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https://www.readbyqxmd.com/read/28806282/adenovirus-infection-in-children-with-acute-myeloid-leukemia-a-report-from-the-canadian-infection-in-acute-myeloid-leukemia-research-group
#1
Samuele Renzi, Salah Ali, Carol Portwine, David Mitchell, David Dix, Victor Lewis, Victoria Price, Michelle Science, Lillian Sung
BACKGROUND: Children with acute myeloid leukemia (AML) are at high risk of life-threatening bacterial and fungal infection. However, little is known about the prevalence or severity of adenovirus infection in this population. Objective was to describe the characteristics, treatments and outcomes of adenovirus infection in children with newly diagnosed AML. METHODS: We performed a retrospective chart review based upon two multi-center cohort studies which focused on identifying risk factors for infection in children with AML...
August 10, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28806274/transfusion-related-immunomodulation-a-reappraisal
#2
Lyla A Youssef, Steven L Spitalnik
PURPOSE OF REVIEW: This review summarizes current and prior observations regarding transfusion-related immunomodulation (TRIM) and puts these ideas into a modern immunological context, incorporating concepts from innate, adaptive, and nutritional immunity. We propose that TRIM research focus on determining whether there are specific, well-defined immunosuppressive effects from transfusing 'pure' red blood cells (RBCs) themselves, along with the by-products produced by the stored RBCs as a result of the 'storage lesion...
August 12, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28806133/autophagy-dictates-metabolism-and-differentiation-of-inflammatory-immune-cells
#3
Thomas Riffelmacher, Felix Clemens Richter, Anna Katharina Simon
The role of macroautophagy/autophagy, a conserved lysosomal degradation pathway, during cellular differentiation has been well studied over the last decade. Particularly, evidence for its role during immune cell differentiation is growing. Despite the description of a variety of dramatic immune phenotypes in tissue-specific autophagy knockout models, the underlying mechanisms are still under debate. One of the proposed mechanisms is the impact of autophagy on the altered metabolic states during immune cell differentiation...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28805931/mrp1-protein-expression-in-leukemic-stem-cells-as-a-negative-prognostic-marker-in-acute-myeloid-leukemia-patients
#4
Maria Paprocka, Aleksandra Bielawska-Pohl, Joanna Rossowska, Agnieszka Krawczenko, Danuta Duś, Marek Kiełbiński, Olga Haus, Maria Podolak-Dawidziak, Kazimierz Kuliczkowski
BACKGROUND: It is well established that expression of multi-drug resistance (MDR) proteins (MDR1, BCRP, MDR3, MRP1 and LRP) in leukemic blasts correlates with AML patients clinical response. Assuming that leukemic stem cells (LSC) are resistant to chemotherapy and responsible for relapse it might be clinically relevant to evaluate the expression level of MDR proteins in LSC and relate it to the clinical outcome. METHODS: Bone marrow samples from 26 patients with de novo AML were labeled with antibodies to distinguish CD34+CD38-CD123+ LSC population and with antibodies against MDR1, BCRP, MDR3, MRP1 or LRP proteins...
August 14, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28805801/small-molecule-studies-identify-cdk8-as-a-regulator-of-il-10-in-myeloid-cells
#5
Liv Johannessen, Thomas B Sundberg, Daniel J O'Connell, Raivo Kolde, James Berstler, Katelyn J Billings, Bernard Khor, Brinton Seashore-Ludlow, Anne Fassl, Caitlin N Russell, Isabel J Latorre, Baishan Jiang, Daniel B Graham, Jose R Perez, Piotr Sicinski, Andrew J Phillips, Stuart L Schreiber, Nathanael S Gray, Alykhan F Shamji, Ramnik J Xavier
Enhancing production of the anti-inflammatory cytokine interleukin-10 (IL-10) is a promising strategy to suppress pathogenic inflammation. To identify new mechanisms regulating IL-10 production, we conducted a phenotypic screen for small molecules that enhance IL-10 secretion from activated dendritic cells. Mechanism-of-action studies using a prioritized hit from the screen, BRD6989, identified the Mediator-associated kinase CDK8, and its paralog CDK19, as negative regulators of IL-10 production during innate immune activation...
