Publications by authors named "Ryuta Ito"

22 Publications

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Comparison between biodegradable- and durable-polymer everolimus-eluting stents in hemodialysis patients with coronary artery disease.

Cardiovasc Interv Ther 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

To investigate the clinical outcomes after biodegradable-polymer (BP) and durable-polymer (DP) everolimus-eluting stent (EES) implantation in hemodialysis (HD) patients with coronary artery disease. We enrolled 221 consecutive HD patients successfully treated with EES implantation for coronary lesions. Over the following 2 years, we assessed the incidence of target lesion revascularization (TLR) and major adverse cardiac event (MACE), defined as the composite endpoint of TLR, all-cause mortality, or myocardial infarction. We performed a propensity-score matching analysis and collected follow-up coronary angiography data. There were 91 patients in the BP-EES group and 130 in the DP-EES group. Male sex and diabetes rates were significantly lower in the BP-EES group than in the DP-EES group. A debulking device was less frequently used in the BP-EES group than in the DP-EES group (7.6% vs. 21.5%, p = 0.006). TLR occurred in 38 patients, while stent thrombosis was observed in 3 patients; 19 patients died. TLR and MACE rates at 2 years were comparable between the two groups (19.2% in the BP-EES group vs. 20.4% in the DP-EES group, p = 0.73 and 26.9% vs. 34.2%, p = 0.93, respectively). In the propensity-score-matched cohort, TLR and MACE rates were similar between the two groups (19.2% in the BP-EES group vs. 18.1% in the DP-EES group, p = 0.69, and 26.9% vs. 30.2%, p = 0.66, respectively). Restenosis rates at follow-up angiography were similar between the two groups (p = 0.79). In hemodialysis patients, BP-EES and DP-EES showed similar 2-year clinical outcomes.
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http://dx.doi.org/10.1007/s12928-021-00827-xDOI Listing
November 2021

Outcomes after drug-coated balloon interventions for de novo coronary lesions in the patients on chronic hemodialysis.

Heart Vessels 2021 Nov 25;36(11):1646-1652. Epub 2021 Apr 25.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

The impact of drug-coated balloon (DCB) on hemodialysis (HD) patients with coronary lesions remains unclear. This study aimed to compare outcomes after DCB treatment between HD and non-HD patients with de novo coronary lesions. A total of 235 consecutive patients who electively underwent DCB treatment for de novo coronary lesions were included (HD group: n = 100; non-HD group: n = 135). Angiographic follow-up was performed 6 months after the procedure. Patients were clinically followed up for 2 years. The incidence rates of target lesion revascularization (TLR) and major adverse cardiac events (MACE) were investigated. Diabetes and a history of coronary bypass grafting were more frequent in the HD group than in the non-HD group (69.0% vs. 50.7%, p = 0.007, and 24.0% vs 9.1%, p = 0.013, respectively). The reference diameter and pre-procedural diameter stenosis were greater in the HD group than in the non-HD group (2.49 mm vs. 2.24 mm, p = 0.007, and 65.9% vs. 59.6%, p = 0.015, respectively). Calcification was observed in 65.5% of all lesions, and rotational atherectomy was performed in 30.2% patients. The average diameter of the DCB was 2.51 mm (2.57 mm, HD group vs. 2.47 mm, non-HD group, p = 0.14). Although post-procedural diameter stenosis was similar between the groups, late lumen loss on follow-up angiography was larger in HD patients than in non-HD patients (0.27 mm vs. - 0.03 mm, p = 0.0009). The 2-year rates of freedom from TLR and MACE were lower in HD patients than in non-HD patients [79.3% vs. 91.7%, hazard ratio (HR) 2.76, 95% confidence interval (CI) 1.23-6.77, p = 0.014; and 61.6% vs. 89.4%, HR 4.60, 95% CI 2.30-10.2, p < 0.001, respectively]. In conclusion, the rates of TLR and MACE after DCB treatment were higher in HD patients than in non-HD patients.
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http://dx.doi.org/10.1007/s00380-021-01858-3DOI Listing
November 2021

Machine Learning for Diagnosis of AD and Prediction of MCI Progression From Brain MRI Using Brain Anatomical Analysis Using Diffeomorphic Deformation.

Front Neurol 2020 5;11:576029. Epub 2021 Feb 5.

Research Institute, Shiga Medical Center, Shiga, Japan.

