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  1. Article ; Online: The current status of bereavement follow-up in Japanese emergency departments: A cross-sectional nationwide survey.

    Ito, Yoshiyasu / Obana, Miyuki / Kawakami, Daisuke / Murakami, Noriko / Sakaguchi, Yukihiro

    International emergency nursing

    2020  Volume 52, Page(s) 100872

    Abstract: Introduction: The aim of this study was to investigate the current status of bereavement follow-up in Japanese emergency departments.: Methods: This study employed a cross-sectional design and conducted a nationwide survey of all emergency ... ...

    Abstract Introduction: The aim of this study was to investigate the current status of bereavement follow-up in Japanese emergency departments.
    Methods: This study employed a cross-sectional design and conducted a nationwide survey of all emergency departments in Japan. Self-reported questionnaires were sent to the nurse leaders of each emergency department.
    Results: Of 289 nurse leaders approached, 145 (50.2%) responded. Only 17.9% emergency departments provided bereavement follow-up strategies, and the most frequent strategy was referral to a specialist for psychological treatment. Most nurse leaders perceived that bereavement follow-up is necessary, and the greatest need of the bereaved as perceived by the nurse leaders was explanation of the patient's death. However, 60% of the nurse leaders perceived bereavement follow-up to be necessary but difficult, and the major challenges in bereavement follow-up were lack of time, knowledge, and skill.
    Conclusion: In contemporary Japan, the prevalence of bereavement follow-up strategies offered by emergency departments was low, and although most nurse leaders perceived follow-up as necessary, it could not be provided because of limitations in human resources and staff training.
    MeSH term(s) Adult ; Bereavement ; Cross-Sectional Studies ; Emergency Service, Hospital ; Female ; Humans ; Japan ; Male ; Nurse's Role ; Professional-Family Relations ; Surveys and Questionnaires
    Language English
    Publishing date 2020-04-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 2420747-0
    ISSN 1878-013X ; 1755-599X
    ISSN (online) 1878-013X
    ISSN 1755-599X
    DOI 10.1016/j.ienj.2020.100872
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Neural activity selects myosin IIB and VI with a specific time window in distinct dynamin isoform-mediated synaptic vesicle reuse pathways.

    Hayashida, Michikata / Tanifuji, Shota / Ma, Huan / Murakami, Noriko / Mochida, Sumiko

    The Journal of neuroscience : the official journal of the Society for Neuroscience

    2015  Volume 35, Issue 23, Page(s) 8901–8913

    Abstract: Presynaptic nerve terminals must maintain stable neurotransmissions via synaptic vesicle (SV) resupply despite encountering wide fluctuations in the number and frequency of incoming action potentials (APs). However, the molecular mechanism linking ... ...

    Abstract Presynaptic nerve terminals must maintain stable neurotransmissions via synaptic vesicle (SV) resupply despite encountering wide fluctuations in the number and frequency of incoming action potentials (APs). However, the molecular mechanism linking variation in neural activity to SV resupply is unknown. Myosins II and VI are actin-based cytoskeletal motors that drive dendritic actin dynamics and membrane transport, respectively, at brain synapses. Here we combined genetic knockdown or molecular dysfunction and direct physiological measurement of fast synaptic transmission from paired rat superior cervical ganglion neurons in culture to show that myosins IIB and VI work individually in SV reuse pathways, having distinct dependency and time constants with physiological AP frequency. Myosin VI resupplied the readily releasable pool (RRP) with slow kinetics independently of firing rates but acted quickly within 50 ms after AP. Under high-frequency AP firing, myosin IIB resupplied the RRP with fast kinetics in a slower time window of 200 ms. Knockdown of both myosin and dynamin isoforms by mixed siRNA microinjection revealed that myosin IIB-mediated SV resupply follows amphiphysin/dynamin-1-mediated endocytosis, while myosin VI-mediated SV resupply follows dynamin-3-mediated endocytosis. Collectively, our findings show how distinct myosin isoforms work as vesicle motors in appropriate SV reuse pathways associated with specific firing patterns.
    MeSH term(s) Action Potentials/drug effects ; Animals ; Animals, Newborn ; Cells, Cultured ; Dynamin I/genetics ; Dynamin I/metabolism ; Electric Stimulation ; Endocytosis/drug effects ; Excitatory Postsynaptic Potentials/drug effects ; Female ; Male ; Nerve Tissue Proteins/metabolism ; Neurons/cytology ; Neurons/drug effects ; Neurons/physiology ; Nonmuscle Myosin Type IIB/genetics ; Nonmuscle Myosin Type IIB/metabolism ; Nonmuscle Myosin Type IIB/pharmacology ; Presynaptic Terminals/drug effects ; Presynaptic Terminals/metabolism ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; RNA, Small Interfering/pharmacology ; Rats ; Rats, Wistar ; Signal Transduction/drug effects ; Superior Cervical Ganglion/cytology ; Synaptic Vesicles/metabolism ; Time Factors ; Ventricular Myosins/genetics ; Ventricular Myosins/metabolism ; Ventricular Myosins/pharmacology
    Chemical Substances Nerve Tissue Proteins ; Protein Isoforms ; RNA, Small Interfering ; amphiphysin (147954-52-7) ; Dynamin I (EC 3.5.1.50) ; Nonmuscle Myosin Type IIB (EC 3.6.1.-) ; Ventricular Myosins (EC 3.6.1.-)
    Language English
    Publishing date 2015-06-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 10.1523/JNEUROSCI.5028-14.2015
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  3. Article ; Online: Differences of Recovery from Rocuronium-induced Deep Paralysis in Response to Small Doses of Sugammadex between Elderly and Nonelderly Patients.

