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https://www.readbyqxmd.com/read/28733353/use-of-proteomics-to-investigate-kidney-function-decline-over-5-years
#1
Axel C Carlsson, Erik Ingelsson, Johan Sundström, Juan Jesus Carrero, Stefan Gustafsson, Tobias Feldreich, Markus Stenemo, Anders Larsson, Lars Lind, Johan Ärnlöv
BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR...
July 21, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28727807/digoxin-reveals-a-functional-connection-between-hiv-1-integration-preference-and-t-cell-activation
#2
Alexander Zhyvoloup, Anat Melamed, Ian Anderson, Delphine Planas, Chen-Hsuin Lee, Janos Kriston-Vizi, Robin Ketteler, Andy Merritt, Jean-Pierre Routy, Petronela Ancuta, Charles R M Bangham, Ariberto Fassati
HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28711718/phospholipase-d1-is-a-regulator-of-platelet-mediated-inflammation
#3
Meike Klier, Nina Sarah Gowert, Sven Jäckel, Christoph Reinhardt, Margitta Elvers
Glycoprotein (GP)Ib is not only required for stable thrombus formation but for platelet-mediated inflammatory responses. Phospholipase (PL)D1 is essential for GPIb-dependent aggregate formation under high shear conditions while nothing is known about PLD1-induced regulation of GPIb in platelet-mediated inflammation and the underlying mechanisms. This study aimed to investigate the relevance of PLD1 for platelet-mediated endothelial and leukocyte recruitment and activation in vitro and in vivo. Pld1(-/-) platelets showed strongly reduced adhesion to TNFα stimulated endothelial cells (ECs) under high shear conditions ex vivo...
July 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28700579/tfh-derived-dopamine-accelerates-productive-synapses-in-germinal-centres
#4
Ilenia Papa, David Saliba, Maurilio Ponzoni, Sonia Bustamante, Pablo F Canete, Paula Gonzalez-Figueroa, Hayley A McNamara, Salvatore Valvo, Michele Grimbaldeston, Rebecca A Sweet, Harpreet Vohra, Ian A Cockburn, Michael Meyer-Hermann, Michael L Dustin, Claudio Doglioni, Carola G Vinuesa
Protective high-affinity antibody responses depend on competitive selection of B cells carrying somatically mutated B-cell receptors by follicular helper T (TFH) cells in germinal centres. The rapid T-B-cell interactions that occur during this process are reminiscent of neural synaptic transmission pathways. Here we show that a proportion of human TFH cells contain dense-core granules marked by chromogranin B, which are normally found in neuronal presynaptic terminals storing catecholamines such as dopamine...
July 12, 2017: Nature
https://www.readbyqxmd.com/read/28699088/sepsis-prediction-in-critically-ill-patients-by-platelet-activation-markers-on-icu-admission-a-prospective-pilot-study
#5
Nathalie Layios, Céline Delierneux, Alexandre Hego, Justine Huart, Christian Gosset, Christelle Lecut, Nathalie Maes, Pierre Geurts, Arnaud Joly, Patrizio Lancellotti, Adelin Albert, Pierre Damas, André Gothot, Cécile Oury
BACKGROUND: Platelets have been involved in both immune surveillance and host defense against severe infection. To date, whether platelet phenotype or other hemostasis components could be associated with predisposition to sepsis in critical illness remains unknown. The aim of this work was to identify platelet markers that could predict sepsis occurrence in critically ill injured patients. METHODS: This single-center, prospective, observational, 7-month study was based on a cohort of 99 non-infected adult patients admitted to ICUs for elective cardiac surgery, trauma, acute brain injury, and post-operative prolonged ventilation and followed up during ICU stay...
December 2017: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/28696349/the-cell-surface-markers-expression-in-postmenopausal-women-and-relation-to-obesity-and-bone-status
#6
Mira Horváthová, Silvia Ilavská, Kornélia Štefíková, Michaela Szabová, Zora Krivošíková, Eva Jahnová, Jana Tulinská, Viera Spustová, Martin Gajdoš
The age-related changes and hormonal deprivation in postmenopausal women are associated with the immune response alteration. The excessive fat accumulation, local and systemic inflammation may lead to dysregulation in immune function and relevant health problems, including obesity and osteoporosis. We analyzed the expression of cell surface markers in the venous blood specimens, stained with fluorophores-conjugated monoclonal antibodies and analysed by multicolour flow cytometry. The significant changes of cytotoxic, naive, and memory T-lymphocytes, plasmacytoid dendritic cells (DCs) were in postmenopausal women versus fertile women...
