted future studies on the clinical relevance of sRAGE changes in physical activity. KEYWORDS: AGEs; RAGE; Paraoxonase1; Exercise; Atherosclerosis.
  • Kotani K, Kimura S, Gugliucci A
    J Physiol Biochem 67(3) 437-441 2011年9月  査読有り筆頭著者責任著者
  • Kazuhiko Kotani, Noriko Asahara-Satoh, Yasuhisa Kato, Rika Araki, Akihiro Himeno, Hajime Yamakage, Kazunori Koyama, Makito Tanabe, Mariko Oishi, Taiichiro Okajima, Akira Shimatsu
    Journal of Clinical Lipidology 5(5) 395-400 2011年9月  査読有り筆頭著者責任著者
    Background: Although the circulating levels of remnant-like particle cholesterol (RLP-C) or serum amyloid A-low-density lipoprotein (SAA-LDL) can individually be increased in subjects with metabolic syndrome (MetS), the correlation between the two markers has not yet been previously studied. In the present study, we aimed to investigate the correlation between RLP-C and SAA-LDL in obese subjects with MetS in comparison to those without MetS. Methods: A total of 436 obese subjects were divided into groups with MetS and without MetS (male/female 75/143, mean age 49 years, current smokers 16% in both groups) by applying the age-, gender-, and smoking habit-matching method based on the database in the multicenter Japan Obesity and Metabolic Syndrome Study (JOMS). The data, including RLP-C and SAA-LDL, were compared in each group. Results: Significantly greater levels of RLP-C or SAA-LDL were observed in subjects with MetS in comparison with those without MetS. There was a significantly positive correlation between RLP-C and SAA-LDL, with a relatively greater correlation in subjects with MetS (coefficient = 0.290, P &lt .01) in comparison with those without MetS (coefficient = 0.181, P &lt .01). Multivariate-adjusted correlation analyses showed a greater correlation between RLP-C and SAA-LDL in subjects with MetS, relative to those without MetS, although the significant correlation decreased in both groups when the hypertriglyceridemic states were taken into account. Conclusions: A relatively greater and positive correlation between greater levels of RLP-C and SAA-LDL in obese subjects with MetS, in comparison with those without MetS, may be linked to the development of MetS-related cardiovascular disease. © Georg Thieme Verlag KG Stuttgart · New York.
  • K. Kotani, S. Kimura, E. Kinugasa, H. Ogata, R. Caccavello, N. Taniguchi, A. Gugliucci
    Journal of International Medical Research 39(4) 1541-1545 2011年8月  査読有り筆頭著者責任著者
    This study investigated the association between ischaemia-modified albumin (IMA), a biomarker of cardiac ischaemia, and increases in the levels of intermediatedensity lipoprotein (IDL), an atherogenic particle that can cause oxidative stress, in haemodialysis patients with end-stage renal disease (ESRD). Fasting levels of serum IMA and lipids/lipoproteins were analysed in 15 patients and 15 healthy control subjects. There was a close positive correlation between IMA and IDL levels in ESRD patients but no significant correlation between IMA and lipids/lipoproteins in control subjects. This suggests a possible link between the characteristic dyslipo - proteinaemia found in ESRD and levels of IMA and, if confirmed in studies with larger sample sizes, may lead to further studies on the potential of the relationship between IMA and IDL as a biomarker in haemodialysis patients with ESRD. © 2011 Field House Publishing LLP.
  • Kiyoka Omoto, Mikihiko Kawano, Toshiyuki Yamada, Nobuyuki Taniguchi, Kei Konno, Yasutomo Fujii, Kazuhiko Kotani, Harumi Koibuchis, Hiroaki Matsunaga
    Rinsho Byori. The Japanese journal of clinical pathology 59(8) 776-780 2011年8月  査読有り
    To foster work-ready general physicians, Jichi Medical University has developed various clinical teaching practices since its foundation. The educational courses for clinical laboratory medicine, being one of them, adopt practical trainings in ultrasonography, which is essential in practical medicine today. The aims and the specifics of the trainings adopted in the seminar of ultrasound and the required or the optional subjects of Bedside Learning (BSL) at Jichi Medical University are reported.
  • Michiaki Miyamoto, Kazuhiko Kotani, Kei Konno, Toshiyuki Yamada, Shun Ishibashi, Nobuyuki Taniguchi
    Rinsho Byori. The Japanese journal of clinical pathology 59(7) 643-648 2011年7月  査読有り責任著者
    The clinical significance of the diameter of common carotid artery (CCA) measured ultrasonographically has not been sufficiently established. The object of this cross-sectional study was to investigate the relationship of the ultrasonic CCA diameter with coronary artery disease (CAD). In the male patients (n=169, mean age: 61 years) who had no apparent carotid arterial stenosis and cerebrovascular disease, a history of CAD, current smoking, body mass index, blood pressure, hemoglobin A1c, serum low-density-lipoprotein cholesterol, estimated glomerular filtration rate and ultrasonic measures of CCA diameter were analyzed. A total of 25 patients had a history of CAD (15%). The CCA diameters of patients with CAD were significantly higher than those of patients without CAD (7.9 +/- 1.0 mm and 7.4 +/- 0.9 mm; p = 0.01). Receiver operating characteristic curve of boundary value of CCA diameter revealed an area under the curve to identify the patients with CAD (0.63, p = 0.04). When the cut off value was considered 8.5 mm, the odds ratio was 4.50 (95% confidence interval = 1.71-11.84, p < 0.01), and the ratio were not largely altered in multivariate logistic regression analyses. The CCA diameter may therefore serve as a useful predictive marker for CAD in men.
  • Kazuhiko Kotani, Naoki Sakane
    Korean Journal of Laboratory Medicine 31(3) 162-166 2011年7月1日  査読有り筆頭著者責任著者
    Background: Circulating leptin:adiponectin ratio (L: A) is a potential surrogate marker for cardiometabolic diseases however, the relationship of the L: A with the occurrence of metabolic syndrome (MetS) has not yet been fully explored in the general Japanese population. Methods: We enrolled 678 Japanese subjects (208 men and 470 women, mean age: 58.8 ± 14.4 [SD] yr mean body mass index: 23.6 ±3.3 kg/m 2) in this study, and determined their MetS status by using the National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP) recommendations with minor modifications for the Japanese population. Biochemical markers such as leptin and adiponectin present in blood were measured.The statistical analyses performed were gender-based. Results: The L:A in subjects with MetS was significantly higher than that in subjects without MetS, regardless of gender. The L: A also showed a significant and gradual increase corresponding to the increase in the number of components of MetS present in both the genders (trend P &lt 0.01 ).The cut-off level of the L: A to detect MetS was 0.59 (sensitivity: 0.72, specificity: 0.70) in men and 1.04 (sensitivity: 0.72, specificity: 0.69) in women. Conclusions:These results suggest that the L: A can serve as a clinically useful marker for detecting MetS characteristics in the general Japanese population.The clinical application of this laboratory index for detecting MetS should be assessed in future studies.
