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https://www.readbyqxmd.com/read/28934563/hemophagocytic-lymphohistiocytosis
#1
Hanny Al-Samkari, Nancy Berliner
Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages resulting in hypercytokinemia and immunemediated injury of multiple organ systems. It is seen in both children and adults and is recognized as primary (driven by underlying genetic mutations that abolish critical proteins required for normal function of cytotoxic T cells and NK cells) or secondary (resulting from a malignant, infectious, or autoimmune stimulus without an identifiable underlying genetic trigger)...
September 13, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/28934507/a-comprehensive-cell-specific-microrna-catalogue-of-human-peripheral-blood
#2
Simonas Juzenas, Geetha Venkatesh, Matthias Hübenthal, Marc P Hoeppner, Zhipei Gracie Du, Maren Paulsen, Philip Rosenstiel, Philipp Senger, Martin Hofmann-Apitius, Andreas Keller, Limas Kupcinskas, Andre Franke, Georg Hemmrich-Stanisak
With this study, we provide a comprehensive reference dataset of detailed miRNA expression profiles from seven types of human peripheral blood cells (NK cells, B lymphocytes, cytotoxic T lymphocytes, T helper cells, monocytes, neutrophils and erythrocytes), serum, exosomes and whole blood. The peripheral blood cells from buffy coats were typed and sorted using FACS/MACS. The overall dataset was generated from 450 small RNA libraries using high-throughput sequencing. By employing a comprehensive bioinformatics and statistical analysis, we show that 3' trimming modifications as well as composition of 3' added non-templated nucleotides are distributed in a lineage-specific manner-the closer the hematopoietic progenitors are, the higher their similarities in sequence variation of the 3' end...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934481/automatic-identification-of-informative-regions-with-epigenomic-changes-associated-to-hematopoiesis
#3
Enrique Carrillo-de-Santa-Pau, David Juan, Vera Pancaldi, Felipe Were, Ignacio Martin-Subero, Daniel Rico, Alfonso Valencia
Hematopoiesis is one of the best characterized biological systems but the connection between chromatin changes and lineage differentiation is not yet well understood. We have developed a bioinformatic workflow to generate a chromatin space that allows to classify 42 human healthy blood epigenomes from the BLUEPRINT, NIH ROADMAP and ENCODE consortia by their cell type. This approach let us to distinguish different cells types based on their epigenomic profiles, thus recapitulating important aspects of human hematopoiesis...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934427/immunologic-profiling-of-human-metapneumovirus-for-the-development-of-targeted-immunotherapy
#4
Ifigeneia Tzannou, Sarah K Nicholas, Premal Lulla, Paibel I Aguayo-Hiraldo, Anisha Misra, Caridad A Martinez, Annette A Machado, Jordan S Orange, Pedro A Piedra, Juan F Vera, Ann M Leen
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934395/abnormal-polyamine-metabolism-is-unique-to-the-neuropathic-forms-of-mps-potential-for-biomarker-development-and-insight-into-pathogenesis
#5
Christian Hinderer, Nathan Katz, Jean-Pierre Louboutin, Peter Bell, Jakub Tolar, Paul J Orchard, Troy C Lund, Mohamad Nayal, Liwei Weng, Clementina Mesaros, Carolina F M de Souza, Amauri Dalla Corte, Roberto Giugliani, James M Wilson
The mucopolysaccharidoses (MPS) are rare genetic disorders marked by severe somatic and neurological symptoms. Development of treatments for the neurological manifestations of MPS has been hindered by the lack of objective measures of central nervous system disease burden. Identification of biomarkers for central nervous system disease in MPS patients would facilitate the evaluation of new agents in clinical trials. High throughput metabolite screening of cerebrospinal fluid (CSF) samples from a canine model of MPS I revealed a marked elevation of the polyamine, spermine, in affected animals, and gene therapy studies demonstrated that reduction of CSF spermine reflects correction of brain lesions in these animals...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934311/characteristics-and-risk-of-chronic-graft-versus-host-disease-of-liver-in-allogeneic-hematopoietic-stem-cell-transplant-recipients
#6
Chien-Ting Chen, Chun-Yu Liu, Yuan-Bin Yu, Chia-Jen Liu, Liang-Tsai Hsiao, Jyh-Pyng Gau, Tzeon-Jye Chiou, Jing-Hwang Liu, Yao-Chung Liu
Chronic graft-versus-host-disease (cGvHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among various organ-specific cGvHD, the cGvHD of liver is less well-characterized. In this study, we applied the National Institutes of Health 2014 scoring criteria of cGvHD to analyze a retrospective cohort of 362 allo-HSCT recipients focusing on cGvHD of liver. The overall incidence of liver cGvHD with a score of 3 by 1.5 years post-transplant was 5.8% (21/362). Poor outcome, in terms of overall survival (OS), were observed in patients with scores of 3 liver cGvHD, comparing to those with scores less than 3 (hazard ratio [HR] 2...
