Updated on 2024/12/26

写真a

 
ITO Takuya
 
Organization
Center Research technology support center
External link

Degree

  • 博士(獣医学) ( 2012.3   岐阜大学 )

Research Interests

  • 実験動物学

  • 胎児生理学

Research Areas

  • Life Science / Laboratory animal science

  • Life Science / Obstetrics and gynecology

Education

  • Obihiro University of Agriculture and Veterinary Medicine   Faculty of Animal Husbandry   School of Veterinary Medicine

    1993.4 - 1999.3

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    Country: Japan

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Research History

  • Asahikawa Medical College   Center for Advanced Research and Education   Associate Professor

    2020.2

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Professional Memberships

Papers

  • Relationship between short term variability (STV) and onset of cerebral hemorrhage at ischemia-reperfusion load in fetal growth restricted (FGR) mice Reviewed

    Takahiro Minato, Takuya Ito, Yoshiyuki Kasahara, Sayaka Ooshio, Tomofumi Fushima, Akiyo Sekimoto, Nobuyuki Takahashi, Nobuo Yaegashi, Yoshitaka Kimura

    Frontiers in Physiology   9 ( MAY )   478   2018.5

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    Fetal growth restriction (FGR) is a risk factor exacerbating a poor neurological prognosis at birth. A disease exacerbating a poor neurological prognosis is cerebral palsy. One of the cause of this disease is cerebral hemorrhage including intraventricular hemorrhage. It is believed to be caused by an inability to autoregulate cerebral blood flow as well as immaturity of cerebral vessels. Therefore, if we can evaluate the function of autonomic nerve, cerebral hemorrhage risk can be predicted beforehand and appropriate delivery management may be possible. Here dysfunction of autonomic nerve in mouse FGR fetuses was evaluated and the relationship with cerebral hemorrhage incidence when applying hypoxic load to resemble the brain condition at the time of delivery was examined. Furthermore, FGR incidence on cerebral nerve development and differentiation was examined at the gene expression level. FGR model fetuses were prepared by ligating uterine arteries to reduce placental blood flow. To compare autonomic nerve function in FGR mice with that in control mice, fetal short term variability (STV) was measured from electrocardiograms. In the FGR group, a significant decrease in the STV was observed and dysfunction of cardiac autonomic control was confirmed. Among genes related to nerve development and differentiation, Ntrk and Neuregulin 1, which are necessary for neural differentiation and plasticity, were expressed at reduced levels in FGR fetuses. Under normal conditions, Neurogenin 1 and Neurogenin 2 are expressed mid-embryogenesis and are related to neural differentiation, but they are not expressed during late embryonic development. The expression of these two genes increased in FGR fetuses, suggesting that neural differentiation is delayed with FGR. Uterine and ovarian arteries were clipped and periodically opened to give a hypoxic load mimicking the time of labor, and the bleeding rate significantly increased in the FGR group. This suggests that FGR deteriorates cardiac autonomic control, which becomes a risk factor for cerebral hemorrhage onset at birth. This study demonstrated that cerebral hemorrhage risk may be evaluated before parturition for FGR management by evaluating the STV. Further, this study suggests that choosing an appropriate delivery timing and delivery method contributes to neurological prognosis improvement.

    DOI: 10.3389/fphys.2018.00478

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  • Animal ethics and welfare education in wet-lab training can foster residents' ethical values toward life. Reviewed

    Yuko Iki, Takuya Ito, Katsuyoshi Kudo, Masafumi Noda, Masahiko Kanehira, Teruko Sueta, Ichiro Miyoshi, Yutaka Kagaya, Yoshinori Okada, Michiaki Unno

    Experimental animals   66 ( 4 )   313 - 320   2017.10

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    Live animals are used in surgical skills training in wet lab, which has undeniable effectiveness for the development of future surgeons. However, where such training is provided, animal welfare is a major consideration. Increasingly, institutions that offer wet-lab training are incorporating animal ethics and welfare-related content into their training courses, but the effectiveness of such animal ethics education has yet to be evaluated quantitatively. We investigated whether the animal ethics content of a training course affected trainees by measuring increase in ethical awareness using visual analog scale questionnaires before and after training. Our results demonstrated a significant and positive increase in awareness of animal ethics (significance level of 5%; 0.0380≤P≤0.0016).

    DOI: 10.1538/expanim.17-0026

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  • Ultrasound Imaging of Mouse Fetal Intracranial Hemorrhage Due to Ischemia/Reperfusion Reviewed

    Kenichi Funamoto, Takuya Ito, Kiyoe Funamoto, Clarissa L. Velayo, Yoshitaka Kimura

    FRONTIERS IN PHYSIOLOGY   8   2017.5

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    Despite vast improvement in perinatal care during the 30 years, the incidence rate of neonatal encephalopathy remains unchanged without any further Progress towards preventive strategies for the clinical impasse. Antenatal brain injury including fetal intracranial hemorrhage caused by ischemia/reperfusion is known as one of the primary triggers of neonatal injury. However, the mechanisms of antenatal brain injury are poorly understood unless better predictive models of the disease are developed. Here we show a mouse model for fetal intracranial hemorrhage in vivo developed to investigate the actual timing of hypoxia-ischemic events and their related mechanisms of injury. Intrauterine growth restriction mouse fetuses were exposed to ischemia/reperfusion cycles by occluding and opening the uterine and ovarian arteries in the mother. The presence and timing of fetal intracranial hemorrhage caused by the ischemia/reperfusion were measured with histological observation and ultrasound imaging. Protein restricted diet increased the risk of fetal intracranial hemorrhage. The monitoring of fetal brains by ultrasound B-mode imaging clarified that cerebral hemorrhage in the fetal brain occurred after the second ischemic period. Three-dimensional ultrasound power Doppler imaging visualized the disappearance of main blood flows in the fetal brain. These indicate a breakdown of cerebrovascular autoregulation which causes the fetal intracranial hemorrhage. This study supports the fact that the ischemia/reperfusion triggers cerebral hemorrhage in the fetal brain. The present method enables us to noninvasively create the cerebral hemorrhage in a fetus without directly touching the body but with repeated occlusion and opening of the uterine and ovarian arteries in the mother.

    DOI: 10.3389/fphys.2017.00340

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  • [Surgical Training Utilizing Swine Under General Anesthesia and Animal Ethics]. Reviewed

    Yuko Iki, Masafumi Noda, Katsuyoshi Kudoh, Teruko Sueta, Masahiko Kanehira, Takuya Ito, Yasushi Matsuda, Yoshinori Okada, Michiaki Unno

    Kyobu geka. The Japanese journal of thoracic surgery   70 ( 5 )   329 - 333   2017.5

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    A cross-sectional study is conducted with primary residents attended wet labs at Tohoku University Hospital Advanced Medical Training Center in order to investigate the efficacy of the training, especially focused on the animal ethics. The 41 participants answered questionnaires in regard to non-technical skills, technical skills and ethics before and after the practice. To identify differences in each ethical question between 2 time points, Wilcoxon signed ranks test was used because the data was not normally distributed. As the result of it, all animal ethical questions showed significant differences(0.0016≤p≤0.0380, α=0.05 level of significance). Beside them, only 1 out of 5 general ethical questions showed it (p=0.0137). This outcome verified that the lecture of animal ethics and the observation of animal care in this center fixed in the training curriculum clearly induced participants' psychological movements.

    DOI: 10.15106/J00349.2017209356

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  • Effect of chronic hypoxia on autonomic nervous system of fetal mice Reviewed

    Ahsan H. Khandoker, Thuraia Al Khoori, Takuya Ito, Takahiro Minato, Yoshitaka Kimura

    Computing in Cardiology   44 ( 1 )   1 - 4   2017

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    Language:English   Publishing type:Research paper (international conference proceedings)   Publisher:IEEE Computer Society  

    The aim of this study is to investigate how chronic hypoxia could affect the autonomic nervous system in fetal mouse (at gestational day 17.5) by using an invasive Fetal Electrocardiography (FECG) technique. Total of 33 pregnant female mice were divided into two groups (sham control (N=13) and chronic hypoxia (N=20)). In chronic hypoxia mice at day 15.5, ligations were placed around the uterine vessels that were tied with nylon thread 0.5 mm in diameter to induce partially chronic hypoxia. Sham mice were operated on in a fashion similarly but without ligation. On 17.5-day beat-to-beat heart intervals were measured for 20 minutes by using an invasive FECG techniques inserting two needle electrodes and a ground. Results show that tone decreases when entropy increases in sham group. On the other hand in chronic hypoxia group tone increases when entropy increases. Therefore, effect of chronic hypoxia is shown to have more pronounced on tone values in the higher range of entropy values (4.2∼6.0). Differences in hypoxic effect on individual fetal mice might represent the differences in maturating sympathetic nervous system because chronic hypoxia induces more sympathetic influences in fetal mice.

    DOI: 10.22489/CinC.2017.332-298

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  • Analysis of an autonomic nervous system of mouse fetus with congenital heart defect

    Kiyoe Funamoto, Rika Sugibayashi, Kenichi Funamoto, Kana Nakanishi, Takuya Ito, Motoyoshi Kawataki, Toshiyuki Hayase, Yoshitaka Kimura

    Proceedings of the 16th International Symposium on Advanced Fluid Information (AFI-2016)   92 - 93   2016.10

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  • OS 21-08 NOVEL REDUCED UTERINE PERFUSION PRESSURE (RUPP) MODEL OF PREECLAMPSIA IN MICE. Reviewed

    Fushima T, Sekimoto A, Minato T, Ito T, Oe Y, Kisu K, Sato E, Funamoto K, Kimura Y, Ito S, Sato H, Takahashi N

    Journal of hypertension   34 Suppl 1 - ISH 2016 Abstract Book   e237   2016.9

  • Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice Reviewed

    Tomofumi Fushima, Akiyo Sekimoto, Takahiro Minato, Takuya Ito, Yuji Oe, Kiyomi Kisu, Emiko Sato, Kenichi Funamoto, Toshiyuki Hayase, Yoshitaka Kimura, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

    PLOS ONE   11 ( 5 )   e0155426   2016.5

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    Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as sFlt-1 followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the role of genes on PE using genetically engineered animals has been problematic because it has been difficult to make a useful RUPP model in mice. To establish a RUPP model of PE in mice, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). Consequently, these mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. This novel RUPP model in mice should be useful for investigating the pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE.

    DOI: 10.1371/journal.pone.0155426

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  • Assessment of Autonomic Neurodevelopment in the mouse fetuses by using Fetal Electrocardiography Reviewed

    Ahsan H. Khandoker, Thuraia Al Khoori, Takuya Ito, Rika Sugibayashi, Yoshitaka Kimura

    2016 38TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC)   2016   2954 - 2957   2016

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    Fetal Electrocardiography (FECG) offers unique capabilities for assessment of beat-to-beat fetal heart rate (FHR) and fetal heart rate variability (FHRV), which are indirect markers of autonomic nervous system, its development. In this study the fetal ECG signals, FHR and FHRV are successfully recorded to assess the neurodevelopment in fetal mice in the second and third trimester from days 12.5 to 18.5 by using direct insertion of fetal ECG electrodes in the uterine. FHR increases from day 12.5 till 15.5 reaching a plateau and then shows a sudden increase on the day 18.5. Development of fetal increasing heart rate variability (FHRV) is clearly evident from the results. Short term FHRV (RMSSD) corresponding to parasympathetic nervous system activity and long term FHRV (SDNN) corresponding to sympathetic and parasympathetic nervous system activities increases till day 16.5 and then decreases from day 17.5. The increases in large fluctuations were noticed on days 17.5 and 18.5, which were thought to have caused by uterine contractions before delivery. The ability to assess FHR and FHRV in fetal mice makes a valuable tool for neurodevelopment research in perinatal medicine.

    DOI: 10.1109/EMBC.2016.7591349

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  • Vaginal LPS changed gene transcriptional regulation response to ischemic reperfusion and increased vulnerability of fetal brain hemorrhage Reviewed

    Yupeng Dong, Yoshitaka Kimura, Takuya Ito, Clarissa Velayo, Takafumi Sato, Rika Sugibayashi, Kiyoe Funamoto, Kudo Hitomi, Keita Iida, Miyuki Endo, Naoaki Sato, Nobuo Yaegashi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   468 ( 1-2 )   228 - 233   2015.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    During pregnancy, both ischemic reperfusion and bacterial agent LPS are known risk factors for fetal brain damage. However, there is a lack of evidence to explain whether vaginal LPS affects the fetus response to ischemic reperfusion. Here we reported that there was more than 2 folds higher vulnerability of fetal brain hemorrhage response to ischemic reperfusion when mother mouse was treated with vaginal LPS. As our previously reported, ischemic reperfusion induces P53-dependent fetal brain damage was based on a molecular mechanism: the transcriptional pattern was changed from HIF-1alpha-dependent to P53-dependent immediately. In the present work, only with vaginal LPS precondition, phosphorylation of activated transcriptional factor (ATF) 2 at Thr71 appeared in response to ischemic reperfusion. Moreover, this phosphorylation was completely blocked by pre-treatment with a P53 inhibitor, pifithrin-alpha. We concluded that vaginal LPS precondition trigged the p53-dependent phosphorylation of ATF2 in response to ischemic reperfusion, which played an important role of increasing vulnerability to hemorrhage in fetus. (C) 2015 The Authors. Published by Elsevier Inc.

