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  1. Article ; Online: Pre-B cell colony enhancing factor (PBEF/NAMPT/Visfatin) and vascular endothelial growth factor (VEGF) cooperate to increase the permeability of the human placental amnion.

    Astern, J M / Collier, A C / Kendal-Wright, C E

    Placenta

    2012  Volume 34, Issue 1, Page(s) 42–49

    Abstract: Fluid efflux across the region of the amnion overlying the placenta is an essential component of the intramembranous absorption pathway that maintains amniotic fluid volume homeostasis. Dysregulation of this pathway may result in adverse pregnancy ... ...

    Abstract Fluid efflux across the region of the amnion overlying the placenta is an essential component of the intramembranous absorption pathway that maintains amniotic fluid volume homeostasis. Dysregulation of this pathway may result in adverse pregnancy outcomes, however the factors controlling amnion permeability are unknown. Here, we report a novel mechanism that increases placental amnion permeability. Pre-B Cell Colony Enhancing Factor (PBEF) is a stress-responsive cytokine expressed by the human amnion, and is known to induce Vascular Endothelial Growth Factor (VEGF) production by other cell types. Interestingly, VEGF is up-regulated in the ovine amnion when intramembranous absorption is augmented. In this study, we show that PBEF induced VEGF secretion by primary human amniotic epithelial cells (AEC) derived from the placental amnion, as well as from the reflected amnion that lines the remainder of the gestational sac. Further, PBEF treatment led to the increased expression of VEGFR2 in placental AEC, but not reflected AEC. To test the hypothesis that PBEF and VEGF increase placental amnion permeability, we monitored the transfer of 2',7'-dichlorofluorescein (DCF) from the fetal to the maternal side of human amnion explants. A treatment regimen including both PBEF and VEGF increased the rate of DCF transfer across the placental amnion, but not the reflected amnion. In summary, our results suggest that by augmenting VEGFR2 expression in the placental amnion, PBEF primes the tissue for a VEGF-mediated increase in permeability. This mechanism may have important implications in amniotic fluid volume control throughout gestation.
    MeSH term(s) Amnion/cytology ; Amnion/drug effects ; Amnion/metabolism ; Cell Membrane Permeability/drug effects ; Cells, Cultured ; Cytokines/pharmacology ; Cytokines/physiology ; Drug Synergism ; Female ; Humans ; Nicotinamide Phosphoribosyltransferase/pharmacology ; Nicotinamide Phosphoribosyltransferase/physiology ; Placenta/cytology ; Placenta/drug effects ; Placenta/metabolism ; Pregnancy ; Primary Cell Culture ; Recombinant Proteins/pharmacology ; Up-Regulation/drug effects ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor A/pharmacology ; Vascular Endothelial Growth Factor A/physiology ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Vascular Endothelial Growth Factor Receptor-2/physiology
    Chemical Substances Cytokines ; Recombinant Proteins ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Nicotinamide Phosphoribosyltransferase (EC 2.4.2.12) ; nicotinamide phosphoribosyltransferase, human (EC 2.4.2.12) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
    Language English
    Publishing date 2012-11-12
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603951-0
    ISSN 1532-3102 ; 0143-4004
    ISSN (online) 1532-3102
    ISSN 0143-4004
    DOI 10.1016/j.placenta.2012.10.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Prevalence of Antibodies to Zika Virus in Mothers from Hawaii Who Delivered Babies with and without Microcephaly between 2009-2012.

    Kumar, Mukesh / Ching, Lauren / Astern, Joshua / Lim, Eunjung / Stokes, Alexander J / Melish, Marian / Nerurkar, Vivek R

    PLoS neglected tropical diseases

    2016  Volume 10, Issue 12, Page(s) e0005262

    Abstract: Zika virus (ZIKV) is an emerging mosquito-borne pathogen. ZIKV infection is linked to the development of severe fetal abnormalities that include spontaneous abortion, stillbirth, hydranencephaly, and microcephaly. ZIKV outbreaks have been recorded in the ...

