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Masato Shingyoji,
Toshihiko Iizasa,
Masahiko Higashiyama,
Fumio Imamura,
Nobuhiro Saruki,
Akira Imaizumi,
Hiroshi Yamamoto,
Takashi Daimon, Osamu Tochikubo,
Toru Mitsushima,
Minoru Yamakado,
Hideki Kimura
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ABSTRACT: BACKGROUND: We have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a PFAA-based, multivariate discrimination index for the early detection of lung cancer. In this study, we aimed to verify the usefulness and robustness of PFAA profiling for detecting lung cancer using new test samples. METHODS: Plasma samples were collected from 171 lung cancer patients and 3849 controls without apparent cancer. PFAA levels were measured by high-performance liquid chromatography (HPLC)--electrospray ionization (ESI)--mass spectrometry (MS). RESULTS: High reproducibility was observed for both the change in the PFAA profiles in the lung cancer patients and the discriminating performance for lung cancer patients compared to previously reported results. Furthermore, multivariate discriminating functions obtained in previous studies clearly distinguished the lung cancer patients from the controls based on the area under the receiver-operator characteristics curve (AUC of ROC = 0.731 ~ 0.806), strongly suggesting the robustness of the methodology for clinical use. Moreover, the results suggested that the combinatorial use of this classifier and tumor markers improves the clinical performance of tumor markers. CONCLUSIONS: These findings suggest that PFAA profiling, which involves a relatively simple plasma assay and imposes a low physical burden on subjects, has great potential for improving early detection of lung cancer.
BMC Cancer 02/2013; 13(1):77. · 3.01 Impact Factor
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ABSTRACT: The plasma free amino acid (PFAA) profile is affected by various nutritional conditions, such as the dietary energy balance. Regarding the clinical use of PFAA profiling, it is of concern that differences in food ingestion patterns may generate systematic errors in a plasma amino acid profile and constitute a confounding factor in assessment. In this study, the overnight impact of the dietary energy balance on the postprandial plasma amino acid profile was investigated to elucidate in particular the effects of high protein meals typical in Japanese cuisine. We conducted diet-controlled, crossover trials in eleven healthy male volunteers aged 40-61 y. They consumed either a normal meal (meal N) or high protein meal (meal H) at dinner. Forearm venous blood was collected, and plasma amino acid concentrations were measured before dinner and the next morning. We found that a high protein meal in the evening that contained 40% energy would significantly increase the PFAA concentration the next morning, even more than 12 hours after the meal. Among amino acids, the most significant difference was observed in the branched-chain amino acids (BCAAs) and in some urea-cycle related compounds. If the subject consumed the high protein diet at dinner, the PFAA profile after overnight fasting might be still affected by the meal even 12 hours after the meal, suggesting that the PFAA profile does not reflect the subject's health condition, but rather the acute effect of high protein ingestion.
PLoS ONE 01/2013; 8(5):e62929. · 4.09 Impact Factor
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ABSTRACT: OBJECTIVE:: We developed a new technique to measure blood pressure (BP) - the triple cuff and pulse delay time technique (TC-PDT) - which measures delay time with a single sensor at a single site unlike the existing delay time methods. This study aimed to evaluate the adequacy and accuracy of TC-PDT. METHODS:: TC-PDT measures delay time, which represents the difference in the arrival time of the arterial pulse wave between the proximal and distal areas of the cuff and provides clear criteria for BP determination based on the mechanism. Adequacy of delay time in TC-PDT was confirmed in comparison with established delay time of the pulse transit time technique (PTT). TC-PDT accuracy was evaluated according to the standard guidelines. RESULTS:: In TC-PDT, delay time showed changes in parallel with those observed in PTT. The correlation coefficient between BP by TC-PDT and that by PTT was 0.98 (P < 0.01) for SBP and 0.93 (P < 0.01) for DBP. According to the International Protocol guidelines (2002), the BP measurements of 33 patients met the recommended values for phase 1, 2.1 and 2.2 measurements. As per the Association for the Advancement of Medical Instrumentation (AAMI) SP10 guidelines (2002), the mean difference in BP measured by TC-PDT and that measured by the auscultatory technique in 85 patients was 1.0 ± 5.1 mmHg for SBP and -0.4 ± 4.5 mmHg for DBP, which conformed to the requirements. CONCLUSION:: TC-PDT is adequate to measure delay time and provides adequate and accurate measurements of BP. This device has the potential to be a standard tool for indirect BP measurement.
