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https://www.readbyqxmd.com/read/27920273/divergent-functions-of-tlr2-on-hematopoietic-and-nonhematopoietic-cells-during-chronic-mycobacterium-tuberculosis-infection
#1
Jill Konowich, Archana Gopalakrishnan, Jillian Dietzold, Sheetal Verma, Kamlesh Bhatt, Wasiulla Rafi, Padmini Salgame
We have reported that TLR2 is crucial for host resistance against chronic Mycobacterium tuberculosis infection; however, which cell types are key players in this response remain unknown. This led us to decipher the relative contribution of TLR2 on nonhematopoietic and hematopoietic cells in resistance against chronic M. tuberculosis infection in mice infected with M. tuberculosis Erdman. Consistent with our previous report, at 8 wk of infection, TLR2 knockout (TLR2KO)→TLR2KO bone marrow chimeric mice exhibited increased bacterial burden, disorganized accumulation of lymphocytes and mononuclear cells, and extensive pulmonary immunopathology compared with wild-type (WT)→WT chimeric mice...
December 5, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27919572/non-fucosylated-cb-cd34-cells-represent-a-good-target-for-enforced-fucosylation-to-improve-engraftment-following-cord-blood-transplantation
#2
Simon N Robinson, Michael W Thomas, Paul J Simmons, Junjun Lu, Hong Yang, Jeannie A Javni, Elizabeth J Shpall, Patrick A Zweidler-Mckay
BACKGROUND AIMS: Despite ethnic diversity and ready availability of cryopreserved, human leukocyte antigen-typed cord blood (CB), delayed engraftment remains a significant hurdle to successful CB transplantation. Suboptimal homing of CB hematopoietic stem and progenitor cells (HSPCs) to the hematopoietic microenvironment (HM) is thought to be responsible and due to low levels of HSPC fucosylation. Fucosylation (decoration with sialyl-Lewis(X)) may improve HSPC homing to HM by increasing the strength of HSPC/E-selectin interactions, where E-selectin is constitutively expressed by HM microvasculature...
December 2, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27919468/somatic-gnaq-mutation-is-enriched-in-brain-endothelial-cells-in%C3%A2-sturge-weber-syndrome
#3
Lan Huang, Javier A Couto, Anna Pinto, Sanda Alexandrescu, Joseph R Madsen, Arin K Greene, Mustafa Sahin, Joyce Bischoff
BACKGROUND: Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by facial and extracraniofacial capillary malformations and capillary-venule malformations in the leptomeninges. A somatic mosaic mutation in GNAQ (c.548G>A; p.R183Q) was found in SWS brain and skin capillary malformations. Our laboratory showed endothelial cells in skin capillary malformations are enriched for the GNAQ mutation. The purpose of this study is to determine whether the GNAQ mutation is also enriched in endothelial cells in affected SWS brain...
October 21, 2016: Pediatric Neurology
https://www.readbyqxmd.com/read/27919187/diagnostic-value-of-serum-ferritin-and-the-risk-factors-and-cytokine-profiles-of-hemophagocytic-syndrome-following-allogeneic-hematopoietic-cell-transplantation
#4
Satoru Nanno, Hideo Koh, Yasuhiro Nakashima, Takako Katayama, Hiroshi Okamura, Shiro Koh, Takuro Yoshimura, Mitsutaka Nishimoto, Yoshiki Hayashi, Mika Nakamae, Asao Hirose, Takahiko Nakane, Masayuki Hino, Hirohisa Nakamae
To examine the diagnostic value of serum ferritin, the associated risk factors, and cytokine profiles of hemophagocytic syndrome (HPS) following allogeneic hematopoietic cell transplantation (allo-HCT), we retrospectively analyzed data from patients undergoing allo-HCT between 2006 and 2012. Of 223 eligible patients, 18 patients developed HPS. A serum ferritin level above 30,000 μg/l was highly specific for the detection of HPS (specificity, 93%). The one-year survival rate for HPS was significantly lower than that of non-HPS patients (37...
