Generation and Application of Rat Monoclonal Antibodies Specific for a Human Blood Coagulation Protein: von Willebrand Factor.
In conclusion, the development of VWF-specific mAbs would be useful in the diagnosis of VWD and AVWS. PMID: 31192778 [PubMed - in process] (Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy)
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - June 14, 2019 Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research

von Willebrand factor promotes wound healing
(Source: Blood)
Source: Blood - June 13, 2019 Category: Hematology Authors: ODonnell, J. S., OSullivan, J. M. Tags: Free Research Articles COMMENTS Source Type: research

The heparin binding domain of von Willebrand factor binds to growth factors and promotes angiogenesis in wound healing
During wound healing, the distribution, availability, and signaling of growth factors (GFs) are orchestrated by their binding to extracellular matrix components in the wound microenvironment. Extracellular matrix proteins have been shown to modulate angiogenesis and promote wound healing through GF binding. The hemostatic protein von Willebrand factor (VWF) released by endothelial cells (ECs) in plasma and in the subendothelial matrix has been shown to regulate angiogenesis; this function is relevant to patients in whom VWF deficiency or dysfunction is associated with vascular malformations. Here, we show that VWF deficien...
Source: Blood - June 13, 2019 Category: Hematology Authors: Ishihara, J., Ishihara, A., Starke, R. D., Peghaire, C. R., Smith, K. E., McKinnon, T. A. J., Tabata, Y., Sasaki, K., White, M. J. V., Fukunaga, K., Laffan, M. A., Lutolf, M. P., Randi, A. M., Hubbell, J. A. Tags: Plenary Papers, Thrombosis and Hemostasis, Vascular Biology Source Type: research

Von Willebrand disease: diagnosis and management
Von Willebrand Disease is a common cause of excessive bruising and bleeding in children. This short article gives advice on diagnosis and management for paediatricians. Given its prevalence and presenting symptoms, VWD should always be considered in the assessment of children suspected of non-accidental injury. Its diagnosis can be challenging, not only because of the various subtypes of the disorder but because of the considerable overlap between VWD and normal individuals. Laboratory diagnosis requires a range of quantitative and qualitative tests of the VWF protein, with targeted gene analysis increasingly used to confi...
Source: Paediatrics and Child Health - June 10, 2019 Category: Pediatrics Authors: Michael Williams, Jonathan Lancashire Tags: Symposium: haematology Source Type: research

Inflammation and Cerebral Small Vessel Disease: A Systematic Review.
Abstract Inflammation is increasingly implicated as a risk factor for dementia, stroke, and small vessel disease (SVD). However, the underlying mechanisms and causative pathways remain unclear. We systematically reviewed the existing literature on the associations between markers of inflammation and SVD (i.e., white matter hyperintensities (WMH), lacunes, enlarged perivascular spaces (EPVS), cerebral microbleeds (CMB)) in cohorts of older people with good health, cerebrovascular disease, or cognitive impairment. Based on distinctions made in the literature, markers of inflammation were classified as systemic infla...
Source: Ageing Research Reviews - June 7, 2019 Category: Genetics & Stem Cells Authors: Low A, Mak E, Rowe JB, Markus HS, O'Brien JT Tags: Ageing Res Rev Source Type: research

The gut microbiota - a modulator of endothelial cell function and a contributing environmental factor to arterial thrombosis.
Authors: Formes H, Reinhardt C Abstract INTRODUCTION: There is emerging evidence linking the commensal gut microbiota with the development of cardiovascular disease and arterial thrombosis. In immunothrombosis, the host clotting system protects against the dissemination of invading microbes, not considering the huge number of microbes that interact with host physiology in a mutualistic fashion. Areas covered: Interestingly, recent research revealed that colonizing gut microbes profoundly influence host innate immune pathways that support arterial thrombus growth. The gut microbiota promotes arterial thrombus format...
Source: Expert Review of Hematology - June 6, 2019 Category: Hematology Tags: Expert Rev Hematol Source Type: research

Effect of Spironolactone for One Year on Endothelial Function and Vascular Inflammation Biomarkers in Renal Transplant Recipients.
BL Abstract BACKGROUND: Kidney transplantation is associated with increased cardiovascular risk. Endothelial dysfunction and vascular inflammation contribute to negative outcome. In experimental models, mineralocorticoid receptor antagonists (MRA) improved endothelial function and reduced inflammation. The current study tested the hypothesis that the MRA spironolactone improves endothelial function and reduces vascular inflammation in renal transplant patients. METHODS: 80 renal transplant patients from an ongoing, double-blind randomized placebo-controlled trial were included. Paired plasma samples before a...
Source: American Journal of Physiology. Renal Physiology - June 5, 2019 Category: Physiology Authors: Mortensen LA, Bistrup C, Stubbe J, Carlström M, Checa A, Wheelock CE, Palarasah Y, Bladbjerg EM, Thiesson HC, Jensen BL Tags: Am J Physiol Renal Physiol Source Type: research

