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https://www.readbyqxmd.com/read/27910913/loss-of-egfr-asap1-signaling-in-metastatic-and-unresectable-hepatoblastoma
#1
Sarangarajan Ranganathan, Mylarappa Ningappa, Chethan Ashokkumar, Brandon W Higgs, Jun Min, Qing Sun, Lori Schmitt, Shankar Subramaniam, Hakon Hakonarson, Rakesh Sindhi
Hepatoblastoma (HBL), the most common childhood liver cancer is cured with surgical resection after chemotherapy or with liver transplantation if local invasion and multifocality preclude resection. However, variable survival rates of 60-80% and debilitating chemotherapy sequelae argue for more informed treatment selection, which is not possible by grading the Wnt-β-catenin over activity present in most HBL tumors. A hypothesis-generating whole transcriptome analysis shows that HBL tumors removed at transplantation are enriched most for cancer signaling pathways which depend predominantly on epidermal growth factor (EGF) signaling, and to a lesser extent, on aberrant Wnt-β-catenin signaling...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905292/the-effect-of-iron-deficiency-on-the-temporal-changes-in-the-expression-of-genes-associated-with-fat-metabolism-in-the-pregnant-rat
#2
Susan M Hay, Harry J McArdle, Helen E Hayes, Valerie J Stevens, William D Rees
Iron is essential for the oxidative metabolism of lipids. Lipid metabolism changes during gestation to meet the requirements of the growing fetus and to prepare for lactation. The temporal effects of iron deficiency during gestation were studied in female rats fed complete or iron-deficient diets. Plasma triglycerides were elevated in the iron-deficient group throughout gestation. There were time-dependent changes in the triglyceride content of the maternal liver, falling at the midpoint of gestation and then increasing on d21...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27902356/luciferase-tagged-wild-type-and-tropism-deficient-mouse-cytomegaloviruses-reveal-early-dynamics-of-host-colonization-following-peripheral-challenge
#3
Helen Farrell, Martha Oliveira, Kate Macdonald, Joseph Yunis, Michael Mach, Kimberley Bruce, Philip Stevenson, Rhonda Cardin, Nicholas Davis-Poynter
Cytomegaloviruses (CMVs) establish persistent, systemic infections and cause disease by maternal-fetal transfer, suggesting that their dissemination is a key target for anti-viral intervention. Late clinical presentation has meant that human CMV dissemination is not well understood. Murine CMV provides a tractable model. Whole mouse imaging of virus-expressed luciferase has proved a useful way to track systemic infections. MCMV, in which the abundant lytic gene M78 was luciferase tagged via a self-cleaving peptide (M78-LUC), allowed serial, unbiased imaging of systemic and peripheral infection without significant virus attenuation...
October 26, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27895323/elevated-cyp2c19-expression-is-associated-with-depressive-symptoms-and-hippocampal-homeostasis-impairment
#4
M M Jukić, N Opel, J Ström, T Carrillo-Roa, S Miksys, M Novalen, A Renblom, S C Sim, E M Peñas-Lledó, P Courtet, A Llerena, B T Baune, D J de Quervain, A Papassotiropoulos, R F Tyndale, E B Binder, U Dannlowski, M Ingelman-Sundberg
The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and decrease in hippocampal volume and adult neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG strain as a tool for preclinical screening of new antidepressants and (3) provide an insight into the molecular underpinnings of the 2C19TG phenotype...
November 29, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27889769/immunohistochemical-heterogeneity-of-the-endothelium-of-blood-and-lymphatic-vessels-in-the-developing-human-liver-and-in-adulthood
#5
Ivan Nikolić, Vera Todorović, Aleksandar Petrović, Vladimir Petrović, Marko Jović, Jelena Vladičić, Nela Puškaš
The endothelium of liver sinusoids in relation to the endothelium of other blood vessels has specific antigen expression similar to the endothelium of lymphatic vessels. Bearing in mind that there is no consensus as to the period or intensity of the expression of certain antigens in the endothelium of blood and lymphatic vessels in the liver, the aim of our study was to immunohistochemically investigate the dynamic patterns of the expression of CD31, CD34, D2-40, and LYVE-1 antigens during liver development and in adulthood on paraffin tissue sections of human livers of 4 embryos, 38 fetuses, 6 neonates, and 6 adults...
