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

 501
  • Harumi Koibuchi, Kazuhiko Kotani, Nobuyuki Taniguchi
    Medical Ultrasonography 15(1) 41-44 2013年3月  査読有り
    Ultrasound probes are usually in a direct contact with the skin when used for detecting pathologic abnormalities. The probe could be a vector of bacterial transmission, but there have been few studies on this topic.We have made such studies, briefly reviewing 1)the conditions governing a possible bacterial transmission by probe, 2) the deterioration of an ultrasound probe by alcohol disinfection, 3) a suitable method for evaluating bacterial contamination of an ultrasound probe, and 4) the best procedure for decontaminating such probes. This paper ,may lead to a formal consideration of the relationship between ultrasound probes and their roles in bacterial transmission in clinical practice.
  • Shizukiyo Ishikawa, Kazuhiko Kotani, Kazuomi Kario, Kazunori Kayaba, Tadao Gotoh, Yosikazu Nakamura, Eiji Kajii
    THROMBOSIS RESEARCH 131(2) E54-E58 2013年2月  査読有り
    Introduction: Although lipoprotein(a) (Lp(a)) is involved in cardiometabolic disease processes, the association between serum Lp(a) and stroke and/or its subtypes has not yet been elucidated among Japanese people. This study investigated the association between Lp(a) and the incidence of stroke and/or its subtypes in the general Japanese population. Materials and Methods: This population-based prospective cohort study included 10,494 community-dwelling participants (4,030 males/6,464 females). The incidence of stroke and its subtypes was the primary outcome. The subjects were divided into tertiles based on their Lp(a) levels, and the risk of all stroke and stroke subtypes was examined using Cox's proportional hazard model. Results: A total of 393 subjects (199 males and 194 females) with stroke were identified during a follow-up duration of 10.7 years. The multivariate-adjusted hazard ratios for all stroke events were 0.55 (95% confidence interval: 0.38-0.81) and 0.69 (0.49-0.99) in the 2nd (9-19 mg/dl) and 3rd tertiles (>= 20 mg/dl) of Lp(a) in reference to the 1st tertile (<9 mg/dl) in males, and 0.85 (0.59-1.24) and 0.76 (0.52-1.11) in 2nd (10-22 mg/dl) and 3rd tertiles (>= 23 mg/dl) of Lp(a) in reference to the 1st tertile (<10 mg/dl) in females. The multivariate-adjusted hazard ratios for cerebral hemorrhage were 0.26 (0.10-0.67) and 0.34 (0.15-0.76) in the 2nd and 3rd tertiles of Lp(a) in reference to the 1st tertile in males, and were 0.48 (0.23-1.04) and 0.44 (0.21-0.96) in the 2nd and 3rd tertiles of Lp(a) in females. Conclusions: Lp(a) was associated with the incidence of cerebral hemorrhage in the general Japanese population, particularly among males, while a similar trend was seen among females. A low Lp(a) level may be a marker of the risk of cerebral hemorrhage in this population. (c) 2012 Elsevier Ltd. All rights reserved.
  • Naoki Sakane, Kazuhiko Kotani, Kaoru Takahashi, Yoshiko Sano, Kokoro Tsuzaki, Kentaro Okazaki, Juichi Sato, Sadao Suzuki, Satoshi Morita, Kazuo Izumi, Masayuki Kato, Naoki Ishizuka, Mitsuhiko Noda, Hideshi Kuzuya
    BMC public health 13 e81 2013年1月29日  査読有り
    BACKGROUND: Lifestyle modifications are considered the most effective means of delaying or preventing the development of type 2 diabetes (T2DM). To contain the growing population of T2DM, it is critical to clarify effective and efficient settings for intervention and modalities for intervention delivery with a wide population reach.The Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1) is a cluster randomized controlled trial to test whether goal-focused lifestyle coaching delivered by telephone can prevent the development of T2DM in high-risk individuals in a real-world setting. This paper describes the study design and recruitment of the study subjects. METHODS: For the recruitment of study subjects and their follow-up annually over 3 years, we employed health checkups conducted annually at communities and worksites. Health care divisions recruited from communities and companies across Japan formed groups as a cluster randomization unit. Candidates for the study, aged 20-65 years with fasting plasma glucose (FPG) of 5.6-6.9 mmol/l, were recruited from each group using health checkups results in 2006. Goal-focused lifestyle support is delivered by healthcare providers via telephone over a one-year period. Study subjects will be followed-up for three years by annual health checkups. Primary outcome is the development of diabetes defined as FPG≥7.0 mmol/l on annual health checkup or based on self-report, which is confirmed by referring to medical cards. RESULTS: Forty-three groups (clusters), formed from 17 health care divisions, were randomly assigned to an intervention arm (22 groups) or control arm (21 clusters) between March 2007 and February 2008. A total of 2840 participants, 1336 from the intervention and 1504 from the control arm, were recruited. Consent rate was about 20%, with no difference between the intervention and control arms. There were no differences in cluster size and characteristics of cluster between the groups. There were no differences in individual characteristics between the study arms. CONCLUSION: We have launched J-DOIT1, a nation-wide trial to prevent the development of T2DM in high-risk individuals using telephone-delivered intervention. This trial is expected to contribute to evidence-based real-world preventive practices. TRIAL REGISTRATION: UMIN000000662.
  • Alejandro Gugliucci, Russell Caccavello, Kazuhiko Kotani, Naoki Sakane, Satoshi Kimura
    Clinica Chimica Acta; international journal of clinical chemistry 415 162-168 2013年1月16日  査読有り
    BACKGROUND: We developed a practical method for analysis of PON-1 enzymatic activity in HDL subclasses. METHODS: The assay uses 4-12% polyacrylamide gradient gels, phenylacetate as substrate coupled with densitometric phenol detection using 4-aminoantipyrine. The measurement PON-1 activity in situ across the HDL subclasses has a strong correlation with the kinetic microplate assay for total PON-1 activity, r=0.91, p<0.001. RESULTS: The same HDL-C level, healthy subjects (n=33) display a large difference in the ratio of PON-1 activity in small vs. large HDL. Since PON-1 activity is larger in HDL(3) we propose that this difference has a potent predictive value for clinical risk assessment and therapeutic choice. Our method also offers the advantage of assessing the distribution of up to six different HDL apolipoproteins in the same gel after transfer. CONCLUSIONS: We seek to further dissect the cause of a different distribution of PON-1 activity in HDL subclasses by employing this method that permits practical, inexpensive analysis of antioxidant function of HDL subclasses and has the potential for application in clinical chemistry and to shed some light on the importance of PON-1 distribution.
  • Kazuhiko Kotani, Naoki Sakane
    Medical Principles and Practice : international journal of the Kuwait University, Health Science Centre 22(2) 189-193 2013年  査読有り筆頭著者責任著者
    OBJECTIVE: To investigate the correlation between gamma-glutamyltransferase (GGT) and remnant-like particle cholesterol (RLP-C) in dyslipidemic patients. SUBJECTS AND METHODS: General cardiometabolic variables, plus serum GGT and RLP-C levels, were measured in 118 dyslipidemic patients (59 males, mean age 58 ± 13 years). Correlation analyses of GGT with other variables, including RLP-C, were performed. RESULTS: The median levels (interquartile ranges) of RLP-C and GGT were 0.21 mmol/l (0.14-0.35) and 26 IU/l (17-39), respectively. A stepwise multiple regression analysis revealed an independent, significant and positive correlation between GGT and RLP-C (β = 0.351, p < 0.001), followed by male gender and BMI. CONCLUSION: There was a significant positive association between GGT and RLP-C, thereby indicating that the association between GGT and cardiovascular disease may be partly due to the interaction with RLP-C in dyslipidemic patients. Further research is therefore warranted to confirm the observed relationship.
