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  1. AU="Kaoru Dohi"
  2. AU="Tornai, Gábor J"
  3. AU="D'Avella, Christopher"
  4. AU="Lim, Boon L."
  5. AU="Heselden, Marie"
  6. AU=Dias?Polak David
  7. AU="Shahid Umar"
  8. AU="Abu-Shmais, Alexandria A"
  9. AU="Takenaka, Haruka"
  10. AU="Bramley, Andrea"
  11. AU="Sang Hong Lee"

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  1. Artikel ; Online: Serum-Induced Expression of Brain Natriuretic Peptide Contributes to Its Increase in Patients with HFpEF

    Ryuji Okamoto / Ryotaro Hashizume / Noboru Suzuki / Rie Ito / Tomoko Tokuhara / Hiroshi Fujiwara / Ye Zhe / Hiromasa Ito / Takaya Abe / Kaoru Dohi

    International Journal of Molecular Sciences, Vol 23, Iss 2991, p

    2022  Band 2991

    Abstract: Brain natriuretic peptide (BNP) levels are increased in both patients with heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF), but the reasons for this remain unclear. Our purpose was to examine whether serum-induced BNP (iBNP) ... ...

    Abstract Brain natriuretic peptide (BNP) levels are increased in both patients with heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF), but the reasons for this remain unclear. Our purpose was to examine whether serum-induced BNP (iBNP) expression partly contributes to increased BNP in patients with HFpEF. BNP reporter cardiomyocytes from pBNP-luc-KI mice were stimulated with serum from patients with HFpEF or HFrEF ( n = 114 and n = 82, respectively). Luciferase activity was examined as iBNP and the iBNP-to-BNP ratio was evaluated. Patient characteristics and clinical parameters were compared, and multivariate regression analysis was performed to determine independent predictors of the iBNP-to-BNP ratio. Female sex and frequencies of atrial fibrillation, hypertension and the use of a calcium channel blocker (CCB) were higher in HFpEF. The iBNP-to-BNP ratio was significantly higher in HFpEF (26.9) than in HFrEF (16.1, p < 0.001). Multivariate regression analysis identified the existence of HFpEF as an independent predictor of the iBNP-to-BNP ratio after adjusting for all other measurements (β = 0.154, p = 0.032). Age, hemoglobin, CCB usage and deceleration time were also independent predictors (β = 0.167, p = 0.025; β = 0.203, p = 0.006; β = 0.138, p = 0.049; and β = 0.143, p = 0.049, respectively). These results indicate that the elevated BNP in patients with HFpEF is partly due to iBNP from the heart.
    Schlagwörter agonist ; brain natriuretic peptide ; cardiomyocyte ; heart failure ; patient’s serum ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2022-03-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Quantification of extracellular volume fraction by cardiac computed tomography for noninvasive assessment of myocardial fibrosis in hemodialysis patients

    Akimasa Yamada / Kakuya Kitagawa / Satoshi Nakamura / Masafumi Takafuji / Yoshitaka Goto / Ryuji Okamoto / Kaoru Dohi / Hajime Sakuma

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Band 10

    Abstract: Abstract Extent of myocardial fibrosis in hemodialysis patients has been associated with poor prognosis. Myocardial extracellular volume (ECV) quantification using contrast enhanced cardiac computed tomography (CT) is a novel method to determine extent ... ...

    Abstract Abstract Extent of myocardial fibrosis in hemodialysis patients has been associated with poor prognosis. Myocardial extracellular volume (ECV) quantification using contrast enhanced cardiac computed tomography (CT) is a novel method to determine extent of myocardial fibrosis. Cardiac CT-based myocardial ECV in hemodialysis patients with those of propensity-matched non-hemodialysis control subjects were compared. Twenty hemodialysis patients (mean age, 67.4 ± 9.6 years; 80% male) and 20 propensity-matched non-hemodialysis controls (mean age, 66.3 ± 9.1 years; 85% male) who underwent comprehensive cardiac CT consisted of calcium scoring, coronary CT angiography, stress perfusion CT and delayed enhancement CT were evaluated. Myocardial ECV was significantly greater in the hemodialysis group than in the control group (33.8 ± 4.7% versus 26.6 ± 2.9%; P < 0.0001). In the hemodialysis group, modest correlation was evident between myocardial ECV and left atrial volume index (r = 0.54; P = 0.01), while there was no correlation between myocardial ECV and other cardiac parameters including left ventricular mass index and severity of myocardial ischemia. Cardiac CT-based myocardial ECV may offer a potential imaging biomarker for myocardial fibrosis in HD patients.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610 ; 616
    Sprache Englisch
    Erscheinungsdatum 2020-09-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Podocyte-specific Crb2 knockout mice develop focal segmental glomerulosclerosis