  • Umabiki M, Kotani K, Tsuzaki K, Higashi A, Sakane N
    Endocr J 58(4) 323-324 2011年4月  査読有り
  • Narumi Nagai, Naoki Sakane, Kazuhiko Kotani, Taku Hamada, Kokoro Tsuzaki, Toshio Moritani
    Nutrition research (New York, N.Y.) 31(4) 255-261 2011年4月  査読有り
    Uncoupling protein 1 (UCP1) plays an important role in thermogenesis in brown adipose tissue. Previously, we reported an association between -3826 A/G single-nucleotide polymorphism (SNP) in the promoter of UCP1 gene and lower thermogenesis in young women, suggesting this SNP has an adverse effect on the regulation of energy balance. Based on the hypothesis that this SNP (G allele) may have resistance against diet-induced weight loss, we examined its effects on anthropometric and metabolic responses to short-term, controlled-energy diet in young women. Seventeen lean women (20.9 ± 0.2 years; body mass index, 22.1 ± 0.5 kg/m(2)) were fed a controlled-energy diet (5.0 MJ/d, 62% carbohydrate, 19% protein, and 19% fat) administered by dietitians for 2 weeks. Clinical measurements were determined at baseline and after the dietary intervention. The subjects' physical activity was obtained using pedometers and self-reporting. The thermoregulatory sympathetic nervous system was evaluated using heart rate variability power spectral analysis. Upon the completion of the intervention, subjects were genotyped using an allele-specific DNA primer assay and results compared with their clinical measurements focusing on with or without the G allele. After dietary intervention, G allele subjects (A/G + G/G, n = 10) showed significantly smaller changes in body weight, body mass index, and waist circumference compared with A/A genotype subjects (n = 7). Similar changes were observed in parameters regarding glucose or lipid metabolism in both groups. These results suggest that the UCP1 gene -3826 G allele may result in smaller weight loss after a short-term, controlled-energy diet in young, lean women.
  • Harumi Koibuchi, Yasutomo Fujii, Kazuhiko Kotani, Kei Konno, Hiroaki Matsunaga, Michiaki Miyamoto, Nobuyuki Taniguchi
    Journal of Medical Ultrasonics 38(2) 97-100 2011年4月  査読有り
    The aim of this study was to clarify the degree of degradation of ultrasonic probes that results from their disinfection with alcohol. No defect in the ultrasound beams was found in any of the probes, but a significant decrease of the brightness was found after a certain period of use of the linear-type probe. Disinfection with alcohol may degrade ultrasound probes despite its high degree of effectiveness in preventing iatrogenic bacterial transmission. © 2010 The Japan Society of Ultrasonics in Medicine.
  • Kazuhiko Kotani, Satoshi Kimura, Ichiro Komada, Naoki Sakane, Alejandro Gugliucci
    Primary Care Respiratory Journal 20(3) 336-337 2011年3月22日  査読有り筆頭著者責任著者
    Nasal continuous positive air pressure (nCPAP) treatment may favourably affect serum levels of advanced glycation end products (AGEs) in patients with obstructive sleep apnoea syndrome (OSAS). At baseline, OSAS patients had significantly higher levels of AGEs than controls. Six months after nCPAP initiation, AGEs decreased significantly. nCPAP treatment could lower AGEs in patients with OSAS. © 2011 Primary Care Respiratory Society UK.
  • Noriko Satoh-Asahara, Takayoshi Suganami, Takafumi Majima, Kazuhiko Kotani, Yasuhisa Kato, Rika Araki, Kazunori Koyama, Taiichiro Okajima, Makito Tanabe, Mariko Oishi, Akihiro Himeno, Shigeo Kono, Akira Sugawara, Masakazu Hattori, Yoshihiro Ogawa, Akira Shimatsu
    Clinical Journal of the American Society of Nephrology 6(2) 265-273 2011年2月1日  査読有り
    Background and Objectives: Obesity and metabolic syndrome (MS) increase the risk of cardiovascular disease (CVD), chronic kidney disease (CKD), and all-cause mortality. Serum cystatin C (S-CysC), a marker of GFR, has been shown to be associated with CVD and CKD. This study was designed to elucidate the association of urinary CysC (U-CysC), a marker of renal tubular dysfunction, with CVD and CKD risk factors in patients with obesity and MS. Design, setting, participants, &amp measurements: The U-CysC-creatinine ratio (UCCR) was examined in 343 Japanese obese outpatients enrolled in the multi-centered Japan Obesity and Metabolic Syndrome Study. Results: UCCR was positively correlated with urine albumin-creatinine ratio (UACR) and S-CysC and negatively correlated with estimated GFR (eGFR). Among obese patients, UCCR was significantly higher in MS patients than in non-MS patients. UCCR had significant correlations with the number of components of MS and arterial stiffness, all of which are CVD predictors, similarly to UACR (P &lt 0.05). Interestingly, diet- and exercise-induced weight reduction for 3 months significantly decreased only UCCR among all of the renal markers examined (P &lt 0.01), in parallel with the decrease in BMI, HbA1c, and arterial stiffness, suggesting the beneficial effect of weight reduction on renal tubular dysfunction. Conclusions: This study demonstrates that UCCR is significantly associated with renal dysfunction, the severity of MS, arterial stiffness, and weight change in obese patients. The data of this study suggest that UCysC could serve as a CVD and CKD risk factor in patients with obesity and MS. Copyright © 2011 by the American Society of Nephrology.
  • Naoki Sakane, Juichi Sato, Kazuyo Tsushita, Satoru Tsujii, Kazuhiko Kotani, Kokoro Tsuzaki, Makoto Tominaga, Shoji Kawazu, Yuzo Sato, Takeshi Usui, Isao Kamae, Toshihide Yoshida, Yutaka Kiyohara, Shigeaki Sato, Hideshi Kuzuya
    BMC public health 11(1) e40 2011年1月17日  査読有り
    BACKGROUND: A randomized control trial was performed to test whether a lifestyle intervention program, carried out in a primary healthcare setting using existing resources, can reduce the incidence of type 2 diabetes in Japanese with impaired glucose tolerance (IGT). The results of 3 years' intervention are summarized. METHODS: Through health checkups in communities and workplaces, 304 middle-aged IGT subjects with a mean body mass index (BMI) of 24.5 kg/m2 were recruited and randomized to the intervention group or control group. The lifestyle intervention was carried out for 3 years by public health nurses using the curriculum and educational materials provided by the study group. RESULTS: After 1 year, the intervention had significantly improved body weight (-1.5 ± 0.7 vs. -0.7 ± 2.5 kg in the control; p = 0.023) and daily non-exercise leisure time energy expenditure (25 ± 113 vs. -3 ± 98 kcal; p = 0.045). Insulin sensitivity assessed by the Matsuda index was improved by the intervention during the 3 years. The 3-year cumulative incidence tended to be lower in the intervention group (14.8% vs.8.2%, log-rank test: p = 0.097). In a sub-analysis for the subjects with a BMI > 22.5 kg/m2, a significant reduction in the cumulative incidence was found (p = 0.027). CONCLUSIONS: The present lifestyle intervention program using existing healthcare resources is beneficial in preventing diabetes in Japanese with IGT. This has important implications for primary healthcare-based diabetes prevention. TRIAL REGISTRATION NUMBER: UMIN000003136.