With the growing momentum for the adoption of machine learning (ML) in medical field, it is likely that reliance on ML for imaging will become routine over the next few years. We have developed a software named BAAD, which uses ML algorithms for the diagnosis of Alzheimer's disease (AD) and prediction of mild cognitive impairment (MCI) progression. We constructed an algorithm by combining a support vector machine (SVM) to classify and a voxel-based morphometry (VBM) to reduce concerned variables. We grouped progressive MCI and AD as an AD spectrum and trained SVM according to this classification. We randomly selected half from the total 1,314 subjects of AD neuroimaging Initiative (ADNI) from North America for SVM training, and the remaining half were used for validation to fine-tune the model hyperparameters. We created two types of SVMs, one based solely on the brain structure (SVMst), and the other based on both the brain structure and Mini-Mental State Examination score (SVMcog). We compared the model performance with two expert neuroradiologists, and further evaluated it in test datasets involving 519, 592, 69, and 128 subjects from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Aging (AIBL), Japanese ADNI, the Minimal Interval Resonance Imaging in AD (MIDIAD) and the Open Access Series of Imaging Studies (OASIS), respectively. BAAD's SVMs outperformed radiologists for AD diagnosis in a structural magnetic resonance imaging review. The accuracy of the two radiologists was 57.5 and 70.0%, respectively, whereas, that of the SVMst was 90.5%. The diagnostic accuracy of the SVMst and SVMcog in the test datasets ranged from 88.0 to 97.1% and 92.5 to 100%, respectively. The prediction accuracy for MCI progression was 83.0% in SVMst and 85.0% in SVMcog. In the AD spectrum classified by SVMst, 87.1% of the subjects were Aβ positive according to an AV-45 positron emission tomography. Similarly, among MCI patients classified for the AD spectrum, 89.5% of the subjects progressed to AD. Our ML has shown high performance in AD diagnosis and prediction of MCI progression. It outperformed expert radiologists, and is expected to provide support in clinical practice.
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http://dx.doi.org/10.3389/fneur.2020.576029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893082PMC
February 2021

Long-term clinical outcomes after self-expandable bare nitinol stent implantation for femoropopliteal occlusive disease in hemodialysis patients.

Catheter Cardiovasc Interv 2021 02 12;97(2):318-324. Epub 2020 Nov 12.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objectives: To compare the long-term clinical outcomes after self-expandable bare nitinol stent (BNS) implantation between hemodialysis (HD) and non-HD patients with femoropopliteal (FP) disease.

Background: Although a BNS has been commonly used in patients with FP disease, the long-term efficacy of BNSs in HD patients remains unknown.

Methods: In total, 427 HD patients treated with a BNS for FP disease were enrolled, along with 157 non-HD patients as a control group. Over the following 5 years, the incidence of target lesion revascularization (TLR), major amputation and mortality was investigated. We also performed propensity-score matching analysis.

Results: The 5-year TLR rate (45.2 vs. 32.5%, p = .013) and mortality rate (39.3 vs. 14.0%, p = .0002) were significantly higher in the HD group than in the non-HD group. The major amputation rate was comparable between the groups (7.2% in the HD group vs. 2.8% in the non-HD group, p = .16). In the propensity-score-matched cohort, the TLR rate, and mortality rate were remained higher in the HD group than in the non-HD group (48.9 vs. 34.1%, hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.30-3.49, p = .0024, and 47.9 vs. 12.0%, HR 3.38, 95% CI 1.86-6.56, p < .0001, respectively). The adjusted amputation rate was consistently similar between the groups (1.7% in the HD group vs. 2.7% in the non-HD group, HR 0.90, 95% CI 0.26-2.99, p = .86).

Conclusions: The TLR rate and mortality at 5 years post BNS implantation for FP disease were significantly higher in HD patients than in non-HD patients, though the limb salvage rate was similar.
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http://dx.doi.org/10.1002/ccd.29372DOI Listing
February 2021

Histologic Distribution and Characteristics on MR Imaging of Ultrasmall Superparamagnetic Iron Oxide in Ethyl-nitrosourea-induced Endogenous Rat Glioma.

Magn Reson Med Sci 2021 Sep 21;20(3):264-271. Epub 2020 Aug 21.

Department of Radiology, Shiga University of Medical Science.

Purpose: (1) To evaluate the enhancement patterns of an ultrasmall superparamagnetic iron oxide contrast agent (USPIO-CA) compared with those of a gadolinium-based contrast agent (Gd-BCA). (2) To compare the histologic distribution of USPIO-related iron particles (USPIO-IPs) with the USPIO-enhancement area in the early vascular and in the cellular imaging phase (E- and L-phase, respectively) after intravenous CA administration.

Methods: We performed USPIO-enhanced MRI of N-ethyl-N-nitrosourea (ENU)-induced endogenous rat glioma, including spin-echo (SE) T-weighted images (TWIs) and gradient-recalled-echo (GRE) T-weighted images (TWIs), before and at 3-6 h after USPIO-CA administration for E-phase images. For L-phase images, MRI was performed at 16-19 and 62-69 h after administration. Two observers determined the USPIO-enhancement area on E-phase images and Gd-enhancement areas. We compared the USPIO-enhancement size (USPIO-ES) and Gd-ES on SE TWIs, and the hypo-intense USPIO-ES on GRE TWIs and Gd-ES using the Wilcoxon signed-rank test. In addition, two raters visually evaluated the correspondence between the histologic distribution of USPIO-IPs and the USPIO-enhancement area on corresponding GRE TWIs at each phase using a 3-rating scale.