Journal of hypertension 12/2012; · 4.02 Impact Factor
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Tomohiko Kanaoka,
Kouichi Tamura,
Masato Ohsawa,
Mai Yanagi,
Sona Haku,
Hiromichi Wakui,
Akinobu Maeda,
Toru Dejima,
Kengo Azushima,
Hiroshi Mitsuhashi,
Yasuko Okano,
Tetsuya Fujikawa,
Yoshiyuki Toya,
Shunsaku Mizushima, Osamu Tochikubo,
Satoshi Umemura
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ABSTRACT: Strict blood pressure (BP) control is reportedly important for the management of hypertensive patients with chronic kidney disease (CKD). The purpose of this cross-sectional study was to examine whether the variables of ambulatory BP and the heart rate (HR) profile, central hemodynamics, and arterial stiffness were closely related to the renal function parameters (urine albumin excretion rate [UACR] and estimated glomerular filtration rate [eGFR]) observed in 25 consecutive hospitalized hypertensive patients with CKD. There were significant positive relationships between UACR and 24-hour, daytime, and nighttime ambulatory systolic BP. In addition, there were significant negative relationships between UACR and 24-hour and daytime HR variability. The circulating B-type natriuretic peptide level and hemoglobin A1c were also positively related to UACR. With respect to eGFR, although the 24-hour and nighttime HR variability were positively associated with eGFR, the circulating pentosidine and nighttime HR had a negative relationship with eGFR. On the other hand, central hemodynamics and arterial stiffness did not exhibit any significant association with renal function parameters. These results indicate that ambulatory BP and the HR profile are closely modulated by renal function deterioration. Further studies are needed to investigate the causal relationship between ambulatory BP and the HR profile and renal function parameters in hypertensive patients with CKD.
Clinical and Experimental Hypertension 05/2012; 34(4):264-9. · 1.07 Impact Factor
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Akinobu Maeda,
Kouichi Tamura,
Tomohiko Kanaoka,
Masato Ohsawa,
Sona Haku,
Kengo Azushima,
Toru Dejima,
Hiromichi Wakui,
Mai Yanagi,
Yasuko Okano,
Tetsuya Fujikawa,
Yoshiyuki Toya,
Shunsaku Mizushima, Osamu Tochikubo,
Satoshi Umemura
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ABSTRACT: Recent guidelines recommend combination antihypertensive therapy to achieve the target blood pressure (BP) and to suppress target organ damage. This study aimed to examine the beneficial effects of combination therapy with candesartan and amlodipine on BP control and markers of target organ function in Japanese essential hypertensive patients (N = 20) who did not achieve the target BP level during the monotherapy period with either candesartan or amlodipine. After the monotherapy period, for patients already being treated with amlodipine, a once-daily 8 mg dose of candesartan was added on during the combination therapy period (angiotensin II receptor blocker [ARB] add-on group, N = 10), and a once-daily 5 mg dose of amlodipine was added on for those already being treated with candesartan (calcium channel blocker [CCB] add-on group, N = 10). Combination therapy with candesartan and amlodipine for 12 weeks significantly decreased clinic and home systolic blood pressure (SBP) and diastolic blood pressure (DBP). In addition, the combination therapy was able to significantly reduce urine albumin excretion without decrease in estimated glomerular filtration ratio and resulted in significant improvements in brachial-ankle pulse wave velocity, central SBP, and insulin sensitivity. Furthermore, the CCB add-on group showed a significantly greater decrease in clinic and home DBP than the ARB add-on group. The calcium channel blocker add-on group also exhibited better improvements in vascular functional parameters than the ARB add-on group. These results suggest that combination therapy with candesartan and amlodipine is an efficient therapeutic strategy for hypertension with pleiotropic benefits.
