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Yamaguchi S.,Gonohashi Clinic | Mori Y.,Mori Orthopedics | Nakajima K.,Nakajima Clinic | Hashimoto S.,Hashimoto Clinic | And 6 more authors.
Journal of Clinical Biochemistry and Nutrition | Year: 2013

Static electric field therapy by high voltage alternating current (EF-HVAC) is a traditional complementary Japanese medicine used for headache, shoulder stiffness, chronic constipation and insomnia. Open-label studies and clinical experience in Japan have suggested that this electric field therapy is safe and effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC therapy in a randomized, double-blinded, sham-controlled trial in patients with active rheumatoid arthritis (RA) in community-based general physician centers. Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp., Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory parameters were used as the outcome variable. Twenty four patients (n = 12 in each group) were analyzed by a per protocol analysis. Although a significant reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared to before treatment, there were no significant differences in DAS28-CRP scores during treatment between two groups. The scale of VAS was also significantly decreased by the treatment with EF-HVAC compared to before treatment, in addition, the scale of VAS in EF-HVAC group was significantly lower than sham group at 8 and 12 weeks. Changes in another parameters including MHAQ were not significant between before and after treatment, or by all comparative study between two groups. There were no adverse events related the treatment. In conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to subjective pain of RA. © 2013JCBN.


Inoue N.,Japan National Cardiovascular Center Research Institute | Okamura T.,Japan National Cardiovascular Center Research Institute | Kokubo Y.,Japan National Cardiovascular Center Research Institute | Fujita Y.,Japan National Cardiovascular Center Research Institute | And 12 more authors.
Clinical Chemistry | Year: 2010

BACKGROUND: Lectin-like oxidized LDL receptor 1 (LOX-1) is implicated in atherothrombotic diseases. Activation of LOX-1 in humans can be evaluated by use of the LOX index, obtained by multiplying the circulating concentration of LOX-1 ligands containing apolipoprotein B (LAB) times that of the soluble form of LOX-1 (sLOX-1) [LOX index = LAB X sLOX-1]. This study aimed to establish the prognostic value of the LOX index for coronary heart disease (CHD) and stroke in a community-based cohort. METHODS: An 11-year cohort study of 2437 residents age 30-79 years was performed in an urban area located in Japan. Of these, we included in the analysis 1094 men and 1201 women without history of stroke and CHD. We measured LAB and sLOX-1 using ELISAs with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody and with 2 monoclonal antibodies against LOX-1, respectively. RESULTS: During the follow-up period, there were 68 incident cases of CHD and 91 cases of stroke (with 60 ischemic strokes). Compared with the bottom quartile, the hazard ratio (HR) of the top quartile of LOX index was 1.74 (95% CI 0.92-3.30) for stroke and 2.09 (1.00-4.35) for CHD after adjusting for sex, age, body mass index, drinking, smoking, hypertension, diabetes, non-HDL cholesterol, and use of lipid-lowering agents. Compared with the bottom quartile of LOX index, the fully adjusted HRs for ischemic stroke were consistently high from the second to the top quartile: 3.39 (95% CI 1.34-8.53), 3.15 (1.22-8.13) and 3.23 (1.24-8.37), respectively. CONCLUSIONS: Higher LOX index values were associated with an increased risk of CHD. Low LOX index values may be protective against ischemic stroke. © 2009 American Association for Clinical Chemistry.


Otsuki T.,Ryutsu Keizai University | Maeda S.,University of Tsukuba | Mukai J.,Biomarker Science Co. | Ohki M.,Biomarker Science Co. | And 2 more authors.
Journal of Clinical Biochemistry and Nutrition | Year: 2015

Lectin-like oxidized lowdensity lipoprotein receptor-1 (LOX -1)is implicated in vascular endothelial function. Vascular endothelial function is a potent regulator of arterial stiffness, an independent risk factor for cardiovascular disease. However, it is unknown whether LOX-1 is associated with arterial stiffness. Plasma concentrations of soluble LOX-1 (sLOX-1) and brachial-ankle pulse wave velocity (baPWV, an index of arterial stiffness) were measured in 143 individuals between 51 and 83 years of age. Plasma sLOX-1 concentration was correlated with baPWV (r = 0.288, p = 0.0005). In stepwise regression analysis, plasma sLOX-1 concentration was associated with baPWV, after adjusting for age; body mass index; blood pressure; heart rate; blood levels of cholesterol, triglycerides, glucose, hemoglobin A1c, and insulin; sex; and use of antihypertensives, lipid-lowering agents, and other medications (R2 = 0.575, p≤0.0001). Multiple logistic regression demonstrated that plasma sLOX-1 concentration was independently associated with elevated baPWV (≥14.0 m/s; odds ratio, 1.01; 95% confidence interval, 1.00-1.03; p = 0.03). These results suggest that LOX-1 is associated with arterial stiffness. Copyright © 2015 JCBN.


