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Hematopoietic diseases

Kipp Weiskopf, Peter J Schnorr, Wendy W Pang, Mark P Chao, Akanksha Chhabra, Jun Seita, Mingye Feng, Irving L Weissman
The hematopoietic stem cell (HSC) is a multipotent stem cell that resides in the bone marrow and has the ability to form all of the cells of the blood and immune system. Since its first purification in 1988, additional studies have refined the phenotype and functionality of HSCs and characterized all of their downstream progeny. The hematopoietic lineage is divided into two main branches: the myeloid and lymphoid arms. The myeloid arm is characterized by the common myeloid progenitor and all of its resulting cell types...
October 2016: Microbiology Spectrum
Joceline S Liu, Matthew I Bury, Natalie J Fuller, Renea M Sturm, Nida Ahmad, Arun K Sharma
Substitution urethroplasty for the treatment of male stricture disease is often accompanied by subsequent tissue fibrosis and secondary stricture formation. Patients with pre-existing morbidities are often at increased risk of urethral stricture recurrence brought upon in-part by delayed vascularization accompanied by overactive inflammatory responses following surgery. Within the context of this study, we demonstrate the functional utility of a cell/scaffold composite graft comprised of human bone marrow-derived mesenchymal stem cells (MSC) combined with CD34+ hematopoietic stem/progenitor cells (HSPC) to modulate inflammation and wound healing in a rodent model of substitution urethroplasty...
October 20, 2016: Scientific Reports
Nirali N Shah, Theresa M Watson, Bonnie Yates, David J Liewehr, Seth M Steinberg, David Jacobsohn, Terry J Fry
BACKGROUND: Diagnosis of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) can be a challenge due to the systemic presentation and alternative etiologies. With a goal of establishing biomarkers to more accurately distinguish ES, we prospectively analyzed levels of cytokines during HSCT. PROCEDURES: We performed a prospective study of children ≤21 years who underwent allogeneic HSCT. Blood samples for interleukin (IL)-6, IL-8, IL-10, IL-1b, IL-12p70, interferon-γ, tumor necrosis factor alpha (TNF-α) and procalcitonin were obtained from each subject prior to conditioning, at day 0, and then biweekly through engraftment and at days 30, 60 and 100...
October 20, 2016: Pediatric Blood & Cancer
Katsuto Takenaka, Kazuya Shimoda, Naoyuki Uchida, Taizo Shimomura, Koji Nagafuji, Tadakazu Kondo, Hirohiko Shibayama, Takehiko Mori, Kensuke Usuki, Taichi Azuma, Yutaka Tsutsumi, Junji Tanaka, Hitomi Dairaku, Keitaro Matsuo, Keiya Ozawa, Mineo Kurokawa, Shunya Arai, Koichi Akashi
We conducted a 17-year nationwide survey (1999-2015) to elucidate the clinical outcomes of patients with primary myelofibrosis (PMF) in Japan. Questionnaires were sent annually to approximately 500 hematology departments. Newly diagnosed patients with PMF were enrolled in this study, and were followed up annually to collect prognostic information. Approximately 50 patients were enrolled per year, yielding a total of 780 patients with PMF included in this study. The median age at diagnosis was 66 years. At the time of analysis, the median survival duration was 47 months, and the 3-year overall survival rate was 59 %...
October 19, 2016: International Journal of Hematology
Florent Elefteriou
The bone marrow microenvironment is characterized by its multicellular nature, and perhaps less obviously by the high mobility of multiple transient and stationary cell lineages present in this environment. The trafficking of hematopoietic and mesenchymal cells between the bone marrow and blood compartments is regulated by a number of bone marrow-derived factors. It is suspected that transformed metastatic cells "hijack" these processes to engraft into the skeleton and eventually cause the skeletal complications associated with metastatic disease...
September 2016: Journal of Bone Oncology
Jessalyn M Ubellacker, Sandra S McAllister
Systemic factors including cytokines, cell-free nucleic acids, microvesicles, and platelets are appreciated as important regulators of adenocarcinoma progression. Research findings using pre-clinical mouse models have revealed that many such systemically acting factors are either secreted by or responsive to peripheral tumors and impact bone and bone marrow (collectively referred to as the bone microenvironment) to initiate processes that ultimately govern disease progression, even in the absence of detectable bone metastases...
September 2016: Journal of Bone Oncology
Hidekazu Nishikii, Byung-Su Kim, Yasuhisa Yokoyama, Yan Chen, Jeanette Baker, Antonio Pierini, Maite Alvarez, Melissa Mavers, Kristina Maas-Bauer, Yuqiong Pan, Shigeru Chiba, Robert S Negrin
CD4(+)Foxp3(+) regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft versus host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation (HCT). We recently demonstrated that a single treatment of the agonistic antibody to DR3 (Death receptor 3, αDR3) to donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated...
