Time filter

Source Type

Tomabechi Y.,Tokai University | Odate Y.,Tokai University | Izumi R.,Research Association for Biotechnology | Haneda K.,Tokai University | Inazu T.,Tokai University
Carbohydrate Research | Year: 2010

To determine the structural specificity of the glycosyl acceptor of the transglycosylation reaction using endo-β-N-acetylglucosaminidase (ENGase) (EC from Mucor hiemalis (Endo-M), several acceptor derivatives were designed and synthesized. The narrow regions of the 1,3-diol structure from the 4- to 6-hydroxy functions of GlcNAc were found to be essential for the transglycosylation reaction using Endo-M. Furthermore, it was determined that Endo-M strictly recognizes a 1,3-diol structure consisting of primary and secondary hydroxyl groups. © 2010 Elsevier Ltd. All rights reserved. Source

Masaike Y.,Tokyo Institute of Technology | Takagi T.,Tokyo Institute of Technology | Hirota M.,Tokyo Institute of Technology | Yamada J.,Tokyo Institute of Technology | And 10 more authors.
Molecular Pharmacology | Year: 2010

Nitrogen-containing bisphosphonates are pyrophosphate analogs that have long been the preferred prescription for treating osteoporosis. Although these drugs are considered inhibitors of prenylation and are believed to exert their effects on bone resorption by disrupting the signaling pathways downstream of prenylated small GTPases, this explanation seems to be insufficient. Because other classes of prenylation inhibitors have recently emerged as potential antiviral therapeutic agents, we first investigated here the effects of bisphosphonates on simian virus 40 and adenovirus infections and, to our surprise, found that viral infections are suppressed by bisphosphonates through a prenylation-independent pathway. By in-house affinity-capture techniques, dynamin-2 was identified as a new molecular target of bisphosphonates. We present evidence that certain bisphosphonates block endocytosis of adenovirus and a model substrate by inhibiting GTPase activity of dynamin-2. Hence, this study has uncovered a previously unknown mechanism of action of bisphosphonates and offers potential novel use for these drugs. © 2010 The American Society for Pharmacology and Experimental Therapeutics. Source

Matsuda H.,International University of Japan | Mizumura S.,Toho University | Nemoto K.,University of Tsukuba | Yamashita F.,Research Association for Biotechnology | And 3 more authors.
American Journal of Neuroradiology | Year: 2012

BACKGROUND AND PURPOSE: The necessity for structural MRI is greater than ever to both diagnose AD in its early stage and objectively evaluate its progression. We propose a new VBM-based software program for automatic detection of early specific atrophy in AD. MATERIALS AND METHODS: A target VOI was determined by group comparison of 30 patients with very mild AD and 40 age-matched healthy controls by using SPM. Then this target VOI was incorporated into a newly developed automated software program independently running on a Windows PC for VBM by using SPM8 plus DARTEL. ROC analysis was performed for discrimination of 116 other patients with AD with very mild stage (n = 45), mild stage (n = 30) and moderate-to-advanced stages (n = 41) from 40 other age-matched healthy controls by using a z score map in the target VOI. RESULTS: Medial temporal structures involving the entire region of the entorhinal cortex, hippocampus, and amygdala showed significant atrophy in the patients with very mild AD and were determined as a target VOI. When we used the severity score of atrophy in this target VOI, 91.6%, 95.8%, and 98.2% accuracies were obtained in the very mild AD, mild AD, and moderate-to-severe AD groups, respectively. In the very mild AD group, a high specificity of 97.5% with a sensitivity of 86.4% was obtained, and age at onset of AD did not influence this accuracy. CONCLUSIONS: This software program with application of SPM8 plus DARTEL to VBM provides a high performance for AD diagnosis by using MRI. Source

Kikuchi M.,Tokyo Medical and Dental University | Kikuchi M.,Niigata University | Kikuchi M.,Research Association for Biotechnology | Ogishima S.,Tohoku University | And 6 more authors.
PLoS ONE | Year: 2013

Alzheimer's disease (AD), the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid β and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than upregulated in the later stages of AD. This suggested that the molecular networks and their constituent modules collapsed along with AD progression. In this study, by using gene expression profiles and protein interaction networks (PINs), we identified the PINs expressed in three brain regions: the entorhinal cortex (EC), hippocampus (HIP) and superior frontal gyrus (SFG). Dividing the expressed PINs into modules, we examined the stability of the modules with AD progression and with normal aging. We found that in the AD modules, the constituent proteins, interactions and cellular functions were not maintained between consecutive stages through all brain regions. Interestingly, the modules were collapsed with AD progression, specifically in the EC region. By identifying the modules that were affected by AD pathology, we found the transcriptional regulation- associated modules that interact with the proteasome-associated module via UCHL5 hub protein, which is a deubiquitinating enzyme. Considering PINs as a system made of network modules, we found that the modules relevant to the transcriptional regulation are disrupted in the EC region, which affects the ubiquitin-proteasome system. © 2013 Kikuchi et al. Source

Maikusa N.,Integrative Brain Imaging Center | Yamashita F.,Iwate Medical University | Tanaka K.,Research Association for Biotechnology | Abe O.,Nihon University | And 8 more authors.
Medical Physics | Year: 2013

Purpose: Serial magnetic resonance imaging (MRI) images acquired from multisite and multivendor MRI scanners are widely used in measuring longitudinal structural changes in the brain. Precise and accurate measurements are important in understanding the natural progression of neurodegenerative disorders such as Alzheimer's disease. However, geometric distortions in MRI images decrease the accuracy and precision of volumetric or morphometric measurements. To solve this problem, the authors suggest a commercially available phantom-based distortion correction method that accommodates the variation in geometric distortion within MRI images obtained with multivendor MRI scanners. Methods: The authors' method is based on image warping using a polynomial function. The method detects fiducial points within a phantom image using phantom analysis software developed by the Mayo Clinic and calculates warping functions for distortion correction. To quantify the effectiveness of the authors' method, the authors corrected phantom images obtained from multivendor MRI scanners and calculated the root-mean-square (RMS) of fiducial errors and the circularity ratio as evaluation values. The authors also compared the performance of the authors' method with that of a distortion correction method based on a spherical harmonics description of the generic gradient design parameters. Moreover, the authors evaluated whether this correction improves the test-retest reproducibility of voxel-based morphometry in human studies. Results: A Wilcoxon signed-rank test with uncorrected and corrected images was performed. The root-mean-square errors and circularity ratios for all slices significantly improved (p < 0.0001) after the authors' distortion correction. Additionally, the authors' method was significantly better than a distortion correction method based on a description of spherical harmonics in improving the distortion of root-mean-square errors (p < 0.001 and 0.0337, respectively). Moreover, the authors' method reduced the RMS error arising from gradient nonlinearity more than gradwarp methods. In human studies, the coefficient of variation of voxel-based morphometry analysis of the whole brain improved significantly from 3.46% to 2.70% after distortion correction of the whole gray matter using the authors' method (Wilcoxon signed-rank test, p < 0.05). Conclusions: The authors proposed a phantom-based distortion correction method to improve reproducibility in longitudinal structural brain analysis using multivendor MRI. The authors evaluated the authors' method for phantom images in terms of two geometrical values and for human images in terms of test-retest reproducibility. The results showed that distortion was corrected significantly using the authors' method. In human studies, the reproducibility of voxel-based morphometry analysis for the whole gray matter significantly improved after distortion correction using the authors' method. © 2013 American Association of Physicists in Medicine. Source

Discover hidden collaborations