    DOI: 10.1016/j.bbrc.2015.10.125

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  • Study of Permeability Changes of Endothelial Cell Monolayer Exposed to Hypoxia

    K. Matsubara, K. Funamoto, I.K. Zervantonakis, K. Funamoto, T. Ito, Y. Kimura, T. Hayase, R.D. Kamm

    Proceedings of the 12th International Conference on Flow Dynamics (ICFD2015)   362 - 363   2015.10

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  • Cardiac Evaluation of Fetal Mice by ECG and Ultrasound

    R. Sugibayashi, T. Ito, K. Funamoto, T. Hayase, Y. Kimura

    Proceedings of the 15th International Symposium on Advanced Fluid Information (AFI-2015)   184 - 185   2015.10

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  • Stabilization of postprandial blood glucose fluctuations by addition of glucagon like polypeptide-analog administration to intensive insulin therapy. Reviewed

    Ogawa, Susumu Nako, Kazuhiro Okamura, Masashi Sakamoto, Takuya Ito, Sadayoshi

    J Diabetes Investig   6 ( 4 )   436 - 442   2015.7

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    DOI: 10.1111/jdi.12314

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  • The strong relation between post-hemodialysis blood methylglyoxal levels and post-hemodialysis blood glucose concentration rise. Reviewed

    Senda, Miho Ogawa, Susumu Nako, Kazuhiro Okamura, Masashi Sakamoto, Takuya Ito, Sadayoshi

    Clin Exp Nephrol   19 ( 3 )   527 - 533   2015.6

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    DOI: 10.1007/s10157-014-1018-6

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  • Evaluation of Permeability of Endothelial Cell Monolayer under Controlled Oxygen Tension

    K. Funamoto, I.K. Zervantonakis, K. Matsubara, K. Funamoto, T. Ito, Y. Kimura, R.D. Kamm

    Proceedings of the 14th International Symposium on Advanced Fluid Information (AFI-2014)   102 - 103   2014.10

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  • Intrauterine Ischemic Reperfusion Switches the Fetal Transcriptional Pattern from HIF-1 alpha- to P53-Dependent Regulation in the Murine Brain Reviewed

    Yupeng Dong, Takuya Ito, Clarissa Velayo, Takafumi Sato, Keita Iida, Miyuki Endo, Kiyoe Funamoto, Naoaki Sato, Nobuo Yaegashi, Yoshitaka Kimura

    PLOS ONE   9 ( 10 )   e110577   2014.10

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    Ischemic reperfusion (IR) during the perinatal period is a known causative factor of fetal brain damage. So far, both morphologic and histologic evidence has shown that fetal brain damage can be observed only several hours to days after an IR insult has occurred. Therefore, to prevent fetal brain damage under these circumstances, a more detailed understanding of the underlying molecular mechanisms involved during an acute response to IR is necessary. In the present work, pregnant mice were exposed to IR on day 18 of gestation by clipping one side of the maternal uterine horn. Simultaneous fetal electrocardiography was performed during the procedure to verify that conditions resulting in fetal brain damage were met. Fetal brain sampling within 30 minutes after IR insult revealed molecular evidence that a fetal response was indeed triggered in the form of inhibition of the Akt-mTOR-S6 synthesis pathway. Interestingly, significant changes in mRNA levels for both HIF-1 alpha and p53 were apparent and gene regulation patterns were observed to switch from a HIF-1 alpha-dependent to a p53-dependent process. Moreover, pre-treatment with pifithrin-alpha, a p53 inhibitor, inhibited protein synthesis almost completely, revealing the possibility of preventing fetal brain damage by prophylactic pifithrin-a treatment.

    DOI: 10.1371/journal.pone.0110577

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  • Automated Estimation of Fetal Cardiac Timing Events From Doppler Ultrasound Signal Using Hybrid Models

    Faezeh Marzbanrad, Yoshitaka Kimura, Kiyoe Funamoto, Rika Sugibayashi, Miyuki Endo, Takuya Ito, Marimuthu Palaniswami, Ahsan H. Khandoker

    IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS   18 ( 4 )   1169 - 1177   2014.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC  

    In this paper, a new noninvasive method is proposed for automated estimation of fetal cardiac intervals from Doppler Ultrasound (DUS) signal. This method is based on a novel combination of empirical mode decomposition (EMD) and hybrid support vector machines-hidden Markov models (SVM/HMM). EMD was used for feature extraction by decomposing the DUS signal into different components (IMFs), one of which is linked to the cardiac valve motions, i.e. opening (o) and closing (c) of the Aortic (A) and Mitral (M) valves. The noninvasive fetal electrocardiogram (fECG) was used as a reference for the segmentation of the IMF into cardiac cycles. The hybrid SVM/HMM was then applied to identify the cardiac events, based on the amplitude and timing of the IMF peaks as well as the sequence of the events. The estimated timings were verified using pulsed doppler images. Results show that this automated method can continuously evaluate beat-to-beat valve motion timings and identify more than 91% of total events which is higher than previous methods. Moreover, the changes of the cardiac intervals were analyzed for three fetal age groups: 16-29, 30-35, and 36-41 weeks. The time intervals from Q-wave of fECG to Ac (Systolic Time Interval, STI), Ac to Mo (Isovolumic Relaxation Time, IRT), Q-wave to Ao (Preejection Period, PEP) and Ao to Ac (Ventricular Ejection Time, VET) were found to change significantly (p < 0.05) across these age groups. In particular, STI, IRT, and PEP of the fetuses with 36-41 week were significantly (p < 0.05) different from other age groups. These findings can be used as sensitive markers for evaluating the fetal cardiac performance.

    DOI: 10.1109/JBHI.2013.2286155

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  • Molecular patterns of neurodevelopmental preconditioning: a study of the effects of antenatal steroid therapy in a protein-restriction mouse model

    Clarissa Velayo, Takuya Ito, Yupeng Dong, Miyuki Endo, Rika Sugibayashi, Kiyoe Funamoto, Keita Iida, Nobuo Yaegashi, Yoshitaka Kimura

    ISRN Obstetrics and Gynecology   2014   1 - 13   2014

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    <italic>Introduction</italic>. Prenatal programming secondary to maternal protein restriction renders an inherent susceptibility to neural compromise in neonates and any addition of glucocorticosteroids results in further damage. This is an investigation of consequent global gene activity due to effects of antenatal steroid therapy on a protein restriction mouse model. <italic>Methods</italic>. C57BL/6N pregnant mice were administered control or protein restricted diets and subjected to either 100 <italic>μ</italic>g/Kg of dexamethasone sodium phosphate with normosaline or normosaline alone during late gestation (E10–E17). Nontreatment groups were also included. Brain samples were collected on embryonic day 17 and analyzed by mRNA microarray analysis. <italic>Results</italic>. Microarray analyses presented 332 significantly regulated genes. Overall, neurodevelopmental genes were overrepresented and a subset of 8 genes allowed treatment segregation through the hierarchical clustering method. The addition of stress or steroids greatly affected gene regulation through glucocorticoid receptor and stress signaling pathways. Furthermore, differences between dexamethasone-administered treatments implied a harmful effect during conditions of high stress. Microarray analysis was validated using qPCR. <italic>Conclusion</italic>. The effects of antenatal steroid therapy vary in fetuses according to maternal-fetal factors and environmental stimuli. Defining the key regulatory networks that signal either beneficial or damaging corticosteroid action would result in valuable adjustments to current treatment protocols.

    DOI: 10.1155/2014/193816

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    Other Link: http://downloads.hindawi.com/archive/2014/193816.xml

  • Effects of Temporal and Spatial Oxygen Heterogeneity on Cell Processes

    K. Funamoto, I. K. Zervantonakis, K. Funamoto, T. Ito, Y. Kimura, R. D. Kamm

    Proceedings of the 13th International Symposium on Advanced Fluid Information (AFI-2013)   92 - 93   2013.11

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  • Eicosapentaenoic acid improves glycemic control in elderly bedridden patients with type 2 diabetes. Reviewed

    Ogawa, Susumu Abe, Takaaki Nako, Kazuhiro Okamura, Masashi Senda, Miho Sakamoto, Takuya Ito, Sadayoshi DIMS, Study Group

    Tohoku J Exp Med   231 ( 1 )   63 - 74   2013

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    DOI: 10.1620/tjem.231.63

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  • Development of fetal cardiac intervals throughout 16 to 41 weeks of gestation

    Faezeh Marzbanrad, Yoshitaka Kimura, Kiyoe Funamoto, Rika Sugibayashi, Miyuki Endo, Takuya Ito, Marimuthu Palaniswami, Ahsan Khandoker

    Computing in Cardiology   40   1155 - 1158   2013

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    In this paper a new noninvasive method is proposed for automated estimation of fetal cardiac intervals from Doppler Ultrasound (DUS) signal and fetal electrocardiogram (fECG) as a reference. The proposed method is based on a combination of Wavelet analysis and hybrid Support Vector Machines- Hidden Markov Models (SVM/HMM). This method provides automated beat by beat identification of cardiac valves' opening and closing which are used to estimate the fetal cardiac intervals. The range of these intervals in different gestational age from 16 to 41 weeks was evaluated in this study. The correlation between beat to beat intervals was also investigated. Results show a significant negative correlation between Pre-Ejection Period (PEP) and Ventricular Ejection Time (VET) (r = -0.61, p &lt
    0.0001), a positive correlation between VET and Systolic Time Interval (STI) (r =0.51, p &lt
    0.0001) and a significant correlation between PEP and Isovolumic Contraction Time (ICT) (r =0.67, p &lt
    0.0001). © 2013 CCAL.

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  • Development of Fetal Cardiac Intervals throughout 16 to 41 Weeks of Gestation Reviewed

    Faezeh Marzbanrad, Yoshitaka Kimura, Kiyoe Funamoto, Rika Sugibayashi, Miyuki Endo, Takuya Ito, Marimuthu Palaniswami, Ahsan Khandoker

    2013 COMPUTING IN CARDIOLOGY CONFERENCE (CINC)   40   1155 - 1158   2013

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    In this paper a new noninvasive method is proposed for automated estimation of fetal cardiac intervals from Doppler Ultrasound (DUS) signal and fetal electrocardiogram (fECG) as a reference. The proposed method is based on a combination of Wavelet analysis and hybrid Support Vector Machines- Hidden Markov Models (SVM/HMM). This method provides automated beat by beat identification of cardiac valves' opening and closing which are used to estimate the fetal cardiac intervals. The range of these intervals in different gestational age from 16 to 41 weeks was evaluated in this study. The correlation between beat to beat intervals was also investigated. Results show a significant negative correlation between Pre-Ejection Period (PEP) and Ventricular Ejection Time (VET) (r = -0.61, p &lt; 0.0001), a positive correlation between VET and Systolic Time Interval (STI) (r = 0.51, p &lt; 0.0001) and a significant correlation between PEP and Isovolumic Contraction Time (ICT) (r = 0.67, p &lt; 0.0001).

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  • Rheological Analysis of the Mechanism of Fetal Brain Hemorrhage

    T. Ito, K. Funamoto, K. Funamoto, T. Hayase, Y. Kimura

    Proceedings of the 12th International Symposium on Advanced Fluid Information and Transdisciplinary Fluid Integration (AFI/TFI-2012)   116 - 117   2012.9

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  • Maternal Undernutrition Induces the Expression of Hypoxia-Related Genes in the Fetal Brain

    Takuya Ito, Kiyoe Funamoto, Naoaki Sato, Ai Nakamura, Kaori Tanabe, Tetsuro Hoshiai, Kaori Suenaga, Junichi Sugawara, Satoru Nagase, Kunihiro Okamura, Nobuo Yaegashi, Yoshitaka Kimura

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE   226 ( 1 )   37 - 44   2012.1

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    Maternal undernutrition during pregnancy is a risk factor for cerebrovascular and cardiovascular diseases in adulthood. Hypoxia-inducible factor 1 alpha (HIF1 alpha) plays an essential role in cellular hypoxic responses, and its increased expression is associated with cerebrovascular and cardiovascular diseases. However, it is not known whether maternal undernutrition influences HIF1 alpha expression in the fetal brain. We therefore analyzed the expression levels of HIFI a and its downstream genes in the fetal brain (day 17.5 of gestation, 1-2 days before birth). Maternal undernutrition did not noticeably affect the fetal body and brain weights. Both HIF1 alpha mRNA and protein levels were increased in the brain under maternal undernutrition, despite the absence of hypoxia, as judged by the staining profile with hypoxyprobe-1 that identifies hypoxic cells. Importantly, maternal undernutrition caused the accumulation of HIF1 alpha protein in oligodendrocyte precursor cells at the subventricular zone, a site of neurogenesis in the fetal brain. Maternal undernutrition also increased the mRNA level of mammalian target of rapamycin (mTOR), which could increase the level of HIF1 alpha protein under normoxia. Furthermore, microarray analysis revealed that expression levels of mRNAs for 10 HIF1 alpha downstream targets, including enolase 1 and hexokinase 1, were increased in the fetal brain under maternal undernutrition. Thus, the biochemical consequence of maternal undernutrition is similar to that of mild hypoxia. In conclusion, maternal undernutrition induces the expression of HIF1 alpha in oligodendrocyte precursor cells at the subventricular zone, and it also induces the expression of hypoxia-related genes in the fetal brain probably via activation of the mTOR pathway.

    DOI: 10.1620/tjem.226.37

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  • Recent Advances in Fetal Electrocardiography

    Yoshitaka Kimura, Naoaki Sato, Junichi Sugawara, Clarissa Velayo, Teturo Hoshiai, Satoru Nagase, Takuya Ito, Yukari Onuma, Asami Katsumata, Kunihiro Okamura, Nobuo Yaegashi

    Open Medical Devices Journal   4   7 - 12   2012

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    Since the first observations of Cremer in 1906, fetal electrocardiogram (ECG) measurements via the maternal abdominal wall have remained a formidable challenge for clinical technicians and engineers in the cutting-edge field of information theory. Previous obstacles in extracting fetal ECG still complicate their acquisition at the present. These include three main difficulties for non-invasive measurement of fetal ECG: first, the low signal to noise ratio
    second, the lack of a standard lead system for fetal ECG on the maternal abdomen
    and third, the factor of fetal movement or non-stationarity during recording. A new extraction system based on blind source separation with reference signals (BSSR) was utilized and our detection rates, both off-line (91%) and on-line (60%), in pregnancies of 20 to 41 weeks of gestation have shown a marked improvement from earlier attempts. With this development, we discuss the potentials and limitations of this new system. © Kimura et al.

    DOI: 10.2174/1875181401204010007

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  • Effects of the Great East Japan Earthquake and huge tsunami on glycaemic control and blood pressure in patients with diabetes mellitus. Reviewed

    Ogawa, Susumu Ishiki, Mikihito Nako, Kazuhiro Okamura, Masashi Senda, Miho Sakamoto, Takuya Ito, Sadayoshi

    BMJ Open   2 ( 2 )   e000830 - e000830   2012

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    DOI: 10.1136/bmjopen-2012-000830

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  • The glucagon-like peptide-1 analog liraglutide suppresses ghrelin and controls diabetes in a patient with Prader-Willi syndrome. Reviewed

    Senda, Miho Ogawa, Susumu Nako, Kazuhiro Okamura, Masashi Sakamoto, Takuya Ito, Sadayoshi

    Endocr J   59 ( 10 )   889 - 894   2012

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    DOI: 10.1507/endocrj.EJ12-0074

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  • Successful Detection of the Fetal Electrocardiogram Waveform Changes during Various States of Singletons

    Naoaki Sato, Tetsuro Hoshiai, Takuya Ito, Kazunari Owada, Hiroshi Chisaka, Ayako Aoyagi, Junichi Sugawara, Nobuo Yaegashi, Kunihiro Okamura, Yoshitaka Kimura

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE   225 ( 2 )   89 - 94   2011.10

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    Accurate assessment of fetal well-being is one of the most important tasks for obstetricians. It is still difficult to measure fetal electrocardiogram (ECG) during fetal movements. Recently, a new method, blind source separation with reference signals, was proposed for stable measurements. This method distinguishes weak signals from noisy mixed signals with little information about the sources. The aim of this study is to estimate the ability of this method for fetal ECG monitoring and to establish standard fetal ECG electrocardiogram values of normal singletons including during fetal movement. The subjects enrolled were 167 pregnant women with normal single pregnancy from 18- to 41-week gestation, who regularly visited Tohoku University Hospital, and 12 pregnant women with fetal abnormality. Fetal signals were successfully separated in 163 of 179 subjects at 91.1% success rate regardless of fetal movements. Time intervals of ECG (P, PR and QRS intervals and QTc) were measured. The standard curves of each interval through the gestational period were obtained. The data in active phase were compared to that in rest phase and the data obtained from normal and abnormal fetuses were investigated. PR intervals in the rest phase were prolonged compared to those in the active phase. Fetal ECG showed anomalous values such as PR interval or QTc prolongation in the abnormal fetuses. The fetal ECG was measured by the new method with or without fetal movements, and the standard fetal ECG values have been established. This study provides a foundation for further detailed clinical studies.

