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https://www.readbyqxmd.com/read/28433996/factor-xii-as-a-risk-marker-for-hemorrhagic-stroke-a-prospective-cohort-study
#1
Kristina Johansson, Jan-Håkan Jansson, Lars Johansson, Ingemar Bylesjö, Torbjörn K Nilsson, Mats Eliasson, Stefan Söderberg, Marcus Lind
BACKGROUND: Coagulation factor XII (FXII) is involved in pathological thrombus formation and is a suggested target of anticoagulants. It is unclear whether FXII levels are correlated with cardiovascular risk factors and whether they are associated with myocardial infarction or ischemic or hemorrhagic stroke. The aim of this study was to investigate the correlation between FXII and cardiovascular risk factors in the general population. We also aimed to study the associations between FXII levels and future myocardial infarction and ischemic and hemorrhagic stroke...
April 21, 2017: Cerebrovascular Diseases Extra
https://www.readbyqxmd.com/read/28394285/diagnosis-and-treatment-of-von-willebrand-disease-and-rare-bleeding-disorders
#2
REVIEW
Giancarlo Castaman, Silvia Linari
Along with haemophilia A and B, von Willebrand disease (VWD) and rare bleeding disorders (RBDs) cover all inherited bleeding disorders of coagulation. Bleeding tendency, which can range from extremely severe to mild, is the common symptom. VWD, due to a deficiency and/or abnormality of von Willebrand factor (VWF), represents the most frequent bleeding disorder, mostly inherited as an autosomal dominant trait. The diagnosis may be difficult, based on a bleeding history and different diagnostic assays, which evaluate the pleiotropic functions of VWF...
April 10, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28392508/a-novel-missense-mutation-in-the-factor-xii-gene-in-a-litter-of-cats-with-factor-xii-deficiency
#3
Haruhiko Maruyama, Haruki Hosoe, Kota Nagamatsu, Rui Kano, Hiroshi Kamata
The feline F12 gene was examined to identify a mutation associated with coagulation factor XII (FXII) deficiency in a litter of 6 cats, including 2 cats with severely reduced FXII activity (7.1% and 9.3%, respectively) and 4 cats with moderately reduced FXII activity (range 36.0 to 46.3%). Cats with severely reduced FXII activity were homozygous for a G to C missense mutation in exon 13 of the F12 gene, resulting in an amino acid change (p.G544A). Cats with moderately reduced FXII activity were heterozygous for this mutation...
April 7, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28392470/pituitary-adenylate-cyclase-activating-polypeptide-pacap-and-its-receptor-1-pac1-in-the-human-infant-brain-and-changes-in-the-sudden-infant-death-syndrome-sids
#4
J Huang, K A Waters, R Machaalani
Pituitary adenylate cyclase activating polypeptide (PACAP) and its complementary receptor, PAC1, are crucial in central respiratory control. PACAP Knockout (KO) mice exhibit a SIDS-like phenotype, with an inability to overcome noxious insults, compression of baseline ventilation, and death in the early post-neonatal period. PAC1 KO demonstrate similar attributes to PACAP-null mice, but with the addition of increased pulmonary artery pressure, consequently leading to heart failure and death. This study establishes a detailed interpretation of the neuroanatomical distribution and localization of both PACAP and PAC1 in the human infant brainstem and hippocampus, to determine whether any changes in expression are evident in infants who died of Sudden Infant Death Syndrome (SIDS) and any relationships to risk factors of SIDS including smoke exposure and sleep related parameters...
April 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28346966/factor-xii-contact-activation
#5
Clément Naudin, Elena Burillo, Stefan Blankenberg, Lynn Butler, Thomas Renné
Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively...
March 27, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28323357/characterisation-of-clotting-factors-anticoagulant-protein-activities-and-viscoelastic-analysis-in-healthy-donkeys
#6
A Perez-Ecija, F J Mendoza
BACKGROUND: Studies have demonstrated differences in commonly measured hemostatic parameters between donkeys and horses. Whether clotting factors, anticoagulant protein activities and thromboelastography parameters also differ between species is still unknown. OBJECTIVES: To characterize hemostatic parameters in healthy donkeys and compare them to those of horses. STUDY DESIGN: Cross-sectional study. METHODS: Clotting Factors (V, VII, VIII, IX, X, XI and XII), and antithrombin III, Protein C and Protein S activities were measured in 80 healthy Andalusian and crossbred donkeys and 40 healthy Andalusian crossbred horses with assays based on human deficient plasmas...