July 11, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28688767/the-activation-of-b-cells-enhances-dc-sign-expression-and-promotes-susceptibility-of-b-cells-to-hpai-h5n1-infection
#7
Prasit Na-Ek, Jutarat Thewsoongnoen, Maytawan Thanunchai, Suwimon Wiboon-Ut, Noppadol Sa-Ard-Iam, Rangsini Mahanonda, Arunee Thitithanyanont
The interplay between highly pathogenic avian influenza (HPAI) H5N1 virus and immune cells has been extensively studied for years, as host immune components are thought to play significant roles in promoting the systemic spread of the virus and in the induction of cytokine storm. Previous studies suggested that the interaction of B cells and monocytes could promote HPAI H5N1 infection by enhancing avian influenza virus receptor expression. In this study, we further investigate the relationship between the HPAI H5N1 virus, activated B cells, and DC-SIGN expression...
July 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28687069/%C3%AE-%C3%AE-tfh-cells-promote-b-cell-maturation-and-antibody-production-in-neuroblastoma
#8
Wenjun Mou, Wei Han, Xiaoli Ma, Xiaolin Wang, Hong Qin, Wen Zhao, Xiaoya Ren, Xi Chen, Wei Yang, Haiyan Cheng, Xisi Wang, Hui Zhang, Xin Ni, Huanmin Wang, Jingang Gui
BACKGROUND: Previous studies have shown that γδ TFH cells are capable of modulating antibody production in immunized and infected mouse model. In recent studies, human γδ TFH cells are shown to contribute to the activation of humoral immunity and promote the maturation of B cells. However, little information is available on their involvement in neuroblastoma (NB) pathogenesis. RESULTS: In the present study, the frequency of γδ TFH cells in 74 NB patients was significantly higher compared with that in 60 healthy controls...
July 7, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28676852/cd40l-and-its-receptors-in-atherothrombosis-an-update
#9
REVIEW
Nathaly Anto Michel, Andreas Zirlik, Dennis Wolf
CD40L (CD154), a member of the tumor necrosis factor superfamily, is a co-stimulatory molecule that was first discovered on activated T cells. Beyond its fundamental role in adaptive immunity-ligation of CD40L to its receptor CD40 is a prerequisite for B cell activation and antibody production-evidence from more than two decades has expanded our understanding of CD40L as a powerful modulator of inflammatory pathways. Although inhibition of CD40L with neutralizing antibodies has induced life-threatening side effects in clinical trials, the discovery of cell-specific effects and novel receptors with distinct functional consequences has opened a new path for therapies that specifically target detrimental properties of CD40L...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28663244/frontline-science-c-myc-regulates-p-selectin-glycoprotein-ligand-1-expression-in-monocytes-during-hiv-1-infection
#10
Ryan Connor, Letitia D Jones, Xing Qiu, Juilee Thakar, Sanjay B Maggirwar
Leukocyte extravasation is a crucial feature of the normal immune response to disease and infection and is implicated in various pathologies during chronic inflammatory disease. P-Selectin glycoprotein ligand-1 (PSGL-1) is critical for leukocyte extravasation; however, despite extensive study, it remains unclear how its expression is regulated, which in turn, impedes a more precise understanding of how its expression level affects transmigration. To investigate the regulation of PSGL-1, 60 subjects, with or without HIV infection, were recruited and PSGL-1 expression in monocytes was measured...