    DOI: 10.1620/tjem.225.89

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  • Successful Detection of the Fetal Electrocardiogram Waveform Changes during Various States of Singletons

    Naoaki Sato, Tetsuro Hoshiai, Takuya Ito, Kazunari Owada, Hiroshi Chisaka, Ayako Aoyagi, Junichi Sugawara, Nobuo Yaegashi, Kunihiro Okamura, Yoshitaka Kimura

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE   225 ( 2 )   89 - 94   2011.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:TOHOKU UNIV MEDICAL PRESS  

    Accurate assessment of fetal well-being is one of the most important tasks for obstetricians. It is still difficult to measure fetal electrocardiogram (ECG) during fetal movements. Recently, a new method, blind source separation with reference signals, was proposed for stable measurements. This method distinguishes weak signals from noisy mixed signals with little information about the sources. The aim of this study is to estimate the ability of this method for fetal ECG monitoring and to establish standard fetal ECG electrocardiogram values of normal singletons including during fetal movement. The subjects enrolled were 167 pregnant women with normal single pregnancy from 18- to 41-week gestation, who regularly visited Tohoku University Hospital, and 12 pregnant women with fetal abnormality. Fetal signals were successfully separated in 163 of 179 subjects at 91.1% success rate regardless of fetal movements. Time intervals of ECG (P, PR and QRS intervals and QTc) were measured. The standard curves of each interval through the gestational period were obtained. The data in active phase were compared to that in rest phase and the data obtained from normal and abnormal fetuses were investigated. PR intervals in the rest phase were prolonged compared to those in the active phase. Fetal ECG showed anomalous values such as PR interval or QTc prolongation in the abnormal fetuses. The fetal ECG was measured by the new method with or without fetal movements, and the standard fetal ECG values have been established. This study provides a foundation for further detailed clinical studies.

    DOI: 10.1620/tjem.225.89

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  • Hypoxia-Like Gene Responses to Maternal Undernutrition in Fetal Heart Reviewed

    Yoshitaka Kimura, Takuya Ito, Kaori Tanabe, Ai Nakamura, Kiyoe Funamoto, Ayako Aoyagi, Kazuyo Sato, Tetsuro Hoshiai, Kaori Suenaga, Junichi Sugawara, Satoru Nagase, Nobuo Yaegashi, Kunihiro Okamura

    JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE   2   S71 - S71   2011.9

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  • Gene Network of Fetal Brain Reacts to Maternal Undernutrition Like-Hypoxia Reviewed

    Takuya Ito, Yoshitaka Kimura, Kaori Tanabe, Ai Nakamura, Kiyoe Funamoto, Ayako Aoyagi, Kazuyo Sato, Tetsuro Hoshiai, Kaori Suenaga, Junichi Sugawara, Satoru Nagase, Kunihiro Okamura, Nobuo Yaegashi

    JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE   2   S90 - S90   2011.9

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  • Aberrant Expression of Hypoxia-Inducible Factor 1 alpha in the Fetal Heart Is Associated with Maternal Undernutrition Reviewed

    Takuya Ito, Kaori Tanabe, Ai Nakamura, Kiyoe Funamoto, Ayako Aoyagi, Kazuyo Sato, Tetsuro Hoshiai, Kaori Suenaga, Junichi Sugawara, Satoru Nagase, Kunihiro Okamura, Nobuo Yaegashi, Yoshitaka Kimura

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE   224 ( 3 )   163 - 171   2011.7

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    Maternal undernutrition during pregnancy is a risk factor that impairs fetal growth and causes cardiovascular diseases. However, the underlying mechanism is still unknown. In this study, we evaluated the effect of maternal undernutrition on the expression levels of transcription factors in the fetal heart. Female mice were given low protein or regular food from 2 weeks before mating and during their pregnancy. The fetal hearts were collected on day 17.5 of gestation, about 1-2 days before birth. Maternal undernutrition resulted in a significant increase in the relative heart weight (heart weight/body weight) in female fetuses, but not in male fetuses. Microarray analysis revealed that expression levels of mRNAs for 133 transcription factors were changed in the fetal heart under maternal undernutrition. Among them, we focused on hypoxia-inducible factor 1 alpha (HIF1 alpha) that is involved in the pathogenesis of cardiovascular diseases on adulthood. Quantitative real-time PCR analysis showed that the expression level of HIF1 alpha mRNA was increased about 1.3-fold in male fetal heart under maternal undernutrition, but remained unchanged in female heart. Moreover, maternal undernutrition increased the mRNA level of prolyl hydroxylase 1 (PHD1), which contributes to degradation of HIF1 alpha, in male heart but not in female heart. Immunohistochemical analysis showed the accumulation of HIF1 alpha protein in the fetal heart of both sexes under maternal undernutrition, without the induction of HIF1 alpha mRNA expression in female heart. These results suggest that maternal undernutrition may induce HIF1 alpha expression in the fetal heart through the distinct mechanisms depending on the sex.

    DOI: 10.1620/tjem.224.163

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  • Aberrant Expression of Hypoxia-Inducible Factor 1 alpha in the Fetal Heart Is Associated with Maternal Undernutrition

    Takuya Ito, Kaori Tanabe, Ai Nakamura, Kiyoe Funamoto, Ayako Aoyagi, Kazuyo Sato, Tetsuro Hoshiai, Kaori Suenaga, Junichi Sugawara, Satoru Nagase, Kunihiro Okamura, Nobuo Yaegashi, Yoshitaka Kimura

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE   224 ( 3 )   163 - 171   2011.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:TOHOKU UNIV MEDICAL PRESS  

    Maternal undernutrition during pregnancy is a risk factor that impairs fetal growth and causes cardiovascular diseases. However, the underlying mechanism is still unknown. In this study, we evaluated the effect of maternal undernutrition on the expression levels of transcription factors in the fetal heart. Female mice were given low protein or regular food from 2 weeks before mating and during their pregnancy. The fetal hearts were collected on day 17.5 of gestation, about 1-2 days before birth. Maternal undernutrition resulted in a significant increase in the relative heart weight (heart weight/body weight) in female fetuses, but not in male fetuses. Microarray analysis revealed that expression levels of mRNAs for 133 transcription factors were changed in the fetal heart under maternal undernutrition. Among them, we focused on hypoxia-inducible factor 1 alpha (HIF1 alpha) that is involved in the pathogenesis of cardiovascular diseases on adulthood. Quantitative real-time PCR analysis showed that the expression level of HIF1 alpha mRNA was increased about 1.3-fold in male fetal heart under maternal undernutrition, but remained unchanged in female heart. Moreover, maternal undernutrition increased the mRNA level of prolyl hydroxylase 1 (PHD1), which contributes to degradation of HIF1 alpha, in male heart but not in female heart. Immunohistochemical analysis showed the accumulation of HIF1 alpha protein in the fetal heart of both sexes under maternal undernutrition, without the induction of HIF1 alpha mRNA expression in female heart. These results suggest that maternal undernutrition may induce HIF1 alpha expression in the fetal heart through the distinct mechanisms depending on the sex.

    DOI: 10.1620/tjem.224.163

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  • Understanding congenital heart defects through abdominal fetal electrocardiography: Case reports and clinical implications

    Clarissa Velayo, Naoaki Sato, Takuya Ito, Hiroshi Chisaka, Nobuo Yaegashi, Kunihiro Okamura, Yoshitaka Kimura

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   37 ( 5 )   428 - 435   2011.5

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    Aims:
    Congenital heart defects are the most common fetal structural anomalies of which a significant number remain unrecognized during postnatal life. Fetal electrocardiography (FECG) is an ideal clinical tool to complement ultrasonography for the screening and management of these cases where early and accurate diagnoses would allow definite rather than palliative treatment. The objective of this report was to correlate the particular FECG results found with the different types of congenital heart defects involved and to further demonstrate the usefulness of FECG in clinical settings.
    Material & Methods:
    This is a report of four cases of prenatally diagnosed congenital heart defects seen at a university hospital in Sendai, Japan. Their complete and thorough evaluation included, among other tests, abdominal FECG analysis.
    Results:
    The presence of premature ventricular contractions, a prolonged pre-ejection period (PEP &gt; 75 msec), and prolonged QTc intervals (QTc &gt; 440 msec) served as markers of hemodynamic alteration but were unlikely determinants of disease severity precluding further investigation.
    Conclusions:
    In practice, similar findings found on FECG should raise the index of suspicion for the presence of congenital heart disease and prompt a targeted ultrasound scan.

    DOI: 10.1111/j.1447-0756.2010.01367.x

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  • Understanding congenital heart defects through abdominal fetal electrocardiography: Case reports and clinical implications Reviewed

    Clarissa Velayo, Naoaki Sato, Takuya Ito, Hiroshi Chisaka, Nobuo Yaegashi, Kunihiro Okamura, Yoshitaka Kimura

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   37 ( 5 )   428 - 435   2011.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY-BLACKWELL  

    Aims:
    Congenital heart defects are the most common fetal structural anomalies of which a significant number remain unrecognized during postnatal life. Fetal electrocardiography (FECG) is an ideal clinical tool to complement ultrasonography for the screening and management of these cases where early and accurate diagnoses would allow definite rather than palliative treatment. The objective of this report was to correlate the particular FECG results found with the different types of congenital heart defects involved and to further demonstrate the usefulness of FECG in clinical settings.
    Material & Methods:
    This is a report of four cases of prenatally diagnosed congenital heart defects seen at a university hospital in Sendai, Japan. Their complete and thorough evaluation included, among other tests, abdominal FECG analysis.
    Results:
    The presence of premature ventricular contractions, a prolonged pre-ejection period (PEP &gt; 75 msec), and prolonged QTc intervals (QTc &gt; 440 msec) served as markers of hemodynamic alteration but were unlikely determinants of disease severity precluding further investigation.
    Conclusions:
    In practice, similar findings found on FECG should raise the index of suspicion for the presence of congenital heart disease and prompt a targeted ultrasound scan.

    DOI: 10.1111/j.1447-0756.2010.01367.x

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  • Maternal Undernutrition with Vaginal Inflammation Impairs the Neonatal Oligodendrogenesis in Mice

    Takuya Ito, Kaori Hoshiai, Kaori Tanabe, Ai Nakamura, Kiyoe Funamoto, Ayako Aoyagi, Hiroshi Chisaka, Kunihiro Okamura, Nobuo Yaegashi, Yoshitaka Kimura

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE   223 ( 3 )   215 - 222   2011.3

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    Maternal undernutrition and infection during pregnancy may impair development of oligodendrocytes, thereby increasing risks of neuropsychiatric disorders of their children. We analyzed the effects of those risk factors on oligodendrogenesis in fetal and neonatal brains. Female mice were given low-protein or regular food for 2 weeks before their pregnancy. On the 14th day of pregnancy, they received a transvaginal injection of lipopolysaccharide to induce inflammation or control solution, consisting of four groups, depending on nutritional conditions with or without vaginal inflammation. We collected fetal brains on embryonic day (E) 17 for evaluating oligodendrocyte precursor cells (OPCs) and neonatal brains on postnatal day (P) 7 for evaluating mature oligodendrocytes. OPCs and mature oligodendrocytes were identified as positive immunostaining for oligodendrocyte-lineage transcription factor 2 and myelin basic protein, respectively. There was no difference in the number of OPCs in E17 brains among the four groups, suggesting that nutritional restriction with or without inflammation exerts no noticeable influence on the differentiation of OPCs. However, the number of mature oligodendrocytes was decreased in P7 brains obtained from nutrient-restricted mice with inflammation, suggesting that their combination impairs oligodendrogenesis in the neonatal brain. We also analyzed reactive astrocytes that express both glial fibrillary acidic protein and nestin for evaluating brain inflammation. The population of reactive astrocytes was increased in P7 brains derived from mice with LPS injection, irrespective of nutritional restriction, indicating that maternal vaginal inflammation induces neonatal brain inflammation. The maternal management of both nutrition and infection is crucial to prevent neuropsychiatric disorders of the children.

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  • Fluid Analysis of the Mechanism of Fetal Brain Hemorrhage

    T. Ito, K. Funamoto, K. Funamoto, K. Tanabe, A. Nakamura, T. Hayase, Y. Kimura

    Proceedings of the tenth International Symposium on Advanced Fluid Information and Transdisciplinary Fluid Integration (AFI/TFI-2010)   78 - 79   2010.11

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  • Effects of Antenatal Steroid Therapy on Neurodevelopment in an IUGR Mouse Model

    Clarissa Velayo, Takuya Ito, Hiroshi Chisaka, Nobuo Yaegashi, Kunihiro Okamura, Yoshitaka Kimura

    FETAL DIAGNOSIS AND THERAPY   28 ( 2 )   79 - 86   2010

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    Background/Objective: To investigate the neurodevelopmental response in postnatal mice secondary to antenatal steroid treatment in association with maternal protein restriction. Methods: C57BL/6N pregnant mice (n = 24; 4 per treatment group) were administered control (C) or protein-restricted (PR) diets and subjected to daily subcutaneous injection stress during late gestation (E10-E17) with either 100 mu l/kg of dexamethasone sodium phosphate in normosaline (C-D/S, PR-D/S) or normosaline alone (C-S, PR-S). Non-treatment groups were also included (C, PR). Brain samples of pups were collected on postnatal day 7 and analyzed by immunohistochemistry and qRT-PCR. Results: Neonatal weights in the treatment groups were smaller than their counterparts in the C group, but there were no significant differences in brain size. Immunohistochemical evaluation of neuroglial cells revealed a pronounced effect of protein restriction on oligodendrocytes and oligodendrocyte precursor cells with distinct fetal responses to stress and dexamethasone. Further evaluation using quantitative RNA analysis showed significant activation of Galr1, Galr2, Igfbp-1, Igfbp-3, Igfbp-6, and Fgf2 by 1- to 2.5-fold in the PR-D/S group and by much higher increments, 1- to 10.5-fold, in the PR-S group. Conclusion: This preliminary investigation revealed the possible role of dexamethasone in further increasing vulnerability to cell damage in injury-prone neuroglial cells. The distribution of key glial markers and the overexpression of several neurotrophic factors depicted ongoing cellular adaptation. Copyright (C) 2010 S. Karger AG, Basel

    DOI: 10.1159/000316102

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  • Antepartum non-invasive evaluation of opening and closing timings of the cardiac valves in fetal cardiac cycle

    Ahsan H. Khandoker, Yoshitaka Kimura, Takuya Ito, Naoaki Sato, Kunihiro Okamura, Marimuthu Palaniswami

    MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING   47 ( 10 )   1075 - 1082   2009.10

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    In this study, we propose a non-invasive algorithm to recognize the timings of fetal cardiac events on the basis of analysis of fetal ECG (FECG) and Doppler ultrasound signals. Multiresolution wavelet analysis enabled the frequency contents of the Doppler signals to be linked to the opening (o) and closing (c) of the heart&apos;s valves (Aortic (A) and Mitral (M)). M-mode, B-mode and pulsed Doppler ultrasound were used to verify the timings of opening and closure of these valves. In normal fetuses, the time intervals from Q-wave of QRS complex of FECG to opening and closing of aortic valve, i.e., Q-Ao and Q-Ac were found to be 79.3 +/- A 17.4 and 224.7 +/- A 13.3 ms, respectively. For the mitral valve, Q-Mc and Q-Mo were found to be 27.7 +/- A 9.4 and 294.6 +/- A 21.3 ms, respectively. Correlations among the timings in opening and closing of cardiac valves were found to be higher in abnormal fetuses than that in normal ones.

