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bone marrow transplantation, immunology

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https://www.readbyqxmd.com/read/29296858/successful-desensitization-with-proteasome-inhibition-and-costimulation-blockade-in-sensitized-nonhuman-primates
#1
Jean Kwun, Christopher Burghuber, Miriam Manook, Brian Ezekian, Jaeberm Park, Janghoon Yoon, John S Yi, Neal Iwakoshi, Adriana Gibby, Jung Joo Hong, Alton B Farris, Allan D Kirk, Stuart J Knechtle
The detrimental effects of donor-directed antibodies in sensitized transplant patients remain a difficult immunologic barrier to successful organ transplantation. Antibody removal is often followed by rebound. Proteasome inhibitors (PIs) deplete antibody-producing plasma cells (PCs) but have shown marginal benefit for desensitization. In an allosensitized nonhuman primate (NHP) model, we observed increased germinal center (GC) formation after PI monotherapy, suggesting a compensatory PC repopulation mediated via GC activation...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29261677/increased-soluble-il-7-receptor-concentrations-associate-with-improved-il-7-therapy-outcomes-in-siv-infected-art-treated-rhesus-macaques
#2
Amanda K Steele, Lorna Carrasco-Medina, Donald L Sodora, Angela M Crawley
The use of interleukin-7 (IL-7) as an immunorestorative therapeutic has proven effective in HIV infection, cancer and bone marrow transplantation. Mediating its activity through membrane-bound IL-7 receptor α (mCD127), IL-7 therapy increases T-cell numbers and survival. A soluble form, sCD127, is found in plasma, and we have previously identified increased plasma sCD127 concentrations in HIV infection. Furthermore, patients with high sCD127 exhibited the best viral control, implicating a role for IL-7 or sCD127 directly in improved virologic/immunologic outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/29241731/efficacy-of-lentiviral-mediated-gene-therapy-in-an-omenn-syndrome-rag2-mouse-model-is-not-hindered-by-inflammation-and-immune-dysregulation
#3
Valentina Capo, Maria Carmina Castiello, Elena Fontana, Sara Penna, Marita Bosticardo, Elena Draghici, Luigi P Poliani, Lucia Sergi Sergi, Rosita Rigoni, Barbara Cassani, Monica Zanussi, Paola Carrera, Paolo Uva, Kerry Dobbs, Nicolò Sacchetti, Luigi D Notarangelo, Niek P van Til, Gerard Wagemaker, Anna Villa
BACKGROUND: Omenn syndrome (OS) is a rare severe combined immunodeficiency associated with autoimmunity, caused by defects of the lymphoid-specific V(D)J recombination. Most patients carry hypomorphic mutations in recombination activating genes (RAG) 1 or 2. Hematopoietic stem cell (HSC) transplantation is the standard treatment, however gene therapy (GT) may represent a valid alternative, especially for patients lacking a matched donor. OBJECTIVE: To determine the efficacy of lentiviral vector (LV) mediated GT in the murine model of OS (Rag2R229Q/R229Q) in correcting immunodeficiency and autoimmunity...
December 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29238707/drug-repurposing-for-the-treatment-of-acute-myeloid-leukemia
#4
REVIEW
Vibeke Andresen, Bjørn T Gjertsen
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accumulation of immature myeloid progenitor cells in the bone marrow, compromising of normal blood cell production and ultimately resulting in bone marrow failure. With a 20% overall survival rate at 5 years and 50% in the 18- to 65-year-old age group, new medicines are needed. It is proposed that development of repurposed drugs may be a part of the new therapy needed. AML is subdivided into recurrent molecular entities based on molecular genetics increasingly accessible for precision medicine...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29188366/pre-operative-neutrophil-count-and-neutrophil-lymphocyte-count-ratio-nlcr-in-predicting-the-histological-grade-of-paediatric-brain-tumours-a-preliminary-study
#5
J R F Wilson, F Saeed, A K Tyagi, J R Goodden, G Sivakumar, D Crimmins, M Elliott, S Picton, P D Chumas
INTRODUCTION: The neutrophil-lymphocyte count ratio (NLCR) is an established prognostic marker for renal, lung and colorectal carcinomas and has been suggested to be predictive of histological grade and outcome in adult intracranial tumours. The purpose of this study was to determine whether a correlation of the pre-operative neutrophil count (NC) and NLCR with the final histological grade exists in paediatric intracranial tumours. METHODS: A retrospective analysis was undertaken at a single centre...
