Publications by authors named "Yoshifumi Abe"

26 Publications

  • Page 1 of 1

Effect of Layer Directions on Internal Structures and Tensile Properties of 17-4PH Stainless Steel Parts Fabricated by Fused Deposition of Metals.

Materials (Basel) 2021 Jan 6;14(2). Epub 2021 Jan 6.

Department of Organic Materials Science, Graduate School of Organic Materials Science, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan.

17-4PH stainless steel specimens were fabricated by fused deposition of metals (FDMet) technology, which combines 17-4PH particles with an organic binder. FDMet promises a low-cost additive manufacturing process. The present research aims to clarify the influence of layer directions in the 3D printing process on the mechanical and shrinkage properties of as-sintered and as-aged specimens. All specimens (the as-sintered and as-aged specimens printed in three layer directions) exhibited high relative density (97.5-98%). The highest ultimate strengths (880 and 1140 MPa in the as-sintered and as-aged specimens, respectively) were obtained when the layer direction was perpendicular to the tensile direction. Conversely, the specimens printed with their layer direction parallel to the tensile direction presented a low ultimate strength and low strain at breakage. The fact that the specimens with their layer direction parallel to the tensile direction presented a low ultimate strength and low strain at breakage is a usual behavior of parts obtained by means of FDM. The SEM images revealed oriented binder domains in the printed parts and oriented voids in the sintered parts. It was assumed that large binder domains in the filament were oriented perpendicular to the layer directions during the fused deposition modeling printing, and remained as oriented voids after sintering. Stress concentration in the oriented void defects was likely responsible for the poor tensile properties of these specimens.
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http://dx.doi.org/10.3390/ma14020243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825416PMC
January 2021

Chd8 mutation in oligodendrocytes alters microstructure and functional connectivity in the mouse brain.

Mol Brain 2020 11 23;13(1):160. Epub 2020 Nov 23.

Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8582, Japan.

CHD8 encodes a chromatin-remodeling factor and is one of the most recurrently mutated genes in individuals with autism spectrum disorder (ASD). Although we have recently shown that mice heterozygous for Chd8 mutation manifest myelination defects and ASD-like behaviors, the detailed mechanisms underlying ASD pathogenesis have remained unclear. Here we performed diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rsfMRI) in oligodendrocyte lineage-specific Chd8 heterozygous mutant mice. DTI revealed that ablation of Chd8 specifically in oligodendrocytes of mice was associated with microstructural changes of specific brain regions including the cortex and striatum. The extent of these changes in white matter including the corpus callosum and fornix was correlated with total contact time in the reciprocal social interaction test. Analysis with rsfMRI revealed changes in functional brain connectivity in the mutant mice, and the extent of such changes in the cortex, hippocampus, and amygdala was also correlated with the change in social interaction. Our results thus suggest that changes in brain microstructure and functional connectivity induced by oligodendrocyte dysfunction might underlie altered social interaction in mice with oligodendrocyte-specific CHD8 haploinsufficiency.
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http://dx.doi.org/10.1186/s13041-020-00699-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686671PMC
November 2020

Diffusion functional MRI reveals global brain network functional abnormalities driven by targeted local activity in a neuropsychiatric disease mouse model.

Neuroimage 2020 12 1;223:117318. Epub 2020 Sep 1.

Departemnt of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan.

Diffusion functional magnetic resonance imaging (DfMRI) has been proposed as an alternative functional imaging method to detect brain activity without confounding hemodynamic effects. Here, taking advantage of this DfMRI feature, we investigated abnormalities of dynamic brain function in a neuropsychiatric disease mouse model (glial glutamate transporter-knockdown mice with obsessive-compulsive disorder [OCD]-related behavior). Our DfMRI approaches consisted of three analyses: resting state brain activity, functional connectivity, and propagation of neural information. We detected hyperactivation and biased connectivity across the cortico-striatal-thalamic circuitry, which is consistent with known blood oxygen-level dependent (BOLD)-fMRI patterns in OCD patients. In addition, we performed ignition-driven mean integration (IDMI) analysis, which combined activity and connectivity analyses, to evaluate neural propagation initiated from brain activation. This analysis revealed an unbalanced distribution of neural propagation initiated from intrinsic local activation to the global network, while these were not detected by the conventional method with BOLD-fMRI. This abnormal function detected by DfMRI was associated with OCD-related behavior. Together, our comprehensive DfMRI approaches can successfully provide information on dynamic brain function in normal and diseased brains.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117318DOI Listing
December 2020

Influence of the Layer Directions on the Properties of 316L Stainless Steel Parts Fabricated through Fused Deposition of Metals.

Materials (Basel) 2020 May 29;13(11). Epub 2020 May 29.

Research Center for GREEN Materials & Advanced Processing, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan.

Metal specimens were fabricated via the fused deposition of metals (FDMet) technique with a filament composed of the 316L stainless steel particles and an organic binder. This process was adopted due to its potential as a low-cost additive manufacturing process. The objective of this study is to investigate the influence of the processing conditions-layer directions and layer thicknesses-on the mechanical and shrinkage properties of the metal components. The specimens were printed in three different layer directions. The highest ultimate strength of 453 MPa and strain at break of 48% were obtained in the specimen printed with the layer direction perpendicular to the tensile direction. On the other hand, the specimen printed in the layer direction parallel to the tensile direction exhibited poor mechanical properties. The reason for the anisotropy of the properties was investigated through systematic SEM observations. The observations revealed the presence of segregated binder domains in the filaments. It was deduced that the binder domain was oriented in the direction perpendicular to that of the layer and remained as oriented voids even after sintering. The voids oriented perpendicular to the tensile direction act as defects that could cause stress concentration, thus resulting in poor mechanical properties.
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http://dx.doi.org/10.3390/ma13112493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321246PMC
May 2020

Direct Impact of Motor Cortical Stimulation on the Blood Oxygen-level Dependent Response in Rats.