December 6, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27919133/-significance-of-urological-surgical-treatment-for-viral-hemorrhagic-cystitis-after-allogeneic-hematopoietic-stem-cell-transplantation
#5
Kazuhiro Kurosawa, Shinji Urakami, Kazuya Ishiwata, Jinpei Miyagawa, Kazushige Sakaguchi, Masashi Fujioka, Hirokatsu Murata, Naoko Inoshita, Shuichi Taniguchi, Toshikazu Okaneya
This study investigated the significance of urological surgical intervention for viral hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 1, 024 patients underwent allo-HSCT at our medical center between January 2006 and July 2014. In the 6 patients (0.58%) who required urological surgical treatment for viral HC, we retrospectively analyzed patient characteristics and outcomes. Two patients underwent nephrostomy for bilateral hydronephrosis due to bladder tamponade...
November 2016: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/27918563/dickkopf-1-promotes-hematopoietic-regeneration-via-direct-and-niche-mediated-mechanisms
#6
Heather A Himburg, Phuong L Doan, Mamle Quarmyne, Xiao Yan, Joshua Sasine, Liman Zhao, Grace V Hancock, Jenny Kan, Katherine A Pohl, Evelyn Tran, Nelson J Chao, Jeffrey R Harris, John P Chute
The role of osteolineage cells in regulating hematopoietic stem cell (HSC) regeneration following myelosuppression is not well understood. Here we show that deletion of the pro-apoptotic genes Bak and Bax in osterix (Osx, also known as Sp7 transcription factor 7)-expressing cells in mice promotes HSC regeneration and hematopoietic radioprotection following total body irradiation. These mice showed increased bone marrow (BM) levels of the protein dickkopf-1 (Dkk1), which was produced in Osx-expressing BM cells...
December 5, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27917411/ptpn22-inhibition-resets-defective-human-central-b-cell-tolerance
#7
Jean-Nicolas Schickel, Marcel Kuhny, Alessia Baldo, Jason M Bannock, Christopher Massad, Haowei Wang, Nathan Katz, Tyler Oe, Laurence Menard, Pauline Soulas-Sprauel, Till Strowig, Richard Flavell, Eric Meffre
The 1858T protein tyrosine phosphatase nonreceptor type 22 (PTPN22 T) allele is one of the main risk factors associated with many autoimmune diseases and correlates with a defective removal of developing autoreactive B cells in humans. To determine whether inhibiting PTPN22 favors the elimination of autoreactive B cells, we first demonstrated that the PTPN22 T allele interfered with the establishment of central B cell tolerance using NOD-scid-common γ chain knockout (NSG) mice engrafted with human hematopoietic stem cells expressing this allele...
2016: Science Immunology
https://www.readbyqxmd.com/read/27917176/graft-immune-cell-composition-associates-with-clinical-outcome-of-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-aml
#8
Ulla Impola, Antti Larjo, Urpu Salmenniemi, Mervi Putkonen, Maija Itälä-Remes, Jukka Partanen
Complications of allogeneic hematopoietic stem cell transplantation (HSCT) have been attributed to immune cells transferred into the patient with the graft. However, a detailed immune cell composition of the graft is usually not evaluated. In the present study, we determined the level of variation in the composition of immune cells between clinical HSCT grafts and whether this variation is associated with clinical outcome. Sizes of major immune cell populations in 50 clinical grafts from a single HSCT Centre were analyzed using flow cytometry...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27916993/devouring-the-hematopoietic-stem-cell-setting-the-table-for-marrow-cell-transplantation
#9
Morton J Cowan, Hans-Peter Kiem
No abstract text is available yet for this article.
November 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/27916847/aortic-root-dilatation-in-mucopolysaccharidosis-i-vii
#10
Meena Bolourchi, Pierangelo Renella, Raymond Y Wang
The prevalence of aortic root dilatation (ARD) in mucopolysaccharidosis (MPS) is not well documented. We investigated aortic root measurements in 34 MPS patients at the Children's Hospital of Orange County (CHOC). The diagnosis, treatment status, age, gender, height, weight and aortic root parameters (aortic valve annulus (AVA), sinuses of Valsalva (SoV), and sinotubular junction (STJ)) were extracted by retrospective chart review and echocardiographic measurements. Descriptive statistics, ANOVA, and paired post-hoc t-tests were used to summarize the aortic dimensions...
