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https://www.readbyqxmd.com/read/29350833/platelets-kill-bacteria-by-bridging-innate-and-adaptive-immunity-via-pf4-and-fc%C3%AE-riia
#1
R Palankar, T P Kohler, K Krauel, J Wesche, S Hammerschmidt, A Greinacher
BACKGROUND: Activated platelets release the chemokine platelet factor 4 (PF4) stored in their granules. PF4 binds to polyanions (P) on bacteria, undergoes a conformational change and exposes neoepitopes. These neoepitopes induce production of anti-PF4/P antibodies. As PF4 binds to a variety of bacteria, anti-PF4/P IgG can bind and opsonize several bacterial species. OBJECTIVE: Here we investigated whether platelets are able to kill bacteria directly after recognizing anti-PF4/P IgG opsonized bacteria in the presence of PF4 via their FcγRIIA...
January 19, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29325985/platelet-activating-antibodies-are-detectable-at-the-earliest-onset-of-heparin-induced-thrombocytopenia-with-implications-for-the-operating-characteristics-of-the-serotonin-release-assay
#2
Theodore E Warkentin, Donald M Arnold, John G Kelton, Jo-Ann I Sheppard, James W Smith, Ishac Nazy
BACKGROUND: HIT is a prothrombotic drug reaction caused by platelet-activating antibodies that recognize PF4/heparin complexes. It is unknown whether platelet-activating antibodies are detectable at the onset of the HIT-related platelet count fall. METHODS: Available blood samples from 18 patients obtained at onset of HIT were tested using the serotonin-release assay (SRA), a test for platelet-activating antibodies, and a PF4-dependent ELISA. Patient samples showing a delay of >2 days between ELISA and SRA seroconversion were tested for subthreshold levels of platelet-activating antibodies using two modifications of the SRA that amplify detection of HIT antibodies...
January 8, 2018: Chest
https://www.readbyqxmd.com/read/29296706/serologic-characterization-of-anti-protamine-heparin-and-anti-pf4-heparin-antibodies
#3
Grace M Lee, Manali Joglekar, Maragatha Kuchibhatla, Sanjay Khandelwal, Rui Qi, Lubica Rauova, Gowthami M Arepally
Anti-protamine (PRT)/heparin antibodies are a newly described class of heparin-dependent antibodies occurring in patients exposed to PRT and heparin during cardiac surgery. To understand the biologic significance of anti-PRT/heparin antibodies, we developed a murine monoclonal antibody (ADA) specific for PRT/heparin complexes and compared it to patient-derived anti-PRT/heparin antibodies, as well as comparing polyclonal and monoclonal antibodies with anti-platelet factor 4 (PF4)/heparin. Using monoclonal antibodies and polyclonal patient-derived antibodies, we show distinctive binding patterns of anti-PRT/heparin antibodies as compared with PF4/heparin antibodies...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29281877/cellular-and-molecular-changes-in-mnu-induced-breast-tumours-injected-with-pf4-or-bfgf
#4
Siti Norasikin Mohd Nafi, Fauziah Idris, Hasnan Jaafar
Background: Angiogenic activity has been considered to reflect important molecular events during breast tumour development. The present study concerned cellular and molecular changes of MNU-induced breast tumours subjected to promotion and suppression of angiogenesis. Methods: Female Sprague Dawley rats at the age of 21 days received MNU at the dose 70 mg/kg of body weight by intraperitoneal injection. Three months post-carcinogen initiation, mammary tumours were palpated and their growth was monitored. When the tumour diameter reached 1...
December 28, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29279524/transcriptional-analysis-of-endothelial-cell-alternation-induced-by-atrial-natriuretic-polypeptide-in-human-umbilical-vein-endothelial-cells
#5
Xuefeng Li, Yu Liang, Zhili Qiao, Jiaoxia Yang, Pengfei Han, Binghai Zhao, Fengxiang Li, Hengjuan Lv, Jifang Guo, Fengmin Gao, Li Li
The aim of this study was to explore how atrial natriuretic polypeptide (ANP) affects the properties and function of endothelial cells. Gene expression data GSE56976 generated at 0, 1, and 6 hours after ANP incubation in human umbilical vein endothelial cells (HUVEC) was used. Microarray data were preprocessed for differentially expressed genes (DEGs) in each time-dependent group. Next, gene ontology (GO), pathway analysis, and transcriptional regulation were performed. Co-expression clustering analysis of DEGs and functional enrichment analysis of co-expression modules were processed...