Magn Reson Med Sci 2021 Mar 17;20(1):83-90. Epub 2020 Apr 17.

School of Engineering, The University of Tokyo.

Purpose: Neuropathic pain is a complex and distressing chronic illness in modern medicine. Since 1990s, motor cortex stimulation (MCS) has emerged as a potential treatment for chronic neuropathic pain; however, the precise mechanisms underlying analgesia induced by MCS are not completely understood. The purpose of the present study was to investigate the blood oxygen-level dependent (BOLD) response in the brain during MCS.

Methods: We inserted a bipolar tungsten electrode into the primary motor cortex (M1) of adult male Wistar rats. Functional magnetic resonance imaging (fMRI) scans were implemented simultaneously with the electrical stimulation of M1 and the BOLD signals taken from the fMRI were used as an index to reflect the response against MCS.

Results: Our results demonstrated that the bilateral M1, ipsilateral caudate-putamen, and ipsilateral primary somatosensory cortex to the stimulation spot were activated after the onset of MCS. The BOLD signal time courses were analysed in these regions and similar temporal characteristics were found.

Conclusion: By conducting direct cortical stimulation of the rodent brain to investigate its instant effect using fMRI, we identified encephalic regions directly involved in the instant motor cortical stimulation effects in healthy rat models. This result may be essential in establishing a foundation for further research on the underlying neuropathways associated with the MCS effects.
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http://dx.doi.org/10.2463/mrms.mp.2019-0156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952200PMC
March 2021

Region- and Cell Type-Specific Facilitation of Synaptic Function at Destination Synapses Induced by Oligodendrocyte Depolarization.

J Neurosci 2019 05 12;39(21):4036-4050. Epub 2019 Mar 12.

Department of Neuropsychiatry.

The axonal conduction of action potentials affects the absolute time it takes to transmit nerve impulses as well as temporal summation at destination synapses. At the physiological level, oligodendrocyte depolarization facilitates axonal conduction along myelinated fibers in the hippocampus; however, the functional significance of this facilitation is largely unknown. In this study, we examined the physiology of the facilitation of axonal conduction by investigating the changes in synaptic responses at destination synapses using male and female mice in which channelrhodopsin-2 expression was restricted to oligodendrocytes. The subiculum, one of the projection areas of the examined axons at the alveus of the hippocampus, is divided into three regions (proximal, mid, and distal) and contains two types of principal neurons: regular firing and bursting pyramidal cells. We found a significant increase in excitatory synaptic responses following optogenetic oligodendrocyte depolarization in bursting neurons at two of the three regions, but not in regular firing neurons at any region. The long-term potentiation (LTP) induced by theta burst stimulation at the synapses showing a significant increase was also enhanced after oligodendrocyte depolarization. Conversely, the reduction of oligodendrocyte depolarization during theta burst stimulation, which was achieved by photostimulation of archaerhodopsin-T expressed selectively on oligodendrocytes, reduced the magnitude of LTP. These results show that oligodendrocyte depolarization contributes to the fine control of synaptic activity between the axons they myelinate and targets subicular cells in a region- and cell type-specific manner, and suggest that oligodendrocyte depolarization during conditioning of stimuli is involved in the induction of LTP. All activity in the nervous system depends on the propagation of action potentials. Changes in the axonal conduction of action potentials influence the timing of synaptic transmission and information processing in neural circuits. At the physiological level, oligodendrocyte depolarization facilitates axonal conduction along myelinated fibers. In this study, we investigated the functional significance of the facilitation of axonal conduction induced by physiological oligodendrocyte depolarization. Using optogenetics and electrophysiological recordings, we demonstrated that oligodendrocyte depolarization in mice expressing channelrhodopsin-2 on oligodendrocytes increased excitatory synaptic responses and enhanced the induction of long-term potentiation at destination synapses in a region- and cell type-specific manner. This facilitation may have a hitherto unappreciated influence on the transfer of information between regions in the nervous system.
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http://dx.doi.org/10.1523/JNEUROSCI.1619-18.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529859PMC
May 2019

Correlative study using structural MRI and super-resolution microscopy to detect structural alterations induced by long-term optogenetic stimulation of striatal medium spiny neurons.

Neurochem Int 2019 05 27;125:163-174. Epub 2019 Feb 27.

Department of Neuropsychiatry, Keio University School of Medicine, Japan.

