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Erythropoiesis

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https://www.readbyqxmd.com/read/28912177/rac1-functions-downstream-of-mir-142-in-regulation-of-erythropoiesis
#1
Natali Rivkin, Elik Chapnik, Yehudit Birger, Eran Yanowski, Caterina Curato, Alexander Mildner, Ziv Porat, Gail Amir, Shai Izraeli, Steffen Jung, Eran Hornstein
"-".
September 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28911146/anemia-in-patients-with-resistance-to-thyroid-hormone-%C3%AE-a-role-for-thyroid-hormone-receptor-%C3%AE-in-human-erythropoiesis
#2
Anja L M van Gucht, Marcel E Meima, Carla Moran, Maura Agostini, Anna Tylki-Szymanska, Malgorzata-Walasek Krajewska, Krystyna Chrzanowska, Alexandra Efthymiadou, Dionisios Chrysis, Korcan Demir, W Edward Visser, Theo J Visser, Krishna Chatterjee, Thamar B van Dijk, Robin P Peeters
Context: Patients with resistance to thyroid hormone (TH) α (RTHα) are characterized by growth retardation, macrocephaly, constipation, and abnormal thyroid function tests. In addition, almost all RTHα patients have mild anemia, the pathogenesis of which is unknown. Animal studies suggest an important role for TH and TH receptor (TR)α in erythropoiesis. Objective: To investigate whether a defect in TRα affects the maturation of red blood cells in RTHα patients...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28910278/defective-erythropoiesis-caused-by-mutations-of-the-thyroid-hormone-receptor-%C3%AE-gene
#3
Sunmi Park, Cho Rong Han, Jeong Won Park, Li Zhao, Xuguang Zhu, Mark Willingham, David M Bodine, Sheue-Yann Cheng
Patients with mutations of the THRA gene exhibit classical features of hypothyroidism, including erythroid disorders. We previously created a mutant mouse expressing a mutated TRα1 (denoted as PV; Thra1PV/+ mouse) that faithfully reproduces the classical hypothyroidism seen in patients. Using Thra1PV/+ mice, we explored how the TRα1PV mutant acted to cause abnormalities in erythropoiesis. Thra1PV/+ mice exhibited abnormal red blood cell indices similarly as reported for patients. The total bone marrow cells and erythrocytic progenitors were markedly reduced in the bone marrow of Thra1PV/+ mice...
September 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28904872/treatment-of-renal-anemia-erythropoiesis-stimulating-agents-and-beyond
#4
REVIEW
Patrick Biggar, Gheun-Ho Kim
Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10-11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events...
September 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28902958/nonregenerative-immune-mediated-anemia-associated-with-a-diffuse-large-b-cell-lymphoma-in-a-captive-jaguar-panthera-onca
#5
Monika A Keresztes, Manfred Henrich, Penelope Baloi, Sascha Gerst, Jens-Christian Rudnick, Judith Langenstein, Andreas Moritz, Natali Bauer
An 18-year-old male castrated jaguar (Panthera onca) was presented with anorexia and continuous bleeding from the oral cavity after a history of fighting with the partner animal. Clinical evaluation revealed ulcerating lesions on the gingiva and hard palate and a hematoma on the tongue. Computed tomography of the head and endoscopic examination of the esophagus and stomach were unremarkable. Hematology and clinical chemistry revealed severe nonregenerative anemia, mild thrombocytopenia, and moderate azotemia...
September 13, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28901048/administration-of-erythropoiesis-stimulating-agents-in-patients-undergoing-haemodialysis-a-time-and-motion-study
#6
David W Johnson, Bruce Cleland, Josette Eris, Tom Rafferty, Kamal Sud, Josephine S Chow
BACKGROUND: International guidelines recommend treatment of anaemia due to chronic kidney disease (CKD) with erythropoiesis-stimulating agents (ESAs). OBJECTIVE: To document the time required and the cost in terms of nursing time to prepare and administer ESAs to patients on facility based haemodialysis (HD) with anaemia due to CKD before and after the introduction of long-acting ESAs. DESIGN: A time and motion study was implemented at four HD units in Australia to determine the time and costs associated with preparing and administering ESAs before and after the introduction of long-acting ESAs...
September 12, 2017: Journal of Renal Care
https://www.readbyqxmd.com/read/28886314/alterations-on-high-hbf-levels-may-be-associated-with-klf1-gene-mutations
#7
M Aydin, E Rencuzogullari, S Bayram, Y Sevgiler, A Genc
The KLF1 gene synthesizes a transcription factor in the zinc finger structure that regulates the transcription of β-, γ-globin, and Foxm1 genes. This factor plays an important role in the erythropoiesis mechanism by modifying the chromatin structure and is involved in the regulation of transcription in the opening of the β-globin gene. β-globin gene expression could be disrupted by a mutation, which may be a possible cause of a disruption in regulation of the promotor of the β-globin gene where the KLF1 transcription factor binds...