    Muramatsu, Takahiro / Isono, Shiroh / Ishikawa, Teruhiko / Nozaki-Taguchi, Natsuko / Okazaki, Junko / Kitamura, Yuji / Murakami, Noriko / Sato, Yasunori

    Anesthesiology

    2018  Volume 129, Issue 5, Page(s) 901–911

    Abstract: What we already know about this topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Complete recovery from rocuronium-induced muscle paralysis with sugammadex is reported to be delayed in elderly patients. The authors tested a hypothesis that ... ...

    Abstract What we already know about this topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Complete recovery from rocuronium-induced muscle paralysis with sugammadex is reported to be delayed in elderly patients. The authors tested a hypothesis that recovery from deep neuromuscular block with low-dose sugammadex is slower (primary hypothesis) and incidence of recurarization is higher (secondary hypothesis) in elderly patients than in nonelderly patients.
    Methods: In anesthetized elderly (n = 20; 76.9 ± 5.0 yr of age) and nonelderly patients (n = 20; 53.7 ± 12.8 yr of age) under deep paralysis with rocuronium, change of train-of-four ratio per minute (primary outcome variable) was measured with an acceleromyograph neuromuscular monitor during spontaneous recovery from rocuronium-induced muscle paralysis (0.6 mg/kg) and after infusion of low-dose sugammadex (50 µg · kg · min). Recurarization was defined as the negative change of train-of-four ratio.
    Results: Spontaneous train-of-four ratio recovery rate was significantly slower in the elderly group (median [25th percentile, 75th percentile]: 1.89 [1.22, 2.90] %/min) than in the nonelderly group (3.45 [1.96, 4.25] %/min, P = 0.024). Train-of-four ratio change rate in response to low-dose sugammadex was significantly slower in elderly (0.55 [-0.29, 1.54] %/min) than in the nonelderly group (1.68 [0.73, 3.13] %/min, P = 0.024). Incidence of recurarization was significantly higher in the elderly group than in the nonelderly group (35% vs. 5%, P = 0.044). Multiple linear regression analyses indicate that slower spontaneous train-of-four ratio recovery rate and impaired renal function are two major contributing factors that decrease train-of-four ratio change rate in response to low-dose sugammadex.
    Conclusions: Elderly patients are at greater risk for recurarization and residual muscle paralysis when low-dose sugammadex is administered.
    MeSH term(s) Accelerometry/statistics & numerical data ; Aged ; Anesthesia Recovery Period ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Middle Aged ; Neuromuscular Nondepolarizing Agents/pharmacology ; Paralysis/chemically induced ; Rocuronium/pharmacology ; Sugammadex/pharmacology ; Time Factors
    Chemical Substances Neuromuscular Nondepolarizing Agents ; Sugammadex (361LPM2T56) ; Rocuronium (WRE554RFEZ)
    Language English
    Publishing date 2018-09-10
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 269-0
    ISSN 1528-1175 ; 0003-3022
    ISSN (online) 1528-1175
    ISSN 0003-3022
    DOI 10.1097/ALN.0000000000002412
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  4. Article ; Online: The importance of patient perspectives in pulmonary hypertension.