Striatal medium spiny neurons (MSNs) control motor function. Hyper- or hypo-activity of MSNs coincides with basal ganglia-related movement disorders. Based on the assumption that lasting alterations in neuronal activity lead to structural changes in the brain, understanding these structural alterations may be used to infer MSN functional abnormalities. To infer MSN function from structural data, understanding how long-lasting alterations in MSN activity affect brain morphology is essential. To address this, we utilized a simplified model of functional induction by stimulating MSNs expressing channelrhodopsin 2 (ChR2). Subsequent structural alterations which induced long-term activity changes in these MSNs were investigated in the striatal pathway and its associated regions by diffusion tensor imaging (DTI) and histological assessment with super-resolution microscopy. DTI detected changes in the striatum, substantia nigra, and motor cortex. Histological assessment found a reduction in the diameter of myelinated cortical axons as well as MSN dendrites and axons. The structural changes showed a high correlation between DTI parameters and histological data. These results demonstrated that long-term neural activation in the MSNs alters the diameter of MSN and cortical neurons fibers. This study provides a tool for understanding the causal relationship between functional and structural alterations.
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http://dx.doi.org/10.1016/j.neuint.2019.02.017DOI Listing
May 2019

Spatial contribution of hippocampal BOLD activation in high-resolution fMRI.

Sci Rep 2019 02 28;9(1):3152. Epub 2019 Feb 28.

Commissariat à l'énergie atomique et aux energies alternatives, DRF, Joliot, NeuroSpin, Paris-Saclay University, Gif-sur-Yvette, France.

While the vascular origin of the BOLD-fMRI signal is established, the exact neurovascular coupling events contributing to this signal are still incompletely understood. Furthermore, the hippocampal spatial properties of the BOLD activation are not elucidated, although electrophysiology approaches have already revealed the precise spatial patterns of neural activity. High magnetic field fMRI offers improved contrast and allows for a better correlation with the underlying neuronal activity because of the increased contribution to the BOLD signal of small blood vessels. Here, we take advantage of these two benefits to investigate the spatial characteristics of the hippocampal activation in a rat model before and after changing the hippocampal plasticity by long-term potentiation (LTP). We found that the hippocampal BOLD signals evoked by electrical stimulation at the perforant pathway increased more at the radiatum layer of the hippocampal CA1 region than at the pyramidal cell layer. The return to the baseline of the hippocampal BOLD activation was prolonged after LTP induction compared with that before most likely due vascular or neurovascular coupling changes. Based on these results, we conclude that high resolution BOLD-fMRI allows the segregation of hippocampal subfields probably based on their underlying vascular or neurovascular coupling features.
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http://dx.doi.org/10.1038/s41598-019-39614-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395694PMC
February 2019

Utility of Regular Management of Physical Activity and Physical Function in Hemodialysis Patients.

Kidney Blood Press Res 2018 4;43(5):1505-1515. Epub 2018 Oct 4.

Department of Rehabilitation Sciences, Kitasato University Graduate School of Medical Sciences, Sagamihara,

Background/aims: Several clinical practice guidelines recommend regular assessment of physical activity and physical function as part of routine care in hemodialysis patients. However, there is no clear evidence to support these recommendations. We investigated whether the proportion of attendance at a regular program for management of physical activity and physical function can predict all-cause mortality and cardiovascular events in hemodialysis patients.

Methods: This retrospective cohort study consisted of 266 hemodialysis patients participating in the management program at least once. Participants were tracked for 3 years after their first attendance at the management program to determine their attendance proportion. The main study outcomes included all-cause mortality and a composite of fatal and nonfatal cardiovascular events.

Results: Median patient age was 64.5 (interquartile range, 56.8 - 72.0) years, 45% were women, and the median time on hemodialysis was 35.5 (interquartile range, 12.0 - 114.3) months at baseline. Sixty-five patients died over a median follow-up of 79 months. The incidence of cardiovascular events was 60 over a median follow-up of 68 months. Even after adjusting for any of the prognostic models, participants who attended ≤ 75% of sessions (n = 140) had higher risks of mortality (hazard ratio (HR), 1.79; 95% confidence interval (CI): 1.00 - 3.36; P = 0.049) and cardiovascular events (HR, 1.84; 95% CI: 1.07 - 3.48; P = 0.03) than those attending > 75% of sessions (n = 126).

Conclusion: Hemodialysis patients in whom physical activity and physical function could be assessed more regularly had better prognosis than those with only intermittent assessment.
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http://dx.doi.org/10.1159/000494016DOI Listing
January 2019

Prognosis of Hippocampal Function after Sub-lethal Irradiation Brain Injury in Patients with Nasopharyngeal Carcinoma.

Sci Rep 2017 10 31;7(1):14697. Epub 2017 Oct 31.

Department of Integrated Biosciences, Graduate School of Frontier Science, The University of Tokyo, Kashiwa, Japan.

This work emphasizes the value of assessing hippocampal function by making a timely MRI-based prognosis following a minor dose of hippocampal irradiation after nasopharyngeal carcinomas (NPC) radiotherapy. A quasi-experiment with case-control design and functional assessments (e.g., neuroimaging analysis with fMRI) was conducted to assess hippocampal function after radiotherapy. We delivered 70 Gy of irradiation to nasopharyngeal carcinomas by 6MV helical radiotherapy and collected data from twenty NPC patients and 24 healthy age-matched subjects. Inevitably, hippocampi also received an average dose of 6.89 Gy (range, 2.0-14 Gy). Seed-based functional connectivity of the hippocampus was applied to estimate the cognitive alteration by time before, one month, and four months after irradiation. Afterward, longitudinal-and-cross-sessional statistical inference was determined with time-dependent measurement analysis of variance (ANOVA) with controlled covariance. Over time, there were longitudinal changes in the functional connectivity of hippocampal-related cortices, including the right middle frontal lobe, left superior temporal lobe, and left postcentral gyrus. The findings indicate the presence of functional plasticity, demonstrating how minor irradiation affects functional performance during the early delayed phase of irradiation-induced brain injury.
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http://dx.doi.org/10.1038/s41598-017-13972-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5665929PMC
October 2017

Quantitative temporal changes in DTI values coupled with histological properties in cuprizone-induced demyelination and remyelination.

