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Giang Huong Nguyen, James Y Wang, Kenneth B Hymes, Cynthia M Magro
Adult T-cell leukemia/lymphoma (ATLL) is a rare and often aggressive lymphoid malignancy known to be associated with human T-cell lymphotropic virus type 1. There are 2 broad categories: acute and chronic. In the acute category, there is a leukemic and a lymphomatous variant, whereas in the designated "chronic" form, there is mild peripheral blood lymphocytosis. The intermediate "smoldering" category is without peripheral blood lymphocytosis with only discernible skin involvement. We present a 68-year-old human T-cell lymphotropic virus type 1 seropositive female with a mild peripheral blood atypical lymphocytosis who had indurated nodules on her hands of 2 years duration and a new scaly ichthyosiform eruption on her lower extremities...
October 12, 2016: American Journal of Dermatopathology
Annalisa Ruggeri, Yuqian Sun, Myriam Labopin, Andrea Bacigalupo, Francesca Lorentino, William Arcese, Stella Santarone, Zafar Gülbas, Didier Blaise, Giuseppe Messina, Ardeshi Ghavamzadeh, Florent Malard, Benedetto Bruno, Jose Luis Diez-Martin, Yener Koc, Fabio Ciceri, Mohamad Mohty, Arnon Nagler
Severe graft-versus-host-disease is a major barrier for non T-cell-depleted haploidentical stem cell transplantation and there is no consensus on the optimal GVHD prophylaxis. This study compared the two most commonly used graft-versus-host-disease prophylaxis regimens (post-transplant-cyclophosphamide-based (PTCY) versus the anti-thymocyte-globulin-based (ATG)) in adults with acute myeloid leukemia reported to the european society for blood and bone marrow transplantation. 308 patients were analyzed, 193 received PTCY and 115 ATG as anti- graft-versus-host-disease prophylaxis...
October 6, 2016: Haematologica
L V Kroth, F F Barreiro, D Saitovitch, M A Traesel, D O L d'Avila, C E Poli-de-Figueiredo
Acute graft pyelonephritis is a very common infection in renal transplantation. The impact of acute graft pyelonephritis (AGPN) on graft and patient outcome has not yet been established. Eight hundred seventy kidney and kidney-pancreas transplants were retrospectively studied, over last 13 years, to verify occurrence of AGPN in the first 30 days post-transplantation. We found that 112 patients (15.8%) presented post-transplantatiom AGPN up to 30 days after a kidney transplantation. The occurrence was higher in older patients (P = ...
September 2016: Transplantation Proceedings
L V Kroth, F F Barreiro, D Saitovitch, M A Traesel, D O L d'Avila, C E Poli-de-Figueiredo
BACKGROUND: Solid organ transplant recipients are susceptible to antibiotic-resistant infections and carbapenem-resistant Acinetobacter baumannii (CRAB) has recently been recognized as a serious complication in solid organ recipients. High mortality rates have been described. METHODS: We retrospectively analyzed 807 transplantations and detected 10 patients who died 24 hours after the diagnosis of septicemia, all with CRAB-positive blood cultures. Recipients were followed up for at least 1 year and were stratified into the following groups: Group 1, patients alive; Group 2, patients that died due to other causes except Acinetobacter infection; and Group 3, patients who died within 24 hours of CRAB diagnosis...
September 2016: Transplantation Proceedings
Thiago Alves da Costa, Rosária Di Gangi, Rodolfo Thomé, Marina Barreto Felisbino, Amanda Pires Bonfanti, Larissa Lumi Watanabe Ishikawa, Alexandrina Sartori, Eva Burger, Liana Verinaud
T cell maturation takes place within the thymus, a primary lymphoid organ that is commonly targeted during infections. Previous studies showed that acute infection with Paracoccidioides brasiliensis (Pb), the causative agent of paracoccidioidomycosis (PCM), promotes thymic atrophy that is associated with the presence of yeast cells in the organ. However, as human PCM is a chronic infection, it is imperative to investigate the consequences of Pb infection over the thymic structure and function in chronic infection...
2016: PloS One
Dane M Newman, Anne K Voss, Tim Thomas, Rhys S Allan
Histone acetylation has an important role in gene regulation, DNA replication, and repair. Because these processes are central to the development of the immune system, we investigated the role of a previously unstudied histone acetyltransferase named KAT7 (also known as Myst2 or HBO1) in the regulation of thymopoiesis and observed a critical role in the regulation of conventional and innate-like T cell development. We found that KAT7-deficient thymocytes displayed normal, positive selection and development into mature single-positive αβ thymocytes; however, we observed few peripheral CD4(+) or CD8(+) T cells...