    McGoon, Michael D / Ferrari, Pisana / Armstrong, Iain / Denis, Migdalia / Howard, Luke S / Lowe, Gabi / Mehta, Sanjay / Murakami, Noriko / Wong, Brad A

    The European respiratory journal

    2019  Volume 53, Issue 1

    Abstract: The assessment of objective measurement of cardiopulmonary status has helped us achieve better clinical outcomes for patients and develop new therapies through to the point of market access; however, patient surveys indicate that more can be done to ... ...

    Abstract The assessment of objective measurement of cardiopulmonary status has helped us achieve better clinical outcomes for patients and develop new therapies through to the point of market access; however, patient surveys indicate that more can be done to improve holistic care and patient engagement. In this multidisciplinary review, we examine how clinical teams can acknowledge and embrace the individual patient's perspective, and thus improve the care for individual patients suffering from pulmonary hypertension by cultivating the importance and relevance of health-related quality of life in direct clinical care. At the individual level, patients should be provided with access to accredited specialist centres which provide a multidisciplinary approach where there is a culture focused on narrative medicine, quality of life, shared decision making and timely access to palliative care, and where there is participation in education. On a larger scale, we call for the development, expansion and promotion of patient associations to support patients and carers, lobby for access to best care and treatments, and provide input into the development of clinical trials and registries, focusing on the patients' perspective.
    MeSH term(s) Health Knowledge, Attitudes, Practice ; Humans ; Hypertension, Pulmonary/psychology ; Hypertension, Pulmonary/therapy ; Palliative Care/methods ; Patient Participation ; Quality of Life/psychology
    Language English
    Publishing date 2019-01-24
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.01919-2018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Malignant Hyperthermia during Thoracoscopic Pulmorrhaphy in a 70-Year-Old Man.

    Sakai, Michihiro / Murakami, Noriko / Kitamura, Yuji / Sato, Shin / Iwama, Hiroshi / Nomura, Akira

    Case reports in anesthesiology

    2014  Volume 2014, Page(s) 250502

    Abstract: Malignant hyperthermia (MH) is a rare but potentially fatal complication that may develop under general anesthesia (GA) and is rarely reported in elderly patients. We encountered a case of mild-onset MH in a 70-year-old patient who was receiving an ... ...

    Abstract Malignant hyperthermia (MH) is a rare but potentially fatal complication that may develop under general anesthesia (GA) and is rarely reported in elderly patients. We encountered a case of mild-onset MH in a 70-year-old patient who was receiving an elective thoracoscopic pulmorrhaphy and had a history of several GA procedures. Anesthesia was induced with propofol, fentanyl, and rocuronium and maintained with sevoflurane and remifentanil. His body temperature (BT) was 37.9°C after induction. During the procedure, the end-tidal CO2 (ETCO2) increased steadily to 47-50 mmHg, presumably in response to the single lung ventilation. At the end, BT was 38.1°C and ETCO2 was 47 mmHg under spontaneous breathing. After extubation, the patient wheezed on inspiration and expiration, and his trachea was reintubated. Sixty minutes after surgery, BT increased to 40.5°C and the arterial blood gas analysis showed severe metabolic acidosis. Based on these findings, MH was suspected and a bolus dose of dantrolene was administered. He responded to the dantrolene, and no complications or recurrence of MH was observed postoperatively. In this patient, the initial signs of MH were so subtle that making the diagnosis of MH was difficult. A high degree of suspicion is necessary to prevent a fulminant MH crisis.
    Language English
    Publishing date 2014-05-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2659087-6
    ISSN 2090-6390 ; 2090-6382
    ISSN (online) 2090-6390
    ISSN 2090-6382
    DOI 10.1155/2014/250502
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  6. Article ; Online: Dyrk1A binds to multiple endocytic proteins required for formation of clathrin-coated vesicles.

