Yoichi M Ito

Hokkaido University, Sapporo, Hokkaidō, Japan

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Publications (44)157.08 Total impact

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    ABSTRACT: (123)I-metaiodobenzylguanidine (MIBG) has been used to estimate cardiac sympathetic nervous innervation. Heterogeneous MIBG distribution is mainly associated with high physiological MIBG uptakes in the liver. We postulate that prone position acquisition might be especially effective for MIBG, providing for separation from high liver uptake similar to that provided by perfusion single-photon emission computed tomography (SPECT). We investigated whether prone-position acquisition improved MIBG image quality by comparing our results to those acquired using supine MIBG and high-quality (11)C-hydroxyephedrine (HED) positron emission tomography/computed tomography PET/CT.
    Annals of Nuclear Medicine 06/2014; · 1.41 Impact Factor
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    ABSTRACT: To address the role of cancer-stroma interactions, we performed gene expression profiling of both cancer and stroma, using matching samples of endometrial cancer (EC), and analyzed the relationship between the gene expression pattern and prognosis in EC. Sixty EC cases were included in this study (38 nonrecurrent and 22 recurrent). Cancer and stroma were separated by performing laser capture microdissection, and microarray analysis was performed separately on cancer and stromal cells. Genes related with progression-free survival (PFS) in cancer and stroma were analyzed using the Cox regression model, and we established a formula, based on the gene expression pattern of cancer and stroma, to predict recurrence using logistic regression. We estimated the accuracy of the formula using the 0.632 method. All cases were classified based on the 79 selected genes of cancer and stroma related to PFS, based on unsupervised clustering. A total of 143 genes in cancer, and 79 genes in stroma were significantly related with PFS. The estimated area under the curve of receiver operating characteristics curve in cancer and stroma to predict recurrence were 0.800 and 0.758, respectively. Based on the 79 genes of cancer, the 22 recurrent cases were divided into two groups, which generally correlated with the histological grade. In contrast, based on the 79 genes of stroma, the 22 recurrent cases displayed homogeneous gene expression, unrelated to the histological grade. We conclude that gene expression profiles of cancer and stroma can predict the recurrence of EC and stromal that gene expression does not depend on the cancer grade. © 2014 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 05/2014; · 3.55 Impact Factor
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    ABSTRACT: Long-acting β2-agonists and leukotriene receptor antagonists are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. The Gly16Arg genotype of the β2-adrenergic receptor (ADRB2) gene may influence the bronchodilator effects of β2-agonists. We hypothesized that differential responses to long-acting β2-agonists or leukotriene receptor antagonists might be determined partly by the Gly16Arg polymorphism in Japanese asthma patients. This randomized, genotype-stratified, two-period crossover study included 80 patients with mild-to-moderate asthma (35 Arg/Arg and 45 Gly/Gly individuals). The primary study outcome was the difference in peak expiratory flow (ΔPEF) (ΔPEF, l/min) by genotype after 16 weeks of treatment with salmeterol (ΔPEFsal) or montelukast (ΔPEFmon). In addition, multivariate analyses were used to identify independent factors that were predictive of responses to each treatment. The mean ΔPEFsal-ΔPEFmon was 19.3±46.6 among Arg/Arg individuals and 16.8±51.5 among Gly/Gly individuals, indicating that the Gly16Arg genotype did not influence the differential bronchodilator effect of the two agents. Multivariate analysis showed that higher peripheral eosinophil counts were associated with better response to salmeterol (P<0.05). The Gly16Arg genotype did not influence the differential bronchodilator effect of salmeterol or montelukast as an add-on therapy to ICS within 16 weeks of follow-up. Higher peripheral eosinophil counts may be associated with better responses to salmeterol in combination with ICS.