December 27, 2017: International Heart Journal
https://www.readbyqxmd.com/read/29220362/optimized-plasma-preparation-is-essential-to-monitor-platelet-stored-molecules-in-humans
#6
Marion Mussbacher, Waltraud C Schrottmaier, Manuel Salzmann, Christine Brostjan, Johannes A Schmid, Patrick Starlinger, Alice Assinger
Platelets store a plethora of different molecules within their granules, modulating numerous pathways, not only in coagulation, but also in angiogenesis, wound healing, and inflammatory diseases. These molecules get rapidly released upon activation and therefore represent an easily accessible indirect marker for platelet activation. Accurate analysis of platelet-derived molecules in the plasma requires appropriate anticoagulation to avoid in vitro activation and subsequent degranulation of platelets, potentially causing artificially high levels and masking biologically relevant differences within translational research studies...
2017: PloS One
https://www.readbyqxmd.com/read/29218266/ensuring-sample-quality-for-blood-biomarker-studies-in-clinical-trials-a-multicenter-international-study-for-plasma-and-serum-sample-preparation
#7
Feng-Ming Spring Kong, Lujun Zhao, Luhua Wang, Yuhchyau Chen, Jie Hu, Xiaolong Fu, Chunxue Bai, Li Wang, Theodore S Lawrence, Mitchell S Anscher, Adam Dicker, Paul Okunieff
Background: Sample quality is critical for biomarker detection in oncology, and platelet degradation and contamination in plasma have a remarkable impact on the ability to accurately quantify many blood-based biomarkers. Platelet factor 4 (PF4) can be used as an indicator to monitor sample quality. This multicenter study aimed to determine the impact of critical components of the blood sample handling process on platelet degradation/contamination and to establish an optimal method for collecting platelet-poor plasma samples...
December 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29204246/constricted-microfluidic-devices-to-study-the-effects-of-transient-high-shear-exposure-on-platelets
#8
Nesreen Z Alsmadi, Sarah J Shapiro, Christopher S Lewis, Vinit M Sheth, Trevor A Snyder, David W Schmidtke
Due to the critical roles that platelets play in thrombosis during many biological and pathological events, altered platelet function may be a key contributor to altered hemostasis, leading to both thrombotic and hemorrhagic complications. Platelet adhesion at arterial shear rates occurs through binding to von Willebrand Factor via the glycoprotein (GP) GPIb receptor. GPIb binding can induce platelet activation distinguishable by P-selectin (CD62P) surface expression and αIIbβ3 activation, resulting in platelet aggregation and formation of the primary hemostatic plug to stop bleeding...
November 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/29198385/platelet-derived-chemokines-in-inflammation-and-atherosclerosis
#9
Constantinos Bakogiannis, Marco Sachse, Kimon Stamatelopoulos, Konstantinos Stellos
Platelets are inflammatory a nuclear cells with a well-established role in the development and manifestation of atherosclerosis. Activated platelets secrete a plethora of chemokines including CXCL4 or platelet factor 4 (PF4), CCL5, CXCL12 or stromal cell derived factor-1α (SDF-1α), CXCL16 and others, which initiate or promote local inflammatory processes at sites of vascular injury. These processes are mainly mediated by the recruitment of circulating haematopoietic stem cells, neutrophils, monocytes or lymphocytes on vascular wall...
November 30, 2017: Cytokine
https://www.readbyqxmd.com/read/29185142/initial-and-long-term-impact-of-a-multi-disciplinary-task-force-in-the-diagnosis-and-management-of-heparin-induced-thrombocytopenia
#10
Ming Y Lim, Joyce Foster, Angela Rourk, Charles S Greenberg
Many medical centers are faced with a major challenge in making an accurate diagnosis of heparin-induced thrombocytopenia (HIT) and ensuring appropriate changes in management strategy in line with guideline recommendations. We report the initial and long-term impact and challenges of institution-wide changes in the diagnosis and management of HIT in the inpatient setting at an academic medical center. We established a HIT Task Force, consisting of a multidisciplinary team of non-malignant hematologists, nursing, pharmacist, pathology, blood bank and clinical lab informatics...
November 28, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29180919/false-positive-immunoassay-for-heparin-induced-thrombocytopenia-in-the-presence-of-monoclonal-gammopathy-a-case-report
#11
Ivana Markovic, Zeljko Debeljak, Bojana Bosnjak, Maja Marijanovic
Heparin induced thrombocytopenia (HIT) is a life-threatening disorder which diagnosis depends on laboratory evaluation. The objective of this report is to present the impact of different laboratory methods for HIT detection on the diagnostic evaluation process. In this case, a 78-year old female patient previously diagnosed with monoclonal gammopathy of undetermined significance (MGUS) was administered with heparin for pulmonary embolism treatment. Patient's initial diagnostic work-up (determination of platelet count and prothrombin time measurement for monitoring of pharmacotherapy) was followed by the clinical estimation of HIT likelihood by "4Ts" score, two immunoassays (ID-PaGIA Heparin/PF4 Antibody Test and ELISA PF4 IgG assay) and one functional test called high-performance liquid chromatography serotonin release assay (HPLC-SRA)...