November 26, 2016: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/27882948/the-non-canonical-wnt-receptor-ryk-regulates-hematopoietic-stem-cell-repopulation-in-part-by-controlling-proliferation-and-apoptosis
#6
Farbod Famili, Laura Garcia Perez, Brigitta Ae Naber, Jasprina N Noordermeer, Lee G Fradkin, Frank Jt Staal
The development of blood and immune cells requires strict control by various signaling pathways in order to regulate self-renewal, differentiation and apoptosis in stem and progenitor cells. Recent evidence indicates critical roles for the canonical and non-canonical Wnt pathways in hematopoiesis. The non-canonical Wnt pathway is important for establishment of cell polarity and cell migration and regulates apoptosis in the thymus. We here investigate the role of the non-canonical Wnt receptor Ryk in hematopoiesis and lymphoid development...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27880904/lyve1-marks-the-divergence-of-yolk-sac-definitive-hemogenic-endothelium-from-the-primitive-erythroid-lineage
#7
Lydia K Lee, Yasamine Ghorbanian, Wenyuan Wang, Yanling Wang, Yeon Joo Kim, Irving L Weissman, Matthew A Inlay, Hanna K A Mikkola
The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YS HSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880037/suppressed-erythropoietin-expression-in-a-nitrofen-induced-congenital-diaphragmatic-hernia
#8
Hajime Takayasu, Koki Hagiwara, Kouji Masumoto
BACKGROUND: Erythropoietin (EPO), an essential stimulator of erythropoiesis produced by the fetal liver, is important both in vascular remodeling and modulation of the endothelial response in the pulmonary vasculature. In addition, EPO guides alveolar development, along with retinoic acid (RA). EPO is a direct target of RA, and the retinoid pathway is altered in the nitrofen-induced congenital diaphragmatic hernia (CDH) model. In the present study, we tested the hypothesis that the synthesis of EPO is suppressed in a rat model of CDH...
November 23, 2016: Pediatric Pulmonology
https://www.readbyqxmd.com/read/27876094/nitric-oxide-has-contrasting-age-dependent-effects-on-the-functionality-of-murine-hematopoietic-stem-cells
#9
Sapana Jalnapurkar, Shweta Singh, Moirangthem Ranjita Devi, Lalita Limaye, Vaijayanti Kale
BACKGROUND: The success of hematopoietic stem cell (HSC) transplantation is dependent on the quality of the donor HSCs. Some sources of HSCs display reduced engraftment efficiency either because of inadequate number (e.g., fetal liver and cord blood), or age-related dysfunction (e.g. in older individuals). Therefore, use of pharmacological compounds to improve functionality of HSCs is a forefront research area in hematology. METHODS: Lineage negative (Lin(-)) cells isolated from murine bone marrow or sort-purified Lin(-)Sca-1(+)c-Kit(+)CD34(-) (LSK-CD34(-)) were treated with a nitric oxide donor, sodium nitroprusside (SNP)...
November 22, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27871472/an-immunohistochemical-study-of-placental-syncytiotrophoblasts-in-neonatal-hemochromatosis
#10
Aiko Shimono, Yuko Imoto, Haruhiko Sakamoto, Yoichi Chiba, Koichi Matsumoto, Machi Kawauchi, Takashi Kusaka, Hirokazu Tanaka, Toshiyuki Hata, Yoshio Kushida, Masaki Ueno
INTRODUCTION: Neonatal hemochromatosis (NH) is a rare neonatal disorder that results in liver cirrhosis with hemosiderin deposition in the liver and other organs, similarly to hereditary hemochromatosis. Excess iron is transferred from the mother to fetus through the placenta in NH. We examined the expression of iron metabolism-related substances in placental syncytiotrophoblasts (STB) by immunostaining to clarify how the transfer of iron through STB increases in NH. METHODS: Immunostaining was performed using formalin-fixed, paraffin-embedded sections of placentae from three NH cases, four gestational age-matched controls, and, depending on the antibody examined, five to seven full-term controls...
December 2016: Placenta
https://www.readbyqxmd.com/read/27867036/dna-methylation-dynamics-of-human-hematopoietic-stem-cell-differentiation
#11
Matthias Farlik, Florian Halbritter, Fabian Müller, Fizzah A Choudry, Peter Ebert, Johanna Klughammer, Samantha Farrow, Antonella Santoro, Valerio Ciaurro, Anthony Mathur, Rakesh Uppal, Hendrik G Stunnenberg, Willem H Ouwehand, Elisa Laurenti, Thomas Lengauer, Mattia Frontini, Christoph Bock
Hematopoietic stem cells give rise to all blood cells in a differentiation process that involves widespread epigenome remodeling. Here we present genome-wide reference maps of the associated DNA methylation dynamics. We used a meta-epigenomic approach that combines DNA methylation profiles across many small pools of cells and performed single-cell methylome sequencing to assess cell-to-cell heterogeneity. The resulting dataset identified characteristic differences between HSCs derived from fetal liver, cord blood, bone marrow, and peripheral blood...