Neurochem Int 2018 10 10;119:151-158. Epub 2017 Oct 10.

Department of Neuropsychiatry, Keio University School of Medicine, Japan. Electronic address:

Diffusion tensor imaging (DTI) is widely used to evaluate microstructural variations in brain tissue. In particular, fractional anisotropy (FA), reflecting the magnitude and orientation of anisotropic water diffusion, allows us to detect pathological events in white matter. An ex vivo DTI study coupled with histological assessment is an efficient strategy to evaluate the myelination process, i.e. demyelination and remyelination. The relationship between DTI values and myelin content or the individual cellular components such as oligodendrocytes, microglia, and astrocytes during both processes of demyelination and remyelination are not well-understood. To address this issue, we employed a cuprizone-inducible demyelination mouse model. Demyelination can be induced in this model during cuprizone exposure and termination of cuprizone exposure induces remyelination. We fed the mice cuprizone-containing chow for 4 weeks and then normal chow for an additional 4 weeks. The ex vivo DTI was performed to evaluate the white matter profiles observed by FA, mean diffusivity (MD), and radial diffusivity (RD) at both demyelinating and remyelinating time points, and then we evaluated histological properties at the same time points. The results indicated a gradual FA decrease during the cuprizone treatment (0, 2, 3, 4 weeks). A lower peak was seen at 1 week after the normal chow was resumed, with recovery to baseline at 2 and 4 weeks. MD and RD showed an opposing pattern to that of FA. These DTI values were positively or negatively correlated with myelin content regardless of the status of the white matter. The RD value was more sensitive to myelination status than FA and MD. We have clarified the temporal changes in the DTI values coupled with histological properties over both the demyelination and remyelination processes.
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http://dx.doi.org/10.1016/j.neuint.2017.10.004DOI Listing
October 2018

Modulation of water diffusion by activation-induced neural cell swelling in Aplysia Californica.

Sci Rep 2017 07 21;7(1):6178. Epub 2017 Jul 21.

NeuroSpin, Bât 145, Joliot Institute, CEA-Paris-Saclay Center, Point Courrier 156, 91191, Gif-sur-Yvette, France.

Diffusion functional magnetic resonance imaging (DfMRI) has been proposed as a method for functional neuroimaging studies, as an alternative to blood oxygenation level dependent (BOLD)-fMRI. DfMRI is thought to more directly reflect neural activation, but its exact mechanism remains unclear. It has been hypothesized that the water apparent diffusion coefficient (ADC) decrease observed upon neural activation results from swelling of neurons or neuron parts. To elucidate the origin of the DfMRI response at cellular level we performed diffusion MR microscopy at 17.2 T in Aplysia californica buccal ganglia and compared the water ADCs at cellular and ganglia levels before and after neuronal activation induced by perfusion with a solution containing dopamine. Neural cell swelling, evidenced from optical microscopy imaging, resulted in an intracellular ADC increase and an ADC decrease at ganglia level. Furthermore, the intracellular ADC increase was found to have a significant positive correlation with the increase in cell size. Our results strongly support the hypothesis that the ADC decrease observed with DfMRI upon neuronal activation at tissue level reflects activation-induced neural cell swelling.
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http://dx.doi.org/10.1038/s41598-017-05586-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522485PMC
July 2017

Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia.

PLoS Biol 2017 04 13;15(4):e2001494. Epub 2017 Apr 13.

NeuroSpin, Joliot Institute, Commissariat à l'énergie atomique et aux énergies alternatives, Gif-sur-Yvette, France.

Diffusion functional MRI (DfMRI) reveals neuronal activation even when neurovascular coupling is abolished, contrary to blood oxygenation level-dependent (BOLD) functional MRI (fMRI). Here, we show that the water apparent diffusion coefficient (ADC) derived from DfMRI increased in specific rat brain regions under anesthetic conditions, reflecting the decreased neuronal activity observed with local field potentials (LFPs), especially in regions involved in wakefulness. In contrast, BOLD signals showed nonspecific changes, reflecting systemic effects of the anesthesia on overall brain hemodynamics status. Electrical stimulation of the central medial thalamus nucleus (CM) exhibiting this anesthesia-induced ADC increase led the animals to transiently wake up. Infusion in the CM of furosemide, a specific neuronal swelling blocker, led the ADC to increase further locally, although LFP activity remained unchanged, and increased the current threshold awakening the animals under CM electrical stimulation. Oppositely, induction of cell swelling in the CM through infusion of a hypotonic solution (-80 milliosmole [mOsm] artificial cerebrospinal fluid [aCSF]) led to a local ADC decrease and a lower current threshold to wake up the animals. Strikingly, the local ADC changes produced by blocking or enhancing cell swelling in the CM were also mirrored remotely in areas functionally connected to the CM, such as the cingulate and somatosensory cortex. Together, those results strongly suggest that neuronal swelling is a significant mechanism underlying DfMRI.
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http://dx.doi.org/10.1371/journal.pbio.2001494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390968PMC
April 2017

Water apparent diffusion coefficient correlates with gamma oscillation of local field potentials in the rat brain nucleus accumbens following alcohol injection.

