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bone marrow transplantation, immunology

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https://www.readbyqxmd.com/read/28320105/anti-fibrotic-potential-of-human-umbilical-cord-mononuclear-cells-and-mouse-bone-marrow-cells-in-ccl4-induced-liver-fibrosis-in-mice
#1
Nageh Ahmed Elmahdy, Samia Salem Sokar, Mohamed Labib Salem, Naglaa Ibrahim Sarhan, Sherin Hamed Abou-Elela
Liver fibrosis is the consequence of hepatocyte injury that leads to the activation of hepatic stellate cells (HSC). The treatment of choice is Liver transplantation; however, it has many problems such as surgery-related complications, immunological rejection and high costs associated with the procedure. Stem cell-based therapy would be a potential alternative, so the aim of this study is to investigate the therapeutic potential of human umbilical cord mononuclear cells (MNC) and mouse bone marrow cells (BMC) against carbon tetrachloride (CCl4) induced liver fibrosis in mice and compare it with that of silymarin...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319446/good-laboratory-practice-preclinical-safety-studies-for-gsk2696273-mlv-vector-based-ex-vivo-gene-therapy-for-adenosine-deaminase-deficiency-severe-combined-immunodeficiency-in-nsg-mice
#2
Nicola Carriglio, Jan Klapwijk, Raisa Jofra Hernandez, Michela Vezzoli, Franck Chanut, Rhiannon Lowe, Draghici Elena, Melanie Nord, Paola Albertini, Patrizia Cristofori, Jane Richards, Hazel Staton, Jonathan Appleby, Alessandro Aiuti, Aisha V Sauer
GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319074/tregs-hype-or-hope-for-allogeneic-hematopoietic-stem-cell-transplantation
#3
REVIEW
F Lussana, M Di Ianni, A Rambaldi
The discovery of T regulatory cells has been one of the most important advances in basic immunology and has opened the door to the development of innovative therapeutic strategies for improving the outcome of solid organ and hematopoietic stem cell transplantation. Basic immunology is rapidly elucidating the complex biology of these cells even though the difficulties in purifying or even expanding them in vitro represent a major limitation to the development of clinical studies. The clinical benefit potentially associated with this therapeutic approach remains to be demonstrated...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28251801/origin-of-enriched-regulatory-t-cells-in-patients-receiving-combined-kidney-bone-marrow-transplantation-to-induce-transplantation-tolerance
#4
Ben Sprangers, Susan DeWolf, Thomas M Savage, Tatsuaki Morokata, Aleksandar Obradovic, Samuel A LoCascio, Brittany Shonts, Julien Zuber, Sai Ping Lau, Ravi Shah, Heather Morris, Valeria Steshenko, Emmanuel Zorn, Frederic I Preffer, Sven Olek, David M Dombkowski, Laurence A Turka, Robert Colvin, Robert Winchester, Tatsuo Kawai, Megan Sykes
We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT) that led to transient chimerism under a previously-published non-myeloablative conditioning regimen (Immune Tolerance Network study ITN036). Polychromatic flow cytometry (FCM) and high throughput sequencing of TCRβ hypervariable regions of DNA from peripheral blood T regulatory cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of regulatory T cells (CD3(+) CD4(+) CD25(high) CD127(low) Foxp3(+) ) in blood that resulted from peripheral proliferation (Ki67(+) ), possibly new thymic emigration (CD31(+) ) and, in one tolerant subject, conversion from non-Tregs...
March 1, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28210842/uric-acid-as-a-novel-biomarker-for-bone-marrow-function-and-incipient-hematopoietic-reconstitution-after-aplasia-in-patients-with-hematologic-malignancies
#5
Sebastian P Haen, Vicky Eyb, Nora Mirza, Aline Naumann, Andreas Peter, Markus W Löffler, Christoph Faul, Wichard Vogel, Wolfgang A Bethge, Hans-Georg Rammensee, Lothar Kanz, Martin Heni
PURPOSE: Prolonged aplasia and graft failure (GF) represent life-threatening complications after hematopoietic cell transplantation (HCT) requiring suitable biomarkers for early detection and differentiation between GF and poor graft function (PGF). Uric acid (UA) is a strong immunological danger signal. METHODS: Laboratory results were analyzed from patients undergoing either allogeneic or autologous HCT or induction chemotherapy for acute leukemia (n = 50 per group, n = 150 total)...