November 16, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27859643/undernourishment-in-utero-and-hepatic-steatosis-in-later-life-a-potential-issue-in-japanese-people-a-review
#12
REVIEW
Hiroaki Itoh, Keiko Muramatsu-Kato, Urmi J Ferdous, Yukiko Kohmura-Kobayashi, Naohiro Kanayama
Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. The prevalence of NAFLD in Japan has nearly doubled in the last 10-15 years. Increasing evidence supports undernourishment in utero being causatively connected with the risk of NAFLD in later life. Low body mass index (BMI) has been common among Japanese women of childbearing age for several decades due to their strong desire to be thin. It is plausible that insufficient maternal energy intake by pregnant Japanese women may underlie the rapid increase in the prevalence of NAFLD in Japan...
November 16, 2016: Congenital Anomalies
https://www.readbyqxmd.com/read/27855487/transfer-of-therapeutic-genes-into-fetal-rhesus-monkeys-using-recombinant-adeno-associated-type-i-viral-vectors
#13
Thomas J Conlon, Cathryn S Mah, Christina A R Pacak, Mary B Rucker Henninger, Kirsten E Erger, Marda L Jorgensen, Charles C Lee, Alice F Tarantal, Barry J Byrne
Neuromuscular disorders such as Pompe disease (glycogen storage disease, type II), result in early and potentially irreversible cellular damage with a very limited opportunity for intervention in the newborn period. Pompe disease is due to deficiency in acid α-glucosidase (GAA) leading to lysosomal accumulation of glycogen in all cell types, abnormal myofibrillogenesis, respiratory insufficiency, neurological deficits, and reduced contractile function in striated muscle. Previous studies have shown that fetal delivery of recombinant adeno-associated virus (rAAV) encoding GAA to the peritoneal cavity of Gaa-/- mice resulted in high-level transduction of the diaphragm...
November 17, 2016: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/27853271/foetal-programming-by-methyl-donor-deficiency-produces-steato-hepatitis-in-rats-exposed-to-high-fat-diet
#14
Anaïs Bison, Aude Marchal-Bressenot, Zhen Li, Ilef Elamouri, Eva Feigerlova, Lu Peng, Remi Houlgatte, Bernard Beck, Gregory Pourié, Jean-Marc Alberto, Remy Umoret, Guillaume Conroy, Jean-Pierre Bronowicki, Jean-Louis Guéant, Rosa-Maria Guéant-Rodriguez
Non-alcoholic steatohepatitis (NASH) is a manifestation of metabolic syndrome, which emerges as a major public health problem. Deficiency in methyl donors (folate and vitamin B12) during gestation and lactation is frequent in humans and produces foetal programming effects of metabolic syndrome, with small birth weight and liver steatosis at day 21 (d21), in rat pups. We investigated the effects of fetal programming on liver of rats born from deficient mothers (iMDD) and subsequently subjected to normal diet after d21 and high fat diet (HF) after d50...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27848279/a-transcriptional-switch-point-during-hematopoietic-stem-and-progenitor-cell-ontogeny
#15
Daisuke Sugiyama, Anagha Joshi, Kasem Kulkeaw, Keai Sinn Tan, Tomoko Yokoo-Inoue, Chiyo Mizuochi-Yanagi, Kaori Yasuda, Atsushi Doi, Tadafumi Iino, Masayoshi Itoh, Sayaka Nagao-Sato, Kenzaburo Tani, Koichi Akashi, Yoshihide Hayashizaki, Harukazu Suzuki, Hideya Kawaji, Piero Carninci, Alistair R R Forrest
During mammalian embryogenesis, hematopoietic stem and progenitor cells (HSPCs) originate from mesoderm-derived endothelial cells in the aorta-gonad-mesonephros (AGM) region and placenta. Later, HSPCs expand in fetal liver and migrate to bone marrow shortly before birth. Understanding global transcriptional regulation governing HSPC emergence from embryonic stem/induced pluripotent stem cells is necessary to devise clinical applications, such as novel transplantation approaches. Here, to assess transcriptional dynamics during development, we performed cap analysis of gene expression (CAGE) on 10 developmental murine HSPC populations isolated from the AGM region, placenta, fetal liver and bone marrow and identified 15,681 transcripts across HSPC ontogeny...