October 12, 2016: Journal of Leukocyte Biology
Ai-Ling Chen, Xi Sun, Wei Wang, Jin-Feng Liu, Xin Zeng, Jing-Fan Qiu, Xin-Jian Liu, Yong Wang
BACKGROUND: Immunosuppression has been described as a consequence of brain injury and infection by different mechanisms. Angiostrongylus cantonensis can cause injury to the central nervous system and eosinophilic meningitis to human. Both T cell and B cell immunity play an essential role in the resistance of the infection. However, whether brain injury caused by A. cantonensis infection can lead to immunosuppression is not clear. Therefore, the present study sought to observe the alteration of immune responses in mice infected with A...
October 12, 2016: Journal of Neuroinflammation
Elisabetta Volpe, Manolo Sambucci, Luca Battistini, Giovanna Borsellino
Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas-FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens...
2016: Frontiers in Immunology
Kensuke Usuki
Treatments of aplastic anemia are comprised of supportive therapy and aplastic anemia-specific therapy aimed at restoring hematopoiesis. Supportive therapies include transfusion, G-CSF, and the administration of iron chelation agents, as well as dealing specifically with individual symptoms. Aplastic anemia-specific treatments given with the aim of achieving hematopoietic recovery include immunosuppressive therapy, allogeneic hematopoietic stem cell transplantation, and anabolic hormone therapy. Although transplantation provides complete recovery of hematopoiesis (cure), there is a risk of death due to transplant-related complications...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Leylagul Kaynar, Koray Demir, Esra Ermiş Turak, Çiğdem Pala Öztürk, Gökmen Zararsız, Zeynep Burçin Gönen, Selma Gökahmetoğlu, Serdar Şıvgın, Bülent Eser, Yavuz Köker, Musa Solmaz, Ali Ünal, Mustafa Çetin
INTRODUCTION: The use of αβ+ T-cell-depleted grafts is a novel approach to prevent graft failure, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) in patients undergoing haploidentical hematopoietic stem cell transplantation. PATIENT AND METHOD: Thirty-four patients with acute leukemia and lacking a match donor were treated with αβ T-cell-depleted allografts from haploidentical family donors. A total of 24 patients had acute myeloid leukemia (AML) and 10 had acute lymphoblastic leukemia...
October 10, 2016: Hematology (Amsterdam, Netherlands)
Yoko Karube, Yoshiyuki Ito, Morimichi Nishihira, Takashi Inoue, Osamu Araki, Sumiko Maeda, Satoshi Kobayashi, Masayuki Chida
A 58-year-old male underwent right lung transplantation from a brain-dead donor, after which acute rejection developed that was resistant to steroid pulse therapy. Rabbit-derived anti-thymocyte globulin (rATG) therapy was successful for controlling the rejection. However, following that therapy, the patient was affected by an opportunistic infection and suffered from repeated empyema. It is important to pay attention to immunosuppressive agent levels in blood following treatment, because ATG is a potent immunosuppressive drug and its effects can continue for more than 6 months after administration...
October 2016: Kyobu Geka. the Japanese Journal of Thoracic Surgery
Nicholas R J Gascoigne, Vasily Rybakin, Oreste Acuto, Joanna Brzostek
Thymocyte selection involves the positive and negative selection of the repertoire of T cell receptors (TCRs) such that the organism does not suffer autoimmunity, yet has the benefit of the ability to recognize any invading pathogen. The signal transduced through the TCR is translated into a number of different signaling cascades that result in transcription factor activity in the nucleus and changes to the cytoskeleton and motility. Negative selection involves inducing apoptosis in thymocytes that express strongly self-reactive TCRs, whereas positive selection must induce survival and differentiation programs in cells that are more weakly self-reactive...
October 6, 2016: Annual Review of Cell and Developmental Biology
Dibyendu Kumar Das, Robert J Mallis, Jonathan S Duke-Cohan, Rebecca E Hussey, Paul W Tetteh, Mark Hilton, Gerhard Wagner, Matthew J Lang, Ellis Reinherz
The pre-T cell receptor (preTCR) is a pTα-β heterodimer functioning in early αβ T-cell development. Although once thought to be ligand-autonomous, recent studies show that preTCRs participate in thymic repertoire formation through recognition of peptides bound to major histocompatibility molecules (pMHC). Using optical tweezers, we probe preTCR bonding with pMHC at the single molecule level. Like the αβTCR, the preTCR is a mechanosensor undergoing force-based structural transitions that dynamically enhance bond lifetimes, and exploiting allosteric control regulated via the Cβ FG loop region...
October 5, 2016: Journal of Biological Chemistry
Jason Perera, Zhong Zheng, Shuyin Li, Herman Gudjonson, Olga Kalinina, Jennifer I C Benichou, Katharine E Block, Yoram Louzoun, Dengping Yin, Anita S Chong, Aaron R Dinner, Martin Weigert, Haochu Huang
B cells are unique antigen-presenting cells because their antigen presentation machinery is closely tied to the B cell receptor. Autoreactive thymic B cells can efficiently present cognate self-antigens to mediate CD4(+) T cell-negative selection. However, the nature of thymocyte-thymic B cell interaction and how this interaction affects the selection of thymic B cell repertoire and, in turn, the T cell repertoire are not well understood. Here we demonstrate that a large percentage of thymic B cells have undergone class switching intrathymically...