November 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916050/-the-clinical-and-pathological-features-of-85-cases-with-positive-cerebrospinal-fluid-cytology-by-thin-layer-centrifugal-cytological-test
#11
W Gao, Z Li, L M Wang, F Lian, C C Liu, D H Lu, Y S Piao
Objective: To evaluate cytological test of cerebrospinal fluid in the diagnosis of meningeal dissemination of tumor cells. Methods: The clinical and imaging features of 85 cases with tumor cells diagnosed by thin-layer centrifugal cytological test of cerebrospinal fluid were retrospectively reviewed. The characteristics of cellular morphology and immunocytochemical staining were analyzed. Results: The main presentations of all the patinets was meningeal irritation and neurological dysfunction. The features of the brain MRI were meningeal thicking and enhancement, intracranial abnormal signals and intracranial space occupying lesion in part of the patients...
December 1, 2016: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/27916046/-a-comparative-study-of-unrelated-donor-and-matched-sibling-donor-allogeneic-hematopoietic-stem-cell-transplantation-in-children-and-adolescents-with-acquired-severe-aplastic-anemia
#12
J Zhou, Y W Fu, L J Liang, Q Wang, L J Han, Y L Zu, Yanli Zhang, X H Zhu, F K Yu, B J Fang, X D Wei, Y P Song
Objective: To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT) for children and adolescents with severe aplastic anemia (SAA). Methods: Clinical data of 34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015. According to the source of donor, the patients were divided into matched sibling donor allo-HSCT group (MSD group) and unrelated donor group (URD group). The clinical outcome of SAA children and adolescents receiving URD allo-HSCT was assessed, and patients in MSD allo-HSCT group were enrolled as control at the same period...
December 1, 2016: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/27915139/impairment-of-fetal-hematopoietic-stem-cell-function-in-the-absence-of-fancd2
#13
Sakiko Suzuki, Ronny R Racine, Nathan A Manalo, Sharon B Cantor, Glen D Raffel
Fanconi Anemia (FA), results from mutations in genes necessary for DNA damage repair and often leads to progressive bone marrow failure. Although the exhaustion of the bone marrow leads to cytopenias in FA patients as they age, evidence from human FA and mouse model fetal livers suggests hematopoietic defects originate in utero which may lead to deficient seeding of the bone marrow. To address this possibility, we examined the consequences of loss of Fancd2, a central component of the FA pathway. Examination of E14...
November 30, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27915031/acid-ceramidase-deficiency-is-characterized-by-a-unique-plasma-cytokine-and-ceramide-profile-that-is-altered-by-therapy
#14
Shaalee Dworski, Ping Lu, Aneal Khan, Bruno Maranda, John J Mitchell, Rossella Parini, Maja Di Rocco, Boris Hugle, Makoto Yoshimitsu, Bo Magnusson, Balahan Makay, Nur Arslan, Norberto Guelbert, Karoline Ehlert, Andrea Jarisch, Janet Gardner-Medwin, Rawane Dagher, Maria Teresa Terreri, Charles Marques Lorenco, Lilianna Barillas-Arias, Pranoot Tanpaiboon, Alexander Solyom, James S Norris, Xingxuan He, Edward H Schuchman, Thierry Levade, Jeffrey A Medin
Acid Ceramidase Deficiency (Farber Disease, FD) is an ultra-rare Lysosomal Storage Disorder that is poorly understood and often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). Hallmarks of FD are accumulation of ceramides, widespread macrophage infiltration, splenomegaly, and lymphocytosis. The cytokines involved in this abnormal hematopoietic state are unknown. There are dozens of ceramide species and derivatives, but the specific ones that accumulate in FD have not been investigated. We used a multiplex assay to analyze cytokines and mass spectrometry to analyze ceramides in plasma from patients and mice with FD, controls, Farber patients treated by hematopoietic stem cell transplantation (HSCT), JIA patients, and patients with Gaucher disease...
