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https://www.readbyqxmd.com/read/28350984/autophagy-it-s-in-your-blood
#1
Sergei Doulatov, George Q Daley
Autophagy, a central pathway for cellular homeostasis, plays diverse roles in development, cancer, aging, and neurodegeneration. In a new report in Nature, Ho et al. (2017) show that autophagy is essential for maintaining the replicative quiescence of hematopoietic stem cells throughout life by limiting the number of active mitochondria.
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28350850/defective-bone-repair-in-mast-cell-deficient-cpa3cre-mice
#2
Jose Luis Ramirez-GarciaLuna, Daniel Chan, Robert Samberg, Mira Abou-Rjeili, Timothy H Wong, Ailian Li, Thorsten B Feyerabend, Hans-Reimer Rodewald, Janet E Henderson, Paul A Martineau
In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh) implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28350553/impact-of-allogeneic-hematopoietic-stem-cell-transplantation-on-the-hiv-reservoir-and-immune-response-in-three-hiv-infected-individuals
#3
K K Koelsch, T A Rasmussen, W J Hey-Nguyen, C Pearson, Y Xu, M Bailey, K H Marks, S C Sasson, M S Taylor, R Tantau, S Obeid, B Milner, C O Morrissey, A N Pinto, K Suzuki, M P Busch, S M Keating, P Kaiser, S Yukl, J K Wong, B M Hiener, S Palmer, J Zaunders, J J Post, D J Chan, S Avery, S T Milliken, A D Kelleher, S R Lewin, D A Cooper
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterisation of HIV infected patients undergoing HSCT is warranted. METHODS: We studied three patients who underwent HSCT after either reduced intensity conditioning or myeloablative conditioning regimen. We measured HIV antigens and antibodies (Ag/Ab), HIV specific CD4+ T cell responses, HIV RNA and DNA in plasma, peripheral blood mononuclear cells (PBMCs), isolated CD4+ T cells from peripheral blood and lymph node cells...
March 24, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28346882/determination-of-prodrug-treosulfan-and-its-biologically-active-monoepoxide-in-rat-plasma-liver-lungs-kidneys-muscle-and-brain-by-hplc-esi-ms-ms-method
#4
Michał Romański, Anna Kasprzyk, Artur Teżyk, Agnieszka Widerowska, Czesław Żaba, Franciszek Główka
A prodrug treosulfan (TREO) is currently investigated in clinical trials for conditioning prior to hematopoietic stem cell transplantation. Bioanalysis of TREO and its active derivatives, monoepoxide (S,S-EBDM) and diepoxide, in plasma and urine underlay the pharmacokinetic studies of these compounds but cannot explain an organ pharmacological action or toxicity. Recently, distribution of TREO and S,S-EBDM into brain, cerebrospinal fluid, and aqueous humor of the eye has been investigated in animal models and the obtained results presented clinical relevance...
March 18, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28346444/genetic-variants-associated-with-mosaic-y-chromosome-loss-highlight-cell-cycle-genes-and-overlap-with-cancer-susceptibility
#5
Daniel J Wright, Felix R Day, Nicola D Kerrison, Florian Zink, Alexia Cardona, Patrick Sulem, Deborah J Thompson, Svanhvit Sigurjonsdottir, Daniel F Gudbjartsson, Agnar Helgason, J Ross Chapman, Steve P Jackson, Claudia Langenberg, Nicholas J Wareham, Robert A Scott, Unnur Thorsteindottir, Ken K Ong, Kari Stefansson, John R B Perry
The Y chromosome is frequently lost in hematopoietic cells, which represents the most common somatic alteration in men. However, the mechanisms that regulate mosaic loss of chromosome Y (mLOY), and its clinical relevance, are unknown. We used genotype-array-intensity data and sequence reads from 85,542 men to identify 19 genomic regions (P < 5 × 10(-8)) that are associated with mLOY. Cumulatively, these loci also predicted X chromosome loss in women (n = 96,123; P = 4 × 10(-6)). Additional epigenome-wide methylation analyses using whole blood highlighted 36 differentially methylated sites associated with mLOY...
March 27, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28346419/evolving-concepts-in-prognostic-scoring-of-chronic-gvhd
#6
REVIEW
A Lazaryan, M Arora
Chronic GvHD (cGvHD) remains one of the most complex and challenging complications after allogeneic hematopoietic cell transplantation. Emerging knowledge about the clinical manifestations and associated organ involvement of cGvHD has led to the establishment of prognostic parameters for post-transplant survival among affected allograft recipients. Studies employing the pre-National Institutes of Health (NIH) consensus data on cGvHD incidence and its risks have led to development of the CIBMTR's cGvHD risk stratification, which serves as the most refined and validated prognostic tool for estimating survival of patients with cGvHD...