June 29, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28659358/b-cell-extrinsic-myd88-and-fcer1g-negatively-regulate-autoreactive-and-normal-b-cell-immune-responses
#11
Rebecca A Sweet, Kevin M Nickerson, Jaime L Cullen, Yujuan Wang, Mark J Shlomchik
MyD88 and FcR common γ-chain (Fcer1g, FcRγ) elicit proinflammatory responses to exogenous Ags. Deletion of these receptors in autoimmune models has generally led to reduced overall disease. In B cells, Myd88 is required for anti-DNA and anti-RNA autoantibody responses, whereas Fcer1g is not expressed in these cells. The roles of these receptors in myeloid cells during B cell autoimmune activation remain less clear. To investigate the roles of Myd88 and Fcer1g in non-B cells, we transferred anti-self-IgG (rheumatoid factor) B cells and their physiologic target Ag, anti-chromatin Ab, into mice lacking Fcer1g, Myd88, or both and studied the extrafollicular plasmablast response...
June 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28642278/rheumatoid-arthritis-and-psoriatic-arthritis-synovial-fluid-stimulates-prolactin-production-by-macrophages
#12
Man Wai Tang, Samuel Garcia, Beatriz Malvar Fernandez, Danielle M Gerlag, Paul-Peter Tak, Kris A Reedquist
Prolactin (PRL) is a neuroendocrine hormone that can promote inflammation. We examined the synovial tissue and fluid levels of PRL in patients with inflammatory arthritis, PRL expression in differentiated Mϕs from patients with arthritis and from healthy donors, and the effects of different stimuli on PRL production by Mϕs. PRL levels were measured in paired synovial fluid (SF) and peripheral blood of patients with rheumatoid arthritis (RA, n = 19), psoriatic arthritis (PsA, n = 11), and gout (n = 11). Synovial-tissue PRL mRNA expression was measured by quantitative PCR in patients with RA (n = 25), PsA (n = 11), and gout (n = 12) and in Mϕs differentiated in SF of patients with RA, PsA, other subtypes of spondyloarthritis (SpA), and gout...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28623810/platelet-granule-release-is-associated-with-reactive-oxygen-species-generation-during-platelet-storage-a-direct-link-between-platelet-pro-inflammatory-and-oxidation-states
#13
Mehran Ghasemzadeh, Ehteramolsadat Hosseini
BACKGROUND: Upon platelet stimulation with agonists, reactive oxygen species (ROS) generation enhances platelet activation and granule release. Whether ROS generation during platelet storage could be directly correlated with the expression of proinflammatory molecules and granule release has been investigated in this study. MATERIAL AND METHOD: PRP-platelet concentrates were subjected to flowcytometry analysis to assess the expression of platelet activation marker, P-selectin and CD40L during storage...
June 10, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28623659/immune-activation-of-platelets-in-response-to-serial-phlebotomy-in-pigtailed-macaques-macaca-nemestrina
#14
Kelly A Metcalf Pate, Meghan S Vermillion, Claire E Lyons, Kevin M Najarro, Robert J Adams
Serial phlebotomy is a common sampling practice for repeated-measures studies in biomedical research. In NHP, the effect ofserial blood collection on RBC parameters has been characterized, but the effects on platelet parameters and other aspects of thehemogram have not been well studied. We sought to characterize the circulating platelet phenotype throughout the course of 7serial phlebotomies spanning 30 d in pigtailed macaques (Macaca nemestrina). Phlebotomy was performed on 23 animals at days0, 2, 4, 7, 10, 21, and 30 to quantify the circulating platelet count and markers of both hemostatic and immune platelet activation...
June 16, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28623282/a-nationwide-study-of-severe-and-protracted-diarrhoea-in-patients-with-primary-immunodeficiency-diseases
#15
Wen-I Lee, Chien-Chang Chen, Tang-Her Jaing, Liang-Shiou Ou, Chuen Hsueh, Jing-Long Huang
Diarrhoea lasting longer than 14 days and failing to respond to conventional management is defined as severe and protracted diarrhoea (SD). In this study, we investigated the prevalence, pathogens and prognosis of SD in primary immunodeficiency diseases (PIDs). Among 246 patients with predominantly paediatric-onset PIDs from 2003-2015, 21 [Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG2 (one each)] and five [CVID (four), SCID (one)] without identified mutations had SD before prophylactic treatment...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28609750/association-of-plasma-cd40l-with-acute-chest-syndrome-in-sickle-cell-anemia
#16
Vanessa Tonin Garrido, Laura Sonzogni, Siana Nkya Mtatiro, Fernando F Costa, Nicola Conran, Swee Lay Thein
Platelet activation and platelet-derived cytokines contribute to the vascular inflammation and increased thrombotic activity known to occur in patients with sickle cell anemia (SCA). CD40 ligand (CD40L), a platelet-associated pro-inflammatory molecule that promotes endothelial cell activation, is elevated in the circulation of SCA patients. We sought to evaluate the association of CD40L and inflammation with sickle-related clinical complications and laboratory variables in SCA patients. Soluble CD40L, thrombospondin (TSP)-1 and tumor necrosis factor (TNF)-α were determined in the platelet-poor plasma of healthy individuals and steady-state SCA patients by ELISA...
