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bone marrow transplantation, immunology

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https://www.readbyqxmd.com/read/29105189/cyclophosphamide-induced-tolerance-in-kidney-transplantation-avoids-long-term-immunosuppressive-therapy
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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. TNF-α blockade is the treatment of choice for the autoinflammation and vascular manifestations. Hematopoietic stem cell transplantation (HSCT) represents a potential definitive treatment. We present a cohort of 14 patients from 6 countries who received HSCT for DADA2...
October 3, 2017: Blood
https://www.readbyqxmd.com/read/28967897/donor-t-cell-responses-and-disease-progression-patterns-of-multiple-myeloma
#8
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...
October 2, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28941186/three-novel-mutations-in-cyba-among-22-iranians-with-chronic-granulomatous-disease
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28721499/treg-protected-donor-lymphocyte-infusions-a-new-tool-to-address-the-graft-versus-leukemia-effect-in-the-absence-of-graft-versus-host-disease-in-patients-relapsed-after-hsct
#14
Mauro Di Ianni, Paola Olioso, Raffaella Giancola, Stella Santarone, Annalisa Natale, Gabriele Papalinetti, Ida Villanova, Stefano Baldoni, Ambra Di Tommaso, Tiziana Bonfini, Patrizia Accorsi, Paolo Di Bartolomeo
In high-risk acute leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), adoptive immunotherapy with T regulatory cells (Tregs) and T conventional cells (Tcons) prevented acute and chronic graft-versus-host disease (GvHD), favored post-transplant immunological reconstitution and was associated with a powerful graft-versus-leukemia (GvL) effect. With a particularly innovative approach, we developed a treatment with a Treg-protected donor lymphocyte infusion (DLI) for patients with early relapse after HSCT and we report here the results obtained in the first patient with APL (M3v) relapsed after a second matched allogeneic HSCT (15% blasts and 75% of donor cells in bone marrow)...
July 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28719147/human-immunology-studies-using-organ-donors-impact-of-clinical-variations-on-immune-parameters-in-tissues-and-circulation
#15
D J Carpenter, T Granot, N Matsuoka, T Senda, B V Kumar, J J C Thome, C L Gordon, M Miron, J Weiner, T Connors, H Lerner, A Friedman, T Kato, A D Griesemer, D L Farber
Organ donors are sources of physiologically healthy organs and tissues for life-saving transplantation, and have been recently used for human immunology studies which are typically confined to the sampling of peripheral blood. Donors comprise a diverse population with different causes of death and clinical outcomes during hospitalization, and the effects of such variations on immune parameters in blood and tissues are not known. We present here a coordinate analysis of innate and adaptive immune components in blood, lymphoid (bone marrow, spleen, lymph nodes), and mucosal (lungs, intestines) sites from a population of brain-dead organ donors (2 months-93 years; n = 291) across eight clinical parameters...
July 18, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28647921/proteome-profile-of-aspergillus-terreus-conidia-at-germinating-stage-identification-of-probable-virulent-factors-and-enzymes-from-mycotoxin-pathways
#16
Raman Thakur, Jata Shankar
Aspergillus terreus is an emerging opportunistic fungal pathogen that causes invasive aspergillosis in immunocompromised individuals. The main risk group of individuals for this organism is leukopenic patients, individuals having cancers, bone marrow transplant persons and those who have immunological disorders. The lack of early diagnostic marker for A. terreus and intrinsic resistance to Amphotericin B, further limits the successful therapy of A. terreus-associated infections. The germination of inhaled conidia is the key step to establish successful invasion in host tissues or organs...
June 24, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28593997/severe-congenital-neutropenias
#17
REVIEW
Julia Skokowa, David C Dale, Ivo P Touw, Cornelia Zeidler, Karl Welte
Severe congenital neutropenias are a heterogeneous group of rare haematological diseases characterized by impaired maturation of neutrophil granulocytes. Patients with severe congenital neutropenia are prone to recurrent, often life-threatening infections beginning in their first months of life. The most frequent pathogenic defects are autosomal dominant mutations in ELANE, which encodes neutrophil elastase, and autosomal recessive mutations in HAX1, whose product contributes to the activation of the granulocyte colony-stimulating factor (G-CSF) signalling pathway...
June 8, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28589946/elevated-prostaglandin-e2-post-bone-marrow-transplant-mediates-interleukin-1%C3%AE-related-lung-injury
#18
G J Martínez-Colón, Q M Taylor, C A Wilke, A B Podsiad, B B Moore
Hematopoietic stem cell transplant (HSCT) treats or cures a variety of hematological and inherited disorders. Unfortunately, patients who undergo HSCT are susceptible to infections by a wide array of opportunistic pathogens. Pseudomonas aeruginosa bacteria can have life-threatening effects in HSCT patients by causing lung pathology that has been linked to high levels of the potent pro-inflammatory cytokine, interleukin-1β (IL-1β). Using a murine bone marrow transplant (BMT) model, we show that overexpression of prostaglandin E2 (PGE2) post-BMT signals via EP2 or EP4 to induce cyclic adenosine monophosphate (cAMP), which activates protein kinase A or the exchange protein activated by cAMP (Epac) to induce cAMP response element binding-dependent transcription of IL-1β leading to exacerbated lung injury in BMT mice...
June 7, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28567072/hyperimmunoglobulin-e-syndrome-genetics-immunopathogenesis-clinical-findings-and-treatment-modalities
#19
REVIEW
Hassan Hashemi, Masoumeh Mohebbi, Shiva Mehravaran, Mehdi Mazloumi, Hamidreza Jahanbani-Ardakani, Seyed-Hossein Abtahi
The hyperimmunoglobulin E syndromes (HIESs) are very rare immunodeficiency syndromes with multisystem involvement, including immune system, skeleton, connective tissue, and dentition. HIES are characterized by the classic triad of high serum levels of immunoglobulin E (IgE), recurrent staphylococcal cold skin abscess, and recurrent pneumonia with pneumatocele formation. Most cases of HIES are sporadic although can be inherited as autosomal dominant and autosomal recessive traits. A fundamental immunologic defect in HIES is not clearly elucidated but abnormal neutrophil chemotaxis due to decreased production or secretion of interferon γ has main role in the immunopathogenesis of syndrome, also distorted Th1/Th2 cytokine profile toward a Th2 bias contributes to the impaired cellular immunity and a specific pattern of infection susceptibility as well as atopic-allergic constitution of syndrome...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/28557197/impaired-immune-function-in-children-and-adults-with-fanconi-anemia
#20
Kasiani C Myers, Sharon Sauter, Xue Zhang, Jacob J Bleesing, Stella M Davies, Susanne I Wells, Parinda A Mehta, Ashish Kumar, Daniel Marmer, Rebecca Marsh, Darron Brown, Melinda Butsch Kovacic
BACKGROUND: Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA. PROCEDURE: We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls...
November 2017: Pediatric Blood & Cancer
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