Read by QxMD icon Read


Fumihiko Katakura, Yuji Sugie, Kiyotaka Hayashi, Kohei Nishiya, Jiro Miyamae, Masaharu Okano, Teruyuki Nakanishi, Tadaaki Moritomo
The development of mammalian megakaryocytes and platelets is regulated by numerous cytokine signals, primarily through the thrombopoietin (TPO)/c-MPL axis. Although non-mammalian vertebrates are known to possess nucleated thrombocytes functionally equivalent to mammalian platelets, the dynamics of the thrombocyte development remains unclear. Here we identified TPO and a splice variant (TPO-v) caused by the intron retention in common carp (Cyprinus carpio). Both the tpo and its variant transcripts were highly expressed in heart and liver...
March 6, 2018: Developmental and Comparative Immunology
Xiaohong Ruby Xu, George M Yousef, Heyu Ni
Platelets have long been recognized as key players in hemostasis and thrombosis; however, growing evidence suggests that they are also significantly involved in cancer, the second leading cause of mortality worldwide. Preclinical and clinical studies showed that tumorigenesis and metastasis can be promoted by platelets through a wide variety of crosstalk between platelets and cancer cells. For example, cancer changes platelet behavior by directly inducing tumor-platelet aggregates, triggering platelet granule and extracellular vesicle release, altering platelet phenotype and platelet RNA profiles, and enhancing thrombopoiesis...
March 8, 2018: Blood
Asuka Sakata, Satoshi Nishimura
Bone imaging using multiphoton microscopy enables dynamic observation of platelet formation in living animals. Two-photon excitation microscopy is superior to confocal microscopy as it enables deeper tissue penetration, efficient light detection, and reduced phototoxicity. Using this microscopy approach, thrombopoiesis by megakaryocytes is clearly visualized in the skull at significant depth from the surface. Here we describe our microscopy setup and dye recipe for visualization of bone marrow in the mouse skull...
2018: Methods in Molecular Biology
M Salzmann, B Hoesel, M Haase, M Mussbacher, W C Schrottmaier, J B Kral-Pointner, M Finsterbusch, A Mazharian, A Assinger, J A Schmid
Transfusion of platelet concentrates represents an important treatment for various bleeding complications. However, the short half-life and frequent contaminations with bacteria restrict the availability of platelet concentrates and raise a clear demand for platelets generated ex vivo. Therefore, in vitro platelet generation from megakaryocytes represents an important research topic. A vital step for this process represents accurate analysis of thrombopoiesis and proplatelet formation, which is usually conducted manually...
February 20, 2018: Platelets
Lucia Sereni, Maria Carmina Castiello, Francesco Marangoni, Achille Anselmo, Dario di Silvestre, Sara Motta, Elena Draghici, Stefano Mantero, Adrian J Thrasher, Silvia Giliani, Alessandro Aiuti, Pierluigi Mauri, Luigi D Notarangelo, Marita Bosticardo, Anna Villa
BACKGROUND: Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by eczema, infections, and susceptibility to autoimmunity and malignancies. Thrombocytopenia is a constant finding, but its pathogenesis remains elusive. OBJECTIVE: To dissect the basis of the WAS platelet defect, we used a novel conditional mouse model (CoWas) lacking Wiskott-Aldrich syndrome protein (WASp) only in the megakaryocytic lineage in the presence of a normal immunologic environment, and in parallel we analyzed samples obtained from patients with WAS...
February 6, 2018: Journal of Allergy and Clinical Immunology
Cuicui Liu, Yiqing Yang, Dan Wu, Wenxia Zhang, Hongtao Wang, Pei Su, Jianfeng Yao, Chen Liang, Sizhou Feng, Mingzhe Han, Fuxu Wang, Erlie Jiang, Jiaxi Zhou
Prolonged isolated thrombocytopenia (PT) is a severe complication in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Whether the megakaryoctic potential of hematopoietic stem cells (HSCs) in bone marrow is intact and what factors drive the pathological process of PT remain elusive. A retrospective study in patients (n=285) receiving HSC transplantation revealed that the occurrence of PT was approximately 8% and the number of platelets and megakaryocytes in PT patients is much lower compared to the control...
January 31, 2018: Biology of Blood and Marrow Transplantation
Kuo-Ming Yu, Johnson Yiu-Nam Lau, Manson Fok, Yuk-Keung Yeung, Siu-Ping Fok, Suxing Zhang, Peizhen Ye, Kezhi Zhang, Xiaobo Li, Juan Li, Qin Xu, Wing-Tak Wong, Qui-Lim Choo
The mono-PEGylated recombinant human interleukin-11 (rhIL-11) was evaluated for its pharmacology and toxicology profile in non-human primates. This PEGylated IL-11 (PEG-IL11) showed a much prolonged circulating half-life of 67h in cynomolgus monkeys as compared to its un-PEGylated counterpart (~3h) through subcutaneous administration, implicating that a single injection of the recommended dose will effectively enhance thrombopoiesis in humans for a much longer period of time compared to rhIL-11 in humans (t1/2=6...
