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https://www.readbyqxmd.com/read/29454962/the-high-bone-mass-phenotype-of-lrp5-mutant-mice-is-not-affected-by-megakaryocyte-depletion
#1
Timur Yorgan, Jean-Pierre David, Michael Amling, Thorsten Schinke
Bone remodeling is a continuously ongoing process mediated by bone-resorbing osteoclasts and bone-forming osteoblasts. One key regulator of bone formation is the putative Wnt co-receptor Lrp5, where activating mutations in the extracellular domain cause increased bone formation in mice and humans. We have previously reported that megakaryocyte numbers are increased the bone marrow of mice carrying a high bone mass mutation (HBM) of Lrp5 (Lrp5G170V ). Since megakaryocytes can promote bone formation, we addressed the question, if the bone remodeling phenotype of Lrp5G170V mice is affected by megakaryocyte depletion...
February 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29448899/dietary-exposure-of-the-belgian-population-to-emulsifiers-e481-sodium-stearoyl-2-lactylate-and-e482-calcium-stearoyl-2-lactylate
#2
Sarah Bel, Thomas Struyf, Tine Fierens, Griet Jacobs, Christine Vinkx, Mia Bellemans, Stefan Voorspoels, Karin De Ridder
A dietary exposure assessment of food emulsifiers E481 (sodium stearoyl-2-lactylate) and E482 (calcium stearoyl-2-lactylate) in the Belgian population was performed. Nationally representative food consumption data from the Belgian National Food Consumption Surveys 2004 (BNFCS2004) and 2014 (BNFCS2014) were used for calculations. A conservative approach (combining individual food consumption data with the maximum permitted level (MPL) of foods (tier 2), was compared with more refined estimates (combining individual food consumption data with actual concentrations measured in food products available on the Belgian market (tier 3))...
February 15, 2018: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/29430853/nfix-promotes-survival-of-immature-hematopoietic-cells-via-regulation-of-c-mpl
#3
Trent Hall, Megan Walker, Miguel Ganuza, Per Holmfeldt, Marie Bordas, Guolian Kang, Wenjian Bi, Lance E Palmer, David Finkelstein, Shannon McKinney-Freeman
Hematopoietic stem and progenitor cells (HSPC) are necessary for life-long blood production and replenishment of the hematopoietic system during stress. We recently reported that nuclear factor I/X (Nfix) promotes HSPC survival post-transplant. Here, we report that ectopic expression of Nfix in primary mouse HSPCs extends their ex vivo culture from about 20 days to 40 days. HSPCs overexpressing Nfix display hypersensitivity to supportive cytokines and reduced apoptosis when subjected to cytokine deprivation relative to controls...
February 12, 2018: Stem Cells
https://www.readbyqxmd.com/read/29426921/the-2016-who-classification-and-diagnostic-criteria-for-myeloproliferative-neoplasms-document-summary-and-in-depth-discussion
#4
REVIEW
Tiziano Barbui, Jürgen Thiele, Heinz Gisslinger, Hans Michael Kvasnicka, Alessandro M Vannucchi, Paola Guglielmelli, Attilio Orazi, Ayalew Tefferi
The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable (MPN-U); of note, mastocytosis is no longer classified under the MPN category...
February 9, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29423036/salvaged-allogeneic-hematopoietic-stem-cell-transplantation-for-pediatric-chemotherapy-refractory-acute-leukemia
#5
Jingbo Wang, Lei Yuan, Haoyu Cheng, Xinhong Fei, Yumin Yin, Jiangying Gu, Song Xue, Junbao He, Fan Yang, Xiaocan Wang, Yixin Yang, Weijie Zhang
There is an ongoing debate concerning the performance of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute refractory leukemia, in whom the prognosis is quite dismal. Few studies have ever been conducted on this subject. This may be partly due to missed opportunities by majority of the patients in such situations. To investigate the feasibility, evaluate the efficiency, and identify the prognostic factors of allo-HSCT in this sub-setting, the authors performed a single institution-based retrospective analysis...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29411299/a-rare-calr-variant-mutation-and-a-review-of-calr-in-essential-thrombocythemia
#6
Robert Diep, Ara Metjian
Essential thrombocythemia (ET) is an indolent myeloproliferative neoplasm characterized by megakaryocyte hyperplasia, thrombocytosis, thrombotic and hemorrhagic complications, and potential transformation into myelofibrosis and acute myeloid leukemia. The vast majority of cases are driven by a somatic mutation in JAK2, CALR, or MPL. CALR, a gene that codes for the calcium-binding chaperone calreticulin, is the predominant mutation in patients with non-mutated JAK2 essential thrombocythemia, accounting for 20-25% of the overall somatic mutation frequency in ET...