  • Vanavanan Somlak, Chaloeysup Sirirat, Kotani Kazuhiko, Srisawasdi Pornpen
    Journal of Electrophoresis 55(1) 23-29 2011年1月  査読有り
    Background/aim: Electrophoresis is useful for examining the lipoprotein fraction patterns. A simultaneous and cost-effective addition of cholesterol levels in each lipoprotein fraction to the lipoprotein patterns can more assist clinical decision-making. This study' aim was to develop the formulas for estimating the fractionated lipoproteins cholesterol levels in a recent system, the agarose gel Sebia HYDRAGEL LIPO+Lp(a) electrophoresis. Methods: Serum samples were analyzed by two Sebia electrophoresis, HYDRAGEL LIPO+Lp(a) and the quantitative HYDRAGEL LDL/HDL-CHOL Direct methods. The formulas for estimation of relative cholesterol (%) of individual lipoprotein fractions were developed using linear regression models. Thereafter, the calculated lipoproteins cholesterol values by multiplying the relative cholesterol with total cholesterol concentrations were compared with the standardized enzymatic assayed values. Results: The equations for calculating % relative cholesterol (y) from % relative lipoprotein (x) were y=x-8, x+21 and 0.75x-6.5 for high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) fractions, respectively. Regression statistics obtained between the calculated assays (y) and the standardized enzymatic assays (x') in samples with and without Lp(a) were y=1.07x'- 0.18 and 1.06x'-0.06, respectively for HDL-cholesterol, y=0.90x'+0.32 and 0.92x'+0.29 for LDL-cholesterol, and y=0.85x'-0.03 and 0.95x'+0.02 for VLDL-cholesterol. Conclusions: The proposed formulas can provide a reliable estimation of cholesterol levels in each major lipoprotein fraction by the HYDRAGEL LIPO+Lp(a) electrophoresis. Further studies with its application are needed.<br>
  • Taku Hamada, Kazuhiko Kotani, Narumi Nagai, Kokoro Tsuzaki, Yoshiko Sano, Yukiyo Matsuoka, Mami Fujibayashi, Natsuki Kiyohara, Seitaro Tanaka, Makiko Yoshimura, Kahori Egawa, Yoshinori Kitagawa, Yoshinobu Kiso, Toshio Moritani, Naoki Sakane
    Nutrition (Burbank, Los Angeles County, Calif.) 27(1) 34-39 2011年1月  査読有り
    OBJECTIVE: Genetic polymorphisms of the renin-angiotensin system have been implicated in cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 3123C/A polymorphism of the angiotensin II type 2 receptor (AT(2)R) gene affect blood pressure and other obesity-related metabolic changes in response to low-energy diets using meal replacement shakes for weight loss. METHODS: Clinical, metabolic, and biochemical profiles were measured before and after a 2-mo intervention in 32 obese women (age 49.9 ± 8.4 [SD] y; BMI 28.4 ± 3.3 kg/m²) restricted to 1200 kcal/d (5021 kJ/d). The polymorphisms were determined with an intercalater-mediated FRET probe assay system. RESULTS: Although weight loss and nutrient intake levels did not differ among the genotypes, the reduction in body fat after weight loss was significantly less in the ACE deletion/deletion (D/D) genotype than insertion/insertion (I/I) plus I/D genotype (-2.25 ± 1.40% versus -0.80 ± 1.57%, P < 0.05). The AT₂R A/A group had significantly less improved levels of systolic blood pressure (-7.23 ± 8.50 versus 2.50 ± 12.6 mmHg, P < 0.05), low-density lipoprotein-cholesterol (-0.36 ± 0.29 versus -0.09 ± 0.25 mmol/L, P < 0.05), carbohydrate (-54.4 ± 27.2 versus -31.8 ± 16.3 mg/min, P < 0.05) and fat oxidation (8.31 ± 11.86 versus 0.05 ± 9.99 mg/min, P < 0.05) than the C/C plus C/A genotypes. CONCLUSION: The present findings suggest that the homozygous form of the ACE gene may hinder the improvement of body fat and that the homozygous form of the AT₂R gene may make improving systolic blood pressure and some obesity-related metabolic parameters through a dietary intervention difficult among obese women.
  • Kazuhiko Kotani, Russell Caccavello, Naoki Sakane, Michiaki Miyamoto, Alejandro Gugliucci
    Pharmacological Reports 63(5) 1248-1251 2011年  査読有り筆頭著者責任著者
    Ischemia-modified albumin (IMA) is considered to be a novel biochemical marker for ischemic and atherosclerotic conditions. This study aimed to investigate the influence of ezetimibe monotherapy on circulating IMAlevels in hypercholesterolemic patients. Atotal of 31 patients (mean age 65.7 years) received 10 mg of ezetimibe daily during a 12-week treatment period. The levels of lowdensity lipoprotein cholesterol and IMA were significantly reduced after ezetimibe treatment. The adjusted regression analyses revealed that the changes in the IMAlevels were not significantly correlated with those of the other atherosclerotic risk markers, such as body mass index, blood pressure, glucose and lipid panels. The significant reduction of the IMAlevels following ezetimibe treatment, which was independent of the reduction of low-density lipoprotein cholesterol levels, suggests that ezetimibe may improve the oxidative stress burden in hypercholesterolemic patients. Copyright © 2011 by Institute of Pharmacology Polish Academy of Sciences.
  • Kazuhiko Kotani, Shingo Yamada, Toshiyuki Yamada, Nobuyuki Taniguchi, Ikunosuke Sakurabayashi
    Lipids in Health and Disease 10 e174 2011年  査読有り筆頭著者責任著者
    Background: Oxidized lipoprotein(a) (oxLp(a)) can be a more potent marker of atherogenesis than native Lp(a), although Lp(a) is considered to be a risk factor for atherosclerotic diseases. Limited clinical data are available regarding the significance of oxLp(a) in atherosclerotic manifestations. This study aimed to investigate the association between the serum oxLp(a) and carotid artery intima-media thickness (CIMT), in comparison to the serum Lp(a) levels, among asymptomatic subjects. Methods. The atheroscrerosis-related variables including Lp(a) and oxLp(a) were measured in 136 cardiovascular disease-free subjects (61 males and 75 females, mean age of 64 years). The serum oxLp(a) level was quantified using a sandwich ELISA system. The CIMT level was ultrasonographically measured on bilateral carotid arteries. Results: The median level of Lp(a) was 120 mol/L, oxLp(a) was 0.06 nmol/L, and CIMT was 0.7 mm, respectively. A simple correlation test showed that the CIMT was significantly and positively correlated with age, systolic blood pressure and oxLp(a) (r = 0.208, P &lt 0.05). A multiple linear regression analysis revealed that oxLp(a) continued to show a significant and positive correlation with the CIMT ( = 0.202, P = 0.01). Although the similar analyses were conducted for Lp(a), it showed only a weak correlation with the CIMT (r = 0.011, = 0.041, both P &lt 0.05). Conclusions: These results suggest that oxLp(a) may be more closely associated with accelerated carotid atherosclerosis, in comparison to Lp(a), in this population. This finding can be important for obtaining a better understanding of the different atherogenic roles played by oxLp(a) in comparison to Lp(a). © 2011 Kotani et al licensee BioMed Central Ltd.
  • Kazuhiko Kotani, Naoki Sakane
    Polskie Archiwum Medycyny Wewnetrznej 121(7-8) 247-252 2011年  査読有り筆頭著者責任著者
    INTRODUCTION: Lipoprotein(a) [Lp(a)] is generally considered a risk factor for cardiovascular disease (CVD). The coexistence of Lp(a) and oxidative status may be associated with the pathophysiology of the Lp(a)-CVD linkage. OBJECTIVES: The aim of the present study was to investigate the correlation between Lp(a) and oxidative status using the diacron Reactive Oxygen Metabolite (d-ROM) test as an oxidative stress-related marker in asymptomatic subjects. PATIENTS AND METHODS: The serum levels of Lp(a) and d-ROM were measured in 322 subjects (male/ female 138/184 mean age 58.5 years) in addition to body mass index, blood pressure, glycemia, and lipid profile. RESULTS: The median levels of Lp(a) were 14.6 mg/dl (interquartile range 6.7-30.3) and the mean levels of d-ROM were 332 ±67 U. Carr. A simple linear regression analysis showed that the d-ROM level was significantly and positively correlated with Lp(a) (correlation coefficient = 0.22, P &lt 0.01). Multivariate-adjusted analyses confirmed this weak but significant correlation, independent of confounding variables. This correlation appeared to be relatively stronger in men than in women. CONCLUSIONS: A positive correlation between Lp(a) and oxidative status, as assessed by d-ROM, in this population may be partially associated with the Lp(a)-CVD relationship. Copyright by Medycyna Praktyczna, 2011.