February 16, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#6
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28180000/haematopoietic-stem-cells-past-present-and-future
#7
REVIEW
Ashley P Ng, Warren S Alexander
The discovery and characterisation of haematopoietic stem cells has required decades of research. The identification of adult bone marrow as a source of haematopoietic cells capable of protecting an organism from otherwise lethal irradiation led to the intense search for their identity and characteristics. Using functional assays along with evolving techniques for isolation of haematopoietic cells, haematopoietic stem cell populations were able to be enriched and their characteristics analysed. The key haematopoietic stem cell characteristics of pluripotentiality and the ability for self-renewal have emerged as characteristics of several haematopoietic stem cell populations, including those that have recently challenged the conventional concepts of the haematopoietic hierarchy...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28147358/hematopoietic-stem-cell-transplantation-in-crohn-s-disease-state-of-the-art-treatment
#8
REVIEW
C J Hawkey
Both autologous and allogeneic haemopoietic stem cell transplantation (HSCT) have been tried in Crohn's disease (CD). In allogeneic HSCT, the host bone marrow is ablated and replaced by bone marrow from a donor. This substitution of a genetically different bone marrow is effective in a number of conditions including those with an immunological basis such as CD. While the toxicity of allogeneic HSCT has precluded its uptake in idiopathic CD, there is interest in its utility in the management of early onset infantile (inflammatory bowel disease), which behaves as a monogenic disorder, with abnormalities of the interleukin 10 signalling system as the best recognized...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28133783/prognostic-impact-of-the-cd34-cd38-cell-burden-in-patients-with-acute-myeloid-leukemia-receiving-allogeneic-stem-cell-transplantation
#9
Madlen Jentzsch, Marius Bill, Deedra Nicolet, Sabine Leiblein, Karoline Schubert, Martina Pless, Ulrike Bergmann, Kathrin Wildenberger, Luba Schuhmann, Michael Cross, Wolfram Pönisch, Georg-Nikolaus Franke, Vladan Vucinic, Thoralf Lange, Gerhard Behre, Krzysztof Mrózek, Clara D Bloomfield, Dietger Niederwieser, Sebastian Schwind
In acute myeloid leukemia (AML), leukemia-initiating cells exist within the CD34+/CD38- cell compartment. They are assumed to be more resistant to chemotherapy, enriched in minimal residual disease cell populations, and responsible for relapse. Here we evaluated clinical and biological associations and the prognostic impact of a high diagnostic CD34+/CD38- cell burden in 169 AML patients receiving an allogeneic stem cell transplantation in complete remission. Here, the therapeutic approach is mainly based on immunological graft-versus-leukemia effects...
April 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28007665/cd25-blockade-delays-regulatory-t-cell-reconstitution-and-does-not-prevent-graft-versus-host-disease-after-allogeneic-hematopoietic-cell-transplantation
#10
Frederick L Locke, Joseph Pidala, Barry Storer, Paul J Martin, Michael A Pulsipher, Thomas R Chauncey, Niels Jacobsen, Nicolaus Kröger, Irwin Walker, Susan Light, Bronwen E Shaw, Francisca Beato, Ginna G Laport, Auayporn Nademanee, Armand Keating, Gerard Socie, Claudio Anasetti
Daclizumab, a humanized monoclonal antibody, binds CD25 and blocks formation of the IL-2 receptor on T cells. A study of daclizumab as acute graft-versus-host disease (GVHD) prophylaxis after unrelated bone marrow transplantation was conducted before the importance of CD25(+)FOXP3(+) regulatory T cells (Tregs) was recognized. Tregs can abrogate the onset of GVHD. The relation between Tregs and a graft-versus-malignancy effect is not fully understood. An international, multicenter, double-blind clinical trial randomized 210 adult or pediatric patients to receive 5 weekly doses of daclizumab at 0...