    DOI: 10.1007/s11517-009-0528-y

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  • Antepartum non-invasive evaluation of opening and closing timings of the cardiac valves in fetal cardiac cycle Reviewed

    Ahsan H. Khandoker, Yoshitaka Kimura, Takuya Ito, Naoaki Sato, Kunihiro Okamura, Marimuthu Palaniswami

    MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING   47 ( 10 )   1075 - 1082   2009.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER HEIDELBERG  

    In this study, we propose a non-invasive algorithm to recognize the timings of fetal cardiac events on the basis of analysis of fetal ECG (FECG) and Doppler ultrasound signals. Multiresolution wavelet analysis enabled the frequency contents of the Doppler signals to be linked to the opening (o) and closing (c) of the heart&apos;s valves (Aortic (A) and Mitral (M)). M-mode, B-mode and pulsed Doppler ultrasound were used to verify the timings of opening and closure of these valves. In normal fetuses, the time intervals from Q-wave of QRS complex of FECG to opening and closing of aortic valve, i.e., Q-Ao and Q-Ac were found to be 79.3 +/- A 17.4 and 224.7 +/- A 13.3 ms, respectively. For the mitral valve, Q-Mc and Q-Mo were found to be 27.7 +/- A 9.4 and 294.6 +/- A 21.3 ms, respectively. Correlations among the timings in opening and closing of cardiac valves were found to be higher in abnormal fetuses than that in normal ones.

    DOI: 10.1007/s11517-009-0528-y

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  • Robustness of the blind source separation with reference against uncertainties of the reference signals.

    Netabayashi T, Kimura Y, Chida S, Ito T, Ohwada K, Katayama N, Okamura K, Nakao M

    Conf Proc IEEE Eng Med Biol Soc   1875 - 1878   2008

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  • Non-Invasive Evaluation of Opening and Closing Timings of the Cardiac Valves in the Fetal Cardiac Cycle

    A. H. Khandoker, Y. Kimura, T. Ito, N. Sato, K. Kamura, M. Palaniswami

    COMPUTERS IN CARDIOLOGY 2008, VOLS 1 AND 2   35   1061 - +   2008

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    In this study, we propose a non-invasive system to recognize the timings of fetal cardiac events on the basis of analysis of fetal ECG and Doppler ultrasound signal together. Fetal ECG was extracted from transabdominal ECG (10 normal subjects, 38-41 weeks of gestation) using blind source separation with the reference signal. Multiresolution wavelet analysis enabled the frequency contents of the Doppler signals to be linked to the opening(o) and closing(c) of the heart's valves (Aortic (A) and mitral(M)). M-mode, B-mode and pulsed Doppler ultrasound were used to examine and verify the timings of opening and closure of aortic as well as mitral valves. The time intervals from Q-wave of QRS complex of fetal ECG to opening and closing of aortic valve, i.e. Q-Ao and Q-Ac were found to be 75.0 +/- 11.9 (msec) and 221.6 +/- 29.0 (msec) respectively. As for the mitral valve, Q-Mc and Q-Mo were found to be 45.0 +/- 18.9 (msec) and 301.6 +/- 20.7 (msec) respectively.

    DOI: 10.1109/CIC.2008.4749228

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  • Food restriction in pregnant mice can induce changes in histone modifications and suppress gene expression in fetus. Reviewed

    Sharif J, Nakamura M, Ito T, Kimura Y, Nagamune T, Mitsuya K, Okamura K

    Nucleic acids symposium series (2004)   ( 51 )   125 - 126   2007

  • Comparison of growth and exploratory behavior in mice fed an exclusively milk formula diet and mice fed a food-pellet diet post weaning. Reviewed International journal

    Toshiaki Ishii, Takuya Ito, Masakazu Nishimura

    Life sciences   78 ( 2 )   174 - 9   2005.11

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    An exclusively milk formula diet stunted the growth of mice immediately following weaning. Milk-fed mice displayed a low-frequency profile of exploratory behavior, while pellet-fed mice showed high-frequency exploration. In contrast to exploratory behavior, feeding behavior did not differ significantly between milk- and pellet-fed mice. Despite showing low-frequency exploratory behavior, mice on an exclusively milk formula diet showed no difference in behavioral activities analyzed by an automatic hole-board apparatus compared to pellet-fed mice. These results suggest that the growth stunt caused by an exclusively milk formula diet retards the acquisition of active exploratory behavior without affecting the emotional state of mice.

    DOI: 10.1016/j.lfs.2005.04.041

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  • 医学教育におけるVisual Analog Scaleの新しい利用方法の提案

    壹岐 裕子, 工藤 克昌, 野田 雅史, 井本 博文, 松田 安史, 伊藤 拓哉, 海野 倫明

    日本シミュレーション医療教育学会雑誌   5   138 - 138   2017.8

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  • 医学教育におけるVisual Analog Scaleの新しい利用方法の提案

    壹岐 裕子, 工藤 克昌, 野田 雅史, 井本 博文, 松田 安史, 伊藤 拓哉, 海野 倫明

    日本シミュレーション医療教育学会雑誌   5   138 - 138   2017.8

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  • 動物を用いた若手医師の外科手術トレーニングと動物倫理

    壹岐 裕子, 野田 雅史, 工藤 克昌, 末田 輝子, 兼平 雅彦, 伊藤 拓哉, 松田 安史, 岡田 克典, 海野 倫明

    胸部外科   70 ( 5 )   329 - 333   2017.5

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    東北大学病院先端医療技術トレーニングセンター(当センター)で開催された、全身麻酔下のブタを用いた外科手術トレーニングに参加した初期研修医41名を対象として、トレーニング内容に関するアンケート調査を行い、動物トレーニングにおける倫理的配慮の妥当性を検証した。アンケートの中から倫理に関する回答のみを抽出し、トレーニング前後の変化を解析した結果、ヒトに対する倫理に関してトレーニング前後の値に有意差を認めた設問は5問中1問であったが、動物に対する倫理に関しては6問中6問すべてに有意差を認め、いずれも動物倫理意識の向上に向かっていた。当センターにおける動物倫理講義を含めた外科手術トレーニングが、受講生の動物倫理的側面において有効な動機付けを与えていることが検証され、意義のあるプログラムであることが確認できた。

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  • 母体腹壁誘導胎児心電図 Invited

    湊敬廣, 伊藤拓哉, 大塩清佳, 佐藤尚明, 木村芳孝, 八重樫伸生

    周産期医学   47 ( 4 )   489 - 493   2017.4

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  • A New Method of Predicting a Brain Hemorrhage Risk in Fetal Growth Restriction.

    Takahiro Minato, Takuya Ito, Naoaki Sato, Yoshitaka Kimura, Nobuo Yaegashi

    REPRODUCTIVE SCIENCES   24   136A - 137A   2017.3

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  • ブタを用いた新たなドナー肺長時間保存法の開発へ向けて

    鈴木 寛利, 松田 安史, 月舘 久勝, 川原 岬, 伊藤 拓哉, 兼平 雅彦, 野田 雅史, 田中 徹, 岡田 克典

    Organ Biology   23 ( 3 )   72 - 72   2016.10

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  • Vaginal LPS Preconditioning Might Protect Fetal Brain from Amniotic LPS Through Fetal Inflammatory Reaction.

    Yupeng Dong, Yoshitaka Kimura, Takuya Ito, Ken Haneda, Takahiro Minato, Kiyoe Funamoto, Rika Sugibayashi, Motoyoshi Kawataki, Nobuo Yaegashi

    REPRODUCTIVE SCIENCES   23   228A - 228A   2016.3

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  • 2D34 Investigation of Permeability of Endothelial Cell Monolayer by Using Microfluidic Device with Controllability of Oxygen Tension

    MATSUBARA Kento, FUNAMOTO Kenichi, ZERVANTONAKIS Ioannis K., FUNAMOTO Kiyoe, ITO Takuya, MASAMUNE Jun, KIMURA Yoshitaka, HAYASE Toshiyuki, KAMM Roger D.

    2016 ( 28 )   "2D34 - 1"-"2D34-5"   2016.1

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    Permeability changes of an endothelial cell (EC) monolayer are related to many diseases. This study evaluated permeability of the EC monolayer under normoxia and hypoxia by using fluorescent dextrans of two different molecular weights in a microfluidic device with controllability of oxygen tension. As the results, permeability of the EC monolayer increased by hypoxic exposure, and the increase of the permeability measured by fluorescent dextran of 10 kDa was smaller than that measured by fluorescent dextran of 70 kDa. The results indicated that the size-selectivity of EC monolayer became weaken under hypoxia.

    CiNii Books

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  • 【難治性の周産期common diseaseへの挑戦】 胎児機能不全 胎児心電図を用いた胎児状態評価 胎児心電図装置を用いた新たな胎児心拍数モニタリングの試み

    湊 敬廣, 木村 芳孝, 伊藤 拓哉, 大塩 清佳, 佐藤 尚明, 西郡 秀和, 八重樫 伸生

    臨床婦人科産科   70 ( 1 )   84 - 88   2016.1

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    現行の分娩監視装置では胎児アシドーシスに対しての検出率が低く,偽陽性となる可能性が高い.胎児心電図を用いた胎児心拍数モニタリングでは現行の分娩監視装置に比べてより多くの情報が得られる.胎児心電図装置ではshort term variabilityの計測が可能となり,これは胎児の脳障害に対する指標となりうる可能性がある.(著者抄録)

    DOI: 10.11477/mf.1409208595

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    Other Link: http://search.jamas.or.jp/link/ui/2016059831

  • 胎児心電図を用いた胎児状態評価~胎児心電図装置を用いた新たな胎児心拍数モニタリングの試み Invited

    湊敬廣, 木村芳孝, 伊藤拓哉, 大塩清佳, 佐藤尚明, 西郡秀和, 八重樫伸生

    臨床婦人科産科   2016

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    DOI: 10.11477/mf.1409208595

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  • ISP-22-5 Can fetal electrocardiograph find high-risk fetal mice of brain hemorrhage?(Group 22 Fetal Complication 2,International Session Poster) :

    Ito Takuya, Sugibayashi Rika, Minato Takahiro, Haneda Ken, Sato Naoaki, Dong Yupeng, Yaegashi Nobuo, Kimura Yoshitaka

    68 ( 2 )   543 - 543   2016

  • ISP-23-1 Vaginal inflammatory preconditioning triggers fetal brain inflammation which contributes to block acute fetal death in response to amniotic LPS(Group 23 Maternal Complication 1,International Session Poster) :

    Dong Yupeng, Haneda Ken, Ito Takuya, Minato Takahiro, Sugibayashi Rika, Yaegashi Nobuo, Kimura Yoshitaka

    68 ( 2 )   544 - 544   2016

  • ISP-25-10 Distribution of core temperature under maternal abdominal wall during pregnancy(Group 25 Nutrition and Metabolism,International Session Poster) :

    Kimura Yoshitaka, Sugibayashi Rika, Ito Takuya, Haneda Ken, Minato Takahiro, Yaegashi Nobuo

    68 ( 2 )   552 - 552   2016

  • ISP-22-8 The study of murine short term variability at each fetal stage(Group 22 Fetal Complication 2,International Session Poster) :

    Minato Takahiro, Ito Takuya, Haneda Ken, Dong Yupeng, Sugibayashi Rika, Sato Naoaki, Kimura Yoshitaka, Yaegashi Nobuo

    68 ( 2 )   544 - 544   2016

  • B106 Measurement of permeability of endothelial monolayer under hypoxia by using microfluidic device

    MATSUBARA Kento, FUNAMOTO Kenichi, ZERVANTONAKIS Ioannis K., FUNAMOTO Kiyoe, ITO Takuya, MASAMUNE Jun, KIMURA Yoshitaka, HAYASE Toshiyuki, KAMM Roger D.