    Pharmacogenetics and Genomics 03/2014; · 3.61 Impact Factor
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    ABSTRACT: The right ventricle (RV) has a high capacity to adapt to pressure or volume overload before failing. However, the mechanisms of RV adaptation, in particular RV energetics, in patients with pulmonary hypertension (PH) are still not well understood. We aimed to evaluate RV energetics including RV oxidative metabolism, power and efficiency to adapt to increasing pressure overload in patients with PH using (11)C-acetate PET. In this prospective study, 27 patients with WHO functional class II/III PH (mean pulmonary arterial pressure 39.8 ± 13.5 mmHg) and 9 healthy individuals underwent (11)C-acetate PET. (11)C-acetate PET was used to simultaneously measure oxidative metabolism (k mono) for the left ventricle (LV) and RV. LV and RV efficiency were also calculated. The RV ejection fraction in PH patients was lower than in controls (p = 0.0054). There was no statistically significant difference in LV k mono (p = 0.09). In contrast, PH patients showed higher RV k mono than did controls (0.050 ± 0.009 min(-1) vs. 0.030 ± 0.006 min(-1), p < 0.0001). PH patients exhibited significantly increased RV power (p < 0.001) and hence increased RV efficiency compared to controls (0.40 ± 0.14 vs. 0.017 ± 0.12 mmHg·mL·min/g, p = 0.001). The RV oxidative metabolic rate was increased in patients with PH. Patients with WHO functional class II/III PH also had increased RV power and efficiency. These findings may indicate a myocardial energetics adaptation response to increasing pulmonary arterial pressure.
    European Journal of Nuclear Medicine 03/2014; · 4.53 Impact Factor
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    ABSTRACT: Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs).
    PLoS ONE 01/2014; 9(8):e103822. · 3.73 Impact Factor
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    ABSTRACT: Radiotherapy for high-grade meningioma (HGM) is one of the essential treatment options for disease control. However, appropriate irradiation timing remains under debate. The object of this study is to discern which prognostic factors impact recurrence in HGM patients and to propose a risk-stratification system for the application of postoperative radiotherapy. We retrospectively reviewed 55 adult patients who were diagnosed with Grade II and III intracranial meningioma. Cox regression models were applied to the analysis for impact on early recurrence in HGM patients without postoperative radiotherapy. Grade III malignancy (P = 0.0073) and transformed histology (P = 0.047) proved to be significantly poor prognostic factors of early recurrence by multivariate analysis. The other candidates for recurrence factors were Simpson Grade 3-5 resection, preoperative Karnofsky Performance status < = 70%, and MIB-1 labeling index > = 15%. According to these prognostic factors, postoperative HGM patients could be stratified into three recurrence-risk groups. The prognoses were significantly different between each group, as the 3-year actual recurrence-free rates were 90% in low-risk group, 31% in intermediate-risk group, and 15% in high-risk group. We propose recurrence-risk stratification for postoperative HGM patients using clinically available factors. Our results suggest that the prognosis for patients with high-risk HGMs is dismal, whereas HGM patients belonging to the low-risk group could have favorable prognoses. This stratification provides us with the criteria necessary to determine whether to apply adjuvant radiotherapy to postoperative HGM patients, and to also help identify potentially curable HGMs without adjuvant radiotherapy.
    PLoS ONE 01/2014; 9(5):e97108. · 3.73 Impact Factor
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    ABSTRACT: The real-time tumor-tracking radiotherapy system with fiducial markers has the advantage that it can be used to verify the localization of the markers during radiation delivery in real-time. We conducted a prospective Phase II study of image-guided local-boost radiotherapy for locally advanced bladder cancer using a real-time tumor-tracking radiotherapy system for positioning, and here we report the results regarding the safety and efficacy of the technique. Twenty patients with a T2-T4N0M0 urothelial carcinoma of the bladder who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection and 40 Gy irradiation to the whole bladder was followed by the transurethral endoscopic implantation of gold markers in the bladder wall around the primary tumor. A boost of 25 Gy in 10 fractions was made to the primary tumor while maintaining the displacement from the planned position at less than ±2 mm during radiation delivery using a real-time tumor-tracking radiotherapy system. The toxicity, local control and survival were evaluated. Among the 20 patients, 14 were treated with concurrent chemoradiotherapy. The median follow-up period was 55.5 months. Urethral and bowel late toxicity (Grade 3) were each observed in one patient. The local-control rate, overall survival and cause-specific survival with the native bladder after 5 years were 64, 61 and 65%. Image-guided local-boost radiotherapy using a real-time tumor-tracking radiotherapy system can be safely accomplished, and the clinical outcome is encouraging. A larger prospective multi-institutional study is warranted for more precise evaluations of the technological efficacy and patients' quality of life.