PubMed | University of Tsukuba, Kyoto Prefectural University of Medicine, Ryutsu Keizai University and Biomarker Science Co.
Type: Journal Article | Journal: Journal of clinical biochemistry and nutrition | Year: 2015

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is implicated in vascular endothelial function. Vascular endothelial function is a potent regulator of arterial stiffness, an independent risk factor for cardiovascular disease. However, it is unknown whether LOX-1 is associated with arterial stiffness. Plasma concentrations of soluble LOX-1 (sLOX-1) and brachial-ankle pulse wave velocity (baPWV, an index of arterial stiffness) were measured in 143 individuals between 51 and 83 years of age. Plasma sLOX-1 concentration was correlated with baPWV (r=0.288, p=0.0005). In stepwise regression analysis, plasma sLOX-1 concentration was associated with baPWV, after adjusting for age; body mass index; blood pressure; heart rate; blood levels of cholesterol, triglycerides, glucose, hemoglobin A1c, and insulin; sex; and use of antihypertensives, lipid-lowering agents, and other medications (R (2)=0.575, p<0.0001). Multiple logistic regression demonstrated that plasma sLOX-1 concentration was independently associated with elevated baPWV (14.0m/s; odds ratio, 1.01; 95% confidence interval, 1.00-1.03; p=0.03). These results suggest that LOX-1 is associated with arterial stiffness.


Iwamoto S.,Japan National Cardiovascular Center Research Institute | Iwamoto S.,Osaka University | Fujita Y.,Japan National Cardiovascular Center Research Institute | Kakino A.,Japan National Cardiovascular Center Research Institute | And 7 more authors.
Journal of Atherosclerosis and Thrombosis | Year: 2011

Aim: We have recently demonstrated that the circulating level of LOX-1 ligand containing apoB (LAB) predicts the risk of cardiovascular events; however, as is the case in other assays measuring oxidized LDL (oxLDL), chemical unstability and inter-lot variance of standard oxLDL may limit the utility of measuring LAB. This study aimed to develop an alternative protein standard that is simultaneously recognized by LOX-1 and anti-apoB antibody instead of copper-oxidized LDL. Methods and Results: cDNAs encoding the variable regions of anti-LOX-1 monoclonal antibody were cloned from hybridomas and reorganized to express anti-LOX-1 single-chain variable fragment (Fv). cDNAs of four regions of human apoB (B1 to B4), which were reported to be epitopes of many anti-apoB antibodies, were also cloned. After confirming the respective reactivity of Fv and apoB fragments to LOX-1 and anti-apoB antibodies, cDNAs of Fv and apoB fragments were connected to express Fv-ApoB chimeric proteins. These fusion proteins were found to be recognized by both LOX-1 and anti-apoB antibodies. Among them, the fusion proteins of Fv-B1 and Fv-B3 gave saturable binding curves against immobilized LOX-1 when detected by anti-apoB antibodies. The binding curves of different Fv-B1 preparations to LOX-1 were almost identical while those of oxLDL varied among the preparations, suggesting better quality control of Fv-B1 preparations. Conclusions: The fusion proteins composed of Fv-form anti-LOX-1 antibody and apoB fragment are useful alternatives to copper-oxidized LDL in determining LAB, which would facilitate the application of modified LDL analyses to the clinical diagnosis and risk evaluation of cardiovascular disease.