October 19, 2016: Blood
Kate Stringaris, David Marin, A John Barrett, Robert Hills, Catherine Sobieski, Kai Cao, Jerome G Saltarrelli, May Daher, Hila Shaim, Nathaniel Smith, David Linch, Rosemary Gale, Christopher Allen, Takuya Sekine, Rohtesh Mehta, Richard Champlin, Elizabeth J Shpall, Hagop Kantarjian, Guillermo Garcia-Manero, Katayoun Rezvani
Myelodysplastic syndromes (MDS) are a group of hematopoietic disorders affecting the myeloid lineage, characterized by cytopenias and clonal evolution to acute myeloid leukemia (AML). We hypothesized that natural killer (NK) cells and their activating killer immunoglobulin-like receptors (aKIRs) influence the immune surveillance and clinical outcome of patients with MDS. Here, we first examined the distribution of aKIR genes and haplotype in two independent cohorts of MDS and AML patients. The median number of aKIR genes was lower in MDS patients than healthy controls (2 vs...
October 19, 2016: Blood
Paul J Martin, Wenhong Fan, Barry E Storer, David M Levine, Lue Ping Zhao, Edus H Warren, Mary E D Flowers, Stephanie J Lee, Paul A Carpenter, Michael Boeckh, Sangeeta Hingorani, Li Yan, Qiang Hu, Leah Preus, Song Liu, Stephen Spellman, Xiaochun Zhu, Marcelo Pasquini, Philip McCarthy, Daniel Stram, Xin Sheng, Loreall Pooler, Christopher A Haiman, Lara Sucheston-Campbell, Theresa Hahn, John A Hansen
Previous studies have identified single-nucleotide polymorphisms (SNPs) associated with the risk of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). The current study determined whether these associations could be replicated in large cohorts of donors and recipients. Each SNP was tested with cohorts of patients having the same donor type (HLA-matched related, unrelated or both) reported in the original publication, and testing was limited to the same genome (recipient or donor) and genetic model (dominant, recessive or allelic) reported in the original study...
October 6, 2016: Blood
Scott N Furlan, Benjamin Watkins, Victor Tkachev, Sarah Cooley, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, Daniel J Hunt, John B Schell, Katie Zeleski, Alison Yu, Cindy Giver, Edmund Waller, Jeffrey S Miller, Bruce R Blazar, Leslie S Kean
One of the central challenges of transplantation is the development of alloreactivity despite the use of multi-agent immunoprophylaxis. Effective control of this immune-suppression-resistant T cell activation represents one of the key unmet needs in the fields of both solid organ and hematopoietic stem cell transplant (HCT). To address this unmet need, we have used a highly-translational non-human primate model to interrogate the transcriptional signature of T cells during Breakthrough Acute GVHD that occurs in the setting of clinically-relevant immune suppression and compared this to the Hyperacute GVHD, that develops in unprophylaxed or sub-optimally prophylaxed transplant recipients...
October 6, 2016: Blood
Yini Wang, Zhao Wang
PURPOSE OF REVIEW: Hemophagocytic lymphohistiocytosis (HLH) is a condition of uncontrolled immune activation with a high mortality rate. The recommended therapeutic guideline for HLH was published by the Histiocyte Society in 1994 and revised in 2004, which greatly improved the survival in patients with HLH. However, HLH is still a refractory disease for which the search for novel treatments continues. This article overviewed recent advances in treatment of HLH. RECENT FINDINGS: Current practices in treatment extend from chemo-immunotherapy to some new cytokine-targeting biologicals, which are more effective to eliminate pathologically activated T cells and resist exaggerated cytokine storm...
October 15, 2016: Current Opinion in Hematology
C Martínez, A S Jorge, A Pereira, M Moreno, J Núñez, J Gayoso, J Gonzalez-Medina, N Revilla, A Sampol, E Domingo-Domenech, F de la Cruz, A Morales, M J Rodriguez-Salazar, S Valiente, E Pérez-Ceballos, J Pérez de Oteyza, R García-Sanz
Autologous hematopoietic cell transplantation (AHCT) is the standard of care for young patients with relapsed/refractory (R/R) Hodgkin's lymphoma (HL). However, there is limited experience of its efficacy and feasibility in older patients. The characteristics and outcomes of 121 patients aged ≥50 years (42 of them are ≥60 years old) with R/R HL who underwent AHCT were reviewed. After a median follow-up of 3.1 years, overall survival (OS) and progression-free survival (PFS) at 5 years were 64 and 55 %, respectively, with no differences between 50-59-year-old and ≥60-year-old patients...
October 18, 2016: Annals of Hematology
Michael Medinger, Claudia Lengerke, Jakob Passweg
Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades...