Inflammatory and coagulatory markers and exposure to different size fractions of particle mass, number and surface area air concentrations in Swedish iron foundries, in particular respirable quartz
ConclusionsThese observed relationships between particle exposure and inflammatory markers may indicate an increased risk of cardiovascular disease among foundry workers with high particulate exposure. (Source: International Archives of Occupational and Environmental Health)
Source: International Archives of Occupational and Environmental Health - June 4, 2019 Category: Occupational Health Source Type: research

ABO blood group and procoagulant factors: the hypercoagulation hypothesis ABO and Procoagulant Factors.
CONCLUSION: There appears to be a time-dependent variation in procoagulant factor levels in preterm newborns. Although the clinical significance remains unclear, prothrombotic factors vWF and FVIII are significantly higher in non-O blood-type preterm neonates in the third week of life. PMID: 31158844 [PubMed - as supplied by publisher] (Source: Pediatric Research)
Source: Pediatric Research - June 3, 2019 Category: Pediatrics Authors: Lai A, Jeske W, Habeeb O, Mooney S, Levin S, DeChristopher PJ, Glynn LA, Muraskas JK Tags: Pediatr Res Source Type: research

Mo1318 THERAPEUTIC INR INCREASES ENDOSCOPIC YIELD OF IDENTIFYING CULPRIT LESION IN LEFT VENTRICULAR ASSIST DEVICE RECIPIENTS PRESENTING WITH UPPER GI BLEEDING
Gastrointestinal bleeding (GIB) is a common and often challenging issue among continuous flow left ventricular assist device (LVAD) recipients. These patients are predisposed to GIB due to a combination of anticoagulation and antiplatelet effects, one of which is an acquired von Willebrand syndrome. Studies have shown that up to 65% of LVAD recipients experience GIB, most commonly due to arteriovenous malformation (AVM) in the upper GI tract. Anticoagulation with a goal International Normalized Ratio (INR) 1.5-2.5 is mandatory in patients with LVAD to prevent device thrombosis, but can predispose to GIB. (Source: Gastrointestinal Endoscopy)
Source: Gastrointestinal Endoscopy - June 1, 2019 Category: Gastroenterology Authors: Prianka Singapura, Andy Y. Lee, Kristen Tecson, Hollie Sheffield, Allen Jacob, Megan Marcom, Srikant Patlolla, Parag Kale, Hemangi Kale Tags: Monday abstract Source Type: research

Effects of storage over a 36-month period on coagulation factors in a canine plasma product obtained by use of plasmapheresis.
Abstract OBJECTIVE: To evaluate stability of coagulation factors in canine plasma obtained by use of plasmapheresis and stored over a 36-month period. SAMPLE: Canine plasma obtained by use of plasmapheresis acquired from a commercial blood bank. PROCEDURES: Coagulation testing for fibrinogen concentration and activity of factors II, V, VII, VIII, and IX and von Willebrand factor was performed on canine plasma obtained by use of plasmapheresis. Samples were obtained for testing at 6-month intervals from plasma stored for up to 36 months. RESULTS: A simple mixed linear regression model was created for...
Source: American Journal of Veterinary Research - May 30, 2019 Category: Veterinary Research Authors: Donahue ME, Fernandez AL Tags: Am J Vet Res Source Type: research

Cleavage of anti-PF4/heparin IgG by a bacterial protease and potential benefit in heparin-induced thrombocytopenia
In conclusion, cleavage of anti-PF4/H IgG by IdeS abolishes heparin-dependent cellular activation induced by HIT antibodies. IdeS injection could be a potential treatment of patients with severe HIT. (Source: Blood)
Source: Blood - May 30, 2019 Category: Hematology Authors: Kizlik-Masson, C., Deveuve, Q., Zhou, Y., Vayne, C., Thibault, G., McKenzie, S. E., Pouplard, C., Loyau, S., Gruel, Y., Rollin, J. Tags: Thrombocytopenia, Platelets and Thrombopoiesis Source Type: research

Isolated angiokeratomas of the tongue: A rare entity
Rizwan Hamid, Altaf H Chalkoo, Inderpreet Singh, Suhail Wani, Sheikh BilalIndian Journal of Dental Research 2019 30(2):322-326Angiokeratomas consist of ectasias of dermal capillaries associated with an acanthotic and hyperkeratotic overlying epidermis. These dark red-to-purple, papular vascular anomalies can vary considerably in size, depth, and location. It is a skin disorder that rarely involves oral cavity. It can occur in localized or generalized form and is often associated with underlying metabolic disorder such as Fabry's disease and fucosidosis. It has many clinical variants with the same underlying histopathol...
Source: Indian Journal of Dental Research - May 29, 2019 Category: Dentistry Authors: Rizwan Hamid Altaf H Chalkoo Inderpreet Singh Suhail Wani Sheikh Bilal Source Type: research

