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https://www.readbyqxmd.com/read/28214347/involvement-of-the-guanine-nucleotide-exchange-factor-vav3-in-central-nervous-system-development-and-plasticity
#1
Annika Ulc, Christine Gottschling, Ina Schäfer, David Wegrzyn, Simon van Leeuwen, Veronika Luft, Jacqueline Reinhard, Andreas Faissner
Small GTP-hydrolysing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a protooncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes...
February 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28212922/organ-specific-biomarkers-in-lupus
#2
REVIEW
Haijing Wu, Jinrong Zeng, Ming Zhao, Qianjin Lu
Systemic lupus erythematosus (SLE) is a complex and highly heterogeneous disease, which affects multiple organs, including joints, skin, kidneys, heart, hematopoietic system, and nerve system. While the etiopathogenesis of SLE still remains unclear, genetic susceptibilities and aberrant epigenetic modifications are believed to be involved. For precision therapy, it is necessary to assess accurately and objectively organ involvements and disease activity, which is difficult by current clinical laboratory tests...
February 14, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28211939/allogeneic-hematopoietic-cell-transplantation-for-primary-refractory-acute-lymphoblastic-leukemia-a-report-from-the-acute-leukemia-working-party-of-the-ebmt
#3
Jiří Pavlů, Myriam Labopin, Anna K Zoellner, Ioanna Sakellari, Matthias Stelljes, Jürgen Finke, Renato Fanin, Gernot Stuhler, Boris V Afanasyev, Adrian J Bloor, Achilles Anagnostopoulos, Mohamad Mohty, Sebastian Giebel, Arnon Nagler
BACKGROUND: Patients with primary refractory acute lymphoblastic leukemia (PREF ALL) who fail to achieve a complete remission (CR) after ≥2 courses of chemotherapy have a dismal prognosis without undergoing allogeneic hematopoietic cell transplantation (HCT). To the authors' knowledge, there currently are no data regarding factors influencing transplantation outcomes. METHODS: The authors retrospectively studied outcomes of transplantation for cases of PREF ALL reported to European Society for Blood and Marrow Transplantation registry...
February 17, 2017: Cancer
https://www.readbyqxmd.com/read/28202548/neutrophil-elastase-regulates-emergency-myelopoiesis-preceding-systemic-inflammation-in-diet-induced-obesity
#4
Jun-Yuan Huang, Qiong Lin Zhou, Chun-Hong Huang, Ye Song, Andria G Sharma, Zhangping Liao, Kavin Zhu, Miles W Massidda, Ryan R Jamieson, Jun-Yuan Zhang, Daniel G Tenen, Zhen Y Jiang
Inflammation plays a significant role in the development of obesity-related complications, but the molecular events that initiate and propagate such inflammation remain unclear. Here, we report that mice fed a high-fat diet (HFD) for as short as one to three days show increased myeloid progenitors differentiation into neutrophils and monocytes but reduced B lymphocyte production in the bone marrow (BM). Levels of neutrophil elastase (NE) and the nuclear factors CCAAT-enhancer-binding protein alpha (C/EBPα) and growth factor independent 1 (GFI-1) are elevated in hematopoietic stem and progenitor cells (HSPCs) from HFD-fed mice, but mice lacking either NE or C/EBPα are resistant to HFD-induced myelopoiesis...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28202390/systemic-injection-of-rpe65-programmed-bone-marrow-derived-cells-prevents-progression-of-chronic-retinal-degeneration
#5
Xiaoping Qi, S Louise Pay, Yuanqing Yan, James Thomas, Alfred S Lewin, Lung-Ji Chang, Maria B Grant, Michael E Boulton
Bone marrow stem and progenitor cells can differentiate into a range of non-hematopoietic cell types, including retinal pigment epithelium (RPE)-like cells. In this study, we programmed bone marrow-derived cells (BMDCs) ex vivo by inserting a stable RPE65 transgene using a lentiviral vector. We tested the efficacy of systemically administered RPE65-programmed BMDCs to prevent visual loss in the superoxide dismutase 2 knockdown (Sod2 KD) mouse model of age-related macular degeneration. Here, we present evidence that these RPE65-programmed BMDCs are recruited to the subretinal space, where they repopulate the RPE layer, preserve the photoreceptor layer, retain the thickness of the neural retina, reduce lipofuscin granule formation, and suppress microgliosis...