    Murakami, Noriko / Bolton, David / Hwang, Yu-Wen

    Biochemistry

    2009  Volume 48, Issue 39, Page(s) 9297–9305

    Abstract: In spite of a nuclear targeting sequence, a substantial amount of dual-specificity tyrosine phosphorylation-regulated kinase (Dyrk1A) is located within the cytoplasm of neurons. Analysis of fractionated rat brains revealed that the majority of Dyrk1A was ...

    Abstract In spite of a nuclear targeting sequence, a substantial amount of dual-specificity tyrosine phosphorylation-regulated kinase (Dyrk1A) is located within the cytoplasm of neurons. Analysis of fractionated rat brains revealed that the majority of Dyrk1A was in the postnuclear precipitate. The kinase in this fraction was resistant to high salt and Triton X-100 extraction at pH 6.5. Hypothesizing that Dyrk1A binds tightly with cell constituents, we searched for Dyrk1A binding proteins in the Triton X-100-insoluble fraction extracted with urea and fractionated by column chromatography. An overlay assay using the recombinant kinase revealed that multiple proteins are capable of binding to Dyrk1A. Among them, we identified clathrin heavy chain and dynamin 1 as potential candidates. An overlay assay using purified and partially purified proteins showed the binding of Dyrk1A with both proteins. Under native conditions, Dyrk1A precipitated with newly formed clathrin cages and with dynamin via the GST-amphiphysin SH3 domain. We also identified another endocytic protein, endophilin 1, as an additional Dyrk1A binding protein. We then tested whether the clathrin-coated vesicle (CCV)-associated proteins could be phosphorylated by Dyrk1A. Multiple proteins apparently distinctive from the known substrates were phosphorylated in the brain CCV. Our findings suggest a role for Dyrk1A in controlling synaptic vesicle recycling processes.
    MeSH term(s) Animals ; Biological Transport ; Brain Chemistry ; Carrier Proteins/chemistry ; Carrier Proteins/metabolism ; Clathrin-Coated Vesicles/enzymology ; Clathrin-Coated Vesicles/metabolism ; Dialysis ; Endocytosis/physiology ; Humans ; Liver/cytology ; Liver/enzymology ; Liver/metabolism ; Mice ; Neurons/enzymology ; Neurons/metabolism ; Phosphorylation ; Protein Binding/physiology ; Protein Serine-Threonine Kinases/chemistry ; Protein Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases/chemistry ; Protein-Tyrosine Kinases/metabolism ; Rats ; Subcellular Fractions/enzymology ; Subcellular Fractions/metabolism ; Transport Vesicles/enzymology ; Transport Vesicles/metabolism ; Dyrk Kinases
    Chemical Substances Carrier Proteins ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2009-08-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108-3
    ISSN 1520-4995 ; 0006-2960
    ISSN (online) 1520-4995
    ISSN 0006-2960
    DOI 10.1021/bi9010557
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  7. Article ; Online: Phosphorylation by Dyrk1A of clathrin coated vesicle-associated proteins: identification of the substrate proteins and the effects of phosphorylation.

    Murakami, Noriko / Bolton, David C / Kida, Elizabeth / Xie, Wen / Hwang, Yu-Wen

    PloS one

    2012  Volume 7, Issue 4, Page(s) e34845

    Abstract: Dyrk1A phosphorylated multiple proteins in the clathrin-coated vesicle (CCV) preparations obtained from rat brains. Mass spectrometric analysis identified MAP1A, MAP2, AP180, and α- and β-adaptins as the phosphorylated proteins in the CCVs. Each protein ... ...

