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Sample records for platelet decorated von

  1. Diagnostic Value of Measuring Platelet Von Willebrand Factor in Von Willebrand Disease

    PubMed Central

    Casonato, Alessandra; Cattini, Maria Grazia; Daidone, Viviana; Pontara, Elena; Bertomoro, Antonella; Prandoni, Paolo

    2016-01-01

    Von Willebrand disease (VWD) may be caused by an impaired von Willebrand factor (VWF) synthesis, its increased clearance or abnormal function, or combinations of these factors. It may be difficult to recognize the different contributions of these anomalies. Here we demonstrate that VWD diagnostics gains from measuring platelet VWF, which can reveal a defective VWF synthesis. Measuring platelet VWF revealed that: severe type 1 VWD always coincided with significantly lower platelet and plasma VWF levels, whereas mild forms revealed low plasma VWF levels associated with low or normal platelet VWF levels, and the latter were associated with a slightly shorter VWF survival; type Vicenza (the archetype VWD caused by a reduced VWF survival) featured normal platelet VWF levels despite significantly reduced plasma VWF levels; type 2B patients could have either normal platelet VWF levels associated with abnormal multimer patterns, or reduced platelet VWF levels associated with normal multimer patterns; type 2A patients could have reduced or normal platelet VWF levels, the former associated mainly with type 2A-I, the latter with type 2A-II; plasma and platelet VWF levels were normal in type 2N, except when the defect was associated with a quantitative VWF mutation. Our findings show that measuring platelet VWF helps to characterize VWD, especially the ambiguous phenotypes, shedding light on the mechanisms underlying the disorder. PMID:27532107

  2. A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets

    NASA Astrophysics Data System (ADS)

    Haji-Valizadeh, Hassan; Modery-Pawlowski, Christa L.; Sen Gupta, Anirban

    2014-04-01

    There is substantial clinical interest in synthetic platelet analogs for potential application in transfusion medicine. To this end, our research is focused on self-assembled peptide-lipid nanoconstructs that can undergo injury site-selective adhesion and subsequently promote site-directed active platelet aggregation, thus mimicking platelet's primary hemostatic actions. For injury site-selective adhesion, we have utilized a coagulation factor FVIII-derived VWF-binding peptide (VBP). FVIII binds to VWF's D'-D3 domain while natural platelet GPIbα binds to VWF's A1 domain. Therefore, we hypothesized that the VBP-decorated nanoconstructs will adhere to VWF without mutual competition with natural platelets. We further hypothesized that the adherent VBP-decorated constructs can enhance platelet aggregation when co-decorated with a fibrinogen-mimetic peptide (FMP). To test these hypotheses, we used glycocalicin to selectively block VWF's A1 domain and, using fluorescence microscopy, studied the binding of fluorescently labeled VBP-decorated nanoconstructs versus platelets to ristocetin-treated VWF. Subsequently, we co-decorated the nanoconstructs with VBP and FMP and incubated them with human platelets to study construct-mediated enhancement of platelet aggregation. Decoration with VBP resulted in substantial construct adhesion to ristocetin-treated VWF even if the A1-domain was blocked by glycocalicin. In comparison, such A1-blocking resulted in significant reduction of platelet adhesion. Without A1-blocking, the VBP-decorated constructs and natural platelets could adhere to VWF concomitantly. Furthermore, the constructs co-decorated with VBP and FMP enhanced active platelet aggregation. The results indicate significant promise in utilizing the FVIII-derived VBP in developing synthetic platelet analogs that do not interfere with VWF-binding of natural platelets but allow site-directed enhancement of platelet aggregation when combined with FMP.There is substantial

  3. Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo.

    PubMed Central

    Sobel, M; McNeill, P M; Carlson, P L; Kermode, J C; Adelman, B; Conroy, R; Marques, D

    1991-01-01

    The intravenous administration of heparin to patients before open heart surgery reduced ristocetin cofactor activity by 58% (P less than 0.01, t test), and this impairment of von Willebrand factor-dependent platelet function was closely related to plasma heparin levels (r2 = 0.9), but not to plasma von Willebrand factor (vWF) levels. We hypothesized that heparin may inhibit vWF-dependent platelet hemostatic functions by directly binding vWF in solution and interfering with vWF-GpIb binding. Using the in vitro techniques of ristocetin-induced platelet agglutination, fluorescent flow cytometric measurement of vWF-platelet binding, and conventional radioligand binding assays we observed that heparin inhibited both vWF-dependent platelet function and vWF-platelet binding in a parallel and dose-dependent manner. Heparin also inhibited platelet agglutination induced by bovine vWF and inhibited the binding of human asialo-vWF to platelets in ristocetin-free systems. The inhibitory potency of heparin was not dependent upon its affinity for antithrombin III, but was molecular weight dependent: homogeneous preparations of lower molecular weight were less inhibitory. Heparin impairment of vWF function may explain why some hemorrhagic complications of heparin therapy are not predictable based on techniques for monitoring the conventional anticoagulant effects of heparin. PMID:2022745

  4. Mutation in the gene encoding the. alpha. chain of platelet glycoprotein Ib in platelet-type von Willebrand disease

    SciTech Connect

    Miller, J.L.; Cunningham, D.; Lyle, V.A.; Finch, C.N. )

    1991-06-01

    Platelet-type von Willebrand disease (PT-vWD) is an autosomal dominant bleeding disorder characterized by abnormally enhanced binding of von Willebrand factor (vWF) by patient platelets. Although the platelet glycoprotein (GP) Ib/IX complex is known to constitute the platelet's ristocetin-dependent receptor for vWF, a unique structural abnormality within this complex has not previously been identified in PT-vWD. Using the poly merase chain reaction to amplify genomic DNA coding for the {alpha} chain of GP Ib (GP IB{alpha}) and then sequencing the amplified DNA following cloning into M13mp18 and M13mp19 phage vectors, the authors have found a single point mutation in the GP Ib{alpha} coding region of PT-vWD DNA resulting in the substitution of valine for glycine at residue 233. This substitution within the vWF-binding region of GP Ib{alpha} is likely to exert a significant influence on the conformation of the resulting protein. Competitive oligonucleotide primer assay for this mutation showed a homozygous wild-type pattern in genomic DNA from the 161 normal volunteers studied and from 6 phenotypically normal members of a PT-vWD family. All 7 affected members of this family studied were heterozygous for the mutant allele. Platelet GP Ib{alpha} mRNA reverse-transcribed and studied by competitive oligonucleotide primer assay showed similar expression of the mutant and wild-type alleles in the affected PT-vWD patients. Absence in the normal population, tight linkage with phenotypic expression of disease, and absence of any additional abnormality of GP Ib{alpha} in these patients identify the glycine-to-valine substitution as a point mutation underlying functional abnormality of the vWF receptor in PT-vWD.

  5. Platelet-type von Willebrand disease: a rare, often misdiagnosed and underdiagnosed bleeding disorder.

    PubMed

    Othman, Maha

    2011-07-01

    Platelet-type von Willebrand disease (PT-VWD) is an autosomal dominant rare bleeding disorder characterized by hyperresponsive platelets. This inherent platelet function defect is due to a gain-of-function mutation within the GP1BA gene coding for the platelet surface glycoprotein Ib alpha protein, the receptor for the adhesive protein von Willebrand factor (VWF). The defect results in excessive and unnecessary platelet-VWF interaction with subsequent removal of the hemostatically efficient high molecular weight VWF as well as platelets from the circulation, leading to thrombocytopenia and bleeding diathesis. Patients with PT-VWD present with mild to moderate mucocutaneous bleeding, which becomes more pronounced during pregnancy and following aspirin ingestion or drugs that have antiplatelet activity. Laboratory testing shows low VWF:ristocetin cofactor and low or normal VWF:antigen and characteristically an enhanced ristocetin-induced platelet agglutination (RIPA). These laboratory features are also indicators of the closely similar and more common bleeding disorder type 2B VWD. Simplified RIPA mixing assays, cryoprecipitate challenge, and flow cytometry can differentiate between the two disorders. However, the gold standard is to identify mutations within the VWF gene (indicating type 2B VWD) or the platelet GP1BA gene (confirming PT-VWD). Treatment is based on making a correct diagnosis of PT-VWD where platelet concentrates instead of VWF/factor VIII preparations should be administered. A recent fairly large retrospective/prospective registry-based international study showed that PT-VWD is very rare, likely to be misdiagnosed as type 2B VWD or idiopathic thrombocytopenic purpura, and represents 15% of type 2B VWD diagnoses. PMID:22102188

  6. Some interactions between human platelets and glass: von Willebrand's disease compared with normal.

    PubMed

    O'Brien, J R; Heywood, J B

    1967-01-01

    If native or heparinized blood is passed slowly through a column of glass beads at room temperature, the number of platelets removed from the initial drop emerging from the column is less than that removed from the final drop. At 4 degrees C. this difference disappears. If the blood is passed rapidly through such columns at room temperature fewer platelets are removed, but the initial-final difference persists. Von Willebrand's platelets are removed normally at slow speeds; at fast speeds abnormally few platelets are removed. Platelets emerging from all such columns are in aggregates. On adding glass beads to normal heparinized plasma, the platelets at once become more rounded and after about 50 seconds' delay they aggregate: the delay and rate of aggregation can be quantitated. Aggregation occurs best at 20 to 30 degrees C. and is not inhibited by the addition of some enzyme inhibitors. In von Willebrand's disease all these glass-induced aggregation phenomena occur normally and aggregation in response to adenosine diphosphate (ADP), serotonin creatinine sulphate (5-HT), adrenaline, collagen, and glass is also normal. PMID:5297360

  7. A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets†

    PubMed Central

    Haji-Valizadeh, Hassa n; Modery-Pawlowski, Christa L.