Clinical and Experimental Hypertension 05/2012; 34(4):249-57. · 1.07 Impact Factor
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ABSTRACT: Observation of early changes in fasting plasma glucose level induced by post-smoking cessation weight gain is useful in predicting the risks of diabetes mellitus (DM) and impaired fasting glucose (IFG). We investigated the effect of post-smoking cessation weight gain on early changes in the risk of a high fasting plasma glucose (IFG) level (≥100 mg/dL).
In 946 subjects who underwent repeated health examinations after smoking cessation, changes in body mass index (BMI) and the odds ratio (OR) for IFG risk (adjusted for sex, age, BMI, fasting plasma glucose at year 1, and alcohol consumption) were calculated every year for 3 years after smoking cessation.
After smoking cessation, the rate of BMI increase significantly increased in quitters: 2.36% at year 2 (never smokers: 0.22%, current smokers: 0.39%) and 0.46% at year 3 (never smokers: 0.14%, current smokers: 0.32%). However, it decreased by 0.15% at year 4 (never smokers: 0.12%, current smokers: 0.26%). The ORs for quitters did not significantly increase at any time during the follow-up period. However, among quitters who had smoked at least 20 cigarettes per day, it was significantly higher (OR 1.51, 95% confidence interval 1.1-2.01 at year 1 and 1.71, 1.23-2.38 at year 2).
The time course of the risk of IFG after smoking cessation was similar to that for the rate of BMI increase. In contrast to the findings of previous reports, the increase in IFG risk after smoking cessation was brief and disappeared in the absence of a significant increase in BMI.
Journal of Epidemiology 11/2011; 21(6):431-9. · 1.86 Impact Factor
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ABSTRACT: We investigated the effectiveness of a workplace intervention program that utilized self-monitoring of daily salt excretion by an electronic salt sensor and sent personalized e-mail advice via cellular phone. Forty-one hypertensive male workers were assigned to intervention and control groups, then counseled together. Intervention group members were asked to measure daily salt excretion and received e-mail advice. After 4 weeks, a greater decrease of blood pressure (BP) was observed in the intervention group, with significant reductions to daily salt excretion and home BP. The new intervention program is considered useful for BP control among hypertensive workers.
Clinical and Experimental Hypertension 01/2011; 33(4):216-22. · 1.07 Impact Factor
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Yohei Miyagi,
Masahiko Higashiyama,
Akira Gochi,
Makoto Akaike,
Takashi Ishikawa,
Takeshi Miura,
Nobuhiro Saruki,
Etsuro Bando,
Hideki Kimura,
Fumio Imamura, [......],
Akihiko Chiba,
Fumihiro Oshita,
Akira Imaizumi,
Hiroshi Yamamoto,
Hiroshi Miyano,
Katsuhisa Horimoto, Osamu Tochikubo,
Toru Mitsushima,
Minoru Yamakado,
Naoyuki Okamoto
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ABSTRACT: Recently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection.
Plasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS). Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer), regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling.
These findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a relatively simple plasma assay and imposes a lower physical burden on subjects when compared to existing screening methods.
PLoS ONE 01/2011; 6(9):e24143. · 4.09 Impact Factor
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ABSTRACT: Although lifestyle modification is the key treatment of metabolic syndrome (MetS), clinical data on the dynamical relationship between metabolic state and MetS has been limited. This study investigated the mutual correlations between demographic and biochemical variables, and the metabolic state based on the plasma amino acid (AA) concentrations, during a lifestyle modification for MetS.