    Abstract Dyrk1A phosphorylated multiple proteins in the clathrin-coated vesicle (CCV) preparations obtained from rat brains. Mass spectrometric analysis identified MAP1A, MAP2, AP180, and α- and β-adaptins as the phosphorylated proteins in the CCVs. Each protein was subsequently confirmed by [(32)P]-labeling and immunological methods. The Dyrk1A-mediated phosphorylation released the majority of MAP1A and MAP2 and enhanced the release of AP180 and adaptin subunits from the CCVs. Furthermore, Dyrk1A displaced adaptor proteins physically from CCVs in a kinase-concentration dependent manner. The clathrin heavy chain release rate, in contrast, was not affected by Dyrk1A. Surprisingly, the Dyrk1A-mediated phosphorylation of α- and β-adaptins led to dissociation of the AP2 complex, and released only β-adaptin from the CCVs. AP180 was phosphorylated by Dyrk1A also in the membrane-free fractions, but α- and β-adaptins were not. Dyrk1A was detected in the isolated CCVs and was co-localized with clathrin in neurons from mouse brain sections and from primary cultured rat hippocampus. Previously, we proposed that Dyrk1A inhibits the onset of clathrin-mediated endocytosis in neurons by phosphorylating dynamin 1, amphiphysin 1, and synaptojanin 1. Current results suggest that besides the inhibition, Dyrk1A promotes the uncoating process of endocytosed CCVs.
    MeSH term(s) Animals ; CHO Cells ; Clathrin-Coated Vesicles/metabolism ; Cricetinae ; Dynamin I/metabolism ; Electrophoresis, Polyacrylamide Gel ; Endocytosis ; Female ; Mice ; Microtubule-Associated Proteins/metabolism ; Monomeric Clathrin Assembly Proteins/metabolism ; Nerve Tissue Proteins/metabolism ; PC12 Cells ; Phosphoric Monoester Hydrolases/metabolism ; Phosphorylation ; Protein Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases/metabolism ; Rats ; Dyrk Kinases
    Chemical Substances Map1a protein, rat ; Microtubule-Associated Proteins ; Monomeric Clathrin Assembly Proteins ; Mtap2 protein, mouse ; Nerve Tissue Proteins ; clathrin assembly protein AP180 ; amphiphysin (147954-52-7) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; synaptojanin (EC 3.1.3.-) ; Phosphoric Monoester Hydrolases (EC 3.1.3.2) ; Dynamin I (EC 3.5.1.50)
    Language English
    Publishing date 2012-04-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0034845
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  8. Article: [GERD and sleep disorder].

    Ozasa, Yumiko / Murakami, Noriko / Fukunaga, Mikihiko / Nakai, Yoshihide

    Nihon rinsho. Japanese journal of clinical medicine

    2006  Volume 64, Issue 7, Page(s) 1391–1395

    Abstract: The prevalence of gastroesophageal reflux disease (GERD) is increasing in Japan. Symptoms of GERD negatively affect their quality of life and sleep. There are several reasons for sleep disorder with GERD as follows. Nocturnal GERD symptoms sometimes ... ...

    Abstract The prevalence of gastroesophageal reflux disease (GERD) is increasing in Japan. Symptoms of GERD negatively affect their quality of life and sleep. There are several reasons for sleep disorder with GERD as follows. Nocturnal GERD symptoms sometimes directly avoid sleeping. Sleep apnea syndrome and GERD are sometimes concomitant. The both are sharing similar risk factor such as obesity and cause sleep disorder. When untypical symptoms of GERD are not diagnosed, patients are severely anxious about their physical condition. Then they feel stressful and sometimes get secondary depressive state including sleep disorder. We had better take care about patients' psychosocial factors and treat symptoms of GERD and sleep disorder together with holistic approach.
    MeSH term(s) Adult ; Aged ; Antidepressive Agents ; Esophagoscopy ; Female ; Gastroesophageal Reflux/complications ; Gastroesophageal Reflux/diagnosis ; Gastroesophageal Reflux/psychology ; Gastroesophageal Reflux/therapy ; Humans ; Hyperphagia/complications ; Life Style ; Male ; Middle Aged ; Obesity/complications ; Quality of Life ; Risk Factors ; Sleep Wake Disorders/etiology ; Stress, Psychological/complications ; Stress, Psychological/therapy
    Chemical Substances Antidepressive Agents
    Language Japanese
    Publishing date 2006-07
    Publishing country Japan
    Document type Case Reports ; English Abstract ; Journal Article ; Review
    ZDB-ID 390903-7
    ISSN 0047-1852
    ISSN 0047-1852
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  9. Article: Folic acid supplementation dysregulates gene expression in lymphoblastoid cells – Implications in nutrition

    Junaid, Mohammed A / Kuizon, Salomon / Cardona, Juan / Azher, Tayaba / Murakami, Noriko / Pullarkat, Raju K / Brown, W. Ted

    Biochemical and biophysical research communications. 2011 Sept. 9, v. 412, no. 4

    2011  

    Abstract: For over a decade, folic acid (FA) supplementation has been widely prescribed to pregnant women to prevent neural tube closure defects in newborns. Although neural tube closure occurs within the first trimester, high doses of FA are given throughout ... ...