  • Kazuhiko Kotani
    Journal of Epidemiology 23(1) 2-3 2013年  査読有り招待有り筆頭著者最終著者責任著者
  • Kazuhiko Kotani, Kokoro Tsuzaki, Shinji Fujiwara, Naoki Sakane
    Medical Principles and Practice : international journal of the Kuwait University, Health Science Centre 22(5) 510-512 2013年  査読有り筆頭著者責任著者
    OBJECTIVE: This study investigated the relationship between sleep adequacy and small dense low-density lipoprotein (sdLDL) in a Japanese population. SUBJECTS AND METHODS: Clinical data, including atherosclerotic risk factors, in addition to the mean LDL particle size (LDL-PS) measured by gel electrophoresis, were evaluated in 136 community-dwelling female subjects (40-80 years old). The sleep status was self-reported and the subjects were divided into those who had inadequate sleep (≤ 6 or ≥ 9 h of sleep) and had adequate sleep (7-8 h). RESULTS: The mean LDL-PS was significantly smaller in subjects with inadequate sleep [n = 68, 26.4 ± 0.4 (SD) nm] than in those with adequate sleep (n = 68, 26.6 ± 0.4 nm, p < 0.05). This difference remained significant and independent after adjusting for confounders (β = 0.15-0.19, p < 0.05). CONCLUSION: Sleep adequacy was associated with the presence of sdLDL, while the influence of the sleep status on LDL-PS was minor in this population. Further research on the associations among sleep, sdLDL and cardiovascular disease prevention is warranted.
  • Kenta Okada, Hiroaki Yagyu, Kazuhiko Kotani, Hisataka Yamazaki, Kazufumi Ozaki, Manabu Takahashi, Shuichi Nagashima, Jun-Ichi Osuga, Shun Ishibashi
    Endocrine Journal 60(7) 913-922 2013年  査読有り
    Postprandial hyperglycemia and/or hyperlipidemia can contribute to development of atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to compare the effects of miglitol and sitagliptin on postprandial glucose and lipid metabolism in patients with T2DM. Thirty-five patients with T2DM were randomized to 2 groups receiving miglitol (150 mg/day) or sitagliptin (50 mg/day). Serum variables related to glucose and lipid metabolism were measured before and after treatment for 10 weeks and at 0, 60, and 120 min using a cookie-loading test (CLT). After 10 weeks of treatment, miglitol (n = 16) and sitagliptin (n = 18) caused a similarly significant decrease in hemoglobin A1c (mean: 7.6% to 7.3% versus 8.0% to 7.6%) and a significant increase in fasting insulin levels, with a greater increase observed in the miglitol group than in the sitagliptin group (p=0.03). In addition, a significant decrease in the change in glucose levels after the CLT was observed in both groups, with a greater decrease observed in the miglitol group than in the sitagliptin group (p=0.02). The miglitol group also showed a greater decrease in the change in insulin levels after the CLT than the sitagliptin group (p<0.01). The lipid and lipoprotein levels did not show any significant differences between the groups after the CLT. Our results suggested that miglitol and sitagliptin treatment resulted in similar glycemic control but that a greater decrease in postprandial glucose and insulin levels was observed with miglitol compared with sitagliptin in patients with T2DM.
  • Michiaki Miyamoto, Kazuhiko Kotani, Kenta Okada, Akihiko Ando, Hideyuki Hasegawa, Hiroshi Kanai, Shun Ishibashi, Toshiyuki Yamada, Nobuyuki Taniguchi
    Journal of Atherosclerosis and Thrombosis 20(8) 678-687 2013年  査読有り責任著者
    AIM: The aim of this study was to investigate the relationship between atherosclerotic manifestations and brachial and radial arterial wall elasticity (AWE) measured using the phased tracking method in patients with type 2 diabetes mellitus (T2DM). METHODS: This study included T2DM patients (n= 220, mean age 59 years) without a history of stroke or coronary artery disease. The brachial AWE, radial AWE, carotid mean intima-media thickness (IMT), max-IMT and flow-mediated vasodilation (FMD) were measured. The patients were classified according to the number of atherosclerotic risk factors, including obesity, dyslipidemia and hypertension. Group 1 included T2DM patients only, group 2 included patients with two risk factors, group 3 included patients with three risk factors and group 4 included patients with four risk factors. The patients were also divided into two groups according to microangiopathic complications, including retinopathy and nephropathy. The between-group differences were analyzed. RESULTS: The brachial AWE (548, 697, 755 and 771 kPa for groups 1, 2, 3 and 4, respectively) and radial AWE (532, 637, 717 and 782 kPa for groups 1, 2, 3 and 4, respectively) significantly increased in association with an increasing number of risk factors. The brachial AWE and radial AWE were significantly higher in the patients with microangiopathic complications than in those without microangiopathic complications (brachial AWE 797 and 694 kPa and radial AWE 780 and 660 kPa, respectively). Receiver operating characteristic curve analyses revealed that, for brachial AWE and radial AWE, the area under the curve was equal to the max-IMT and higher than the mean-IMT and FMD. CONCLUSIONS: Upper limb AWE measurement can reflect the degree of atherosclerosis risk overload and may be useful for evaluating vascular complications in T2DM patients.
  • Tsogzolbaatar Enkh-Oyun, Kazuhiko Kotani, Dambadarjaa Davaalkham, Ritei Uehara, Atsuko Sadakane, Yasuko Aoyama, Satoshi Tsuboi, Yosikazu Nakamura
    Ethnicity & Disease 23(3) 363-368 2013年  査読有り
    OBJECTIVES: Although hypertension is the primary cause of morbidity and mortality from cardiovascular diseases in Mongolia, reviews about hypertension in this country have not been reported, to our knowledge. Information on the overview of this disease may be useful to establish measures and policy to prevent hypertension and its related complications. The aim of our article is to summarize the current situation vis-à-vis hypertension in Mongolia. METHODS: Population-based studies that provided relevant information on hypertension in Mongolia were searched through PubMed, abstract books of the Mongolian Medical University resources from cardiologists, epidemiological databases and reliable websites of national organizations. Available articles from 1970 to present were selected. RESULTS: A high prevalence of hypertension, which varied according to geographic location, exists among Mongolian people. The prevalence of hypertension may be influenced by nutritional factors, sedentary lifestyle, socioeconomic status and environmental factors in particular. CONCLUSIONS: The high prevalence of hypertension among Mongolian people can be a serious health problem in this country. Defining ethnic features of hypertension and related conditions will be the initial step that may lead to prevention of this disease. Further research and positive efforts to prevent hypertension appear necessary for Mongolians.
  • Yosikazu Nakamura, Eiko Aso, Mayumi Yashiro, Satoshi Tsuboi, Takao Kojo, Yasuko Aoyama, Kazuhiko Kotani, Ritei Uehara, Hiroshi Yanagawa
    Journal of Epidemiology 23(6) 429-434 2013年  査読有り
    BACKGROUND: The long-term outcomes of Kawasaki disease (KD) are unknown. METHODS: Fifty-two collaborating hospitals collected data on all patients who had received a new definite diagnosis of KD between July 1982 and December 1992. Patients were followed until December 31, 2009 or death. Standardized mortality ratios (SMRs) were calculated based on Japanese vital statistics data. RESULTS: Of the 6576 patients enrolled, 46 (35 males and 11 females) died (SMR: 1.00; 95% CI: 0.73-1.34). Among persons without cardiac sequelae, SMRs were not high after the acute phase of KD (SMR: 0.65; 95% CI: 0.41-0.96). Among persons with cardiac sequelae, 13 males and 1 female died during the observation period (SMR: 1.86; 95% CI: 1.02-3.13). CONCLUSIONS: In this cohort, the mortality rate among Japanese with cardiac sequelae due to KD was significantly higher than that of the general population. In contrast, the rates for males and females without sequelae were not elevated.