2017: PloS One
https://www.readbyqxmd.com/read/28934113/sphingosine-1-phosphate-signaling-and-its-pharmacological-modulation-in-allogeneic-hematopoietic-stem-cell-transplantation
#7
REVIEW
Philip Smith, Catherine O'Sullivan, Peter Gergely
Allogeneic haemopoietic stem cell transplantation (HSCT) is increasingly used to treat haematological malignant diseases via the graft-versus-leukaemia (GvL) or graft-versus-tumour effects. Although improvements in infectious disease prophylaxis, immunosuppressive treatments, supportive care, and molecular based tissue typing have contributed to enhanced outcomes, acute graft-versus-host disease and other transplant related complications still contribute to high mortality and significantly limit the more widespread use of HSCT...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28933777/generation-and-use-of-a-humanized-bone-marrow-ossicle-niche-for-hematopoietic-xenotransplantation-into-mice
#8
Andreas Reinisch, David Cruz Hernandez, Katharina Schallmoser, Ravindra Majeti
Xenotransplantation is frequently used to study normal and malignant hematopoiesis of human cells. However, conventional mouse xenotransplantation models lack essential human-specific bone-marrow (BM)-microenvironment-derived survival, proliferation, and self-renewal signals for engraftment of normal and malignant blood cells. As a consequence, many human leukemias and other hematologic disorders do not robustly engraft in these conventional models. Here, we describe a complete workflow for the generation of humanized ossicles with an accessible BM microenvironment that faithfully recapitulates normal BM niche morphology and function...
October 2017: Nature Protocols
https://www.readbyqxmd.com/read/28933643/economic-burden-following-allogeneic-hematopoietic-stem-cell-transplant-in-patients-with-diffuse-large-b-cell-lymphoma
#9
Richard T Maziarz, Yanni Hao, Annie Guerin, Genevieve Gauthier, Marjolaine Gauthier-Loiselle, Simu K Thomas, Lamis Eldjerou
This study describes short-term and long-term healthcare resource utilization (HRU) and costs following an allogeneic hematopoietic stem cell transplant (HSCT) in adult patients with diffuse large B-cell lymphoma (DLBCL) in a real-world setting. Among 101 patients with DLBCL receiving an allogeneic HSCT, HRU and direct healthcare costs for up to three years after the allogeneic HSCT are described. HRU and costs were substantial, with the most intensive HRU and highest healthcare costs observed during the first year after HSCT (38 inpatient days; 68 days with office visits and average healthcare costs of $455,741)...
September 21, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28931765/a-type-of-human-skin-dendritic-cell-marked-by-cd5-is-associated-with-the-development-of-inflammatory-skin-disease
#10
Daniel Korenfeld, Laurent Gorvel, Adiel Munk, Joshua Man, Andras Schaffer, Thomas Tung, Caroline Mann, Eynav Klechevsky
Dendritic cells (DCs) are important in regulating immunity and tolerance and consist of functionally distinct subsets that differentially regulate T lymphocyte function. The underlying basis for this subset specificity is lacking, particularly in humans, where the classification of tissue DCs is currently incomplete. Examination of healthy human epidermal Langerhans cells and dermal skin cells revealed a tissue CD5-expressing DC subtype. The CD5+ DCs were potent inducers of cytotoxic T cells and Th22 cells...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931624/the-first-wave-of-t-lymphopoiesis-in-zebrafish-arises-from-aorta-endothelium-independent-of-hematopoietic-stem-cells
#11
Ye Tian, Jin Xu, Shachuan Feng, Sicong He, Shizheng Zhao, Lu Zhu, Wan Jin, Yimei Dai, Lingfei Luo, Jianan Y Qu, Zilong Wen
T lymphocytes are key cellular components of the adaptive immune system and play a central role in cell-mediated immunity in vertebrates. Despite their heterogeneities, it is believed that all different types of T lymphocytes are generated exclusively via the differentiation of hematopoietic stem cells (HSCs). Using temporal-spatial resolved fate-mapping analysis and time-lapse imaging, here we show that the ventral endothelium in the zebrafish aorta-gonad-mesonephros and posterior blood island, the hematopoietic tissues previously known to generate HSCs and erythromyeloid progenitors, respectively, gives rise to a transient wave of T lymphopoiesis independent of HSCs...