    2015-01-01

    There is substantial clinical interest in synthetic platelet analogs for potential application in transfusion medicine. To this end, our research is focused on self-assembled peptide–lipid nanoconstructs that can undergo injury site-selective adhesion and subsequently promote site-directed active platelet aggregation, thus mimicking platelet’s primary hemostatic actions. For injury site-selective adhesion, we have utilized a coagulation factor FVIII-derived VWF-binding peptide (VBP). FVIII binds to VWF’s D′–D3 domain while natural platelet GPIbα binds to VWF’s A1 domain. Therefore, we hypothesized that the VBP-decorated nanoconstructs will adhere to VWF without mutual competition with natural platelets. We further hypothesized that the adherent VBP-decorated constructs can enhance platelet aggregation when co-decorated with a fibrinogen-mimetic peptide (FMP). To test these hypotheses, we used glycocalicin to selectively block VWF’s A1 domain and, using fluorescence microscopy, studied the binding of fluorescently labeled VBP-decorated nanoconstructs versus platelets to ristocetin-treated VWF. Subsequently, we co-decorated the nanoconstructs with VBP and FMP and incubated them with human platelets to study construct-mediated enhancement of platelet aggregation. Decoration with VBP resulted in substantial construct adhesion to ristocetin-treated VWF even if the A1-domain was blocked by glycocalicin. In comparison, such A1-blocking resulted in significant reduction of platelet adhesion. Without A1-blocking, the VBP-decorated constructs and natural platelets could adhere to VWF concomitantly. Furthermore, the constructs co-decorated with VBP and FMP enhanced active platelet aggregation. The results indicate significant promise in utilizing the FVIII-derived VBP in developing synthetic platelet analogs that do not interfere with VWF-binding of natural platelets but allow site-directed enhancement of platelet aggregation when combined with FMP. PMID

  8. Evidence that the primary binding site of von Willebrand factor that mediates platelet adhesion on subendothelium is not collagen.

    PubMed Central

    de Groot, P G; Ottenhof-Rovers, M; van Mourik, J A; Sixma, J J

    1988-01-01

    We have studied the binding of von Willebrand factor to extracellular matrices of endothelial cells and to the vessel wall of human umbilical arteries in relation to its function in supporting platelet adhesion. CLB-RAg 201, an MAb against von Willebrand factor, completely inhibits the binding of von Willebrand factor to collagen type I and type III. CLB-RAg 201 does not inhibit the binding of 125I-von Willebrand factor to extracellular matrices of endothelial cells, to smooth muscle cells, or to the subendothelium. CLB-RAg 201 partly inhibits platelet adhesion to these surfaces, but this directly affects the interaction between von Willebrand factor and platelets and is not due to inhibition of binding of von Willebrand factor to these surfaces. Another MAb, CLB-RAg 38, does not inhibit the binding of von Willebrand factor to collagen. CLB-RAg 38 completely inhibits the binding of von Willebrand factor to extracellular matrices. CLB-RAg 38 inhibits platelet adhesion to cellular matrices completely insofar as it is dependent on plasma von Willebrand factor. CLB-RAg 38 does not inhibit the total binding of von Willebrand factor to subendothelium, as there are too many different binding sites, but it completely inhibits the functional binding sites for von Willebrand factor that support platelet adhesion. The epitopes for CLB-RAg 38 and 201 on the von Willebrand factor molecule are located on different fragments of the molecule. These results indicate that von Willebrand factor binds to subendothelium and matrices of cultured cells by a mechanism that is different from that by which it binds to collagen. Images PMID:2839553

  9. Paradoxical Effect of Nonphysiological Shear Stress on Platelets and von Willebrand Factor.

    PubMed

    Chen, Zengsheng; Mondal, Nandan K; Ding, Jun; Koenig, Steven C; Slaughter, Mark S; Wu, Zhongjun J

    2016-07-01

    Blood can become hypercoagulable by shear-induced platelet activation and generation of microparticles. It has been reported that nonphysiological shear stress (NPSS) could induce shedding of platelet receptor glycoprotein (GP) Ibα, which may result in an opposite effect to hemostasis. The aim of this study was to investigate the influence of the NPSS on platelets and von Willebrand factor (vWF). Human blood was exposed to two levels of NPSS (25 Pa, 125 Pa) with an exposure time of 0.5 s, generated by using a novel blood-shearing device. Platelet activation (P-selectin expression, GPIIb/IIIa activation and generation of microparticles) and shedding of three platelet receptors (GPIbα, GPVI, GPIIb/IIIa) in sheared blood were quantified using flow cytometry. Aggregation capacity of sheared blood induced by ristocetin and collagen was evaluated using an aggregometer. Shear-induced vWF damage was characterized with Western blotting. Consistent with the published data, the NPSS caused significantly more platelets to become activated with increasing NPSS level. Meanwhile, the NPSS induced the shedding of platelet receptors. The loss of the platelet receptors increased with increasing NPSS level. The aggregation capacity of sheared blood induced by ristocetin and collagen decreased. There was a loss of high molecular weight multimers (HMWMs) of vWF in sheared blood. These results suggest that the NPSS induced a paradoxical effect. More activated platelets increase the risk of thrombosis, while the reduction in platelet receptors and the loss of HMWM-vWF increased the propensity of bleeding. The finding might provide a new perspective to understand thrombosis and acquired bleeding disorder in patients supported with blood contacting medical devices. PMID:26582038

  10. Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress

    PubMed Central

    Reininger, Armin J.; Heijnen, Harry F. G.; Schumann, Hannah; Specht, Hanno M.; Schramm, Wolfgang; Ruggeri, Zaverio M.

    2006-01-01

    We describe here the mechanism of platelet adhesion to immobilized von Willebrand factor (VWF) and subsequent formation of platelet-derived microparticles mediated by glycoprotein Ibα (GPIbα) under high shear stress. As visualized in whole blood perfused in a flow chamber, platelet attachment to VWF involved one or few membrane areas of 0.05 to 0.1 μm2 that formed discrete adhesion points (DAPs) capable of resisting force in excess of 160 pN. Under the influence of hydrodynamic drag, membrane tethers developed between the moving platelet body and DAPs firmly adherent to immobilized VWF. Continued stretching eventually caused the separation of many such tethers, leaving on the surface tube-shaped or spherical microparticles with a diameter as low as 50 to 100 nm. Adhesion receptors (GPIbα, αIIbβ3) and phosphatidylserine were expressed on the surface of these microparticles, which were procoagulant. Shearing platelet-rich plasma at the rate of 10 000 s–1 in a cone-and-plate viscosimeter increased microparticle counts up to 55-fold above baseline. Blocking the GPIb-VWF interaction abolished microparticle generation in both experimental conditions. Thus, a biomechanical process mediated by GPIbα-VWF bonds in rapidly flowing blood may not only initiate platelet arrest onto reactive vascular surfaces but also generate procoagulant microparticles that further enhance thrombus formation. PMID:16449527

  11. Von Willebrand factor availability in platelet concentrates stored for 5 days.

    PubMed

    Cesar, J M; García-Avello, A; Monteagudo, J; Espinosa, J I; Lodos, J C; Castillo, R; Navarro, J L

    1994-02-01

    Von Willebrand factor (vWF) availability was assessed in platelet concentrates (PCs). After 5 days of storage, 82 +/- 9% of basal levels of ristocetin cofactor activity (vWF:RCo) remained in PCs. vWF antigen (vWF:Ag) increased up to 166 +/- 38% (P < 0.05) in the same period. Autoradiograph pattern of vW:Ag showed an increase in low molecular weight multimers, and fast migrating multimeric forms were visualized by crossed immunoelectrophoresis on day 5. Studies carried out in platelet free plasma stored as PCs showed similar changes in vWF:RCo but increments in vWF:Ag were not detected. These data indicate that PCs maintain vWF:RCo levels of clinical value even after 5 days of storage and suggest that vWF comes out from platelets to plasma during storage. PMID:8141116