August 30, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28885393/the-association-between-red-cell-distribution-width-erythropoietin-levels-and-coronary-artery-disease
#8
Yuanmin Li, Min Li, Yufang Teng, Chen Zhang, Qinghua Liu, Haifeng Hou
BACKGROUND: Red cell distribution width (RDW) is a cardiac marker for risk stratification and prognostic evaluation of coronary artery disease (CAD); however, the underlying mechanism remains unclear. Erythropoietin (EPO), a crucial factor affecting erythropoiesis, has been reported to be a protective molecule regulating the process of myocardial ischemia and relevant damage. No study has as yet reported the relationship between RDW and endogenous EPO in CAD patients. This cross-sectional study aimed to establish the association between endogenous EPO levels and increases in RDW in CAD patients...
September 6, 2017: Coronary Artery Disease
https://www.readbyqxmd.com/read/28881804/altered-erythropoiesis-and-decreased-number-of-erythrocytes-in-children-with-neuroblastoma
#9
Fabio Morandi, Sebastiano Barco, Sara Stigliani, Michela Croce, Luca Persico, Corrado Lagazio, Francesca Scuderi, Maria Luisa Belli, Mariapina Montera, Giuliana Cangemi, Sarah Pozzi, Valentina Rigo, Paola Scaruffi, Loredana Amoroso, Giovanni Erminio, Vito Pistoia, Silvano Ferrini, Maria Valeria Corrias
Neuroblastoma (NB) is a pediatric tumor presenting at diagnosis either as localized or metastatic disease, which mainly involves the bone marrow (BM). The physical occupancy of BM space by metastatic NB cells has been held responsible for impairment of BM function. Here, we investigated whether localized or metastatic NB may alter hematopoietic lineages' maturation and release of mature cells in the periphery, through gene expression profiling, analysis of BM smears, cell blood count and flow cytometry analysis...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880867/oral-tetrahydrouridine-and-decitabine-for-non-cytotoxic-epigenetic-gene-regulation-in-sickle-cell-disease-a-randomized-phase-1-study
#10
RANDOMIZED CONTROLLED TRIAL
Robert Molokie, Donald Lavelle, Michel Gowhari, Michael Pacini, Lani Krauz, Johara Hassan, Vinzon Ibanez, Maria A Ruiz, Kwok Peng Ng, Philip Woost, Tomas Radivoyevitch, Daisy Pacelli, Sherry Fada, Matthew Rump, Matthew Hsieh, John F Tisdale, James Jacobberger, Mitch Phelps, James Douglas Engel, Santhosh Saraf, Lewis L Hsu, Victor Gordeuk, Joseph DeSimone, Yogen Saunthararajah
BACKGROUND: Sickle cell disease (SCD), a congenital hemolytic anemia that exacts terrible global morbidity and mortality, is driven by polymerization of mutated sickle hemoglobin (HbS) in red blood cells (RBCs). Fetal hemoglobin (HbF) interferes with this polymerization, but HbF is epigenetically silenced from infancy onward by DNA methyltransferase 1 (DNMT1). METHODS AND FINDINGS: To pharmacologically re-induce HbF by DNMT1 inhibition, this first-in-human clinical trial (NCT01685515) combined 2 small molecules-decitabine to deplete DNMT1 and tetrahydrouridine (THU) to inhibit cytidine deaminase (CDA), the enzyme that otherwise rapidly deaminates/inactivates decitabine, severely limiting its half-life, tissue distribution, and oral bioavailability...
September 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28877957/identification-of-a-new-adtrp1-tfpi-regulatory-axis-for-the-specification-of-primitive-myelopoiesis-and-definitive-hematopoiesis
#11
Li Wang, Xiaojing Wang, Longfei Wang, Muhammad Yousaf, Jia Li, Mengxia Zuo, Zhongcheng Yang, Dongzhi Gou, Binghao Bao, Lei Li, Ning Xiang, Haibo Jia, Chengqi Xu, Qiuyun Chen, Qing Kenneth Wang
A genomic variant in the human ADTRP [androgen-dependent tissue factor (TF) pathway inhibitor (TFPI) regulating protein] gene increases the risk of coronary artery disease, the leading cause of death worldwide. TFPI is the TF pathway inhibitor that is involved in coagulation. Here, we report that adtrp and tfpi form a regulatory axis that specifies primitive myelopoiesis and definitive hematopoiesis, but not primitive erythropoiesis or vasculogenesis. In zebrafish, there are 2 paralogues for adtrp (i.e., adtrp1 and adtrp2)...