  • Kazuhiko Kotani, Jui-Tung Chen, Nobuyuki Taniguchi
    Clinical and Investigative Medicine 34(3) E125-E130 2011年  査読有り筆頭著者責任著者
    Purpose: Menopause can affect the reportedly inverse association between adiponectin and blood pressure (BP) however, this relationship is still poorly understood. the present study cross-sectionally compared the relationship between adiponectin and BP in pre- and postmenopausal women. Methods: Healthy, asymptomatic women on no medication (n = 262) were divided into a premenopausal group (n = 125, mean age 44.7 years) and a postmenopausal group (n = 137, mean age 65.6 years). Fasting values of serum adiponectin and BP were measured, in addition to body mass index (BMI), blood glucose and lipids. The correlation between the levels of adiponectin/BMI and mean BP (MBP) was analyzed with a linear regression model for the respective groups. Results: the median adiponectin/BMI did not significantly differ between the pre- and postmenopausal groups (0.37 and 0.42, P = 0.08), and the premenopausal group had a significantly lower level of mean MBP than the postmenopausal group (87.6 and 100.7 mmHg, P &lt 0.001). In an unadjusted analysis, adiponectin/BMI was found to be significantly and inversely correlated with MBP in the premenopausal group (r = -0.499, P &lt 0.001) and the postmenopausal group (r = -0.203, P &lt 0.01), respectively. In a stepwise multivariate-adjusted analysis, adiponectin/BMI remained significantly, inversely and independently correlated with MBP in the premenopausal group (β = -0.383, P &lt 0.001), while no significant correlation was found between adiponectin/BMI and MBP for the postmenopausal group. Conclusions: the adiponectin-BP relationship appears to be associated with premenopausalstate. © 2011 CIM.
  • Alejandro Gugliucci, Eriko Kinugasa, Kazuhiko Kotani, Russell Caccavello, Satoshi Kimura
    Clinical Chemistry and Laboratory Medicine 49(1) 61-67 2011年1月  査読有り
    Background: The mechanism of paraoxonase 1 (PON1) atheroprotective remains elusive. The lactonizing/lactonase activity of PON1 is gaining favor as the most significant in physiology. Methods: We studied 42 end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) and 49 control subjects. We measured PON1 lactonase, arylesterase and triesterase activities by kinetic methods. Results: Serum lactonase activity was 11% lower in ESRD patients (p&lt 0.0001) and did not correlate with high-density lipoprotein (HDL) cholesterol when controlling for confounders. Lactonase activity was significantly higher after dialysis. Using a repeated measure-ANOVA adjusted for the confounders (age, gender, total cholesterol, triglyceride and HDL cholesterol) we show that the changes in lactonase after dialysis were significant (p&lt 0.0001). HD increases lactonase activity to levels indistinguishable from those of control subjects. In simple linear regression analyses we showed a significant inverse correlation between changes in lactonase and those of creatinine by dialysis (rs-0.339, ps0.028). Conclusions: ESRD patients maybe more susceptible to lipid peroxidation and to protein homocysteinylation than healthy subjects due to the decreased activity of lactonase. A lower serum lactonase activity would be coupled with delayed catabolism of oxidized phospholipids in low-density lipoprotein and oxidized macrophages, and with greater protein homocysteinylation, accelerating atherogenesis. One mechanism for lower lactonase activity in ESRD patients may be inhibition by uremic toxins and oxidative stress. The pathophysiology of reduced lactonase activity in uremia and the beneficial effects of HD need further investigation. © 2011 by Walter de Gruyter.
  • Michiaki Miyamoto, Kazuhiko Kotani, Shun Ishibashi, Nobuyuki Taniguchi
    Medical Principles and Practice 20(2) 187-190 2011年1月  査読有り責任著者
    Objective: The aim of this study was to investigate the relationship between metabolic risk factors and oxidative stress using urinary 8-hydroxydeoxyguanosine (8-OHdG), a recently utilized biological marker, in asymptomatic subjects. Methods: Ninety subjects (males/females = 30/60 mean age = 52 years), who were nonsmoking, nondiabetic and not on any medicine, were enrolled in the study. The body mass index, blood pressure, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and glucose as well as urinary 8-OHdG and creatinine were measured. Results: The median level of 8-OHdG was 9.3 ng/mg creatinine (interquartile range: 5.8-23.2). TG (Pearson's correlation: r = 0.262, p = 0.013) and HDL-C (r = -0.259, p = 0.014) showed a significant correlation with 8-OHdG. A multiple linear regression analysis adjusted for all the variables revealed that only TG had an independently significant and positive correlation with 8-OHdG (β = 0.231, p = 0.046). Conclusion: The data in this population suggest that, among metabolic risk factors, hypertriglyceridemia may be weakly but significantly associated with hyperoxidative stress as assessed by 8-OHdG. Copyright © 2011 S. Karger AG, Basel.
  • Kazuhiko Kotani, Naoki Sakane, Toshiyuki Yamada, Nobuyuki Taniguchi
    Clinical Chemistry and Laboratory Medicine 48(12) 1773-1776 2010年12月  査読有り筆頭著者責任著者
    Background: Cardiometabolic disorders including cardiovascular disease (CVD) where the relevance of regular coffee consumption is debatable, has been linked with the development of chronic kidney disease (CKD). A more recent study suggests that coffee consumption is associated with normal or increased kidney function as assessed by the estimated glomerular filtration rate (eGFR). The present study investigated whether the association between coffee and the eGFR was independent of chronic inflammation, and whether adding sugar to coffee could affect the eGFR. Methods: A total of 114 age- and gender-matched Japanese individuals (females/males=68/46, mean age=59.5 years), without CVD and severe CKD, were studied. Clinical variables, such as body mass index, blood pressure, blood glucose, lipids and high-sensitivity C-reactive protein (hsCRP), in addition to eGFR [the Modification of Diet in Renal Disease (MDRD) study equation], were measured. Results: Coffee drinkers had higher eGFR values [73.9±16.5 (SD) mL/min/1.73 m2] than non-coffee drinkers (68.6±11.7). The difference remained significant (F=5.04, p=0.027), independently of clinical variables, including hsCRP. The eGFR values among coffee drinkers were similar between the subjects with and without use of sugar. Conclusions: The association of coffee drinking habits to eGFR may occur independently of inflammation as assessed by hsCRP. The use of sugar may have no effect on GFR. Further research is needed to clarify this phenomenon. © 2010 by Walter de Gruyter Berlin New York.
  • Shuichi Tsuchida, Yutaka Yamada, Emiko Fukui, Tomohiro Kawada, Toshinori Omi, Asami Tsuchida, Toshinori Sako, Hitoshi Hatakeyama, Kazuhiko Kotani
    Journal of Veterinary Medical Science 72(12) 1609-1614 2010年12月  査読有り最終著者
    The chemokine (C-X-C) receptor 1 (CXCR1) expressed on the neutrophil surfaces interacts primarily with interleukin-8 (IL- 8) and has an important role in immune response. Two interesting single nucleotide polymorphisms (SNPs), SNP CXCR1+777G&gt C and SNP CXCR1-1768T&gt A, that exhibit an association with subclinical mastitis and milk quality in dairy cattle, respectively, have been reported in the bovine CXCR1 gene. The aim of this study was to demonstrate the presence of the two SNPs in the CXCR1 gene of Japanese Black cattle and examine the association between the SNPs and clinical diseases including intestinal and respiratory diseases in calves. Genotyping of the SNPs in healthy Japanese Black cattle showed that the SNPs were also present in Japanese Black cattle with gene frequencies of 0.37 and 0.15 for the C-type allele in SNP CXCR1+777 and for the A-type allele in SNP CXCR1-1768, respectively. Statistical analysis of the genotype distribution of the SNPs in the bovine CXCR1 gene in healthy and clinical intestinal or respiratory diseased Japanese Black cattle indicated no significant association of the SNPs with clinical diseases in the calves. However, a significant correlation of the number of A alleles in SNP CXCR1-1768 with white blood cell (WBC) and platelet counts was found in the disease group. It is possible that the SNP in the bovine CXCR1 gene plays a role in modulating the hematological profile of WBC and platelet counts.