    Akiko Tanoue / Kan Katayama / Yugo Ito / Kensuke Joh / Masaaki Toda / Taro Yasuma / Corina N. D’Alessandro-Gabazza / Hiroshi Kawachi / Kunimasa Yan / Masaaki Ito / Esteban C. Gabazza / Karl Tryggvason / Kaoru Dohi

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Band 16

    Abstract: Abstract Crb2 is a cell polarity-related type I transmembrane protein expressed in the apical membrane of podocytes. Knockdown of crb2 causes glomerular permeability defects in zebrafish, and its complete knockout causes embryonic lethality in mice. ... ...

    Abstract Abstract Crb2 is a cell polarity-related type I transmembrane protein expressed in the apical membrane of podocytes. Knockdown of crb2 causes glomerular permeability defects in zebrafish, and its complete knockout causes embryonic lethality in mice. There are also reports of Crb2 mutations in patients with steroid-resistant nephrotic syndrome, although the precise mechanism is unclear. The present study demonstrated that podocyte-specific Crb2 knockout mice develop massive albuminuria and microhematuria 2-month after birth and focal segmental glomerulosclerosis and tubulointerstitial fibrosis with hemosiderin-laden macrophages at 6-month of age. Transmission and scanning electron microscopic studies demonstrated injury and foot process effacement of podocytes in 6-month aged podocyte-specific Crb2 knockout mice. The number of glomerular Wt1-positive cells and the expressions of Nphs2, Podxl, and Nphs1 were reduced in podocyte-specific Crb2 knockout mice compared to negative control mice. Human podocytes lacking CRB2 had significantly decreased F-actin positive area and were more susceptible to apoptosis than their wild-type counterparts. Overall, this study's results suggest that the specific deprivation of Crb2 in podocytes induces altered actin cytoskeleton reorganization associated with dysfunction and accelerated apoptosis of podocytes that ultimately cause focal segmental glomerulosclerosis.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 572 ; 616
    Sprache Englisch
    Erscheinungsdatum 2021-10-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Gap junction protein beta 4 plays an important role in cardiac function in humans, rodents, and zebrafish.

    Ryuji Okamoto / Itaru Goto / Yuhei Nishimura / Issei Kobayashi / Ryotaro Hashizume / Yoshinori Yoshida / Rie Ito / Yuhko Kobayashi / Misato Nishikawa / Yusuf Ali / Shunsuke Saito / Toshio Tanaka / Yoshiki Sawa / Masaaki Ito / Kaoru Dohi

    PLoS ONE, Vol 15, Iss 10, p e

    2020  Band 0240129

    Abstract: Aims GJB4 encodes a transmembrane connexin protein (Cx30.3) that is a component of gap junctions. This study investigated whether GJB4 plays an important role in human heart disease and function. Methods and results We examined a patient and her older ... ...

    Abstract Aims GJB4 encodes a transmembrane connexin protein (Cx30.3) that is a component of gap junctions. This study investigated whether GJB4 plays an important role in human heart disease and function. Methods and results We examined a patient and her older brother who both presented with complicated severe hypertrophic cardiomyopathy (HCM) and whose parents are healthy married cousins. The gene exome analysis showed 340 single nucleotide polymorphisms (SNPs) that caused amino acid changes for which the patient was homozygous and both parents were heterozygous. After excluding all known common (>10%) SNP gene mutations, the gene for GJB4 was the only identified gene that is possibly associated with cardiac muscle. The resultant E204A substitution exists in the 4th transmembrane domain. GJB4-E204A impaired the binding with gap junction protein A1 (GJA1) compared with GJB4-WT. The expression of GJB4 was induced in rat disease models of left and right ventricle hypertrophy and mouse disease models of adriamycin-induced cardiomyopathy and myocardial infarction, while it was not detected at all in control. An immunohistochemical study was performed for autopsied human hearts and the explanted heart of the patient. GJB4 was expressed and colocalized with GJA1 in intercalated discs in human diseased hearts, which was extensively enhanced in the explanted heart of the patient. The abnormal expression and localization of GJB4 were observed in beating spheres of patient's induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs). We generated knockout zebrafish of GJB4 by CRISPR/Cas9 and the endodiastolic volume and the ventricular ejection fraction were significantly lower in GJB4-deficient than in wild-type zebrafish at five days post-fertilization. Conclusions These results indicate both that GJB4 is defined as a new connexin in diseased hearts, of which mutation can cause a familial form of HCM, and that GJB4 may be a new target for the treatment of cardiac hypertrophy and dysfunction.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2020-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Data on correlation between CT-derived and MRI-derived myocardial extracellular volume