J Cereb Blood Flow Metab 2017 Sep 6;37(9):3193-3202. Epub 2017 Jan 6.

NeuroSpin, Commissariat à l'Energie Atomique et aux Energies Alternatives, CEA Saclay, Gif-sur-Yvette, France.

Ethanol is a vasoactive agent as well as psychoactive drug. The neurovascular response, coupled with neuronal activity, can be disturbed by alcohol intake. Hence, blood oxygenation level-dependent (BOLD) fMRI, which relies on neurovascular coupling, might not be reliable to reflect alcohol-induced neuronal responses. Recently, diffusion fMRI has been shown to be more sensitive to neural activity than BOLD fMRI even when neurovascular coupling is disrupted. Especially, the apparent diffusion coefficient (ADC) is sensitive to changes occurring in the cellular tissue structure upon activation. In the present study, we compared BOLD fMRI signals, ADC, and local field potentials (LFPs) in the nucleus accumbens (NAc) following injection of an ethanol solution (0.4 g/kg body weight) in rats under medetomidine anesthesia. An increase in the gamma oscillation power of LFP and an ADC decrease were observed 5 min after the injection of EtOH. The BOLD signals showed a negative slow drift, similar to mean arterial pressure with a peak approximately 10 min after the injection. These results confirm that DfMRI can be a better marker of the neuronal activity than BOLD fMRI, especially when the brain hemodynamic status is changed by vasoactive drugs such as ethanol.
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http://dx.doi.org/10.1177/0271678X16685104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584694PMC
September 2017

Determinants of Slow Walking Speed in Ambulatory Patients Undergoing Maintenance Hemodialysis.

PLoS One 2016 28;11(3):e0151037. Epub 2016 Mar 28.

Hemodialysis Center, Sagami Junkanki Clinic, Sagamihara, Kanagawa, Japan.

Walking ability is significantly lower in hemodialysis patients compared to healthy people. Decreased walking ability characterized by slow walking speed is associated with adverse clinical events, but determinants of decreased walking speed in hemodialysis patients are unknown. The purpose of this study was to identify factors associated with slow walking speed in ambulatory hemodialysis patients. Subjects were 122 outpatients (64 men, 58 women; mean age, 68 years) undergoing hemodialysis. Clinical characteristics including comorbidities, motor function (strength, flexibility, and balance), and maximum walking speed (MWS) were measured and compared across sex-specific tertiles of MWS. Univariate and multivariate logistic regression analyses were performed to examine whether clinical characteristics and motor function could discriminate between the lowest, middle, and highest tertiles of MWS. Significant and common factors that discriminated the lowest and highest tertiles of MWS from other categories were presence of cardiac disease (lowest: odds ratio [OR] = 3.33, 95% confidence interval [CI] = 1.26-8.83, P<0.05; highest: OR = 2.84, 95% CI = 1.18-6.84, P<0.05), leg strength (OR = 0.62, 95% CI = 0.40-0.95, P<0.05; OR = 0.57, 95% CI = 0.39-0.82, P<0.01), and standing balance (OR = 0.76, 95% CI = 0.63-0.92, P<0.01; OR = 0.81, 95% CI = 0.68-0.97, P<0.05). History of fracture (OR = 3.35, 95% CI = 1.08-10.38; P<0.05) was a significant factor only in the lowest tertile. Cardiac disease, history of fracture, decreased leg strength, and poor standing balance were independently associated with slow walking speed in ambulatory hemodialysis patients. These findings provide useful data for planning effective therapeutic regimens to prevent decreases in walking ability in ambulatory hemodialysis patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151037PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809595PMC
August 2016

Predominance of PCR-ribotypes, 018 (smz) and 369 (trf) of Clostridium difficile in Japan: a potential relationship with other global circulating strains?

J Med Microbiol 2015 Oct 31;64(10):1226-1236. Epub 2015 Jul 31.

Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan.

Global spread and evolutionary links of an epidemic Clostridium difficile strain (PCR-ribotype 027) have been noted in recent decades. However, in Japan, no outbreaks caused by type 027 have been reported to date. A total of 120 C. difficile isolates from patients at 15 hospitals during non-outbreak seasons between 2011 and 2013 as well as 18 and 21 isolates collected from two hospitals in 2010 and 2009, respectively, in outbreak periods in Japan, were examined. Among these 120 isolates, Japan-ribotypes smz and ysmz (subtype variant of smz) were the most predominant (39.2 %) followed by Japan-ribotype trf (15.8 %). Types smz/ysmz and trf were also concurrently predominant at two hospitals in the outbreak settings. Out of the five binary toxin-positive isolates observed, only one was PCR-ribotype 027 and another PCR-ribotype 078. Type smz was later found to correspond to PCR-ribotype 018. High rates of resistance against gatifloxacin, moxifloxacin, erythromycin and clindamycin were observed in the PCR-ribotype 018 isolates. Interestingly, all trf isolates were toxin A-negative, toxin B-positive, but they did not correspond to PCR-ribotype 017, thus being assigned a new ribotype (PCR-ribotype 369). In conclusion, PCR-ribotypes 018 (smz) and 369 (trf) were identified as major circulating strains in both outbreak and non-outbreak settings in Japan. Given their epidemiological relevance, molecular investigations are warranted to clarify potential evolutionary links with related strains found elsewhere, such as PCR-ribotypes 018 and 017 from Europe and North America.
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http://dx.doi.org/10.1099/jmm.0.000149DOI Listing
October 2015

Relationship between lower extremity muscle strength and all-cause mortality in Japanese patients undergoing dialysis.