  • Kazuhiko Kotani, Toshiyuki Yamada, Alejandro Gugliucci
    BioMed Research International 2013 e481437 2013年  査読有り筆頭著者責任著者
    Paraoxonase 1 (PON1) and serum amyloid A (SAA) are proteins carried by high-density lipoprotein (HDL) particles. Among the HDL-associated protein molecules, SAA, an inflammation-related marker, and PON1, an antioxidant marker, tend to change in relatively clear opposite directions in physiological situations. In clinical chemistry, paired measurements of both markers may provide useful information to understand dysfunctional HDL in diseases with inflammation and oxidative stress conditions. Actually, limited clinical studies have suggested that the combined use of PON1 and SAA may be a tool for observing the pathophysiology of some disease entities. From the findings of experimental studies, PON1 appears to be cooperatively regulated by inflammation- and oxidative stress-related molecules linked with SAA regulation in humans. More studies remain to be performed to ascertain the value of paired measurements of both promising markers in clinical practice.
  • Naomi Hayashida, Misa Imaizumi, Hiroki Shimura, Noriyuki Okubo, Yasushi Asari, Takeshi Nigawara, Sanae Midorikawa, Kazuhiko Kotani, Shigeyuki Nakaji, Akira Otsuru, Takashi Akamizu, Masafumi Kitaoka, Shinichi Suzuki, Nobuyuki Taniguchi, Shunichi Yamashita, Noboru Takamura
    PLOS ONE 8(12) e83220 2013年  査読有り
    Due to the likelihood of physical and mental health impacts following the unprecedented accident at the Fukushima Dai-ichi Nuclear Power Plant, the Fukushima prefectural government decided to conduct the Fukushima Health Management Survey to assist in the long-term health management of residents. This included thyroid ultrasound examination for all children in Fukushima. For appropriate evaluation of ultrasound screening of the thyroid, it is important to understand its reference data of thyroid findings in children in general. In order to analyze the frequencies of specific thyroid findings, we conducted ultrasound screening of the thyroid by the same procedures as used in Fukushima in 4,365 children, aged 3 to 18 years, from three Japanese prefectures. Overall, thyroid cysts were identified in 56.88% and thyroid nodules in 1.65% of the participants. Thyroid cysts and nodules with a maximum diameter of more than 5 mm were identified in 4.58% and 1.01%, respectively, and age-adjusted prevalences were 3.82% and 0.99%, respectively. Although the prevalence of cysts and nodules varied among the examination areas, no significant differences were observed among the three examination areas in the prevalence of cysts and nodules with a maximum diameter of more than 5 mm. Also, the prevalence of thyroid cysts and nodules, especially those with a maximum diameter of more than 5 mm, significantly increased with age, and showed a female predominance. We also identified ectopic thymus (1.95%), diffuse goiter (1.40%), ultimobranchial body (0.73%), lymph node swelling (0.21%) and thyroid agenesis (0.05%). This is the first ultrasound description of the age-adjusted prevalence of thyroid cysts and nodules, or of the prevalence of abnormalities other than cysts and nodules, such as ectopic thymus, in relation to age, in the general Japanese child population. We contend that this can provide relevant information for the Fukushima Health Management Survey and future population studies.
  • Kazuhiko Kotani, Naoki Sakane, Nobuyuki Taniguchi
    Medical Principles and Practice 22(1) 65-69 2012年12月  査読有り
    Objective: The present study investigated the association between the angiotensin II type 2 receptor (AT2R) gene adenine/cytosine (A/C)-3123 polymorphism and cardiometabolic variables in subjects with and without hypertension. Methods: Cardiometabolic variables, in addition to genotyping by an allele-specific DNA assay, were measured in 161 asymptomatic community-dwelling Japanese women (age range 30-83 years). They were divided into hypertensive (n = 82, age 50-81 years) and nonhypertensive (n = 79, age 30-83 years) subjects. Results: The A-allele carriers (n = 53) showed significantly lower high-density lipoprotein cholesterol (HDL-C) levels than the non-A-allele carriers (n = 26) among nonhypertensive subjects (1.45 ± 0.38 vs. 1.66 ± 0.33 mmol/l, p = 0.02). Even when multiple-adjusted analyses were performed, the HDL-C levels continued to differ significantly and independently of other variables, including the body mass index and insulin resistance index, between A-allele and non-A-allele carriers. However, this association was not observed among hypertensive subjects. Conclusion: The present study demonstrated that A-allele carriers had significantly lower HDL-C levels than did non-A-allele carries among nonhypertensive women, while this association was not observed among hypertensive women. This indicates that the A/C3124 polymorphism may be a marker associated with HDL metabolism by hypertension. This was a small study, so further research is warranted to confirm the observed association. Copyright © 2012 S. Karger AG, Basel.
  • Jui-Tung Chen, Kazuhiko Kotani
    International Journal of Preventive Medicine 3(12) 893-896 2012年12月  査読有り最終著者
    Background: Oral contraceptive therapy (OCT) is associated with an increased risk of deep vein thrombosis, venous thromboembolism and stroke. However, the underlying mechanisms have not yet been elucidated. The objective of this study was to investigate the influence of OCT on blood levels of an oxidative stress maker in pre-menopausal women. Methods: Oxidative stress was determined in 87 pre-menopausal healthy women (24 with and 63 without OCT) using a blood assay for reactive oxygen metabolites (by the d-ROMs test). The subjects with OCT received a triphasic preparation consisting of ethinyl estradiol and norethisterone. Results: Subjects with OCT showed significantly higher d-ROMs levels (median: 380 interquartile range: 328-502 Carr U) than those without OCT (325 [271-369] P &lt 0.05). The results remained the same after adjusting for potential confounders. Conclusions: The use of OCT may increase oxidative stress levels, independent of traditional cardiovascular risk factors, in pre-menopausal women, providing new insights to the primary prevention of vascular complications in these subjects.
  • Kazuhiko Kotani, Russell Caccavello, Takako Mutou, Toshiyuki Yamada, Nobuyuki Taniguchi, Alejandro Gugliucci
    Australasian Journal on Ageing 31(4) 222-226 2012年12月  査読有り筆頭著者責任著者
    Aim: Considering the beneficial effects of physical activity on health and disease in older people, the aim of the present study was to investigate the changes in reactive oxygen metabolites and paraoxonase 1 (PON1) activity during an intervention period on increased physical activity among older people. Methods: Serum diacron reactive oxygen metabolites (d-ROMs), PON1 activity and cardiometabolic variables were measured in 43 asymptomatic Japanese volunteers (18 men/25 women, mean age 68.9 years) in the pre- and post-phase of a 6-month intervention program aiming at a mild but sustained increase in physical activity. Results: While the d-ROMs and PON1 activity levels were not significantly altered after the intervention, there was an inverse correlation between percentage changes of d-ROMs and PON1 activity during this intervention period. Multiple regression analysis revealed their significant and inverse correlation as independent of percentage changes of the other cardiometabolic variables (β=-0.3, P &lt 0.05). Conclusions: The inverse d-ROMs-PON1 relationship may indicate the value of concurrent measurement of these two components of oxidation-antioxidation balance when studying the effects of physical activity in an older population. Further studies are necessary to confirm the observed relationship. © 2012 The Authors. Australasian Journal on Ageing © 2012 ACOTA.
  • Kazuhiko Kotani, R. Caccavello, N. Taniguchi, A. Gugliucci
    Journal of International Medical Research 40(5) 1878-1883 2012年10月1日  査読有り筆頭著者責任著者
    OBJECTIVE: There is growing evidence that circulating soluble receptor for advanced glycation end products (sRAGE) exerts antiatherogenic effects as a decoy receptor that abolishes RAGE signalling. A previous study reported that oxidized low-density lipoprotein (oxLDL) can be one of the RAGE ligands. The present cross-sectional study investigated the clinical association between sRAGE and oxLDL in humans. METHODS: Serum levels of the conventional atherosclerotic risk factors, sRAGE and malondialdehyde-modified low-density lipoprotein (MDA–LDL) were analysed in asymptomatic subjects MDA–LDL was measured as a biomarker of oxLDL. RESULTS: Mean serum levels of sRAGE and MDA–LDL were 1101 ng/l and 57.6 IU/l, respectively, in 33 subjects of mean age 65 years. Simple linear regression analysis showed a significant inverse correlation between sRAGE and MDA–LDL. Stepwise multiple linear regression analysis confirmed MDA–LDL to be independently, significantly and inversely correlated with sRAGE. CONCLUSIONS: An independent, significant and inverse correlation was shown to exist between circulating levels of sRAGE and oxLDL (MDA–LDL), which suggests that part of the antiatherosclerotic effects of sRAGE may be related to oxLDL quenching.