February 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28197965/allogeneic-stem-cell-transplantation-for-adult-patients-with-acute-lymphoblastic-leukemia-who-had-central-nervous-system-involvement-a-study-from-the-adult-all-working-group-of-the-japan-society-for-hematopoietic-cell-transplantation
#6
Akio Shigematsu, Shinichi Kako, Kenjiro Mitsuhashi, Koji Iwato, Naoyuki Uchida, Yoshinobu Kanda, Takahiro Fukuda, Masashi Sawa, Yasushi Senoo, Hiroyasu Ogawa, Koichi Miyamura, Satoru Takada, Tokiko Nagamura-Inoue, Yasuo Morishima, Tatsuo Ichinohe, Yoshiko Atsuta, Shuichi Mizuta, Junji Tanaka
The prognosis for adult acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement (CNS+) who received allogeneic hematopoietic stem cell transplantation (allo-SCT) remains unclear. We retrospectively compared the outcomes of allo-SCT for patients with CNS involvement and for patients without CNS involvement (CNS-) using a database in Japan. The eligibility criteria for this study were as follows: diagnosis of ALL, aged more than 16 years, allo-SCT between 2005 and 2012, and first SCT...
February 14, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28197380/the-influence-of-gut-decontamination-prophylactic-antibiotics-on-acute-graft-versus-host-disease-and-survival-following-allogeneic-hematopoietic-stem-cell-transplantation
#7
Bertrand Routy, Caroline Letendre, David Enot, Maxime Chénard-Poirier, Vikram Mehraj, Noémie Charbonneau Séguin, Khaled Guenda, Kathia Gagnon, Paul-Louis Woerther, David Ghez, Silvy Lachance
The intestinal microbiota plays a key role in the pathogenesis of acute graft-versus-host disease (aGVHD). High-dose conditioning regimens given prior to allogeneic hematopoietic stem cell transplantation (aHSCT) modulate the composition of gut microbiota and damage the gut epithelial barrier, resulting in increased systemic inflammation. We assessed whether gut decontamination with antibiotics (ATB) prior to aHSCT influenced the frequency of aGVHD and mortality in 500 patients from two Canadian centers between 2005 and 2012...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196699/-sarcoidosis-flare-after-autologous-stem-cell-transplantation-an-immune-paradox
#8
A Marchal, F Charlotte, P Maksud, J Haroche, F Lifferman, M Miyara, S Choquet, Z Amoura, F Cohen Aubart
INTRODUCTION: Sarcoidosis is a systemic granulomatous disorder of unknown cause. Apparition or flare of previously diagnosed sarcoidosis following hematopoietic stem cell transplantation (HSCT) has rarely been reported. OBSERVATION: We report a 62-year-old woman who presented a radiological flare of sarcoidosis post-autologous stem cell transplantation for a POEMS syndrome. Imaging findings and lymph node histology, which revealed non-caseating granuloma, were consistent with the sarcoidosis diagnosis...
February 10, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28196601/cholinergic-signals-from-the-cns-regulate-g-csf-mediated-hsc-mobilization-from-bone-marrow-via-a-glucocorticoid-signaling-relay
#9
Halley Pierce, Dachuan Zhang, Claire Magnon, Daniel Lucas, John R Christin, Matthew Huggins, Gary J Schwartz, Paul S Frenette
Hematopoietic stem cells (HSCs) are mobilized from niches in the bone marrow (BM) to the blood circulation by the cytokine granulocyte colony-stimulating factor (G-CSF) through complex mechanisms. Among these, signals from the sympathetic nervous system regulate HSC egress via its niche, but how the brain communicates with the BM remains largely unknown. Here we show that muscarinic receptor type-1 (Chrm1) signaling in the hypothalamus promotes G-CSF-elicited HSC mobilization via hormonal priming of the hypothalamic-pituitary-adrenal (HPA) axis...
February 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28196514/defining-the-contribution-of-neuroinflammation-to-parkinson-s-disease-in-humanized-immune-system-mice
#10
Gunjan Dhawan Manocha, Angela Marie Floden, Kendra Lynn Puig, Kumi Nagamoto-Combs, Clemens R Scherzer, Colin Kelly Combs
BACKGROUND: Reactive microglia have been associated with the histological changes that occur in Parkinson's disease brains and mouse models of the disease. Multiple studies from autopsy brains have verified the presence of microgliosis in several brain regions including substantia nigra, striatum, hippocampus and various cortical areas. MPTP injections in rodents have also shown striato-nigral microgliosis correlating with the loss of dopaminergic neurons. However, consistent data with respect to cytokine and immune cell changes during Parkinson's disease have not been fully defined...