February 2, 2018: Toxicology and Applied Pharmacology
Yuan Kong, Min-Min Shi, Yuan-Yuan Zhang, Xie-Na Cao, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang
Prolonged isolated thrombocytopenia (PT) is a serious complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). According to murine studies, endothelial progenitor cells (EPCs) play a crucial role in the regulation of hematopoiesis and thrombopoiesis in the bone marrow (BM) microenvironment. We previously showed that the reduced frequency of BM EPCs was an independent risk factor for the occurrence of PT following allo-HSCT. However, the functional role of BM EPCs and methods to improve the impaired BM EPCs in PT patients are unknown...
February 2, 2018: American Journal of Hematology
Kansuke Koyama, Shinshu Katayama, Tomohiro Muronoi, Ken Tonai, Yuya Goto, Toshitaka Koinuma, Jun Shima, Shin Nunomiya
INTRODUCTION: The pathogenesis of thrombocytopenia in patients with sepsis is not fully understood. The aims of this study were to investigate changes in thrombopoietic activity over time by using absolute immature platelet counts (AIPC) and to examine the impact of platelet production on thrombocytopenia and mortality in patients with sepsis. METHODS: This retrospective observational study included adult patients with sepsis admitted to the intensive care unit at a university hospital...
2018: PloS One
Naohiro Miyashita, Masahiro Onozawa, Koji Hayasaka, Takahiro Yamada, Ohsuke Migita, Kenichiro Hata, Kohei Okada, Hideki Goto, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Takeshi Kondo, Shinji Kunishima, Takanori Teshima
We identified a novel heterozygous ITGB3 p.T720del mutation in a pedigree with macrothrombocytopenia exhibiting aggregation dysfunction. Platelet aggregation induced by ADP and collagen was significantly reduced, while ristocetin aggregation was normal. Integrin αIIbβ3 was partially activated in a resting status, but platelet expression of αIIbβ3 was downregulated. Functional analysis using a cell line showed spontaneous phosphorylation of FAK in αIIb/β3 (p.T720del)-transfected 293T cells in suspension conditions...
January 29, 2018: Annals of Hematology
Jose Perdomo, Feng Yan, Halina H L Leung, Beng H Chong
Platelet production occurs principally in the bone marrow in a process known as thrombopoiesis. During thrombopoiesis, hematopoietic progenitor cells differentiate to form platelet precursors called megakaryocytes, which terminally differentiate to release platelets from long cytoplasmic processes termed proplatelets. Megakaryocytes are rare cells confined to the bone marrow and are therefore difficult to harvest in sufficient numbers for laboratory use. Efficient production of human megakaryocytes can be achieved in vitro by culturing CD34+ cells under suitable conditions...
December 27, 2017: Journal of Visualized Experiments: JoVE
Hongtao Wang, Cuicui Liu, Xin Liu, Mengge Wang, Dan Wu, Jie Gao, Pei Su, Tatsutoshi Nakahata, Wen Zhou, Yuanfu Xu, Lihong Shi, Feng Ma, Jiaxi Zhou
Human pluripotent stem cells (hPSCs) provide an unlimited source for generating various kinds of functional blood cells. However, efficient strategies for generating large-scale functional blood cells from hPSCs are still lacking, and the mechanism underlying human hematopoiesis remains largely unknown. In this study, we identified myeloid ectopic viral integration site 1 homolog (MEIS1) as a crucial regulator of hPSC early hematopoietic differentiation. MEIS1 is vital for specification of APLNR+ mesoderm progenitors to functional hemogenic endothelial progenitors (HEPs), thereby controlling formation of hematopoietic progenitor cells (HPCs)...
January 17, 2018: Stem Cell Reports
Yun He, Lin-Lin Xu, Fei-Er Feng, Qian-Ming Wang, Xiao-Lu Zhu, Chen-Cong Wang, Jia-Min Zhang, Hai-Xia Fu, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Immune thrombocytopenia (ITP) is an autoimmune disease. Mesenchymal stem cells (MSCs) play important roles in the physiology and homeostasis of the haematopoietic system, including supporting megakaryocytic differentiation from CD34+ haematopoietic progenitor cells. Tumour necrosis factor alpha-induced protein 3 (TNFAIP3, also termed A20) plays a key role in terminating NF-κB signalling. Human genetic studies showed that the polymorphisms of the TNFAIP3 gene may contribute to ITP susceptibility. In this study, we showed a significant decrease in TNFAIP3 and increase in NF-κB/SMAD7 in ITP-MSCs...
January 12, 2018: British Journal of Haematology
Cédric Cleyrat, Romain Girard, Eun H Choi, Éric Jeziorski, Thierry Lavabre-Bertrand, Sylvie Hermouet, Serge Carillo, Bridget S Wilson
Thrombopoietin (Tpo) and its receptor (Mpl) are the principal regulators of early and late thrombopoiesis and hematopoietic stem cell maintenance. Mutations in MPL can drastically impair its function and be a contributing factor in multiple hematologic malignancies, including congenital amegakaryocytic thrombocytopenia (CAMT). CAMT is characterized by severe thrombocytopenia at birth, which progresses to bone marrow failure and pancytopenia. Here we report unique familial cases of CAMT that presented with a previously unreported MPL mutation: T814C (W272R) in the background of the activating MPL G117T (K39N or Baltimore) mutation...