Results: Significantly smaller hyper-intense, hypo-intense and combined hyper-/hypo-intense areas were observed on USPIO-enhanced SE TWIs compared with Gd-enhanced images (all P < 0.001). The hypo-intense USPIO-ES on GRE TWIs was significantly smaller than the Gd-ES (P = 0.001). The distribution of USPIO-IPs on histopathological specimen and USPIO-enhancement on GRE TWIs exhibited poor agreement in 5 of 9 tumors with enhancement from rats sacrificed early. The distribution of microglia containing USPIO-IPs corresponded with the pattern of USPIO-enhancement in the 2 tumors with late enhancement.

Conclusion: The enhancement pattern and size of USPIO-CA in a rat glioma model were statistically different from those of Gd-BCA. Our histological data suggests that USPIO-enhanced MRI offers vascular bed imaging in E-phase and might depict the intra-tumoral distribution of immune effector cells in L-phase.
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http://dx.doi.org/10.2463/mrms.mp.2019-0134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424023PMC
September 2021

Association of protein-energy wasting and inflammation status with mortality after coronary revascularisation in patients on haemodialysis.

Open Heart 2020 07;7(2)

Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objective: Protein-energy wasting is associated with chronic inflammation and advanced atherosclerosis in haemodialysis (HD) patients. We investigated association of geriatric nutritional risk index (GNRI), C reactive protein (CRP) with prediction of mortality after coronary revascularisation in chronic HD patients.

Methods: We enrolled 721 HD patients electively undergoing coronary revascularisation. They were divided into tertiles according to preprocedural GNRI levels (tertile 1 (T1):<91.5, T2: 91.5-98.1 and T3:>98.1) and CRP levels (T1:≤1.4 mg/L, T2: 1.5-7.0 mg/L and T3:≥7.1 mg/L).

Results: Kaplan-Meier 10 years survival rates were 32.3%, 44.8% and 72.5% in T1, T2 and T3 of GNRI and 60.9%, 49.2% and 23.5% in T1, T2 and T3 of CRP, respectively (p<0.0001 in both). Declined GNRI (HR 2.40, 95% CI 1.58 to 3.74, p<0.0001 for T1 vs T3) and elevated CRP (HR 2.31, 95% CI 1.58 to 3.43, p<0.0001 for T3 vs T1) were identified as independent predictors of mortality. In combined setting of both variables, risk of mortality was 5.55 times higher (95% CI 2.64 to 13.6, p<0.0001) in T1 of GNRI with T3 of CRP than in T3 of GNRI with T1 of CRP. Addition of GNRI and CRP in a model with established risk factors improved C-statistics (0.648 to 0.724, p<0.0001) greater than that of each alone.

Conclusion: Preprocedural declined GNRI and elevated CRP were closely associated with mortality after coronary revascularisation in chronic HD patients. Furthermore, combination of both variables not only stratified risk of mortality but also improved the predictability.
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http://dx.doi.org/10.1136/openhrt-2020-001276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380732PMC
July 2020

Safety and Long-Term Efficacy of Drug-Coated Balloon Angioplasty following Rotational Atherectomy for Severely Calcified Coronary Lesions Compared with New Generation Drug-Eluting Stents.

J Interv Cardiol 2019 13;2019:9094178. Epub 2019 Mar 13.

Department of Cardiology, Matsunami General Hospital, Gifu, Japan.

Objectives: This study sought to assess the safety and long-term efficacy of drug-coated balloons (DCB) following aggressive intracoronary image-guided rotational atherectomy (iRA) for severe coronary artery calcification (CAC), and to compare this strategy with new generation drug-eluting stents (nDES) following iRA.

Background: Ischemic events following the treatment of CAC is still relatively high. Thus, more innovative strategies are required.

Methods: We evaluated 123 consecutive patients (166 lesions) with de novo CAC undergoing an iRA (burr size; 0.7 of the mean reference diameter by intracoronary imaging) followed by DCB (DCB-iRA; 54 patients, 68 lesions) or nDES (nDES-iRA; 69 patients, 98 lesions). Follow-up angiography was obtained at > 6 months.