    Proceedings of the ... JSME Conference on Frontiers in Bioengineering   2015 ( 26 )   35 - 36   2015.10

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  • 当施設における研修医を対象にしたブタを用いた外科手術トレーニングについて

    伊藤 拓哉, 壹岐 裕子, 兼平 雅彦, 工藤 克昌, 野田 雅史, 海野 倫明

    日本獣医学会学術集会講演要旨集   158回   441 - 441   2015.8

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  • Effects of Maternal Inflammation on the Fetal Brain in a Murine Model

    Yupeng Dong, Takuya Ito, Clarissa Velayo, Rika Sugibayashi, Kiyoe Funamoto, Keita Iida, Miyuki Endo, Naoaki Sato, Takahiro Minato, Ken Haneda, Sayaka Oshio, Motoyoshi Kawataki, Nobuo Yaegashi, Yoshitaka Kimura

    REPRODUCTIVE SCIENCES   22   368A - 368A   2015.3

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  • 1C34 Evaluation of permeability of endothelial monolayer by using hypoxia microfluidic device

    MATSUBARA Kento, FUNAMOTO Kenichi, Zervantonakis Ioannis, FUNAMOTO Kiyoe, ITO Takuya, MASAMUNE Jun, KIMURA Yoshitaka, HAYASE Toshiyuki, KAMM Roger

    2015 ( 27 )   121 - 122   2015.1

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  • ISP-14-1 Intrauterine Ischemic reperfusion switches the fetal transcriptional pattern from HIF-1α-to P53-dependent regulation in the murine brain(Group 14 Perinatology 4,IS Poster,International Session) :

    Dong Yupeng, Ito Takuya, Sugibayashi Rika, Iida Keita, Sato Naoaki, Yaegashi Nobuo, Kimura Yoshitaka

    67 ( 2 )   1039 - 1039   2015

  • 繰り返す虚血再灌流負荷は母体低栄養マウス胎仔の脳出血発症リスクを増大させる

    伊藤 拓哉, 杉林 里佳, 木村 芳孝, 董 宇鵬, 飯田 渓太, 佐藤 尚明, 八重樫 伸生

    日本産科婦人科学会雑誌   66 ( 2 )   580 - 580   2014.2

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  • 胎児心拍細変動における胎児心電図の抽出アルゴリズムの検討(I)

    飯田 渓太, 木村 芳孝, 伊藤 拓哉, 董 宇鵬, 羽根田 健, 大塩 清佳, 西郡 秀和, 八重樫 伸生

    日本産科婦人科学会雑誌   66 ( 2 )   719 - 719   2014.2

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    Other Link: https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=452705

  • 胎児心拍細変動における胎児心電図の抽出アルゴリズムの検討(II)

    木村 芳孝, 飯田 渓太, 伊藤 拓哉, 董 宇鵬, 羽根田 健, 大塩 清佳, 西郡 秀和, 八重樫 伸生

    日本産科婦人科学会雑誌   66 ( 2 )   719 - 719   2014.2

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  • ISP-9-7 Phosphorylation of ATF2 at Thr71 in the fetal brain response to global Ischemic Reperfusion is triggered by vaginal LPS administration(Group 9 Perinatology 1,IS Poster,International Session) :

    Dong Yupeng, Ito Takuya, Sugibayashi Rika, Iida Keita, Sato Naoaki, Kimura Yoshitaka, Yaegashi Nobuo

    66 ( 2 )   944 - 944   2014

  • 医工連携によるイノベーションの実際 薬事承認・保健医療化の実例と課題 周産期における近未来イノベーションと臨床応用

    木村 芳孝, 伊藤 拓哉, 西郡 秀和, Verayo Clarissa, 八重樫 伸生

    医工学治療   25 ( Suppl. )   141 - 141   2013.4

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  • ISP-2-5 Why fetal heart rate monitoring cannot detect fetal brain hemorrhage : Multi-fractal structural changes during fetal brain hemorrhage(Group 2 Perinatology 2,IS Poster,International Session) :

    Kimura Yoshitaka, Ito Takuya, Nishigori Hidekazu, Haneda Ken, Sugibayashi Rika, Sugawara Junichi, Sugiyama Takashi, Yaegashi Nobuo

    65 ( 2 )   986 - 986   2013

  • 胎児脳出血はp53シグナル不活化で抑制される Reviewed

    伊藤拓哉, 木村芳孝, 佐藤尚明, 星合哲郎, 八重樫伸生

    東北医学雑誌   125 ( 1 )   88 - 90   2013

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  • Reconstruction of fetal vector electrocardiogram from maternal abdominal signals under fetus body rotations. International journal

    Nabeshima Y, Kimura Y, Ito T, Ohwada K, Karashima A, Katayama N, Nakao M

    Conf Proc IEEE Eng Med Biol Soc.   2013   7338 - 41   2013

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    Fetal electrocardiogram (fECG) and its vector form (fVECG) could provide significant clinical information concerning physiological conditions of a fetus. So far various independent component analysis (ICA)-based methods for extracting fECG from maternal abdominal signals have been proposed. Because full extraction of component waves such as P, Q, R, S, and T, is difficult to be realized under noisy and nonstationary situations, the fVECG is further hard to be reconstructed, where different projections of the fetal heart vector are required. In order to reconstruct fVECG, we proposed a novel method for synthesizing different projections of the heart vector, making good use of the fetus movement. This method consists of ICA, estimation of rotation angles of fetus, and synthesis of projections of the heart vector. Through applications to the synthetic and actual data, our method is shown to precisely estimate rotation angle of the fetus and to successfully reconstruct the fVECG.

    DOI: 10.1109/EMBC.2013.6611253

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  • K2-10-3 胎児脳出血はp53シグナル不活化で抑制される(高得点演題10,周産期医学4)

    伊藤 拓哉, 木村 芳孝, 佐藤 尚明, 星合 哲郎, 八重樫 伸生

    日本産科婦人科學會雜誌   64 ( 2 )   587 - 587   2012

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  • 脳出血における遺伝的背景の解析

    佐藤 多代, 伊藤 拓哉, 末永 香緒里, 星合 哲郎, 木村 芳孝, 八重樫 伸生

    日本産科婦人科学会雑誌   63 ( 2 )   545 - 545   2011.2

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  • 母体低栄養は胎仔の虚血再還流脳傷害を誘発する

    伊藤 拓哉, 木村 芳孝, 末永 香緒里, 佐藤 多代, 星合 哲郎, 八重樫 伸生

    日本産科婦人科学会雑誌   63 ( 2 )   546 - 546   2011.2

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  • Rheological analysis of the mechanism of fetal brain hemorrhage.

    T. Ito, K. Funamoto, K. Funamoto, K. Tanabe, A. Nakamura, T. Hayase, Y. Kimura

    Eighth International Conference on Flow Dynamics   86 - 87   2011

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  • Rheological analysis of the mechanism of fetal brain hemorrhage.

    T. Ito, K. Funamoto, K. Funamoto, K. Tanabe, A. Nakamura, T. Hayase, Y. Kimura

    Eighth International Conference on Flow Dynamics   86 - 87   2011

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  • P1-15-2 脳出血における遺伝的背景の解析(Group27 妊娠・分娩・産褥と社会2・胎児・新生児の病理,一般演題,第63回日本産婦人科学会学術講演会)

    佐藤 多代, 伊藤 拓哉, 末永 香緒里, 星合 哲郎, 木村 芳孝, 八重樫 伸生

    日本産科婦人科學會雜誌   63 ( 2 )   545 - 545   2011

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  • ブラインド信号分離による胎児ベクトル心電図の推定

    鍋島裕司, 木村芳孝, 伊藤拓哉, 佐藤尚明, 辛島彰洋

    電子情報通信学会技術研究報告   111 ( 314 )   13 - 17   2011

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  • 非接触広域接地型高感度電極法による胎児心電図の治験・臨床応用の確立

    菊地克史, 木村芳孝, 佐藤尚明, 伊藤拓哉

    臨床評価   39 ( 2 )   249 - 254   2011

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  • Establishment of a Novel Fetal Electrocardiogram Extracted from the Composite Maternal Abdominal Signals and the Clinical Application.

    Hiroshi Chisaka, Yoshitaka Kimura, Naoaki Sato, Takuya Ito, Kunihiro Okamura, Nobuo Yaegashi

    REPRODUCTIVE SCIENCES   17 ( 3 )   99A - 99A   2010.3

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  • K3-24 母体葉酸欠乏が及ぼす胎仔胎盤発育およびIgf-axisの発現制御のエピジェネティック基盤解析(高得点演題11 周産期,高得点演題プログラム,第62回日本産科婦人科学会学術講演会)

    松田 尚美, 伊藤 拓哉, 千坂 泰, 木村 芳孝, 岡村 州博, 八重樫 伸生

    日本産科婦人科學會雜誌   62 ( 2 )   620 - 620   2010

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  • "Pre-conditioning" in Mice Fetal Heart Affected by Maternal Malnutrition

    T. Ito, K. Tanabe, A. Nakamura, K. Funamoto, A. Aoyagi, H. Chisaka, N. Yaegashi, K. Okamura, Y. Kimura

    NEW HORIZONS IN CARDIOVASCULAR DISEASES   13 - 15   2010

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    A well-known hypothesis, DOHaD, proposes intrauterine environment, including maternal malnutrition, would lead lifestyle disease, including cardiovascular disease, in adulthood. However, its mechanism is still unknown. In this study, we assessed the involvement of HIF-1a, the main factor of pre-conditioning and adapts to hypoxia condition, to maternal malnutrition. A group was given adequate nutrition for gestation, while another group was given malnutrition. Microarray and immunohistochemical analysis showed HIF-1a and mTOR, upstream of HIF-1a, in fetal hearts collected on Day 17.5 of gestation in the malnutrition group was upregulated comparing to that in the adequate nutrition group. It might be established fetal pre-conditioning via maternal nutrition as in DOHaD.

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  • Case reports of fetal bradycardia diagnosed by fetal electrocardiogram via maternal abdomen.

    A. Aoyagi, Y. Kimura, T. Ito, C. Chisaka, K. Tanabe, K. Funamoto, K. Okamura, N. Yaegashi

    NEW HORIZONS IN CARDIOVASCULAR DISEASES   41 - 44   2010

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  • Case reports of fetal bradycardia diagnosed by fetal electrocardiogram via maternal abdomen.

    A. Aoyagi, Y. Kimura, T. Ito, C. Chisaka, K. Tanabe, K. Funamoto, K. Okamura, N. Yaegashi

    NEW HORIZONS IN CARDIOVASCULAR DISEASES   41 - 44   2010

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  • A Simulation Study of Single-BSS with References

    HATAYA Toshiaki, KIMURA Yoshitaka, ITO Takuya, KARASHIMA Akihiro, KATAYAMA Norihiro, YAEGASHI Nobuo, NAKAO Mitsuyuki

    IEICE technical report. ME and bio cybernetics   109 ( 279 )   37 - 40   2009.11

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    Single-ICA can be very useful method to extract independent components from signal observed by single channel. But there is still a problem in the accuracy of separation and a lot to work on. We propose a simple single-ICA algorithm using blind source separation with references, and investigate the changes in the accuracy of separation and time gap between extracted signal and source signal, by altering the dimension and the lag time of the multi-dimensional embedded matrix. Then the result is that each extracted signal shows different change characteristics for the increase of dimension and lag time. Considering the property that causes these change characteristics, we are expecting these results to be helpful for optimal design of dimension and lag time.

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  • 【子宮疾患・子宮内膜症の臨床 基礎・臨床研究のアップデート】 外傷・術後・その他 子宮破裂 最近の傾向と今後の研究

    木村 芳孝, 伊藤 拓哉, 松田 尚美, 千坂 泰, 岡村 州博

    日本臨床   67 ( 増刊5 子宮疾患・子宮内膜症の臨床 )   485 - 489   2009.8

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  • 【周産期モニタリングup to dateとその応用】 胎児心電図

    木村 芳孝, 伊藤 拓哉, 鈴木 則嗣, 佐藤 尚明, 千坂 泰, 八重樫 伸生, 岡村 州博

    周産期医学   39 ( 4 )   459 - 463   2009.4

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  • Gestational Stage- and Sex-Specific Impact of Maternal Folate Deficiency on Fetal Growth and Epigenetic Regulation of Gene Expression in Fetus

    Naomi Matsuda, Clarissa Lim Velayo, Takuya Ito, Hiroshi Chisaka, Yoshitaka Kimura, Kunihiro Okamora, Jafar Sharif

    REPRODUCTIVE SCIENCES   16 ( 3 )   140A - 141A   2009.3

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  • Maternal Protein Restriction during Late Gestation Induces Sex-Specific and Reciprocal Regulation of the Igf2/Igfbp1 Gene Expression Ratio in Placenta: A Possible Association between Nutrition and Epigenetics

    Clarissa Lim Velayo, Naomi Matsuda, Takuya Ito, Hiroshi Chisaka, Yoshitaka Kimura, Kunihiro Okamura, Jafar Sharif

    REPRODUCTIVE SCIENCES   16 ( 3 )   347A - 347A   2009.3

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  • 低栄養マウスにおける胎児虚血時の網羅的遺伝子解析

    木村 芳孝, 伊藤 拓哉, 佐藤 尚明, 千坂 泰, 八重樫 伸生, 岡村 州博

    日本産科婦人科学会雑誌   61 ( 2 )   722 - 722   2009.2

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  • 母体葉酸欠乏が及ぼす胎仔胎盤発育における影響とそのエピジェネティック制御機構解析

    松田 尚美, 伊藤 拓哉, 千坂 泰, 木村 芳孝, 八重樫 伸生, 岡村 州博

    日本産科婦人科学会雑誌   61 ( 2 )   647 - 647   2009.2

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  • GESTATIONAL FOLATE RESTRICTION SHOWS SEX SPECIFIC AND EPIGENETIC IMPACT OF FOLATE ON PLACENTAL DEVELOPMENT AND REGULATION OF THE IGF-AXIS IN THE PLACENTA

    Naomi Matsuda, Takuya Ito, Clarissa Velayo, Hiroshi Chisaka, Yoshitaka Kimura, Jafar Sharif, Kunihiro Okamura

    PLACENTA   29 ( 10 )   916 - 916   2008.10

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  • 心電図の参照系信号分離における参照信号の最適化

    根田林 知之, 木村 芳孝, 千田 新一, 伊藤 拓哉, 大和田 一成, 辛島 彰洋, 片山 統裕, 岡村 州博, 中尾 光之

    電子情報通信学会技術研究報告(MEとバイオサイバネティックス)   107 ( 351 )   1 - 4   2007.11

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    独立成分分析(ICA)は信号分離技術として、脳波、胎児心電図などの解析に広く用いられてきている。中でも参照系を用いた独立成分分析(Blind Source Separation with Reference signal:BSSR)は、ある特徴量を持った信号が含まれている場合、非常に有効である。これまで、この参照信号のタイミングに対するロバスト性が示唆されてきたが、その理由については明らかにされていない。本研究では、参照信号を構成するスパイク波の欠落、スパイク幅の増大、評価関数の次数に対するBSSRの分離結果について評価した。スパイク波数の欠落については単調に分離精度が低下した。スパイク幅の増加によって分離精度は低下したが、低下率は小さかった。評価関数の次数については、4次の評価関数が最適であることが確認された。以上により、参照信号の変容に対する分離結果のロバスト性の様子が明らかになった。これらの結果を基に、ロバスト性を制御する評価式を導出し、適切な参照信号の設計に役立てたい。(著者抄録)

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  • Maternal undernutrition aggravates fetal brain damage caused by infection

    T. Ito, K. Uchida, M. Nakamura, H. Chisaka, Y. Kimura, K. Okamura

    EARLY HUMAN DEVELOPMENT   83   S117 - S117   2007.10

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  • 神経幹細胞の分化撹乱による生後オリゴデンドロサイトの減少