December 19, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27998825/hematopoietic-arginase-1-deficiency-results-in-decreased-leukocytosis-and-increased-foam-cell-formation-but-does-not-affect-atherosclerosis
#11
Baoyan Ren, Erik Van Kampen, Theo J C Van Berkel, Sheena M Cruickshank, Miranda Van Eck
BACKGROUND AND AIMS: Arginase1 (Arg1), an M2 macrophage marker, plays a critical role in a number of immunological functions in macrophages, which are the main cell type facilitating atherosclerotic lesion development. Arg1 uses the substrate l-arginine to create l-ornithine, a precursor molecule required for collagen formation and vascular smooth muscle cell differentiation. By reducing l-arginine availability, Arg1 limits the production of nitric oxide (NO), a pro-atherogenic factor in macrophages...
January 2017: Atherosclerosis
https://www.readbyqxmd.com/read/27974567/human-cytomegalovirus-requires-epidermal-growth-factor-receptor-signaling-to-enter-and-initiate-the-early-steps-in-the-establishment-of-latency-in-cd34-human-progenitor-cells
#12
Jung Heon Kim, Donna Collins-McMillen, Jason C Buehler, Felicia D Goodrum, Andrew D Yurochko
The establishment of human cytomegalovirus (HCMV) latency and persistence relies on the successful infection of hematopoietic cells, which serve as sites of viral persistence and contribute to viral spread. Here, using blocking antibodies and pharmacological inhibitors, we document that HCMV activation of the epidermal growth factor receptor (EGFR) and downstream phosphatidylinositol 3-kinase (PI3K) mediates viral entry into CD34(+) human progenitor cells (HPCs), resulting in distinct cellular trafficking and nuclear translocation of the virus compared to that in other immune cells, such as we have documented in monocytes...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27881982/milestones-of-hematopoietic-stem-cell-transplantation-from-first-human-studies-to-current-developments
#13
REVIEW
Mateja Kralj Juric, Sakhila Ghimire, Justyna Ogonek, Eva M Weissinger, Ernst Holler, Jon J van Rood, Machteld Oudshoorn, Anne Dickinson, Hildegard T Greinix
Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27879593/triptolide-reduces-the-required-dose-of-tacrolimus-by-attenuating-inflammation-enhancing-immunosuppression-and-increasing-donor-chimerism-in-a-heterotopic-hindlimb-transplantation-model
#14
Chuan Gu, Fei Liu, Xusong Luo, Xianyu Zhou, Jun Yang, L Scott Levin
BACKGROUND: Induction of tolerance and minimizing the toxicity of immunosuppression are two fundamental goals in vascularized composite allotransplantation. Accumulating data indicate that triptolide is an agent that may have the capacity to suppress inflammation and immunologic rejection. METHODS: A heterotopic hindlimb allotransplantation model from Brown Norway to Lewis rats was established and treated with different doses of tacrolimus combined with or without triptolide...
December 2016: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27860293/thrombocytopenia-in-chronic-liver-disease
#15
REVIEW
Markus Peck-Radosavljevic
Thrombocytopenia is a common haematological disorder in patients with chronic liver disease. It is multifactorial and severity of liver disease is the most influential factor. As a result of the increased risk of bleeding, thrombocytopenia may impact upon medical procedures, such as surgery or liver biopsy. The pathophysiology of thrombocytopenia in chronic liver disease has long been associated with the hypothesis of hypersplenism, where portal hypertension causes pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes, in the enlarged and congested spleen...