Results: The target vessels (right coronary and circumflex), bifurcation (67.6% versus 47.9%), reference diameter (2.28mm versus 2.49mm), and lesion length (11.89mm versus 18.78mm) were significantly different between the two groups. The median follow-up was 732 days. TLR and TVR in DCB-iRA and nDES-iRA at 3 years were similar: 15.6% versus 16.3% (=0.99) and 15.6% versus 23.3% (=0.38). In 41 well-matched lesion pairs after propensity score analysis, the cumulative incidence of TLR and TVR in DCB-iRA and nDES-iRA at 3 years was 12.9% versus 16.3% (P=0.70) and 12.9% versus 26.1% (P=0.17), respectively. On QCA analysis, although the acute gain was smaller in DCB-iRA (0.85 mm versus 1.53 mm, P<0.001), the minimum lumen diameter at follow-up was similar (1.69 mm versus 1.87 mm, P=0.29). The late lumen loss was lower (0.09 mm versus 0.52 mm, P=0.009) in DCB-iRA.

Conclusions: DCB-iRA is feasible for CAC.
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http://dx.doi.org/10.1155/2019/9094178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739772PMC
February 2020

Lipoarabinomannan in sputum to detect bacterial load and treatment response in patients with pulmonary tuberculosis: Analytic validation and evaluation in two cohorts.

PLoS Med 2019 04 12;16(4):e1002780. Epub 2019 Apr 12.

Otsuka Pharmaceutical Development & Commercialization, Rockville, Maryland, United States of America.

Background: Lipoarabinomannan (LAM) is a major antigen of Mycobacterium tuberculosis (MTB). In this report, we evaluated the ability of a novel immunoassay to measure concentrations of LAM in sputum as a biomarker of bacterial load prior to and during treatment in pulmonary tuberculosis (TB) patients.

Methods And Findings: Phage display technology was used to isolate monoclonal antibodies binding to epitopes unique in LAM from MTB and slow-growing nontuberculous mycobacteria (NTM). Using these antibodies, a sandwich enzyme-linked immunosorbent assay (LAM-ELISA) was developed to quantitate LAM concentration. The LAM-ELISA had a lower limit of quantification of 15 pg/mL LAM, corresponding to 121 colony-forming units (CFUs)/mL of MTB strain H37Rv. It detected slow-growing NTMs but without cross-reacting to common oral bacteria. Two clinical studies were performed between the years 2013 and 2016 in Manila, Philippines, in patients without known human immunodeficiency virus (HIV) coinfection. In a case-control cohort diagnostic study, sputum specimens were collected from 308 patients (aged 17-69 years; 62% male) diagnosed as having pulmonary TB diseases or non-TB diseases, but who could expectorate sputum, and were then evaluated by smear microscopy, BACTEC MGIT 960 Mycobacterial Detection System (MGIT) and Lowenstein-Jensen (LJ) culture, and LAM-ELISA. Some sputum specimens were also examined by Xpert MTB/RIF. The LAM-ELISA detected all smear- and MTB-culture-positive samples (n = 70) and 50% (n = 29) of smear-negative but culture-positive samples (n = 58) (versus 79.3%; 46 positive cases by the Xpert MTB/RIF), but none from non-TB patients (n = 56). Among both LAM and MGIT MTB-culture-positive samples, log10-transformed LAM concentration and MGIT time to detection (TTD) showed a good inverse relationship (r = -0.803, p < 0.0001). In a prospective longitudinal cohort study, 40 drug-susceptible pulmonary TB patients (aged 18-69 years; 60% male) were enrolled during the first 56 days of the standard 4-drug therapy. Declines in sputum LAM concentrations correlated with increases of MGIT TTD in individual patients. There was a 1.29 log10 decrease of sputum LAM concentration, corresponding to an increase of 221 hours for MGIT TTD during the first 14 days of treatment, a treatment duration often used in early bactericidal activity (EBA) trials. Major limitations of this study include a relatively small number of patients, treatment duration up to only 56 days, lack of quantitative sputum culture CFU count data, and no examination of the correlation of sputum LAM to clinical cure.

Conclusions: These results indicate that the LAM-ELISA can determine LAM concentration in sputum, and sputum LAM measured by the assay may be used as a biomarker of bacterial load prior to and during TB treatment. Additional studies are needed to examine the predictive value of this novel biomarker on treatment outcomes.
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http://dx.doi.org/10.1371/journal.pmed.1002780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461223PMC
April 2019

Long-term clinical outcomes after coronary artery bypass graft versus everolimus-eluting stent implantation in chronic hemodialysis patients.

Coron Artery Dis 2018 09;29(6):489-494

Department of Cardiology, Nagoya University Graduate School of Medicine.

Background: It remains controversial whether coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) should be optimized to treat coronary artery disease in patients on chronic hemodialysis (HD). Recently, further refinement of drug-eluting stents, such as the everolimus-eluting stent (EES), has led to marked development in this field. We compared long-term clinical outcomes after CABG versus PCI with EES implantation in patients on chronic HD.

Patients And Methods: We compared 138 patients undergoing CABG and 187 patients treated with EES implantation. The endpoint was major adverse cardiac events (MACE) as a composite outcome, including any revascularization, nonfatal myocardial infarction, or mortality. To reduce the selection bias for the two procedures, propensity score-matching was performed.

