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Hiuge-Shimizu A.,Osaka University | Kishida K.,Osaka University | Funahashi T.,Osaka University | Ishizaka Y.,Center for Multiphasic Health Testing and Services | And 13 more authors.
Annals of Medicine

Background. The management of cardiovascular risk factors is important for prevention of atherosclerotic cardiovascular diseases (ACVD). Visceral fat accumulation plays an important role in the clustering of cardiovascular risk factors, leading to ACVD. The present study investigated the gender-and age-specific relationship between obesity-related cardiovascular risk factor accumulation and computed tomography (CT)-measured fat distribution in a large-scale Japanese general population. Methods and results. Fat distribution was measured on CT scans in 12,443 subjects (males/females = 10,080/2,363), who underwent medical health check-up at 9 centers in Japan. The investigated obesity-related cardiovascular risk factors were hyperglycemia, dyslipidemia, and elevated blood pressure. Visceral fat area (VFA) for all males and old females showed almost symmetric distribution, while that of young females showed skewed distribution with a marked left shift. Only a small proportion of young females had large visceral fat and cardiovascular risk accumulation. The mean number of risk factors exceeded 1.0 at around 100 cm 2 for VFA in all groups, irrespective of gender, age (cut-off age 55), and BMI (cut-off BMI 25 kg/m 2). Conclusions. In this large-scale Japan-wide general population study, an absolute VFA value of about 100 cm 2 equated with obesity-related cardiovascular risk factor accumulation, irrespective of gender, age, and BMI. © 2012 Informa UK, Ltd. Source

Miyagi Y.,Kanagawa Cancer Center | Higashiyama M.,Japan National Cardiovascular Center Research Institute | Gochi A.,Okayama University of Science | Akaike M.,Kanagawa Cancer Center | And 18 more authors.

Background: 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. Methods and Findings: 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. Conclusions: 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. © 2011 Miyagi et al. Source

Shingyoji M.,Chiba Cancer Center | Iizasa T.,Chiba Cancer Center | Higashiyama M.,Japan National Cardiovascular Center Research Institute | Imamura F.,Japan National Cardiovascular Center Research Institute | And 8 more authors.
BMC Cancer

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. © 2013 Shingyoji et al; licensee BioMed Central Ltd. Source

Yamaji Y.,University of Tokyo | Mitsushima T.,Kameda Medical Center Makuhari | Koike K.,University of Tokyo
Digestive and Liver Disease

Background: Although both colorectal neoplasms and atherosclerosis may be induced by visceral fat accumulation, no association between these factors has yet been elucidated. Methods: Among Japanese participants in our colonoscopic screening and annual surveillance programs, asymptomatic subjects were investigated. Visceral fat area was measured by computed tomography, and the ankle-brachial index and pulse-wave velocity (markers of systemic atherosclerosis) were also estimated. Colorectal findings during screening were investigated in association with these parameters. Results: Nine hundred and seven subjects (males: 71.9%; mean age: 57.3. ±. 8.7 years) were enrolled. Colorectal adenomas were identified during colorectal screening of 407 subjects (44.9%). The prevalence of all colorectal adenoma and advanced neoplasia increased with an elevated pulse-wave velocity from 32.2% (advanced neoplasia, 2.6) to 62.1% (8.4%) in higher quartiles (. p<. 0.001 and p=. 0.003). The risk of advanced neoplasia was higher in subjects with an abnormal ankle-brachial index (33% vs. 4.6%, p<. 0.001). Upon multivariate analysis, visceral fat area and pulse-wave velocity were associated with all adenoma, and the ankle-brachial index with advanced neoplasia. Conclusions: The risk of colorectal adenoma was strongly associated with visceral fat area and markers of atherosclerosis. Colorectal adenoma and atherosclerosis may share a common pathogenesis and the same populations are at high-risk. © 2014 Editrice Gastroenterologica Italiana S.r.l. Source

Takahashi Y.,University of Tokyo | Yamamichi N.,University of Tokyo | Shimamoto T.,Kameda Medical Center Makuhari | Mochizuki S.,University of Tokyo | And 8 more authors.
Journal of Gastroenterology

Background: Our aim is to elucidate causative factors for gallstones, especially focusing on Helicobacter pylori (HP) infection. Methods: We analyzed 15,551 Japanese adults who had no history of gastrectomy, cholecystectomy, HP eradication, and didn't use proton pump inhibitors, anti-diabetic drugs, or anti-cholesterol drugs. 1,057 subjects who previously had HP eradication were analyzed separately. Results: Gallstones were detected in 409 of 8,625 men (4.74 %) and 285 of 6,926 women (4.11 %) by ultrasonography. Among the 25 factors univariately analyzed, age, HP infection, alcohol intake, weight, body mass index (BMI), and 14 blood test values (AST, ALT, ALP, γ-GTP, T-Chol, HDL-Chol, LDL-Chol, TG, TP, Hb, HbA1c, pepsinogen I, pepsinogen II, and pepsinogen I/II ratio) displayed significant association with gallstones (p < 0.05), whereas gender, smoking, height, and three blood test values (Alb, T-Bil, MCV) did not. Multivariate analysis showed that age, gender, alcohol intake, BMI, γ-GTP, LDL-Chol, TP, and HP infection had significant association (p < 0.05). Successive multiple logistic regression analysis calculating odds ratio (OR) and standardized coefficients (β) showed that age (OR/β = 1.57/0.450), BMI (OR/β = 1.30/0.264), HP infection (OR/β = 1.51/0.206), lower alcohol intake (OR/β = 1.33/0.144), γ-GTP (OR/β = 1.15/0.139), and pepsinogen I/II ratio (OR/β = 1.08/0.038) have significant positive association with gallstones, whereas gender does not. The gallstone prevalence among HP-negative, HP-eradicated, and HP-positive subjects was 3.81, 4.73 and 6.08 %, respectively. The matched analysis controlling age, BMI, γ-GTP, alcohol intake, pepsinogen I/II ratio and gender also demonstrated that gallstone prevalence among HP-eradicated subjects was significantly lower compared with HP-positive subjects (p < 0.05). Conclusions: HP infection is positively associated with gallstones. HP eradication may lead to prevention of gallstones. © 2013 Springer. Source

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