  12. Structural origins of misfolding propensity in the platelet adhesive von Willebrand factor A1 domain.

    PubMed

    Zimmermann, Michael T; Tischer, Alexander; Whitten, Steven T; Auton, Matthew

    2015-07-21

    The von Willebrand factor (VWF) A1 and A3 domains are structurally isomorphic yet exhibit distinct mechanisms of unfolding. The A1 domain, responsible for platelet adhesion to VWF in hemostasis, unfolds through a molten globule intermediate in an apparent three-state mechanism, while A3 unfolds by a classical two-state mechanism. Inspection of the sequences or structures alone does not elucidate the source of this thermodynamic conundrum; however, the three-state character of the A1 domain suggests that it has more than one cooperative substructure yielding two separate unfolding transitions not present in A3. We investigate the extent to which structural elements contributing to intermediate conformations can be identified using a residue-specific implementation of the structure-energy-equivalence-of-domains algorithm (SEED), which parses proteins of known structure into their constituent thermodynamically cooperative components using protein-group-specific, transfer free energies. The structural elements computed to contribute to the non-two-state character coincide with regions where Von Willebrand disease mutations induce misfolded molten globule conformations of the A1 domain. This suggests a mechanism for the regulation of rheological platelet adhesion to A1 based on cooperative flexibility of the α2 and α3 helices flanking the platelet GPIbα receptor binding interface. PMID:26200876

  13. Structural Origins of Misfolding Propensity in the Platelet Adhesive Von Willebrand Factor A1 Domain

    PubMed Central

    Zimmermann, Michael T.; Tischer, Alexander; Whitten, Steven T.; Auton, Matthew

    2015-01-01

    The von Willebrand factor (VWF) A1 and A3 domains are structurally isomorphic yet exhibit distinct mechanisms of unfolding. The A1 domain, responsible for platelet adhesion to VWF in hemostasis, unfolds through a molten globule intermediate in an apparent three-state mechanism, while A3 unfolds by a classical two-state mechanism. Inspection of the sequences or structures alone does not elucidate the source of this thermodynamic conundrum; however, the three-state character of the A1 domain suggests that it has more than one cooperative substructure yielding two separate unfolding transitions not present in A3. We investigate the extent to which structural elements contributing to intermediate conformations can be identified using a residue-specific implementation of the structure-energy-equivalence-of-domains algorithm (SEED), which parses proteins of known structure into their constituent thermodynamically cooperative components using protein-group-specific, transfer free energies. The structural elements computed to contribute to the non-two-state character coincide with regions where Von Willebrand disease mutations induce misfolded molten globule conformations of the A1 domain. This suggests a mechanism for the regulation of rheological platelet adhesion to A1 based on cooperative flexibility of the α2 and α3 helices flanking the platelet GPIbα receptor binding interface. PMID:26200876

  14. Platelets

    MedlinePlus

    ... are related to immunity and fighting infection. Platelet Production Platelets are produced in the bone marrow, the ... platelet destruction and also decreased bone marrow platelet production. These problems are caused by autoantibodies. Antibodies are ...

  15. Circulating but not immobilized N-deglycosylated von Willebrand factor increases platelet adhesion under flow conditions

    PubMed Central

    Fallah, M. A.; Huck, V.; Niemeyer, V.; Desch, A.; Angerer, J. I.; McKinnon, T. A. J.; Wixforth, A.; Schneider, S. W.; Schneider, M. F.

    2013-01-01

    The role of von Willebrand factor (VWF) as a shear stress activated platelet adhesive has been related to a coiled-elongated shape conformation. The forces dominating this transition have been suggested to be controlled by the proteins polymeric architecture. However, the fact that 20% of VWF molecular weight originates from glycan moieties has so far been neglected in these calculations. In this study, we present a systematic experimental investigation on the role of N-glycosylation for VWF mediated platelet adhesion under flow. A microfluidic flow chamber with a stenotic compartment that allows one to mimic various physiological flow conditions was designed for the efficient analysis of the adhesion spectrum. Surprisingly, we found an increase in platelet adhesion with elevated shear rate, both qualitatively and quantitatively fully conserved when N-deglycosylated VWF (N-deg-VWF) instead of VWF was immobilized in the microfluidic channel. This has been demonstrated consistently over four orders of magnitude in shear rate. In contrast, when N-deg-VWF was added to the supernatant, an increase in adhesion rate by a factor of two was detected compared to the addition of wild-type VWF. It appears that once immobilized, the role of glycans is at least modified if not—as found here for the case of adhesion—negated. These findings strengthen the physical impact of the circulating polymer on shear dependent platelet adhesion events. At present, there is no theoretical explanation for an increase in platelet adhesion to VWF in the absence of its N-glycans. However, our data indicate that the effective solubility of the protein and hence its shape or conformation may be altered by the degree of glycosylation and is therefore a good candidate for modifying the forces required to uncoil this biopolymer. PMID:24404057

  16. Comparison of PFA-100 testing and bleeding time for detecting platelet hypofunction and von Willebrand disease in clinical practice.

    PubMed

    Posan, Emoke; McBane, Robert D; Grill, Diane E; Motsko, Cheri L; Nichols, William L

    2003-09-01

    The PFA-100 instrument (Platelet Function Analyzer, Dade Behring) has been reported to be superior to the bleeding time (BT) as a screening test of primary hemostasis. However evaluation of this device has been principally limited to selected populations. The study's aim was to determine testing performance in clinical practice, by comparing the PFA-100 to the BT for the identification of von Willebrand disease (VWD) and intrinsic platelet hypofunction. From 1998-2000, PFA-100 closure time (CT) for epinephrinecollagen (EPI) and ADP-collagen (ADP) cartridges and modified Ivy BTs were performed on outpatients referred for testing for suspected or known hemorrhagic diathesis (n = 346). Evaluation included assays of von Willebrand factor and platelet aggregometry in addition to platelet flow cytometry and electron microscopy when indicated. The normal distribution of PFA-100 CTs was determined using blood samples from 61 normal donors studied on 155 occasions. Results show that thirty-four patients met the diagnostic criteria for VWD and 31 patients were diagnosed with congenital or acquired intrinsic platelet hypofunction. The sensitivity of the PFA-100 for identification of VWD was significantly better (p < 0.01) than the BT with similar specificity. In contrast, the PFA-100 was comparable, but not superior to the BT for detecting platelet hypofunction. We conclude that the PFA-100 performance compares favorably to the BT for the identification of intrinsic platelet hypofunction in clinical practice with superior sensitivity for detecting VWD. Therefore, the PFA-100 could replace the BT for purposes of screening for VWD and intrinsic platelet hypofunction. When clinical suspicion is strong, testing should be supplemented with assays of von Willebrand factor and platelet aggregometry. PMID:12958618

  17. Functional domains on von Willebrand factor. Recognition of discrete tryptic fragments by monoclonal antibodies that inhibit interaction of von Willebrand factor with platelets and with collagen.

    PubMed Central

    Sixma, J J; Sakariassen, K S; Stel, H V; Houdijk, W P; In der Maur, D W; Hamer, R J; de Groot, P G; van Mourik, J A

    1984-01-01

    We have identified two functional domains on the von Willebrand factor (VWF) moiety of the Factor VIII-von Willebrand factor complex (FVIII-VWF), one interacting with blood platelets, and one interacting with vessel wall collagens, by means of two monoclonal antibodies directed against the VWF molecule, CLB-RAg 35 and CLB-RAg 201. The monoclonal antibody CLB-RAg 35 inhibited virtually all platelet adherence to artery subendothelium and to purified vessel wall collagen type III, at relatively high wall shear rates. CLB-RAg 35 also inhibited the ristocetin-induced platelet aggregation and the binding of FVIII-VWF to the platelet in the presence of ristocetin but did not affect the binding of FVIII-VWF to collagen. The monoclonal antibody CLB-RAg 201 inhibited the binding of FVIII-VWF to purified vessel wall collagen type I and III and all platelet adherence to collagen type III and the platelet adherence to subendothelium that was mediated by FVIII-VWF in plasma. The two functional domains on FVIII-VWF that were recognized by CLB-RAg 35 and CLB-RAg 201 were identified by means of immunoprecipitation studies of trypsin-digested FVIII-VWF. The domains resided on different polypeptide fragments, with a Mr of 48,000 for the collagen binding domain and a Mr of 116,000 for the platelet binding domain. The 116,000-mol wt fragment consisted of subunits of 52,000/56,000 mol wt and 14,000 mol wt after reduction. The 52,000/56,000-mol wt subunits possessed the epitope for CLB-RAg 35. Images PMID:6332119

  18. Identification of a Small Molecule That Modulates Platelet Glycoprotein Ib-von Willebrand Factor Interaction*

    PubMed Central

    Broos, Katleen; Trekels, Mieke; Jose, Rani Alphonsa; Demeulemeester, Jonas; Vandenbulcke, Aline; Vandeputte, Nele; Venken, Tom; Egle, Brecht; De Borggraeve, Wim M.; Deckmyn, Hans; De Maeyer, Marc

    2012-01-01

    The von Willebrand factor (VWF) A1-glycoprotein (GP) Ibα interaction is of major importance during thrombosis mainly at sites of high shear stress. Inhibitors of this interaction prevent platelet-dependent thrombus formation in vivo, without major bleeding complications. However, the size and/or protein nature of the inhibitors currently in development limit oral bioavailability and clinical development. We therefore aimed to search for a small molecule protein-protein interaction inhibitor interfering with the VWF-GPIbα binding. After determination of putative small molecule binding pockets on the surface of VWF-A1 and GPIbα using site-finding algorithms and molecular dynamics, high throughput molecular docking was performed on both binding partners. A selection of compounds showing good in silico docking scores into the predicted pockets was retained for testing their in vitro effect on VWF-GPIbα complex formation, by which we identified a compound that surprisingly stimulated the VWF-GPIbα binding in a ristocetin cofactor ELISA and increased platelet adhesion in whole blood to collagen under arterial shear rate but in contrast inhibited ristocetin-induced platelet aggregation. The selected compound adhering to the predicted binding partner GPIbα could be confirmed by saturation transfer difference NMR spectroscopy. We thus clearly identified a small molecule that modulates VWF-GPIbα binding and that will now serve as a starting point for further studies and chemical modifications to fully characterize the interaction and to manipulate specific activity of the compound. PMID:22232560

  19. Molecular Imaging of Platelet-Endothelial Interactions and Endothelial Von Willebrand Factor In Early and Mid-Stage Atherosclerosis

    PubMed Central

    Shim, Chi Young; Liu, Ya Ni; Atkinson, Tamara; Xie, Aris; Foster, Ted; Davidson, Brian P.; Treible, Mackenzie; Qi, Yue; López, José A.; Munday, Adam; Ruggeri, Zaverio; Lindner, Jonathan R.