Results: During the follow-up period (43 months), 95 (29.2%) MACEs, including 43 (13.2%) revascularizations, 14 (4.3%) nonfatal myocardial infarctions, and 63 (19.4%) deaths, occurred. The freedom rate from MACE and mortality at 5 years were comparable between groups (69.7 vs. 66.7%, P=0.82 and 75.0 vs. 80.6%, P=0.10, respectively); however, those from revascularization at 5 years was higher in the CABG group than the EES group (89.4 vs. 81.0%, P=0.030). In propensity score-matched patients (n=92), the freedom rate from revascularization at 5 years was still higher in the CABG group than in the EES group (93.4 vs. 79.1%, P=0.013). Similarly, the freedom rates from MACE and mortality were comparable (70.0 vs. 66.3%, P=0.69 and 73.8 vs. 79.7%, P=0.30, respectively).

Conclusion: Even in the second-generation drug-eluting stent era, CABG is still superior for preventing revascularization in patients on chronic HD. However, PCI with EES implantation might not have disadvantages compared with CABG in terms of MACE.
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http://dx.doi.org/10.1097/MCA.0000000000000628DOI Listing
September 2018

Clinical Outcomes after Isolated Infrapopliteal Revascularization in Hemodialysis Patients with Critical Limb Ischemia: Endovascular Therapy versus Bypass Surgery.

J Atheroscler Thromb 2018 Sep 23;25(9):799-807. Epub 2018 Jan 23.

Department of Cardiology, Nagoya University Graduate School of Medicine.

Aim: To investigate the long-term clinical outcome of endovascular therapy (EVT) or bypass surgery in patients on hemodialysis (HD) with critical limb ischemia due to isolated infrapopliteal disease.

Methods: We enrolled 254 consecutive HD patients successfully undergoing infrapopliteal revascularization by EVT (126 patients) and bypass surgery (128 patients). They were followed up for five years. Amputation-free survival (AFS) and incidence of any re-intervention were evaluated. A propensity score from all baseline variables was incorporated into Cox analysis.

Results: In the EVT group, age was higher (p=0.039), diabetes and coronary artery disease were more frequent (p=0.004 and p=0.0052, respectively), and tissue loss was more rarely observed (p< 0.0001) than in the bypass group. During the follow-up period, 21 major amputations and 64 deaths occurred. The propensity score-adjusted AFS rate at 5 years was comparable between groups (61.0% in EVT group vs. 55.1% in the bypass group, adjusted hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.52-1.42, p=0.58). The adjusted survival rates were also similar between groups for amputation and all-cause mortality. However, freedom from any re-intervention was markedly lower in the EVT than in the bypass group (48.6% vs. 84.6%, adjusted-HR, 3.56, 95% CI 1.95-6.75, p< 0.0001).

Conclusions: The rate of AFS was broadly comparable between the two strategies, although compared with bypass surgery, EVT had much higher rates for re-intervention.
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http://dx.doi.org/10.5551/jat.42648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143781PMC
September 2018

Outcomes after drug-coated balloon treatment for patients with calcified coronary lesions.

J Interv Cardiol 2018 Aug 20;31(4):436-441. Epub 2017 Dec 20.

Department of Cardiology, Matsunami General Hospital, Kasamatsu, Japan.

Objectives: To investigate the efficacy of drug-coated balloon (DCB) for calcified coronary lesions.

Background: Calcified coronary lesions is associated with poor clinical outcomes after revascularization. Recently, DCB is emerging as an alternative strategy for de novo coronary lesions. However, reports describing the efficacy of DCB for calcified coronary lesions are limited.

Methods: A total of 81 patients (96 lesions) who electively underwent DCB treatment for de novo coronary lesions were enrolled: 46 patients (55 lesions) in the calcified group and 35 patients (41 lesions) in the non-calcified group. Angiographic follow-up data and clinical outcomes after the procedure were evaluated.

Results: The diameter of the DCB used was 2.5 ± 0.5 mm. No bail-out stenting was observed after DCB treatment. Rotational atherectomy was used in 82% of lesions in the calcified group. Follow-up angiography (median, 6.5 months after intervention) was performed for 59 patients (30 in the calcified group and 29 in the non-calcified group). Late lumen loss and rates of restenosis were comparable between the groups (0.03 mm in the calcified group vs -0.18 mm in the non-calcified group, P = 0.093 and 13.9% vs 3.03%, P = 0.095, respectively). The survival rates for target lesion revascularization free survival and major adverse cardiac events at 2 years were comparable between the groups (85.3% vs 93.4%, P = 0.64 and 81.4% vs 88.5%, P = 0.57, respectively).

Conclusion: Calcified coronary lesions might dilute the effect of DCB. However, clinical outcomes in the calcified group were similar to those in the non-calcified group.
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http://dx.doi.org/10.1111/joic.12484DOI Listing
August 2018

[Diffusion-weighted MR Imaging: Basic Principles and Clinical Applications].

