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Minami Y.,University of Tokyo | Kaneda H.,Okinaka Memorial Institute for Medical Research | Kaneda H.,Translational Research Informatics Center | Inoue M.,Omigawa General Hospital | And 3 more authors.
International Journal of Cardiology | Year: 2013

Background: While several studies have reported endothelial dysfunction after drug-eluting stent (DES) implantation, their study methods differed and the results were varied. Methods and results: A literature search was performed using PubMed where 14 clinical studies (537 patients) including two randomized trials were identified. All studies assessed endothelial dysfunction 3-14 months after stent implantation. In the acetylcholine (ACh) loading studies, significant vasoconstrictions were observed in proximal and distal segments after implantation of sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) and a milder diameter change was observed after zotarolimus-eluting stent (ZES) implantation. Coronary diameter changes were greater in distal segments. Significant diameter change was not detected after bare metal stent (BMS) implantation. In the exercise examinations, vasoconstriction was observed in distal and proximal segments following SES and PES implantation, whereas vasodilation was observed in BMS. In the pacing examinations, vasoconstriction was observed in both SES and PES implantations in distal and proximal segments, whereas vasodilation was observed in not only BMS but ZES and biolimus-eluting stents (BES) as well. Conclusion: In the chronic phase following stent implantation, marked abnormal vasoconstriction distally in the stent was observed in SES and PES implantation but not in ZES or BES, compared with BMS. To clarify the clinical implications and possible mechanisms of these findings, longer-term evaluation with larger patients is needed. © 2012 Elsevier Ireland Ltd.


Sotozono C.,Kyoto Prefectural University of Medicine | Inatomi T.,Kyoto Prefectural University of Medicine | Nakamura T.,Kyoto Prefectural University of Medicine | Koizumi N.,Kyoto Prefectural University of Medicine | And 7 more authors.
Ophthalmology | Year: 2013

Purpose: To report the effectiveness, disease-specific outcomes, and safety of cultivated oral mucosal epithelial sheet transplantation (COMET), with the primary objective of visual improvement. Design: Noncomparative, retrospective, interventional case series. Participants: This study involved 46 eyes in 40 patients with complete limbal stem cell deficiency (LSCD) who underwent COMET for visual improvement. These LSCD disorders fell into the following 4 categories: Stevens-Johnson syndrome (SJS; 21 eyes), ocular cicatricial pemphigoid (OCP; 10 eyes), thermal or chemical injury (7 eyes), or other diseases (8 eyes). Methods: Best-corrected visual acuity (BCVA) and ocular surface grading score were examined before surgery; at the 4th, 12th, and 24th postoperative week; and at the last follow-up. Data on COMET-related adverse events and postoperative management were collected. The outcomes in each disease category were evaluated separately. Main Outcome Measures: The primary outcome was the change in median logarithm of the minimum angle of resolution (logMAR) BCVA at the 24th postoperative week. The secondary outcome was the ocular surface grading score. Results: Median logMAR BCVA at baseline was 2.40 (range, 1.10 to 3.00). In SJS, logMAR BCVA improved significantly during the 24 weeks after surgery. In contrast, the BCVA in OCP was improved significantly only at the 4th postoperative week. In 6 of the 7 thermal or chemical injury cases, logMAR BCVA improved after planned penetrating keratoplasty or deep lamellar keratoplasty. Grading scores of ocular surface abnormalities improved in all categories. Of 31 patients with vision loss (logMAR BCVA, >2) at baseline, COMET produced improvement (logMAR BCVA, ≤2) in 15 patients (48%). Visual improvement was maintained with long-term follow-up (median, 28.7 months). Multivariate stepwise logistic regression analysis showed that corneal neovascularization and symblepharon were correlated significantly with logMAR BCVA improvement at the 24th postoperative week (P = 0.0023 and P = 0.0173, respectively). Although postoperative persistent epithelial defects and slight to moderate corneal infection occurred in the eyes of 16 and 2 patients, respectively, all were treated successfully with no eye perforation. Conclusions: Long-term visual improvement was achievable in cases of complete LSCD. Cultivated oral mucosal epithelial sheet transplantation offered substantial visual improvement even for patients with end-stage severe ocular surface disorders accompanying severe tear deficiency. Patients with corneal blindness such as SJS benefited from critical improvement of visual acuity. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in anymaterials discussed in this article. © 2013 American Academy of Ophthalmology.