  • Kazuhiko Kotani, Toshiyuki Yamada, Michiaki Miyamoto, Kazuomi Kario, Shun Ishibashi, Nobuyuki Taniguchi
    Heart and Vessels 27(5) 499-504 2012年9月  査読有り筆頭著者責任著者
    Chronic inflammation has received a great deal of attention due to the role it plays in cardiovascular disease (CVD). The cardio-ankle vascular index (CAVI) has recently been developed to evaluate arterial stiffness. This index is independent of blood pressure at the time that it is measured, making it a better measure for clinical studies on the prevention of CVD. Information on the association of serum amyloid A (SAA) with arterial stiffness in relatively healthy subjects is still scarce. The aim of the present study was to investigate the potential correlation between SAA and CAVI in asymptomatic Japanese subjects. In addition to SAA and CAVI, data on smoking status, body mass index, blood pressure, and serum/plasma biochemical indices such as glucose and total cholesterol were collected in 387 nonmedicated and CVD-free adult subjects during a health check examination (male/female 191/196, mean age 61.8 years). Among them, a randomly selected subgroup of 256 subjects (male/female 133/123, mean age 62.4 years) had a full dataset, including low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and hemoglobin A1c. Among the whole population, CAVI levels were significantly higher in males than in females [mean 8.5 ± (SD 1.1) vs. 8.2 ± 1.1, p &lt 0.05], while SAA levels were slightly but nonsignificantly higher in females than in males [median 6.4 (interquartile range 4.0-9.3) μg/mL vs. 5.1 (3.5-8.4)]. In a multiple linear regression analysis, CAVI was weakly but significantly, independently, and positively correlated with SAA (β-coefficient 0.200, p &lt 0.01). The results of the same analyses for the randomly selected subgroup were relatively similar to the findings for the whole population. SAA may be a positive inflammatory factor associated with arterial stiffness, and the clinical relevance and the biological mechanism for this relationship should be established in future studies. © Springer 2011.
  • Kazuhiko Kotani, Naoki Sakane, Masashi Ueda, Shinichi Mashiba, Yasuyuki Hayase, Kokoro Tsuzaki, Toshiyuki Yamada, Alan T. Remaley
    Clinica Chimica Acta 414 125-129 2012年9月1日  査読有り筆頭著者責任著者
    Background Oxidized high-density lipoprotein (oxHDL) has reduced capacity for cholesterol efflux and some of other anti-atherogenic properties of HDL, but the role of oxHDL in the pathogenesis of cardiometabolic disease has not been fully demonstrated. This study investigated the association of oxHDL with plasma glucose (PG) and the other atherosclerotic risk variables in non-diabetic dyslipidemic subjects. Methods Conventional atherosclerotic markers and LDL particle size (LDL-PS), as determined by gel electrophoresis, were measured in 155 non-diabetic subjects (mean age of 57 years) with dyslipidemia. Serum oxHDL levels were quantified using an antibody against oxidized human apoA-I in a sandwich ELISA format. Results Multiple regression analysis adjusted for possible confounders revealed that HDL-cholesterol was independently, significantly and positively correlated with LDL-PS and oxHDL. By multiple regression analysis, oxHDL was independently, significantly and positively correlated with fasting PG (β = 0.19, P = 0.01). Subjects in the highest PG tertile group had approximately 30% higher oxHDL levels than the lowest PG tertile group. Conclusions These results suggest that high PG levels may contribute to the HDL oxidation, irrespective of HDL-cholesterol levels, even in non-diabetic subjects with dyslipidemia, and that the measurement of oxHDL may be a useful marker of dysfunctional HDL.
  • Mitsue Yamaguchi, Kazuhiko Kotani, Naoki Sakane, Kokoro Tsuzaki, Ayaka Takagi, Shiori Wakisaka, Toshio Moritani, Narumi Nagai
    Physiology and Behavior 107(1) 87-91 2012年8月20日  査読有り
    Circadian locomotor output cycles kaput (CLOCK) molecule plays major roles in circadian rhythmicity and regulates daily physiological processes including digestive activity. Therefore, we hypothesized that the CLOCK 3111T/C single nucleotide polymorphism (SNP) might have adverse effects on the regulation of gastric motility. Based on the hypothesis, we investigated whether this SNP was associated with morning gastric motility. Ninety-five female university students (19.6 ± 0.2. years) completed life-style questionnaires. Gastric motility, evaluated by electrogastrography (EGG), blood pressure (BP), and heart rate variability (HRV) were measured at 8:30. a.m. after an overnight fast. To determine the gastric motility, the spectral powers and dominant frequency (DF, a peak of the spectrum) of the EGG were calculated. No significant differences were found in breakfast frequency, energy intake, or HRV between CLOCK 3111T/C minor C allele (T/C or C/C) and T/T subjects. However, C allele carriers showed significantly lower DF than T/T subjects, suggesting slower gastric motility. Moreover, C allele carriers had a lower heart rate (HR) and tended to have lower diastolic BP compared with T/T subjects. These results support our hypothesis that this SNP is likely correlated with morning gastric motility. Such attenuated gastric and cardiovascular function that characterized CLOCK 3111C allele carriers could be affecting biological behavior in the morning. © 2012 Elsevier Inc.
  • Okada,Kenta, Osuga,Jun-ichi, Kotani,Kazuhiko, Yagyu,Hiroaki, Miyamoto,Michiaki, Nagasaka,Shoichiro, Ishibashi,Shun
    Tob Induc Dis 10(1) e12 2012年8月  査読有り
  • Sakane N, Kotani K, Tsuzaki K, Sano Y, Takenaka S, Hasegawa M, Ikegawa Y
    Jpn J Prophy Vet Med 4(1) 13-18 2012年6月  査読有り
  • Kazuhiko Kotani, Kokoro Tsuzaki, Naoki Sakane, Nobuyuki Taniguchi
    Journal of clinical medicine research 4(3) 161-6 2012年6月  査読有り筆頭著者責任著者
    BACKGROUND: Small dense low-density lipoprotein (sdLDL), which has a small LDL particle size with a greater susceptibility to oxidation, is considered a risk marker for cardiovascular disease (CVD). The diacron reactive oxygen metabolites (d-ROMs) have recently been introduced as a clinically useful oxidative stress-related marker. Physical activity can reduce the CVD risk. The present study investigated the correlation between the changes of the mean LDL particle size and the oxidative stress status, as assessed by the d-ROMs, in a physical activity intervention in hyperlipidemic subjects. METHODS: We performed a 6-month intervention study of 30 hyperlipidemic subjects (12 male/18 female, mean age 64 years), focusing on a moderate physical activity increase. The clinical data, including the atherosclerotic risk factors besides the mean LDL particle size measured with the gel electrophoresis and the d-ROMs, were evaluated pre- and post-intervention. RESULTS: The mean LDL particle size was significantly larger in the post-intervention than in the pre-intervention evaluation (26.9 ± 0.3 (SD) vs. 27.1 ± 0.4 nm, P < 0.01), while the d-ROMs levels were significantly reduced in the post-intervention period compared to those at pre-intervention (319 ± 77 vs. 290 ± 73 U. Carr., P < 0.05). A stepwise multiple regression analysis revealed that there was an independent, significant and inverse correlation between the pre- and post-intervention changes of the d-ROMs and the mean LDL particle size (β = -0.55, P < 0.01). CONCLUSIONS: The intervention study suggests that sdLDL and oxidative stress can concomitantly affect the risk of developing CVD and that both factors can improve by even a moderate increase in physical activity among hyperlipidemic subjects.