    2015-01-01

    Background Non-thrombotic platelet-endothelial interactions may contribute to atherosclerotic plaque development, although in vivo studies examining mechanism without platelet pre-activation are lacking. Using in vivo molecular imaging at various stages of atherosclerosis, we quantified platelet-endothelial interactions and evaluated the contribution of major adhesion pathways. Methods and Results Mice deficient for the LDL-receptor and Apobec-1 were studied as an age-dependent model of atherosclerosis at 10, 20, 30, and 40 wks of age, which provided progressive increase in stage from very early fatty streak (10 wks) to large complex plaques without rupture (40 wks). Platelet-targeted contrast ultrasound molecular imaging of the thoracic aorta performed with microbubbles targeted to GPIbα demonstrated selective signal enhancement as early as 10 weeks of age. This signal increased progressively with age (almost 8-fold increase from 10 to 40 weeks, ANOVA p<0.001). Specificity for platelet targeting was confirmed by the reduction in platelet-targeted signal commensurate with the decrease in platelet count after immunodepletion with anti-GPIb or anti-CD41 antibody. Inhibition of P-selectin in 20 and 40 wk atherosclerotic mice resulted in a small (15-30%) reduction in platelet signal. Molecular imaging with microbubbles targeted to the A1 domain of von Willebrand factor (VWF) demonstrated selective signal enhancement at all time points which did not significantly increase with age. Treatment of 20 and 40 week mice with recombinant ADAMTS13 eliminated platelet and VWF molecular imaging signal. Conclusions Platelet-endothelial interactions occur in early atherosclerosis. These interactions are in part due to endothelial VWF large multimers which can be reversed with exogenous ADAMTS13. PMID:26156014

  20. Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor

    SciTech Connect

    Ware, J.; Dent, J.A.; Azuma, Hiroyuki; Sugimoto, Mitsuhiko; Kyrle, P.A.; Yoshioka, Akira; Ruggeri, Z.M. )

    1991-04-01

    von Willebrand factor (vWF) supports platelet adhesion on thrombogenic surfaces by binding to platelet membrane glycoprotein (GP) Ib in the GP Ib-IX receptor complex. This interaction is physiologically regulated so that it does not occur between circulating vWF and platelets but, rather, only at a site of vascular injury. The abnormal vWF found in type IIB von Willebrand disease, however, has a characteristically increased affinity for GP Ib and binds to circulating platelets. The authors have analyzed the molecular basis of this abnormality by sequence analysis of a type IIB vWF cDNA and have identified a single amino acid change, Trp{sup 550} to Cys{sup 550}, located in the GP IB-binding domain of the molecule comprising residues 449-728. Bacterial expression of recombinant fragments corresponding to this vWF domain yielded molecules that, whether containing a normal Trp{sup 550} or a mutant Cys{sup 550} residue, bound directly to GP Ib in the absence of modulators and with similar affinity. These results identify a region of vWF that, although not thought to be directly involved in binding to GP Ib, may modulate the interaction through conformational changes.

  1. Ionizing radiation enhances platelet adhesion to the extracellular matrix of human endothelial cells by an increase in the release of von Willebrand factor

    SciTech Connect

    Verheij, M.; Dewit, L.G.H. ); Boomgaard, M.N.; Brinkman, H.J.M.; Mourik, J.A. van )

    1994-02-01

    The effect of radiation on the secretion of von Willebrand factor by endothelial cells was studied in a three-compartment culture system. The release of von Willebrand factor was significantly increased at 48 h after a single [gamma]-radiation dose of 20 Gy in both the luminal and abluminal direction by 23 (P < 0.05) and 41% (P < 0.02), respectively. To establish whether the enhanced production of von Willebrand factor affected the thrombogenicity of the extracellular matrix, platelet adhesion to the matrix produced by a monolayer of cultured endothelial cells during 48 h after irradiation was analyzed in a perfusion chamber at high shear rate (1300 s[sup [minus]1]). Platelet adhesion was significantly increased by irradiation both in the presence and in the absence of plasmatic von Willebrand factor by 65 (P < 0.05) and 34.5% (P < 0.005), respectively. Incubation of the perfusate with a monoclonal antibody that blocks the binding of von Willebrand factor to platelet GPIb (CLB-RAg 35) resulted in an almost complete inhibition of platelet adhesion. These data indicate that radiation enhances platelet adhesion to the extracellular matrix by an increase in the release of von Willebrand factor by endothelial cells. This event may be important in early radiation-induced vascular pathology. 37 refs., 2 figs., 2 tabs.

  2. Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor.

    PubMed Central

    Ware, J; Dent, J A; Azuma, H; Sugimoto, M; Kyrle, P A; Yoshioka, A; Ruggeri, Z M

    1991-01-01

    von Willebrand factor (vWF) supports platelet adhesion on thrombogenic surfaces by binding to platelet membrane glycoprotein (GP) Ib in the GP Ib-IX receptor complex. This interaction is physiologically regulated so that it does not occur between circulating vWF and platelets but, rather, only at a site of vascular injury. The abnormal vWF found in type IIB von Willebrand disease, however, has a characteristically increased affinity for GP Ib and binds to circulating platelets. We have analyzed the molecular basis of this abnormality by sequence analysis of a type IIB vWF cDNA and have identified a single amino acid change, Trp550 to Cys550, located in the GP Ib-binding domain of the molecule comprising residues 449-728. Bacterial expression of recombinant fragments corresponding to this vWF domain yielded molecules that, whether containing a normal Trp550 or a mutant Cys550 residue, bound directly to GP Ib in the absence of modulators and with similar affinity. In contrast, mammalian cell expression of the same segment of sequence yielded molecules that, when containing the normal Trp550, did not bind to GP Ib directly but, like native vWF, bound in the presence of ristocetin. However, molecules containing the point mutation (Cys550) behaved like type IIB vWF--namely, bound to GP Ib even without ristocetin modulation and, in the presence of ristocetin, had 10-fold higher affinity than molecules with normal sequence. These results identify a region of vWF that, although not thought to be directly involved in binding to GP Ib, may modulate the interaction through conformational changes. Images PMID:2011604

  3. von Willebrand factor (VWF) propeptide binding to VWF D′D3 domain attenuates platelet activation and adhesion

    PubMed Central

    Madabhushi, Sri R.; Shang, Chengwei; Dayananda, Kannayakanahalli M.; Rittenhouse-Olson, Kate; Murphy, Mary; Ryan, Thomas E.; Montgomery, Robert R.

    2012-01-01

    Noncovalent association between the von Willebrand factor (VWF) propeptide (VWFpp) and mature VWF aids N-terminal multimerization and protein compartmentalization in storage granules. This association is currently thought to dissipate after secretion into blood. In the present study, we examined this proposition by quantifying the affinity and kinetics of VWFpp binding to mature VWF using surface plasmon resonance and by developing novel anti-VWF D′D3 mAbs. Our results show that the only binding site for VWFpp in mature VWF is in its D′D3 domain. At pH 6.2 and 10mM Ca2+, conditions mimicking intracellular compartments, VWFpp-VWF binding occurs with high affinity (KD = 0.2nM, koff = 8 × 10−5 s−1). Significant, albeit weaker, binding (KD = 25nM, koff = 4 × 10−3 s−1) occurs under physiologic conditions of pH 7.4 and 2.5mM Ca2+. This interaction was also observed in human plasma (KD = 50nM). The addition of recombinant VWFpp in both flow-chamber–based platelet adhesion assays and viscometer-based shear-induced platelet aggregation and activation studies reduced platelet adhesion and activation partially. Anti-D′D3 mAb DD3.1, which blocks VWFpp binding to VWF-D′D3, also abrogated platelet adhesion, as shown by shear-induced platelet aggregation and activation studies. Our data demonstrate that VWFpp binding to mature VWF occurs in the circulation, which can regulate the hemostatic potential of VWF by reducing VWF binding to platelet GpIbα. PMID:22452980

  4. Functional behavior of vessels from pigs with von Willebrand disease. Values of platelet deposition are identical to those obtained on normal vessels

    SciTech Connect

    Badimon, L.; Badimon, J.J.; Turitto, V.T.; Rand, J.; Fuster, V.