February 14, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28196110/ethnic-variation-in-medical-and-lifestyle-risk-factors-for-b-cell-non-hodgkin-lymphoma-a-case-control-study-among-israelis-and-palestinians
#11
Geffen Kleinstern, Rania Abu Seir, Riki Perlman, Areej Khatib, Ziad Abdeen, Husein Elyan, Ronit Nirel, Gail Amir, Asad Ramlawi, Fouad Sabatin, Paolo Boffetta, Eldad J Dann, Meirav Kedmi, Martin Ellis, Arnon Nagler, Dina Ben Yehuda, Ora Paltiel
BACKGROUND: Risk factors for B-cell non-Hodgkin lymphoma (B-NHL) have not been assessed among Palestinian Arabs (PA) and Israeli Jews (IJ). METHODS: In a case-control study we investigated self-reported medical and lifestyle exposures, reporting odds ratios (ORs) and 95% confidence intervals [CIs], by ethnicity, for overall B-NHL and subtypes. RESULTS: We recruited 823 cases and 808 healthy controls. Among 307 PA/516 IJ B-NHL cases (mean age at diagnosis = 51 [±17] versus 60 [±15] years, respectively) subtype distributions differed, with diffuse large B-cell lymphoma (DLBCL) being prominent among PA (71%) compared to IJ (41%); follicular lymphoma (FL), was observed in 14% versus 28%, and marginal zone lymphoma, in 2% versus 14%, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28193723/regulation-of-hematopoiesis-and-hematological-disease-by-tgf-%C3%AE-family-signaling-molecules
#12
Kazuhito Naka, Atsushi Hirao
Throughout the lifetime of an individual, hematopoietic stem cells (HSCs) maintain the homeostasis of normal hematopoiesis through the precise generation of mature blood cells. Numerous genetic studies in mice have shown that stem-cell quiescence is critical for sustaining primitive long-term HSCs in vivo. In this review, we first examine the crucial roles of transforming growth factor β (TGF-β) and related signaling molecules in not only regulating the well-known cytostatic effects of these molecules but also governing the self-renewal capacity of HSCs in their in vivo microenvironmental niche...
February 13, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28191782/preventing-pluripotent-cell-teratoma-in-regenerative-medicine-applied-to-hematology-disorders
#13
Aurelie Bedel, François Beliveau, Isabelle Lamrissi-Garcia, Benoit Rousseau, Isabelle Moranvillier, Benoit Rucheton, Veronique Guyonnet-Dupérat, Bruno Cardinaud, Hubert de Verneuil, François Moreau-Gaudry, Sandrine Dabernat
Iatrogenic tumorigenesis is a major limitation for the use of human induced pluripotent stem cells (hiPSCs) in hematology. The teratoma risk comes from the persistence of hiPSCs in differentiated cell populations. Our goal was to evaluate the best system to purge residual hiPSCs before graft without compromising hematopoietic repopulation capability. Teratoma risk after systemic injection of hiPSCs expressing the reporter gene luciferase was assessed for the first time. Teratoma formation in immune-deficient mice was tracked by in vivo bioimaging...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28191767/concise-review-paracrine-functions-of-vascular-niche-cells-in-regulating-hematopoietic-stem-cell-fate
#14
Joshua P Sasine, Kelly T Yeo, John P Chute
The functions of endothelial cells (ECs) in regulating oxygen delivery, nutrient exchange, coagulation, and transit of inflammatory cells throughout the body are well--established. ECs have also been shown to regulate the maintenance and regeneration of organ-specific stem cells in mammals. In the hematopoietic system, hematopoietic stem cells (HSCs) are dependent on signals from the bone marrow (BM) vascular niche for their maintenance and regeneration after myelosuppressive injury. Recent studies have demonstrated the essential functions of BM ECs and perivascular stromal cells in regulating these processes...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28188810/an-efficient-and-simple-method-to-increase-the-level-of-displayed-protein-on-the-yeast-cell-surface
#15
Jing-Zhuang Zhao, Li-Ming Xu, Miao Liu, Yong-Sheng Cao, Scott E LaPatra, Jia-Sheng Yin, Hong-Bai Liu, Tong-Yan Lu
BACKGROUND: The development of oral vaccines using yeast surface display technology is an area of intensive study in vaccine development, but the protein level displayed on yeast surfaces is not currently high enough to obtain a robust immune response. METHODS: To address this issue, we established an efficient and simple method of increasing the level of displayed protein on the yeast cell surface. We used the single chain variable fragment (scFv) of an antibody against the infectious hematopoietic necrosis virus isolate Sn1203 as a target display protein...