September 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28875480/erratum-to-rationale-and-design-of-observational-clinical-research-in-chronic-kidney-disease-patients-with-renal-anemia-renal-prognosis-in-patients-with-hyporesponsive-anemia-to-erythropoiesis-stimulating-agents-darbepoetin-alfa-brighten-trial
#12
Hideki Kato, Masaomi Nangaku, Hideki Hirakata, Takashi Wada, Terumasa Hayashi, Hiroshi Sato, Yasushi Yamazaki, Takao Masaki, Tatsuo Kagimura, Hiroyasu Yamamoto, Hiroki Hase, Masahiro Kamouchi, Enyu Imai, Kyoichi Mizuno, Manabu Iwasaki, Tadao Akizawa, Yoshiharu Tsubakihara, Shoichi Maruyama, Ichiei Narita
No abstract text is available yet for this article.
September 5, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28871174/erythropoietin-enhances-kupffer-cell-number-and-activity-in-the-challenged-liver
#13
Dafna Gilboa, Yasmin Haim-Ohana, Naamit Deshet-Unger, Nathalie Ben-Califa, Sahar Hiram-Bab, Debby Reuveni, Ehud Zigmond, Max Gassmann, Yankel Gabet, Chen Varol, Drorit Neumann
Erythropoietin (EPO) is the main hormone driving mammalian erythropoiesis, with activity mediated via the surface receptor, EPO-R, on erythroid progenitor cells. Recombinant human EPO is currently used clinically for the treatment of anemia in patients with end-stage renal disease, and in certain cancer patients suffering from anemia induced either by the tumor itself or by chemotherapy. EPO-R expression is also detected in non-erythroid cells, including macrophages present in the peritoneum, spleen, and bone marrow (BM)...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871148/editing-an-%C3%AE-globin-enhancer-in-primary-human-hematopoietic-stem-cells-as-a-treatment-for-%C3%AE-thalassemia
#14
Sachith Mettananda, Chris A Fisher, Deborah Hay, Mohsin Badat, Lynn Quek, Kevin Clark, Philip Hublitz, Damien Downes, Jon Kerry, Matthew Gosden, Jelena Telenius, Jackie A Sloane-Stanley, Paula Faustino, Andreia Coelho, Jessica Doondeea, Batchimeg Usukhbayar, Paul Sopp, Jacqueline A Sharpe, Jim R Hughes, Paresh Vyas, Richard J Gibbons, Douglas R Higgs
β-Thalassemia is one of the most common inherited anemias, with no effective cure for most patients. The pathophysiology reflects an imbalance between α- and β-globin chains with an excess of free α-globin chains causing ineffective erythropoiesis and hemolysis. When α-thalassemia is co-inherited with β-thalassemia, excess free α-globin chains are reduced significantly ameliorating the clinical severity. Here we demonstrate the use of CRISPR/Cas9 genome editing of primary human hematopoietic stem/progenitor (CD34+) cells to emulate a natural mutation, which deletes the MCS-R2 α-globin enhancer and causes α-thalassemia...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28870615/luspatercept-for-the-treatment-of-anaemia-in-patients-with-lower-risk-myelodysplastic-syndromes-pace-mds-a-multicentre-open-label-phase-2-dose-finding-study-with-long-term-extension-study
#15
Uwe Platzbecker, Ulrich Germing, Katharina S Götze, Philipp Kiewe, Karin Mayer, Jörg Chromik, Markus Radsak, Thomas Wolff, Xiaosha Zhang, Abderrahmane Laadem, Matthew L Sherman, Kenneth M Attie, Aristoteles Giagounidis
BACKGROUND: Myelodysplastic syndromes are characterised by ineffective erythropoiesis. Luspatercept (ACE-536) is a novel fusion protein that blocks transforming growth factor beta (TGF β) superfamily inhibitors of erythropoiesis, giving rise to a promising new investigative therapy. We aimed to assess the safety and efficacy of luspatercept in patients with anaemia due to lower-risk myelodysplastic syndromes. METHODS: In this phase 2, multicentre, open-label, dose-finding study (PACE-MDS), with long-term extension, eligible patients were aged 18 years or older, had International Prognostic Scoring System-defined low or intermediate 1 risk myelodysplastic syndromes or non-proliferative chronic myelomonocytic leukaemia (white blood cell count <13 000/μL), and had anaemia with or without red blood cell transfusion support...