    Japanese Journal of Clinical Oncology 12/2013; · 1.90 Impact Factor
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    ABSTRACT: Exacerbations are among the major factors that may affect the natural history of chronic obstructive pulmonary disease (COPD). The aim was to investigate the clinical characteristics and determinants of COPD exacerbations in our 5-year observational cohort study that had a very low exacerbation frequency.A total of 279 patients with COPD participated in the Hokkaido COPD cohort study, and 268 subjects who had clinical data for multiple visits were analysed. Exacerbation was defined in multiple ways: patient's subjective complaint, symptom definition, requiring prescription change, requiring antibiotic treatment, and requiring hospital admission.Exacerbation frequency (events/person/year) was 0.78±1.16 (subjective complaint), 0.24±0.47 (symptom definition), 0.20±0.43 (prescription definition), 0.13±0.28 (antibiotic definition), and 0.06±0.19 (admission definition). Exacerbation events did not significantly affect the annual decline in FEV1. A high St. George's Respiratory Questionnaire total score, especially its Activity score, and a low body mass index were strongly associated with exacerbation-free survival, exacerbation frequency, and development of recurrent exacerbations.Despite the low exacerbation frequency in our cohort study, impaired health-related quality of life and weight loss were found to be independent risk factors for COPD exacerbations.
    European Respiratory Journal 11/2013; · 6.36 Impact Factor
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    ABSTRACT: Perfluoroalkyl acids (PFAAs) are persistent organic pollutants that are used in a wide range of consumer products. Recent epidemiological studies have shown that prenatal exposure to toxic levels of PFAAs in the environment may adversely affect fetal growth and humoral immune response in infants and children. Here we have characterized levels of prenatal exposure to PFAA between 2003 and 2011 in Hokkaido, Japan, by measuring PFAA concentrations in plasma samples from pregnant women. The study population comprised 150 women who enrolled in a prospective birth cohort study conducted in Hokkaido. Eleven PFAAs were measured in maternal plasma samples using simultaneous analysis by ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry. At the end of the study, in 2011, age- and parity-adjusted mean concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorotridecanoic acid (PFTrDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) were 1.35ng/mL, 1.26ng/mL, 0.66ng/mL, 1.29ng/mL, 0.25ng/mL, 0.33ng/mL, 0.28ng/mL, and 3.86ng/mL, respectively. Whereas PFOS and PFOA concentrations declined 8.4%/y and 3.1%/y, respectively, PFNA and PFDA levels increased 4.7%/y and 2.4%/y, respectively, between 2003 and 2011. PFUnDA, PFDoDA, and PFTrDA were detected in the vast majority of maternal samples, but no significant temporal trend was apparent. Future studies must involve a larger population of pregnant women and their children to determine the effects of prenatal exposure to PFAA on health outcomes in infants and children.
    Environment international 09/2013; 60C:89-96. · 6.25 Impact Factor
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    ABSTRACT: The present study examined whether tricuspid annular plane systolic excursion (TAPSE) can simply predict right ventricular ejection fraction (RVEF) in patients with pulmonary hypertension (PH). The TAPSE cut-off value to predict reduced RVEF was also evaluated. The association between TAPSE and cardiac magnetic resonance imaging (CMRI)-derived RVEF was examined in 53 PH patients. The accuracy of the prediction equation to calculate RVEF using TAPSE was also evaluated. In PH patients, TAPSE was strongly correlated with CMRI-derived RVEF in PH patients (r = 0.86, p < 0.0001). We then examined the accuracy of the two equations: the original regression equation (RVEF = 2.01 × TAPSE + 0.6) and the simplified prediction equation (RVEF = 2 × TAPSE). Bland-Altman plot showed that the mean difference ± limits of agreement was 0.0 ± 10.6 for the original equation and -0.6 ± 10.6 for the simplified equation. Intraclass correlation coefficient was 0.84 for the original and 0.82 for the simplified equation. Normal RVEF was considered to be ≥40 % based on the data from 53 matched controls, and the best TAPSE cut-off value to determine reduced RVEF (<40 %) was calculated to be 19.7 mm (sensitivity 88.9 %, specificity 84.6 %). A simple equation of RVEF = 2 × TAPSE enables easy prediction of RVEF using TAPSE, an easily measurable M-mode index of echocardiography. TAPSE of 19.7 mm predicts reduced RVEF in PH patients with clinically acceptable sensitivity and specificity.