Phys Ther 2014 Jul 27;94(7):947-56. Epub 2014 Feb 27.

N. Takahira, PhD, Department of Rehabilitation Sciences, Graduate School of Medical Sciences, Kitasato University.

Background: Skeletal muscle wasting is common and insidious in patients who are undergoing hemodialysis. However, the association between lower extremity muscle strength and all-cause mortality remains unclear in this population.

Objective: The purpose of this study was to investigate the prognostic significance of lower extremity muscle strength on 7-year survival in a cohort of patients who were clinically stable and undergoing hemodialysis.

Design: A prospective cohort study was conducted.

Methods: A total of 190 Japanese outpatients who were undergoing maintenance hemodialysis 3 times per week at a hemodialysis center were followed for up to 7 years. Lower extremity muscle strength was evaluated using a handheld dynamometer at the time of patient enrollment in the study. Muscle strength data were divided by dry weight and expressed as a percentage. A Cox proportional hazards regression model was used to assess the contribution of lower extremity muscle strength to all-cause mortality.

Results: The median age (25th and 75th percentiles) of this study population was 64 years (57 and 72 years), 53.2% of the patients were women, and the time on hemodialysis was 39.0 months (15.9 and 110.5 months) at baseline. During a median follow-up of 36.0 months, there were 30 deaths. With a multivariate Cox model, the hazard ratio in the group with a knee extensor strength of <40% was 2.73 (95% confidence interval=1.14-6.52) compared with that in the ≥40% group.

Limitations: This was a small-scale observational study, and the mechanisms underlying the higher mortality risk in patients with poor muscle strength undergoing hemodialysis than in other patients undergoing hemodialysis remain to be elucidated.

Conclusions: Decreased lower extremity muscle strength was strongly associated with increased mortality risk in patients undergoing hemodialysis.
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http://dx.doi.org/10.2522/ptj.20130270DOI Listing
July 2014

Association of habitual physical activity measured by an accelerometer with high-density lipoprotein cholesterol levels in maintenance hemodialysis patients.

ScientificWorldJournal 2013 21;2013:780783. Epub 2013 Dec 21.

Department of Rehabilitation Sciences, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 252-0373, Japan.

After confirming the relationship between high-density lipoprotein cholesterol (HDL-C) levels and mortality in hemodialysis patients for study 1, we investigated the effect of physical activity on their HDL-C levels for study 2. In study 1, 266 hemodialysis patients were monitored prospectively for five years, and Cox proportional hazard regression confirmed the contribution of HDL-C to mortality. In study 2, 116 patients were recruited after excluding those with severe comorbidities or requiring assistance from another person to walk. Baseline characteristics, such as demographic factors, physical constitution, primary kidney disease, comorbid conditions, smoking habits, drug use, and laboratory parameters, were collected from patient hospital records. An accelerometer measured physical activity as the number of steps per day over five consecutive days, and multiple regression evaluated the association between physical activity and HDL-C levels. Seventy-seven patients died during the follow-up period. In study 1, we confirmed that HDL-C level was a significant predictor of mortality (P = 0.03). After adjusting for patient characteristics in study 2, physical activity was independently associated with HDL-C levels (adjusted R (2) = 0.255; P = 0.005). In conclusion, physical inactivity was strongly associated with decreased HDL-C levels in hemodialysis patients.
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http://dx.doi.org/10.1155/2013/780783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881674PMC
June 2014

Involvement of glial P2Y₁ receptors in cognitive deficit after focal cerebral stroke in a rodent model.

J Neuroinflammation 2013 Jul 29;10:95. Epub 2013 Jul 29.

Department of Integrated Biosciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.

Background: Neuroinflammation is associated with many conditions that lead to dementia, such as cerebrovascular disorders or Alzheimer's disease. However, the specific role of neuroinflammation in the progression of cognitive deficits remains unclear. To understand the molecular mechanisms underlying these events we used a rodent model of focal cerebral stroke, which causes deficits in hippocampus-dependent cognitive function.

Methods: Cerebral stroke was induced by middle cerebral artery occlusion (MCAO). Hippocampus-dependent cognitive function was evaluated by a contextual fear conditioning test. The glial neuroinflammatory responses were investigated by immunohistochemical evaluation and diffusion tensor MRI (DTI). We used knockout mice for P2Y₁ (P2Y₁KO), a glial ADP/ATP receptor that induces the release of proinflammatory cytokines, to examine the links among P2Y₁-mediated signaling, the neuroinflammatory response, and cognitive function.

Results: Declines in cognitive function and glial neuroinflammatory response were observed after MCAO in both rats and mice. Changes in the hippocampal tissue were detected by DTI as the mean diffusivity (MD) value, which corresponded with the cognitive decline at 4 days, 1 week, 3 weeks, and 2 months after MCAO. Interestingly, the P2Y₁KO mice with MCAO showed a decline in sensory-motor function, but not in cognition. Furthermore, the P2Y₁KO mice showed neither a hippocampal glial neuroinflammatory response (as assessed by immunohistochemistry) nor a change in hippocampal MD value after MCAO. In addition, wild-type mice treated with a P2Y₁-specific antagonist immediately after reperfusion did not show cognitive decline.