Heyde Syndrome
Heyde described aortic stenosis and gastrointestinal bleeding in the 1950s. Since then, a link with intestinal angiodysplasia and abnormalities of von Willebrand factor (VWF) has been noted. Loss of the highest-molecular-weight multimers of VWF and bleeding also have been described in subaortic stenosis in hypertrophic cardiomyopathy, in isolated mitral and aortic insufficiency, in endocarditis, in patients with prosthetic valve stenosis or regurgitation, and in patients with left ventricular assist devices (LVADs). Bleeding tends to recur with local treatment of angiodysplasias, whereas cardiac repair or removal of LVAD e...
Source: Clinics in Geriatric Medicine - May 27, 2019 Category: Geriatrics Authors: Joseph L. Blackshear Source Type: research

The scavenger receptor SCARA5 is an endocytic receptor for von Willebrand factor expressed by littoral cells in the human spleen.
CONCLUSIONS: SCARA5 is an adhesive and endocytic receptor for VWF. In human tissues, SCARA5 is expressed by kidney podocytes and splenic littoral endothelial cells. SCARA5 may have a modest influence on VWF clearance in humans. This article is protected by copyright. All rights reserved. PMID: 31126000 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - May 24, 2019 Category: Hematology Authors: Swystun LL, Ogiwara K, Lai JD, Ojala JRM, Rawley O, Lassalle F, Notley C, Rengby O, Michels A, Nesbitt K, Tryggvason K, Lillicrap D Tags: J Thromb Haemost Source Type: research

An update on pathogenesis and diagnosis of thrombotic thrombocytopenic purpura.
Authors: Joly BS, Coppo P, Veyradier A Abstract INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, consumption thrombocytopenia, and organ injury. TTP pathophysiology is based on a severe ADAMTS13 deficiency, the specific von Willebrand factor (VWF)-cleaving protease. Areas covered: VWF/ADAMTS13 interaction is specific, and ADAMTS13 conformation has been elucidated recently. ADAMTS13 deficiency is congenital or acquired. Several targets are used in TTP treatment. Expert opinion: Differential diagnosis ...
Source: Expert Review of Hematology - May 22, 2019 Category: Hematology Tags: Expert Rev Hematol Source Type: research

Accumulation of endothelial progenitor cells in the lung of pulmonary arterial hypertension: 89Zr-oxine cell trafficking with PET imaging in a rat model
Conclusions: 89Zr-oxine can be used to delineate EPCs in lung of PAH by PET imaging and may provide a noninvasive EPCs monitoring tool. Figure legend A. Immunostaining and flow cytometric analysis of EPCs revealed expression of endothelial cell-specific markers CD31 (green), CD144 (green), and vWF (green), CD146 (red), KDR and the progenitor cell marker CD34. Nuclei were counterstained with DAPI (blue). Abbreviations: DAPI, 4,6-diamidino-2-phenylindole; vWF, von Willebrand factor; KDR, kinase insert domain receptor. B. Whole-body microPET/CT imaging of 89Zr-oxine EPCs in health rats. Maximum intensity projections (MIPs) of...
Source: Journal of Nuclear Medicine - May 21, 2019 Category: Nuclear Medicine Authors: Liu, Y., Zhao, X., Ding, J., Xing, Y., Wang, X., Huo, L., Yang, J. Tags: Cardiovascular Basic Science: Metabolism and Molecular Imaging Source Type: research

Absolute immature platelet count dynamics of thrombotic thrombocytopenic purpura patients with high ADAMTS13 inhibitor
Acquired/idiopathic thrombotic thrombocytopenic purpura (TTP) is manifested by auto-antibody formation to ADAMTS13 which leads to accumulation of ultra-large molecular weight von Willebrand Factor multimers, thrombocytopenia, and diffuse microvascular thrombi [1]. A recent report has given support that a TTP diagnosis should be limited to patients with ADAMTS13 deficiency secondary to autoantibody formation who mostly respond to therapeutic plasma exchange (TPE) [2]. (Source: Thrombosis Research)
Source: Thrombosis Research - May 18, 2019 Category: Hematology Authors: Hamza N. Gokozan, Hollie M. Reeves, Robert W. Maitta Tags: Letter to the Editors-in-Chief Source Type: research