  • Kazuhiko Kotani, Naoki Sakane
    International Journal of Preventive Medicine 3(6) 428-431 2012年6月  査読有り筆頭著者責任著者
    OBJECTIVES: Chronic inflammation and oxidative stress are associated with health and the disease status. The objective of the present study was to investigate the association among white blood cell (WBC) counts, neutrophil counts as a WBC subpopulation, and diacron reactive oxygen metabolites (d-ROMs) levels in an asymptomatic population. METHODS: The clinical data, including general cardiovascular risk variables and high-sensitivity C-reactive protein (hs-CRP), were collected from 100 female subjects (mean age, 62 years) in outpatient clinics. The correlation of the d-ROMs with hs-CRP, WBC, and neutrophil counts was examined. RESULTS: The mean/median levels were WBC counts 5.9 × 10(9)/L, neutrophil counts 3.6 × 10(9)/L, hs-CRP 0.06 mg/dL, and d-ROMs 359 CURR U. A simple correlation analysis showed a significant positive correlation of the d-ROMs with the WBC counts, neutrophil counts, or hs-CRP levels. The correlation between d-ROMs and neutrophil counts (β = 0.22, P < 0.05), as well as that between d-ROMs and hs-CRP (β = 0.28, P < 0.01), remained significant and independent in a multiple linear regression analysis adjusted for other variables. A multiple linear regression analysis showed that WBC counts had only a positive correlation tendency to the d-ROMs. CONCLUSIONS: Neutrophils may be slightly but more involved in the oxidative stress status, as assessed by d-ROMs, in comparison to the overall WBC. Further studies are needed to clarify the biologic mechanism(s) of the observed relationship.
  • Kazuhiko Kotani, Toshiyuki Yamada, Shuumarjav Uurtuya, Nobuyuki Taniguchi
    Ethnicity and Disease 22(3) 329-334 2012年6月  査読有り筆頭著者責任著者
    Objective: Chronic inflammation and oxidative stress are associated with lifestyle-related diseases. Research into the pathophysiology of lifestyle-related diseases is important for Mongolian people. Our study investigated the correlation among the d-ROMs test (a measure of the total oxidant capacity of blood), serum amyloid A (SAA) and high-sensitivity C-reactive protein (hs-CRP) levels in a young Mongolian population. Methods: The data, including anthropometric and biochemical markers, were collected from 78 Mongolian volunteers (male/female = 27/51, mean age 21 years). The correlation between the SAA and d-ROMs levels was examined, as well as the correlation between the hs-CRP and d-ROMs levels. Results: The SAA levels were 3.2 μg/mL (median), hs-CRP .04 mg/dL (median) and d- ROMs 309 CARR U, respectively. There was a significant and positive correlation between the SAA and d-ROMs levels (r5.40, P&lt .01), in addition to a significant and positive correlation between the hs-CRP and d-ROMs levels (r5.32, P&lt .01). These significant correlations remained independent in a multiple linear regression analysis. A subgroup analysis by sex revealed the positive correlation between the SAA and d-ROMs levels to be greater, relative to that between the hs-CRP and d-ROMs levels, particularly in the female group. Conclusions: The coexistence of chronic inflammation and oxidative stress can be present even in young Mongolian people, suggesting that their coexistence may be a target of early prevention of lifestyle-related diseases. In addition, not only hs-CRP, but also SAA can be used to evaluate the relationship of oxidative stress in this population. Further studies are necessary to confirm the observed relationship.
  • Kazuhiko Kotani, Naoki Sakane, Toshiyuki Yamada
    Ethnicity and Disease 22(3) 324-328 2012年6月  査読有り筆頭著者責任著者
    Objective: The relationship among alcohol metabolism, lipid profile and cardiovascular disease has been a matter of concern, and aldehyde dehydrogenase-2 (ALDH2) is one of the key enzymes involved in alcohol metabolism. The frequency of ALDH2 gene G/A polymorphism (with the substitution of glutamic acid to lysine) varies widely among ethnic groups the polymorphism is prevalent among Asian people but rare in other ethnic groups. The objective of our study was to investigate the association between the ALDH2 gene G/A polymorphism and lipid profile, including the low-density lipoprotein cholesterol (LDL-C) status, in a general Japanese population with no or light-to-moderate alcohol drinking habits. Methods: Anthropometric and biochemical variables including lipid- and glucose-related factors were measured in a total of 383 Japanese participants (170 males and 213 females mean age, 45 ± 8.6 years), free of cardiovascular disease. All participants were genotyped by an allele-specific DNA assay. Results: The numbers of participants with the G/G, G/A and A/A genotypes were 213, 139 and 31, respectively. The percentages of hyper-LDL-cholesterolemia (identified by LDL-C ≥ 3.63 mmol/L) were 31.9%, 45.3% and 29.0% in participants with the G/G, G/A and A/A genotypes, respectively. Carrying the G/A + A/A genotype was a significant and positive factor related to hyper-LDL-cholesterolemia with an odds ratio of 1.62 (95% CI: 1.04-2.52) after adjusting for the other variables including drinking status. Conclusion: Our findings suggest that the ALDH2 gene G/A polymorphism can affect the lipid profile such as LDL-C status in this population. The association between the polymorphism and LDL-C status warrants further investigation.
  • Kazuhiko Kotani, Toshiyuki Yamada
    Australasian Journal on Ageing 31(2) 124-127 2012年6月  査読有り筆頭著者責任著者
    Aim: One of the methods to evaluate oxidative stress in clinical medical settings is the reactive oxygen metabolites (d-ROMs) test. While metabolic syndrome (MetS) is considered an oxidative condition, the oxidative status in MetS has not been fully examined using this test. The aim of the present study was to investigate the possible association between oxidative stress as evaluated by the d-ROMs test and the MetS component number, in a Japanese female population. Methods: The serum oxidant capacity (measured by the d-ROMs test) was cross-sectionally determined in cardiovascular disease-free and non-smoking women who were not taking medications (n= 180 mean age, 60 ± 10 (standard deviation) years). Their MetS state was determined by the National Cholesterol Education Program Adult Treatment Panel recommendations with minor modifications for a Japanese population. Results: Patients with MetS (n= 60, 362 ± 53 CARR U) showed a significantly higher oxidant capacity by d-ROMs than those without MetS (n= 120, 324 ± 55 CARR U, P &lt 0.01). Moreover, the significant increase in the oxidant capacity by d-ROMs was closely associated with an increase in the MetS component number (trend P &lt 0.01). Conclusions: These results showed a significantly positive association between the oxidant capacity (by d-ROMs) and the MetS component number in this population. Further studies are required to establish the clinical applications of this test to MetS practice and clarify the biological mechanisms of the observed relationships. © 2012 The Authors. Australasian Journal on Ageing © 2012 ACOTA.