March 21, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28286749/factors-xi-and-xii-as-targets-for-new-anticoagulants
#7
REVIEW
Jeffrey I Weitz, James C Fredenburgh
Compared with vitamin K antagonists, the direct oral anticoagulants (DOACs) are simpler to administer and are associated with less intracranial bleeding. Nonetheless, even with the DOACs, bleeding still occurs and many patients with atrial fibrillation fail to receive anticoagulant thromboprophylaxis because of the fear of bleeding. Therefore, there is an urgent need for safer anticoagulants. Recent investigations into the biochemistry of hemostasis and thrombosis have identified new targets for development of novel anticoagulants...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28266177/tnf-%C3%AE-promotes-survival-and-migration-of-mscs-under-oxidative-stress-via-nf-%C3%AE%C2%BAb-pathway-to-attenuate-intimal-hyperplasia-in-vein-grafts
#8
Xiao Bai, Jie Xi, Yanwen Bi, Xin Zhao, Weidong Bing, Xiangbin Meng, Yimin Liu, Zhonglai Zhu, Guangmin Song
The oxidative stress caused by endothelial injury is involved in intimal hyperplasia (IH) in vein grafts. Mesenchymal stem cells (MSCs) can home to injured intima and promote endothelial repair. However, MSC apoptosis is increased accompanied by decreased functional activity under oxidative stress. Thus, we investigate whether tumour necrosis factor-α (TNF-α) can promote the survival and activity of MSCs under oxidative stress to reduce IH more effectively, and establish what role the NF-κB pathway plays in this...
March 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28263027/coagulation-factors-anticoagulant-proteins-and-plasminogen-in-mexican-older-adults
#9
E Hernández Zamora, L O González-Espinosa, C Zavala-Hernández, E Rosales-Cruz, E Reyes-Maldonado
INTRODUCTION: Hemostasis protects upon the occurrence of vascular endothelial damage, with involving of different factors. The interaction of these factors in older adults is poorly known, and has been associated with different disorders. Therefore, we determined the activity of coagulation factors (CF), anticoagulant proteins (AP), and plasminogen (Plg), as well as the frequency of deficiencies of these proteins in a population of healthy Mexican older adults (OA). METHODS: CF (I, II, V, VII, VIII, IX, X, and XI y XII), AP [protein C (PC), protein S (PS), and antithrombin (AT)], and Plg were determined from 244 plasma samples of OA using commercial kits in a coagulometer ACL Elite Pro...
March 6, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28260111/molecular-characterization-of-metastatic-osteosarcoma-differentially-expressed-genes-transcription-factors-and-micrornas
#10
Lisong Heng, Zhen Jia, Jie Bai, Kun Zhang, Yangjun Zhu, Jianbing Ma, Jun Zhang, Honghao Duan
The present study aimed to understand the molecular mechanisms underlying osteosarcoma metastasis. Microarray dataset GSE49003 was downloaded from the Gene Expression Omnibus database and used for analysis. Raw expression data were preprocessed using the preprocessCore, impute and aggregate packages in R. Differentially expressed genes (DEGs) between metastatic and non‑metastatic osteosarcoma cell lines were screened using the limma package following exclusion of DEGs with a higher significance in intra‑groups compared with inter‑groups using the genefilter package...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28242605/depletion-of-coagulation-factor-xii-ameliorates-brain-pathology-and-cognitive-impairment-in-alzheimer-s-disease-mice
#11
Zu-Lin Chen, Alexey S Revenko, Pradeep Singh, A Robert MacLeod, Erin H Norris, Sidney Strickland
Vascular abnormalities and inflammation are found in many Alzheimer's disease (AD) patients, but whether these changes play a causative role in AD is not clear. The factor XII-initiated contact system can trigger both vascular pathology and inflammation and is activated in AD patients and AD mice. We have investigated the role of the contact system in AD pathogenesis. Cleavage of high molecular weight kininogen (HK), a marker for the inflammatory arm of the contact system, is increased in a mouse model of AD, and this cleavage is temporally correlated with the onset of brain inflammation...