Developments in the use of plasma exchange and adjunctive therapies to treat immune-mediated thrombotic thrombocytopenic purpura.
Authors: Picod A, Coppo P Abstract INTRODUCTION: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disease characterized by a severe functional deficit in the von-Willebrand cleaving protease ADAMTS13, due to autoantibody production. The once-dismal prognosis of the disease has been changed by the discovery of the dramatic efficiency of therapeutic plasma exchange (TPE). Areas covered: This review focuses on the history and recent developments in the use of TPE for iTTP with a special emphasis on the consequences for TPE practice of the recent introduction of new highly effective immu...
Source: Expert Review of Hematology - May 17, 2019 Category: Hematology Tags: Expert Rev Hematol Source Type: research

Risk stratification and prognostic evaluation of endothelial cell-specific molecule1, von Willebrand factor, and a disintegrin-like and metalloprotease with thrombospondin type 1 motif for sepsis in the emergency department: An observational study.
This study evaluated endothelial cell-specific molecule1 (endocan), von Willebrand factor (vWF), and A disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS-13), alone or in combination, in the risk stratification and prognosis prediction of patients with sepsis. Clinical data of 301 patients were prospectively analyzed, and divided into systemic inflammatory reaction syndrome, sepsis, severe sepsis, and septic shock groups. A total of 40 healthy individuals were studied as the control group. Endocan, vWF, ADAMTS-13, vWF/ADAMTS-13, and procalcitonin levels were measured, and Acute Physiology and Chr...
Source: Experimental and Therapeutic Medicine - May 17, 2019 Category: General Medicine Tags: Exp Ther Med Source Type: research

von Willebrand factor in experimental malaria-associated acute respiratory distress syndrome.
CONCLUSIONS: This study suggests that parasite load together with malarial anemia, rather than alveolar leakage, might contribute to shortened survival in PbNK65-infected Vwf-/- mice. VWF deficiency is associated with early reticulocytosis following PbNK65 infection, which potentially explains the increase in parasite load. This article is protected by copyright. All rights reserved. PMID: 31099973 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - May 17, 2019 Category: Hematology Authors: Kraisin S, Verhenne S, Pham TT, Martinod K, Tersteeg C, Vandeputte N, Deckmyn H, Vanhoorelbeke K, Van den Steen PE, De Meyer SF Tags: J Thromb Haemost Source Type: research

The “Double Whammy” of a Continuous Flow Left Ventricular Assist Device on von Willebrand Factor
(Source: The Journal of Thoracic and Cardiovascular Surgery)
Source: The Journal of Thoracic and Cardiovascular Surgery - May 16, 2019 Category: Cardiovascular & Thoracic Surgery Authors: Jay R. Hydren, Russell S. Richardson, Omar Wever-Pinzon, Stavros G. Drakos Source Type: research

Hemostatic Abnormalities in Dementia: A Systematic Review and Meta-Analysis
Semin Thromb Hemost DOI: 10.1055/s-0039-1688444Alzheimer's disease (AD) is considered the most frequent cause of dementia. It is known that vascular risk factors play an important role in the development and progression of this condition. Alterations in vascular walls represent documented findings in patients with AD and other dementias affecting elderly people. The authors performed a systematic review and meta-analysis, aiming to synthesize observational studies that evaluated how the hemostatic system may contribute to cognitive decline in the elderly, using papers published until April 2018 and as indexed in Medline (P...
Source: Seminars in Thrombosis and Hemostasis - May 16, 2019 Category: Hematology Authors: Loures, Cristina de Mello Gomide Duarte, Rita Carolina Figueiredo Silva, Marcos Vin ícius Ferreira Cicarini, Walter Batista de Souza, Leonardo Cruz Caramelli, Paulo Borges, Karina Braga Gomes Carvalho, Maria das Gra ças Tags: Review Article Source Type: research

Effects of A Fully Magnetically Levitated Centrifugal-Flow Or Axial-Flow Left Ventricular Assist Device on Von Willebrand Factor: A Prospective Multicenter Clinical Trial
Increased shear stress conferred upon the circulation by continuous flow pumps is associated with hemocompatibility related adverse events, principally bleeding within the gastrointestinal system, and linked to degradation of high molecular weight multimers (HMWM) of von Willebrand factor (vWF). We evaluated the structure and functional characteristics of vWF HMWM in patients with the fully magnetically levitated centrifugal-flow HeartMate 3 (HM3) and the continuous axial-flow HeartMate II (HMII) pump. (Source: The Journal of Heart and Lung Transplantation)
Source: The Journal of Heart and Lung Transplantation - May 16, 2019 Category: Transplant Surgery Authors: Aditya Bansal, Nir Uriel, Paolo C. Colombo, Keerthy Narisetty, James W. Long, Arvind Bhimaraj, Joseph C. Cleveland, Daniel J. Goldstein, John Stulak, Samer S. Najjar, David E. Lanfear, Eric D. Adler, Walter Dembitsky, Sami I. Somo, Daniel L. Crandall, Don Tags: Original Clinical Science Source Type: research