Naito Y.,Kyoto Prefectural University of Medicine | Ichikawa H.,Doshisha University | Akagiri S.,Kyoto Prefectural University of Medicine | Akagiri S.,Kobe College | And 11 more authors.
Journal of Clinical Biochemistry and Nutrition | Year: 2016

Recent evidence has indicated that total fiber intake is inversely related to type 2 diabetes risk. The present study aimed to investigate the effects of chronic administration of partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, on the occurrence of diabetes and its complications, fatty liver and nephropathy. We also identified predictive serum biomarkers of treatment response to PHGG by mass spectroscopy-based proteomic analysis using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a good model of human non-insulin-dependent diabetes mellitus. In this study, at 5 weeks of age, OLETF rats and control strain Long-Evans Tokushima Otsuka (LETO) rats were fed a control diet or a high-fiber diet (5% PHGG) for 57 weeks. Body weight, food intake, oral glucose tolerance test, plasma insulin levels, and urine glucose and protein levels were regularly measured. Oral glucose tolerance tests (OGTT) and storage of serum in a deep freezer were conducted at the beginning of the experiment and every 4 weeks after overnight fasting during the experiments. PHGG treatment affected neither meal patterns nor the body weight of OLETF and LETO rats. Repeated measure analysis of variance revealed significant differences in fasting plasma glucose and plasma glucose at 2 h after OGTT between control OLETF (OLETF-C) rats and OLETF rats treated with PHGG (OLETF-F). The glucose response determined by the area under the curve of OGTT was significantly greater in OLETF-C rats than that in OLETF-F rats at 25 weeks of age. HOMA-IR, an index of insulin resistance, increased at 25 weeks of age in OLETF-C rats, while this increase was significantly inhibited in OLETF-F rats. At 62 weeks of age, PHGG treatment significantly improved hepatic steatosis as well as renal mesangial matrix accumulation in OLETF rats. To identify the risk marker for diabetes mellitus by SELDI-TOF MS, we collected sera from 21-week-old individuals. Among the 12 specific peaks that were risk marker candidates for diabetes mellitus, the m/z 13,720 peak was identified as that of cysteinylated transthyretin by sequencing of four tryptic peptides using tandem mass spectrometry and peak distribution around the m/z 13,720 peak in the SELDI-TOF spectra. In conclusion, we found that chronic treatment with PHGG improved insulin resistance, delayed the onset of diabetes, and inhibited the development of diabetic complications, as well as identified cysteinylated transthyretin as a predictive biomarker of treatment response to PHGG in OLETF rats. © 2016 JCBN.


Suehiro A.,Health Science University | Wakabayashi I.,Hyogo College of Medicine | Uchida K.,Biomarker Science Co. | Yamashita T.,Kobe Gakuin University | Yamamoto J.,Kobe Gakuin University
Thrombosis Research | Year: 2012

Introduction: In patients with metabolic syndrome (MetS), activity of the fibrinolytic system is generally surmised to be decreased through increased plasminogen activator inhibitor-1 (PAI-1) generation. However, there have been no detailed reports describing whether the clot lysis activity is more dominant than increased clot formation activity for production of the thrombotic state in MetS. Methods: The global thrombosis test (GTT) is a novel method designed to test both clot formation and clot lysis activities under physiological conditions by using non-anticoagulated blood samples in vitro. We used the GTT to examine the thrombotic or thrombolytic states in males with MetS. Results: Lysis time, which reflects spontaneous clot lysis activity, was significantly longer in MetS subjects (median, 1494 s; range, 865-3596 s; n = 30) than in control subjects (median 1246 s; range, 667-2239 s; n = 53). There was no significant difference between the two groups in occlusion time, which reflects platelet function. The mean level of PAI-1 was significantly higher in MetS subjects than in controls (mean ± SE, 8.7 ± 1.1 and 5.0 ± 0.5 ng/mL, respectively). PAI-1 level and lysis time were significantly correlated (r = 0.400, P < 0.01). Conclusion: These results suggest that male patients with MetS are more likely than controls to experience a thrombotic state through decreased fibrinolytic activity due to increased PAI-1 generation, and that the GTT is useful for evaluating fibrinolytic activity in vitro. © 2011 Elsevier Ltd. All rights reserved.


Fukui M.,Kyoto Prefectural University of Medicine | Tanaka M.,Kyoto Prefectural University of Medicine | Senmaru T.,Kyoto Prefectural University of Medicine | Nakanishi M.,Kyoto Prefectural University of Medicine | And 6 more authors.
Metabolism: Clinical and Experimental | Year: 2013

Objective The aim of this study was to investigate whether serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), which mediates initiation and progression of atherosclerosis in endothelial cells, could be a novel marker for peripheral artery disease (PAD) in patients with type 2 diabetes. Methods We evaluated relationships of serum sLOX-1 to ankle-brachial index (ABI) and examined the association of serum sLOX-1 with PAD in 410 patients with type 2 diabetes. Results Serum sLOX-1 was inversely correlated with ABI (r = - 0.197, P < 0.0001). Stepwise regression analysis demonstrated that serum sLOX-1 (β = - 0.168, F = 5.571, P < 0.05) was independently associated with ABI, and multiple logistic regression analysis demonstrated that serum sLOX-1 (16.254 (1.237-213.651), P = 0.0339) was independently associated with PAD. Conclusions Serum sLOX-1 is associated with ABI and it could be a novel marker for PAD in patients with type 2 diabetes. © 2013 Elsevier Inc. All rights reserved.