February 27, 2017: Blood
https://www.readbyqxmd.com/read/28236427/procoagulant-extracellular-vesicles-in-amniotic-fluid
#12
Lena Hell, Lukas Wisgrill, Cihan Ay, Andreas Spittler, Michael Schwameis, Bernd Jilma, Ingrid Pabinger, Peter Altevogt, Johannes Thaler
Embolization of amniotic fluid (AF) into the blood circulation leads to disseminated intravascular coagulation (DIC). Procoagulant phosphatidylserine (PS)- and tissue factor (TF)-exposing extracellular vesicles (EVs) might play an important role in AF embolism-induced DIC. It was the aim of the present study to perform analyses of the procoagulant properties of AF with a panel of functional coagulation assays and flow cytometry. We applied a prothrombinase assay (that quantifies PS exposure on EVs), an EV-associated TF activity assay, a fibrin generation assay, a thrombin generation assay, a whole blood clotting model, and flow cytometry in AF and control plasma...
February 4, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28219400/alleviation-of-secondary-brain-injury-posttraumatic-inflammation-and-brain-edema-formation-by-inhibition-of-factor-xiia
#13
Sarah Hopp, Marc W Nolte, Christian Stetter, Christoph Kleinschnitz, Anna-Leena Sirén, Christiane Albert-Weissenberger
BACKGROUND: Traumatic brain injury (TBI) is a devastating neurological condition and a frequent cause of permanent disability. Posttraumatic inflammation and brain edema formation, two pathological key events contributing to secondary brain injury, are mediated by the contact-kinin system. Activation of this pathway in the plasma is triggered by activated factor XII. Hence, we set out to study in detail the influence of activated factor XII on the abovementioned pathophysiological features of TBI...
February 20, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28185002/-multiple-thrombophilic-risk-markers-in-patients-%C3%A2-%C2%BA65%C3%A2-years-of-age-with-retinal-vein-occlusion
#14
C Kuhli-Hattenbach, P Hellstern, W Miesbach, T Kohnen, L-O Hattenbach
BACKGROUND: The potential impact of multiple thrombophilic defects on retinal venous occlusive (RVO) diseases with regard to age and various risk factors has not been studied extensively. MATERIALS AND METHODS: In a retrospective, multicenter study, thrombophilia data of 128 patients <65 years of age with RVO and 110 healthy subjects were evaluated. The main measure outcome was the prevalence of multiple thrombophilic disorders. RESULTS: Multiple thrombophilic defects were significantly more prevalent among RVO patients (18...
February 9, 2017: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
https://www.readbyqxmd.com/read/28150893/egf-domain-of-coagulation-factor-ix-is-conducive-to-exposure-of-phosphatidylserine
#15
Chiaki Hidai, Yusuke Fujiwara, Shinichiro Kokubun, Hisataka Kitano
Lipid rafts are an initiation site for many different signals. Recently, we reported that an EGF domain in activated coagulation factor IX (EGF-F9) increases lipid raft formation and accelerates cell migration. However, the detailed mechanism is not well understood. This study aimed to evaluate the effects of EGF-F9 on the cell membrane. A431 cells (derived from human squamous cell carcinoma) were treated with recombinant EGF-F9. Cells were immunocytochemically stained with probes for lipid rafts or phosphatidylserine (PS)...
April 2017: Cell Biology International
https://www.readbyqxmd.com/read/28148841/platelet-localized-fxi-promotes-a-vascular-coagulation-inflammatory-circuit-in-arterial-hypertension
#16
Sabine Kossmann, Jeremy Lagrange, Sven Jäckel, Kerstin Jurk, Moritz Ehlken, Tanja Schönfelder, Yvonne Weihert, Maike Knorr, Moritz Brandt, Ning Xia, Huige Li, Andreas Daiber, Matthias Oelze, Christoph Reinhardt, Karl Lackner, Andras Gruber, Brett Monia, Susanne H Karbach, Ulrich Walter, Zaverio M Ruggeri, Thomas Renné, Wolfram Ruf, Thomas Münzel, Philip Wenzel
Multicellular interactions of platelets, leukocytes, and the blood vessel wall support coagulation and precipitate arterial and venous thrombosis. High levels of angiotensin II cause arterial hypertension by a complex vascular inflammatory pathway that requires leukocyte recruitment and reactive oxygen species production and is followed by vascular dysfunction. We delineate a previously undescribed, proinflammatory coagulation-vascular circuit that is a major regulator of vascular tone, blood pressure, and endothelial function...