    Yoshie Kurita / Kakuya Kitagawa / Yusuke Kurobe / Shiro Nakamori / Hiroshi Nakajima / Kaoru Dohi / Masaaki Ito / Hajime Sakuma

    Data in Brief, Vol 7, Iss , Pp 1045-

    2016  Band 1047

    Abstract: This article describes data related to a research article titled “Estimation of myocardial extracellular volume fraction with cardiac CT in subjects without clinical coronary artery disease: A feasibility study”, Kurita et al. (in press) [1]. Myocardial ... ...

    Abstract This article describes data related to a research article titled “Estimation of myocardial extracellular volume fraction with cardiac CT in subjects without clinical coronary artery disease: A feasibility study”, Kurita et al. (in press) [1]. Myocardial extracellular volume fraction (ECV) is an imaging biomarker that can elevate in various heart diseases. This article describes correlation between CT-derived and MRI-derived ECV in 24 myocardial segments in 8 patients. CT-derived ECV was obtained from pre-contrast and delayed-phase images acquired by using dual-source CT system. MRI-derived ECV was obtained by using modified Look-Locker inversion recovery sequence implemented on a 3 T MRI system.
    Schlagwörter Computer applications to medicine. Medical informatics ; R858-859.7 ; Science (General) ; Q1-390
    Sprache Englisch
    Erscheinungsdatum 2016-06-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: New Isoform of Cardiac Myosin Light Chain Kinase and the Role of Cardiac Myosin Phosphorylation in α1-Adrenoceptor Mediated Inotropic Response.

    Masaya Taniguchi / Ryuji Okamoto / Masaaki Ito / Itaru Goto / Satoshi Fujita / Katsuhisa Konishi / Hideo Mizutani / Kaoru Dohi / David J Hartshorne / Takeo Itoh

    PLoS ONE, Vol 10, Iss 10, p e

    2015  Band 0141130

    Abstract: Cardiac myosin light chain kinase (cMLCK) plays an obligatory role in maintaining the phosphorylation levels of regulatory myosin light chain (MLC2), which is thought to be crucial for regulation of cardiac function. To test this hypothesis, the role ... ...

    Abstract Cardiac myosin light chain kinase (cMLCK) plays an obligatory role in maintaining the phosphorylation levels of regulatory myosin light chain (MLC2), which is thought to be crucial for regulation of cardiac function. To test this hypothesis, the role played by ventricular MLC2 (MLC2v) phosphorylation was investigated in the phenylephrine-induced increase in twitch tension using the naturally-occurring mouse strain, C57BL/6N, in which cMLCK is down regulated.By Western blot and nanoLC-MS/MS analysis, cMLCKs with molecular mass of 61-kDa (cMLCK-2) and/or 86-kDa were identified in mice heart. Among various mouse strains, C57BL/6N expressed cMLCK-2 alone and the closest relative strain C57BL/6J expressed both cMLCKs. The levels of MLC2v phosphorylation was significantly lower in C57BL/6N than in C57BL/6J. The papillary muscle twitch tension induced by electrical field stimulation was smaller in C57BL/6N than C57BL/6J. Phenylephrine had no effect on MLC2v phosphorylation in either strains but increased the twitch tension more potently in C57BL/6J than in C57BL/6N. Calyculin A increased papillary muscle MLC2v phosphorylation to a similar extent in both strains but increased the phenylephrine-induced inotropic response only in C57BL/6N. There was a significant positive correlation between the phenylephrine-induced inotropic response and the levels of MLC2v phosphorylation within ranges of 15-30%.We identified a new isoform of cMLCK with a molecular mass of 61kDa(cMLCK-2) in mouse heart. In the C57BL/6N strain, only cMLCK-2 was expressed and the basal MLC2v phosphorylation levels and the phenylephrine-induced inotropic response were both smaller. We suggest that a lower phenylephrine-induced inotropic response may be caused by the lower basal MLC2v phosphorylation levels in this strain.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 571
    Sprache Englisch
    Erscheinungsdatum 2015-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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