March 27, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28346418/first-experience-of-hematopoietic-stem-cell-transplantation-treatment-of-shwachman-diamond-syndrome-using-unaffected-hla-matched-sibling-donor-produced-through-preimplantation-hla-typing
#7
A A Isaev, R V Deev, A Kuliev, I L Plaxa, N V Stancheva, A S Borovkova, I V Potapov, E A Pomerantseva, A G Chogovadze, K Y Boyarsky, A E Semenenko, A V Mikhailov, K G Shevchenko, A V Prikhodko, S Rechitsky, O V Paina, I M Barchatov, L S Zubarovskaya, O Verlinsky, I Y Bozo, B V Afanasyev
The only proven cure for Shwachman-Diamond syndrome (SDS) bone marrow failure is allogeneic hematopoietic stem cell transplantation (HSCT). However HSCT with donors other than HLA-identical siblings is associated with high mortality and unfavorable prognosis. This paper presents the first experience of HSCT treatment of SDS using an unaffected HLA-identical sibling produced through preimplantation genetic diagnosis (PGD). The patient was a 6-year-old blood transfusion-dependent SDS baby girl with secondary myelodysplastic syndrome, for whom no HLA-identical donor was available...
March 27, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28346417/bacterial-bloodstream-infections-in-the-allogeneic-hematopoietic-cell-transplant-patient-new-considerations-for-a-persistent-nemesis
#8
REVIEW
C E Dandoy, M I Ardura, G A Papanicolaou, J J Auletta
Bacterial bloodstream infections (BSI) cause significant transplant-related morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). This manuscript reviews the risk factors for and the bacterial pathogens causing BSIs in allo-HCT recipients in the contemporary transplant period. In addition, it offers insight into emerging resistant pathogens and reviews clinical management considerations to treat and strategies to prevent BSIs in allo-HCT patients.Bone Marrow Transplantation advance online publication, 27 March 2017; doi:10...
March 27, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28346415/haplo-cord-transplantation-compared-to-haploidentical-transplantation-with-post-transplant-cyclophosphamide-in-patients-with-aml
#9
M Kwon, G Bautista, P Balsalobre, I Sánchez-Ortega, P Montesinos, A Bermúdez, A de Laiglesia, P Herrera, C Martin, K Humala, A Zabalza, M Torres, L Bento, L L Corral, I Heras, D Serrano, I Buño, J Anguita, C Regidor, R Duarte, R Cabrera, J Gayoso, J L Diez-Martin
For patients with AML, the best alternative donor remains to be defined. We analyze outcomes of patients who underwent myeloablative umbilical cord blood or haploidentical hemopoietic stem cell transplantation (HSCT) in Spain. Fifty-one patients underwent single umbilical cord blood transplantation supported by a third party donor (Haplo-Cord) between 1999 and 2012, and 36 patients received an haploidentical HSCT with post-transplant cyclophosphamide (PTCY-haplo) between 2012 and 2014 in GETH centers. The Haplo-Cord cohort included a higher proportion of patients with high disease risk index and use of TBI in the conditioning regimen, and hematopoietic cell transplantation-age Comorbidity Age Index was higher in PTCY-haplo patients...
March 27, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28346414/nivolumab-before-and-after-allogeneic-hematopoietic-cell-transplantation
#10
F Covut, R Pinto, B W Cooper, B Tomlinson, L Metheny, E Malek, H M Lazarus, M de Lima, P F Caimi
No abstract text is available yet for this article.