    加藤 英政, 内田 香, 仲村 三千代, 伊藤 拓哉, 菅原 準一, 木村 芳孝, 岡村 州博

    解剖学雑誌   82 ( 2 )   75 - 75   2007.6

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  • 【今、改めて"母子救急"を考える】 子宮破裂

    木村 芳孝, 伊藤 拓哉, 千坂 泰, 佐藤 尚明, 岡村 州博

    産婦人科治療   94 ( 2 )   190 - 196   2007.2

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    子宮破裂の頻度は減少しておらず、逆に、その要因はますます複雑になってきている。ハイリスク群としては、既往帝王切開後の分娩、既往子宮手術、事故、プロスタグランジン製剤などによる無謀な分娩誘発、感染、多胎、多産、肥満、児頭骨盤不適合、双角子宮などの子宮奇形などがある。現在のところ子宮破裂の予測は難しく、ハイリスク群の慎重な管理と厳重なインフォームドコンセントが重要と考えられる。(著者抄録)

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    Other Link: http://search.jamas.or.jp/link/ui/2007161832

  • 遅発一過性徐脈時の胎児心電図波形変化

    木村 芳孝, 伊藤 拓哉, 内田 香, 仲村 三千代, 千坂 泰, 菅原 準一, 岡村 州博

    日本産科婦人科学会雑誌   59 ( 2 )   521 - 521   2007.2

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    Other Link: https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=439393

  • A novel extraction method of fetal electrocardiogram from the composite abdominal signal

    Michiyoshi Sato, Yoshitaka Kimura, Shinichi Chida, Takuya Ito, Norihiro Katayama, Kunihiro Okamura, Mitsuyuki Nakao

    IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING   54 ( 1 )   49 - 58   2007.1

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    In contrast to the ultrasonic measurement of fetal heart motion, the fetal electrocardiogram (ECG) provides clinically significant information concerning the electrophysiological state of a fetus. In this paper, a novel method for extracting the fetal ECG from abdominal composite signals is proposed. This method consists of the cancellation of the mother's ECG and blind source separation with the reference signal (BSSR). The cancellation of the mother's ECG component was performed by subtracting the linear combination of mutually orthogonal projections of the heart vector. The BSSR is a fixed-point algorithm, the Lagrange function of which includes the higher order cross-correlation between the extracted signal and the reference signal as the cost term rather than a constraint. This realizes the convexity of the Lagrange function in a simple form, which guarantees the convergence of the algorithm. By practical application, the proposed method has been shown to be able to extract the P and T waves in addition to the R wave. The reliability and accuracy of the proposed method was confirmed-by comparing the extracted signals with the directly recorded ECG at the second stage of labor. The gestational age-dependency of the physiological parameters of the extracted fetal ECG also coincided well with that of the magnetocardiogram, which proves the clinical applicability of the proposed method.

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  • A novel extraction method of fetal electrocardiogram from the composite abdominal signal

    Michiyoshi Sato, Yoshitaka Kimura, Shinichi Chida, Takuya Ito, Norihiro Katayama, Kunihiro Okamura, Mitsuyuki Nakao

    IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING   54 ( 1 )   49 - 58   2007.1

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    In contrast to the ultrasonic measurement of fetal heart motion, the fetal electrocardiogram (ECG) provides clinically significant information concerning the electrophysiological state of a fetus. In this paper, a novel method for extracting the fetal ECG from abdominal composite signals is proposed. This method consists of the cancellation of the mother's ECG and blind source separation with the reference signal (BSSR). The cancellation of the mother's ECG component was performed by subtracting the linear combination of mutually orthogonal projections of the heart vector. The BSSR is a fixed-point algorithm, the Lagrange function of which includes the higher order cross-correlation between the extracted signal and the reference signal as the cost term rather than a constraint. This realizes the convexity of the Lagrange function in a simple form, which guarantees the convergence of the algorithm. By practical application, the proposed method has been shown to be able to extract the P and T waves in addition to the R wave. The reliability and accuracy of the proposed method was confirmed-by comparing the extracted signals with the directly recorded ECG at the second stage of labor. The gestational age-dependency of the physiological parameters of the extracted fetal ECG also coincided well with that of the magnetocardiogram, which proves the clinical applicability of the proposed method.

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  • A study to determine the robustness of reference signals for BSSR signal extraction method

    Y. Kimural, T. Netabayashi, T. Ito, S. Jafar, S. Chida, N. Katayama, K. Owada, K. Okamura, M. Nakao

    NOISE AND FLUCTUATIONS   922   705 - +   2007

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    Blind source separation with reference signals (BSSR) is an excellent method to extract target independent components from linearly mixed observed signals when prior rough information about target signals is given. Usually the slight change of reference signal form does not affect the extraction ability of BSSR, but the extent of this robustness is not yet precisely known. We studied the main parameters of the robustness through examples of fetal electrocardiogram extraction.

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  • Non-Invasive Determination of Electromechanical Time Intervals of Cardiac Cycle Using Abdominal ECG and Doppler Ultrasound Signals from Fetal Hearts

    A. H. Khandoker, Y. Kimura, T. Ito, M. Palaniswami

    COMPUTERS IN CARDIOLOGY 2007, VOL 34   34   657 - +   2007

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    Fetal ECG and Doppler ultrasound signals provide clinically significant information concerning the physiological state of a fetus. In this study, we propose a non-invasive system to recognize the timings of fetal cardiac events on the basis of analysis of fetal ECG and Doppler ultrasound signal together. Fetal ECG was extracted from transabdominal ECG (10 normal subjects, 38-41 weeks of gestation) using blind source separation with the reference signal. Multiresolution wavelet analysis enabled the frequency contents of the Doppler signals to be linked to the opening and closing of the heart's valves (Aortic and mitral). The time intervals from R peak of fetal ECG to opening and closing of aortic valve were found to he 99.16 +/- 22.07 (msec) and 222.70 +/- 21.83 (msec) respectively. The time intervals from R peak to opening and closing of mitral valve were found to be 305.32 +/- 22.71 (msec) and 3 7.84 +/- 18.23 (msec) respectively.

    DOI: 10.1109/CIC.2007.4745571

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  • Non-Invasive Determination of Electromechanical Time Intervals of Cardiac Cycle Using Abdominal ECG and Doppler Ultrasound Signals from Fetal Hearts

    A. H. Khandoker, Y. Kimura, T. Ito, M. Palaniswami

    COMPUTERS IN CARDIOLOGY 2007, VOL 34   34   657 - +   2007

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    Fetal ECG and Doppler ultrasound signals provide clinically significant information concerning the physiological state of a fetus. In this study, we propose a non-invasive system to recognize the timings of fetal cardiac events on the basis of analysis of fetal ECG and Doppler ultrasound signal together. Fetal ECG was extracted from transabdominal ECG (10 normal subjects, 38-41 weeks of gestation) using blind source separation with the reference signal. Multiresolution wavelet analysis enabled the frequency contents of the Doppler signals to be linked to the opening and closing of the heart's valves (Aortic and mitral). The time intervals from R peak of fetal ECG to opening and closing of aortic valve were found to he 99.16 +/- 22.07 (msec) and 222.70 +/- 21.83 (msec) respectively. The time intervals from R peak to opening and closing of mitral valve were found to be 305.32 +/- 22.71 (msec) and 3 7.84 +/- 18.23 (msec) respectively.

    DOI: 10.1109/CIC.2007.4745571

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  • P1-23 低栄養による母体感染時の胎仔脳傷害の悪化(高得点周産期医学1,高得点演題プログラム,第59回日本産科婦人科学会学術講演会)

    伊藤 拓哉, 内田 香, 仲村 三千代, 千坂 泰, 菅原 準一, 木村 芳孝, 岡村 州博, 加藤 英政

    日本産科婦人科學會雜誌   59 ( 2 )   356 - 356   2007

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  • A Study to Determine the Robustness of Reference Signals for BSSR Signal Extraction Method.

    Y Kimura, T Netabayashi, T Ito, S Jafar, S Chida, N Katayama, K Owada, K Okamura, M Nakao

    2007 American Institute of Physics   705 - 708   2007

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  • Food Restriction in pregnancy mice can induce changes in histone modidications and suppress gene expression in fetus

    afar Sharif, Michiyo Nakamura, Takuya Ito, Yoshitaka Kimura, Teruyuki Nagamune, Kohzoh Mituya, Kunihiro Okamura

    Nucleic Aacids Symposium Series 2007 Oxford University Press   51   125 - 126   2007

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  • 【胎児・新生児の神経系の評価】 心拍モニター 胎児心拍数による自律神経系の評価

    木村 芳孝, 伊藤 拓哉, 千坂 泰, 菅原 準一, 岡村 州博

    周産期医学   36 ( 10 )   1231 - 1235   2006.10

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  • Measurement method for the fetal electrocardiogram

    Yoshitaka Kimura, Takuya Ito, Fumiaki Matuyama, Shinichi Chida, Norihiro Katayama, Mitsuyuki Nakao, Kunihiro Okamura

    MINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES   15 ( 4 )   214 - 217   2006.8

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    A fetal electrocardiogram ( ECG) provides clinically significant information concerning the electrophysiological states of a fetus. Since the first attempt by Cremer in 1906, for about 100 years nobody has been able to non-invasively extract the fetal ECG popularly used in clinical situations. The low amplitude of the fetal signals and the high background noise and the non-linearity of the ECG signals mainly have been interfering with the noninvasive extraction of the fetal ECG. The aim of this paper is to introduce a new nonlinear filtering method to extract the fetal electrocardiogram detected from the mother's abdominal wall. This method consists of two steps: The rough extraction step performed by blind source separation (BSS) with references and the precise extraction step with fast non-linear state space projection (FNSSP) based on a nonlinear state space projection ( NSSP), which needs several complicated conditions or has limitations. So, it takes a lot of time to calculate. Our new method does not require such conditions, and it has about a thirty-fold speedup when compared with the previous method. Our new method has been successfully applied to on-line recordings with fetal components and will be useful for monitoring the fetal electrocardiogram in clinical applications.

    DOI: 10.1080/13645700600845654

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  • Measurement method for the fetal electrocardiogram

    Yoshitaka Kimura, Takuya Ito, Fumiaki Matuyama, Shinichi Chida, Norihiro Katayama, Mitsuyuki Nakao, Kunihiro Okamura

    MINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES   15 ( 4 )   214 - 217   2006.8

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    A fetal electrocardiogram ( ECG) provides clinically significant information concerning the electrophysiological states of a fetus. Since the first attempt by Cremer in 1906, for about 100 years nobody has been able to non-invasively extract the fetal ECG popularly used in clinical situations. The low amplitude of the fetal signals and the high background noise and the non-linearity of the ECG signals mainly have been interfering with the noninvasive extraction of the fetal ECG. The aim of this paper is to introduce a new nonlinear filtering method to extract the fetal electrocardiogram detected from the mother's abdominal wall. This method consists of two steps: The rough extraction step performed by blind source separation (BSS) with references and the precise extraction step with fast non-linear state space projection (FNSSP) based on a nonlinear state space projection ( NSSP), which needs several complicated conditions or has limitations. So, it takes a lot of time to calculate. Our new method does not require such conditions, and it has about a thirty-fold speedup when compared with the previous method. Our new method has been successfully applied to on-line recordings with fetal components and will be useful for monitoring the fetal electrocardiogram in clinical applications.

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  • 母体腹部誘導心電図からの胎児心電図の分離抽出

    松山 文昭, 木村 芳孝, 千田 新一, 伊藤 拓哉, 辛島 彰洋, 片山 統裕, 岡村 州博, 中尾 光之

    電子情報通信学会技術研究報告(MEとバイオサイバネティックス)   105 ( 402 )   25 - 28   2005.11

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    胎児心電図は胎児心臓の電気活動を知る上で重要な役割を担うと考えられる.これの抽出にはブラインド信号分離(BSS)を適用した方法が主流となっている.しかし,抽出波形において,T波やP波の判別が難しいなど,この方法による抽出結果が心電図として十分な信頼性を有しているとはいえない.信号の非線形性(ゆがみ)がその要因と考えられる.この問題を解決するためにBSSのような線形変換に代わる新しい方法として高速非線形状態空間射影法(FNSSP)を開発したので,その適用結果について述べる(著者抄録)

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    Other Link: http://search.jamas.or.jp/link/ui/2006069539

  • The mesencephalic trigeminal sensory nucleus is involved in the control of feeding and exploratory behavior in mice

    T Ishii, H Furuoka, T Ito, N Kitamura, M Nishimura

    BRAIN RESEARCH   1048 ( 1-2 )   80 - 86   2005.6

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    The mesencephalic trigeminal nucleus (Me5), which receives input from oral proprioceptors and projects to higher brain regions, is involved in mastication-induced modulation of satiation. To investigate how the Me5 is involved in the control of feeding and exploratory behavior, we examined the effect of bilateral electrolytic lesions of the Me5 on feeding and exploratory behavior in mice. Mouse feeding and exploratory behaviors were analyzed using a food- search-compulsion-apparatus (FSCA), which was designed to distinguish between the two behaviors under standard living conditions. To assess anxiety in mice in an unfamiliar environment, exploratory activity was analyzed in an automated hole-board apparatus. Mice with bilateral Me5 lesions had unique feeding and exploratory behavior profiles in the FSCA compared with sham-operated mice. Me5-lesioned mice spent more time in the food chamber during each trial in the FSCA, but the number of entries into the food chamber was decreased by 40% compared to sham-operated mice. Moreover, Me5 lesions markedly inhibited exploratory behavior, manifested as low-frequency exploration. In spite of the low frequency exploration in the FSCA, Me5 lesions had no effect on various exploratory activities analyzed in the hole-board apparatus, i.e., total locomotor activity, frequency and duration of rearing and head-dipping, and latency to the first head-dipping. These results suggest that the Me5 is involved in the control of feeding and exploratory behavior through its ascending neuronal pathways in mice without modulating the emotional state. (c) 2005 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2005.04.038

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  • The mesencephalic trigeminal sensory nucleus is involved in the control of feeding and exploratory behavior in mice

    T Ishii, H Furuoka, T Ito, N Kitamura, M Nishimura

    BRAIN RESEARCH   1048 ( 1-2 )   80 - 86   2005.6

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    The mesencephalic trigeminal nucleus (Me5), which receives input from oral proprioceptors and projects to higher brain regions, is involved in mastication-induced modulation of satiation. To investigate how the Me5 is involved in the control of feeding and exploratory behavior, we examined the effect of bilateral electrolytic lesions of the Me5 on feeding and exploratory behavior in mice. Mouse feeding and exploratory behaviors were analyzed using a food- search-compulsion-apparatus (FSCA), which was designed to distinguish between the two behaviors under standard living conditions. To assess anxiety in mice in an unfamiliar environment, exploratory activity was analyzed in an automated hole-board apparatus. Mice with bilateral Me5 lesions had unique feeding and exploratory behavior profiles in the FSCA compared with sham-operated mice. Me5-lesioned mice spent more time in the food chamber during each trial in the FSCA, but the number of entries into the food chamber was decreased by 40% compared to sham-operated mice. Moreover, Me5 lesions markedly inhibited exploratory behavior, manifested as low-frequency exploration. In spite of the low frequency exploration in the FSCA, Me5 lesions had no effect on various exploratory activities analyzed in the hole-board apparatus, i.e., total locomotor activity, frequency and duration of rearing and head-dipping, and latency to the first head-dipping. These results suggest that the Me5 is involved in the control of feeding and exploratory behavior through its ascending neuronal pathways in mice without modulating the emotional state. (c) 2005 Elsevier B.V. All rights reserved.