Authors:
Ryuta Ito

Nihon Hoshasen Gijutsu Gakkai Zasshi 2015 Oct;71(10):1027-34

Department of Radiology, Shiga University of Medical Science Ho spital.

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http://dx.doi.org/10.6009/jjrt.2015_JSRT_71.10.1027DOI Listing
October 2015

Investigation of association between TLR9 gene polymorphisms and VKH in Japanese patients.

Ocul Immunol Inflamm 2011 Jun;19(3):202-5

Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.

Purpose: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder affecting melanocytes in the skin, eyes, inner ear, and meninges. The Epstein-Barr virus and cytomegalovirus (CMV) antigen have been hypothesized as possible triggering factors for the disease. Toll-like receptors (TLRs) play an important role in the induction of defense mechanisms of the innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR9 recognizes unmethylated 2'-deoxyribo (cytidine-phosphate guanosine)(CpG) DNA motifs that are frequently present in viruses and plays a central role in the host defense against viral infection. The aim of this study was to investigate whether TLR9 polymorphisms were associated with VKH in a Japanese population.

Methods: Ninety-four Japanese patients diagnosed with VKH and 125 healthy control subjects were recruited. Five single-nucleotide polymorphisms (SNPs: rs187084, rs5743836, rs352139, rs352140, rs5743845) in the TLR9 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects.

Results: Strong linkage disequilibrium was observed among three SNPs (D' > 0.99), which were located in one haplotype block. Two SNPs (rs5743836 and rs5743845) were monopolymorphic in both cases and controls. No statistically significant association was observed for any of the SNPs between cases and controls.

Conclusion: Three SNPs in the TLR9 gene were not significantly associated with susceptibility to VKH.
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http://dx.doi.org/10.3109/09273948.2011.553981DOI Listing
June 2011

[The measurement of fractional anisotropy values at the corpus callosum in an irradiated-rat model by 7T-MRI: comparison with quantitative histological evaluation].

No Shinkei Geka 2009 Feb;37(2):147-55

Department of Neurosurgery, Shiga University of Medical Science.

Radiation-induced white matter injury has recently been evaluated by fractional anisotropy (FA) values using diffusion tensor image (DTI) data on magnetic resonance (MR) imaging. However, controversy remains as to which histological components affect anisotropy. FA values were compared with histological findings in rat irradiated brains. Forty Gy whole brain radiation was performed on 9 rats, with another 9 rats not subjected to irradiation prepared as the control group. DTI data for the corpus callosum were obtained using a 7.0 Tesla MR scanner at post radiation 18+2 to 48 +/- 2 weeks (p18w-p48w), and the mean FA value (mFA) was calculated. Histological parameters were assessed at p24w, p36w, and p48w in hematoxylin-eosin stained and immunohistochemically processed sections. Numbers of dilated vessels, hypertrophic glial fibrillary acidic protein (GFAP)-positive cells and Olig2-positive cells were quantitatively evaluated. Qualitative assessment of change in neurofilament (NF)-and myelin basic protein (MBP)-positive structures at each time point was also performed. The mFA decreased from p30w to p42w, significantly decreasing at p42w compared to the control group. However, It recovered to control levels at p48w. Histological examination showed that hypertrophic GFAP-positive cells and dilated vessels had increased at p48w. Olig2-positive cells decreased significantly at p48w compared to p24w and p36w (p<0.05). Although NF-positive structures continued to decrease over time, MBP-positive structures recovered at p48w in agreement with the change in mFA. In the subacute/chronic stage, rat irradiated brain FA value in the corpus callosum appears to mainly reflect the change in myelin structure.
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February 2009

Staphylococcus aureus surface protein SasG contributes to intercellular autoaggregation of Staphylococcus aureus.

Biochem Biophys Res Commun 2008 Dec 5;377(4):1102-6. Epub 2008 Nov 5.

Laboratory of Bacterial Genomics, Center for Pathogen Genomics, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.

Staphylococcus aureus surface protein G (SasG) is one of cell surface proteins with cell-wall sorting motif. The sasG mutant showed significantly reduced cell aggregation and biofilm formation. SasG is comprised of variable A domain and multiple tandem repeats of B domain, native-PAGE and in vitro formaldehyde cross-linking experiments revealed that the recombinant protein of the A domain showed homo-oligomerization as an octamer, but B domain did not. This study shows that SasG-A domain contributes to intercellular autoaggregation by homo-oligomerization, and that may facilitate the adherence to host-tissues in the infection of S. aureus.
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http://dx.doi.org/10.1016/j.bbrc.2008.10.134DOI Listing
December 2008

Maturational changes in diffusion anisotropy in the rat corpus callosum: comparison with quantitative histological evaluation.