Aoi W.,Kyoto Prefectural University | Takanami Y.,Otsuma Women's University | Kawai Y.,Louis Pasteur Center for Medical Research | Morifuji M.,Meiji Seika Kaisha Ltd. | And 7 more authors.
Nutrition | Year: 2011

Objective: It has been shown that dietary whey protein accelerates glucose uptake by altering glycoregulatory enzyme activity in skeletal muscle. In the present study, we investigated the effect of dietary whey protein on endurance and glycogen resynthesis and attempted to identify plasma proteins that reflected the physical condition by a comprehensive proteomics approach. Methods: Male c57BL/6 mice were divided into four groups: sedentary, sedentary with whey protein hydrolysate, exercise, and exercise with whey protein hydrolysate. The mice in the exercise groups performed treadmill running exercise five times per week for 4 wk. Protein profiling of plasma sample obtained from individuals was performed, as were measurements of endurance performance and the glycogen content of gastrocnemius muscle. Results: After the training period, the endurance of mice fed the whey diet was improved compared with that of mice fed the control diet. Muscle glycogen content was significantly increased after 4 wk of exercise, and intake of whey protein led to a further increase in glycogen. Apolipoproteins A-II and C-I and β2-glycoprotein-1 were found to be altered by training combined with the intake of whey protein, without significant changes induced by exercise or whey protein alone. Conclusion: Results of the present study suggest that these three proteins may be potential biomarkers of improved endurance and glycogen resynthesis and part of the mechanism that mediates the benefits of whey protein. © 2011 Elsevier Inc.


PubMed | Kyoto Prefectural University of Medicine, Taiyo Kagaku Co., Doshisha University and Biomarker Science Co.
Type: Journal Article | Journal: Journal of clinical biochemistry and nutrition | Year: 2016

Recent evidence has indicated that total fiber intake is inversely related to type 2 diabetes risk. The present study aimed to investigate the effects of chronic administration of partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, on the occurrence of diabetes and its complications, fatty liver and nephropathy. We also identified predictive serum biomarkers of treatment response to PHGG by mass spectroscopy-based proteomic analysis using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a good model of human non-insulin-dependent diabetes mellitus. In this study, at 5 weeks of age, OLETF rats and control strain Long-Evans Tokushima Otsuka (LETO) rats were fed a control diet or a high-fiber diet (5% PHGG) for 57 weeks. Body weight, food intake, oral glucose tolerance test, plasma insulin levels, and urine glucose and protein levels were regularly measured. Oral glucose tolerance tests (OGTT) and storage of serum in a deep freezer were conducted at the beginning of the experiment and every 4 weeks after overnight fasting during the experiments. PHGG treatment affected neither meal patterns nor the body weight of OLETF and LETO rats. Repeated measure analysis of variance revealed significant differences in fasting plasma glucose and plasma glucose at 2h after OGTT between control OLETF (OLETF-C) rats and OLETF rats treated with PHGG (OLETF-F). The glucose response determined by the area under the curve of OGTT was significantly greater in OLETF-C rats than that in OLETF-F rats at 25 weeks of age. HOMA-IR, an index of insulin resistance, increased at 25 weeks of age in OLETF-C rats, while this increase was significantly inhibited in OLETF-F rats. At 62 weeks of age, PHGG treatment significantly improved hepatic steatosis as well as renal mesangial matrix accumulation in OLETF rats. To identify the risk marker for diabetes mellitus by SELDI-TOF MS, we collected sera from 21-week-old individuals. Among the 12 specific peaks that were risk marker candidates for diabetes mellitus, the m/z 13,720 peak was identified as that of cysteinylated transthyretin by sequencing of four tryptic peptides using tandem mass spectrometry and peak distribution around the m/z 13,720 peak in the SELDI-TOF spectra. In conclusion, we found that chronic treatment with PHGG improved insulin resistance, delayed the onset of diabetes, and inhibited the development of diabetic complications, as well as identified cysteinylated transthyretin as a predictive biomarker of treatment response to PHGG in OLETF rats.

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