  • Kotani K, Hazama A, Hagimoto A, Saika K, Shigeta M, Katanoda K, Nakamura M
    J Atheroscler Thromb 19(9) 787-794 2012年5月  査読有り筆頭著者責任著者
  • Kazuhiko Kotani, Naoki Sakane
    Journal of Clinical Medicine Research 4(2) 130-134 2012年4月  査読有り筆頭著者責任著者
    BACKGROUND: Elevated and extreme circulating levels of lipoprotein(a) (Lp(a)) are considered to be an atherosclerotic risk factor, although additional studies on the low levels of Lp(a) are necessary to provide confirmation. The carotid intima-media thickness (CIMT) is known as a surrogate index of atherosclerosis. The aim of the present study was to investigate the correlation between the serum Lp(a) and CIMT in asymptomatic subjects with a relatively low Lp(a) level. METHODS: The study included 65 asymptomatic female Japanese subjects (mean age: 60 years) with a serum Lp(a) level < 30 mg/dL. Clinical data including the serum Lp(a) and CIMT were measured, and their correlations were examined. RESULTS: The median Lp(a) level was 18.6 mg/dL and the mean CIMT level was 0.8 mm. There was a significant and inverse correlation between the CIMT and Lp(a) (r = - 0.24, P ≤ 0.05), in addition to a significant and positive correlation between the CIMT and subject age and systolic blood pressure. A stepwise multiple linear regression analysis identified the Lp(a) to be correlated independently, significantly and inversely with the CIMT. CONCLUSIONS: The Lp(a) levels were inversely correlated with the CIMT in this population, suggesting that subjects with a low Lp(a) level may have a predisposition to carotid atherosclerosis. This finding was preliminary and should be investigated further in larger studies and in additional settings. KEYWORDS: Lp(a); Carotid artery; IMT; Atherosclerosis.
  • Kazuhiko Kotani, Kokoro Tsuzaki, Nobuyuki Taniguchi, Naoki Sakane
    International Journal of Preventive Medicine 3(3) 160-166 2012年3月  査読有り筆頭著者責任著者
    OBJECTIVES: Small dense low-density lipoprotein (sdLDL) which has a small LDL particle size with greater susceptibility to oxidation is regarded as a risk marker for cardiovascular disease. The diacron reactive oxygen metabolites (d-ROMs) test has recently been introduced as an oxidative stress-related marker in the clinic. The aim of the present study was to investigate the correlation between the mean LDL particle size and the oxidative stress status as evaluated by the d-ROMs in dyslipidemic patients. METHODS: The study included 278 dyslipidemic patients (121 male and 157 female, mean age, 60 years). Clinical data including the conventional atherosclerotic risk factors in addition to the mean LDL particle size measured with the gel electrophoresis and the d-ROMs were collected. RESULTS: Male patients had a significantly smaller mean LDL particle size than females (262.2 ± 7.5 [SD] vs. 264.3 ± 6.7 Å, P<0.05), while female patients had a significantly higher d-ROMs level than males (318 ± 68 vs. 350 ± 72 U. Carr., P<0.01). A multiple regression analysis revealed that there was an independent, significant, and inverse correlation between the mean LDL particle size and the d-ROMs (β=-0.19, P<0.05). CONCLUSIONS: These findings of the co-existence of both markers suggest that sdLDL and oxidative stress can be cooperative in atherogenesis, possibly leading to the incidence of CVD, in dyslipidemic patients.
  • Kazuhiko Kotani, Nobuyuki Taniguchi
    Journal of Clinical Medicine Research 4(1) 52-55 2012年2月  査読有り筆頭著者責任著者
    BACKGROUND: Inflammation and oxidative stress are associated with human health and the disease status. The present study aimed to investigate the longitudinal correlation between the diacron reactive oxygen metabolites (d-ROMs) level, as an oxidative stress-related marker, and high-sensitivity C-reactive protein (hsCRP), as an inflammatory marker, during a one-year period among asymptomatic subjects. METHODS: The data, including anthropometric and biochemical markers, were collected at baseline and after the one-year period from 71 participants (male/female = 41/30, mean age 50 years). The correlation between the changes of the d-ROMs and hsCRP levels during the study period was examined. RESULTS: A simple correlation analysis showed a significant and positive correlation to exist between the changes of the d-ROMs and hsCRP levels (r = 0.40, P < 0.01). This significant correlation remained independent in a multiple linear regression analysis adjusted for confounding factors. CONCLUSIONS: The present findings suggest that the relationship between the d-ROMs and hsCRP levels could be prospectively followed, and that monitoring both markers may help to better understand the cooperation of inflammation and oxidative stress in association with health and disease. Further studies are necessary to clarify the biological mechanism(s) responsible for the observed relationship. KEYWORDS: Oxidative stress; Oxygen reactive species; Inflammation; CRP.
  • Michiaki Miyamoto, Kazuhiko Kotani, Kenta Okada, Yasutomo Fujii, Kei Konno, Shun Ishibashi, Nobuyuki Taniguchi
    Acta Diabetologica 49(1) 63-68 2012年2月  査読有り責任著者
    The clinical significance of the diameter of the common carotid artery (CCA) measured ultrasonographically in diabetic practice has not been sufficiently established. The objective of this study was to investigate the relationship of the ultrasonic CCA diameter with atherosclerotic measures and diabetic retinopathy as a microvascular complication in patients with type 2 diabetes mellitus (T2DM). This hospital-based cross-sectional study included 102 patients with T2DM (men: 65%, mean age: 57 years) who had no apparent carotid arterial stenosis and no history of cardiovascular or severe renal disease. The current smoking status, body mass index, blood pressure, hemoglobin A1c, serum low-density lipoprotein cholesterol, and ultrasonic measures of carotid arteries (CCA diameter, intima-media thickness (IMT), plaque score) were measured. The cardio-ankle vascular index (CAVI) and the presence of diabetic retinopathy were also assessed. The CCA diameter showed a significant positive correlation with the mean IMT or plaque score. The CAVI had a significant positive correlation with the mean IMT, plaque score, and CCA diameter, while diabetic retinopathy had a significant positive correlation with the CCA diameter, but not the mean IMT or plaque score. These results were unaltered after adjusting for multiple confounders. The CCA diameter may serve as a useful marker for atherosclerosis and diabetic retinopathy, and in particular, may be a marker associated with diabetic retinopathy more clearly than the carotid IMT and plaque score, in patients with T2DM. © Springer-Verlag 2011.
  • Kazuhiko Kotani, Naoki Sakane, Nobuyuki Taniguchi
    Medical Principles and Practice 21(2) 134-138 2012年2月  査読有り筆頭著者責任著者
    To investigate the influence of ezetimibe monotherapy on remnant-like particle cholesterol (RLP-C) in subjects with metabolic syndrome (MetS). Materials and Methods: Ezetimibe (10 mg/daily) was prescribed over a 12-week period for hypercholesterolemic subjects divided into groups with MetS (n = 28 male/female = 13/15 mean age 67 years) and without MetS (n = 22 male/female = 9/13 mean age 66 years). In the pre- and post-treatment phases, BMI, blood pressure and fasting blood levels of glucose, lipid panels and RLP-C were measured. Results: The group with MetS showed significantly higher RLP-C levels than the group without MetS [median level: 0.18 vs. 0.12 mmol/l (7.1 vs. 4.4 mg/dl), p &lt 0.01] in the pre-treatment phase. In the posttreatment phase, the low-density lipoprotein cholesterol levels were significantly reduced in both groups to a similar level (p &lt 0.001 in both), while there was a significantly greater reduction in RLP-C in the group with MetS than the group without MetS [median level: 0.12 vs. 0.11 mmol/l (4.8 vs. 4.1 mg/dl), p &lt 0.05]. This difference in RLP-C remained signifi-cant after adjusting for confounding factors. Conclusion: Ezetimibe monotherapy may be associated with a greater reduction in RLP-C levels in subjects with MetS than in those without MetS. © 2011 S. Karger AG, Basel.