Conclusion: Our findings indicate that glial P2Y₁ receptors are involved in the hippocampal inflammatory response. The findings from this study may contribute to the development of a therapeutic strategy for brain infarction, targeting the P2Y₁ receptor.
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http://dx.doi.org/10.1186/1742-2094-10-95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733849PMC
July 2013

Walking speed in patients with first acute myocardial infarction who participated in a supervised cardiac rehabilitation program after coronary intervention.

Int Heart J 2012 ;53(6):347-52

Graduate School of Medical Sciences, Kitasato University, Japan.

This study aimed to evaluate the degree of reduction in walking speed in patients with acute myocardial infarction (AMI) compared to age-matched community-dwelling people and identify factors associated with walking speed. The subjects were 210 middle-aged and 188 elderly patients with a first AMI (AMI group) and 198 age-matched community-dwelling people with no medical events (non-AMI group). We measured maximum walking speed in all subjects and collected clinical data, including that related to motor function, at the end of a supervised cardiac rehabilitation program in the AMI group. Data were analyzed based on age and sex. Walking speed in men and women in the middle-aged AMI subgroup decreased to 77.9% and 75.7% relative to that of the non-AMI subgroup matched by sex, respectively; walking speed in men and women in the elderly AMI subgroup decreased to 78.7% and 74.2% relative to that of the non-AMI subgroup matched by sex, respectively. Moreover, 6.4% of men and 23.8% of women in the middle-aged AMI subgroup, and 28.8% of men and 43.5% of women in the elderly AMI subgroup, had a slower walking speed compared to their respective non-AMI groups, which may contribute to an increased risk for cardiovascular mortality. Stepwise multiple regression analysis for motor function revealed that only leg strength in the middle-aged AMI subgroup, and both leg strength and standing balance in the elderly AMI subgroup, were associated with walking speed, regardless of sex after adjusting for clinical characteristics. These results suggest that evaluation and management of walking speed are necessary in implementing effective disease management for patients with first AMI.
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http://dx.doi.org/10.1536/ihj.53.347DOI Listing
February 2013

Opto-fMRI analysis for exploring the neuronal connectivity of the hippocampal formation in rats.

Neurosci Res 2012 Dec 5;74(3-4):248-55. Epub 2012 Sep 5.

Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.

In recent years, optical stimulation of neurons that bear a light-gated cation channel, "Optogenetics", has opened a new avenue for exploring neuronal connectivity of the nervous system. In this study, we applied a technique, "Opto-fMRI", which combined optogenetics with blood oxygenation level-dependent (BOLD) functional MRI (fMRI), for examining the neuronal connectivity of the hippocampal formation in rats. Although the hippocampal formation is very important for memory formation and retrieval, there is little information on its neuronal connectivity, especially on its longitudinal axis of connection. For this purpose, we utilized a transgenic rat strain, expressing the light-gated cation channel channelrhodopsin-2 (ChR2) under the regulation of the Thy1.2 promoter which permits the expression of the integrated gene in neurons. After optical stimulation targeting the dentate gyrus of the transgenic rat, we detected BOLD response of not only the dentate gyrus (DG) but also at the CA3 area. In addition, we detected the longitudinal-axis activation of the hippocampus after optical stimulation. Our study suggests that Opto-fMRI could be a tool for exploring the neuronal connectivity of the hippocampal formation, to understand the neural basis of memory formation and retrieval.
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http://dx.doi.org/10.1016/j.neures.2012.08.007DOI Listing
December 2012

Habitual physical activity measured by accelerometer and survival in maintenance hemodialysis patients.

Clin J Am Soc Nephrol 2012 Dec 13;7(12):2010-6. Epub 2012 Sep 13.

Department of Rehabilitation Sciences, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan.

Background And Objectives: The association between mortality and physical activity based on self-report questionnaire in hemodialysis patients has been reported previously. However, because self-report is a subjective assessment, evaluating true physical activity is difficult. This study investigated the prognostic significance of habitual physical activity on 7-year survival in a cohort of clinically stable and adequately dialyzed patients.

Design, Setting, Participants, & Measurements: A total of 202 Japanese outpatients who were undergoing maintenance hemodialysis three times per week at the hemodialysis center of Sagami Junkanki Clinic (Japan) from October 2002 to February 2012 were followed for up to 7 years. Physical activity was evaluated using an accelerometer at study entry and is expressed as the amount of time a patient engaged in physical activity on nondialysis days. Cox proportional hazard regression was used to assess the contribution of habitual physical activity to all-cause mortality.

Results: The median patient age was 64 (25th, 75th percentiles, 57, 72) years, 52.0% of the patients were women, and the median time on hemodialysis was 40.0 (25th, 75th percentiles, 16.8, 119.3) months at baseline. During a median follow-up of 45 months, 34 patients died. On multivariable analysis, the hazard ratio for all-cause mortality per 10 min/d increase in physical activity was 0.78 (95% confidence interval, 0.66-0.92; P=0.002).

Conclusions: Engaging in habitual physical activity among outpatients undergoing maintenance hemodialysis was associated with decreased mortality risk.
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http://dx.doi.org/10.2215/CJN.03660412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513746PMC
December 2012

Dysadherin: expression and clinical significance in thyroid carcinoma.

J Clin Endocrinol Metab 2003 Sep;88(9):4407-12

Pathology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.