March 27, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28346229/clinical-efficacy-of-gene-modified-stem-cells-in-adenosine-deaminase-deficient-immunodeficiency
#11
Kit L Shaw, Elizabeth Garabedian, Suparna Mishra, Provaboti Barman, Alejandra Davila, Denise Carbonaro, Sally Shupien, Christopher Silvin, Sabine Geiger, Barbara Nowicki, E Monika Smogorzewska, Berkley Brown, Xiaoyan Wang, Satiro de Oliveira, Yeong Choi, Alan Ikeda, Dayna Terrazas, Pei-Yu Fu, Allen Yu, Beatriz Campo Fernandez, Aaron R Cooper, Barbara Engel, Greg Podsakoff, Arumugam Balamurugan, Stacie Anderson, Linda Muul, G Jayashree Jagadeesh, Neena Kapoor, John Tse, Theodore B Moore, Ken Purdy, Radha Rishi, Kathey Mohan, Suzanne Skoda-Smith, David Buchbinder, Roshini S Abraham, Andrew Scharenberg, Otto O Yang, Kenneth Cornetta, David Gjertson, Michael Hershfield, Rob Sokolic, Fabio Candotti, Donald B Kohn
BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS: Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345823/mutation-analysis-of-isocitrate-dehydrogenase-idh1-2-and-dna-methyltransferase-3a-dnmt3a-in-thai-patients-with-newly-diagnosed-acute-myeloid-leukemia
#12
Tanasan Sirirat, Suporn Chuncharunee, Pimjai Nipaluk, Teerapong Siriboonpiputtana, Takol Chareonsirisuthigul, Nittaya Limsuwannachot, Budsaba Rerkamnuaychoke
Acute myeloid leukemia (AML) is a clonal hematopoietic stem/progenitor cell disorder which features several genetic mutations. Recurrent genetic alterations identified in AML are recognized as causes of the disease, finding application as diagnostic, prognostic and monitoring markers, with potential use as targets for cancer therapy. Here, we performed a pyrosequencing technique to investigate common mutations of IDH1, IDH2 and DNMT3A in 81 newly diagnosed AML patients. The prevalences of IDH1, IDH2 and DNMT3A mutations were 6...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28345003/expansion-of-human-tregs-from-cryopreserved-umbilical-cord-blood-for-gmp-compliant-autologous-adoptive-cell-transfer-therapy
#13
Howard R Seay, Amy L Putnam, Judit Cserny, Amanda L Posgai, Emma H Rosenau, John R Wingard, Kate F Girard, Morey Kraus, Angela P Lares, Heather L Brown, Katherine S Brown, Kristi T Balavage, Leeana D Peters, Ashley N Bushdorf, Mark A Atkinson, Jeffrey A Bluestone, Michael J Haller, Todd M Brusko
Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344999/long-term-engraftment-and-fetal-globin-induction-upon-bcl11a-gene-editing-in-bone-marrow-derived-cd34-hematopoietic-stem-and-progenitor-cells
#14
Kai-Hsin Chang, Sarah E Smith, Timothy Sullivan, Kai Chen, Qianhe Zhou, Jason A West, Mei Liu, Yingchun Liu, Benjamin F Vieira, Chao Sun, Vu P Hong, Mingxuan Zhang, Xiao Yang, Andreas Reik, Fyodor D Urnov, Edward J Rebar, Michael C Holmes, Olivier Danos, Haiyan Jiang, Siyuan Tan
To develop an effective and sustainable cell therapy for sickle cell disease (SCD), we investigated the feasibility of targeted disruption of the BCL11A gene, either within exon 2 or at the GATAA motif in the intronic erythroid-specific enhancer, using zinc finger nucleases in human bone marrow (BM) CD34(+) hematopoietic stem and progenitor cells (HSPCs). Both targeting strategies upregulated fetal globin expression in erythroid cells to levels predicted to inhibit hemoglobin S polymerization. However, complete inactivation of BCL11A resulting from bi-allelic frameshift mutations in BCL11A exon 2 adversely affected erythroid enucleation...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344987/safe-and-effective-gene-therapy-for-murine-wiskott-aldrich-syndrome-using-an-insulated-lentiviral-vector
#15
Swati Singh, Iram Khan, Socheath Khim, Brenda Seymour, Karen Sommer, Matthew Wielgosz, Zachary Norgaard, Hans-Peter Kiem, Jennifer Adair, Denny Liggitt, Arthur Nienhuis, David J Rawlings
Wiskott-Aldrich syndrome (WAS) is a life-threatening immunodeficiency caused by mutations within the WAS gene. Viral gene therapy to restore WAS protein (WASp) expression in hematopoietic cells of patients with WAS has the potential to improve outcomes relative to the current standard of care, allogeneic bone marrow transplantation. However, the development of viral vectors that are both safe and effective has been problematic. While use of viral transcriptional promoters may increase the risk of insertional mutagenesis, cellular promoters may not achieve WASp expression levels necessary for optimal therapeutic effect...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344563/a-review-of-demographic-medical-and-treatment-variables-associated-with-health-related-quality-of-life-hrqol-in-survivors-of-hematopoietic-stem-cell-hsct-and-bone-marrow-transplantation-bmt-during-childhood