  • Alejandro Gugliucci, Kazuhiko Kotani, Eriko Kinugasa, Ricardo Hermo, Russell Caccavello, Satoshi Kimura
    Annals of Clinical Biochemistry 47(6) 559-563 2010年11月  査読有り
    Background: Studies regarding aspirin metabolism can be important in patients with renal failure who have an increased risk of cardiovascular diseases. We undertook this study to assess the aspirin esterase (AE) status in end-stage renal disease (ESRD) patients. Methods: A total of 42 patients on long-term haemodialysis (HD) with a mean dialysis course of 6.1 y were recruited. Results: Serum AE levels were 44% lower and cholinesterase (ChE) levels were 22% lower in ESRD patients before dialysis as compared with control subjects (P = 0.0001). A very strong correlation was found between AE and ChE levels. AE levels increased on average 28% after dialysis with adjustments for age, gender, total cholesterol, triglyceride and high-density lipoprotein cholesterol (P = 0.002). In addition, ChE levels were significantly increased (48%) after dialysis (P = 0.0001). Changes in AE activity were significantly and positively correlated with those of ChE (r = 0.427, P = 0.005). When we adjusted for several confounders, we found that the changes in AE activity operated by dialysis are significant independently of age, gender, aspirin (ASA) intake, cholesterol, triglycerides, high-density lipoprotein cholesterol and ChE. Conclusions: We report that serum AE activity is significantly lower in ESRD and that treatment by HD results in an increase of activity. We confirm that AE is associated with lipid parameters and ChE. Our results show variations in ASA catabolism between the dialysis sessions, suggesting an oscillating pattern in ASA disposal in these patients. The mechanisms for reduced AE activity in uraemia and the effects of HD need further investigation.
  • Kokoro Tsuzaki, Kazuhiko Kotani, Yoshiko Sano, Shinji Fujiwara, Kaoru Takahashi, Naoki Sakane
    BMC Medical Genetics 11(1) e150 2010年10月21日  査読有り
    Background: The clock molecule plays major roles in circadian rhythmicity and regulating lipid and glucose metabolism in peripheral organs. Disruption of the circadian rhythm can lead to cardiometabolic disorders. The existence of small dense low-density lipoprotein (sdLDL) in the circulation, an abnormality of lipid metabolism, in part associated with lifestyle, is also one of risk parameters for cardiometabolic disorders. The 3111 T/C single nucleotide polymorphism (SNP) of the Clock gene has been reported to be associated with lifestyle including morning/evening preference. We investigated whether the Clock 3111 T/C SNP may affect lipids and lipoproteins including sdLDL.Methods: In 365 community-dwelling subjects (170 men and 195 women, mean age 63 ± 14 years), the 3111 T/C SNP was genotyped using a fluorescent allele-specific DNA primer assay system. The levels of sdLDL were measured with the electrophoretic separation of lipoproteins employing the Lipoprint system.Results: The frequency of the Clock 3111 C allele was 0.14. The area of sdLDL did not differ between the subjects with obesity and those without. In carriers of T/T homozygotes, the area of sdLDL was significantly higher compared with carriers of the C allele (T/C or C/C) (1.7 ± 3.4 vs. 0.8 ± 1.9% p &lt 0.05). A multiple regression analysis showed that the area of sdLDL was significantly and negatively correlated with the Clock 3111 T/C SNP (β = -0.114, p &lt 0.05), independently of age, sex, body mass index, and exercise habits.Conclusion: Our findings indicated that the Clock 3111 T/C SNP might be associated with the existence of sdLDL. © 2010 Tsuzaki et al licensee BioMed Central Ltd.
  • Yosikazu Nakamura, Takeshi Ito, Izumi Chihara, Atsuko Sadakane, Kazuhiko Kotani, Yasuko Aoyama, Ritei Uehara
    [Nihon koshu eisei zasshi] Japanese journal of public health 57(9) 807-815 2010年9月  査読有り
    PURPOSE: To reveal the epidemiologic features of suicides in Tochigi Prefecture using police data, and to discuss critical points to improve suicide prevention and advantages and disadvantages of police data. METHODS: Individual data for suicides during a 2 year period of 2007 and 2008 provided by the Tochigi Police were analyzed. RESULTS: In the observed 2 years, there were 1166 cases of suicide (865 males and 301 females), a higher rate per population in Tochigi than that for the whole of Japan. The age-specific number was highest in the 50's among males, whereas the numbers were similar between the 30's and 70's among females. The age-specific number per population was higher than that for the whole of Japan for individuals in their 20's and 30's. The number was highest in early morning at around 10 o'clock in the weekdays. Of all cases, 58.1% committed suicides at home, and 58.0% were by hanging. As causes of suicides, selected as the 3 most common by the police, health problems were top (61.3%), followed by economic (22.7%) and familial (17.3%) difficulties. With health problems, physical and mental diseases each accounted for approximately half. Those committing suicides because of the economic problems were dominantly males aged 20-69 years, many of whom had multiple debts. One third of the deceased cases left testamentary letters, and 15.9% had experiences of attempted suicide in the past. According to these results, we consider that the following 6 points are important to prevent suicides in Tochigi (1) improvement of school and occupational health targeting males aged 20 to 39 years; (2) persons at high risk should be kept always under close observation by someone such as a family member; (3) those having experience of attempted suicides should be formally treated as high risk persons; (4) consultation systems for various problems, especially for multiple debts, should be prepared and appropriately advertised; (5) mental health care should be provided for patients with physical disorders; and (6) treatment and management for patients with mental illness should be comprehensive. In addition, we noted that the causes of suicides in the police data were based on inferences of police officers investigating the suicide cases so that the validity was poorer than that of psychological autopsy. However, the advantage of the police data was that there was less selection bias because police data covered all the suicides in the area. CONCLUSIONS: Using police data, the epidemiologic features of suicide in Tochigi Prefecture could here be demonstrated, and guidelines for prevention are indicated. Utility of police data for revealing the epidemiologic features of suicides to provide information for suicide prevention was confirmed.
  • Kazuhiko Kotani, Noriko Satoh, Toshiyuki Yamada, Alejandro Gugliucci
    Clinical Lipidology 5(4) 489-495 2010年8月  査読有り招待有り筆頭著者責任著者
  • Shuumarjav Uurtuya, Kazuhiko Kotani, Hideki Yoshioka, Toshiyuki Yamada, Nobuyuki Taniguchi
    Ethnicity and Disease 20(3) 257-260 2010年6月  査読有り最終著者
    Objective: Atherosclerotic risk factors contribute to carotid atherosclerosis. Carotid intima-media thickness (IMT), as assessed using a non-invasive high-resolution ultrasound, can predict cardiovascular disease (CVD). Whereas the control of CVD is crucial for the Mongolian people, the studies on carotid atherosclerosis are lacking. The present population-based survey was a crosssectional investigation of the determinants of carotid IMT in the general Mongolian population. Methods: A total of 344 Mongolian volunteers, aged 18 to 69 years, without CVD and on no medication, were recruited from a health screening setting. The current smoking habits, body mass index, mean blood pressure (MBP), blood total cholesterol (TC), glucose, insulin and carotid IMT (maximum level) were measured. Results: Mongolian males had a significantly higher prevalence of current smoking and a higher level of IMT than females (average5 .58 mmin males vs .46 in females). Both a single and multiple regression analysis adjusted for all the measures revealed that IMT was significantly and positively correlated with age, male sex, MBP, TC and glucose among all of the participants. IMT was significantly and positively correlated with age, followed by MBP, TC and glucose among males, while among females, IMT was significantly and positively correlated with age, followed by MBP and TC. Conclusions: Age was the strongest determinant of carotid atherosclerosis, and the increases in blood pressure and cholesterol levels were also important measures in both sexes as well as glucose levels in males in particular, thus suggesting a preventive strategy for CVD in the general Mongolian population.