August 14, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28805660/prolyl-hydroxylase-2-inactivation-enhances-glycogen-storage-and-promotes-excessive-neutrophilic-responses
#6
Pranvera Sadiku, Joseph A Willson, Rebecca S Dickinson, Fiona Murphy, Alison J Harris, Amy Lewis, David Sammut, Ananda S Mirchandani, Eilise Ryan, Emily R Watts, A A Roger Thompson, Helen M Marriott, David H Dockrell, Cormac T Taylor, Martin Schneider, Patrick H Maxwell, Edwin R Chilvers, Massimilliano Mazzone, Veronica Moral, Chris W Pugh, Peter J Ratcliffe, Christopher J Schofield, Bart Ghesquiere, Peter Carmeliet, Moira Kb Whyte, Sarah R Walmsley
Fully activated innate immune cells are required for effective responses to infection, but their prompt deactivation and removal are essential for limiting tissue damage. Here, we have identified a critical role for the prolyl hydroxylase enzyme Phd2 in maintaining the balance between appropriate, predominantly neutrophil-mediated pathogen clearance and resolution of the innate immune response. We demonstrate that myeloid-specific loss of Phd2 resulted in an exaggerated inflammatory response to Streptococcus pneumonia, with increases in neutrophil motility, functional capacity, and survival...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28805489/atorvastatin-attenuates-experimental-contrast-induced-acute-kidney-injury-a-role-for-tlr4-myd88-signaling-pathway
#7
Rongzheng Yue, Chuan Zuo, Jing Zeng, Baihai Su, Ye Tao, Songmin Huang, Rui Zeng
OBJECTIVES: To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. METHODS: Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28805251/wiskott-aldrich-syndrome-protein-emerging-mechanisms-in-immunity
#8
REVIEW
Elizabeth Rivers, Adrian J Thrasher
The Wiskott Aldrich syndrome protein (WASP) participates in innate and adaptive immunity through regulation of actin cytoskeleton-dependent cellular processes, including immune synapse formation, cell signaling, migration and cytokine release. There is also emerging evidence for a direct role in nuclear transcription programmes uncoupled from actin polymerization. A deeper understanding of some of the more complex features of Wiskott Aldrich syndrome (WAS) itself, such as the associated autoimmunity and inflammation, has come from identification of defects in the number and function of anti-inflammatory myeloid cells and regulatory T and B cells, as well as defects in positive and negative B-cell selection...
August 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28805019/cd11b-gr1-dim-tolerogenic-dendritic-cell-like-cells-are-expanded-in-interstitial-lung-disease-in-skg-mice
#9
Sho Sendo, Jun Saegusa, Takaichi Okano, Soshi Takahashi, Kengo Akashi, Akio Morinobu
OBJECTIVE: SKG mice develop interstitial lung disease (ILD) resembling rheumatoid arthritis-associated ILD (RA-ILD) in human. The aim of this study is to clarify the mechanism behind the lung pathology by analyzing the lung-infiltrating cells in ILD of SKG mice. METHODS: We assessed the severity of zymosan A (ZyA)-induced ILD in SKG mice histologically, and examined lung-infiltrating cells by flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (M-MDSCs) were cultured in vitro with GM-CSF (and IL-4)...
August 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28804680/treatment-of-older-patients-with-acute-myeloid-leukemia-aml-revised-canadian-consensus-guidelines
#10
REVIEW
Joseph M Brandwein, Nancy Zhu, Rajat Kumar, Brian Leber, Mitchell Sabloff, Irwindeep Sandhu, Jeannine Kassis, Harold J Olney, Mohamed Elemary, Andre C Schuh
The treatment of acute myeloid leukemia (AML) in older patients is undergoing rapid changes, with a number of important publications in the past five years. Because of this, a group of Canadian leukemia experts has produced an update to the Canadian Consensus Guidelines that were published in 2013, with several new agents recommended, subject to availability. Recent studies have supported the survival benefit of induction chemotherapy for patients under age 80, except those with major co-morbidities or those with adverse risk cytogenetics who are not candidates for allogeneic hematopoietic stem cell transplantation (HSCT)...