November 29, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/29178692/-management-of-vaccination-in-children-receiving-an-allogeneic-marrow-transplant
#6
S Blumental, A Ferster, N Azzi, P Lepage
Over the last decades, significant advances in the diagnosis and therapeutics have considerably improved success rate from bone marrow transplant in patients suffering from otherwise life-threatening diseases, allowing now for prolonged survival and better quality of life after an allograft. However, infectious diseases remain one of the most serious complication in this population, hence associated with a high morbidity and mortality. Prevention, in particular through vaccination, constitutes a cornerstone of the management of immunocompromised hosts, since this procedure aims to protect them once back to life in community after long periods of hospitalization...
2017: Revue Médicale de Bruxelles
https://www.readbyqxmd.com/read/29152615/scid-pigs-an-emerging-large-animal-nk-model
#7
Ellis J Powell, Joan E Cunnick, Christopher K Tuggle
Severe Combined ImmunoDeficiency (SCID) is defined as the lack or impairment of an adaptive immune system. Although SCID phenotypes are characteristically absent of T and B cells, many such SCID cellular profiles include the presence of NK cells. In human SCID patients, functional NK cells may impact the engraftment success of life saving procedures such as bone marrow transplantation. However, in animal models, a T cell-, B cell-, NK cell+ environment provides a valuable tool for asking specific questions about the extent of the innate immune system function as well as emerging NK targeted therapies against cancer...
2017: Journal of Rare Diseases Research & Treatment
https://www.readbyqxmd.com/read/29105189/cyclophosphamide-induced-tolerance-in-kidney-transplantation-avoids-long-term-immunosuppressive-therapy
#8
REVIEW
Ario Takeuchi, Koji Kato, Koichi Akashi, Masatoshi Eto
There has recently been remarkable progress in immunosuppressive agents, such as tacrolimus and cyclosporine. Therefore, the rate of organ establishment has improved in transplantation. However, immunosuppressive agents generally suppress the function of T cells. Thus, opportunistic infections, such as cytomegalovirus infection, are still a major problem in kidney transplantation. Induction of specific tolerance to avoid immunosuppressive drug therapy after kidney transplantation is considered as the ultimate goal of transplantation...
November 3, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29101827/differential-t-cell-subsets-and-cytokine-profile-between-steady-state-and-g-csf-primed-bone-marrow-and-its-association-with-graft-versus-host-disease
#9
Eucario León-Rodríguez, Monica M Rivera-Franco, Diana Gómez-Martín, Jorge Romo-Tena, Guillermo Juárez-Vega, Javier Merayo-Chalico, Jorge Alcocer-Varela
Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). At our Institution, patients transplanted using G-CSF-primed bone marrow (G-BM), have a lower incidence of GVHD when compared to other sources. The objective of this study was to analyze and compare T cell subsets and cytokines in donor G-BM and steady-state BM (SS-BM). A prospective study was performed in 48 donor samples. Mononuclear cells were isolated by gradient density. T cell subsets and cytokine production in supernatants were analyzed by multiparametric flow cytometry...
November 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29100944/regulatory-dendritic-cells-for-promotion-of-liver-transplant-operational-tolerance-rationale-for-a-clinical-trial-and-accompanying-mechanistic-studies
#10
REVIEW
Angus W Thomson, Abhinav Humar, Fadi G Lakkis, Diana M Metes
Dendritic cells (DC) are rare, bone marrow (BM)-derived innate immune cells that critically maintain self-tolerance in the healthy steady-state. Regulatory DC (DCreg) with capacity to suppress allograft rejection and promote transplant tolerance in pre-clinical models can readily be generated from BM precursors or circulating blood monocytes. These DCreg enhance allograft survival via various mechanisms, including promotion of regulatory T cells. In non-human primates receiving minimal immunosuppressive drug therapy (IS), infusion of DCreg of donor origin, one week before transplant, safely prolongs renal allograft survival and selectively attenuates anti-donor CD8(+) memory T cell responses in the early post-transplant period...