    1989-03-01

    Vessels from normal pigs and pigs with severe von Willebrand disease were exposed for up to 30 minutes to both nonanticoagulated and heparinized blood from normal pigs in an ex vivo perfusion system. Shear rates at the vessel surface were varied over a broad physiological range, gamma w = 212 to 3380 sec-1. The deposition of /sup 111/In-labeled platelets was determined by radiometric counting. For all shear rates and exposure times investigated, the levels of platelet deposition on de-endothelialized thoracic aorta of normal and von Willebrand disease pigs were not significantly different. Thus, the functional activity of the vessels correlated with the results obtained previously by immunofluorescence. Namely, the von Willebrand factor protein in the thoracic subendothelium of normal pigs is significantly diminished or absent and is comparable to the levels observed in von Willebrand disease pigs.

  5. A molten globule intermediate of the Von Willebrand Factor A1 domain firmly tethers platelets under shear flow

    PubMed Central

    Tischer, Alexander; Madde, Pranathi; Blancas-Mejia, Luis. M.; Auton, Matthew

    2014-01-01

    Clinical mutations in patients diagnosed with Type 2A von Willebrand disease (vWD) have been identified that break the single disulfide bond linking N- and C-termini in the vWF A1 domain. We have modeled the effect of these mutations on the disulfide-bonded structure of A1 by reducing and carboxy-amidating these cysteines. Solution biophysical studies show that loss of this disulfide bond induces a molten globule conformational state lacking global tertiary structure but retaining residual secondary structure. The conformational dependence of platelet adhesion to these native and molten globule states of A1 is quantitatively compared using real-time high-speed video microscopy analysis of platelet translocation dynamics under shear flow in a parallel plate micro-fluidic flow chamber. While normal platelets translocating on surface-captured native A1 domain retain the catch-bond character of pause times that increase as a function of shear rate at low shear and decrease as a function of shear rate at high shear, platelets that interact with A1 lacking the disulfide bond remain stably attached and do not translocate. Based on these findings, we propose that the shear stress-sensitive regulation of the A1-GPIb interaction is due to folding the tertiary structure of this domain. Removal of the tertiary structure by disrupting the disulfide bond destroys this regulatory mechanism resulting in high-strength interactions between platelets and vWF A1 that are dependent only on residual secondary structure elements present in the molten globule conformation. PMID:24265179

  6. A molten globule intermediate of the von Willebrand factor A1 domain firmly tethers platelets under shear flow.

    PubMed

    Tischer, Alexander; Madde, Pranathi; Blancas-Mejia, Luis M; Auton, Matthew

    2014-05-01

    Clinical mutations in patients diagnosed with Type 2A von Willebrand disease (VWD) have been identified that break the single disulfide bond linking N- and C-termini in the vWF A1 domain. We have modeled the effect of these mutations on the disulfide-bonded structure of A1 by reducing and carboxy-amidating these cysteines. Solution biophysical studies show that loss of this disulfide bond induces a molten globule conformational state lacking global tertiary structure but retaining residual secondary structure. The conformational dependence of platelet adhesion to these native and molten globule states of A1 is quantitatively compared using real-time high-speed video microscopy analysis of platelet translocation dynamics under shear flow in a parallel plate microfluidic flow chamber. While normal platelets translocating on surface-captured native A1 domain retain the catch-bond character of pause times that increase as a function of shear rate at low shear and decrease as a function of shear rate at high shear, platelets that interact with A1 lacking the disulfide bond remain stably attached and do not translocate. Based on these findings, we propose that the shear stress-sensitive regulation of the A1-GPIb interaction is due to folding the tertiary structure of this domain. Removal of the tertiary structure by disrupting the disulfide bond destroys this regulatory mechanism resulting in high-strength interactions between platelets and vWF A1 that are dependent only on residual secondary structure elements present in the molten globule conformation. PMID:24265179

  7. Changes in thermodynamic stability of von Willebrand factor differentially affect the force-dependent binding to platelet GPIbalpha.

    PubMed

    Auton, Matthew; Sedlák, Erik; Marek, Jozef; Wu, Tao; Zhu, Cheng; Cruz, Miguel A

    2009-07-22

    In circulation, plasma glycoprotein von Willebrand Factor plays an important role in hemostasis and in pathological thrombosis under hydrodynamic forces. Mutations in the A1 domain of von Willebrand factor cause the hereditary types 2B and 2M von Willebrand disease that either enhance (2B) or inhibit (2M) the interaction of von Willebrand factor with the platelet receptor glycoprotein Ibalpha. To understand how type 2B and 2M mutations cause clinically opposite phenotypes, we use a combination of protein unfolding thermodynamics and atomic force microscopy to assess the effects of two type 2B mutations (R1306Q and I1309V) and a type 2M mutation (G1324S) on the conformational stability of the A1 domain and the single bond dissociation kinetics of the A1-GPIbalpha interaction. At physiological temperature, the type 2B mutations destabilize the structure of the A1 domain and shift the A1-GPIbalpha catch to slip bonding to lower forces. Conversely, the type 2M mutation stabilizes the structure of the A1 domain and shifts the A1-GPIbalpha catch to slip bonding to higher forces. As a function of increasing A1 domain stability, the bond lifetime at low force decreases and the critical force required for maximal bond lifetime increases. Our results are able to distinguish the clinical phenotypes of these naturally occurring mutations from a thermodynamic and biophysical perspective that provides a quantitative description of the allosteric coupling of A1 conformational stability with the force dependent catch to slip bonding between A1 and GPIbalpha. PMID:19619477

  8. Frequency of platelet type versus type 2B von Willebrand disease. An international registry-based study.

    PubMed

    Hamilton, Alexander; Ozelo, Margareth; Leggo, Jayne; Notley, Colleen; Brown, Hannah; Frontroth, Juan Pablo; Angelillo-Scherrer, Anne; Baghaei, Fariba; Enayat, Said M; Favaloro, Emmanuel; Lillicrap, David; Othman, Maha

    2011-03-01

    Less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD) worldwide. Several reports have discussed the diagnostic challenge of this disease versus the closely similar disorder type 2B VWD. However, no systematic study has evaluated this dilemma globally. Over three years, a total of 110 samples/data from eight countries were analysed. A molecular approach was utilised, analysing exon 28 of the von Willebrand factor (VWF) gene, and in mutation negative cases the platelet GP1BA gene. Our results show that 48 cases initially diagnosed as putative type 2B/PT-VWD carried exon 28 mutations consistent with type 2B VWD, 17 carried GP1BA mutations consistent with a PT-VWD diagnosis, three had other VWD types (2A and 2M) and five expressed three non-previously published exon 28 mutations. Excluding 10 unaffected family members and one acquired VWD, 26 cases did not have mutations in either genes. Based on our study, the percentage of type 2B VWD diagnosis is 44% while the percentage of misdiagnosis of PT-VWD is 15%. This is the first large international study to investigate the occurrence of PT-VWD and type 2B VWD worldwide and to evaluate DNA analysis as a diagnostic tool for a large cohort of patients. The study highlights the diagnostic limitations due to unavailability/poor application of RIPA and related tests in some centres and proposes genetic analysis as a suitable tool for the discrimination of the two disorders worldwide. Cases that are negative for both VWF and GP1BA gene mutations require further evaluation for alternative diagnoses. PMID:21301777

  9. High-density lipoprotein modulates thrombosis by preventing von Willebrand factor self-association and subsequent platelet adhesion.

    PubMed

    Chung, Dominic W; Chen, Junmei; Ling, Minhua; Fu, Xiaoyun; Blevins, Teri; Parsons, Scott; Le, Jennie; Harris, Jeff; Martin, Thomas R; Konkle, Barbara A; Zheng, Ying; López, José A

    2016-02-01

    The ability of von Willebrand factor (VWF) to initiate platelet adhesion depends on the number of monomers in individual VWF multimers and on the self-association of individual VWF multimers into larger structures. VWF self-association is accelerated by shear stress. We observed that VWF self-association occurs during adsorption of VWF onto surfaces, assembly of secreted VWF into hyperadhesive VWF strings on the endothelial surface, and incorporation of fluid-phase VWF into VWF fibers. VWF adsorption under static conditions increased with increased VWF purity and was prevented by a component of plasma. We identified that component as high-density lipoprotein (HDL) and its major apolipoprotein ApoA-I. HDL and ApoA-I also prevented VWF on the endothelium from self-associating into longer strands and inhibited the attachment of fluid-phase VWF onto vessel wall strands. Platelet adhesion to VWF fibers was reduced in proportion to the reduction in self-associated VWF. In a mouse model of thrombotic microangiopathy, HDL also largely prevented the thrombocytopenia induced by injection of high doses of human VWF. Finally, a potential role for ApoA-I in microvascular occlusion associated with thrombotic thrombocytopenic purpura and sepsis was revealed by the inverse relationship between the concentration of ApoA-I and that of hyperadhesive VWF. These results suggest that interference with VWF self-association would be a new approach to treating thrombotic disorders. PMID:26552698

  10. Congenital platelet function defects

    MedlinePlus

    Kottke-Marchant K. Platelet disorders. In: Hsi ED, ed. Hematopathology . 2nd ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 2. Nichols WL. Von Willebrand disease and hemorrhagic abnormalities of platelet ...