    The international journal of cardiovascular imaging 09/2013; · 2.15 Impact Factor
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    ABSTRACT: PURPOSE: Cardiac involvement in sarcoidosis is one of the leading causes of death associated with abnormalities of the conduction system. (18)F-FDG PET is useful for detecting inflammatory lesions in cardiac sarcoidosis. However, the relationship between ECG abnormalities and focal (18)F-FDG uptake has not been studied. The aim of this study was to evaluate the relationship between electrocardiogram (ECG) abnormalities and the location of elevated myocardial (18)F-FDG uptake in patients with sarcoidosis. METHODS: Included in the study were 50 patients (56.3 ± 14.9 years old) with histologically proven sarcoidosis with suspected cardiac involvement based on ECG or echocardiography. All patients had fasted for at least 6 h and were given unfractionated heparin (50 IU/kg) intravenously to reduce the physiological (18)F-FDG uptake in the myocardium. The left ventricle (LV) wall was divided into 17 segments by visual analysis. Obvious accumulation in each segment was defined as positive. RESULTS: Of the 50 patients, 33 showed some ECG abnormalities, including atrioventricular (AV) block in 13. Patients with abnormal ECG findings had a higher number of regions with (18)F-FDG uptake than patients without ECG abnormality (3.48 ± 2.73 vs. 1.41 ± 2.09 regions, p = 0.0051). Among ECG abnormalities, the predictor for interventricular septum wall (18)F-FDG involvement was AV block (p = 0.0025). CONCLUSION: Patients with ECG abnormalities showed a higher number of abnormal (18)F-FDG myocardial uptake regions than patients without ECG abnormalities. In particular, focal (18)F-FDG uptake in the interventricular septum in cardiac sarcoidosis was associated with AV block. Therefore, determination of regional (18)F-FDG distribution might contribute to patient management in cardiac sarcoidosis.
    European Journal of Nuclear Medicine 05/2013; · 4.53 Impact Factor
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    ABSTRACT: Purpose: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. Patients and Methods: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy (plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0-1 RP (RPG≤1) group and the Grade 2-5 RP (RPG≥2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. Results: Of these 86 patients, 10 (12%) developed RPG≥2 (Grade 2, n = 2 patients; Grade 3, n = 3; Grade 4, n = 3; Grade 5, n = 2). The patients in the RPG≤1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RPG≥2 group. There were two advantages gained from the proposed plan for V5 (<55%) and V10 (< 37%) values and the conformity of the PTV. Conclusion: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP.
    Journal of Radiation Research 05/2013; · 1.45 Impact Factor
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    ABSTRACT: PURPOSE: To investigate the specific imaging findings of multidetector row CT (MDCT) and PET/CT with(18)F-FDG in cardiac dominant diffuse large B-cell lymphoma (DLBCL) in comparison with other cardiac tumours. METHODS: Five patients with DLBCL and 12 patients with other cardiac tumours including pericardial tumours were retrospectively reviewed. Among the patients with other cardiac tumours, seven had metastatic tumours, three had benign tumours, and two had other malignant cardiac tumours. The location of the cardiac mass, the encasement of the coronary artery surrounded by the mass, and pericardial effusion were evaluated using MDCT. The disease activity of the cardiac tumour was also evaluated by PET/CT. RESULTS: Four of the five DLBCL patients had primarily right-sided cardiac lesions, which was seen significantly more frequently in DLBCL than in other cardiac tumours (p = 0.028). All cardiac DLBCL lesions were located around the atrioventricular groove and encased the coronary arteries. ECG-gated cardiac MDCT showed that there was no apparent stenosis of the coronary arteries. Large amounts of pericardial effusion were seen in all DLBCL patients. PET/CT revealed significantly higher FDG uptake in DLBCL than in other cardiac malignant tumours, with no overlap (p = 0.0007). CONCLUSION: The combination of a right-sided cardiac mass with a large pericardial effusion and no apparent stenosis of the encased coronary artery revealed by MDCT and a high maximum standard uptake value were the specific findings in cardiac dominant DLBCL.