June 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28589354/crispr-cas9-mediated-in-vitro-mutagenesis-in-gc-like-b-cells
#17
Van Trung Chu, Robin Graf, Klaus Rajewsky
The CRISPR/Cas9 technology has developed into a powerful tool for genome editing, both in terms of gene silencing and the insertion of precise mutations. However, the application of CRISPR/Cas9-mediated mutagenesis in primary immune cells, in particular in B cells, is still in its infancy because of the difficulty to deliver the CRISPR/Cas9 system into these cells. Here, we describe a new method to use CRISPR/Cas9 for manipulating genes in germinal center (GC)-like B cells in vitro. We isolated Cas9-expressing B cells from R26-Cas9iGFP/+ mice (expressing Cas9 constitutively from the Rosa26 locus) and mixed them with control B cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28583714/il-21-anti-tim1-cd40-ligand-promotes-b10-activity-in-vitro-and-alleviates-bone-loss-in-experimental-periodontitis-in-vivo
#18
Yang Hu, Pei Yu, Xinbo Yu, Xingxue Hu, Toshihisa Kawai, Xiaozhe Han
IL-10-expressing regulatory B cells (B10) play an essential role in immune system balance by suppressing excessive inflammatory responses. In this study, we investigated induction of B 10 cell's IL-10 competency in vitro and its effect on ligature-induced experimental periodontitis in vivo. Spleen B cells were isolated from C57BL/6J mice and cultured for 48h under the following conditions: control, CD40L, IL-21, anti-Tim1, CD40L+IL-21, CD40L+anti-Tim1, CD40L+IL-21+anti-Tim1. Silk ligatures were tied around both maxillary second molars of C57BL/6J mice for two weeks...
June 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28567041/pathogen-reactive-t-helper-cell-analysis-in-the-pig
#19
Friederike Ebner, Patrycja Schwiertz, Svenja Steinfelder, Robert Pieper, Jürgen Zentek, Nicole Schütze, Christoph G Baums, Gottfried Alber, Peter Geldhof, Susanne Hartmann
There is growing interest in studying host-pathogen interactions in human-relevant large animal models such as the pig. Despite the progress in developing immunological reagents for porcine T cell research, there is an urgent need to directly assess pathogen-specific T cells-an extremely rare population of cells, but of upmost importance in orchestrating the host immune response to a given pathogen. Here, we established that the activation marker CD154 (CD40L), known from human and mouse studies, identifies also porcine antigen-reactive CD4(+) T lymphocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28559404/peripheral-t-cell-reactivity-to-heat-shock-protein-70-and-its-cofactor-grpe-from-tropheryma-whipplei-is-reduced-in-patients-with-classical-whipple-s-disease
#20
Lucia Trotta, Kathleen Weigt, Katina Schinnerling, Anika Geelhaar-Karsch, Gerrit Oelkers, Federico Biagi, Gino Roberto Corazza, Kristina Allers, Thomas Schneider, Ulrike Erben, Verena Moos
Background: Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response towards Tropheryma (T.) whipplei in genetically predisposed individuals. The cofactor GrpE of heat-shock protein 70 (Hsp70) from T. whipplei was previously identified as B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific pro-inflammatory T-cell responses.Methods: Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before CD40L, CD69, perforin, granzyme B, CD107a, and interferon (IFN)γ were determined in T cells by flow cytometry...
May 30, 2017: Infection and Immunity
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