  • Kazuhiko Kotani, Seiji Adachi, Kokoro Tsuzaki, Naoki Sakane, Alejandro Gugliucci
    International Journal of Cardiology 141(2) 193-194 2010年5月28日  査読有り筆頭著者責任著者
  • Kazuhiko Kotani, Noriko Satoh, Toshiyuki Yamada
    European Journal of Internal Medicine 21(2) e10 2010年4月  査読有り筆頭著者責任著者
  • Mika Umabiki, Kokoro Tsuzaki, Kazuhiko Kotani, Narumi Nagai, Yoshiko Sano, Yukiyo Matsuoka, Kaori Kitaoka, Yukiko Okami, Naoki Sakane, Akane Higashi
    The Tohoku Journal of Experimental Medicine 220(4) 267-271 2010年4月  査読有り
    Leptin may influence sweet taste sensitivity. However, there are no reports on an association between the sweet taste threshold and serum leptin levels during weight loss in humans. We investigated the changes in the sweet taste threshold and the serum leptin levels during a weight-loss program, in connection with a leptin receptor polymorphism (Lys109Arg) that may be related to insulin and glucose metabolism. The study included 20 obese, but otherwise healthy, females (mean age: 55 +/- 7 years, body mass index: 26.1 +/- 1.7 kg/m(2)). Participants completed a 12-week weight-loss program based on energy restriction through diet and exercise, which aimed at achieving their optimal weight. The sweet taste threshold was determined according to the whole-mouth gustatory method. Genetic analyses were performed using the allele-specific DNA assay. Serum leptin levels were decreased from 9.2 +/- 4.5 to 7.9 +/- 4.9 ng/ml (p = 0.014) after body weight loss. The sweet taste threshold also decreased significantly from 0.59 +/- 0.42 to 0.22 +/- 0.20% in a solution of sucrose (p = 0.004). In contrast, there were no differences in changes of the threshold between participants with and without the Lys109 allele. A multiple regression analysis revealed that the changes in serum leptin levels were significantly correlated with those in the sweet taste threshold, independent of the initial threshold levels and the Lys109 allele. In conclusion, the serum leptin levels are decreased significantly during a weight-loss program in obese females, which may be associated with the decrease in the sweet taste threshold.
  • Shinji Fujiwara, Kazuhiko Kotani, Phillip J Brantley, Kokoro Tsuzaki, Yukiyo Matsuoka, Masayuki Domichi, Yoshiko Sano, Eiji Kajii, Naoki Sakane
    Asia Pacific Family Medicine 9(1) e6 2010年2月25日  査読有り
    BACKGROUND: Residents of rural communities are often more socially connected compared to urban dwellers. Using family and community support to motivate health behavior change may be useful in rural settings. The objective of this study was to pilot a salt reduction (SR) intervention for rural albuminuria patients using support from family and neighborhood residents compared to a usual care condition. The primary outcome was change in urine albumin-creatinine ratio (ACR). METHODS: All consecutive outpatients with an ACR >= 30 mg/gCr were recruited from the Koyadaira Clinic. Patients self-selected their participation in the intervention group (IG) or the control group (CG) because the rural population expressed concern about not being treated at the same time. In the IG, patients and their families were educated in SR for 30 minutes in their home by experienced dieticians. In addition, patients, families and neighborhood residents were also educated in SR for 2 hours at a public town meeting hall, with educational content encouraging reduction in salt intake through interactive activity. The CG received conventional treatment, and ACR and blood pressure (BP) were measured after 3 months. RESULTS: Of the 37 subjects recruited (20 male, 16 female, mean age; 72.8 +/- 9.2 years), 36 completed the 3-month follow up and were analyzed. In the IG, ACR decreased significantly from baseline (706 +/- 1,081 to 440 +/- 656; t = 2.28, p = 0.04) and was reduced compared to the CG (213 +/- 323 to 164 +/- 162; F = 3.50, p = 0.07), a treatment effect approaching significance. Systolic BP in the IG (145 +/- 14 to 131 +/- 13 mmHg; t = 3.83, p = 0.002) also decreased significantly compared to the CG (135 +/- 13 to 131 +/- 14; F = 4.40, p = 0.04). CONCLUSIONS: Simultaneous education of patients, their families and neighborhood residents may be important in rural areas for treatments and interventions requiring health behavior change. TRIAL REGISTRATION: UMIN000001972.
  • K. Tsuzaki, K. Kotani, S. Fujiwara, N. Sakane
    Diabetes Care 33(1) e11 2010年1月1日  査読有り
  • Kazuhiko Kotani, Nobuyuki Taniguchi
    Preventive Cardiology 13(3) 148 2010年  査読有り筆頭著者責任著者
  • Kazuhiko Kotani, Michiaki Miyamoto, Nobuyuki Taniguchi
    Current Hypertension Reviews 6(4) 251-253 2010年  査読有り筆頭著者責任著者
    Increased blood pressure and hypertension are a major atherosclerotic risk factor. Arterial stiffness is recognized to be reflective to the atherosclerotic states. The pulse wave velocity (PWV) is a noninvasive, simple, easy and reproducible index that can be used to assess arterial stiffness in association with blood pressure. The cardio-ankle vascular index (CAVI) has recently been developed to evaluate arterial stiffness similarly to PWV, but theoretically, this index is less influenced by blood pressure. There have been several clinical reports on the use of the CAVI in patients with hypertension. The CAVI levels are reported to be significantly and positively correlated with the ultrasonographical atherosclerotic parameters of carotid arteries, as a surrogate marker of atherosclerotic events, in hypertensive patients. Intervention studies of anti-hypertensive therapy using CAVI have shown that candesartan, olmesartan and efonidipine can improve the CAVI levels. These results suggest that the CAVI is clinically helpful for the assessment of atherosclerotic risk and the management with drug treatment in patients with hypertension. However, compared with PWV, there is not much evidence of using CAVI in a clinical setting future research is therefore necessary. © 2010 Bentham Science Publishers Ltd.
  • Kazuhiko Kotani, Toshiyuki Yamada, Nobuyuki Taniguchi
    Lipids in Health and Disease 9 e147 2010年  査読有り筆頭著者責任著者
    Background. Oxidized low-density lipoprotein (LDL) may act as an atheroprotective (anti-atherosclerotic) agent under some conditions. While the 1-antitrypsin (AT)-LDL complex is considered a type of oxidized LDL, its clinical relevance remains unknown. The aim of the present study was to investigate the association between AT-LDL and anti-atherosclerotic variables such as HDL-cholesterol and adiponectin in subjects with and without metabolic syndrome (MetS). Methods. In asymptomatic females (n = 194 mean age, 54 years) who were divided into non-MetS (n = 108) and MetS groups (n = 86), the fasting levels of serum AT-LDL, adiponectin and glucose/lipid panels were measured, in addition to body mass index (BMI) and blood pressure. Results. The MetS group showed significantly higher BMI, blood pressure, glucose and triglyceride levels as well as significantly lower levels of HDL-cholesterol and adiponectin than the non-MetS group. A multivariate-adjusted analysis revealed that in the non-MetS group, AT-LDL was significantly, independently and positively correlated with adiponectin (β = 0.297, P &lt 0.05), along with HDL-cholesterol (β = 0.217, P &lt 0.05). In the MetS group, AT-LDL was significantly, independently and positively correlated with LDL-cholesterol only (β = 0.342, P &lt 0.05). Conclusions. These data suggest that AT-LDL may exert anti-atherosclerotic effects in female subjects without MetS. More studies are required to clarify the clinical roles of AT-LDL in relation to the pathophysiology of MetS. © 2010 Kotani et al licensee BioMed Central Ltd.