    European Journal of Nuclear Medicine 05/2013; · 4.53 Impact Factor
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    ABSTRACT: Tumor hypoxia is well known to be radiation resistant. (18)F-fluoromisonidazole ((18)F-FMISO) PET has been used for noninvasive evaluation of hypoxia. Quantitative evaluation of (18)F-FMISO uptake is thus expected to play an important role in the planning of dose escalation radiotherapy. However, the reproducibility of (18)F-FMISO uptake has remained unclarified. We therefore investigated the reproducibility of tumor hypoxia by using quantitative analysis of (18)F-FMISO uptake. METHODS: Eleven patients with untreated head and neck cancer underwent 2 (18)F-FMISO PET/CT scans ((18)F-FMISO(1) and (18)F-FMISO(2)) with a 48-h interval prospectively. All images were acquired at 4 h after (18)F-FMISO injection for 10 min. The maximum standardized uptake (SUVmax), tumor-to-blood ratio (TBR), and tumor-to-muscle ratio (TMR) of (18)F-FMISO uptake were statistically compared between the 2 (18)F-FMISO scans by use of intraclass correlation coefficients (ICCs). The hypoxic volume was calculated as the area with a TBR of greater than or equal to 1.5 or the area with a TMR of greater than or equal to 1.25 to assess differences in hypoxic volume between the 2 (18)F-FMISO scans. The distances from the maximum uptake locations of the (18)F-FMISO(1) images to those of the (18)F-FMISO(2) images were measured to evaluate the locations of (18)F-FMISO uptake. RESULTS: The SUVmax (mean ± SD) for (18)F-FMISO(1) and (18)F-FMISO(2) was 3.16 ± 1.29 and 3.02 ± 1.12, respectively, with the difference between the 2 scans being 7.0% ± 4.6%. The TBRs for (18)F-FMISO(1) and (18)F-FMISO(2) were 2.98 ± 0.83 and 2.97 ± 0.64, respectively, with a difference of 9.9% ± 3.3%. The TMRs for (18)F-FMISO(1) and (18)F-FMISO(2) were 2.25 ± 0.71 and 2.19 ± 0.67, respectively, with a difference of 7.1% ± 5.3%. The ICCs for SUVmax, TBR, and TMR were 0.959, 0.913, and 0.965, respectively. The difference in hypoxic volume based on TBR was 1.8 ± 1.8 mL, and the difference in hypoxic volume based on TMR was 0.9 ± 1.3 mL, with ICCs of 0.986 and 0.996, respectively. The maximum uptake locations of the (18)F-FMISO(1) images were different from those of the (18)F-FMISO(2) images and were within the full width at half maximum of the PET/CT scanner, except in 1 case. CONCLUSION: The values for (18)F-FMISO PET uptake and hypoxic volume in head and neck tumors between the 2 (18)F-FMISO scans were highly reproducible. Such high reproducibility of tumor hypoxia is promising for accurate radiation planning.
    Journal of Nuclear Medicine 01/2013; · 5.77 Impact Factor
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    ABSTRACT: BACKGROUND: Most of the glycan changes reported in cancers were based on the examinations of a small number of patients or particular proteins. The aim of this study was to determine the changes of the serum N-glycan profile comprehensively in a large number of pancreatic cancer patients and investigate its clinical utility. METHODS: Glycan levels in the serum of 92 pancreatic cancer patients and 243 healthy volunteers (HLT) were examined by comprehensive quantitative high-throughput glycome analysis and were compared with clinical parameters. RESULTS: Out of 66 glycans detected, 15 were differentially expressed in pancreatic cancer, and 10 out of the 15 glycans were significantly up-regulated in cases with distant metastasis. There was a clear increase in overall expression of serum glycans, especially highly-branched glycans with fucose moieties, in pancreatic cancer. Among these 15 glycans, a tri-antennary complex type glycan (m/z 3195) showed the highest area under the receiver operating characteristic curve (AUROC = 0.799) for the diagnosis of pancreatic cancer. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) was found to be significantly higher in pancreatic cancer than in HLT (median = 1.11 and 0.41, respectively; p < 0.0001, AUROC = 0.831). For this pair ratio, the hazard ratio for survival (2.60, 95 % CI = 1.44-4.79) was higher than that of any single glycan and 1-year survival of patients with a high and low ratio was 36.9 and 69.2 %, respectively, (p = 0.001). CONCLUSIONS: Comprehensive glycome analysis can be used to know the presence of pancreatic cancer, distant metastasis, and patient prognosis, simultaneously.