Japanese subjects, consisting of 54 patients with MetS [MetS(+)] and 35 persons without MetS [MetS(-)] were included in the study. Before a lifestyle modification program, the levels of glutamate metabolism-related AA (Glu-mAA), aromatic AA metabolism-related AA (Aromatic-mAA) and alanine metabolism-related AA (Ala-mAA) were significantly higher, while those of glycine-serine-threonine metabolism-related AA (Gly-Ser-Thr-mAA) were significantly lower compared to those in MetS(-). After a lifestyle modification, significant reductions (P<0.05) in the BMI (-1.4 kg/m(2)), mean blood pressure (-7.9 mmHg), hemoglobin A(1c) (-0.4%), and triglycerides (-30.6 mg/dl) were observed, and significant differences in the plasma AA levels between MetS(+) and MetS(-) were resolved. In addition, the diagnostic items of MetS were positively correlated with the levels of Glu-mAA, Ala-mAA, branched chain AA (BCAA)-mAA, Aromatic-mAA, and negatively correlated with the levels of Gly-Ser-Thr-mAA.
As MetS subsided, the abnormality of mean plasma AA levels of the MetS(+) group returned to similar values as those in the MetS(-) group, suggesting a novel viewpoint regarding the metabolic mechanism of lifestyle modification.
Circulation Journal 11/2010; 74(11):2434-40. · 3.77 Impact Factor
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ABSTRACT: It is well known that the sour milk containing lactotripeptides has a blood pressure lowering effect. The aim of this study was to evaluate the blood pressure (BP) lowering effect of lactotripeptides by monitoring home blood pressure, 24-h ambulatory measurements (ABPM), and daily urinary salt excretion. A total of 30 volunteers were given 200 ml of sour milk twice a day for 8 weeks after a 1-week run-in period. This preparation contained the lactotripeptides valine-proline-proline 2.66 mg and isoleucine-proline-proline 1.38 mg. The study participants had daily measurements of urinary salt excretion determined by an electric salt sensor and home blood pressure for each week during the run-in period, before the 4-and 8-week time points. 24-h ABPM was measured at the end of each week. Mean systolic blood pressure (SBP) during night sleep including base BP at 4 and 8 weeks were significantly lower than baseline values. Mean SBP and diastolic blood pressure (DBP) during night sleep of the 22 participants who belonged to the criteria of hypertension by 24-h ABPM was significantly decreased at 4 and 8 weeks. The change in 24-h mean SBP significantly correlated with mean urinary salt excretion over the three measurement periods. The 22 hypertensive subjects without taking lactotripeptides did not show significant change of blood pressure during 24 hours at 4 and 8 weeks. Our study confirmed the BP lowering effect of lactotripeptides during night-time sleep and showed that a lower intake of salt may increase the BP lowering effect of lactotripeptides through 24 hours in hypertensive subjects.
Clinical and Experimental Hypertension 07/2010; 32(4):214-20. · 1.07 Impact Factor
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ABSTRACT: The aim of the present study was to examine the relationships between the anti-hypertensive effects, autonomic function, and health-related quality of life (HRQOL) following treatment of hypertensive subjects with angiotensin receptor blockers (ARBs) in hypertensives. Nineteen patients with hypertension were assigned randomly to daily treatment with ARBs. After 16 weeks of treatment, blood pressure (BP) and 24 h the ratio of low frequency to high frequency component (LF/HF), an index of sympathovagal balance were decreased by ARBs. The HRQOL scores improved during the study. In this study, ARB therapy was associated with an improvement in BP, autonomic function, and HRQOL.
Clinical and Experimental Hypertension 11/2009; 31(8):680-9. · 1.07 Impact Factor
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ABSTRACT: Variation in 24-h blood pressure (BP) is associated with multiple factors, but the association has not been thoroughly examined in young adults. To elucidate the potential factors associated with variation in 24-h BP, 331 healthy medical students were investigated. Awake mean BP negatively correlated with sleep duration in males. Sixty-seven subjects (20.2%) had a high 24-h BP according to the ESH/ESC 2007 guidelines (systolic blood pressure (SBP) 125 and/or diastolic blood pressure (DBP) 80 mmHg). After multivariate analysis for confounding factors, male gender, body mass index (BMI), smoking, the 24-h low/high frequency component (heart rate variability spectral analysis), and short sleep (5 h or less) were found to be associated with high BP. The present study is the first to demonstrate the multivariate risk factors for elevated 24-h BP in a large number of young adults. Further investigation is required to determine the causal relationship between modifiable BP-related factors and elevated 24-h BP in young adults.