November 17, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27859595/recipient-bone-marrow-derived-stromal-cells-prolong-graft-survival-in-a-rat-hind-limb-allotransplantation-model
#16
Ryosuke Ikeguchi, Ryosuke Kakinoki, Souichi Ohta, Hiroki Oda, Hirofumi Yurie, Yukitoshi Kaizawa, Hiroto Mitsui, Tomoki Aoyama, Junya Toguchida, Shuichi Matsuda
BACKGROUND: Recent studies have indicated that bone marrow-derived stromal cells (BMSCs) have immunomodulatory properties that suppress the T cell responses that cause graft rejection. The purpose of this study is to evaluate the effect of recipient BMSCs intravenous infusion for immunomodulation in a rat vascularized composite allotransplantation model. METHODS: A total of nine Wistar (WIS) rats and thirty Lewis (LEW) rats were used. BMSCs were harvested from three LEW rats...
November 17, 2016: Microsurgery
https://www.readbyqxmd.com/read/27855369/effect-of-extracellular-vesicles-on-neural-functional-recovery-and-immunologic-suppression-after-rat-cerebral-apoplexy
#17
Beilei Hu, Songfang Chen, Ming Zou, Zhiyong He, Shengmin Shao, Baohua Liu
BACKGROUND: Previous studies have demonstrated that mesenchymal stem cells (MSCs) can promote the recovery of neural function after cerebral apoplexy by secreting multiple cytokines. In addition, cell factor-derived extracellular vesicles play an important role in recovery of neural function. The aim of this study was to determine the effect of extracellular vesicles on neural functional recovery and brain tissue remodeling after cerebral apoplexy in a rat model. METHODS: The rat models with local ischemic stroke was established and three random groups were created...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27847830/early-differentiation-of-human-cd11c-nk-cells-with-%C3%AE-%C3%AE-t-cell-activation-properties-is-promoted-by-dialyzable-leukocyte-extracts
#18
Dalia Ramírez-Ramírez, Eduardo Vadillo, Lourdes Andrea Arriaga-Pizano, Héctor Mayani, Sergio Estrada-Parra, Marco Antonio Velasco-Velázquez, Sonia Mayra Pérez-Tapia, Rosana Pelayo
Reconstitution of the hematopoietic system during immune responses and immunological and neoplastic diseases or upon transplantation depends on the emergent differentiation of hematopoietic stem/progenitor cells within the bone marrow. Although in the last decade the use of dialyzable leukocyte extracts (DLE) as supportive therapy in both infectious and malignant settings has increased, its activity on the earliest stages of human hematopoietic development remains poorly understood. Here, we have examined the ability of DLE to promote replenishment of functional lymphoid lineages from CD34(+) cells...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27824136/lrba-is-essential-for-allogeneic-responses-in-bone-marrow-transplantation
#19
Mi Young Park, Raki Sudan, Neetu Srivastava, Sudha Neelam, Christie Youngs, Jia-Wang Wang, Robert W Engelman, William G Kerr
The PH-BEACH-WD40 (PBW) protein family members play a role in coordinating receptor signaling and intracellular vesicle trafficking. LPS-Responsive-Beige-like Anchor (LRBA) is a PBW protein whose immune function remains elusive. Here we show that LRBA-null mice are viable, but exhibit compromised rejection of allogeneic, xenogeneic and missing self bone-marrow grafts. Further, we demonstrate that LRBA-null Natural Killer (NK) cells exhibit impaired signaling by the key NK activating receptors, NKp46 and NKG2D...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27812432/treatment-of-rapidly-progressive-systemic-sclerosis-current-and-futures-perspectives
#20
Fabian A Mendoza, Maryah Mansoor, Sergio A Jimenez
INTRODUCTION: Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by severe and often progressive cutaneous, pulmonary, cardiac and gastrointestinal tract fibrosis, cellular and humoral immunologic alterations, and pronounced fibroproliferative vasculopathy. There is no effective SSc disease modifying therapy. Patients with rapidly progressive SSc have poor prognosis with frequent disability and very high mortality. AREAS COVERED: This paper reviews currently available therapeutic approaches for rapidly progressive SSc and discuss novel drugs under study for SSc disease modification...
2016: Expert Opinion on Orphan Drugs
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