    Abstract Zika virus (ZIKV) is an emerging mosquito-borne pathogen. ZIKV infection is linked to the development of severe fetal abnormalities that include spontaneous abortion, stillbirth, hydranencephaly, and microcephaly. ZIKV outbreaks have been recorded in the United States. We recently demonstrated the first congenital ZIKV infection in the United States. In this study, we investigated archived blood samples from six mothers who gave birth to babies with microcephaly and 12 mothers who gave birth to healthy babies in Hawaii between 2009 and 2012. We tested maternal blood for the presence of ZIKV IgM and IgG antibodies using commercially available human ZIKV IgM and IgG ELISA kits. Blood from one mother who delivered babies with microcephaly tested positive for ZIKV IgM antibody (16.6%) and blood from three mothers tested positive for ZIKV IgG antibody (50%). ZIKV showed a trend toward significance with microcephaly. ZIKV IgG antibody positive mothers were more likely to deliver babies with microcephaly than mothers who were negative for ZIKV IgG antibodies (Odds ratio [OR] = 11.0, 95% confidence interval [CI] = 0.8-147.9, p = 0.083). Similarly, ZIKV IgM antibody positive mothers were also more likely to deliver babies with microcephaly than mothers who were negative for ZIKV IgM antibody (OR = 6.8, 95% CI = 0.2-195.1). These data provide further evidence of a link between ZIKV infection and microcephaly and suggests presence of ZIKV positive cases and associated microcephaly in the United States as early as 2009.
    MeSH term(s) Adult ; Antibodies, Viral/blood ; Blood Banks ; Enzyme-Linked Immunosorbent Assay ; Female ; Hawaii/epidemiology ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Microcephaly/etiology ; Microcephaly/immunology ; Microcephaly/virology ; Mothers ; Pregnancy ; Prevalence ; Young Adult ; Zika Virus/immunology ; Zika Virus Infection/complications ; Zika Virus Infection/epidemiology ; Zika Virus Infection/immunology ; Zika Virus Infection/virology
    Chemical Substances Antibodies, Viral ; Immunoglobulin G ; Immunoglobulin M
    Language English
    Publishing date 2016-12-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2727
    ISSN (online) 1935-2735
    ISSN 1935-2727
    DOI 10.1371/journal.pntd.0005262
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Medical school hotline: the research mission of the cell and molecular biology department and program at the john a. Burns school of medicine.

    Berry, Marla J / Astern, Joshua / Bellinger, Frederick / Brampton, Christopher / Cann, Rebecca / Gerschenson, Mariana / Haymer, David / James, Nicholas G / Jameson, David M / LeSaux, Olivier / Hoffmann, Peter R / Nichols, Robert / Pitts, Matthew / Seale, Lucia / Seifried, Steven / Stokes, Alexander J / Todorovic, Cedomir

    Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health

    2014  Volume 74, Issue 4, Page(s) 150–153

    MeSH term(s) Hawaii ; Humans ; Molecular Biology/education ; Molecular Biology/organization & administration ; Research/trends ; Schools, Medical/trends ; Universities/organization & administration
    Language English
    Publishing date 2014-11-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2653459-9
    ISSN 2165-8242 ; 2165-8218
    ISSN (online) 2165-8242
    ISSN 2165-8218
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Myeloperoxidase interacts with endothelial cell-surface cytokeratin 1 and modulates bradykinin production by the plasma Kallikrein-Kinin system.

    Astern, Joshua M / Pendergraft, William F / Falk, Ronald J / Jennette, J Charles / Schmaier, Alvin H / Mahdi, Fakhri / Preston, Gloria A

    The American journal of pathology

    2007  Volume 171, Issue 1, Page(s) 349–360

    Abstract: During an inflammatory state, functional myeloperoxidase (MPO) is released into the vessel as a result of intravascular neutrophil degradation. One mechanism of resulting cellular injury involves endothelial internalization of MPO, which causes oxidative ...

    Abstract During an inflammatory state, functional myeloperoxidase (MPO) is released into the vessel as a result of intravascular neutrophil degradation. One mechanism of resulting cellular injury involves endothelial internalization of MPO, which causes oxidative damage and impairs endothelial signaling. We report the discovery of a protein that facilitates MPO internalization, cytokeratin 1 (CK1), identified using affinity chromatography and mass spectrometry. CK1 interacts with MPO in vitro, even in the presence of 100% human plasma, thus substantiating biological relevance. Immunofluorescent microscopy confirmed that MPO added to endothelial cells can co-localize with endogenously expressed CK1. CK1 acts as a scaffolding protein for the assembly of the vasoregulatory plasma kallikrein-kinin system; thus we explored whether MPO and high molecular weight kininogen (HK) reside on CK1 together or whether they compete for binding. The data support cooperative binding of MPO and HK on cells such that MPO masked the plasma kallikrein cleavage site on HK, and MPO-generated oxidants caused inactivation of both HK and kallikrein. Collectively, interactions between MPO and the components of the plasma kallikrein-kinin system resulted in decreased bradykinin production. This study identifies CK1 as a facilitator of MPO-mediated vascular responses and thus provides a new paradigm by which MPO affects vasoregulatory systems.
    MeSH term(s) Bradykinin/biosynthesis ; Carrier Proteins ; Cell Membrane/metabolism ; Cells, Cultured ; Endothelial Cells/metabolism ; Endothelial Cells/ultrastructure ; Endothelium, Vascular/metabolism ; Humans ; Kallikrein-Kinin System/physiology ; Keratin-1/metabolism ; Keratin-1/physiology ; Keratin-9/metabolism ; Kininogen, High-Molecular-Weight/metabolism ; Macromolecular Substances/metabolism ; Peroxidase/physiology
    Chemical Substances Carrier Proteins ; Keratin-1 ; Keratin-9 ; Kininogen, High-Molecular-Weight ; Macromolecular Substances ; Peroxidase (EC 1.11.1.7) ; Bradykinin (S8TIM42R2W)
    Language English
    Publishing date 2007-06-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.2353/ajpath.2007.060831
    Database MEDical Literature Analysis and Retrieval System OnLINE

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