Clinical and Experimental Hypertension 11/2009; 31(8):705-12. · 1.07 Impact Factor
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ABSTRACT: Patients with orthostatic hypotension have pathologic hemodynamics related to changes in body posture. A new cephalic laser blood flowmeter that can be worn on the tragus to investigate the hemodynamics upon rising from a sitting or squatting posture was developed.
The relationship between cephalic hemodynamics and cerebral ischemic symptoms in 63 subjects in a sitting, squatting, and standing positions using the new device was evaluated. Transient decrease in blood pressure within 15 s after rising to an erect position possibly causes dizziness, syncope, and fall. Subjects exhibiting dizziness upon standing showed a significant decrease in the cephalic blood flow (CBF) and indirect beat-to-beat systolic blood pressure, as monitored by the Finometer, and a significant correlation was observed between the drop ratio (drop value on rising/mean value in the squatting position) of CBF and that of systolic blood pressure.
This new wearable CBF-meter is potentially useful for estimating cephalic hemodynamics and objectively diagnosing cerebral ischemic symptoms of subjects in a standing posture.
Circulation Journal 09/2009; 73(10):1950-5. · 3.77 Impact Factor
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Clinical and Experimental Nephrology 08/2009; · 1.37 Impact Factor
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ABSTRACT: The metabolic syndrome caused by visceral-fat obesity is a major risk factor for atherosclerosis. This study used a new information communication technology (ICT) to investigate body weight (BW) and blood pressure (BP) changes in response to nutritional guidance. Obese subjects with hypertension, hyperlipidemia, or impaired glucose tolerance received guidance with the ICT method (n = 13) or face-to-face according to conventional methods (n = 39). The effects of the methods were compared. After 12 weeks, significant weight loss and BP reduction were observed in the ICT group. Also, significant higher improvements were observed in total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and HbA(1c) in the ICT-group compared with those groups using the conventional method. The effectiveness of the ICT method in reducing BW, BP, total and LDL cholesterol, and HbA(1c) was demonstrated.
Clinical and Experimental Hypertension 06/2009; 31(3):231-40. · 1.07 Impact Factor
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ABSTRACT: We report the relationship between 24-hour (24-h) blood pressure, autonomic function, and health-related quality of life (HRQOL) in normotensives and hypertensives. The aim of this study was to determine whether there is a relationship between 24-h blood pressure, autonomic function, and HRQOL during treatment with an angiotensin receptor blocker (ARB) in patients with hypertension. Thirteen patients with hypertension were randomly treated with losartan (25-50 mg, n = 5), candesartan (4-8 mg, n = 4), valsartan (80 mg, n = 1), telmisartan (40 mg, n = 2), and olmesartan (10 mg, n = 1), daily. 24-h ambulatory blood pressure (BP) was measured before treatment and 3 months after treatment. Sympathetic nervous activity (the ratio of low frequency to high frequency component (LF/HF)) and parasympathetic nervous activity (high frequency component (HF)) were calculated by analyzing heart rate variability. HRQOL was assessed using a medical outcome study short-form 36-item health survey (SF-36) questionnaire. All of the participants completed the study. Angiotensin receptor blocker treatment reduced 24-h mean BP (MBP) from 107 +/- 9 to 100 +/- 9 mmHg. 24-h MBP positively correlated with 24-h LF/HF in all subjects who received ARB (R = 0.568, p < 0.04). There were no differences in heart rate, serum albumin level, BUN level, creatinine level, potassium level, or HRQOL score. These findings indicated that ARB reduced BP; however, treatment with ARB did not affect the scores of HRQOL and the relationship between 24-h blood pressure and autonomic function.