  11. Modification of the platelet binding domain of von Willebrand Factor (vWF)

    SciTech Connect

    Silverman, C.; Mascelli, M.A.; Karl, D.W.; Kirby, E.P.

    1986-05-01

    Bovine vWF has been modified with /sup 125/I-Bolton Hunter reagent (I/sup */-BHR) with a concomittant loss of its platelet agglutinating activity and a reduction in its ability to bind to platelets. BHR labels free alpha and epsilon amino groups. The I/sup */-BHR-vWF migrated as a single band of M/sub r/ = 210kD on reduced SDS polyacrylamide gels. Its multimeric composition on SDS agarose gels was identical to unlabeled vWF. Incorporation of an average of 1.2 moles of I/sup */-BHR/subunit vWF at pH 8.5 caused a 50% loss of platelet agglutinating activity. This represents less than 2% of the 118 lysine residues in each subunit vWF. No I/sup */-BHR was released after treatment with 1M hydroxylamine which would cleave O-acylated tyrosines. Digestion of both unlabeled and I/sup */-BHR-vWF with Protease 1, a metalloprotease from the venom of western diamondback rattlesnake, produces two fragments which have an M/sub r/ of 250kD and 200kD. The 250kD fragment contains the platelet binding site and is composed of 3 peptide chains with M/sub r/ 125kD, 78kD and 45kD. Gels of the 250kD fragment from I/sup */-BHR-vWF revealed radioactivity predominantly in the 125kD fragment, suggesting that the platelet binding site resides on the 125kD fragment.

  12. The N-terminal flanking region of the A1 domain regulates the force-dependent binding of von Willebrand factor to platelet glycoprotein Ibα.

    PubMed

    Ju, Lining; Dong, Jing-fei; Cruz, Miguel A; Zhu, Cheng

    2013-11-01

    Binding of platelet glycoprotein Ibα (GPIbα) to von Willebrand factor (VWF) initiates platelet adhesion to disrupted vascular surface under arterial blood flow. Flow exerts forces on the platelet that are transmitted to VWF-GPIbα bonds, which regulate their dissociation. Mutations in VWF and/or GPIbα may alter the mechanical regulation of platelet adhesion to cause hemostatic defects as found in patients with von Willebrand disease (VWD). Using a biomembrane force probe, we observed biphasic force-decelerated (catch) and force-accelerated (slip) dissociation of GPIbα from VWF. The VWF A1 domain that contains the N-terminal flanking sequence Gln(1238)-Glu(1260) (1238-A1) formed triphasic slip-catch-slip bonds with GPIbα. By comparison, using a short form of A1 that deletes this sequence (1261-A1) abolished the catch bond, destabilizing its binding to GPIbα at high forces. Importantly, shear-dependent platelet rolling velocities on these VWF ligands in a flow chamber system mirrored the force-dependent single-bond lifetimes. Adding the Gln(1238)-Glu(1260) peptide, which interacted with GPIbα and 1261-A1 but not 1238-A1, to whole blood decreased platelet attachment under shear stress. Soluble Gln(1238)-Glu(1260) reduced the lifetimes of GPIbα bonds with VWF and 1238-A1 but rescued the catch bond of GPIbα with 1261-A1. A type 2B VWD 1238-A1 mutation eliminated the catch bond by prolonging lifetimes at low forces, a type 2M VWD 1238-A1 mutation shifted the respective slip-catch and catch-slip transition points to higher forces, whereas a platelet type VWD GPIbα mutation enhanced the bond lifetime in the entire force regime. These data reveal the structural determinants of VWF activation by hemodynamic force of the circulation. PMID:24062306

  13. von Willebrand Factor-Rich Platelet Thrombi in the Liver Cause Sinusoidal Obstruction Syndrome following Oxaliplatin-Based Chemotherapy

    PubMed Central

    Nishigori, Naoto; Matsumoto, Masanori; Koyama, Fumikazu; Hayakawa, Masaki; Hatakeyayama, Kinta; Ko, Saiho; Fujimura, Yoshihiro; Nakajima, Yoshiyuki

    2015-01-01

    Oxaliplatin-based chemotherapy is widely used to treat advanced colorectal cancer (CRC). Sinusoidal obstruction syndrome (SOS) due to oxaliplatin is a serious type of chemotherapy-associated liver injury (CALI) in CRC patients. SOS is thought to be caused by the sinusoidal endothelial cell damage, which results in the release of unusually-large von Willebrand factor multimers (UL-VWFMs) from endothelial cells. To investigate the pathophysiology of CALI after oxaliplatin-based chemotherapy, we analyzed plasma concentration of von Willebrand factor (VWF) and the distribution of VWFMs in CRC patients. Twenty-three patients with advanced CRC who received oxaliplatin-based chemotherapy with (n = 6) and without (n = 17) bevacizumab were analyzed. CALI (n = 6) and splenomegaly (n = 9) were found only in patients who did not treated with bevacizumab. Plasma VWF antigen (VWF:Ag) and serum aspartate aminotransferase (AST) levels increased after chemotherapy only in patients without bevacizumab. VWFM analysis in patients who did not receive bevacizumab showed the presence of UL-VWFMs and absence of high molecular weight VWFMs during chemotherapy, especially in those with CALI. In addition, plasma VWF:Ag and AST levels increased after chemotherapy in patients with splenomegaly (n = 9), but not in patients without splenomegaly (n = 14). Histological findings in the liver tissue of patients who did not receive bevacizumab included sinusoidal dilatation and microthrombi in the sinusoids. Many microthrombi were positive for both anti-IIb/IIIa and anti-VWF antibodies. Plasma UL-VWFM levels might be increased by damage to endothelial cells as a result of oxaliplatin-based chemotherapy. Bevacizumab could prevent CALI and splenomegaly through inhibition of VWF-rich platelet thrombus formation. PMID:26580395

  14. von Willebrand factor fibers promote cancer-associated platelet aggregation in malignant melanoma of mice and humans.

    PubMed

    Bauer, Alexander T; Suckau, Jan; Frank, Kathrin; Desch, Anna; Goertz, Lukas; Wagner, Andreas H; Hecker, Markus; Goerge, Tobias; Umansky, Ludmila; Beckhove, Philipp; Utikal, Jochen; Gorzelanny, Christian; Diaz-Valdes, Nancy; Umansky, Viktor; Schneider, Stefan W

    2015-05-14

    Tumor-mediated procoagulatory activity leads to venous thromboembolism and supports metastasis in cancer patients. A prerequisite for metastasis formation is the interaction of cancer cells with endothelial cells (ECs) followed by their extravasation. Although it is known that activation of ECs and the release of the procoagulatory protein von Willebrand factor (VWF) is essential for malignancy, the underlying mechanisms remain poorly understood. We hypothesized that VWF fibers in tumor vessels promote tumor-associated thromboembolism and metastasis. Using in vitro settings, mouse models, and human tumor samples, we showed that melanoma cells activate ECs followed by the luminal release of VWF fibers and platelet aggregation in tumor microvessels. Analysis of human blood samples and tumor tissue revealed that a promoted VWF release combined with a local inhibition of proteolytic activity and protein expression of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type I repeats 13) accounts for this procoagulatory milieu. Blocking endothelial cell activation by the low-molecular-weight heparin tinzaparin was accompanied by a lack of VWF networks and inhibited tumor progression in a transgenic mouse model. Our findings implicate a mechanism wherein tumor-derived vascular endothelial growth factor-A (VEGF-A) promotes tumor progression and angiogenesis. Thus, targeting EC activation envisions new therapeutic strategies attenuating tumor-related angiogenesis and coagulation. PMID:25977583

  15. Platelet glycoprotein Ibalpha forms catch bonds with human WT vWF but not with type 2B von Willebrand disease vWF.

    PubMed

    Yago, Tadayuki; Lou, Jizhong; Wu, Tao; Yang, Jun; Miner, Jonathan J; Coburn, Leslie; López, José A; Cruz, Miguel A; Dong, Jing-Fei; McIntire, Larry V; McEver, Rodger P; Zhu, Cheng