Saito F.,Kansai Medical University | Nakatani T.,Kansai Medical University | Iwase M.,Kansai Medical University | Maeda Y.,Kansai Medical University | And 4 more authors.
Restorative Neurology and Neuroscience | Year: 2012

Purpose: To determine whether intrathecal administration of cultured autologous bone marrow stromal cells (BMSCs) is safe and feasible for treatment of subacute spinal injury. Methods: Five patients with complete tetraplegia due to cervical spinal injury on admission were included. A small amount of bone marrow was obtained during surgery for spinal fusion. BMSCs were cultured, reaching 10 7-10 8 cells. The properties and functional efficacy of the BMSCs were verified with surface marker analysis and a neurite extension test. BMSCs were administered by lumbar puncture. The patients were closely observed for 6 months, and the Committee on Effectiveness and Safety of Clinical Treatment (CESCT) evaluated safety. Results: No adverse responses were observed in biochemical and radiographic examinations. The CESCT did not recognize any harmful effects of the transplantation, and concluded it was safe for treatment. The patients were further followed up for 1 to 4 years with no adverse responses. The recovery of American Spinal Injury Association Impairment Scale (AIS) B and C patients at transplantation was rapid and remarkable, but gradual or limited in AIS A patients. Conclusion: This study demonstrated that intrathecal administration of cultured autologous BMSCs is safe and feasible for treatment of spinal cord injury. © 2012 - IOS Press and the authors. All rights reserved.


Ohno T.,Translational Research Informatics Center | Kaneda H.,Translational Research Informatics Center | Nagai Y.,Translational Research Informatics Center | Fukushima M.,Translational Research Informatics Center
Journal of Atherosclerosis and Thrombosis | Year: 2012

Critical limb ischemia (CLI) is commonly caused by atherosclerotic arterial obstruction or stenosis in the leg, as demonstrated by rest pain, skin ulcers and gangrene (Fontaine III or IV), often fails to respond to conservative treatments, and carries a high risk for limb amputation, with a particularly dismal prognosis. Although surgical revascularization techniques may be used for certain CLI patients, such techniques are not indicated for most CLI patients due to the diffuse nature of the responsible lesions, distal location of the obstruction, or coexisting systemic comorbidities. For such CLI patients with no alternative treatments, the potential utility of cell therapies has been investigated. Indeed many clinical trials are being carried out by academic sectors, and their achievements will facilitate clinical development by pharmaceutical companies. In order to understand the situation regarding competitive international R&D of revascularization seeds for CLI, we surveyed the status of clinical trials. As a result, we identified 58 clinical trials on revascularization for CLI, with the majority in the early phase (


Kaneda H.,Okinaka Memorial Institute for Medical Research | Kaneda H.,Translational Research Informatics Center | Terashima M.,Toyohashi Heart Center | Yamaguchi H.,Tenyoukai Central Hospital
Current Atherosclerosis Reports | Year: 2012

New imaging techniques have been used to examine surrogate markers of atherosclerotic burden to determine the effects of pharmacologic intervention. In this review, we discuss the role of intravascular ultrasound (IVUS) in the determination of progression and regression of coronary artery disease. Several methodologic issues are discussed (selection of segments to analyze, measurement error, high drop out rate, and optimal IVUS variables). Usefulness of new IVUS-derived variables (plaque composition by radiofrequency analysis, deformability by palpography, and endothelial shear stress by three-dimensional coronary anatomy reconstructed from IVUS and angiography) will be determined. Based on comparisons between IVUS and clinical studies, IVUS variables seem to be a valid surrogate in studies using atorvastatin in patients with dyslipidemia. It remains unclear whether IVUS variables are valid surrogates for other drugs/diseases. As such, further studies are needed to determine whether IVUS can serve as an efficient surrogate for clinical events in coronary disease trials. © Springer Science+Business Media, LLC 2012.


Zhou B.,Translational Research Informatics Center | Nakatani E.,Translational Research Informatics Center | Nakatani E.,Kyoto University | Teramukai S.,Kyoto University | And 2 more authors.
Journal of Alzheimer's Disease | Year: 2012

The objective of this study was to develop new risk classifications for conversion to Alzheimer's disease (AD) by comparing the relative reliability of classifiers in patients with mild cognitive impairment (MCI). The 397 MCI subjects and all baseline data, including characteristics, neuropsychological tests, cerebrospinal fluid biomarkers and MRI findings in Alzheimer's Disease Neuroimaging Initiative (ADNI), were used for analysis by Cox proportional hazard regression, bootstrap sampling, and c-index. Multivariate Cox regression analysis revealed the following factors to be associated with increased risk of conversion from MCI to AD during the 53-month follow-up period: AVLT 30-minute delayed recall, AVLT trial 1, Boston naming, logical delayed recall, trail-making B, CDR-sob, ADAS13, the cortical thickness of the right inferior temporal lobe (st91ta), and the left hippocampus volume. The combinations of ADAS13 at a cutoff point of 15.67 with CDR-sob at 1.5 or with the cortical thickness of the right inferior temporal lobe at 2.56 mm 3 produced high conversion rates of 92.7% (82.4%-100.0%) and 88.8% (77.3%-100.0%), respectively, at 48 months. The discriminative ability based on c-index for the proposed combination was 0.68. The sample size was estimated as 504 in the group with a combination of ADAS13 and CDR-sob whose conversion rate is highest. The combination of ADAS13 with CDR-sob at an optimal cutoff point has a high reliability in classifying the MCI patients into high-and low-risk conversion to AD and will be benefit for patients' assessment and potentially facilitate the clinical development of novel therapeutics. © 2012-IOS Press and the authors. All rights reserved.