October 15, 2017: Biochemia Medica: časopis Hrvatskoga Društva Medicinskih Biokemičara
https://www.readbyqxmd.com/read/29172900/development-of-a-high-yield-expression-and-purification-system-for-platelet-factor-4
#12
Angela Huynh, Donald M Arnold, Jane C Moore, James W Smith, John G Kelton, Ishac Nazy
Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction characterized by IgG antibodies bound to complexes of platelet factor 4 (PF4) and heparin. The majority of diagnostic tests for HIT rely on an exogenous source of PF4 to identify anti-PF4/heparin antibodies. These include the PF4-dependent enhanced serotonin release assay (PF4-SRA) among others. Using a bacterial expression system, we developed a novel and efficient method of producing recombinant human PF4 (rhPF4) that is biochemically and antigenically similar to platelet-derived human PF4...
November 27, 2017: Platelets
https://www.readbyqxmd.com/read/29164662/laboratory-tests-for-identification-or-exclusion-of-heparin-induced-thrombocytopenia-hit-or-miss
#13
Emmanuel J Favaloro
Heparin induced thrombocytopenia (HIT) is a potentially fatal condition that arises subsequent to formation of antibodies against complexes containing heparin, usually platelet-factor 4-heparin ('anti-PF4-heparin'). Assessment for HIT involves both clinical evaluation and, if indicated, laboratory testing for confirmation or exclusion, typically using an initial immunological assay ('screening'), and only if positive, a secondary functional assay for confirmation. Many different immunological and functional assays have been developed...
November 22, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29157747/multiplex-proximity-ligation-assay-to-identify-potential-prognostic-biomarkers-for-improved-survival-in-locally-advanced-pancreatic-cancer-patients-treated-with-stereotactic-body-radiation-therapy
#14
Avani D Rao, Yufei Liu, Rie von Eyben, Charles C Hsu, Chen Hu, Lauren M Rosati, Arti Parekh, Kendall Ng, Amy Hacker-Prietz, Lei Zheng, Timothy M Pawlik, Daniel A Laheru, Elizabeth M Jaffee, Matthew J Weiss, Dung T Le, Ralph H Hruban, Ana De Jesus-Acosta, Christopher L Wolfgang, Amol K Narang, Daniel T Chang, Albert C Koong, Joseph M Herman
PURPOSE: To explore seromarker levels for associations with outcomes in locally advanced pancreatic cancer (LAPC) patients who received chemotherapy and stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Serum from LAPC patients in 2 prospective trials of hypofractionated SBRT (5-6.6 Gy × 5) was collected before SBRT. Proximity ligation assay quantified the expression levels of 36 pancreatic cancer-specific candidate seromarkers: Axl, BMP2, CA 125, CA 19-9, CEA, CXCL-1/6/9/10, EGFR, Gas6, Her2, IGF-2, IGFBP-2/3/7, IL-6/6Ra/7/8/12, mesothelin, MMP-1/2/3/7, osteopontin, PDGFRa, PDK1, PF4, RegIV, SPARC, TGF-β, VEGF-A/D, and YKL40...
October 12, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29146335/antioxidant-activity-and-sensory-characteristics-of-maillard-reaction-products-derived-from-different-peptide-fractions-of-soybean-meal-hydrolysate
#15
Min Yu, Shudong He, Mingming Tang, Zuoyong Zhang, Yongsheng Zhu, Hanju Sun
Four peptide fractions PF1 (>5;kDa), PF2 (3-5;kDa), PF3 (1-3;kDa), PF4 (<1;kDa) were isolated from soybean hydrolysate using the ultrafiltration method. Then, d-xylose and l-cysteine were reacted with specific peptide solution at 120;°C for 2;h, and the molecular weight distribution (MWD), pH, colour, browning intensity, DPPH radical-scavenging activity, free amino acids and sensory characteristics of corresponding Maillard reaction products (MRPF1, MRPF2, MRPF3 and MRPF4) were evaluated, respectively...