    Abstract For over a decade, folic acid (FA) supplementation has been widely prescribed to pregnant women to prevent neural tube closure defects in newborns. Although neural tube closure occurs within the first trimester, high doses of FA are given throughout pregnancy, the physiological consequences of which are unknown. FA can cause epigenetic modification of the cytosine residues in the CpG dinucleotide, thereby affecting gene expression. Dysregulation of crucial gene expression during gestational development may have lifelong adverse effects or lead to neurodevelopmental defects, such as autism. We have investigated the effect of FA supplementation on gene expression in lymphoblastoid cells by whole-genome expression microarrays. The results showed that high FA caused dysregulation by ⩾four-fold up or down to more than 1000 genes, including many imprinted genes. The aberrant expression of three genes (FMR1, GPR37L1, TSSK3) was confirmed by Western blot analyses. The level of altered gene expression changed in an FA concentration-dependent manner. We found significant dysregulation in gene expression at concentrations as low as 15ng/ml, a level that is lower than what has been achieved in the blood through FA fortification guidelines. We found evidence of aberrant promoter methylation in the CpG island of the TSSK3 gene. Excessive FA supplementation may require careful monitoring in women who are planning for, or are in the early stages of pregnancy. Aberrant expression of genes during early brain development may have an impact on behavioural characteristics.
    Keywords DNA methylation ; Western blotting ; adverse effects ; autism ; blood ; brain ; cytosine ; epigenetics ; folic acid ; gene expression ; genes ; genomic islands ; guidelines ; microarray technology ; monitoring ; neonates ; nutrition ; planning ; pregnancy ; pregnant women
    Language English
    Dates of publication 2011-0909
    Size p. 688-692.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2011.08.027
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition.

    Junaid, Mohammed A / Kuizon, Salomon / Cardona, Juan / Azher, Tayaba / Murakami, Noriko / Pullarkat, Raju K / Brown, W Ted

    Biochemical and biophysical research communications

    2011  Volume 412, Issue 4, Page(s) 688–692

    Abstract: For over a decade, folic acid (FA) supplementation has been widely prescribed to pregnant women to prevent neural tube closure defects in newborns. Although neural tube closure occurs within the first trimester, high doses of FA are given throughout ... ...

    Abstract For over a decade, folic acid (FA) supplementation has been widely prescribed to pregnant women to prevent neural tube closure defects in newborns. Although neural tube closure occurs within the first trimester, high doses of FA are given throughout pregnancy, the physiological consequences of which are unknown. FA can cause epigenetic modification of the cytosine residues in the CpG dinucleotide, thereby affecting gene expression. Dysregulation of crucial gene expression during gestational development may have lifelong adverse effects or lead to neurodevelopmental defects, such as autism. We have investigated the effect of FA supplementation on gene expression in lymphoblastoid cells by whole-genome expression microarrays. The results showed that high FA caused dysregulation by ≥ four-fold up or down to more than 1000 genes, including many imprinted genes. The aberrant expression of three genes (FMR1, GPR37L1, TSSK3) was confirmed by Western blot analyses. The level of altered gene expression changed in an FA concentration-dependent manner. We found significant dysregulation in gene expression at concentrations as low as 15 ng/ml, a level that is lower than what has been achieved in the blood through FA fortification guidelines. We found evidence of aberrant promoter methylation in the CpG island of the TSSK3 gene. Excessive FA supplementation may require careful monitoring in women who are planning for, or are in the early stages of pregnancy. Aberrant expression of genes during early brain development may have an impact on behavioural characteristics.
    MeSH term(s) Cell Line ; DNA Methylation/drug effects ; Diet ; Dietary Supplements ; Folic Acid/administration & dosage ; Gene Expression/drug effects ; Genomic Imprinting/drug effects ; Humans ; Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic ; Protein-Serine-Threonine Kinases/genetics
    Chemical Substances Folic Acid (935E97BOY8) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TSSK3 protein, human (EC 2.7.11.1)
    Language English
    Publishing date 2011-09-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2011.08.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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