J Magn Reson Imaging 2008 Oct;28(4):847-54

Department of Neurosurgery, Shiga University of Medical Science, Otsu, Shiga, Japan.

Purpose: To determine the main histological components that affect fractional anisotropy (FA) in postnatal development of the rat corpus callosum and compare FA values with histological changes evaluated quantitatively.

Materials And Methods: Diffusion tensor image (DTI) data of the rat (postnatal 1-10 weeks) corpus callosum were obtained with a 7.0 T MR scanner. Histological parameters were quantitatively assessed in toluidine blue-stained semithin sections. Simple and multiple linear regression analyses were performed to investigate relationships between FA values and histological variables.

Results: The mean FA value (mFA) increased significantly in the early growth stages, whereas the change became smaller after postnatal week 4. Simple regression analysis showed a high correlation between the area of myelin sheath and mFA (r = 0.856; P < 0.01). The area of extracellular space correlated negatively with mFA (r = -0.813; P < 0.01). In a forward stepwise analysis, the area of myelin sheath had the strongest influence on mFA (P < 0.001), followed by the number of unmyelinated axons (P = 0.113). Multiple linear regression analysis revealed that both parameters predicted mFA with a highly significant adjusted correlation coefficient (r(2) adj. = 0.738, P < 0.001).

Conclusion: During the early development stage in the rat corpus callosum, the strongest contribution to FA value is the area of myelin sheath.
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http://dx.doi.org/10.1002/jmri.21496DOI Listing
October 2008

Sesquiterpene farnesol as a competitive inhibitor of lipase activity of Staphylococcus aureus.

FEMS Microbiol Lett 2007 Aug 7;273(1):28-34. Epub 2007 Jun 7.

Department of Microbiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Staphylococcus aureus lipase (SAL) is known to possess broad substrate specificity for triacylglycerides. We found that a sub-minimum inhibitory concentration of farnesol (1000 mg L(-1)) inhibits this lipase activity on a Mueller-Hinton agar containing 1% Tween substrates. A quantitative lipase assay using p-nitrophenyl palmitate (pNPP) revealed that the inhibitory action of farnesol appears to be the result of the inhibition of lipase activity rather than of its secretion into the culture medium. The inhibition was observed in all the tested 8 methicillin-susceptible S. aureus and 31 methicillin-resistant S. aureus clinical isolates. Using homogeneous lipase purified by hydrophobic interaction chromatography, it was revealed that farnesol could competitively inhibit the lipase activity against the substrate pNPP.
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http://dx.doi.org/10.1111/j.1574-6968.2007.00772.xDOI Listing
August 2007

Evaluation of treatment-induced cerebral white matter injury by using diffusion-tensor MR imaging: initial experience.

AJNR Am J Neuroradiol 2005 Oct;26(9):2200-6

Departments of Radiology, Shiga University of Medical Science, Shiga, Japan.

Background And Purpose: Treatment with chemotherapy and radiation therapy for brain tumors can cause white matter (WM) injury. Conventional MR imaging, however, cannot always depict treatment-induced transient WM abnormalities. We investigated the ability of diffusion-tensor (DT) MR imaging and proton MR spectroscopy to detect the treatment-induced transient changes within normal-appearing WM.

Methods: DT MR imaging and proton MR spectroscopy were performed in 8 patients treated with a combination of surgery, chemotherapy, and radiation therapy for brain tumors (17 examinations) and 11 age-matched controls. Apparent diffusion coefficient (ADC) value, fractional anisotropy (FA) value, and N-acetylaspartate (NAA)/creatine (Cr) ratio were obtained from 27 hemispheres with normal-appearing WM in the patients. We divided the datasets of isotropic ADC, FA, and NAA/Cr, on the basis of the time period after completion of radiation therapy, into 4 groups: group 1 (0-2 months; n = 10), group 2 (3-5 months; n = 5), group 3 (6-9 months; n = 7), and group 4 (10-12 months; n = 5). We compared averages of mean isotropic ADC, mean FA, and NAA/Cr of each patient group with those of the control group by using a t test.

Results: In the group 2, averages of mean FA and NAA/Cr decreased and average of mean isotopic ADC increased in comparison with those of the control group (P = .004, .04, and .0085, respectively). There were no significant differences in the averages between the control group and patient groups 1, 3, and 4.

Conclusion: DT MR imaging and proton MR spectroscopy can provide quantitative indices that may reflect treatment-induced transient derangement of normal-appearing WM.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976122PMC
October 2005

Estimation of cerebral perfusion reserve by blood oxygenation level-dependent imaging: comparison with single-photon emission computed tomography.

J Cereb Blood Flow Metab 2003 Jan;23(1):121-35

Department of Neurosurgery, Shiga University of Medical Science, Seta, Ohtsu, Japan.