February 6, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29399328/jak-inhibitors-for-the-treatment-of-myeloproliferative-neoplasms-and-other-disorders
#7
REVIEW
William Vainchenker, Emilie Leroy, Laure Gilles, Caroline Marty, Isabelle Plo, Stefan N Constantinescu
JAK inhibitors have been developed following the discovery of the JAK2 V617F in 2005 as the driver mutation of the majority of non- BCR-ABL1 myeloproliferative neoplasms (MPNs). Subsequently, the search for JAK2 inhibitors continued with the discovery that the other driver mutations ( CALR and MPL ) also exhibited persistent JAK2 activation. Several type I ATP-competitive JAK inhibitors with different specificities were assessed in clinical trials and exhibited minimal hematologic toxicity. Interestingly, these JAK inhibitors display potent anti-inflammatory activity...
2018: F1000Research
https://www.readbyqxmd.com/read/29397860/-advances-in-pathogenesis-of-essential-thrombocythemia-review
#8
Dian Zhou, Wei Chen, Kai-Lin Xu
Essential thrombocythemia(ET) is one of the Ph chromosome-negative myeloproliferative neoplasms. Some studies discovered that the mutation of JAK2 V617F existed in 50%-70% patients with ET. Recently, many significant advances in researches about pathogenesis of ET, such as mutations of JAK2V617F, MPL, CALR and other related mutation; the epigenetic abnomalities in incidence of ET; the changes of bone marrow microenvironment of ET and the regulation of related cytokines were obtained. In this article, the advances of above mentioned aspects of ET are summarized...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29390868/selected-parameters-of-angiogenesis-and-the-jak2-calr-and-mpl-mutations-in-patients-with-essential-thrombocythemia
#9
Grażyna Gadomska, Alicja Bartoszewska-Kubiak, Joanna Boinska, Karolina Matiakowska, Katarzyna Ziołkowska, Olga Haus, Danuta Rość
The aim of the study was to evaluate selected angiogenic factors in patients with essential thrombocythemia (ET) depending on JAK2V617F, calreticulin gene (CALR) and myeloproliferative leukemia virus oncogene (MPL) mutations. Sixty ET patients and 20 healthy volunteers were enrolled in the study. The following tests were performed: vascular endothelial growth factor- A (VEGF-A), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1),soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), platelet-derived growth factor( PDGF-BB), and stromal-derived factor-1α (SDF-1α)...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29361084/lactobacillus-brevis-kb290-with-vitamin-a-ameliorates-murine-intestinal-inflammation-associated-with-the-increase-of-cd11c-macrophage-cd103-dendritic-cell-ratio
#10
Nobuo Fuke, Tomohisa Takagi, Yasuki Higashimura, Toshifumi Tsuji, Ryohei Umeda, Katsura Mizushima, Makoto Tanaka, Hiroyuki Suganuma, Koichi Aizawa, Nobuhiro Yajima, Yuji Naito
Background: The ratio of colonic anti-inflammatory CD11c+ macrophages (MPs) to inflammatory CD103- dendritic cells (DCs) plays pivotal roles in intestinal inflammation. Little is known about how the ratio is regulated by lactic acid bacteria (LAB) and bifidobacteria (Bif). We investigated the contribution of LAB/Bif to this ratio. Methods: We established an in vitro experimental system using human myeloblastic KG-1 cells, which differentiate into CD11c+ MP-like (CD11c+ MPL) and CD103- DC-like (CD103- DCL) cells, and explored effective LAB/Bif strains...