Recombinant Von Willebrand factor concentrate in 2A Von Willebrand disease: comparison to plasma-derived Von Willebrand factor concentrate therapy
We describe a patient with Type 2A VWD who had persistent refractory epistaxis despite treatment with PD-VWFC. We describe differences in VWF multimeric composition and Factor VIII (FVIII) levels after plasma-derived and rVWF concentrates. Despite similar VWF levels, VWF multimeric composition after PD-VWFC remained abnormal while it corrected with rVWFC. Post-PD-VWFC, high levels of FVIII were seen, which were not observed after rVWFC. Recombinant VWFC may offer some advantages over PD-VWFC. This finding needs to be confirmed in larger studies. (Source: Blood Coagulation and Fibrinolysis)
Source: Blood Coagulation and Fibrinolysis - May 15, 2019 Category: Hematology Tags: CASE REPORTS Source Type: research

Case report of two siblings with type 2A von Willebrand disease involving a novel mutation within the calcium-binding site of the A2 domain of von Willebrand factor
We report a novel VWF variant, a heterozygous single nucleotide change, c.4493A>G, occurring at the p.Asp1498 residue of the calcium-binding site of the A2 domain in two sisters with type 2A von Willebrand disease. Modest increase in the VWF propeptide/VWF:Ag ratio (2.4 and 2.7) supports increased clearance of VWF. A literature review provided insight into the integral role of p.Asp1498 residue in calcium-binding and its role in the stabilization of other residues including p.Arg1597 and p.Asn1602. Studies done by other groups on engineered mutations involving p.Asp1498 reported increased susceptibility to ADAMTS13 prot...
Source: Blood Coagulation and Fibrinolysis - May 15, 2019 Category: Hematology Tags: CASE REPORTS Source Type: research

The Course of von Willebrand Factor and Factor VIII Activity in Patients with von Willebrand Disease during Pregnancy
Conclusion: For the majority of the observed patients, the von Willebrand parameters increased during pregnancy.Acta Haematol (Source: Acta Haematologica)
Source: Acta Haematologica - May 14, 2019 Category: Hematology Source Type: research

The Course of von Willebrand Factor and Factor VIII Activity in Patients with von Willebrand Disease during Pregnancy.
CONCLUSION: For the majority of the observed patients, the von Willebrand parameters increased during pregnancy. PMID: 31085919 [PubMed - as supplied by publisher] (Source: Acta Haematologica)
Source: Acta Haematologica - May 14, 2019 Category: Hematology Authors: Delbrück C, Miesbach W Tags: Acta Haematol Source Type: research

Development of Human in vitro Brain-blood Barrier Model from Induced Pluripotent Stem Cell-derived Endothelial Cells to Predict the in vivo Permeability of Drugs
AbstractAnin vitro blood-brain barrier (BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous system. Though many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data forin vivo BBB drug transport. Induced-pluripotent stem cell (iPSC) technology provides reproducible cell resources forin vitro BBB modeling. Here, we generated a humanin vitro BBB model by differentiating the human iPSC (hiPSC) line GM25256 into brain endothelial-typ...
Source: Neuroscience Bulletin - May 11, 2019 Category: Neuroscience Source Type: research

Cadmium regulates von Willebrand factor and occludin expression in glomerular endothelial cells of mice in a TNF- α-dependent manner.
CONCLUSIONS: These results suggest that TNF-α acts to balance homeostasis of glomerular endothelium after Cd treatments. PMID: 31057027 [PubMed - in process] (Source: Renal Failure)
Source: Renal Failure - May 8, 2019 Category: Urology & Nephrology Tags: Ren Fail Source Type: research

Tumor ‑type‑dependent effects on the angiogenic abilities of endothelial cells in an in vitro rat cell model.
Tumor‑type‑dependent effects on the angiogenic abilities of endothelial cells in an in vitro rat cell model. Oncol Rep. 2019 May 02;: Authors: Al-Abboodi M, An R, Weber M, Schmid R, Klausing A, Horch RE, Boos AM, Kengelbach-Weigand A Abstract Adequate vascularization is pivotal for tumor progression and metastasis. Tumor angiogenesis is based on a sequence of interactions between the tumor and surrounding cells and the extracellular matrix. It is widely known that a tumor can influence and control its surroundings to create favorable conditions for further growth. To investigate the influence of va...
Source: Oncology Reports - May 8, 2019 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery: comment.
This article is protected by copyright. All rights reserved. PMID: 31058403 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - May 6, 2019 Category: Hematology Authors: Miesbach W Tags: J Thromb Haemost Source Type: research