September 26, 2017: Blood Advances
Anne Zufferey, Edwin R Speck, Kellie R Machlus, Rukhsana Aslam, Li Guo, Mark J McVey, Michael Kim, Rick Kapur, Eric Boilard, Joseph E Italiano, John W Semple
Megakaryocytes (MKs) are bone marrow-derived cells that are primarily responsible for generating platelets for the maintenance of hemostasis. Although MK can variably express major histocompatibility complex (MHC) class I and II molecules during their differentiation, little is known whether they can elicit nonhemostatic immune functions such as T-cell activation. Here, we demonstrate that mature CD34- MHC class II- CD41+ MKs can endocytose exogenous ovalbumin (OVA) and proteolytically generate its immunogenic peptide ligand, which is crosspresented on their surface in association with MHC class I molecules...
September 12, 2017: Blood Advances
Hiroshi Yoshida, Hajime Yamada, Wataru Nogami, Keiji Dohi, Tomomi Kurino-Yamada, Koji Sugiyama, Koji Takahashi, Yoshinari Gahara, Motoji Kitaura, Minoru Hasegawa, Itsuki Oshima, Kenji Kuwabara
Lusutrombopag (S-888711), an oral small-molecule thrombopoietin receptor (TPOR) agonist, has gained first approval as a drug to treat thrombocytopenia of chronic liver disease in patients undergoing elective invasive procedures in Japan. Preclinical studies were performed to evaluate its efficacy against megakaryopoiesis and thrombopoiesis. To investigate the proliferative activity and efficacy of megakaryocytic colony formation via human TPOR, lusutrombopag was applied to cultured human c-Mpl-expressing Ba/F3 (Ba/F3-hMpl) cells and human bone marrow-derived CD34-positive cells, respectively...
December 20, 2017: Experimental Hematology
Kuan-Hung Lin, Meng-Wei Li, Ya-Chi Chang, Yu-Nung Lin, Ya-Hsuan Ho, Wei-Chun Weng, Chang-Jen Huang, Bei-En Chang, Chao-Ling Yao, Hsinyu Lee
Lysophosphatidic acid (LPA) is a membrane-derived lysophospholipid that exists in the plasma and platelets. It exerts its functions through activation of various LPA receptors (LPARs), which belong to the family of G protein-coupled receptors. Activation of LPARs has important roles in stem cell differentiation. However, how LPA affects human hematopoietic stem cell (HSC) differentiation remains elusive. In our previous studies, we have suggested that LPA receptor 2 (LPA2 ) and LPA receptor 3 (LPA3 ) play opposing roles and may act as a molecular switch during megakaryocytic differentiation in K562 cells...
February 1, 2018: Stem Cells and Development
Ulrike Ratsch, Thorsten Kaiser, Holger Stepan, Alexander Jank
BACKGROUND: Bone marrow function in pregnancy is influencing blood cell concentration of platelets. The steady state of consumption, recovery and production of platelets is essential for coagulation and bleeding prevention. Reticulated platelets are an intermediate form of thrombocytes during thrombopoiesis representing platelet production. The immature platelet fraction (IPF) represents these platelets as percentage of all thrombocytes. Until now, there is little knowledge on IPF during pregnancy...
October 2017: Pregnancy Hypertension
Shilei Chen, Mengjia Hu, Mingqiang Shen, Yang Xu, Cheng Wang, Xinmiao Wang, Fengju Li, Dongfeng Zeng, Fang Chen, Gaomei Zhao, Mo Chen, Fengchao Wang, Tianmin Cheng, Yongping Su, Jinghong Zhao, Song Wang, Junping Wang
Dopamine (DA), a catecholamine neurotransmitter, is known to for its diverse roles on hematopoiesis, yet its function in thrombopoiesis remains poorly understood. This study shows that DA stimulation can directly induce platelet production from megakaryocytes (MKs) in the final stages of thrombopoiesis via a reactive oxygen species (ROS)-dependent pathway. The mechanism was suggested by the results that DA treatment could significantly elevate the ROS levels in MKs, and time-dependently activate oxidative stress-mediated signaling, including p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, and caspase-3 signaling pathways, while the antioxidants N-acetylcysteine and L-glutathione could effectively inhibit the activation of these signaling pathways, as well as the ROS increase and platelet production triggered by DA...
November 9, 2017: Platelets
Usman Ali, Gavin Knight, Roz Gibbs, Dimitris A Tsitsikas
BACKGROUND: Immature platelet fraction (IPF) estimation is a non-invasive and sensitive test that is available on recently introduced Sysmex XN-series of automated haematology analysers. It is a direct cellular indicator of thrombopoiesis. The aim of this study was to establish reference intervals for IPF, for both absolute (A-IPF) and percentage (%-IPF) measurements. MATERIAL AND METHODS: A total of 2366 samples that met the inclusion criteria were assayed for full blood count on the Sysmex XN-10 and a non-parametric percentile method was used for calculating the reference intervals...
November 9, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"