  • Kenta Okada, Hiroaki Yagyu, Kazuhiko Kotani, Michiaki Miyamoto, Jun-ichi Osuga, Shoichiro Nagasaka, Shun Ishibashi
    Endocrine Journal 57(10) 903-908 2010年  査読有り
    To date, there are very few clinical reports that have compared the effects of ezetimibe on lipid parameters between hypercholesterolemic patients with and without type 2 diabetes mellitus (T2DM). In this study, we recruited patients for hypercholesterolemic groups with T2DM (n = 42 men/women = 24/18 HbA1c = 6.7 ± 5.4%) and without T2DM (n = 21 men/women = 7/14 HbA1c = 5.3 ± 0.4%). Patients were prescribed ezetimibe at a dose of 10 mg/daily for the course of the 12-week study. At baseline and after 12 weeks of treatment, several lipid parameters, including serum lowdensity-lipoprotein cholesterol (LDL-C), non-high-density-lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP), and cholesterol synthesis/absorption-related markers, were measured. Compared with those at the baseline, the levels of LDL-C, non-HDL-C, campesterol, and sitosterol were significantly reduced after 12 weeks of ezetimibe treatment in both groups. After adjusting for confounding factors, such as age, gender, smoking, and BMI, the levels of LDL-C and non-HDL-C displayed significantly greater reductions in the patients with T2DM (-25.1 ± 13.6% in LDL-C, -20.5 ± 11.2% in non-HDL-C) than those without T2DM (-20.5 ± 7.8% in LDL-C, P &lt 0.05 -17.4 ± 7.6% in non-HDL-C, P &lt 0.05). The reduction of the level of cholestanol was significantly and positively correlated with those of LDL-C and non-HDL-C in the patients with T2DM. Taken together, these findings indicate that ezetimibe could reduce the levels of atherogenic lipoproteins to a greater extent in hypercholesterolemic patients with T2DM than in those without T2DM. © The Japan Endocrine Society.
  • Yosikazu Nakamura, Mayumi Yashiro, Ryusuke Ae, Izumi Chihara, Atsuko Sadakane, Yasuko Aoyama, Kazuhiko Kotani, Ritei Uehara, Shohei Harada
    Journal of Epidemiology 20(6) 429-432 2010年  査読有り
    Background: Although regular nationwide surveys of Kawasaki disease (KD) are conducted in Japan, there is no system for detecting the real-time epidemic status of this disease. Methods: A web-based surveillance system for KD was developed. After consideration of the number of patients reported by prefecture to the 19th nationwide survey, 355 pediatric departments were asked to participate in the surveillance, and 225 agreed. Since January 2008, pediatricians in these 225 hospitals have reported KD patient data immediately after diagnosis. The daily numbers of patients are available to the public via the internet at http://www.kawasaki-disease.net/kawasakidata/. The validity of the data in 2008 was evaluated using the Japanese 20th nationwide survey of KD as the gold standard. Results: A total of 3376 patients were reported to the web-based surveillance system from the 1st week through 52nd week of 2008. The number of patients reported to the nationwide survey during the same period was 11 680: a total of 4950 patients from the hospitals participating in the web-based surveillance and 6730 from other hospitals. The epidemic curves were similar, and the correlation coefficient between the web-based surveillance and the total numbers in the nationwide survey was 0.806 (P &lt 0.01). Conclusions: The web-based surveillance system for Kawasaki disease in Japan demonstrated good validity. © 2010 by the Japan Epidemiological Association.
  • Kazuhiko Kotani, Noriko Satoh, Kazunori Yamada, Nobuyuki Taniguchi, Akira Shimatsu
    Journal of Physiological Anthropology 29(5) 157-160 2010年  査読有り筆頭著者責任著者
    Metabolic syndrome (MetS) and chronic kidney disease (CKD) are individual risk factors for cardiovascular disease (CVD). Abnormal hemorheology may be associated with CVD in both disorders. The present study investigated the impact of MetS and CKD on hemorheology. We studied 138 adults (women/men=63/75, mean age=52.2 years), who included 87 participants with MetS and 33 with CKD. The hemorheology was assessed by the index of 'whole blood passage time (WBPT)' using the Micro Channel array Flow ANalyzer (MC-FAN). The WBPT values of MetS participants were significantly higher than those of non-MetS participants (52.5±13.1 vs. 46.3±7.7 sec, p=0.03). The WBPT values of CKD participants were significantly higher than those of non-CKD (55.5±12.7 vs. 48.6±11.0 sec, p=0.003). The significant influence of MetS and CKD on WBPT was qualified by their effect modification to WBPT (p=0.04). There was a significantly greater influence of the combination of MetS and CKD on WBPT (59.9±13.4 sec) in comparison to the influence of non-MetS and CKD (46.6±3.5) or non-CKD and MetS (50.0±12.2). The influence of the combination of MetS and CKD was clearer in men, relative to women. Abnormal hemorheology as assessed using MC-FAN may be enhanced by the combination of MetS and CKD.
  • Kazuhiko Kotani, Shingo Yamada, Shuumarjav Uurtuya, Toshiyuki Yamada, Nobuyuki Taniguchi, Ikunosuke Sakurabayashi
    Lipids in Health and Disease 9 e103 2010年  査読有り筆頭著者責任著者
    Background. Oxidized lipoproteins play important roles in the atherosclerotic processes. Oxidized lipoprotein(a) (oxLp(a)) may be more potent in atherosclerotic pathophysiology than native Lp(a), a cardiovascular disease-relevant lipoprotein. Increased blood glucose concentrations can induce oxidative modification of lipoproteins. The aim of this study was to investigate the association between circulating oxLp(a) and cardiometabolic variables including blood glucose in healthy volunteers within the normal range of blood glucose. Methods. Several cardiometabolic variables and serum oxLp(a) (using an ELISA system) were measured among 70 healthy females (mean age, 22 years). Results. Lp(a) and glucose were significantly and positively correlated with oxLp(a) in simple correlation test. Furthermore, a multiple linear regression analysis showed oxLp(a) to have a weakly, but significantly positive and independent correlation with only blood glucose ( = 0.269, P &lt 0.05). Conclusions. These results suggest that increased glucose may enhance the oxidization of Lp(a) even at normal glucose levels. © 2010 Kotani et al licensee BioMed Central Ltd.
  • Michiaki Miyamoto, Kazuhiko Kotani, Hiroaki Yagyu, Harumi Koibuchi, Yasutomo Fujii, Kei Konno, Toshiyuki Yamada, Shun Ishibashi, Nobuyuki Taniguchi
    Journal of Physiological Anthropology 29(4) 149-152 2010年  査読有り責任著者
    We examined the relationship between the coefficient of variation in the R-R intervals (CVR-R) using electrocardiograms and the ultrasonic intima-media thickness (IMT) of the carotid artery, an atherosclerotic parameter, in type 2 diabetes mellitus (DM) patients with diabetic neuropathy (n=47, males/females: 29/18 mean age: 62 years). In this study, the CVR-R-related indexes, including CVR-R at rest (CVR-Rrest), CVR-R with deep breaths (CVR-Rbreath) and their difference (CVR-Rbreath minus CVR-Rrest: CVR-Rdif), were defined. Data such as body mass index, smoking habits, hemoglobin A1c, blood pressure, and serum low-density lipoprotein were collected. A significant inverse correlation was observed between max-IMT and CVR-Rdif (β=-0.34, p=0.042), but not CVR-Rrest or CVR-Rbreath, in multivariate analyses adjusted for all the data. Therefore, the CVR-Rdif may serve as a clinical index for the diabetic autonomic neuropathy-atherosclerosis relation in type 2 DM patients.
  • Kazuhiko Kotani, Satoshi Kimura, Tetsu Ebara, Russell Caccavello, Alejandro Gugliucci
    Diabetology and Metabolic Syndrome 2(1) e50 2010年  査読有り筆頭著者責任著者
    Background: Aspirin esterase (AE) activity can account for part of aspirin pharmacokinetics in the circulation, possibly being associated with the impairment of aspirin effectiveness as an inhibitor of platelet aggregation. Aims: The study was aimed at investigating the correlations of serum AE activity with cholinesterase (ChE) and metabolic variables in healthy subjects in comparison to subjects with type 2 diabetes mellitus (T2DM). Methods: In cardiovascular disease-free T2DM subjects and healthy controls, the AE activity levels and/or the correlation patterns between AE and the other variables were analyzed. Results: Neither AE nor ChE activities were higher in the subjects with T2DM. Serum AE activity strongly correlated with ChE as well as glucose/lipids variables such as total cholesterol and triglyceride in healthy subjects, while the correlations between AE and glucose/lipids variables were not present in T2DM subjects. Conclusions: These data may reflect the pathophysiological changes between healthy and T2DM subjects. Our data may thus provide the basis for future studies to unravel the mechanisms. © 2010 Kotani et al licensee BioMed Central Ltd.