    2008-09-01

    Arterial blood flow enhances glycoprotein Ibalpha (GPIbalpha) binding to vWF, which initiates platelet adhesion to injured vessels. Mutations in the vWF A1 domain that cause type 2B von Willebrand disease (vWD) reduce the flow requirement for adhesion. Here we show that increasing force on GPIbalpha/vWF bonds first prolonged ("catch") and then shortened ("slip") bond lifetimes. Two type 2B vWD A1 domain mutants, R1306Q and R1450E, converted catch bonds to slip bonds by prolonging bond lifetimes at low forces. Steered molecular dynamics simulations of GPIbalpha dissociating from the A1 domain suggested mechanisms for catch bonds and their conversion by the A1 domain mutations. Catch bonds caused platelets and GPIbalpha-coated microspheres to roll more slowly on WT vWF and WT A1 domains as flow increased from suboptimal levels, explaining flow-enhanced rolling. Longer bond lifetimes at low forces eliminated the flow requirement for rolling on R1306Q and R1450E mutant A1 domains. Flowing platelets agglutinated with microspheres bearing R1306Q or R1450E mutant A1 domains, but not WT A1 domains. Therefore, catch bonds may prevent vWF multimers from agglutinating platelets. A disintegrin and metalloproteinase with a thrombospondin type 1 motif-13 (ADAMTS-13) reduced platelet agglutination with microspheres bearing a tridomain A1A2A3 vWF fragment with the R1450E mutation in a shear-dependent manner. We conclude that in type 2B vWD, prolonged lifetimes of vWF bonds with GPIbalpha on circulating platelets may allow ADAMTS-13 to deplete large vWF multimers, causing bleeding. PMID:18725999

  16. New assay for measuring binding of platelet glycoprotein IIb/IIIa to unpurified von Willebrand factor.

    PubMed

    Veyradier, A; Jumilly, A L; Ribba, A S; Obert, B; Houllier, A; Meyer, D; Girma, J P

    1999-07-01

    Among the numerous variants of vWD, no patient with an abnormal vWF binding to GPIIb/IIIa has been described to date. To search for such potential variants, we developed a two-site assay for measuring the binding of purified GPIIb/IIIa to vWF in biological fluids and we used it to study a large series of plasmas from various types of von Willebrand disease (vWD) and recombinant vWF (rvWF). vWF in plasma or rvWF in culture medium was immobilized onto anti-vWF monoclonal antibodies (MoAb)-coated wells of microtiter plates. After incubation with either unlabeled GPIIb/IIIa and a 125I-anti-GPIIb/IIIa MoAb or 125I-GPIIb/IIIa, binding curves and binding isotherms were respectively established. Normal pool plasma and wild-type rvWF were used as reference samples. We tested plasmas from 85 normal subjects, 115 patients with different types of vWD (64 type 1, 2 type 3, 9 type 2A, 4 type 2M, 16 type 2B, 15 type 2N, 3 type IID and 2 acquired forms) and 50 patients with various bleeding disorders. Four mutated rvWF with 2A (Glu875Lys and Pro885Ser) or 2B (Dupl.Met540 and Val551Phe) substitutions and one rvWF mutated in the RGD domain of the C-terminal part of vWF-subunit (Asp1746Gly) were also studied. Among the various samples tested, only rvWF Asp1746Gly had no affinity for GPIIb/IIIa. In contrast, GPIIb/IIIa similarly bound to the other vWF, independently of the proteic environment, the factor VIII level, the degree of multimerization or the mutation of vWF. Our results indicate that subjects with an abnormal vWF binding to GPIIb/IIIa are probably rare and difficult to target for a specific screening. PMID:10456467

  17. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR) Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease

    PubMed Central

    Leo, Vincenzo C.; Sabi, Essa; Cunningham, Margaret R.; Eikenboom, Jeroen C.; Lethagen, Stefan; Schneppenheim, Reinhard; Goodeve, Anne C.; Watson, Steve P.; Mundell, Stuart J.; Daly, Martina E.

    2015-01-01

    The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12) could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =), both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N) was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =). Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder. PMID:26630678

  18. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR) Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

    PubMed

    Stockley, Jacqueline; Nisar, Shaista P; Leo, Vincenzo C; Sabi, Essa; Cunningham, Margaret R; Eikenboom, Jeroen C; Lethagen, Stefan; Schneppenheim, Reinhard; Goodeve, Anne C; Watson, Steve P; Mundell, Stuart J; Daly, Martina E

    2015-01-01

    The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12) could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =), both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N) was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =). Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder. PMID:26630678

  19. Role of factor VIII-von Willebrand factor and fibronectin in the interaction of platelets in flowing blood with monomeric and fibrillar human collagen types I and III.

    PubMed

    Houdijk, W P; Sakariassen, K S; Nievelstein, P F; Sixma, J J

    1985-02-01

    Platelet adhesion to monomeric collagen types I and III, which were purified from human umbilical arteries, was studied in a perfusion chamber under well defined flow conditions. For this purpose, glass coverslips were coated with 20-30 micrograms/cm2 of collagen types I and III by spraying a solution of these collagens with a retouching air brush. Platelet deposition increased with the time of perfusion. Adhesion to both collagen types was similar in the first 3 min, but increased platelet deposition occurred on collagen type III after 3 min due to thrombus formation. Adhesion at a shear rate of 800 s-1 was strongly impaired with plasma of a patient with von Willebrand's disease or with fibronectin-free plasma. Addition of purified fibronectin to fibronectin-free plasma restored adhesion to the level obtained with normal plasma. Platelet deposition in normal plasma increased with increasing shear rates. Platelet deposition in VWD-plasma was normal at 490 s-1, but there was no increase at higher shear rates. Platelet deposition in fibronectin-free plasma was diminished at all shear rates studied from 490 to 1,300 s-1. Perfusion with a human albumin solution (HAS) to which purified Factor VIII-von Willebrand factor complex (FVIII-VWF) and fibronectin had been added gave similar platelet deposition as with normal plasma. Preincubation of collagen with FVIII-VWF and perfusion with HAS containing fibronectin, or, conversely, preincubation with fibronectin and perfusion with HAS containing FVIII-VWF, also resulted in adhesion similar to that observed in normal plasma. Similar adhesion was also observed after preincubation with both FVIII-VWF and fibronectin and subsequent perfusion with HAS alone. Sequential preincubations with first FVIII-VWF and then fibronectin, or with first fibronectin and then FVIII-VWF followed by perfusion with HAS, also gave a similar adhesion as observed with normal plasma. These data indicate that platelet adhesion to monomeric collagen types

  20. Role of factor VIII-von Willebrand factor and fibronectin in the interaction of platelets in flowing blood with monomeric and fibrillar human collagen types I and III.

    PubMed Central

    Houdijk, W P; Sakariassen, K S; Nievelstein, P F; Sixma, J J

    1985-01-01

    Platelet adhesion to monomeric collagen types I and III, which were purified from human umbilical arteries, was studied in a perfusion chamber under well defined flow conditions. For this purpose, glass coverslips were coated with 20-30 micrograms/cm2 of collagen types I and III by spraying a solution of these collagens with a retouching air brush. Platelet deposition increased with the time of perfusion. Adhesion to both collagen types was similar in the first 3 min, but increased platelet deposition occurred on collagen type III after 3 min due to thrombus formation. Adhesion at a shear rate of 800 s-1 was strongly impaired with plasma of a patient with von Willebrand's disease or with fibronectin-free plasma. Addition of purified fibronectin to fibronectin-free plasma restored adhesion to the level obtained with normal plasma. Platelet deposition in normal plasma increased with increasing shear rates. Platelet deposition in VWD-plasma was normal at 490 s-1, but there was no increase at higher shear rates. Platelet deposition in fibronectin-free plasma was diminished at all shear rates studied from 490 to 1,300 s-1. Perfusion with a human albumin solution (HAS) to which purified Factor VIII-von Willebrand factor complex (FVIII-VWF) and fibronectin had been added gave similar platelet deposition as with normal plasma. Preincubation of collagen with FVIII-VWF and perfusion with HAS containing fibronectin, or, conversely, preincubation with fibronectin and perfusion with HAS containing FVIII-VWF, also resulted in adhesion similar to that observed in normal plasma. Similar adhesion was also observed after preincubation with both FVIII-VWF and fibronectin and subsequent perfusion with HAS alone. Sequential preincubations with first FVIII-VWF and then fibronectin, or with first fibronectin and then FVIII-VWF followed by perfusion with HAS, also gave a similar adhesion as observed with normal plasma. These data indicate that platelet adhesion to monomeric collagen types

  1. Apoptotic Platelet Events Are Not Observed in Severe von Willebrand Disease-Type 2B Mutation p.V1316M

    PubMed Central

    Berrou, Eliane; Kauskot, Alexandre; Adam, Frédéric; Harel, Amélie; Legendre, Paulette; Lavenu Bombled, Cécile; Rothschild, Chantal; Prevost, Nicolas; Christophe, Olivier D.; Lenting, Peter J.; Denis, Cécile V.; Rosa, Jean-Philippe; Bryckaert, Marijke

    2015-01-01

    Thrombocytopenia and increased platelet clearance observed in von Willebrand disease-type 2B (VWD-2B) may be explained by platelet apoptosis triggered by the constitutive binding of VWF to its receptor, glycoprotein Ib (GPIb). Apoptosis was assessed in platelets from two patients with a severe VWD-2B mutation VWF/p.V1316M and from mice transiently expressing VWF/p.V1316M. We now report that the VWD-2B mutation VWF/p.V1316M which binds spontaneously to its receptor GPIbα does not induce apoptosis. In 2 unrelated patients (P1 and P2) exhibiting different VWF plasma levels (70% and 36%, respectively, compared with normal pooled human plasma given as 100%), inner transmembrane depolarization of mitochondria, characteristic of apoptotic events was undetectable in platelets, whether washed or in whole blood. No or a moderate phosphatidyl serine (PS) exposure as measured by annexin-V staining was observed for P1 and P2, respectively. Expression of pro-apoptotic proteins Bak and Bax, and caspase-3 activity were similar to control platelets. In the VWD-2B mouse model expressing high levels of mVWF/p.V1316M (423%), similar to what is found in inflammatory pathologies, no significant difference was observed between mice expressing mVWF/WT and mVWF/p.V1316M. These results strongly argue against apoptosis as a mechanism for the thrombocytopenia of severe VWD-2B exhibiting the VWF/p.V1316M mutation. PMID:26645283