January 18, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29344089/bone-marrow-failure-may-be-caused-by-chromosome-anomalies-exerting-effects-on-runx1t1-gene
#11
R Valli, L Vinti, A Frattini, M Fabbri, G Montalbano, C Olivieri, A Minelli, F Locatelli, F Pasquali, E Maserati
Background: The majority of the cases of bone marrow failure syndromes/aplastic anaemias (BMFS/AA) are non-hereditary and considered idiopathic (80-85%). The peripheral blood picture is variable, with anaemia, neutropenia and/or thrombocytopenia, and the patients with idiopathic BMFS/AA may have a risk of transformation into a myelodysplastic syndrome (MDS) and/or an acute myeloid leukaemia (AML), as ascertained for all inherited BMFS. We already reported four patients with different forms of BMFS/AA with chromosome anomalies as primary etiologic event: the chromosome changes exerted an effect on specific genes, namely RUNX1, MPL, and FLI1, leading to the disease...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29342439/review-of-ophthalmology-medical-professional-liability-claims-in-the-united-states-from-2006-through-2015
#12
Atalie C Thompson, P Divya Parikh, Eleonora M Lad
PURPOSE: To describe characteristics of closed medical professional liability (MPL) claims against ophthalmologists in the United States. DESIGN: Retrospective analysis of MPL claims from 2006-2015. Data were obtained from the Physician Insurers Association of America (PIAA) Data Sharing Project (DSP). Comparison was made between ophthalmology and all healthcare specialties for physician demographics, prevalence and costs associated with closed claims, and resolution of claims...
January 13, 2018: Ophthalmology
https://www.readbyqxmd.com/read/29333748/near-infrared-light-sensitive-polyvinyl-alcohol-hydrogel-photoresist-for-spatiotemporal-control-of-cell-instructive-3d-microenvironments
#13
Xiao-Hua Qin, Xiaopu Wang, Markus Rottmar, Bradley J Nelson, Katharina Maniura-Weber
Advanced hydrogel systems that allow precise control of cells and their 3D microenvironments are needed in tissue engineering, disease modeling, and drug screening. Multiphoton lithography (MPL) allows true 3D microfabrication of complex objects, but its biological application requires a cell-compatible hydrogel resist that is sufficiently photosensitive, cell-degradable, and permissive to support 3D cell growth. Here, an extremely photosensitive cell-responsive hydrogel composed of peptide-crosslinked polyvinyl alcohol (PVA) is designed to expand the biological applications of MPL...
January 15, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29328961/vaginal-delivery-related-changes-in-the-pelvic-organ-position-and-vaginal-cross-sectional-area-in-the-general-population
#14
Shotaro Naganawa, Eriko Maeda, Akifumi Hagiwara, Shiori Amemiya, Wataru Gonoi, Shouhei Hanaoka, Takeharu Yoshikawa, Kuni Ohtomo
PURPOSE: Evaluate the effect of vaginal delivery on pelvic organ positions and vaginal cross-sectional areas. METHODS: MRI of 119 premenopausal women were grouped according to the number of deliveries. The distances from the three 3-reference points (bladder, uterus, and rectum) to two 2-lines (pubococcygeal-line (PCL) and midpubic-line (MPL)), length of H- and M-lines and vaginal cross-sectional area were compared between the groups. RESULTS: With increasing parity, distance from the rectum to PCL tended to increase (nullipara vs...
December 15, 2017: Clinical Imaging
https://www.readbyqxmd.com/read/29325188/comparison-of-radiographic-measurements-of-the-femur-in-yorkshire-terriers-with-and-without-medial-patellar-luxation
#15
Michal Žilinčík, Marián Hluchý, Ladislav Takáč, Valent Ledecký
OBJECTIVE:  This article aimed to compare measurements of anatomical angles of the femurs, based on radiography, in Yorkshire Terriers without or with various grades of medial patellar luxation (MPL) based on radiography. METHODS:  The skeletally mature Yorkshire Terrier dogs without MPL and with various grades of MPL were included in this prospective study. Cases with other orthopaedic disorders were excluded. For inclusion of the dog, it was required that standardized digital radiographs of both femurs in craniocaudal and axial directions were available...
January 2018: Veterinary and Comparative Orthopaedics and Traumatology: V.C.O.T
https://www.readbyqxmd.com/read/29323541/development-of-a-targeted-next-generation-sequencing-assay-to-detect-diagnostically-relevant-mutations-of-jak2-calr-and-mpl-in-myeloproliferative-neoplasms
#16
Thomas Frawley, Cathal P O'Brien, Eibhlin Conneally, Elisabeth Vandenberghe, Melanie Percy, Stephen E Langabeer, Karl Haslam
BACKGROUND: The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), consisting of polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a heterogeneous group of neoplasms that harbor driver mutations in the JAK2, CALR, and MPL genes. The detection of these mutations has been incorporated into the recent World Health Organization (WHO) diagnostic criteria for MPN. Given a pressing clinical need to screen for these mutations in a routine diagnostic setting, a targeted next-generation sequencing (NGS) assay for the detection of MPN-associated mutations located in JAK2 exon 14, JAK2 exon 12, CALR exon 9, and MPL exon 10 was developed to provide a single platform alternative to reflexive, stepwise diagnostic algorithms...