2016: Leukemia Research Reports
Steven Wang, Jie Yan, Guangde Zhou, Rebecca Heintzelman, J Steve Hou
Myeloproliferative neoplasms (MPNs) are hematopoietic malignancies characterized by unchecked proliferation of differentiated myeloid cells. The most common BCR-ABL1-negative MPNs are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The discovery of JAK2 V617F mutation has improved our understanding of the molecular basis of MPN. The high frequency of JAK2 mutation in MPN makes JAK2 mutation testing an essential diagnostic tool and potential therapeutic target for MPN. Here, we present a rare case of a 34-year-old patient who was initially diagnosed with acute myeloid leukemia (AML) with mutated NPM1...
2016: Case Reports in Hematology
Juan Gea-Banacloche, Krishna Komanduri, Paul Carpenter, Sophie Paczesny, Stefanie Sarantopoulos, Jo-Anne Young, Nahed El Kassar, Robert Q Le, Kirk Schultz, Linda M Griffith, Bipin Savani, John R Wingard
Immune reconstitution following hematopoietic stem cell transplantation (HCT) beyond one year is not completely understood. Many transplant recipients who are free of graft versus host disease (GVHD) and not receiving any immunosuppression more than a year after transplant seem to be able to mount appropriate immune responses to common pathogens and respond adequately to immunizations. However, two large registry studies over the last two decades seem to indicate that infection is a significant cause of late mortality in some patients, even in the absence of concomitant GVHD...
October 14, 2016: Biology of Blood and Marrow Transplantation
Raziyeh Tootoonchian, Fatemeh Pak, Ali M Ardekani, Nasrin Sehati, Manuchehr Abedi-Valugerdi, Parviz Kokhaei
The present study tried to explain CD56+ lymphocyte cells activities and possible prognostic role of these cells in Graft-Versus-Host-Disease (GVHD). The role of IL-12 activation and function is of interest in this study. Peripheral blood samples of 51 Hematopoietic Stem Cell Transplantation (HSCT) recipients collected at before (day -8) and after (days 7 and 14). PBMC were collected by Ficoll separation and analyzed by Flow Cytometry using triple antibody (CD45-PerCP, CD56-FITC, and CD69-PE staining and control antibody...
October 14, 2016: Transplant Immunology
Loïc Peter, Diana Mateus, Pierre Chatelain, Denis Declara, Noemi Schworm, Stefan Stangl, Gabriele Multhoff, Nassir Navab
The examination of biopsy samples plays a central role in the diagnosis and staging of numerous diseases, including most cancer types. However, because of the large size of the acquired images, the localization and quantification of diseased portions of a tissue is usually time-consuming, as pathologists must scroll through the whole slide to look for objects of interest which are often only scarcely distributed. In this work, we introduce an approach to facilitate the visual inspection of large digital histopathological slides...
October 5, 2016: Medical Image Analysis
Marina Cavazzana, Jean-Antoine Ribeil, Chantal Lagresle-Peyrou, Isabelle André-Schmutz
When considering inherited diseases that can be treated by gene transfer into Hematopoietic stem cells (HSCs), there are only two in which the HSC and progenitor cell distribution inside the bone marrow and its microenvironment are exactly the same as in a healthy subject: metachromatic leukodystrophy (MLD) and ALD. In all other settings (X-linked severe combined immunodeficiency (SCID-X1), adenosine deaminase deficiency, Wiskott-Aldrich syndrome and β-hemoglobinopathies), the bone marrow content of the different stem and precursor cells and the cells' relationship with the stroma have very specific characteristics...
October 17, 2016: Stem Cells and Development
Kenji Kishimoto, Ryoji Kobayashi, Daiki Hori, Hirozumi Sano, Daisuke Suzuki, Kazue Yasuda, Kunihiko Kobayashi
To determine whether pretransplant PSD affects the clinical outcomes in HSCT, a retrospective cohort analysis of 73 pediatric and adolescent patients who underwent HSCT was performed. Pretransplant PSD was defined as the presence of a fluid level or mucosal swelling or total opacity on sinus X-ray or CT examination performed before HSCT. Pretransplant PSD was observed in 21 (29%) patients. The probability of 2-year OS after HSCT was 42% in patients with pretransplant PSD (PSD group), and 64% in those without (non-PSD group) (P=...
October 17, 2016: Pediatric Transplantation
Rachel Mourot-Cottet, Frédéric Maloisel, François Séverac, Olivier Keller, Thomas Vogel, Martine Tebacher, Jean-Christophe Weber, Georges Kaltenbach, Jacques-Eric Gottenberg, Bernard Goichot, Jean Sibilia, Anne-Sophie Korganow, Raoul Herbrecht, Emmanuel Andrès
BACKGROUND: Little data is currently available in the literature on neutropenia and agranulocytosis in the elderly, and, to our knowledge, idiosyncratic drug-induced agranulocytosis is particularly poorly covered, or not at all. OBJECTIVE: We herein describe the clinical picture and outcome of patients aged ≥75 years with established idiosyncratic drug-induced agranulocytosis. PATIENTS AND METHODS: Data from 61 patients over 75 years old with idiosyncratic drug-induced agranulocytosis were retrospectively reviewed...
September 5, 2016: Drugs—Real World Outcomes
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