Clinical and Experimental Hypertension 06/2009; 31(3):250-8. · 1.07 Impact Factor
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Clinical and Experimental Hypertension - CLIN EXP HYPERTENSION. 01/2009; 31(8):680-689.
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ABSTRACT: The human sapovirus (SaV) causes acute gastroenteritis mainly in infants and young children. A food-borne outbreak of gastroenteritis associated with SaV occurred among junior high school students in Yokohama, Japan, during and after a study trip. The nucleotide sequences of the partial capsid gene derived from the students exhibited 98% homology to a SaV genogroup IV strain, Hu/Angelholm/SW278/2004/SE, which was isolated from an adult with gastroenteritis in Solna, Sweden. An identical nucleotide sequence was detected from a food handler at the hotel restaurant, suggesting that the causative agent of the outbreak was transmitted from the food handler. This is the first description of a food-borne outbreak associated with the SaV genogroup IV strain in Japan.
Japanese journal of infectious diseases 12/2008; 61(6):438-41. · 1.49 Impact Factor
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ABSTRACT: The aim of the present study was to measure peripheral blood flow (BF) with a new finger-occlusion plethysmograph (FOP) and to compare this to BF measured with a laser Doppler flowmeter (LDF). An additional objective was to investigate the relationship between hypertension-related clinical parameters and peripheral vascular resistance (PVR) estimated from BF and mean blood pressure (BP) (PVR=mean BP/BF) in young subjects.
The present study employed 101 young volunteers (61 males, 40 females, mean age 23.2+/-2.5 years). The FOP was attached to the third finger and an LDF to the fourth fingertip of each subject. BF was measured simultaneously by the 2 devices. A multi-biomedical recorder (TM2425) measured 24-h BP. A high correlation was observed between BF measured by the FOP and LDF (r=0.79, p<0.001). In multiple linear regression analysis, PVR was independently correlated with a family history of hypertension (p<0.01) and with base diastolic BP during sleep (p<0.01), which is a sensitive predictor of severity of hypertension.
Our newly developed FOP can estimate peripheral absolute BF easily. Furthermore, BF determined by the FOP can be used to calculate PVR, and an elevated PVR may be a useful predictor of hypertension.
Circulation Journal 08/2008; 72(8):1329-35. · 3.77 Impact Factor
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ABSTRACT: Objective. This study aimed to determine whether mental stress influences the plasma total homocysteine level or blood pressure in young men. Method. Twenty-seven male university students were assigned to a normal blood pressure group (24-h systolic blood pressure <125 mmHg and diastolic blood pressure <75 mmHg; 13 subjects) or a high blood pressure group (24-h systolic blood pressure > or =125 mmHg, or 24-h diastolic blood pressure > or =75 mmHg; 14 subjects). Wearing an ambulatory blood pressure monitoring device, subjects rested for 30 minutes, underwent an arithmetic test for 15 minutes, and rested again for 15 minutes. Blood samples were taken before and after the test. Plasma total homocysteine levels were measured. Heart rate, blood pressure, and sympathovagal balance were determined during the test. Results. The mean total homocysteine level at rest in the high blood pressure group was slightly, but not significantly, higher than that in the normal blood pressure group. The resting total homocysteine level was significantly higher in subjects with parental history of hypertension than in those without (p < 0.01). Blood pressure, heart rate, and the plasma total homocysteine level were increased significantly by mental stress (p < 0.05). The change in total homocysteine correlated significantly with the changes in systolic blood pressure and sympathovagal balance (p < 0.05). Conclusion. Resting total homocysteine level was significantly higher in male students with a parental history of hypertension than in those without. It was shown that mental stress elevates heart rate, blood pressure, sympathovagal activity, and the plasma total homocysteine level in young men.
Clinical and Experimental Hypertension 04/2008; 30(3):233-41. · 1.07 Impact Factor