#16
REVIEW
Trude Reinfjell, Marta Tremolada, Lonnie K Zeltzer
Hematopoietic stem cell transplantation (HSCT) is a standard treatment after disease relapse and failure of conventional treatments for cancer in childhood or as a first line treatment for some high-risk cancers. Since hematopoietic stem cells can be found in the marrow (previously called a bone marrow transplantation) or periphery, we refer to HSCT as inclusive of HSCT regardless of the origin of the stem cells. HSCT is associated with adverse side effects, prolonged hospitalization, and isolation. Previous studies have shown that survivors of HSCT are at particularly high risk for developing late effects and medical complications, and thus, in addition to survival, quality of life in survivors of HSCT is an important outcome...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28344059/gastrointestinal-toxicity-systemic-inflammation-and-liver-biochemistry-in-allogeneic-haematological-stem-cell-transplantation
#17
K Jordan, P Pontoppidan, H Uhlving, K Kielsen, D G Burrin, S Weichendorff, I J Christensen, M H Jørgensen, C Heilmann, H Sengeløv, K Müller
INTRODUCTION: Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity and levels of immune regulating cytokines during the early post-transplant period. METHODS: We prospectively included 81 children and adults undergoing HSCT after myeloablative conditioning...
March 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28344057/ruxolitinib-as-salvage-therapy-in-steroid-refractory-acute-graft-versus-host-disease-in-pediatric-hematopoietic-stem-cell-transplant-patients
#18
Pooja Khandelwal, Ashley Teusink-Cross, Adam S Nelson, Christopher E Dandoy, Javier El-Bietar, Rebecca A Marsh, Ashish R Kumar, Michael S Grimley, Stella M Davies, Sonata Jodele, Kasiani C Myers
We describe our retrospective clinical experience with ruxolitinib for steroid-refractory acute graft versus host disease (GVHD) in pediatric allogeneic hematopoietic stem cell transplant (HSCT) patients. Ruxolitinib was administered orally at 5 mg twice daily for children ≥ 25 kg or 2.5 mg twice daily if < 25 kg. We excluded patients who received new immune suppressive agents within two weeks before initiation of ruxolitinib from response analysis. Patients were called a treatment failure if ruxolitinib was stopped before completion of 4 weeks of therapy due to adverse effects and not because of progression of acute GVHD...
March 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28343776/a-effective-dna-vaccine-against-diverse-genotype-j-infectious-hematopoietic-necrosis-virus-strains-prevalent-in-china
#19
Liming Xu, Jingzhuang Zhao, Miao Liu, Gael Kurath, Guangming Ren, Scott E Lapatra, Jiasheng Yin, Hongbai Liu, Jian Feng, Tongyan Lu
Infectious hematopoietic necrosis virus (IHNV) is the most important pathogen threatening the aquaculture of salmonid fish in China. In this study, a DNA vaccine, designated pIHNch-G, was constructed with the glycoprotein (G) gene of a Chinese IHNV isolate SD-12 (also called Sn1203) of genotype J. The minimal dose of vaccine required, the expression of the Mx-1 gene in the muscle (vaccine delivery site) and anterior kidney, and the titers of the neutralizing antibodies produced were used to evaluate the vaccine efficacy...
March 23, 2017: Vaccine
https://www.readbyqxmd.com/read/28342908/intestinal-dendritic-cell-licensing-through-tlr4-is-required-for-oral-tolerance-in-allergic-contact-dermatitis
#20
Feriel Hacini-Rachinel, Mercedes Gomez de Agüero, Reem Kanjarawi, Ludovic Moro-Sibilot, Jean-Benoit Le Luduec, Claire Macari, Gilles Boschetti, Emilie Bardel, Philippe Langella, Bertrand Dubois, Dominique Kaiserlian
BACKGROUND: Induction of oral tolerance to haptens is an efficient way to prevent allergic contact dermatitis (ACD) in mice. Toll-like receptor (TLRs)-mediated sensing of the microbiota contributes to gut homeostasis, yet whether it contributes to induction of oral tolerance has not been documented. OBJECTIVE: We examined whether oral tolerance to the contact sensitizer DNFB depends on microbiota/TLRs and evaluated the role of TLR4 on the tolerogenic function of intestinal dendritic cells (DCs)...
March 22, 2017: Journal of Allergy and Clinical Immunology
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