February 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28137735/contact-system-activation-and-high-thrombin-generation-in-hyperthyroidism
#17
Namhee Kim, Ja-Yoon Gu, Hyun Ju Yoo, Se Eun Han, Young Il Kim, Il Sung Nam-Goong, Eun Sook Kim, Hyun Kyung Kim
BACKGROUND: Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extracellular traps (NET) has emerged as an important trigger of thrombosis, we hypothesized that the contact system is activated along with active NET formation in hyperthyroidism and that their markers correlate with disease severity. SUBJECTS AND METHODS: In 61 patients with hyperthyroidism and 40 normal controls, the levels of coagulation factors (fibrinogen, and factor VII, VIII, IX, XI and XII), D-dimer, thrombin generation assay (TGA) markers, NET formation markers (histone-DNA complex, double-stranded DNA and neutrophil elastase) and contact system markers (activated factor XII (XIIa), high-molecular-weight kininogen (HMWK), prekallikrein and bradykinin) were measured...
May 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28130211/plasma-kallikrein-mediates-brain-hemorrhage-and-edema-caused-by-tissue-plasminogen-activator-therapy-in-mice-after-stroke
#18
Fabrício Simão, Tuna Ustunkaya, Allen C Clermont, Edward P Feener
Thrombolytic therapy using tissue plasminogen activator (tPA) in acute stroke is associated with increased risks of cerebral hemorrhagic transformation and angioedema. While plasma kallikrein (PKal) has been implicated in contributing to both hematoma expansion and thrombosis in stroke, its role in the complications associated with the therapeutic use of tPA in stroke is not yet available. We investigated the effects of tPA on plasma prekallikrein (PPK) activation and the role of PKal on cerebral outcomes in a murine thrombotic stroke model treated with tPA...
January 27, 2017: Blood
https://www.readbyqxmd.com/read/28069606/proteolytic-properties-of-single-chain-factor-xii-a-mechanism-for-triggering-contact-activation
#19
Ivan Ivanov, Anton Matafonov, Mao-Fu Sun, Qiufang Cheng, S Kent Dickeson, Ingrid M Verhamme, Jonas Emsley, David Gailani
When blood is exposed to variety of artificial surfaces and biologic substances, the plasma proteins factor XII (FXII) and prekallikrein undergo reciprocal proteolytic conversion to the proteases αFXIIa and α-kallikrein by a process called contact activation. These enzymes contribute to host-defense responses including coagulation, inflammation, and fibrinolysis. The initiating event in contact activation is debated. To test the hypothesis that single-chain FXII expresses activity that could initiate contact activation, we prepared human FXII variants lacking the Arg353 cleavage site required for conversion to αFXIIa (FXII-R353A), or lacking the 3 known cleavage sites at Arg334, Arg343, and Arg353 (FXII-T, for "triple" mutant), and compared their properties to wild-type αFXIIa...
March 16, 2017: Blood
https://www.readbyqxmd.com/read/28067447/importance-of-eif2%C3%AE-phosphorylation-as-a-protective-mechanism-against-heat-stress-in-mouse-male-germ-cells
#20
Jungbin Yoon, Kyosun Park, Deog Su Hwang, Kunsoo Rhee
Mammalian male germ cells are exceptionally labile to heat stress. A temporal arrest of translation is one immediate response to heat, which involves heat-induced phosphorylation of eukaryotic initiation factor 2α (eIF2α) to block the formation of the translational initiation complex. Here, we investigated the protective mechanisms against heat stress in mouse male germ cells. All known eIF2α kinases were expressed in lineage- and developmental stage-specific manners in the testis; noteworthy was the presence of Gcn2 (General control nonderepressible 2 kinase) in spermatocytes of all seminiferous tubules...
January 9, 2017: Molecular Reproduction and Development
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