March 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29107969/assessing-single-stranded-oligonucleotide-drug-induced-effects-in-vitro-reveals-key-risk-factors-for-thrombocytopenia
#16
Sabine Sewing, Adrian B Roth, Michael Winter, Andreas Dieckmann, Cristina Bertinetti-Lapatki, Yann Tessier, Claudia McGinnis, Sylwia Huber, Erich Koller, Corinne Ploix, John C Reed, Thomas Singer, Andreas Rothfuss
Single-stranded oligonucleotides (ON) comprise a promising therapeutic platform that enables selective modulation of currently undruggable targets. The development of novel ON drug candidates has demonstrated excellent efficacy, but in certain cases also some safety liabilities were reported. Among them are events of thrombocytopenia, which have recently been evident in late stage trials with ON drugs. The underlying mechanisms are poorly understood and the risk for ON candidates causing such events cannot be sufficiently assessed pre-clinically...
2017: PloS One
https://www.readbyqxmd.com/read/29104956/deletion-of-the-arp2-3-complex-in-megakaryocytes-leads-to-microthrombocytopenia-in-mice
#17
David S Paul, Caterina Casari, Congying Wu, Raymond Piatt, Swetha Pasala, Robert A Campbell, Kathryn O Poe, Dorsaf Ghalloussi, Robert H Lee, Jeremy D Rotty, Brian C Cooley, Kellie R Machlus, Joseph E Italiano, Andrew S Weyrich, James E Bear, Wolfgang Bergmeier
Actin reorganization regulates key processes in platelet activation. Here we examined the role of the Arp2/3 complex, an essential component in actin filament branching, in platelet function. The Arpc2 gene, encoding the p34 subunit of the Arp2/3 complex, was deleted in the megakaryocyte lineage (Arpc2(fl/fl)PF4-Cre). Deletion of the Arp2/3 complex resulted in marked microthrombocytopenia in mice, caused by premature platelet release into the bone marrow compartment and impaired platelet survival in circulation...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29098740/does-non-contact-low-frequency-ultrasound-nlfu-therapy-contribute-to-wound-healing-at-the-molecular-level
#18
Cornelia Wiegand, Kyle Bittenger, Robert D Galiano, Vickie R Driver, Gary W Gibbons
Non-contact low frequency ultrasound (NLFU) is used to treat various types of chronic wounds including venous, diabetic and pressure ulcers. The objective for this sub study of the IN BALANCE RCT VLU trial was to characterize and compare the NLFU treatment group and patients receiving standard of care (SOC) with respect to the effect of the assigned study treatment on content/quantity of inflammatory cytokines and fibrinogen as well as bacteria. Higher mean wound area reduction was observed in the NLFU treatment group (67...
November 2, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/29048130/beneficial-effect-of-exogenous-platelet-factor-4-for-detecting-pathogenic-heparin-induced-thrombocytopenia-antibodies
#19
Caroline Vayne, Eve-Anne Guery, Claire Kizlik-Masson, Jérôme Rollin, Anne Bauters, Yves Gruel, Claire Pouplard
The laboratory diagnosis of heparin-induced thrombocytopenia (HIT) is based on an enzyme immunoassay combined with a functional test, and serotonin release assay (SRA) is the gold standard for detecting activating HIT antibodies. However, a recent atypical history of HIT prompted us to evaluate whether addition of platelet factor 4 (PF4) during SRA could improve its ability to detect pathogenic HIT antibodies. Using 5B9, a monoclonal antibody to PF4/H with a human Fc fragment, we first defined the optimal PF4 concentration for detecting low amounts of platelet-activating IgG with SRA...
December 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28991552/a-platelet-factor-4-dependent-platelet-activation-assay-facilitates-early-detection-of-pathogenic-heparin-induced-thrombocytopenia-antibodies
#20
Curtis G Jones, Shannon M Pechauer, Brian R Curtis, Daniel W Bougie, Mehraboon S Irani, Binod Dhakal, Brenda Pierce, Richard H Aster, Anand Padmanabhan
Heparin-induced thrombocytopenia (HIT) is a dangerous complication of heparin therapy. HIT diagnosis is established by recognizing thrombocytopenia and/or thrombosis in an affected patient and from the results of serological tests such as the platelet factor 4 (PF4)/heparin immunoassay (PF4 ELISA) and serotonin release assay (SRA). Recent studies suggest that HIT antibodies activate platelets by recognizing PF4 in a complex with platelet glycosaminoglycans (and/or polyphosphates) and that an assay based on this principle, the PF4-dependent P-selectin expression assay (PEA), may be even more accurate than the SRA for HIT diagnosis...
October 2017: Chest
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