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https://www.readbyqxmd.com/read/29214154/the-search-for-biomarkers-in-hereditary-angioedema
#1
REVIEW
Allen P Kaplan, Coen Maas
The unpredictable nature of attacks of tissue swelling in hereditary angioedema requires the identification of reliable biomarkers to monitor disease activity as well as response to therapy. At present, one can assess a C4 level (by ELISA) to assist in diagnosis but neither C4 nor C1 inhibitor levels reflect clinical course or prognosis. We will here review a collection of plasma proteins involved in blood coagulation, fibrinolysis, and innate immunity (Figure 1). A main focus is those proteins that are key to the formation of bradykinin (BK); namely, factor XII, plasma prekallikrein/kallikrein, high-molecular weight kininogen, and BK itself since overproduction of BK is key to the disease...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29176937/proteomic-profiling-identifies-markers-for-inflammation-related-tumor-fibroblast-interaction
#2
Daniel Drev, Andrea Bileck, Zeynep N Erdem, Thomas Mohr, Gerald Timelthaler, Andrea Beer, Christopher Gerner, Brigitte Marian
Background: Cancer associated fibroblasts are activated in the tumor microenvironment and contribute to tumor progression, angiogenesis, extracellular matrix remodeling, and inflammation. Methods: To identify proteins characteristic for fibroblasts in colorectal cancer we used liquid chromatography-tandem mass spectrometry to derive protein abundance from whole-tissue homogenates of human colorectal cancer/normal mucosa pairs. Alterations of protein levels were determined by two-sided t test with greater than threefold difference and an FDR of < 0...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/29122754/limited-role-of-kininogen-in-the-host-response-during-gram-negative-pneumonia-derived-sepsis
#3
Chao Ding, Cornelis Van't Veer, Joris J T H Roelofs, Meenal Shukla, Keith R McCrae, Alexey S Revenko, Jeff Crosby, Tom van der Poll
High molecular weight kininogen (HK), together with Factor XI, Factor XII and prekallikrein, is part of the contact system, which has proinflammatory, prothrombotic and vasoactive properties. We hypothesized that HK plays a role in the host response during pneumonia derived sepsis. To this end mice were depleted of kininogen (KNG) to plasma HK levels of 28% of normal by repeated treatment with a specific antisense oligonucleotide (KNG ASO) for three weeks prior to infection with the common human sepsis pathogen Klebsiella pneumoniae via the airways...
November 9, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29091393/a-positively-charged-surface-triggers-coagulation-activation-through-factor-vii-activating-protease-fsap
#4
Claudia Sperling, Manfred F Maitz, Simona Grasso, Carsten Werner, Sandip Kanse
Contact between biomedical materials and blood often initiates undesirable pro-coagulant and pro-inflammatory processes. On negatively charged materials blood coagulation is known to be triggered through auto-activation of Factor XII, while activation on cationic surfaces follows a distinct and so far enigmatic mechanism. As Factor VII activating protease (FSAP), is known to be activated on positively and on negatively charged macromolecules in plasma, we have investigated its interaction with charged biomaterials and its consequences for coagulation...
November 1, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29075790/differential-contribution-of-tissue-factor-and-factor%C3%A2-xii-to-thrombin-generation-triggered-by-breast-and-pancreatic-cancer-cells
#5
Aurélie Rousseau, Annette K Larsen, Patrick Van Dreden, Michele Sabbah, Ismail Elalamy, Grigoris T Gerotziafas
Most cancer cells trigger thrombin generation (TG) to various extent. In the present study, we dissected the mechanisms responsible for the procoagulant activity of pancreatic adenocarcinoma cells (BXPC3), a highly thrombogenic cancer type, and breast cancer cells (MCF7), a less thombogenic tumor type. TG of normal plasma was assessed by the Thrombinoscope (CAT®) in the presence or absence of cancer cells. TG was also assessed in plasma depleted of clotting factors, in plasma spiked with tissue factor (TF) and/or procoagulant phospholipids, in plasma spiked with an anti-TF monoclonal antibody or with corn trypsin inhibitor (CTI)...
October 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29072555/streptococcus-gallolyticus-subsp-gallolyticus-endocarditis-isolate-interferes-with-coagulation-and-activates-the-contact-system
#6
Julia Isenring, Juliane Köhler, Masanobu Nakata, Marcus Frank, Christoph Jans, Pierre Renault, Camille Danne, Shaynoor Dramsi, Bernd Kreikemeyer, Sonja Oehmcke-Hecht
Streptococcus gallolyticus subsp. gallolyticus, formerly classified as S. bovis biotype I, is an increasing cause of bacteremia and infective endocarditis in the elderly. The physiopathology of infective endocarditis is poorly understood and involves immune and coagulation systems. In this study, we found that S. gallolyticus subsp. gallolyticus activates the human contact system, which in turn has two consequences: cleavage of high-molecular-weight kininogen (HK) resulting in release of the potent pro-inflammatory peptide bradykinin, and initiation of the intrinsic pathway of coagulation...