Von Willebrand Factor Sialylation - A Critical Regulator Of Biological Function.
This article is protected by copyright. All rights reserved. PMID: 31055873 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - May 4, 2019 Category: Hematology Authors: Ward S, O'Sullivan JM, O'Donnell JS Tags: J Thromb Haemost Source Type: research

Structure and interactions of the archaeal motility repression module ArnA-ArnB that modulates archaellum gene expression in Sulfolobus acidocaldarius [Signal Transduction]
Phosphorylation-dependent interactions play crucial regulatory roles in all domains of life. Forkhead-associated (FHA) and von Willebrand type A (vWA) domains are involved in several phosphorylation-dependent processes of multiprotein complex assemblies. Although well-studied in eukaryotes and bacteria, the structural and functional contexts of these domains are not yet understood in Archaea. Here, we report the structural base for such an interacting pair of FHA and vWA domain-containing proteins, ArnA and ArnB, in the thermoacidophilic archaeon Sulfolobus acidocaldarius, where they act synergistically and negatively modu...
Source: Journal of Biological Chemistry - May 3, 2019 Category: Chemistry Authors: Lena Hoffmann, Katrin Anders, Lisa F. Bischof, Xing Ye, Julia Reimann, Sunia Khadouma, Trong K. Pham, Chris van der Does, Phillip C. Wright, Lars-Oliver Essen, Sonja-Verena Albers Tags: Microbiology Source Type: research

Lipoxin A4 restores oxidative stress-induced vascular endothelial cell injury and thrombosis-related factor expression by its receptor-mediated activation of Nrf2-HO-1 axis.
Abstract Venous thromboembolism (VTE) constitutes a common cause of hospital-related morbidity and mortality, with the proverbial clinical feature of deep venous thrombosis (DVT). Endothelial cell injury and dysfunction comprise the critical contributor for the development of DVT. Lipoxin A4 (LXA4) fulfills pleiotropic roles in injury repair. However, its role in DVT remains poorly elucidated. In the present study, LXA4 supplementation dampened H2O2-evoked cytotoxic injury in human umbilical vein endothelial cells (HUVECs) by increasing cell viability, suppressing cell apoptosis and caspase-3 activity. Moreover, t...
Source: Cellular Signalling - May 3, 2019 Category: Cytology Authors: Yang S, Zheng Y, Hou X Tags: Cell Signal Source Type: research

Structural analysis of ischemic stroke thrombi: histological indications for therapy resistance.
er SF Abstract Ischemic stroke is caused by a thromboembolic occlusion of cerebral arteries. Treatment is focused on fast and efficient removal of the occluding thrombus, either via intravenous thrombolysis or via endovascular thrombectomy. Recanalization, however, is not always successful and factors contributing to failure are not completely understood. Although the occluding thrombus is the primary target of acute treatment, little is known about its internal organization and composition. The aim of this study, therefore, was to better understand the internal organization of ischemic stroke thrombi on a molecul...
Source: Haematologica - May 2, 2019 Category: Hematology Authors: Staessens S, Denorme F, François O, Desender L, Dewaele T, Vanacker P, Deckmyn H, Vanhoorelbeke K, Andersson T, De Meyer SF Tags: Haematologica Source Type: research

[Haematological aspects of the gut flora].
te; J Abstract The relationship between the gut flora and various diseases (obesity, diabetes mellitus, metabolic disorders, allergic and autoimmune diseases, inflammatory bowel diseases, liver failure, infections, certain neuropsychiatric disorders, tumors) has been highlighted in recent years. Depletion of microbiotics inhibits bone marrow healing. Infections and their antibiotic treatment may also affect hematopoiesis. Intestinal flora may also affect the severity of the graft-versus-host disease and may also play a role in the pathogenesis of immunthrombocytopenia through the T-regulator cells. The study summa...
Source: Orvosi Hetilap - May 1, 2019 Category: General Medicine Authors: Szerafin L, Jakó J Tags: Orv Hetil Source Type: research

Severe Leptospirosis Features in the Spleen Indicate Cellular Immunosuppression Similar to That Found in Septic Shock
Conclusion: The results suggest that an immunosuppressive state develops at the terminal stage of severe leptospirosis with pulmonary hemorrhage and shock similar to that of patients with septic shock, with diffuse endothelial activation in the spleen, splenitis, and signs of disturbance in the innate and adaptive immunity in the spleen. The presence of leptospiral antigens in 73% of the spleens of the leptospirosis patients suggests the etiological agent contributes directly to the pathogenesis of the lesions. Our results support therapeutic approaches involving antibiotic and immunomodulatory treatments for leptospirosis...
Source: Frontiers in Immunology - April 30, 2019 Category: Allergy & Immunology Source Type: research