Fukushima M.,Translational Research Informatics Center
Transactions of Japanese Society for Medical and Biological Engineering | Year: 2014

In this lecture, the progress, the accomplishment, and the foresight of national programs initiated by MEXT and MHLW will be discussed. The outcomes from the Translational Research (TR) program started in FY 2007 and the subsequent program started in FY 2012 is remarkable, for example 22 IND trials registration (including 9 devices and 7 regenerating medicines), and 5 manufacturing and distribution approval (including 4 devices) by the regulatory agency, from the MEXT program. Thereby, research and development based on the Pharmaceutical Affairs Law became the common practice and the R&D pipeline in academic sector has been established. Should the new funding agency to be in operation in FY 2015, apply well-designed instructions and proposal forms for budget application, and rigorous review procedure based on the regulatory science principle, along with the precise project management, our country would become the most prominent innovation-oriented nation in the world. © 2014, Japan Soc. of Med. Electronics and Biol. Engineering. All rights reserved.


Guo Q.-H.,Fudan University | Zhou B.,Translational Research Informatics Center | Zhao Q.-H.,Fudan University | Wang B.,Fudan University | Hong Z.,Fudan University
BMC Neurology | Year: 2012

Background: Mild cognitive impairment (MCI), defined as a transitional zone between normal cognition and dementia, requires a battery of formal neuropsychological tests administered by a trained rater for its diagnosis. The objective of this study was to develop a screening tool for MCI.Methods: One hundred ninety seven cognitively normal controls (NC), one hundred sixteen patients with amnestic MCI -single domain (aMCI-sd), one hundred ninety five patients with amnestic MCI-multiple domain (aMCI-md), and two hundred twenty eight patients with mild Alzheimer's disease (AD) were evaluated by comprehensive neuropsychological tests and by the Memory and Executive Screening (MES).Results: Correlation analysis showed that the three indicators of the MES were significantly negatively related with age (P<0.05), yet not related with education (P>0.05). There was no ceiling or floor effect. Test completion averaged seven minutes (421.14±168.31 seconds). The receiver operating characteristics (ROC) analyses performed on the aMCI-sd group yielded 0.89 for the area under the curve (AUC) (95% CI, 0.85-0.92) for the MES-total score, with sensitivity of 0.795 and specificity of 0.828. There was 81% correct classification rate when the cut-off was set at less than 75. Meanwhile, the aMCI-md group yielded 0.95 for the AUC (95% CI, 0.93-0.97) for the MES-total score, with sensitivity of 0.87 and specificity of 0.91, and 90% correct classification rate when the cut-off was set at less than 72.Conclusion: The MES, minimally time-consuming, may be a valid and easily administered cognitive screening tool with high sensitivity and specificity for aMCI, with single or multiple domain impairment. © 2012 Guo et al.; licensee BioMed Central Ltd.


Fujita Y.,Foundation Medicine | Kawamoto A.,Foundation Medicine | Kawamoto A.,Translational Research Informatics Center
Clinical Pharmacology and Therapeutics | Year: 2016

A new legal framework consisting of three laws for cell-based and tissue-based therapies went into effect in November 2014 in Japan. Among the provisions of the laws, the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act) allows conditional and time-limited approval for regenerative medical products based on the ensured safety and estimated efficacy in small-scale clinical trials. The new legislation is expected to accelerate safe and fast provision of the innovative products to patients with intractable diseases. © 2015 American Society for Clinical Pharmacology and Therapeutics.


News Article | December 7, 2016
Site: www.nature.com

Bodies wear out. Tissue thins and tears. Organs stop functioning. Cells lose their biological way. Trauma breaks things. And as a result, we become ill or disabled. This has always been our fate. Regenerative medicine is the bold collection of techniques and technologies that aim to restore our physiology to something that resembles its original condition. Its roots trace back to antiquity (see page S50) but it has, in recent years, become much more effective. For example, 3D printers can construct tissue and organs that in some cases can function as well as the originals (S56). The central nervous system, however, has proved stubbornly difficult to repair. Scientists hope that stem-cell advances might finally restore mobility to those with spinal-cord injuries (S52). Excitement is already building over the potential of these intriguing cells to create drug-free treatments for chronic diseases such as type 1 diabetes (S60). Regeneration researchers are also taking cues from the animal world: species such as salamanders have the power to regrow limbs. Understanding the cellular mechanisms behind this ability might lead to techniques that can work in humans (S58). Indeed, one scientist argues that for progress to continue, researchers will need to do a better job of emulating and working alongside natural systems (S55). The creation of these therapies brings with it questions of how to regulate them. Clinics are sprouting up to offer dubious stem-cell-based treatments for dire conditions, and policymakers are crafting rules to accelerate the availability of effective treatments without endangering desperate patients (S64). We are pleased to acknowledge financial support for this Outlook from Translational Research Informatics Center (TRI), Clio, Inc., Sapporo Medical University and CYBERDYNE, INC. As always, Nature retains sole responsibility for all editorial content.

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