February 7, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28187462/recombinant-tat-bmi-1-fusion-protein-induces-ex-vivo-expansion-of-human-umbilical-cord-blood-derived-hematopoietic-stem-cells
#16
Bruna Codispoti, Nicola Rinaldo, Emanuela Chiarella, Michela Lupia, Cristina Barbara Spoleti, Maria Grazia Marafioti, Annamaria Aloisio, Stefania Scicchitano, Marco Giordano, Giovanna Nappo, Valeria Lucchino, Malcolm A S Moore, Pengbo Zhou, Maria Mesuraca, Heather Mandy Bond, Giovanni Morrone
Transplantation of hematopoietic stem cells (HSCs) is a well-established therapeutic approach for numerous disorders. HSCs are typically derived from bone marrow or peripheral blood after cytokine-induced mobilization. Umbilical cord blood (CB) represents an appealing alternative HSC source, but the small amounts of the individual CB units have limited its applications. The availability of strategies for safe ex vivo expansion of CB-derived HSCs (CB-HSCs) may allow to extend the use of these cells in adult patients and to avoid the risk of insufficient engraftment or delayed hematopoietic recovery...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186688/mechanisms-of-tolerance-induction-by-hematopoietic-chimerism-the-immune-perspective
#17
EDITORIAL
Esma S Yolcu, Haval Shirwan, Nadir Askenasy
Hematopoietic chimerism is one of the effective approaches to induce tolerance to donor-derived tissue and organ grafts without administration of life-long immunosuppressive therapy. Although experimental efforts to develop such regimens have been ongoing for decades, substantial cumulative toxicity of combined hematopoietic and tissue transplants precludes wide clinical implementation. Tolerance is an active immunological process that includes both peripheral and central mechanisms of mutual education of coresident donor and host immune systems...
January 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28182332/challenging-the-great-vascular-wall-can-we-envision-a-simple-yet-comprehensive-therapy-for-stroke
#18
Marta Machado-Pereira, Tiago Santos, Lino Ferreira, Liliana Bernardino, Raquel Ferreira
Stroke is a leading cause of death in adult life, closely behind ischemic heart disease, and causes a significant and abiding socioeconomic burden. However, current therapies are not able to ensure full neurologic and/or sequelae-free recovery to all stroke survivors. We believe treatment efficacy and patient rehabilitation could be enhanced significantly by targeting blood-brain barrier (BBB) deregulation and inflammation-induced barrier loss occurring after stroke. In this pathological context, bone marrow-derived endothelial progenitor cells (EPC) enter the bloodstream towards the lesion site but their insufficient numbers and impaired angiogenic ability compromise neurovascular regeneration...
February 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28182011/tak1-regulates-resident-macrophages-by-protecting-lysosomal-integrity
#19
Yosuke Sakamachi, Sho Morioka, September R Mihaly, Giichi Takaesu, Julie F Foley, Michael B Fessler, Jun Ninomiya-Tsuji
Hematopoietic cell survival and death is critical for development of a functional immune system. Here, we report that a protein kinase, TAK1, is selectively required for resident macrophage integrity during embryogenesis. Hematopoietic lineage-specific deletion of Tak1 gene (Tak1(HKO)) caused accumulation of cellular debris in the thymus in perinatal mice. Although no overt alteration in thymocytes and blood myeloid populations was observed in Tak1(HKO) mice, we found that thymic and lung macrophages were diminished...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28179276/runx-transcription-factors-in-the-development-and-function-of-the-definitive-hematopoietic-system
#20
Marella de Bruijn, Elaine Dzierzak
The Runx family of transcription factors (Runx1, 2 and 3) are highly conserved and encode proteins involved in a variety of cell lineages, including blood and blood-related cell lineages during developmental and adult stages of life. They perform activation and repressive functions in the regulation of gene expression. The requirement for Runx1 in the normal hematopoietic development, and its dysregulation through chromosomal translocations and loss-of-function mutations as found in acute myeloid leukemias highlights the importance of this transcription factor in the healthy blood system...
February 8, 2017: Blood
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