Caplacizumab in acquired thrombotic thrombocytopenic purpura: a profile of its use
AbstractCaplacizumab (Cablivi ™), an anti-von Willebrand factor Nanobody®, is indicated for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP), in conjunction with plasma exchange and immunosuppression. When combining the results of phase  2 and 3 trials in patients with aTTP, caplacizumab reduced the time to normalization of platelet count compared with placebo, and was associated with reductions in the rate of aTTP-related death, aTTP recurrence or a major thromboembolic event. Although caplacizumab was associated with more bleedi ng-related adverse event...
Source: Drugs and Therapy Perspectives - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

Large Renal Arteriovenous Malformation in a patient with von Willebrand disease
We describe a rare case of a large renal arteriovenous malformation in a patient with von Willebrand disease. Initial attempts at technically challenging embolization failed requiring a nephrectomy. Extra-intestinal vascular malformations are rare in von Willebrand disease. However, there is more recent evidence of von Willebrand factor's regulatory role in angiogenesis and vascular malformations. (Source: Urology)
Source: Urology - April 30, 2019 Category: Urology & Nephrology Authors: Charles Schlaepfer, Jonathan Weese, Daniel Picus, Ramakrishna Venkatesh Source Type: research

Update on Molecular Testing in von Willebrand Disease
This article discusses the pros and cons of molecular testing in VWD considering the experience obtained through the multicenter project “Molecular and Clinical Profile of VWD in Spain (PCM-EVW-ES).” [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text (Source: Seminars in Thrombosis and Hemostasis)
Source: Seminars in Thrombosis and Hemostasis - April 30, 2019 Category: Hematology Authors: Batlle, Javier P érez-Rodríguez, Almudena Corrales, Irene Borr às, Nina Costa Pinto, Joana L ópez-Fernández, María Fernanda Vidal, Francisco Tags: Review Article Source Type: research

Mouse model to study pulmonary intravascular macrophage recruitment and lung inflammation in acute necrotizing pancreatitis
AbstractPatients suffering from severe acute pancreatitis (AP) can develop acute lung injury (ALI) with poor outcomes and the mechanisms involved remain incompletely understood. Pulmonary intravascular macrophages (PIMs), which are credited as promoters of ALI, are not constitutively present in humans and rodents; however, there is evidence of PIM recruitment in rodents during some pathological conditions, such as hepatic diseases. Therefore, this study assesses PIM recruitment in the lungs of a mouse model of acute necrotizing pancreatitis (ANP) induced withl-arginine monohydrochloride. Mice were euthanized after 24  ...
Source: Cell and Tissue Research - April 29, 2019 Category: Cytology Source Type: research

Alteration in GPIIb/IIIa Binding of VWD-Associated von Willebrand Factor Variants with C-Terminal Missense Mutations.
MA Abstract The platelet receptor glycoprotein (GP) IIb/IIIa, formed by integrins αIIb and β3, plays an important role in platelet adhesion and aggregation. Its major binding site is the arginine-glycine-aspartic acid (RGD) sequence present in several adhesive proteins. Upon platelet activation, inside-out signaling activates the complex permitting binding to RGD motif containing proteins, such as von Willebrand factor (VWF). VWF is a large multidomain plasma GP essential to primary hemostasis, which can directly interact with platelets because it exhibits binding sites for GPIbα and GPIIb/IIIa i...
Source: Thrombosis and Haemostasis - April 29, 2019 Category: Hematology Authors: König G, Obser T, Marggraf O, Schneppenheim S, Budde U, Schneppenheim R, Brehm MA Tags: Thromb Haemost Source Type: research

Prothrombotic State in Atrial Fibrillation Patients With One Additional Risk Factor of the CHA2DS2-VASc Score (Beyond Sex)
Publication date: May 2019Source: Canadian Journal of Cardiology, Volume 35, Issue 5Author(s): Błażej Głowicki, Paweł T. Matusik, Krzysztof Plens, Anetta UndasAbstractBackgroundIt is unclear whether a prothrombotic state occurs in atrial fibrillation (AF) with low stroke risk.MethodsWe studied 118 patients with AF with the Congestive Heart Failure, Hypertension, Age (≥ 75 years), Diabetes, Stroke/Transient Ischemic Attack/Systemic Embolism, Vascular Disease, Age (65-74 years), Sex (Female) (CHA2DS2-VASc) score of 1 in men or 2 in women vs 52 patients with AF with the CHA2DS2-VASc score of 0 in men or 1 in women. Pla...
Source: Canadian Journal of Cardiology - April 27, 2019 Category: Cardiology Source Type: research