November 30, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27914967/survival-advantage-and-comparable-toxicity-in-reduced-toxicity-treosulfan-based-vs-reduced-intensity-busulfan-based-conditioning-regimen-in-mds-and-aml-patients-post-allogeneic-hematopoietic-cell-transplantation
#15
Ioanna Sakellari, Despina Mallouri, Eleni Gavriilaki, Ioannis Batsis, Maria Kaliou, Varnavas Constantinou, Apostolia Papalexandri, Chrysavgi Lalayanni, Chrysanthi Vadikolia, Anastasia Athanasiadou, Evangelia Yannaki, Damianos Sotiropoulos, Christos Smias, Achilles Anagnostopoulos
Treosulfan has been incorporated in conditioning regimens for sustained remissions without substantial toxicity and treatment related mortality (TRM). We aimed to analyze the safety and efficacy of FluTreo conditioning regimen (fludarabine 150mg/m(2), treosulfan 42g/m(2)) in medically infirm patients. Patients' outcome was compared with a similar historical group treated with FluBuATG (fludarabine 150-180mg/m(2), busulfex 6.4mg/Kg, thymoglobulin-ATG 5-7.5mg/kg). Thirty one consecutive patients suffering from AML (21), MDS (6) or treatment-related AML (4) received FluTreo conditioning...
November 30, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27914462/recombinant-mhc-tetramers-for-isolation-of-virus-specific-cd8-cells-from-healthy-donors-potential-approach-for-cell-therapy-of-posttransplant-cytomegalovirus-infection
#16
A S Vdovin, S Y Filkin, P R Yefimova, S A Sheetikov, N M Kapranov, Y O Davydova, E S Egorov, E G Khamaganova, M Y Drokov, L A Kuzmina, E N Parovichnikova, G A Efimov, V G Savchenko
Patients undergoing allogeneic hematopoietic stem cell transplantation have a high risk of cytomegalovirus reactivation, which in the absence of T-cell immunity can result in the development of an acute inflammatory reaction and damage of internal organs. Transfusion of the virus-specific donor T-lymphocytes represents an alternative to a highly toxic and often ineffective antiviral therapy. Potentially promising cell therapy approach comprises transfusion of cytotoxic T-lymphocytes, specific to the viral antigens, immediately after their isolation from the donor's blood circulation without any in vitro expansion...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27913635/screening-and-analysis-of-janelia-flylight-project-enhancer-gal4-strains-identifies-multiple-gene-enhancers-active-during-hematopoiesis-in-normal-and-wasp-challenged-drosophila-larvae
#17
Tsuyoshi Tokusumi, Yumiko Tokusumi, Mark S Brahier, Victoria Lam, Jessica R Stoller-Conrad, Paul T Kroeger, Robert A Schulz
A GFP expression screen has been conducted on greater than one thousand Janelia FlyLight Project enhancer-Gal4 lines to identify transcriptional enhancers active in the larval hematopoietic system. A total of 190 enhancers associated with 87 distinct genes showed activity in cells of the third instar larval lymph gland and hemolymph. That is, gene enhancers were active in cells of the lymph gland posterior signaling center (PSC), medullary zone (MZ), and/or cortical zone (CZ), while certain of the transcriptional control regions were active in circulating hemocytes...
December 2, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27913602/clonal-conversion-of-b-lymphoid-leukemia-reveals-cross-lineage-transfer-of-malignant-states
#18
Rajesh Somasundaram, Josefine Åhsberg, Kazuki Okuyama, Jonas Ungerbäck, Henrik Lilljebjörn, Thoas Fioretos, Tobias Strid, Mikael Sigvardsson
Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913534/myelodysplastic-and-myeloproliferative-disorders-of-childhood
#19
Henrik Hasle
Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913527/myelofibrosis-to-transplant-or-not-to-transplant
#20
Rebecca Devlin, Vikas Gupta
Hematopoietic cell transplantation (HCT) is the only curative therapeutic modality for myelofibrosis (MF) at present. The optimal timing of HCT is not known in the presence of wider availability of less risky nontransplant therapies such as JAK 1/2 inhibitors. Careful review of patient, disease, and transplant-related factors is required in the appropriate selection of HCT vs the best available nontransplant therapies. We highlight some of the relevant issues and positioning of HCT in light of evolving data on JAK 1/2 inhibitors...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
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