2017: American Journal of Blood Research
https://www.readbyqxmd.com/read/28804542/significant-association-of-trem-1-with-hmgb1-tlrs-and-rage-in-the-pathogenesis-of-insulin-resistance-in-obese-diabetic-populations
#11
Saravanan Subramanian, Pradeep K Pallati, Poonam Sharma, Devendra K Agrawal, Kalyana C Nandipati
Activated cell surface and intracellular receptors lead to insulin resistance in obesity. Among these receptors, triggering receptors expressed on myeloid cells (TREM)-1, toll like receptors (TLRs), and receptors for advanced glycation end products (RAGE) play a significant role in the induction of inflammatory response in innate immunity. TREM-1 potentially amplifies TLRs and RAGE synergistically with DNA-binding high-mobility group box 1 (HMGB-1). The objective of the study was to analyze the association between TREM-1/DAP12 and HMGB-1, RAGE and TLRs in obesity-induced insulin resistance...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28803964/tgf%C3%AE-smad-signalling-modulates-mll-and-mll-af4-mediated-5-lipoxygenase-promoter-activation
#12
Meike J Saul, Florian Groher, Anett B Hegewald, Michaela Müller-McNicoll, Rolf Marschalek, Beatrix Suess, Dieter Steinhilber
5-Lipoxygenase (5-LO) catalyzes the initial two steps of the conversion of arachidonic acid to leukotrienes which represent a group of pro-inflammatory lipid mediators involved in immune defense reactions as well as inflammation, allergy and cancer. Transforming growth factor-β (TGFβ) and calcitriol strongly upregulate 5-LO expression during myeloid cell differentiation and MLL-AF4 has been shown to strongly activate the 5-LO promoter. Here, we investigated the role of TGFβ/SMAD signalling in 5-LO promoter activation...
August 10, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28803924/differential-regulation-of-the-tlr4-signalling-pathway-in-post-mortem-prefrontal-cortex-and-cerebellum-in-chronic-schizophrenia-relationship-with-sp-transcription-factors
#13
Karina S MacDowell, Raquel Pinacho, Juan C Leza, Joan Costa, Belén Ramos, Borja García Bueno
Alterations in innate immunity may underlie the pathophysiology of schizophrenia (SZ). Toll-like receptor-4 (TLR4) is a master element of innate immunity. The specificity proteins (SPs), transcription factors recently implicated in SZ, are putative regulatory agents of this. This work was aimed at describing alterations in the TLR4 signalling pathway in postmortem brain prefrontal cortex (PFC) and cerebellum (CB) of 16 chronic SZ patients and 14 controls. The possible association of TLR4 pathway with SP1 and SP4 and SZ negative symptomatology is explored...
August 10, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28803825/cardiovascular-events-after-exposure-to-nilotinib-in-chronic-myeloid-leukemia-long-term-follow-up
#14
Nazanin Aghel, Jeffrey Howard Lipton, Eshetu G Atenafu, Dennis Dong Hwan Kim, Diego Hernan Delgado
INTRODUCTION: Nilotinib is a highly effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML). However, reports of cardiovascular toxicities caused by nilotinib have recently raised critical concerns. The aim of the present study was to evaluate the incidence of cardiovascular events (CVEs) and frequency of asymptomatic peripheral arterial disease (PAD) after long-term exposure to nilotinib. PATIENTS AND METHODS: In the present retrospective cohort, we evaluated the incidence of CVEs in 63 CML patients treated with nilotinib...
July 15, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28803258/the-impact-of-antimicrobial-prophylaxis-in-morbidity-and-infections-during-azacitidine-treatment
#15
Natalia Lorenzana, Laura Francisca Avila, Sara Alonso, Enrique Colado, Teresa Bernal
The clinical consequences of the infectious events in patients receiving azacitidine are poorly documented. Likewise, the role of primary antimicrobial prophylaxis is unknown. In this retrospective, single-center study, we compare the impact of prophylaxis on the incidence of infection and morbidity in all consecutive higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients, during the first 4 azacitidine cycles. Seventy-six patients, corresponding to 283 azacitidine cycles, were studied...