October 31, 2017: Human Immunology
https://www.readbyqxmd.com/read/29050459/third-party-regulatory-t-cells-prevent-murine-acute-graft-versus-host-disease
#11
Jung-Yeon Lim, Keon-Il Im, Yunejin Song, Nayoun Kim, Young-Sun Nam, Young-Woo Jeon, Seok-Goo Cho
Background/Aims: Adoptive therapy with regulatory T (Treg) cells to prevent graft-versus-host disease (GVHD) would benefit from a strategy to improve homing to the sites of inflammation following hematopoietic stem cell transplantation (HSCT). Although donor-derived Treg cells have mainly been used in these models, third-party-derived Treg cells are a promising alternative for cell-based immunotherapy, as they can be screened for pathogens and cell activity, and banked for GVHD prevention...
October 19, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29044226/bone-marrow-transplant-induced-alterations-in-notch-signaling-promote-pathologic-th17-responses-to-%C3%AE-herpesvirus-infection
#12
S J Gurczynski, X Zhou, M Flaherty, C A Wilke, B B Moore
Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects...
October 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29023302/complete-resolution-of-lymphoid-interstitial-pneumonia-in-a-patient-with-juvenile-myelomonocytic-leukemia-treated-with-allogeneic-bone-marrow-transplant-killing-2-birds-with-1-stone
#13
Anant Vatsayan, Ravi Talati, Kristen Nagle, Linda Cabral, Sloane Cammock, Amy Dimarino, Rachel Egler, Shahrazad Saab, Jignesh Dalal
Lymphoid interstitial pneumonia (LIP) is a rare disease characterized by benign reactive polyclonal proliferation of bronchus-associated lymphoid tissue after exposure to inhaled or circulating antigen(s), leading to a disease symptomatology similar to idiopathic interstitial pneumonia. Its association with diseases that are caused due to immune dysregulation (autoimmune diseases, congenital/acquired immunodeficiency, and allogeneic bone marrow transplant) and response to immunomodulatory/suppressive medications suggests an immunologic pathophysiology...
October 11, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28974505/hematopoietic-stem-cell-transplantation-rescues-the-hematological-immunological-and-vascular-phenotype-in-dada2
#14
MULTICENTER STUDY
Hasan Hashem, Ashish R Kumar, Ingo Müller, Florian Babor, Robbert Bredius, Jignesh Dalal, Amy P Hsu, Steven M Holland, Dennis D Hickstein, Stephen Jolles, Robert Krance, Ghadir Sasa, Mervi Taskinen, Minna Koskenvuo, Janna Saarela, Joris van Montfrans, Keith Wilson, Barbara Bosch, Leen Moens, Michael Hershfield, Isabelle Meyts
Deficiency of adenosine deaminase 2 (DADA2) is caused by biallelic deleterious mutations in CECR1 DADA2 results in variable autoinflammation and vasculopathy (recurrent fevers, livedo reticularis, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency and bone marrow failure. Tumor necrosis factor-α blockade is the treatment of choice for the autoinflammation and vascular manifestations. Hematopoietic stem cell transplantation (HSCT) represents a potential definitive treatment...
December 14, 2017: Blood
https://www.readbyqxmd.com/read/28967897/donor-t-cell-responses-and-disease-progression-patterns-of-multiple-myeloma
#15
M Eefting, L C de Wreede, P A Von dem Borne, C J M Halkes, S Kersting, E W A Marijt, H Putter, H Veelken, J Schetelig, J H F Falkenburg
Donor T-cells transferred after allogeneic stem cell transplantation (alloSCT) can result in long-term disease control in myeloma by the graft-versus-myeloma (GvM) effect. However, T-cell therapy may show differential effectiveness against bone marrow (BM) infiltration and focal myeloma lesions resulting in different control and progression patterns. Outcomes of 43 myeloma patients who underwent T-cell-depleted alloSCT with scheduled donor lymphocyte infusion (DLI) were analyzed with respect to diffuse BM infiltration and focal progression...