    Journal of Gastroenterology 01/2013; · 3.79 Impact Factor
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    ABSTRACT: This study investigated the major clinical determinants of late gadolinium enhancement (LGE) at ventricular insertion points (VIPs) commonly seen in patients with pulmonary hypertension (PH). Forty-six consecutive PH patients (mean pulmonary artery pressure ≥25 mmHg at rest) and 21 matched controls were examined. Right ventricular (RV) morphology, function and LGE mass volume at VIPs were assessed by cardiac magnetic resonance (CMR). Radial motion of the left ventricular (LV) wall and interventricular septum (IVS) was assessed by speckle-tracking echocardiography. Paradoxical IVS motion index was then calculated. Univariate and multivariate regression analysis were conducted to characterize the relationship between LGE volume at VIPs and PH-related clinical indices, including the paradoxical IVS motion index. Mean pulmonary arterial pressure (MPAP) of PH patients was 38±9 mmHg. LGE at VIPs was observed in 42 of 46 PH patients, and the LGE volume was 2.02 mL (0.47-2.99 mL). Significant correlations with LGE volume at VIPs were observed for MPAP (r = 0.50) and CMR-derived parameters [RV mass index (r = 0.53), RV end-diastolic volume index (r = 0.53), RV ejection fraction (r = -0.56), and paradoxical IVS motion index (r = 0.77)]. In multiple regression analysis, paradoxical IVS motion index alone significantly predicted LGE volume at VIPs (p<0.001). LGE at VIPs seen in patients with PH appears to reflect altered IVS motion rather than elevated RV pressure or remodeling. Long-term studies would be of benefit to characterize the clinical relevance of LGE at VIPs.
    PLoS ONE 01/2013; 8(6):e66724. · 3.73 Impact Factor
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    ABSTRACT: A major problem of current cancer research and therapy is prediction of tumor recurrence after initial treatment, rather than the simple biological characterization of the malignancy and proliferative properties of tumors. Breast conservation therapy (BCT) is a well-approved, standard treatment for patients with early stages of breast cancer, which consists of lumpectomy and whole-breast irradiation. In spite of extensive studies, only 'age' and 'Ki-67 positivity' have been identified to be well correlated with local recurrence after BCT. An Arf6 pathway, activated by GEP100 under receptor tyrosine kinases (RTKs) and employs AMAP1 as its effector, is crucial for invasion and metastasis of some breast cancer cells. This pathway activates β1 integrins and perturbs E-cadherin-based adhesions, hence appears to be integral for epithelial-mesenchymal transdifferentiation (EMT). We here show that expression of the Arf6 pathway components statistically correlates with rapid local recurrence after BCT. We retrospectively analyzed four hundred seventy-nine patients who received BCT in Hokkaido University Hospital, and found 20 patients had local recurrence. We then analyzed pathological samples of patients who experienced local recurrence by use of Kaplan-Meier analysis, Stepwise regression analysis and the t-test, coupled with immunostaining, and found that co-overexpression of GEP100 and AMAP1 correlates with rapidity of the local recurrence. Their margin-status, node-positivity, and estrogen receptor (ER)- or progesterone receptor (PgR)-positivity did not correlated with the rapidity. This study is the first to show that expression of a certain set of proteins correlates with the rapidity of local recurrence. Our results are useful not only for prediction, but highlight the possibility of developing novel strategies to block local recurrence. We also discuss why mRNAs encoding these proteins have not been identified to correlate with local recurrence by previous conventional gene expression profiling analyses.
    PLoS ONE 01/2013; 8(10):e76791. · 3.73 Impact Factor
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    ABSTRACT: Diffusion tensor imaging (DTI) is considered to be able to non-invasively quantify white matter integrity. This study aimed to use DTI to evaluate white matter integrity in non-geriatric patients with major depressive disorder (MDD) who were free of antidepressant medication. DTI was performed on 19 non-geriatric patients with MDD, free of antidepressant medication, and 19 age-matched healthy subjects. Voxel-based and histogram analyses were used to compare fractional anisotropy (FA) and mean diffusivity (MD) values between the two groups, using two-sample t tests. The abnormal DTI indices, if any, were tested for correlation with disease duration and severity, using Pearson product-moment correlation analysis. Voxel-based analysis showed clusters with FA decrease at the bilateral frontal white matter, anterior limbs of internal capsule, cerebellum, left putamen and right thalamus of the patients (uncorrected P<0.001). Histogram analysis revealed lower peak position of FA histograms in the patients (P=0.00097). FA values of the abnormal clusters and peak positions of FA histograms of the patients exhibited moderate correlation with disease duration and severity (P<0.05). These results suggest implication of frontal-subcortical circuits and cerebellum in MDD, and the potential utility of FA in evaluation of brain parenchymal integrity.