October 26, 2017: Virulence
https://www.readbyqxmd.com/read/29053871/cellular-and-morphological-characterization-of-blastoderms-from-freshly-laid-broiler-eggs
#7
N Pokhrel, E Ben-Tal Cohen, O Genin, D Sela-Donenfeld, Y Cinnamon
The pioneering study of Eyal-Giladi and Kochav (EG&K; Eyal-Giladi and Kochav, 1976) on the early developmental stages-from fertilization, through oviposition, to the gastrulation process-set the standard for characterizing chicken embryos, and has been used in numerous studies over the years. During uterine development, the chicken embryo undergoes dramatic changes, extremely rapid cell cycles, massive cell death, and axial determination processes. However, once the egg is laid, the temperature drops and the embryo enters into a diapause-like state...
October 5, 2017: Poultry Science
https://www.readbyqxmd.com/read/29034235/coagulofibrinolytic-changes-in-patients-with-post-cardiac-arrest-syndrome
#8
REVIEW
Takeshi Wada
Whole-body ischemia and reperfusion due to cardiac arrest and subsequent return of spontaneous circulation constitute post-cardiac arrest syndrome (PCAS), which consists of four syndromes including systemic ischemia/reperfusion responses and post-cardiac arrest brain injury. The major pathophysiologies underlying systemic ischemia/reperfusion responses are systemic inflammatory response syndrome and increased coagulation, leading to disseminated intravascular coagulation (DIC), which clinically manifests as obstruction of microcirculation and multiple organ dysfunction...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29017903/successful-perinatal-management-of-hereditary-angioedema-with-normal-c1-esterase-inhibitor-and-factor-xii-mutation-using-c1-esterase-inhibitor-therapy
#9
Kathleen R Gibbons, Tina Abraham, Monica Sandhu, Brian P Peppers, Julia F Girzhel, Robert W Hostoffer
No abstract text is available yet for this article.
October 7, 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28993777/the-procoagulant-activity-of-apoptotic-cells-is-mediated-by-interaction-with-factor-xii
#10
Aizhen Yang, Fengwu Chen, Chao He, Junsong Zhou, Yi Lu, Jihong Dai, Raymond B Birge, Yi Wu
Apoptotic cells, by externalizing phosphatidylserine (PS) as a hallmark feature, are procoagulant. However, the mechanism by which apoptotic cells activate coagulation system remains unknown. Intrinsic coagulation pathway is initiated by coagulation factor XII (FXII) of contact activation system. The purpose of this study was to determine whether FXII is involved in procoagulant activity of apoptotic cells. Using western blotting and chromogenic substrate assay, we found that incubation with apoptotic cells, but not with viable cells, resulted in rapid cleavage and activation of FXII in the presence of prekallikrein and high molecular weight kininogen (HK), other two components of contact activation system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28986851/protocols-to-assess-coagulation-following-in-vitro-infection-with-hemorrhagic-fever-viruses
#11
Melissa L Tursiella, Shannon L Taylor, Connie S Schmaljohn
During the course of infection with a hemorrhagic fever virus (HFV), the checks and balances associated with normal coagulation are perturbed resulting in hemorrhage in severe cases and, in some patients, disseminated intravascular coagulopathy (DIC). While many HFVs have animal models that permit the analyses of systemic coagulopathy, animal infection models do not exist for all HFVs and moreover do not always recapitulate the pathology observed in human tissues. Furthermore, molecular analyses of how coagulation is affected are not always straightforward or practical when using ex-vivo animal-derived samples, thus reinforcing the importance of cell culture studies...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28966616/factor-xii-driven-inflammatory-reactions-with-implications-for-anaphylaxis
#12
REVIEW
Lysann Bender, Henri Weidmann, Stefan Rose-John, Thomas Renné, Andy T Long
Anaphylaxis is a life-threatening allergic reaction. It is triggered by the release of pro-inflammatory cytokines and mediators from mast cells and basophils in response to immunologic or non-immunologic mechanisms. Mediators that are released upon mast cell activation include the highly sulfated polysaccharide and inorganic polymer heparin and polyphosphate (polyP), respectively. Heparin and polyP supply a negative surface for factor XII (FXII) activation, a serine protease that drives contact system-mediated coagulation and inflammation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28950949/g-protein-coupled-kinin-receptors-and-immunity-against-pathogens
#13
Julio Scharfstein, Pablo I P Ramos, Manoel Barral-Netto
For decades, immunologists have considered the complement system as a paradigm of a proteolytic cascade that, acting cooperatively with the immune system, enhances host defense against infectious organisms. In recent years, advances made in thrombosis research disclosed a functional link between activated neutrophils, monocytes, and platelet-driven thrombogenesis. Forging a physical barrier, the fibrin scaffolds generated by synergism between the extrinsic and intrinsic (contact) pathways of coagulation entrap microbes within microvessels, limiting the systemic spread of infection while enhancing the clearance of pathogens by activated leukocytes...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28918098/identifying-novel-factor-xiia-inhibitors-with-pca-ga-svm-developed-vhts-models