Measurement of cerebrovascular reserve capacity predicts the risk of ischemic insult in patients with major vessel occlusion. Blood oxygenation level-dependent (BOLD) imaging has the potential to estimate reserve capacity of the cerebral circulation noninvasively based on changes in the signal that reflect differences in the magnetic susceptibility of intravascular oxyhemoglobin and deoxyhemoglobin. The authors examined the feasibility of using the BOLD technique to assess cerebrovascular reserve capacity in patients with cerebrovascular occlusive disease by comparing results with an established method of measuring CBF. Ten patients with severe or complete occlusion of the internal carotid artery were compared with 17 healthy subjects to evaluate regional differences and identify variables that indicate a change in the BOLD signal. Dilation of cerebral vessels was induced by breath holding, and the R2* change was examined with gradient-echo, echo-planar imaging. Before measuring the regional change in the BOLD signal, actual timing of "activated" and "rest" periods was corrected by shifting the phase of a sine-wave template to obtain the largest correlation coefficient. Percent signal change was calculated on a pixel-by-pixel basis and was compared with CBF measured by single-photon emission computed tomography (SPECT) before and after acetazolamide challenge. The degree of impairment and the distribution of impaired areas detected by the BOLD study correlated with the results of SPECT. Overall sensitivity and specificity of the BOLD technique by visual inspection were 100% and 98.4%, respectively. A negative response (decreased CBF) frequently was observed in areas of exhausted reserve capacity, suggesting that a "steal" phenomenon exists. The percent change and the (Delta)CBF were well correlated (P < 0.01). The mean percent change in most areas of impaired reserve capacity was more than 2 SD below the mean values in healthy subjects. The present method of semiquantitative BOLD analysis can be used to create a map of the cerebral hemodynamic state. Furthermore, the development of reliable, generally accessible techniques for evaluating cerebral hemodynamics opens the door for clinical studies to monitor and treat patients with compromised reserve. This study is an attempt to develop such analysis.
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http://dx.doi.org/10.1097/01.WCB.0000037546.46809.CADOI Listing
January 2003

Cortical representation of hearing restoration in patients with sudden deafness.

Neuroreport 2002 Oct;13(14):1829-32

Department of Otolaryngology, Shiga University of Medical Science, Seta, Otsu, Japan.

To characterize brain activity in response to auditory stimuli during recovery from acute hearing loss, fMRI was performed at two time points in 11 patients with sudden deafness in the right ear, and 10 subjects with normal hearing. In the acute phase, right-ear auditory stimulation induced only a small response in the auditory cortex, limited to the left hemisphere. In the recovery phase, the auditory response was more extensive than in the acute phase. Stimulation of the left ear induced a more extensive response in the left than right hemisphere in both acute and recovery phases, which differed from the pattern in normal subjects. The changes in cortical activation patterns were seen within 1 week of sudden deafness. Thus, alteration of cortical response in deafness occurs earlier than suggested by previous reports.
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http://dx.doi.org/10.1097/00001756-200210070-00029DOI Listing
October 2002

Common neural processing regions for dynamic and static stereopsis in human parieto-occipital cortices.

Neurosci Lett 2002 Jul;327(1):29-32

Department of Ophthalmology, Shiga University of Medical Science, Seta, Tsukinowa, Otsu 520-2192, Japan.

We performed functional magnetic resonance imaging to identify the neural processing regions in the parieto-occipital cortices for human dynamic and static stereopsis. The subjects were ten ophthalmologists professionally trained to do microscopic surgery. Visual stimuli for dynamic or static stereopsis were performed with solid stereograms displayed in the image guides of a binocular visual stimulation device that we developed. The dorsal occipital portion and the superior parietal lobule (i.e. dorsal parieto-occipital portion) were activated not only in static stereopsis, but also in dynamic stereopsis. The activation showed a right hemispherical dominancy. On the other hand, the temporo-occipital junction (i.e. human MT (middle temporal area) / MST (medial superior temporal area) complex) was activated in dynamic stereopsis. This demonstrates that the dorsal parieto-occipital portion is a common neural processing region for dynamic and static stereopsis.
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http://dx.doi.org/10.1016/s0304-3940(02)00353-1DOI Listing
July 2002

Diffusion tensor brain imaging and tractography.

Neuroimaging Clin N Am 2002 Feb;12(1):1-19

Department of Radiology, Shiga University of Medical Science, Otsu, Shiga, Japan.

Diffusion-tensor MR imaging is a promising tool to evaluate white-matter integrity by quantitative and graphic maps including neural fiber tractogram. Current challenges afoot are to obtain higher quality diffusion-weighted MR images (high SNR, isotropic voxel, and high spatial resolution), to create a robust mathematical framework to process the data, to construct a user-friendly computer-based algorithm, to reveal determinants of diffusion process, and to establish analytical methodology.
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http://dx.doi.org/10.1016/s1052-5149(03)00067-4DOI Listing
February 2002
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