November 16, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27847654/the-case-for-improved-interprofessional-care-fatal-analgesic-overdose-secondary-to-acute-dental-pain-during-pregnancy
#16
Sarah K Y Lee, Rocio B Quinonez, Alice Chuang, Stephanie M Munz, Darya Dabiri
Prenatal oral health extends beyond the oral cavity, impacting the general well-being of the pregnant patient and her fetus. This case report follows a 19-year-old pregnant female presenting with acute liver failure secondary to acetaminophen overdose for management of dental pain following extensive dental procedures. Through the course of her illness, the patient suffered adverse outcomes including fetal demise, acute kidney injury, spontaneous bacterial peritonitis, and septic shock before eventual death from multiple organ failure...
2016: Case Reports in Dentistry
https://www.readbyqxmd.com/read/27845231/streptozotocin-diabetes-increases-mrna-expression-of-ketogenic-enzymes-in-the-rat-heart
#17
George A Cook, Eduard N Lavrentyev, Kevin Pham, Edwards A Park
BACKGROUND: Diabetic cardiomyopathy develops in insulin-dependent diabetic patients who have no hypertension, cardiac hypertrophy or vascular disease. Diabetes increases cardiac fatty acid oxidation, but cardiac hypertrophy limits fatty acid oxidation. Here we examined effects of diabetes on gene expression in rat hearts. METHODS: We used oligonucleotide microarrays to examine effects of insulindependent diabetes in the rat heart. RTQ PCR confirmed results of microarrays...
November 11, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27832434/monitoring-of-venus-transgenic-cell-migration-during-pregnancy-in-non-transgenic-rabbits
#18
N Lipták, O I Hoffmann, A Kerekes, G Iski, D Ernszt, K Kvell, L Hiripi, Z Bősze
Cell transfer between mother and fetus were demonstrated previously in several species which possess haemochorial placenta (e.g. in humans, mice, rats, etc.). Here we report the assessment of fetal and maternal microchimerism in non-transgenic (non-TG) New Zealand white rabbits which were pregnant with transgenic (TG) fetuses and in non-TG newborns of TG does. The TG construct, including the Venus fluorophore cDNA driven by a ubiquitous cytomegalovirus enhancer, chicken ß-actin promoter (CAGGS), was previously integrated into the rabbit genome by Sleeping Beauty transposon system...
November 10, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27831662/loss-of-the-tgf-%C3%AE-effector-%C3%AE-2sp-promotes-genomic-instability
#19
Jian Chen, Vivek Shukla, Patrizia Farci, Jaclyn Andricovich, Wilma Jogunoori, Lawrence N Kwong, Lior H Katz, Kirti Shetty, Asif Rashid, Xiaoping Su, Jon White, Lei Li, Alan Yaoqi Wang, Boris Blechacz, Gottumukkala S Raju, Marta Davila, Bao-Ngoc Nguyen, John R Stroehlein, Junjie Chen, Sang Soo Kim, Heather Levin, Keigo Machida, Hidekazu Tsukamoto, Peter Michaely, Alexandros Tzatsos, Lopa Mishra
Exposure to genotoxins such as ethanol-derived acetaldehyde leads to DNA damage and liver injury, and promotes the development of cancer. We report here a major role for the TGF-β/Smad3 adaptor β2-Spectrin (β2SP, gene Sptbn1) in maintaining genomic stability following alcohol-induced DNA damage. β2SP supports DNA repair through β2SP-dependent activation of Fancd2, a core component of the Fanconi anemia complex. Loss of β2SP leads to decreased Fancd2 levels and sensitizes β2SP mutants to DNA damage by ethanol treatment, leading to phenotypes that closely resemble those observed in animals lacking both Aldh2 and Fancd2, and resemble human fetal alcohol syndrome...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27830561/report-on-liver-cell-transplantation-using-human-fetal-liver-cells
#20
Giada Pietrosi, Cinzia Chinnici
In an era of organ shortage, human fetuses donated after medically indicated abortion could be considered a potential liver donor for hepatic cell isolation. We investigated transplantation of fetal liver cells as a strategy to support liver functionality in end-stage liver disease. Here, we report our protocol of human fetal liver cells (hFLC) isolation in fetuses from 17 to 22 gestational weeks, and our clinical procedure of hFLC transplantation through the splenic artery.
2017: Methods in Molecular Biology
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