von Willebrand Disease in Pediatrics: Evaluation and Management
Publication date: June 2019Source: Hematology/Oncology Clinics of North America, Volume 33, Issue 3Author(s): Sarah H. O’Brien, Surbhi Saini (Source: Hematology Oncology Clinics of North America)
Source: Hematology Oncology Clinics of North America - April 26, 2019 Category: Hematology Source Type: research

von Willebrand Disease in Pediatrics
This article reviews these recent advances, as well as currently available treatment options, including desmopressin, antifibrinolytics, and both plasma-based and recombinant von Willebrand factor products. The diagnosis of VWD remains complex and this article provides an understanding of the various subtypes and phenotypes of VWD, as well as the appropriateness and interpretation of the many available laboratory tests. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - April 26, 2019 Category: Cancer & Oncology Authors: Sarah H. O ’Brien, Surbhi Saini Source Type: research

Pulmonary Endothelial Mechanical Sensing and Signaling, a Story of Focal Adhesions and Integrins in Ventilator Induced Lung Injury
Conclusion Ventilator induced lung injury is characterized by compromised vascular endothelial barrier protection and the production of edemagenic agents in response to mechanical stretch that may lead to overdistention depending upon tidal volume and ventilation frequency (Dos Santos and S.sky, 2000; Lionetti et al., 2005; Birukova et al., 2006). This mechanical-force initiated cellular injury results in cytoskeletal rearrangement. FAs play a central role in mechanotransduction and cytoskeletal rearrangement (De et al., 2010; Ladoux and Nicolas, 2012; Iskratsch et al., 2014; De, 2018). Here, we present the known picture ...
Source: Frontiers in Physiology - April 26, 2019 Category: Physiology Source Type: research

Selective endothelialization and alleviation of neointimal hyperplasia by functionalizing the Ti-O surface with L-selenocystine and KREDVC
Publication date: Available online 23 April 2019Source: Colloids and Surfaces B: BiointerfacesAuthor(s): Yinhong Xie, Zheng Zeng, Yonghong Fan, Yu Zhang, Junfeng Liu, Weijie Li, Yajun WengAbstractDue to their relatively good biocompatibility and inactivity, titanium oxide films (Ti-O) are used in the coating of coronary stents, which reduces metal corrosion, slows metal ion release, and improves endothelial cell (EC) compatibility [1]. Here, we report further functionalizing Ti-O with biological cues for selective endothelialization. Selenocystine with an L- or a D-enantiomer was first immobilized on the Ti-O film via poly...
Source: Colloids and Surfaces B: Biointerfaces - April 25, 2019 Category: Biochemistry Source Type: research

Phylogenetic and functional analysis of ADAMTS13 identifies highly conserved domains essential for allosteric regulation
The metalloprotease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats member 13) prevents microvascular thrombosis by cleaving von Willebrand factor (VWF) within platelet-rich thrombi, and cleavage depends on allosteric activation of ADAMTS13 by the substrate VWF. Human ADAMTS13 has a short propeptide, metalloprotease (M), disintegrin-like (D), thrombospondin-1 (T), Cys-rich (C), and spacer (S) domains (proximal domains), followed by 7 T and 2 CUB (complement components C1r and C1s, sea urchin protein Uegf, and bone morphogenetic protein-1) domains (distal domains). Distal domains inhibit the c...
Source: Blood - April 25, 2019 Category: Hematology Authors: Muia, J., Zhu, J., Greco, S. C., Vanhoorelbeke, K., Gupta, G., Westfield, L. A., Sadler, J. E. Tags: Thrombosis and Hemostasis Source Type: research

Exploring the "minimal" structure of a functional ADAMTS13 by mutagenesis and small-angle X-ray scattering
Human ADAMTS13 is a multidomain protein with metalloprotease (M), disintegrin-like (D), thrombospondin-1 (T), Cys-rich (C), and spacer (S) domains, followed by 7 additional T domains and 2 CUB (complement components C1r and C1s, sea urchin protein Uegf, and bone morphogenetic protein-1) domains. ADAMTS13 inhibits the growth of von Willebrand factor (VWF)–platelet aggregates by cleaving the cryptic Tyr1605-Met1606 bond in the VWF A2 domain. ADAMTS13 is regulated by substrate-induced allosteric activation; without shear stress, the distal T8-CUB domains markedly inhibit VWF cleavage, and binding of VWF domain D4 or sel...
Source: Blood - April 25, 2019 Category: Hematology Authors: Zhu, J., Muia, J., Gupta, G., Westfield, L. A., Vanhoorelbeke, K., Tolia, N. H., Sadler, J. E. Tags: Thrombosis and Hemostasis Source Type: research