December 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28941186/three-novel-mutations-in-cyba-among-22-iranians-with-chronic-granulomatous-disease
#16
M Badalzadeh, S Tajik, M R Fazlollahi, M Houshmand, F Fattahi, Z Alizadeh, M Movahedi, Z Adab, G T Khotaei, A A Hamidieh, H Heidarnazhad, Z Pourpak
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defect in one of the components of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase enzyme. The enzyme is at least composed of membrane-bound subunits gp91-phox and p22-phox (also named cytochrome b558 ), and cytosolic ones p40-phox, p47-phox and p67-phox. A defect in the enzyme activity leads to impaired intracellular killing of phagocytic cells. The CYBA gene encoding p22-phox is located on chromosome 16q24. In this study, new genetic changes of CYBA gene in 22 Iranian patients with autosomal recessive-CGD (AR-CGD) were identified...
September 20, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28940837/a-case-of-the-nephrotic-syndrome-in-bone-marrow-transplantation-recipient-histologically-showing-overlapped-glomerular-lesions-of-thrombotic-microangiopathy-and-membranous-nephropathy
#17
Naoko Masuzawa, Ayako Nishimura, Takashi Kitani, Keiichi Tamagaki, Mio Sugitani, Hisao Nagoshi, Junya Kuroda, Eiichi Konishi
Nephrotic syndrome (NS) rarely occurs in post-hematopoietic stem cell transplantation (HSCT) recipients but represents the renal manifestation of graft-versus-host disease (GVHD). Membranous nephropathy (MN) accounts for almost two thirds of post-HSCT NS and is caused by immune complex deposition. Renal thrombotic microangiopathy (TMA) without fulfillment of clinical criteria for TMA has been underreported because of reduced opportunity for histological examination. However, renal TMA has recently been reported in association with GVHD and humoral immunological reactions...
September 20, 2017: Pathology International
https://www.readbyqxmd.com/read/28935847/cd56-bright-natural-killer-regulatory-cells-in-filgrastim-primed-donor-blood-or-marrow-products-regulate-chronic-graft-versus-host-disease-the-canadian-blood-and-marrow-transplant-group-randomized-0601-study-results
#18
Amina Kariminia, Sabine Ivison, Bernard Ng, Jacob Rozmus, Susanna Sung, Avani Varshney, Mahmoud Aljurf, Sylvie Lachance, Irwin Walker, Cindy Toze, Jeff Lipton, Stephanie J Lee, Jeff Szer, Richard Doocey, Ian Lewis, Clayton Smith, Naeem Chaudhri, Megan K Levings, Raewyn Broady, Gerald Devins, David Szwajcer, Ronan Foley, Sara Mostafavi, Steven Pavletic, Donna A Wall, Stephan Couban, Tony Panzarella, Kirk R Schultz
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease...
November 2017: Haematologica
https://www.readbyqxmd.com/read/28890868/surgical-and-immune-reconstitution-murine-models-in-bone-marrow-research-potential-for-exploring-mechanisms-in-sepsis-trauma-and-allergy
#19
REVIEW
Pedro Xavier-Elsas, Renato Nunes Ferreira, Maria Ignez C Gaspar-Elsas
Bone marrow, the vital organ which maintains lifelong hemopoiesis, currently receives considerable attention, as a source of multiple cell types which may play important roles in repair at distant sites. This emerging function, distinct from, but closely related to, bone marrow roles in innate immunity and inflammation, has been characterized through a number of strategies. However, the use of surgical models in this endeavour has hitherto been limited. Surgical strategies allow the experimenter to predetermine the site, timing, severity and invasiveness of injury; to add or remove aggravating factors (such as infection and defects in immunity) in controlled ways; and to manipulate the context of repair, including reconstitution with selected immune cell subpopulations...
August 20, 2017: World Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28774824/hla-frequency-in-candidates-to-transplant-without-compatible-cord-blood-at-the-national-center-of-blood-transfusion-mexico
#20
Julieta Rojo-Medina, Juan Manuel Bello-López
INTRODUCTION: Umbilical Cord Blood Units (UCBU) for transplantation, are a therapeutic possibility for patients with a wide range of oncohaematological diseases and other immunologic disorders. The search of compatible donors for bone marrow transplantation is increasingly difficult for patients of mixed ethnicity. The aim of this work was determine the HLA frequency of candidates for transplantation without compatible UCBU at the National Center of from Blood Transfusion (NCBT) - Mexico...
July 19, 2017: Transfusion and Apheresis Science
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