Dysadherin is a cancer-associated cell membrane glycoprotein. Its cDNA encodes 178 amino acids, including a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Dysadherin is believed to down-regulate the expression of E-cadherin, the prime mediator of cell-cell adhesion in epithelial cells, by a posttranscriptional mechanism and promote the metastasis of carcinoma cells. To evaluate the association between dysadherin expression and E-cadherin expression in thyroid carcinoma, immunostaining for dysadherin and E-cadherin was performed in 51 papillary, 10 follicular, and 31 undifferentiated carcinomas. Immunoreactivity for dysadherin, localized at cell-cell boundaries, was detected in 39 of the 51 papillary carcinomas and all 31 undifferentiated carcinomas but not in the follicular carcinomas or normal thyroid tissue controls. Dysadherin expression was significantly higher in undifferentiated carcinoma than in papillary carcinoma and follicular carcinoma and showed significant negative correlation with E-cadherin expression. The degree of dysadherin expression was significantly associated with the prognosis, occurrence of secondary undifferentiated carcinomas, size of the primary tumor, and metastasis to the regional lymph nodes and lungs. In conclusion, a process involving increased dysadherin expression may lead to an adverse clinical outcome.
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http://dx.doi.org/10.1210/jc.2002-021757DOI Listing
September 2003

Expression of RET in follicular cell-derived tumors of the thyroid gland: prevalence and implication of morphological type.

Pathol Int 2003 Mar;53(3):146-53

Division of Nephrology and Metabolism, Department of Internal Medicine and Department of Pathology, Tokai University School of Medicine, Isehara, Japan.

Expression of the wild-type RET proto-oncogene has been observed in non-medullary, follicular cell-derived tumors (FCDT), but the relation with the histopathological features has not been fully demonstrated. To assess the expression of RET and protein products in relation to morphological types of FCDT, including follicular adenoma (FA), papillary carcinoma (PTC), follicular carcinoma (FTC) and anaplastic carcinoma (AnC), 58 non-neoplastic and neoplastic samples using pathological paraffin sections by immunohistochemistry (IHC), reverse transcriptase-polymerase chain reaction (RT-PCR) and laser capture microdissection (LCM) methods were analyzed. Expression of RET proto-oncogene was detected in 27.3% of FCDT by IHC and 25.5% by RT-PCR using a primer set at a regular break point. The present study also found higher expression ratios of RET in FA (50.0%) and the follicular variant of PTC (50.0%), in contrast to FTC (20.0%), ordinary PTC (20.0%) and poorly differentiated or AnC (14.3%) by RT-PCR. One patient with PTC showed a discrepancy in the results by RT-PCR using a different primer set at the C-terminus of RET. The study found that the RET proto-oncogene is often stimulated in FCDT, not only in PTC but also in follicular tumors (FA and FTC), and may contribute to tumorigenesis of these tumors.
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http://dx.doi.org/10.1046/j.1440-1827.2003.01447.xDOI Listing
March 2003

Expression and significance of c-met protein in papillary thyroid carcinoma.

Tokai J Exp Clin Med 2002 Aug;27(2):43-9

Division of Nephrology, Endocrinology, and Metabolism, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.

The c-met protein, encoded by the c-met oncogene and its ligand, the hepatocellular growth factor/scatter factor, are known to be responsible for the motility and mitogenesis of epithelial cells including cancer cells. Recent studies have reported the prognostic significance of the c-met protein in malignant tumors. Papillary thyroid carcinoma, the most common histological type of thyroid carcinoma, can easily metastasize to regional lymph nodes, reflecting the activated motility and invasiveness of the carcinoma cells. We examined the expression of c-met protein in papillary thyroid carcinomas to assess its significance. Immunohistochemical staining of the c-met protein was performed on archival materials. The c-met protein was expressed in 10 cases of papillary thyroid carcinoma with recurrence, and in 5 of 10 cases without recurrence. Normal thyroids were negative for c-met protein. Expression of the c-met protein was statistically associated with recurrence of the thyroid carcinoma (p = 0.016). It is suggested that expression of the c-met protein plays a role in the recurrence of papillary thyroid carcinoma.
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August 2002

Discordant secretion of calcitonin and chromogranin in the human medullary thyroid carcinoma cell line.

Endocr Pathol 1991 Mar;2(1):16-23

Radiation Effects Research Foundation, Nagasaki, Japan.

A cell fine of human medullary carcinoma of the thyroid, abundantly producing calcitonin (Ct) and related hormones, has proved remarkably useful as an endocrine tumor model for the study of the secretion mechanism. This cell line (TT cell) was used in studies to elucidate the dynamics of the release of Ct and chromogranin (Cg) to culture medium. The studies evaluated the intracellular concentration of Ct and Cg and the concentration changes elicited by the protein kinase C activator, phorbol ester (TPA); the adenylate cyclase-associated protein kinase A activator, forskolin; and the calcium ionophore, A23187. In addition, immunogold labeling of Ct and Cg was carried out to investigate the ultrastructural changes resulting from the stimulations. All these secretagogues effected the release of Ct and Cg into the medium in a dose-dependent manner, and the rate of the increase in the Ct secretion was consistently and markedly higher than that of Cg in more than certain dosages of the secretagogues. Most cells contained secretory granules immunolabeled for both Ct and Cg, and a considerable decrease was noted in the poststimulation count of the granules containing both substances, with the cells retaining more Cg than Ct. The discordance may be explained by different secretory pathways of the two proteins or different rates of synthesis.
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http://dx.doi.org/10.1007/BF02915322DOI Listing
March 1991