September 1, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28869184/the-treatment-landscape-of-myelofibrosis-before-and-after-ruxolitinib-approval
#16
Andrew T Kuykendall, Chetasi Talati, Najla Al Ali, Kendra Sweet, Eric Padron, David A Sallman, Jeffrey E Lancet, Alan F List, Kenneth S Zuckerman, Rami S Komrokji
INTRODUCTION/BACKGROUND: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that presents with a heterogeneous clinical phenotype and prognosis. Before the US Food and Drug Administration approval of ruxolitinib, treatment options were varied and had limited effect. The increased use of ruxolitinib has drastically altered the MF treatment landscape. In this study, we aimed to clarify the clinical situations in which ruxolitinib is being used and analyze its effect on this landscape...
August 5, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28867537/thermal-injury-of-the-skin-induces-g-csf-dependent-attenuation-of-epo-mediated-stat-signaling-and-erythroid-differentiation-arrest-in-mice
#17
John G Noel, Benjamin J Ramser, Jose A Cancelas, Francis X McCormack, Jason C Gardner
Inflammation mediated impairment of erythropoiesis, plays a central role in the development of the anemia of critical illness (ACI). ACI develops despite elevation of endogenous erythropoietin (EPO), does not respond to exogenous EPO supplementation, and contributes significantly to transfusion requirements in burned patients. We have previously reported that the reduction of red blood cell mass in the bone marrow of a burn-injured ACI mouse model is G-CSF dependent. Given that elevated G-CSF levels have also been associated with lower hemoglobin levels and increased transfusion requirements in trauma victims, we postulated that G-CSF mediates post burn EPO resistance...
August 31, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28864822/hepcidin-is-regulated-by-promoter-associated-histone-acetylation-and-hdac3
#18
Sant-Rayn Pasricha, Pei Jin Lim, Tiago L Duarte, Carla Casu, Dorenda Oosterhuis, Katarzyna Mleczko-Sanecka, Maria Suciu, Ana Rita Da Silva, Kinda Al-Hourani, João Arezes, Kirsty McHugh, Sarah Gooding, Joe N Frost, Katherine Wray, Ana Santos, Graça Porto, Emmanouela Repapi, Nicki Gray, Simon J Draper, Neil Ashley, Elizabeth Soilleux, Peter Olinga, Martina U Muckenthaler, Jim R Hughes, Stefano Rivella, Thomas A Milne, Andrew E Armitage, Hal Drakesmith
Hepcidin regulates systemic iron homeostasis. Suppression of hepcidin expression occurs physiologically in iron deficiency and increased erythropoiesis but is pathologic in thalassemia and hemochromatosis. Here we show that epigenetic events govern hepcidin expression. Erythropoiesis and iron deficiency suppress hepcidin via erythroferrone-dependent and -independent mechanisms, respectively, in vivo, but both involve reversible loss of H3K9ac and H3K4me3 at the hepcidin locus. In vitro, pan-histone deacetylase inhibition elevates hepcidin expression, and in vivo maintains H3K9ac at hepcidin-associated chromatin and abrogates hepcidin suppression by erythropoietin, iron deficiency, thalassemia, and hemochromatosis...
September 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28864529/thyroid-hormone-receptor-beta-and-ncoa4-regulate-terminal-erythrocyte-differentiation
#19
Xiaofei Gao, Hsiang-Ying Lee, Wenbo Li, Randall Jeffrey Platt, M Inmaculada Barrasa, Qi Ma, Russell R Elmes, Michael G Rosenfeld, Harvey F Lodish
An effect of thyroid hormone (TH) on erythropoiesis has been known for more than a century but the molecular mechanism(s) by which TH affects red cell formation is still elusive. Here we demonstrate an essential role of TH during terminal human erythroid cell differentiation; specific depletion of TH from the culture medium completely blocked terminal erythroid differentiation and enucleation. Treatment with TRβ agonists stimulated premature erythroblast differentiation in vivo and alleviated anemic symptoms in a chronic anemia mouse model by regulating erythroid gene expression...
September 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28859237/cystathionine-%C3%AE-synthase-is-required-for-body-iron-homeostasis
#20
Yu-Fu Zhou, Xiao-Mei Wu, Gan Zhou, Ming-Dao Mu, Fa-Li Zhang, Fe-Mi Li, Christopher Qian, Fang Du, Wing-Ho Yung, Zhong-Ming Qian, Ya Ke
Cystathionine β-synthase (CBS) catalyzes the transsulfuration pathway and contributes, among other functions, to the generation of hydrogen sulfide (H2 S). In view of the exceptionally high expression of CBS in the liver and the common interleukin-6 (IL-6) pathway utilized in the regulatory systems of H2 S and hepcidin, we speculate that CBS is involved in body iron homeostasis. We found that CBS knock-out (CBS(-/-) ) mice exhibited anemia and a significant increase in iron content in the serum, liver, spleen and heart, along with severe damage to the liver, displaying a hemochromatosis-like phenotype...
August 31, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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