August 13, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28803141/the-poly-proline-tail-of-sivmac-vpx-provides-gain-of-function-for-resistance-to-a-cryptic-proteasome-dependent-degradation-pathway
#16
Nannan Zhang, Haoran Guo, Jiaxin Yang, Guanchen Liu, Shuang Li, Siying Li, Dongyin Wang, Rui Li, Chang Shu, Hongmei Xu, Zhentong Wei, Honglan Huang, Songling Zhang, Pujun Gao, Shan Cen, Richard Markham, Yongsheng Wang, Xiao-Fang Yu, Wei Wei
The lentiviral accessory protein Vpx is critical for viral infection of myeloid cells and acts by hijacking CRL4(DCAF1) E3 ubiquitin ligase to induce the degradation of the host restriction factor SAMHD1. It has been observed that the sequences from HIV-2 and SIVsmm/SIVmac Vpx contain a poly-proline tail which is distinct from other SIV Vpx proteins. However, the role of this region in Vpx function is controversial. Herein, we found proteasome-dependent degradation of a Vpx mutant lacking the poly-proline tail in the nucleus in a CRL4(DCAF1) E3 ligase-independent fashion...
August 10, 2017: Virology
https://www.readbyqxmd.com/read/28803005/safety-and-feasibility-of-therapeutic-platelet-depletion-with-spectra-optia-in-a-pregnant-woman
#17
Roman Małachowski, Olga Grzybowska-Izydorczyk, Nelly Besson, Anna Szmigielska-Kapłon, Mateusz Nowicki, Agnieszka Wierzbowska
INTRODUCTION: Thrombocytapheresis is an alternative treatment beneficial in rare circumstances, when cytoreductive agents are contraindicated, drug therapy gave no response or the expected response would be too slow. Here we present a case of a pregnant woman who underwent 5 thrombocytaphereses using Spectra Optia device to reduce circulating platelets (PLT) count and prepare for Cesarian section. PATIENT CHARACTERISTICS AND PERFORMED TREATMENT: A 39-year-old woman with diagnosed chronic myeloid leukemia (CML) was treated with interferon because of too high PLT count...
July 27, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28802907/the-who-how-and-why-allogeneic-transplant-for-acute-myeloid-leukemia-in-patients-older-than-60years
#18
REVIEW
Sarah A Wall, Steven Devine, Sumithira Vasu
Acute myelogenous leukemia (AML) is primarily a disease of the elderly, and as such, our approach to treatment needs to be tailored to address an aging population. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative treatment for intermediate and high risk AML, and until recently, its use had been limited to a younger population and dependent on availability of a donor. Advances in conditioning regimens, supportive care, and the use of alternative donor sources have greatly expanded access to this therapy...
July 15, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28802867/novel-single-cell-technologies-in-acute-myeloid-leukemia-research
#19
REVIEW
Soumyasri Das Gupta, Zohar Sachs
Acute myeloid leukemia (AML) is a lethal malignancy because patients who initially respond to chemotherapy eventually relapse with treatment refractory disease. Relapse is caused by leukemia stem cells (LSCs) that reestablish the disease through self-renewal. Self-renewal is the ability of a stem cell to produce copies of itself and give rise to progeny cells. Therefore, therapeutic strategies eradicating LSCs are essential to prevent relapse and achieve long-term remission in AML. AML is a heterogeneous disease both at phenotypic and genotypic levels, and this heterogeneity extends to LSCs...
July 25, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28802852/autophagy-regulates-accumulation-and-functional-activity-of-granulocytic-myeloid-derived-suppressor-cells-via-stat3-signaling-in-endotoxin-shock
#20
Guanjun Dong, Chuanping Si, Qingqing Zhang, Fenglian Yan, Chunxia Li, Hui Zhang, Qun Ma, Jun Dai, Zhihua Li, Hui Shi, Bo Wang, Junfeng Zhang, Jiankuo Ming, Yuan Hu, Shuo Geng, Yao Zheng, Liwu Li, Huabao Xiong
Autophagy extensively participates in immune responses and inflammatory diseases. Myeloid-derived suppressor cells (MDSCs) are derived from CD11b(+)Gr1(+) cells under pathological conditions and play an immunosuppressive role in the pathogenesis of cancer and inflammatory diseases. However, the role of autophagy in regulating the accumulation and activity of MDSCs remains unknown. In the present study, we evaluated the effects and mechanisms of autophagy on regulating accumulation and activity of MDSCs. We first found that granulocytic MDSCs (G-MDSCs), but not monocytic MDSCs (M-MDSCs), were accumulated in mice challenged by lipopolysaccharide (LPS) and showed an elevated autophagy activity...
August 9, 2017: Biochimica et Biophysica Acta
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