October 4, 2016: Cell Reports
Rick Admiraal, Caroline A Lindemans, Charlotte van Kesteren, Marc B Bierings, A Birgitta Versluys, Stefan Nierkens, Jaap Jan Boelens
Successful immune reconstitution (IR) is associated with improved outcomes following pediatric cord blood transplantation (CBT). Usage and timing of anti-thymocyte globulin (ATG), introduced to the conditioning to prevent graft-versus-host-disease and graft failure, negatively influences T-cell IR. We studied the relation between ATG exposure, IR and clinical outcomes. All pediatric patients receiving a first CBT between 2004-2015 at the University Medical Center Utrecht were included. ATG-exposure measures were determined with a validated PK-model...
October 4, 2016: Blood
Gaurang Jhala, Jonathan Chee, Prerak M Trivedi, Claudia Selck, Esteban N Gurzov, Kate L Graham, Helen E Thomas, Thomas W H Kay, Balasubramanian Krishnamurthy
High-affinity self-reactive thymocytes are purged in the thymus, and residual self-reactive T cells, which are detectable in healthy subjects, are controlled by peripheral tolerance mechanisms. Breakdown in these mechanisms results in autoimmune disease, but antigen-specific therapy to augment natural mechanisms can prevent this. We aimed to determine when antigen-specific therapy is most effective. Islet autoantigens, proinsulin (PI), and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) were expressed in the antigen-presenting cells (APCs) of autoimmune diabetes-prone nonobese diabetic (NOD) mice in a temporally controlled manner...
July 7, 2016: JCI Insight
Coco de Koning, Stefan Nierkens, Jaap Jan Boelens
T-cell immune reconstitution (IR) after allogeneic hematopoietic cell transplantation (allo-HCT) is highly variable between patients and may take several months to even years. Patients with delayed or unbalanced T-cell IR have a higher probability of developing transplantation-related-morbidity, -mortality, and relapse of disease. Hence, there is a need for strategies to better predict and improve IR to reduce these limitations of allo-HCT. In this review, we provide an update of current and in near-future clinically relevant strategies before, during, and after transplantation to achieve successful T-cell IR...
October 3, 2016: Blood
Staci L Haney, G Michael Upchurch, Jana Opavska, David Klinkebiel, Ryan A Hlady, Sohini Roy, Samikshan Dutta, Kaustubh Datta, Rene Opavsky
DNA methyltransferase 3A (DNMT3A) is an enzyme involved in DNA methylation that is frequently mutated in human hematologic malignancies. We have previously shown that inactivation of Dnmt3a in hematopoietic cells results in chronic lymphocytic leukemia in mice. Here we show that 12% of Dnmt3a-deficient mice develop CD8+ mature peripheral T cell lymphomas (PTCL) and 29% of mice are affected by both diseases. 10% of Dnmt3a+/- mice develop lymphomas, suggesting that Dnmt3a is a haploinsufficient tumor suppressor in PTCL...
September 2016: PLoS Genetics
Isabelle Mothe-Satney, Joseph Murdaca, Brigitte Sibille, Anne-Sophie Rousseau, Raphaëlle Squillace, Gwenaëlle Le Menn, Akila Rekima, Frederic Larbret, Juline Pelé, Valérie Verhasselt, Paul A Grimaldi, Jaap G Neels
Metabolism plays an important role in T cell biology and changes in metabolism drive T cell differentiation and fate. Most research on the role of metabolism in T lymphocytes focuses on mature T cells while only few studies have investigated the role of metabolism in T cell development. In this study, we report that activation or overexpression of the transcription factor Peroxisome Proliferator-Activated Receptor β (PPARβ) increases fatty acid oxidation in T cells. Furthermore, using both in vivo and in vitro models, we demonstrate that PPARβ activation/overexpression inhibits thymic T cell development by decreasing proliferation of CD4(-)CD8(-) double-negative stage 4 (DN4) thymocytes...
September 29, 2016: Scientific Reports
Basile Lebailly, Francina Langa, Christian Boitard, Philip Avner, Ute Christine Rogner
Nonobese diabetic (NOD) mice are a model for type 1 diabetes that displays defects in central immune tolerance, including impairment of thymocyte apoptosis and proliferation. Thymocyte apoptosis is decreased in NOD/Lt mice compared to nondiabetic C3H/HeJ and C57BL/6 mice. Analysis of a set of NOD.C3H and NOD.B6 congenic mouse strains for distal chromosome 6 localizes the phenotype to the 700 kb Idd6.3 interval. Idd6.3 contains the type 1 diabetes candidate gene aryl hydrocarbon receptor nuclear translocator-like 2 (Arntl2), encoding a circadian rhythm-related transcription factor...
September 26, 2016: Mammalian Genome: Official Journal of the International Mammalian Genome Society
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