September 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28931604/sublethal-total-body-irradiation-causes-long-term-deficits-in-thymus-function-by-reducing-lymphoid-progenitors
#12
Shiyun Xiao, Ivo D Shterev, Wen Zhang, Lauren Young, Jae-Hung Shieh, Malcolm Moore, Marcel van den Brink, Gregory D Sempowski, Nancy R Manley
Total body irradiation (TBI) damages hematopoietic cells in the bone marrow and thymus; however, the long-term effects of irradiation with aging remain unclear. In this study, we found that the impact of radiation on thymopoiesis in mice varied by sex and dose but, overall, thymopoiesis remained suppressed for ≥12 mo after a single exposure. Male and female mice showed a long-term dose-dependent reduction in thymic cKit(+) lymphoid progenitors that was maintained throughout life. Damage to hematopoietic stem cells (HSCs) in the bone marrow was dose dependent, with as little as 0...
September 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28931525/ectopic-ilt3-controls-bcr-dependent-activation-of-akt-in-b-cell-chronic-lymphocytic-leukemia
#13
Vanessa Zurli, Giuliana Wimmer, Francesca Cattaneo, Veronica Candi, Emanuele Cencini, Alessandro Gozzetti, Donatella Raspadori, Giuseppe Campoccia, Francesca Sanseviero, Monica Bocchia, Cosima Tatiana Baldari, Anna Kabanova
The high proportion of long-term non-progressors among chronic lymphocytic leukemia (CLL) patients suggests the existence of a regulatory network which restrains the proliferation of tumor B cells. The identification of molecular determinants composing such network is hence fundamental for our understanding of CLL pathogenesis. Based on our previous finding establishing a deficiency in the signaling adaptor p66Shc in CLL cells, we undertook to identify unique phenotypic traits caused by this defect. Here we show that a lack of p66Shc shapes the transcriptional profile of CLL cells and leads to an upregulation of the surface receptor ILT3, the immunoglobulin-like transcript 3 which is normally found on myeloid cells...
September 20, 2017: Blood
https://www.readbyqxmd.com/read/28931467/clinical-features-and-molecular-epidemiology-of-diarrheagenic-escherichia-coli-pathotypes-identified-by-fecal-gastrointestinal-multiplex-nucleic-acid-amplification-in-patients-with-cancer-and-diarrhea
#14
Andrew W Chao, Micah Bhatti, Herbert L DuPont, James P Nataro, Lily G Carlin, Pablo C Okhuysen
Diarrheagenic Escherichia coli (DEC) pathotypes with differing epidemiology and clinical features, are known causes of disease with worldwide occurrence. At a major cancer center in the U.S., we studied patients with cancer and diarrhea for whom a GI Biofire FilmArray multiplex GI panel (BFM) was performed. An enteropathogen was identified in 382 of 2017 (19%) samples distributed across 311 patients. Of these, 60/311(19%) were positive for DEC. Patients receiving hematopoietic stem cell transplants (HSCT) 29/60 (48%) or with a hematologic malignancy 17/60 (28%) accounted for the majority of DEC cases...