#14
Jonathan Jun Feng Chen, Donald P Visco
There currently is renewed interest in blood clotting Factor XII as a potential target for thrombosis inhibition. Historically untargeted, there is little drug information with which to start drug candidate searches. Typical high-throughput screening can identify potential drug candidates, but is inefficient. Virtual high-throughput screening can be used to raise efficiency by focusing experimental efforts on compounds predicted to be active and is applied here to identify new Factor XIIa inhibitors. We combine principal component analysis, genetic algorithm and support vector machine to create the models used in the virtual high-throughput screening...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28915237/dna-replication-stress-restricts-ribosomal-dna-copy-number
#15
Devika Salim, William D Bradford, Amy Freeland, Gillian Cady, Jianmin Wang, Steven C Pruitt, Jennifer L Gerton
Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28912585/matrisome-profiling-during-intervertebral-disc-development-and-ageing
#16
Joana Caldeira, Cátia Santa, Hugo Osório, Maria Molinos, Bruno Manadas, Raquel Gonçalves, Mário Barbosa
Intervertebral disc (IVD) degeneration is often the cause of low back pain. Degeneration occurs with age and is accompanied by extracellular matrix (ECM) depletion, culminating in nucleus pulpous (NP) extrusion and IVD destruction. The changes that occur in the disc with age have been under investigation. However, a thorough study of ECM profiling is needed, to better understand IVD development and age-associated degeneration. As so, iTRAQ LC-MS/MS analysis of foetus, young and old bovine NPs, was performed to define the NP matrisome...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28898903/inhibition-of-factors-xi-and-xii-for-prevention-of-thrombosis-induced-by-artificial-surfaces
#17
Benjamin Tillman, David Gailani
No abstract text is available yet for this article.
September 12, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28875494/abundance-of-small-mammals-in-the-atlantic-forest-asmaf-a%C3%A2-data-set-for-analyzing-tropical-community-patterns
#18
Marcos S L Figueiredo, Camila S Barros, Ana C Delciellos, Edú B Guerra, Pedro Cordeiro-Estrela, Maja Kajin, Martin R Alvarez, Paulo H Asfora, Diego Astúa, Helena G Bergallo, Rui Cerqueira, Lena Geise, Rosana Gentile, Carlos Eduardo V Grelle, Gilson E Iack-Ximenes, Leonardo C Oliveira, Marcelo Weksler, Marcus V Vieira
Local abundance results from the interaction between populational and environmental processes. The abundance of the species in a community is also one of the most basic descriptors of its structure. Despite its importance, information about species abundances is fragmentary, creating a knowledge gap about species abundances known as the Prestonian Shortfall. Here we present a comprehensive data set of small mammal abundance in the Atlantic Forest. Data were extracted from 114 published sources and from unpublished data collected by our research groups spanning from 1943 to 2017...
November 2017: Ecology
https://www.readbyqxmd.com/read/28835790/n-acylbenzenesulfonamide-dihydro-1-3-4-oxadiazole-hybrids-seeking-selectivity-toward-carbonic-anhydrase-isoforms
#19
Giulia Bianco, Rita Meleddu, Simona Distinto, Filippo Cottiglia, Marco Gaspari, Claudia Melis, Angela Corona, Rossella Angius, Andrea Angeli, Domenico Taverna, Stefano Alcaro, Janis Leitans, Andris Kazaks, Kaspars Tars, Claudiu T Supuran, Elias Maccioni
A series of N-acylbenzenesulfonamide dihydro-1,3,4-oxadiazole hybrids (EMAC8000a-m) was designed and synthesized with the aim to target tumor associated carbonic anhydrase (hCA) isoforms IX and XII. Most of the compounds were selective inhibitors of the tumor associated hCA XII. Moreover, resolution of EMAC8000d racemic mixture led to the isolation of the levorotatory eutomer exhibiting an increase of hCA XII inhibition potency and selectivity with respect to hCA II. Computational studies corroborated these data...
August 10, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28816340/coagulation-factor-xii-regulates-inflammatory-responses-in-human-lungs
#20
Rosanna Hess, Lukasz Wujak, Christina Hesse, Katherina Sewald, Danny Jonigk, Gregor Warnecke, Hans-Gerd Fieguth, Steven de Maat, Coen Maas, Francesco Bonella, Klaus T Preissner, Benjamin Weiss, Liliana Schaefer, Wolfgang M Kuebler, Philipp Markart, Malgorzata Wygrecka
Increased procoagulant activity in the alveolar compartment and uncontrolled inflammation are hallmarks of the acute respiratory distress syndrome (ARDS). Here, we investigated whether the contact phase system of coagulation is activated and may regulate inflammatory responses in human lungs. Components of the contact phase system were characterized in bronchoalveolar lavage fluids (BALF) from 54 ARDS patients and 43 controls, and their impact on cytokine/chemokine expression in human precision cut lung slices (PCLS) was assessed by a PCR array...
October 5, 2017: Thrombosis and Haemostasis
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