    Psychiatry research. 11/2012;
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    ABSTRACT: BACKGROUND: Few studies have focused on right atrial (RA) structure and function in pulmonary hypertension (PH). We sought to evaluate RA volume and phasic function using cardiac magnetic resonance (CMR), and to examine their clinical relevance in PH. METHODS: We prospectively studied 50 PH patients and 21 control subjects. RA volume and indices of phasic function (reservoir volume, ejection fraction [EF], and conduit volume) were evaluated by CMR. RESULTS: Maximum RA volume index was significantly higher in PH patients (56 [44-70] ml/m(2)) than in controls (40 [30-48] ml/m(2)) (p<0.001). Reservoir volume index was significantly lower in PH than in controls (p<0.001), but conduit volume index was higher in PH than in controls (p=0.008). RA EF was similar when comparing the two groups (p=0.925). Interestingly, RA EF was increased in PH patients with WHO functional class III patients as compared with controls (p<0.001) but was reduced in advanced PH patients with WHO functional class IV (p<0.01). Maximum RA volume and RA EF significantly correlated with pulmonary hemodynamic indices, atrial and brain natriuretic hormone levels, and CMR-derived right ventricular indices. By contrast, RA reservoir volume correlated with cardiac index and 6-minute walk distance. CONCLUSIONS: PH is associated with increased size, decreased reservoir function, and increased conduit function of the right atrium. RA systolic function indicated by RA EF increases in patients with mild to moderate PH but decreases in patients with advanced PH. Varying associations between RA indices and conventional PH indices suggest their unique role in the management of PH.
    International journal of cardiology 10/2012; · 6.18 Impact Factor
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    ABSTRACT: Hyperintense putaminal rim (HPR) is an important magnetic resonance imaging (MRI) sign for multiple system atrophy (MSA). Recent studies have suggested that it can also be observed in normal subjects at 3 T. Whether it can be observed in normal subjects at 1.5 T is not known. This study aimed to determine whether HPR could be observed in normal subjects at 1.5 T; and if so, to establish its prevalence, the MRI characteristics, and the features which distinguish from HPR in MSA patients. Axial T2-weighted images of 130 normal subjects were evaluated for the prevalence of HPR, its age and gender distribution, laterality, maximum dimension, association with hypointensity of nearby putamen, and presence of discontinuity. To distinguish from that observed in MSA, axial T2-weighted images of 6 MSA patients with predominant parkinsonism (MSA-P) and 15 MSA patients with predominant cerebellar symptoms (MSA-C) were also evaluated. The characteristics of HPR were compared between these patients and age-matched normal subjects. The mean diffusivity (MD) values of putamen were also compared. Fisher's exact test, t-test, and one way analysis of variance were used to determine significance at corrected p < 0.05. HPR was observed in 38.5% of normal subjects. Age and gender predilection and laterality were not observed. In most cases, it occupied the full length or anterior half of the lateral margin of putamen, and was continuous throughout its length. Maximum transverse dimension was 2 mm. There was no association with hypointensity of nearby putamen. However, in MSA-P, HPR was located predominantly at the posterolateral aspect of putamen, and associated with putaminal atrophy. Discontinuity of HPR was more frequently observed in MSA-P. On visual analysis, the characteristics of HPR were similar between MSA-C patients and normal subjects. Patients with MSA of either type had significantly higher MD values of putamen than normal subjects. HPR can be observed in 38.5% of normal subjects at 1.5 T. Thin linear hyperintensity without discontinuity, occupying the full length or anterior half of the lateral margin of the putamen, is suggestive of "normal." In doubtful cases, measurement of the MD values of nearby putamen may be valuable.
    BMC Neurology 06/2012; 12:39. · 2.56 Impact Factor

Publication Stats

240 Citations
157.08 Total Impact Points

Institutions

  • 2011–2014
    • Hokkaido University
      • Department of Nuclear Medicine
      Sapporo, Hokkaidō, Japan
  • 2013
    • Okayama University
      Okayama, Okayama, Japan
  • 2011–2013
    • Hokkaido University Hospital
      • Division of Diagnostic and Interventional Radiology
      Sapporo-shi, Hokkaido, Japan
  • 2009
    • Tokyo Medical University
      • Division of Pediatrics
      Edo, Tōkyō, Japan
  • 2006–2009
    • The University of Tokyo
      • Department of Health Science and Nursing
      Edo, Tōkyō, Japan