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  • Fetal ECG Extraction with Fast Nonlinear State Space Projections.

    Yoshitaka Kimura, Takuya Ito, Fumiaki Matuyama, Shinichi Chida, Masato Seno, Norihiro Katayama, Kunihiro Okamura, Mitsuyuki Nakao

    Proceedigs of the Fifth International Workshop on Biosignal Interpritation(BIS)   45 - 47   2005

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  • Fetal ECG Extraction with Fast Nonlinear State Space Projections.

    Yoshitaka Kimura, Takuya Ito, Fumiaki Matuyama, Shinichi Chida, Masato Seno, Norihiro Katayama, Kunihiro Okamura, Mitsuyuki Nakao

    Proceedigs of the Fifth International Workshop on Biosignal Interpritation(BIS)   45 - 47   2005

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  • 参照信号系を持つ独立成分分析法による胎児心電図の解析

    松山文昭, 木村芳孝, 佐藤道由, 伊藤拓哉, 千田新一, 妹尾匡人, 中尾光之

    日本生体医工学会誌   43   567   2005

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  • 参照信号系を持つ独立成分分析法による胎児心電図の解析

    松山文昭, 木村芳孝, 佐藤道由, 伊藤拓哉, 千田新一, 妹尾匡人, 中尾光之

    日本生体医工学会誌   43   567   2005

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  • 離乳期に顕彰する自給本能発現における中脳路核(Me5)の役割

    石井 利明, 古岡 秀文, 伊藤 拓哉, 佐藤 栄輝, 西村 昌数

    日本獣医学会学術集会講演要旨集   133回   182 - 182   2002.3

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  • マウスの対象獲得行動におけるVMH破壊の影響

    伊藤拓哉, 石井利明, 竹脇義, 西村昌数

    日本味と匂学会誌   9 ( 3 )   708   2002

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  • マウスの対象獲得行動におけるVMH破壊の影響

    伊藤拓哉, 石井利明, 竹脇義, 西村昌数

    日本味と匂学会誌   9 ( 3 )   708   2002

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  • マウスにおける実験的離乳後の食探索行動

    石井 利明, 古岡 秀文, 伊藤 拓哉, 佐藤 栄輝, 西村 昌数

    日本獣医学会学術集会講演要旨集   131回   169 - 169   2001.3

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  • 新規に開発した装置によるマウスの摂餌欲、飲水欲に伴う対象物獲得行動の測定

    伊藤拓哉, 三宅伸子, 石井利明, 竹脇義, 西村昌数

    日本味と匂学会誌   8 ( 3 )   527 - 530   2001

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  • 新規に開発した装置によるマウスの摂餌欲、飲水欲に伴う対象物獲得行動の測定

    伊藤拓哉, 三宅伸子, 石井利明, 竹脇義, 西村昌数

    日本味と匂学会誌   8 ( 3 )   527 - 530   2001

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  • マウスにおける離乳後のミルク食が食探索行動に及ぼす影響

    石井 利明, 伊藤 拓哉, 佐藤 栄輝, 西村 昌数

    日本獣医学会学術集会講演要旨集   129回   175 - 175   2000.3

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Presentations

  • 胎児脳出血はp53シグナル不活化で抑制される

    第64回日本産婦人科学会学術講演会  2012.4 

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  • ウサギの吸入麻酔 Invited

    伊藤 拓哉

    第66回日本実験動物学会総会  2019.5 

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  • 低栄養による母体感染時の胎仔脳傷害の悪化

    伊藤 拓哉, 内田 香, 仲村 三千代, 千坂 泰, 菅原 準一, 木村 芳孝, 岡村 州博, 加藤 英政

    第59回日本産科婦人科学会学術講演会  2007.4 

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  • 妊娠マウスを対象にしたMMB麻酔投与条件の検討

    伊藤拓哉

    第167回日本獣医学会学術集会  2024.9 

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    Event date: 2024.9

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  • マウス胎子心拍変動に対するMMB麻酔の影響

    伊藤拓哉

    第20回北海道実験動物研究会学術集会  2024.7 

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    Event date: 2024.7

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  • Evaluation by High-Frequency Ultrasound B-mode Imaging of Cerebral Hemorrhage in Mouse Fetal Brain Resulting from Ischemia/Reperfusion

    Kenichi Funamoto, Takuya Ito, Kiyoe Funamoto, Clarissa Velayo, Toshiyuki Hayase, Yoshitaka Kimura

    15th International Conference on Biomedical Engineering  2013 

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    Event date: 2013.12

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  • The Relationship between R-Wave Amplitude and Gestational Weeks by Abdominal Fetal Electrocardiography

    Rika Sugibayashi, Clarissa Lim Velayo, Miyuki Endo, Kiyoe Funamoto, Yupeng Dong, Takuya Ito, Haruhiko Sago, Yoshitaka Kimura, Nobuo Yaegashi

    12th World Congress in Fetal Medicine  2013 

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    Event date: 2013.6

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  • Molecular patterns of neurodevelopmental preconditioning: a study of the effects of antenatal steroid therapy in a protein-restriction mouse model

    Clarissa Lim Velayo, Takuya Ito, Yupeng Dong, Miyuki Endo, Kiyoe Funamoto, Rika Sugibayashi, Nobuo Yaegashi, Yoshitaka Kimura

    12th World Congress in Fetal Medicine  2013.6 

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  • Detection of fetal brain hemorrhage by fetal electrocardiography

    KIMURA Yoshitaka, ITO Takuya, SUGIBAYASHI Rika, VELAYO Clarissa, DONG Yupeng, FUNAMOTO Kiyoe, ENDO Miyuki, YAEGASHI Nobuo

    12th World Congress in Fetal Medicine  2013 

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  • Maternal undernutri,on induces the expression of hypoxia­‐related genes in the fetal brain

    Takuya Ito, Kiyoe Fnamoto, Naoaki Sato,, Ai Nakamura, Kaori Tanabe, Tetsuro Hoshiai, Kaori Suenaga, Junich Sugawara, Satoru Nagase, Kunihiro Okamura, Nobuo Yaegashi, Yoshitaka Kimura

    11th World Congress in Fetal Medicine  2012 

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  • Gene network of fetal brain reacts to maternal undernutrition like-hypoxia

    7th World Congress on Developmental Origins of Health and Disease  2011 

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    Event date: 2011.9

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  • 母体葉酸欠乏が及ぼす胎仔胎盤発育およびIgf-axisの発現制御のエピジェネティック基盤解析

    松田 尚美, 伊藤 拓哉, 千坂 泰, 木村 芳孝, 岡村 州博, 八重樫 伸生

    2010.4 

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    Event date: 2010.4

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  • 弱酸性次亜塩素酸水溶液の​ 生体使用に伴う組織学的影響

    半田紀子, 清水真理子, 栗田瑞希, 伊藤昌紀, 宮澤和志, 兼田裕司, 古林与志安, 伊藤拓哉, 國田智

    第55回日本実験動物技術者協会  2021.9 

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  • 動物実験に関する法律・指針について考える

    伊藤拓哉

    67回日本動物学会北海道支部大会  2023.3 

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  • 心拍変動による​ 胎子脆弱性検出の試み

    伊藤拓哉

    第18回 北海道実験動物研究会学術集会  2022.7 

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  • 当施設における研修医を対象にしたブタを用いた外科手術トレーニングについて

    伊藤拓哉, 壹岐裕子, 兼平雅彦, 工藤克昌, 野田雅史, 海野倫明

    第158回日本獣医学会学術集会  2015.8 

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  • Anesthetic management for neonatal pig.

    ITO Takuya

    2018.5 

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  • 何故、今ブタなのか? Invited

    伊藤拓哉

    第11回 実験用ブタ勉強会  2023.4 

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  • Cardiac Evaluation of Fetal Mice by ECG and Ultrasound

    Takuya Ito, Kenichi Funamoto, Rika Sugibayashi, Kiyoe Funamoto, Clarissa Velayo, Miyuki Endo, Yupeng Dong, Toshiyuki Hayase, Yoshitaka Kimura

    IFS Collaborative Research Forum 2013  2013.11 

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  • Repeated ischemia reperfusion in a maternal protein restriction model increases the risk of fetal brain hemorrhage via p53-signal activation

    Takuya Ito,, Kenichi Funamoto, Kiyoe Funamoto, Clarissa L. Velayo, Yupeng Dong, Miyuki Endo, Rika Sugibayashi, Keita Iida, Toshiyuki Hayase, Nobuo Yaegashi, Yoshitaka Kimura

    8th World Congress on Developmental Origins of Health and Disease  2013.11 

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  • 繰り返す虚血再灌流負荷は母体低栄養マウス胎仔の脳出血発症リスクを増大させる

    伊藤拓哉, 木村芳孝, 杉林 里佳, 佐藤尚明, 董 宇鵬, 飯田 渓太, 八重樫伸生

    第66回日本産科婦人科学会学術講演会  2014 

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  • 動物を介して生命倫理観を高めるトレーニングプログラム構築の試み

    壹岐裕子, 伊藤拓哉, 兼平雅彦, 工藤克昌, 野田雅史, 海野倫明

    第62回日本実験動物学会総会  2015.4 

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  • 心電計によるマウス胎仔の心機能発達評価

    伊藤拓哉, 杉林里佳, 佐藤尚明, 船本聖絵, 遠藤美雪, 飯田渓太, 董宇鵬, 木村芳孝

    第62回日本実験動物学会総会  2015.4 

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  • Increased Susceptibility of Injury Prone Neuroglial Cells Due to Antenatal Steroid Treatment: A Case of Double Jeopardy

    CLARISSA VELAYO, TAKUYA ITO, HIROSHI CHISAKA, NOBUO YAEGASHI, KUNIHIRO OKAMURA, YOSHITAKA KIMURA

    Society for Gynecologic Investigation (SGI) 3rd SGI International summit  2009.11 

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  • Fluid Analysis of The Mechanism of Fetal Brain Hemorrhage.

    T. Ito, K. Funamoto, K. Funamoto, K. Tanabe, A. Nakamura, T. Hayase, Y. Kimura

    Seventh International Conference on Flow Dynamics  2010 

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  • “Pre-conditioning” in Mice Fetal Heart Affected by Maternal Malnutrition

    Takuya ITO, Kaori TANABE, Ai NAKAMURA, Kiyoe FUNAMOTO, Ayako AOYAGI, Hiroshi CHISAKA, Nobuo YAEGASHI, Kunihiro OKAMURA, Yoshitaka KIMURA

    15th World Congress on Heart Disease  2010 

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Industrial property rights

  • 胎児状態推定装置、胎児状態推定方法、及び、胎児状態推定プログラム

    木村 芳孝, 佐藤 尚明, 八重樫 伸生, 伊藤 拓哉, 遠藤 美雪, 大塩 清佳, 西郡 秀和, 鍋島 裕司, 中尾 光之

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    Applicant:国立大学法人東北大学

    Application no:特願2016-509716  Date applied:2014.3

    Patent/Registration no:特許第6324490号  Date issued:2018.4

    J-GLOBAL

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  • 生体状態推定装置、生体状態推定方法、及び、生体状態推定プログラム

    木村 芳孝, 八重樫 伸生, 岡村 州博, 伊藤 拓哉, 小出 邦博, 遠藤 美雪

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    Applicant:国立大学法人東北大学

    Application no:特願2016-509717  Date applied:2014.3

    Announcement no:WO2015-145625  Date announced:2015.10

    Patent/Registration no:特許第6359084号  Date registered:2018.6 

    J-GLOBAL

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  • SIGNAL EXTRACTING APPARATUS

    Yoshitaka KImura, Mitsuyuki Nakao, Takuya Ito, Kazunari Ohwada

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    Application no:特願10816898.0  Date applied:2010.9

    Announcement no:特開2478835  Date announced:2011.3

    Patent/Registration no:特許EP 2 478 835 B1  Date registered:2018.1 

    US8,808,192 B2

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  • SIGNAL EXTRACTING APPARATUS

    Yoshitaka Kimura, Nobuo Yaegashi, Mitsuyuki Nakao, Takuya Ito

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    Application no:特願PCT/JP2010/005687  Date applied:2010.9

    Announcement no:特開WO 2011/033784 A1  Date announced:2011.3

    Patent/Registration no:特許US8,808,192 B2  Date registered:2014.8 

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  • 信号抽出装置

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    Application no:JP2010005687  Date applied:2010.9

    Announcement no:WO2011-033784  Date announced:2011.3

    W0211/033784

    J-GLOBAL

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  • 1信号からの独立成分分析による信号抽出装置、その信号抽出プログラム及びその信号抽出装置

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    Application no:特願特願2011-531797  Date applied:2010.9

    Patent/Registration no:特許特許5769309  Date registered:2015.8 

    特許第5769309号

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  • 1計測信号からの独立成分分析による信号抽出装置、その信号抽出プログラム及びその信号抽出方法

    木村 芳孝, 八重樫 伸生, 中尾 光之, 伊藤 拓哉

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    Applicant:国立大学法人東北大学

    Application no:特願2011-531797  Date applied:2010.9

    Patent/Registration no:特許第5769309号  Date issued:2015.7

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  • 脳性麻痺発症仔の作製方法

    木村 芳孝, 伊藤 拓哉, 船本 健一, 早瀬 敏幸

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    Applicant:国立大学法人東北大学

    Application no:特願2009-176683  Date applied:2009.7

    Announcement no:特開2011-030430  Date announced:2011.2

    J-GLOBAL

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  • 胎児心電図信号計測方法およびその装置

    木村 芳孝, 中尾 光之, 伊藤 拓哉, 大和田 一成

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    Applicant:株式会社 東北テクノアーチ

    Application no:JP2008050756  Date applied:2008.1

    Announcement no:WO2008-090862  Date announced:2008.7

    J-GLOBAL

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  • FETUS ELECTROCADIOGRAM SIGNAL MEASURING METHOD AND ITS DEVICE.