August 12, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28930976/detection-of-residual-donor-erythroid-progenitor-cells-after-hematopoietic-stem-cell-transplantation-for-patients-with-hemoglobinopathies
#15
Roman Crazzolara, Gabriele Kropshofer, Michael Steurer, Sieghart Sopper, Wolfgang Schwinger
The presence of incomplete chimerism is noted in a large proportion of patients following bone marrow transplant for thalassemia major or sickle cell disease. This observation has tremendous implications, as subsequent therapeutic immunomodulation strategies can improve clinical outcome. Conventionally, polymerase chain reaction-based analysis of short tandem repeats is used to identify chimerism in donor-derived blood cells. However, this method is restricted to nucleated cells and cannot distinguish between dissociated single-cell lineages...
September 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930689/integrating-enhancer-mechanisms-to-establish-a-hierarchical-blood-development-program
#16
Charu Mehta, Kirby D Johnson, Xin Gao, Irene M Ong, Koichi R Katsumura, Skye C McIver, Erik A Ranheim, Emery H Bresnick
Hematopoietic development requires the transcription factor GATA-2, and GATA-2 mutations cause diverse pathologies, including leukemia. GATA-2-regulated enhancers increase Gata2 expression in hematopoietic stem/progenitor cells and control hematopoiesis. The +9.5-kb enhancer activates transcription in endothelium and hematopoietic stem cells (HSCs), and its deletion abrogates HSC generation. The -77-kb enhancer activates transcription in myeloid progenitors, and its deletion impairs differentiation. Since +9...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930521/multifactorial-role-of-long-non-coding-rnas-lncrnas-in-hematopoiesis
#17
Muhammad Babar Khawar, Rabia Mehmood, Muddasir Hassan Abbasi, Nadeem Sheikh
  Human genome project unveiled that only 1.5.-2.0.% of the genome is protein coding. ENCODE and related studies showed that most part of the genome transcribed into RNAs, and most of them do not code for a functional proteins, hence the name non-coding RNAs (ncRNAs). ncRNAs are small ncRNAs (less than 200 nucleotides) and long ncRNAs (longer than 200 nucleotides up to 10 kb). They act as a direct link between highly ordered chromosome structures, gene expression and serve as a bridge between genome and chromatin modification complexes as guides, scaffolds, and decoys...
January 1, 2018: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28930024/enterovirus-d68-associated-acute-flaccid-myelitis-in-immunocompromised-woman-italy
#18
Emanuela Giombini, Martina Rueca, Walter Barberi, Anna Paola Iori, Maurizio Inghilleri, Concetta Castilletti, Paola Scognamiglio, Francesco Vairo, Giuseppe Ippolito, Maria Rosaria Capobianchi, Maria Beatrice Valli
In Italy in 2016, acute flaccid myelitis developed in a woman who had received a hematopoietic stem cell transplant. Enterovirus D68 viral genome was detected in respiratory and cerebrospinal fluid samples, and the viral protein 1 sequence clustered with lineage B3. Immunocompromised adults may be at risk for enterovirus D68-associated neurologic complications.
October 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28928957/update-on-umbilical-cord-blood-transplantation
#19
REVIEW
Karen Ballen
Allogeneic hematopoietic cell transplant is a curative procedure for many patients with leukemia, lymphoma, myelodysplasia, myeloproliferative neoplasms, and genetic disorders. Umbilical cord blood transplantation is a graft source for patients who do not have a matched donor in their family or in the unrelated registry. It is particularly difficult for Black, Hispanic, and White patients of non-Western European background to find fully matched adult volunteer donors. An estimated 700,000 umbilical cord blood units have been donated for public use, and over 40,000 umbilical cord blood transplantations have been performed...
2017: F1000Research
https://www.readbyqxmd.com/read/28928278/an-interview-with-george-daley
#20
Aidan Maartens
George Daley is Dean of the Faculty of Medicine, Professor of Biological Chemistry and Molecular Pharmacology, and Caroline Shields Walker Professor of Medicine at Harvard Medical School. A former Howard Hughes Medical Institute Investigator and President of the International Society for Stem Cell Research (ISSCR) from 2007-2008, his lab works on the biology and clinical application of stem cells, with a particular focus on hematopoiesis. He was awarded the Public Service Award at the ISSCR 2017 meeting in Boston, where we caught up with him to discuss his move from the lab to the clinic and back again, his quest to derive human hematopoietic stem cells in vitro, and his advocacy for science in uncertain political times...
September 15, 2017: Development
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