  • Kazuhiko Kotani, Russell Caccavello, Ricardo Hermo, Toshiyuki Yamada, Nobuyuki Taniguchi, Alejandro Gugliucci
    International Journal of Medical Sciences 7(2) 90-93 2010年  査読有り筆頭著者責任著者
    OBJECTIVE: Metabolism of aspirin (acetylsalicylic acid), commonly used in older people for the prevention of cardiovascular disease, is important to the effectiveness of this drug. Whereas part of aspirin hydrolysis occurs in blood, there is a paucity of information in regards to circulating aspirin esterase activity in various physiological and pathological conditions. High aspirin esterase activity, corresponding to faster aspirin hydrolysis (thus aspirin non-responsiveness), may occur in cardiovascular disease-prone states. The objective of this study was to inv estigate the effects of cardio-metabolic variables such as cholesterol on serum aspirin esterase activity in older people who participated in an intervention study on physical activity. METHODS: A total of 18 non-medicated subjects (7 men/11 women, mean age 67.8 years, body mass index = 23.4 ± 3.3 kg/m2), who completed a 3-month interventional program for a mild-to-moderate increase in physical activity, were analyzed. The body mass index, plasma glucose, serum total cholesterol and aspirin esterase activity were measured in the pre- and post-interventional phases of the study. RESULTS: During the interventional period, the changes in aspirin esterase activity correlated significantly and positively with those of total cholesterol concentrations (r = 0.542, P = 0.020 β = 0.609, P = 0.035 in a multiple linear regression analysis after adjusting for all the measured variables). CONCLUSION: The results suggest that cholesterol metabolism alterations may be associated with aspirin metabolism in older people. © Ivyspring International Publisher.
  • Yosikazu Nakamura, Mayumi Yashiro, Ritei Uehara, Atsuko Sadakane, Izumi Chihara, Yasuko Aoyama, Kazuhiko Kotani, Hiroshi Yanagawa
    Journal of Epidemiology 20(4) 302-307 2010年  査読有り
    Background: The most recent epidemiologic features of Kawasaki disease (KD) are unknown. Methods: The 20th nationwide survey of KD was conducted in 2009, and included patients treated for the disease in 2007 and 2008. Hospitals specializing in pediatrics, and hospitals with pediatric departments and 100 or more beds, were asked to report all patients with KD during the 2 survey years. Results: From a total of 1540 departments and hospitals, 23 337 patients (11 581 in 2007 and 11 756 in 2008) were reported: 13 523 boys and 9814 girls. The annual incidence rates were 215.3 and 218.6 per 100 000 children aged 0-4 years in 2007 and 2008, respectively. These were the highest annual KD incidence rates ever recorded in Japan. The monthly number of patients peaked during the winter months smaller increases were noted in the summer months. The age-specic incidence rate showed a monomodal distribution with a peak at age 9-11 months. The prevalences of both cardiac lesions during the acute phase of the disease and cardiac sequelae were higher among infants and older age groups. Conclusions: The incidence rate and number of patients with KD in Japan continue to increase. © 2010 by the Japan Epidemiological Association.
  • Kazuhiko Kotani, Naoki Sakane, Michiaki Miyamoto, Kazunori Yamada, Nobuyuki Taniguchi
    Medical Principles and Practice 19(5) 415-417 2010年  査読有り筆頭著者責任著者
    Objective: To assess the influence of smoking on glycated albumin (GA) to hemoglobin A1c (HbA1c) ratio among type 1 diabetes mellitus (T1DM) patients. Subjects and Methods: Eighty-one T1DM patients (49 females, 32 males, mean age 48 ± 18 years) were recruited, and data concerning GA/HbA1c ratio and smoking were collected. Results: The median levels of GA and HbA1c were 23.3 and 7.4%, respectively. Independent of age, sex and/or body mass index, the GA/HbA1c ratio in smokers was significantly lower than that in nonsmokers (3.0 vs. 3.3, p &lt 0.05). Conclusion: The data suggest that smoking might affect the GA/HbA1c ratio among T1DM patients. © 2010 S. Karger AG.
  • Hiroaki Matsunaga, Kazuhiko Kotani, Nobuyuki Taniguchi
    Kidney and Blood Pressure Research 33(3) 209-212 2010年  査読有り責任著者
    Background/Aims: It is important to establishthe association between insulin resistance and renal function however, the reported associations differ across studies. Different underlying pathophysiologies of the studied populations may affect the associations. There have been no reports on the relationship between insulin resistance and renal function in the presence of hypertension (HT). We investigated the correlation between a homeostasis model assessment of insulin resistance (HOMA-IR) and the estimated glomerular filtration rate (eGFR) in subjects with and without HT. Methods: The study included 214 individuals (mean age: 65.6 years) who were nonmedicated and cardiovascular disease-free. Clinical variables, including blood pressure (BP), creatinine, glucose and lipid panels, were measured. Results: The HT group showed significantly higher levels of systolic/diastolic BP than the non-HT group. A multiple linear regression analysis revealed that the eGFR in the non-HT group was independently, significantly and inversely correlated with HOMA-IR, while the eGFR in the HT group was independently, significantly and inversely correlated with systolic BP, but not with HOMA-IR. Conclusions: A clearer correlation between HOMA-IR and eGFR was observed in the non-HT group than the HT group, suggesting that HT may attenuate the direct correlation between the insulin resistance and renal function indices. Copyright © 2010 S. Karger AG.
  • Shuumarjav Uurtuya, Kazuhiko Kotani, Nobuyuki Taniguchi, Hideki Yoshioka, Kazuomi Kario, Shun Ishibashi, Toshiyuki Yamada, Mikihiko Kawano, Nyamdavaa Khurelbaatar, Kouichi Itoh, Tserenkhuu Lkhagvasuren
    Journal of Atherosclerosis and Thrombosis 17(2) 181-188 2010年  査読有り責任著者
    Aim: Cardiovascular disease is becoming increasingly more problematic in Mongolia. The cardioankle vascular index (CAVI) and circulating C-reactive protein (CRP) are new atherosclerosis-related parameters, but no comparative studies of atherosclerotic parameters including CAVI and CRP are available between Mongolian and Japanese populations, such as disease populations of hypertension (HT) and diabetes mellitus (DM). Our study objective was to examine atherosclerotic profiles in HT and DM patients in both countries. Methods: From a hospital-based population, 156 Mongolian outpatients with HT and DM (men: 46%, mean age: 57.1 years) and 156 age- and sex-matched Japanese outpatients with HT and DM (men: 46%, age: 57.7) were recruited. Body mass index (BMI), heart rate (HR), blood pressure (BP), pulse pressure (PP), ankle-brachial index (ABI), ultrasonographic carotid intima-media thickness (IMT), blood total cholesterol (T-Cho), glucose, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were measured, in addition to CAVI and CRP. Results: The levels of BMI, HR, BP, PP, insulin and IMT were significantly higher and T-Cho and glucose were significantly lower in the Mongolian patients in comparison to the Japanese patients. Particularly, the levels of CAVI (mean ± SD) (8.1 ± 1.1 vs. 8.8 ± 1.2) and CRP (median [interquartile range]) (0.05 [0.03-0.12] vs. 0.19 [0.09-0.42] mg/dL) were significantly higher in Mongolian than Japanese patients. These significant differences remained unchanged, even after taking into account multiple variables, including BP and HOMA-IR. In addition, except for CAVI in the subgroup of DM, generally similar trends regarding atherosclerotic parameters were seen in the subgroup by sex and disease (HT, DM and HT plus DM). Conclusion: These findings suggest that Mongolian patients with HT and DM may be at higher risk for cardiovascular disease than Japanese patients.

MISC

 145

共同研究・競争的資金等の研究課題

 38