    Yoshitaka Kimura, Mitsuyuki Nakao, ITO Takuya, Kazunari Ohwada

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    Application no:特願PCT/JP2008/05076  Date applied:2008.1

    Announcement no:特開WO 2008/090862 A1  Date announced:2008.7

    Patent/Registration no:特許US 8,340,748 B2  Date registered:2012.12 

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  • オリゴデンドロサイト発達障害モデル非ヒト哺乳動物

    加藤 英政, 伊藤 拓哉

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    Applicant:国立大学法人東北大学

    Application no:特願2006-314709  Date applied:2006.11

    Announcement no:特開2008-125452  Date announced:2008.6

    J-GLOBAL

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  • NON-LINEAR SIGNAL SEPARATION METHOD USING NON-LINER STATESPACE PROJECTION METHOD

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    Application no:特願PCT/JP2006/316386  Date applied:2006.8

    Announcement no:特開WO 2007/029485 A1  Date announced:2007.3

    Patent/Registration no:特許US8,116,857B2  Date registered:2012.2 

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  • 非線形状態空間射影法による非線形信号の分離方法

    木村 芳孝, 千田 新一, 中尾 光之, 岡村 州博, 伊藤 拓哉

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    Applicant:国立大学法人東北大学

    Application no:特願2007-534311  Date applied:2006.8

    Patent/Registration no:特許第4792584号  Date issued:2011.8

    J-GLOBAL

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  • NON-LINEAR SIGNAL SEPARATION METHOD USING NON-LINER STATESPACE PROJECTION METHOD

    Yoshitaka Kimura, Shinichi Chida, Mitsuyuki Nakao, Kunihiro Okamura, Takuya Ito

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    Applicant:Tohoku University NUC, Tohoku Techno Arch Co Ltd

    Application no:特願JP2005256300  Date applied:2005.9

    Patent/Registration no:EP1935335B1  Date registered:2019.5 

    US8,116,857B2

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  • ELECTROCADIOGRAM SIGNAL-PROCESSING METHOD AND ELECTROCARDIOGRAM SIGNAL-PROCESSING DEVICE

    Yoshitaka Kimura, Mitsuyuki Nakao, Shinichi Chida, Kunihiro Okamura, Michiyoshi Sato, Takuya Ito, Takayuki Shimazaki, Junichi Sugawara, Masato Senoo

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    Application no:特願PCT/JP2005/023601  Date applied:2005.5

    Announcement no:特開WO2006/080167  Date announced:2006.8

    Patent/Registration no:特許US 8,175,692 B2  Date registered:2012.5  Date issued:2012.5

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  • 心電図信号処理方法および心電図信号処理装置

    木村 芳孝, 中尾 光之, 千田 新一, 岡村 州博, 佐藤 道由, 伊藤 拓哉, 島崎 隆如, 菅原 準一, 妹尾 匡人

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    Applicant:国立大学法人東北大学

    Application no:特願2005-023982  Date applied:2005.1

    Announcement no:特開2006-204759  Date announced:2006.8

    Patent/Registration no:特許第4590554号  Date issued:2010.9

    J-GLOBAL

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  • ELECTROCARDIOGRAM SIGNAL-PROCESSING METHOD AND ELECTROCARDIOGRAM SIGNAL-PROCESSING DEVICE

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    Application no:特願JP2005023982A  Date applied:2005.1

    Announcement no:特開AU2005326223A1  Date announced:2006.8

    国立大学法人 東北大学

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Works

  • 心電計と超音波を融合したマウス胎仔心機能評価

    2015 - 2016

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  • 心電計と超音波を融合したマウス胎仔心機能評価

    2015 - 2016

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  • 心電計と超音波を融合したマウス胎仔心機能評価

    2014 - 2015

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  • 心電計と超音波を融合したマウス胎仔心機能評価

    2014 - 2015

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  • 胎児心電図実用化促進のための橋渡し研究

    2013 - 2014

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  • 心電計と超音波を融合したマウス胎仔心機能評価

    2013 - 2014

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  • 細胞の低酸素応答ダイナミクスの解明

    2013 - 2014

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  • 胎児心電図実用化促進のための橋渡し研究

    2013 - 2014

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  • 心電計と超音波を融合したマウス胎仔心機能評価

    2013 - 2014

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  • 細胞の低酸素応答ダイナミクスの解明

    2013 - 2014

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  • 胎児心電図実用化促進のための橋渡し研究

    2012 - 2013

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  • 胎児心電図実用化促進のための橋渡し研究

    2012 - 2013

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  • 胎仔脳出血メカニズムの流体力学的解析

    2010 - 2013

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  • 胎仔脳出血メカニズムの流体力学的解析

    2010 - 2013

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Research Projects

  • Optimization for pregnancy mouse condition with MMD combination anaesthesia focusing on fetal autonomic nerve activity

    Grant number:22K06052  2022.4 - 2025.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

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    Authorship:Principal investigator 

    Grant amount:\4,160,000 ( Direct Cost: \3,200,000 、 Indirect Cost:\960,000 )

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  • Attempt new detection of embryonic neurodevelopment abnormalities by fetal electrocardiography

    Grant number:16K11079  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    NISHIGORI Hidekazu, ITO Takuya

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    Grant amount:\4,680,000 ( Direct Cost: \3,600,000 、 Indirect Cost:\1,080,000 )

    In fertile hen`s egg-embryo-chick system, the ratio of low frequency are component/high frequency area (LF/HF), which is an indicator of sympathetic nerve activity, was significantly decreased in the hypothyroid model (methimazole group) compared with the control group. On the other hand, there was no significant difference in the mother stress model (glucocortisol group). In a mouse experiment, the LF/HF ratio was significantly decreased in fetuses of the valproic acid group. We examined the level of brain mRNA expression by using CAGE. Dozens of kinds of increasing and decreasing mRNAs were found in each group compared with the control group. In a human study, we analyzed measurements of fetal electrocardiography in thyroid diseases, the antiepileptic drug group, and pregnant women complicated with neuropsychiatric disorders. Currently, we are analyzing them.

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  • Challenge for development of placenta-on-a-chip

    Grant number:15K12500  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    Funamoto Kenichi, YOSHINO Daisuke, ITO Takuya, SUGIBAYASHI Rika, FUNAMOTO Kiyoe

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    Grant amount:\3,510,000 ( Direct Cost: \2,700,000 、 Indirect Cost:\810,000 )

    A placenta-on-a-chip was developed in this study in order to reproduce the structure and function of the microenvironment of a human placenta. Media channels, which model intervillous space and fetal blood vessel, were placed flanking the three parallel gel channels which mimic the extracellular matrix. Gas channels through which gas mixtures are supplied to control the oxygen tension inside the chip were placed above the media channels. A method to form monolayers of human choriocarcinoma cells (JEG3s) and human umbilical vein endothelial cells (HUVECs) in the media channels, and a method to measure the permeability of the monolayers were established. The co-culture of JEG3s and HUVECs under a controlled oxygen tension at different concentrations showed variations of cell morphology and cell junctions, implying that oxygen tension can influence the cell-cell interaction.

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  • マウス胎仔由来遊離核酸を用いた低酸素バイオマーカーの探索

    Grant number:25461639  2013.4 - 2014.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    クラリッサ ヴェラヨ

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    Grant type:Competitive

    Grant amount:\5,070,000 ( Direct Cost: \3,900,000 、 Indirect Cost:\1,170,000 )

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  • Artificial sight produced by transducing genes into primary visual cortex

    Grant number:23659804  2011.4 - 2012.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    TOMITA Hiroshi, SUGANO Eriko

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    Grant type:Competitive

    Grant amount:\3,640,000 ( Direct Cost: \2,800,000 、 Indirect Cost:\840,000 )

    The transduction efficiency to the cortex using AAV type 2/5 was higher than that using AAV2/2. However we could not succeed to transfer to the broad area. It was limited to the only injection site. We tested two types of AAVs including a CAG or CaMKII promoter. Different light responsivities elicited by ChR2 transferred cortex were recorded depending on the promoter the AAV included. These results indicated that it is important to choose appropriate promoter to transfer a gene into the cortex.

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  • 子宮内胎児機能不全モデルによる脳出血発生機序の研究

    Grant number:22659294  2010.4 - 2012.3

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    伊藤 拓哉

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2,140,000 ( Direct Cost: \1,900,000 、 Indirect Cost:\240,000 )

    研究2年目である平成23年度は正常飼育および低栄養飼育したマウスの胎仔に胎児心電図装置による循環動態の監視下で虚血再還流を負荷した。虚血再灌流負荷前後の胎仔脳を採材し(各6検体、計24検体)、母体栄養条件による遺伝子発現変動をマイクロアレイ解析によって母体栄養条件による胎仔脳の虚血再灌流に対する遺伝子発現応答を比較、評価を実施した。
    ・虚血再灌流負荷前:低栄養飼育由来の胎仔脳ではHIFlaおよびその下流遺伝子の発現量が有意に増加し、低酸素状態と同様の遺伝子発現プロファイルを示した。またCOX4i1などのミトコンドリア構成遺伝子群のmRNA発現量や成人で脳出血との関連が報告されているs100a10のmRNA発現量と転写因子p53のmRNA発現量の関係を精査したところ、虚血再灌流前はこれらの遺伝子群のmRNA発現量とp53mRNA発現量の分布は母体栄養条件による際を認めなかった
    ・虚血再灌流負荷後:低栄養飼育由来の胎仔脳ではミトコンドリア構成遺伝子群のmRNA発現量やs100a10のmRNA発現量が有意に増加していた。またp53mRNA発現量との関係は母体栄養条件によって明確に異なる分布を示した。脳出血発症時にミトコンドリアは活性酸素を産生することが知られていることから虚血再灌流負荷後に有意に発現が増加するCOX4i1などのミトコンドリア構成遺伝子群およびp53が脳出血の発症に関与していると考えられた。

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  • The research and development of new electrodes to measure fetal electrocardiogram via maternal abdominal wall of pregnant mothers in the field

    Grant number:20591904  2008.4 - 2010.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KIMURA Yoshitaka, ITO Takuya, SATO Naoaki

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    Grant type:Competitive

    Grant amount:\4,030,000 ( Direct Cost: \3,100,000 、 Indirect Cost:\930,000 )

    This project has aimed to develop new electrodes to measure fetal electrocardiogram signals in specific situations, such as measuring extremely-low-voltage fetal ECG via the abdominal walls of pregnant mothers, who are receiving home care in remote places where shielded rooms are not available. The voltage of the specific measurement is set less than 10 u V, which is significantly low, thus it requires new technology to perform the task and obtain accurate results.
    Among various materials, a special gel was chosen as the most optimal material for creating electrode; then the optimal size, figure, and proportion are calculated. Although single-sheeted electrode was assumed most optimal, as the result, a set of three sheets has been found most optimal.

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  • Basic study of fetal heart ischemia by using a multi-electrodes fetal electrocardiogram via maternal abdomen for all gestational period fetuses

    Grant number:18390306  2006 - 2007

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    KIMURA Yoshitaka, ITO Takuya, CHISAKA Hiroshi

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    Grant amount:\13,820,000 ( Direct Cost: \12,500,000 、 Indirect Cost:\1,320,000 )

    Methods: Experiments were performed with pregnant C57BL/6N mice and 17 dpc fetuses. The measurements were carried out in the Fluid Dynamics Laboratory of the Tohoku University to take advantage of their ultrasonogram experimental facilities for animals. Caesarean section was carried out in pregnant mice after anesthesia and electrodes were attached to the fetuses to measure fetal ultrasonogram. 5 minute clipping and 5 minute release of the branches of the uterine artery was performed three times in tandem and the results were monitored by ultrasonogram.
    Results: The fetal heart potential was as low as a few microvolts (μV) and because of this low signal extraction of the fetal electrocardiogram proved to be very troublesome. To overcome this problem, we developed a needle electrode that contained a signal amplification mechanism and were able to reduce the noise to a minimal level. To our knowledge, we are the first group in the world to report the successful measurement of the fetal electrocardiogram. Moreover, based on these investigations, we were able to identify the characteristic "T-wave" from the fetal electrocardiogram that had been so far believed to be nonexistent in mice. Next, we investigated the alterations in the electrocardiogram pattern and fetal heart rate because of the periodic constraint and release (5 minutes each, 3 times repeated) of the branches of the uterine artery. The results showed increase of the T-wave during constraint by clipping of the branches of the artery, accompanied with frequent arrhythmia, which lead to a reduction of fetal heart rate. After release of the clipping, frequent arrhythmia was again observed and the heart rate gradually improved to a normal level. Furthermore, during these analyses we were able to extract an ultrasonogram from the fetal brain that showed the blood flow in the branches of the middle cerebral artery. However, due to the breathing of the mother, it was difficult to obtain a clear image from the ultrasonogram that showed the area of interest in the brain. Because of this hindrance, we were unable to produce a real-time image of the blood flow in the brain during constraint and release of the branches of the uterine artery.
    Discussion: Our analysis shows that fetal electrocardiogram and ultrasonogram can be a useful tool to monitor fetal ischemia.

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  • あらゆる妊娠週数の全胎児で観測可能な胎児心電図の可能性の基礎研究

    Grant number:17659327  2005 - 2007

    日本学術振興会  科学研究費助成事業 萌芽研究  萌芽研究

    木村 芳孝, 伊藤 拓哉, 妹尾 匡人

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    Grant amount:\1,500,000 ( Direct Cost: \1,500,000 )

    研究方法
    胎齢17日の妊娠後期マウス胎仔(C57BL/6N)を用いて実験を行った。母体麻酔下で開腹し、対象となる一仔に電極を装着した。装着する電極の種類や配置場所を変更し、ノイズの混入や有効信号の導出の有無などを精査し、有効な電極の開発及び配置法を検討した。
    研究結果
    マウス胎仔の心電位は数μVと極めて小さく、電源の低ノイズ化などシールドの強化を図ったが信号の抽出は困難を極めた。この様な状況ではS/N比が極端に低いために通常の電極では有効な信号が含まれているかの判断は不可能であった。そのため有効な電極配置の検討すらできない状態であった。我々は容量結合による信号導出に着目し、高インピーダンスな特性を有する針電極を開発した。この高インピーダンス電極を用いることでノイズの混入を低減することに成功した。また胎仔を傷つけることなく心電位の導出が可能な電極の配置法を発見した。今までに開発した非線形フィルターを併用し、母体心電位や筋電位を除去した結果、世界で初めてマウスの胎仔心電位の計測に成功した。記録した心電図の解析した所、マウスでは存在しないとされていたT波の存在を胎仔で確認した。
    数μVと極めて小さな信号に対して、シールドルームなど特殊な設備を有していない通常の環境でも使用可能である新しい高インピーダンス電極とその配置法及び非線形フィルターの開発し、あらゆる妊娠週数での胎児心電図測定を可能とする基礎技術を得ることができた。

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Teaching Experience

  • 実験動物学

    2022.10 Institution:北海道医学技術専門学校

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  • pharmacology

    2022.4 Institution:Asahikawa University

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    2021.6 - 2022.9 Institution:Asahikawa Medical College

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    2021.2 Institution:Asahikawa Medical College

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  • 基礎医学修練

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  • 医学概論

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  • 医学研究法概論

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  • 体と健康・学生と健康

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