  • Kotani K, Fujiwara S, Tsuzaki K, Sano Y, Sakane N
    Exp Clin Endocrinol Diabetes 120(1) 59-61 2012年1月  査読有り筆頭著者責任著者
  • Miyamoto M, Kotani K, Ishibashi S, Taniguchi N
    Int J Vasc Med 2012 e453264 2012年1月  査読有り責任著者
  • Alejandro Gugliucci, Kazuhiko Kotani, Satoshi Kimura
    Journal of lipids 2012 e726048 2012年  査読有り
    In this review we summarize the findings from the literature and our own laboratory on the decreased PON1 activity in renal failure, the mechanisms proposed and the effect of interventions. In addition to profound alterations in lipoproteins, reduced serum PON1 activity has been clearly established in the past decade and could contribute to accelerated development of atherosclerosis in ESRD and in HD. PON1 lactonase activity is lower in ESRD patients. Hemodialysis partially restores PON1 lactonase and the other activities. PON1 activity recovery after dialysis suggests that uremic toxins may play a mechanistic role in PON1 inactivation. Lower PON1 activity in CRF patients is associated with low thiol concentration, high CRP, and is beneficially enhanced with vitamin C and flavonoids. Changes in HDL subclasses, namely lower HDL(3) in these patients may also play a role in PON1 lower activity. Future research should focus on: (1) mechanistic studies on causes for low PON1 activity and mass; (2) prospective studies focusing on whether there is an added predictive value in measuring PON1 activity (and PON1 activity in HDL(3)) in this patient population; (3) intervention studies attempting to increase PON1 activity.
  • Shigesumi Kinchiku, Kazuhiko Kotani, Shoko Kajiya, Kanoko Yodo, Yukiko Maruguchi, Hitoshi Uenomachi
    Journal of Primary Health Care 4(4) 294-298 2012年  査読有り
    INTRODUCTION: Self-monitoring of blood glucose (SMBG) helps patients with diabetes mellitus main-tain glycemic control. However, few reports exist on whether ambient temperature can influence SMBG values. AIM: To investigate the effect of ambient temperature on the association between SMBG and plasma glucose (PG) values. METHODS: The study was conducted between 2003 and 2010 in diabetic patients (n=2777, male/fe-male = 1216/1561, mean age = 60. 5 ±13. 6 years) for whom the measurements of SMBG and PG were per-formed simultaneously (66 197 samples were measured). SMBG and PG were both measured by enzyme methods. Correlation coefficients were determined between SMBG and PG values, and the differences between their values were compared based on the temperature. RESULTS: SMBG and PG were closely correlated at each temperature. The PG-SMBG difference was smallest at an ambient temperature of 20°C, around which SMBG differed from PG with temperature namely, the SMBG value decreased as the ambient temperature increased, while the SMBG value in-creased as the ambient temperature decreased. DISCUSSION: The present data indicate that the ambient temperature can minimally but significantly influence SMBG values. Further studies about the relevance of these findings on patient self-care are warranted.
  • Kazuhiko Kotani, Nobuyuki Taniguchi
    Annals of Clinical and Laboratory Science 42(4) 435-438 2012年  査読有り筆頭著者責任著者
    While daily step counts are considered to be a useful measure of cardiovascular health, the biochemical predictors of step counts have not been fully characterized. This study investigated the correlation between pedometer-determined daily step counts and cardiometabolic variables, including the serum level of malondialdehyde-modified low-density lipoprotein (MDA-LDL), among asymptomatic subjects (n = 50, mean age 63 years). Simple and stepwise multiple linear correlation tests revealed that there was a significant inverse correlation between the step counts and MDA-LDL levels (r = -0.41, P &lt 0.01 β = -0.38, P &lt 0.01). The data suggest that daily steps may be beneficially associated with atherosclerosis in correlation with reduced oxidized low-density lipoprotein, and in addition that the MDA-LDL level may be used as a measure reflective of the daily steps. © 2012 by the Association of Clinical Scientists, Inc.
  • Yosikazu Nakamura, Mayumi Yashiro, Ritei Uehara, Atsuko Sadakane, Satoshi Tsuboi, Yasuko Aoyama, Kazuhiko Kotani, Enkh-Oyun Tsogzolbaatar, Hiroshi Yanagawa
    Journal of Epidemiology 22(3) 216-221 2012年  査読有り
    Background: Although the number of patients and incidence rate of Kawasaki disease (KD) are increasing in Japan, the most recent epidemiologic features of KD are not known. Methods: The 21st nationwide survey of KD was conducted in 2011 and included patients treated for the disease in 2009 and 2010. Hospitals specializing in pediatrics, and hospitals with a total of 100 or more beds and a pediatric department, were asked to report all patients with KD during the 2 survey years. Results: A total of 1445 departments and hospitals reported 23 730 KD patients (10 975 in 2009 and 12 755 in 2010): 13 515 boys and 10 215 girls. The annual incidence rates were 206.2 and 239.6 per 100 000 children aged 0 to 4 years in 2009 and 2010, respectively the 2010 rate was the highest ever reported in Japan. Monthly number of patients peaked during winter to spring months lower peaks were noted during summer months. However, the seasonal patterns in 2009 and 2010 differed from those of previous years. The age-specific incidence rate had a monomodal distribution, with a peak during the latter half of the year of birth. The prevalences of cardiac lesions during acute KD and cardiac sequelae were higher among infants and older age groups. Despite a decrease in prevalence, the proportion of patients with giant coronary aneurysms-the most severe sequela of KD-did not substantially decrease. Conclusions: The incidence rate and number of patients with KD continue to increase in Japan. © 2011 by the Japan Epidemiological Association.
  • Kazuhiko Kotani, Naoki Sakane
    Journal of International Medical Research 40(3) 1074-1081 2012年  査読有り筆頭著者責任著者
    Objective: This cross-sectional study investigated the correlation between diacron reactive oxygen metabolites (d- ROMs) and high-sensitivity C-reactive protein (hs-CRP) in subjects with or without metabolic syndrome. METHODS: Cardiometabolic risk factors, d-ROMs and hs-CRP were determined in 457 women: 123 with metabolic syndrome and 334 without metabolic syndrome. The correlation between d-ROMs and hs-CRP levels was compared between the two groups. RESULTS: The group with metabolic syndrome had significantly higher d-ROMs and hs-CRP levels than the group without metabolic syndrome. While the d-ROMs level was significantly and positively correlated with the hs-CRP level in both groups, the correlation level between the two groups was significantly different. Multiple linear regression analysis adjusted for other cardio - metabolic risk factors also showed significant positive correlation between d- ROMs and hs-CRP levels in both groups. CONCLUSION: Subjects with metabolic syndrome may have a closer relationship between inflammation and oxidative stress than subjects without metabolic syndrome, possibly reflecting their increased predisposition to atherosclerosis. Further studies are necessary to confirm the observed relationship. © 2012 Field House Publishing LLP.
  • Kazuhiko Kotani, Toshiyuki Yamada, Michiaki Miyamoto, Shun Ishibashi, Nobuyuki Taniguchi, Alejandro Gugliucci
    Pharmacological Reports 64(1) 212-216 2012年  査読有り筆頭著者責任著者
    The complex of serum amyloid A(SAA) and low-density lipoprotein (LDL), SAA-LDL, is considered a new and unique marker of oxidatively-modified LDL particles, which is associated with atherosclerotic conditions. This study investigated the influence of atorvastatin treatment on circulating SAA-LDL levels among asymptomatic hypercholesterolemic patients. A total of 26 patients (mean age 63 years) received 10 mg/daily atorvastatin during a 12-week treatment period. The levels of LDL cholesterol and SAA-LDL, but not high-sensitivity C-reactive protein and SAA, were significantly reduced after the treatment. Stepwise adjusted regression analyses revealed that changes of SAA-LDL were significantly and positively correlated with those of SAA, while absolute changes were small, which warrants further investigation. The results suggest that atorvastatin may beneficially reduce SAA-LDL, and SAA-LDL may be a sensitive measure for monitoring the efficacy and antioxidant functions of atorvastatin. Copyright © 2012 by Institute of Pharmacology Polish Academy of Sciences.