January 11, 2018: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29321520/essential-thrombocythemia-treatment-algorithm-2018
#17
REVIEW
Ayalew Tefferi, Alessandro M Vannucchi, Tiziano Barbui
Current drug therapy for myeloproliferative neoplasms, including essential thrombocythemia (ET) and polycythemia vera (PV), is neither curative nor has it been shown to prolong survival. Fortunately, prognosis in ET and PV is relatively good, with median survivals in younger patients estimated at 33 and 24 years, respectively. Therefore, when it comes to treatment in ET or PV, less is more and one should avoid exposing patients to new drugs that have not been shown to be disease-modifying, and whose long-term consequences are suspect (e...
January 10, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29313460/thrombopoietin-and-its-receptor-expression-in-pediatric-patients-with-chronic-immune-thrombocytopenia
#18
Shanshan Li, Jingbo Shao, Min Xia, Na Zhang, Jingwei Yang, Hong Li, Hui Jiang
OBJECTIVES: Chronic immune thrombocytopenia (cITP) is common in children. However, the pathogenesis has not been fully elucidated. This study aimed to determine whether thrombopoietin (TPO) and its receptor c-mannosylation of the TPO receptor (c-Mpl) have an impact on childhood cITP. METHODS: Sixty-four patients with newly diagnosed ITP (nITP), 64 patients with persistent ITP, 80 patients with cITP, and 64 healthy children (control) were enrolled in this study. Plasma TPO was measured with an ELISA, and c-Mpl was determined by flow cytometry...
January 9, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29306106/quantitative-assessment-of-jak2-v617f-and-calr-mutations-in-philadelphia-negative-myeloproliferative-neoplasms
#19
Ambrus Gángó, Réka Mózes, Zsófia Boha, Béla Kajtár, Botond Timár, Péter Attila Király, Richárd Kiss, Viktória Fésüs, Noémi Nagy, Judit Demeter, Gábor Körösmezey, Zita Borbényi, Imelda Marton, Anita Szőke, Tamás Masszi, Péter Farkas, Judit Várkonyi, Márk Plander, Éva Pósfai, Miklós Egyed, Katalin Pál, Gáspár Radványi, Aryan Hamed, Judit Csomor, András Matolcsy, Donát Alpár, Csaba Bödör
BACKGROUND: Philadelphia negative myeloproliferative neoplasms (MPNs) are characterized by frequent mutations of driver genes including JAK2, CALR and MPL. While the influence of JAK2 V617F mutant allele burden on the clinical phenotype of MPN patients is well-described, the impact of CALR mutant allele burden on clinical features needs further investigation. PATIENTS AND METHODS: Quantitative assessment of JAK2 and CALR mutations was performed on diagnostic DNA samples from 425 essential thrombocythemia (ET) and 227 primary myelofibrosis patients using real-time quantitative PCR and fragment length analysis...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29296963/novel-tpo-receptor-agonist-ta-316-contributes-to-platelet-biogenesis-from-human-ips-cells
#20
Ayako Aihara, Tomo Koike, Natsuki Abe, Sou Nakamura, Akira Sawaguchi, Takanori Nakamura, Naoshi Sugimoto, Hiromitsu Nakauchi, Taito Nishino, Koji Eto
Signaling by thrombopoietin (TPO) in complex with its receptor, c-MPL, is critical for hematopoietic stem cell (HSC) homeostasis and platelet generation. Here we show that TA-316, a novel chemically synthesized c-MPL agonist (CMA), is useful for ex vivo platelet generation from human-induced pluripotent stem (iPS) cell-derived immortalized megakaryocyte progenitor cell lines (imMKCLs). Moreover, the generation is clinically applicable, because self-renewal expansion and platelet release is tightly controllable...
February 28, 2017: Blood Advances
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