  • Kazuhiko Kotani, Shinji Fujiwara, Kokoro Tsuzaki, Naoki Sakane
    Journal of Investigative Medicine 60(2) 514-516 2012年  査読有り筆頭著者責任著者
    The fat mass and obesity-associated (FTO) gene has recently attracted attention as one of the obesity-related genes. Obesity-related gene polymorphisms may be associated with the development of atherothrombosis in relation to platelets. The present study investigated the association between FTO gene polymorphisms (rs1558902, T/A) and hematological parameters, in particular the platelet counts. Anthropometric, hematological, and biochemical parameters, in addition to genotyping by an allele-specific DNA assay, were measured in 209 asymptomatic community-dwelling Japanese subjects (male/female: 80/129 mean age, 65 years mean [SD] bodymass index, 24.0 [3.0] kg/m2). The subjects with the A-allele (n = 73) showed significantly higher platelet counts than those without the A-allele (mean [SD], 237 [58] vs 217 [57] × 109/L, P &lt 0.05). Even when multiple-adjusted analyses were performed, the platelet counts continued to differ significantly and independently of other variables, including obesity-related parameters such as the index of insulin resistance or high-sensitivity C-reactive protein, between the subjects with and without the A-allele. The FTO gene polymorphisms may be associated with the minor but significant modulation of platelet counts in this population. © 2012 by The American Federation for Medical Research.
  • Kokoro Tsuzaki, Kazuhiko Kotani, Yoshiko Sano, Shinji Fujiwara, Irene F. Gazi, Moses Elisaf, Naoki Sakane
    Metabolism: Clinical and Experimental 61(1) 17-21 2012年1月  査読有り
    This study examined the association among serum adiponectin levels, a single nucleotide polymorphism (SNP) of the adiponectin gene, and the size of serum high-density lipoprotein (HDL) particles in a general population. A total of 275 subjects were examined as part of the community-based Mima study. Serum adiponectin levels were measured with an enzyme-linked immunosorbent assay. Serum small-sized HDL was measured with the electrophoretic separation of lipoproteins using the Lipoprint system. Single nucleotide polymorphism G276T (rs1501299, SNP276) of the adiponectin gene was determined with a fluorescent allele-specific DNA primer assay system. Age- and sex-adjusted correlation test revealed a significant inverse relationship between small-sized HDL and adiponectin levels (r = -0.236, P &lt .001). More percentages of small-sized HDL were observed in the subjects with the SNP276 G/G and G/T genotypes than in those with the T/T genotype (5.5% ± 5.0% vs 3.0% ± 2.9%, P =.016). In a multiple regression analysis, small-sized HDL was significantly and independently correlated with triglycerides levels (β = 0.133, P =.030), adiponectin levels (β = -0.242, P &lt .001), and the SNP276 G allele (β = -0.142, P =.014). Our findings indicated that adiponectin and SNP276 of the adiponectin gene may modify the size of HDL particles. © 2012 Elsevier Inc. All rights reserved.
  • Kazuhiko Kotani, Shinji Fujiwara, Kokoro Tsuzaki, Yoshiko Sano, Narumi Nagai, Toshiyuki Yamada, Naoki Sakane
    Journal of Clinical Medicine Research 3(6) 319-324 2011年12月  査読有り筆頭著者責任著者
    BACKGROUND: Limited studies have shown inconsistent data about the association between the uncoupling protein 1 (UCP1) gene A-3826G polymorphism and high-density lipoprotein (HDL) cholesterol levels. The present study investigated the association between the A-3826G polymorphism and low HDL-cholesterolemia in non-obese and obese subjects. METHODS: Anthropometric and biochemical factors, in addition to genotyping by an allele-specific DNA assay, were measured in 294 community-dwelling Japanese subjects (male/female: 127/167, mean age: 65 years). Obesity was defined as a body mass index (BMI) ≥ 25 kg/m(2), and low HDL-cholesterolemia was defined as < 1.04 mmol/L of HDL-cholesterol. RESULTS: The subjects with the G/G genotype (n = 27) showed a significantly higher prevalence of low HDL-cholesterolemia (37%) than those with the A/A + A/G genotype (13%) in the obese group (n = 102). There was a non-significant difference in the prevalence of low HDL-cholesterolemia between subjects with the G/G genotype (n = 45, 13%) and with the A/A + A/G genotype (15%) in the non-obese group (n = 192). A multivariate-adjusted logistic regression analysis of the presence of low HDL-cholesterolemia revealed that carrying the G/G genotype was an independent and significant factor positively associated with low HDL-cholesterolemia [odds ratio (OR): 6.85, 95% confidence interval (CI): 1.65-28.49] in the obese group, while carrying the G/G genotype exhibited a non-significant but reduced OR, by one-half, for low HDL-cholesterolemia (OR: 0.51, 95% CI: 0.13-1.96) in the non-obese group. CONCLUSIONS: The obesity status could have opposing impacts on the relationship between the G/G genotype and low HDL-cholesterolemia, providing insight into the need to consider the obesity levels when studying the association between the UCP-1 gene A-3826G polymorphism and HDL-cholesterol. KEYWORDS: Obesity; Body mass index; HDL-C; Atherosclerotic risk.
  • Kazuhiko Kotani, Naoki Sakane, Munetada Kamimoto, Nobuyuki Taniguchi
    Australasian Journal on Ageing 30(4) 231-233 2011年12月  査読有り筆頭著者責任著者
    Aim: Oxidative stress may be associated with the pathophysiology of knee osteoarthritis (OA), a health-care issue. The present study aimed to compare oxidative status levels of patients with and without knee OA, using the Reactive Oxygen Metabolites (d-ROMs, Diacron, Italy) test, which has proved to be clinically useful as an oxidative stress marker. Methods: Forty-nine women (mean age 71.3 ± 5.8 years, mean body mass index 24.4 ± 2.2kg/m 2) with mildly severe knee OA and 49, without knee OA, female controls' serum d-ROMs concentrations were assessed together with mean blood pressure, fasting plasma glucose and serum total cholesterol concentrations, using the age-, sex- and body mass index-matched method. Results: Patients with knee OA showed significantly higher d-ROMs levels than controls (338 ± 56 vs 315 ± 47 U. Carr., P &lt 0.05). This difference remained statistically significant after adjusting for other clinical variables. Conclusions: The present results suggested that knee OA might be an impaired oxidative condition. Further studies are necessary to establish the knee OA-oxidative status relationship, which may lead to its clinical application in the management of knee OA. © 2011 The Authors Australasian Journal on Ageing © 2011 ACOTA.
  • Uurtuya Shuumarjav, Kazuhiko Kotani, Nobuyuki Taniguchi
    Ethnicity and Disease 21(1) 74-78 2011年12月  査読有り責任著者
    Objective: Metabolic syndrome (MetS) is associated with chronic inflammation and cardiovascular disease. The present study's aim was to investigate the relationship between serum C-reactive protein (CRP) and MetS in the Mongolian population in comparison to the Japanese population. Methods: Two-hundred and eighty-five Mongolian volunteers (males/females: 115/170, mean age 44.9 years) and 326 Japanese volunteers (males/females: 137/189, mean age 43.6 years) were recruited from health check-up settings. Cardiometabolic variables including CRP were measured. The patients were divided into three groups by the number of MetS risk factors (&lt 1, 1-2 or ≥3). Results: The percentages of patients with MetS were 39.6% in the Mongolians and 31.1% in the Japanese. The median CRP levels were .05, .12 and .19 mg/dL in the &lt 1, 1-2 and ≥3 MetS risk factor groups among Mongolians, and .03, .05 and .07 mg/dL in these same groups among Japanese. The significance for the trend for CRP levels within each ethnic group was P&lt .001, and the significance for the difference in CRP levels between the respective groups by the MetS risk factors was P=.03 in subjects with &lt 1, P&lt .001 in subjects with 1-2, P&lt .001 in subjects with ≥3. These results were similar in the subgroup analyses by sex. Conclusions: While higher serum CRP levels were seen with increased MetS risk factors in both ethnic groups, in some cases we observed a higher serum CRP level increase in the Mongolian population than in the Japanese population. Mongolian people may be at greater risk for cardiovascular disease.
  • 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 &lt; 18.5 kg/m(2)), normal weight (18.5 a parts per thousand currency sign BMI &lt; 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.

MISC

 142

共同研究・競争的資金等の研究課題

 38