  2. A Mechanism for Localized Dynamics-driven Affinity Regulation of the Binding of von Willebrand Factor to Platelet Glycoprotein Ibα*

    PubMed Central

    Liu, Guangjian; Fang, Ying; Wu, Jianhua

    2013-01-01

    Binding of the A1 domain of von Willebrand factor (vWF) to glycoprotein Ibα (GPIbα) results in platelet adhesion, activation, and aggregation that initiates primary hemostasis. Both the elevated shear stress and the mutations associated with type 2B von Willebrand disease enhance the interaction between A1 and GPIbα. Through molecular dynamics simulations for wild-type vWF-A1 and its eight gain of function mutants (R543Q, I546V, ΔSS, etc.), we found that the gain of function mutations destabilize the N-terminal arm, increase a clock pendulum-like movement of the α2-helix, and turn a closed A1 conformation into a partially open one favoring binding to GPIbα. The residue Arg578 at the α2-helix behaves as a pivot in the destabilization of the N-terminal arm and a consequent dynamic change of the α2-helix. These results suggest a localized dynamics-driven affinity regulation mechanism for vWF-GPIbα interaction. Allosteric drugs controlling this intrinsic protein dynamics may be effective in blocking the GPIb-vWF interaction. PMID:23902764

  3. Platelet-collagen adhesion enhances platelet aggregation induced by binding of VWF to platelets

    SciTech Connect

    Laduca, F.M.; Bell, W.R.; Bettigole, R.E. State Univ. of New York, Buffalo )

    1987-11-01

    Ristocetin-induced platelet aggregation (RIPA) was evaluated in the presence of platelet-collagen adhesion. RIPA of normal donor platelet-rich plasma (PRP) demonstrated a primary wave of aggregation mediated by the binding of von Willebrand factor (VWF) to platelets and a secondary aggregation wave, due to a platelet-release reaction, initiated by VWF-platelet binding and inhibitable by acetylsalicylic acid (ASA). An enhanced RIPA was observed in PRP samples to which collagen had been previously added. These subthreshold concentrations of collagen, which by themselves were insufficient to induce aggregation, caused measurable platelet-collagen adhesion. Subthreshold collagen did not cause microplatelet aggregation, platelet release of ({sup 3}H)serotonin, or alter the dose-responsive binding of {sup 125}I-labeled VWF to platelets, which occurred with increasing ristocetin concentrations. However, ASA inhibition of the platelet release reaction prevented collagen-enhanced RIPA. These results demonstrate that platelet-collagen adhesion altered the platelet-release reaction induced by the binding of VWF to platelets causing a platelet-release reaction at a level of VWF-platelet binding not normally initiating a secondary aggregation. These findings suggest that platelet-collagen adhesion enhances platelet function mediated by VWF.

  4. How Is von Willebrand Disease Diagnosed?

    MedlinePlus

    ... of your von Willebrand factor. The test helps your doctor diagnose what type of VWD you have. Platelet function test. This test measures how well your platelets are working. You may have these tests ...

  5. Characterization of a myeloma patient with a life-threatening hemorrhagic diathesis: presence of a lambda dimer protein inhibiting shear-induced platelet aggregation by binding to the A1 domain of von Willebrand factor.

    PubMed

    Shinagawa, Atsushi; Kojima, Hiroshi; Berndt, Michael C; Kaneko, Shin; Suzukawa, Kazumi; Hasegawa, Yuichi; Shigeta, Osamu; Nagasawa, Toshiro

    2005-05-01

    We have identified a patient with IgD lambda-type multiple myeloma who was characterized by a severe bleeding tendency, especially after puncture of arterial vessels. Both the bleeding time (>25 min) and activated partial thromboplastin time (APTT) were prolonged. To clarify the underlying pathogenesis, we purified the APTT-prolonging activity from the patient's serum. The purified protein was a highly negatively-charged homodimer of the lambda light chain. The lambda dimer protein (M-protein) inhibited ristocetinand high shear-induced platelet aggregation, dependent on platelet glycoprotein Ibalpha (GPIbalpha), but not epinephrine-, collagen-, ADP-, thrombin-, or botrocetin-induced platelet aggregation. The lambda dimer protein inhibited the binding of platelets to immobilized or ristocetin-treated von Willebrand factor (VWF). Furthermore, a 39/34 kD fragment of VWF encompassing the A1 domain specifically bound to the immobilized lambda dimer protein in the presence of ristocetin, suggesting that the lambda dimer protein directly binds to the A1 domain of VWF. To help elucidate the binding site within the A1 domain, binding of ristocetin-treated VWF to the immobilized lambda dimer protein was assayed in the presence of various anti-A1 domain monoclonal antibodies. Based on these data, we conclude that the lambda dimer protein binds to the region of the A1 domain composed of helices alpha3 and alpha4 and thus interferes with VWF-GPIbalpha interaction. The existence of a protein that inhibits high shear-induced platelet aggregation in acquired von Willebrand disease (VWD) has only rarely been reported. The results suggest that the hemostatic function in arteries with high shear force is profoundly disrupted if the binding of GPIbalpha to VWF is abrogated, supporting the relevance of shear-induced VWF interaction with GPIbalpha in the initiation of the hemostatic process. PMID:15886805

  6. Platelets and galectins

    PubMed Central

    2014-01-01

    A major function of platelets is keeping the vascular system intact. Platelet activation at sites of vascular injury leads to the formation of a hemostatic plug. Activation of platelets is therefore crucial for normal hemostasis; however, uncontrolled platelet activation may also lead to the formation of occlusive thrombi that can cause ischemic events. Although they are essential for proper hemostasis, platelet function extends to physiologic processes such as tissue repair, wound remodeling and antimicrobial host defense, or pathologic conditions such as thrombosis, atherosclerosis, chronic inflammatory diseases and cancer. Platelets can be activated by soluble molecules including thrombin, thromboxane A2 (TXA2), adenosine diphosphate (ADP), serotonin or by adhesive extracellular matrix (ECM) proteins such as von Willebrand factor (vWF) and collagen. Here we describe recent advances in the activation of platelets by non-canonical platelet agonists such as galectins. By acting either in soluble or immobilized form, these glycan-binding proteins trigger all platelet activation responses through modulation of discrete signaling pathways. We also offer new hypotheses and some speculations about the role of platelet-galectin interactions not only in hemostasis and thrombosis but also in inflammation and related diseases such as atherosclerosis and cancer. PMID:25405160

  7. Analysis of the role of von Willebrand factor, platelet glycoprotein VI-, and α2β1-mediated collagen binding in thrombus formation

    PubMed Central

    Shida, Yasuaki; Rydz, Natalia; Stegner, David; Brown, Christine; Mewburn, Jeffrey; Sponagle, Kate; Danisment, Ozge; Crawford, Bredon; Vidal, Barbara; Hegadorn, Carol A.; Pruss, Cynthia M.; Nieswandt, Bernhard

    2014-01-01

    Rare missense mutations in the von Willebrand factor (VWF) A3 domain that disrupt collagen binding have been found in patients with a mild bleeding phenotype. However, the analysis of these aberrant VWF-collagen interactions has been limited. Here, we have developed mouse models of collagen-binding mutants and analyzed the function of the A3 domain using comprehensive in vitro and in vivo approaches. Five loss-of-function (p.S1731T, p.W1745C, p.S1783A, p.H1786D, A3 deletion) and 1 gain-of-function (p.L1757A) variants were generated in the mouse VWF complementary DNA. The results of these various assays were consistent, although the magnitude of the effects were different: the gain-of-function (p.L1757A) variant showed consistent enhanced collagen binding whereas the loss-of-function mutants showed variable degrees of functional deficit. We further analyzed the impact of direct platelet-collagen binding by blocking glycoprotein VI (GPVI) and integrin α2β1 in our ferric chloride murine thrombosis model. The inhibition of GPVI demonstrated a comparable functional defect in thrombosis formation to the VWF−/− mice whereas α2β1 inhibition demonstrated a milder bleeding phenotype. Furthermore, a delayed and markedly reduced thrombogenic response was still evident in VWF−/−, GPVI, and α2β1 blocked animals, suggesting that alternative primary hemostatic mechanisms can partially rescue the bleeding phenotype associated with these defects. PMID:25051961

  8. Approaches to synthetic platelet analogs.

    PubMed

    Modery-Pawlowski, Christa L; Tian, Lewis L; Pan, Victor; McCrae, Keith R; Mitragotri, Samir; Sen Gupta, Anirban

    2013-01-01

    Platelet transfusion is routinely used for treating bleeding complications in patients with hematologic or oncologic clotting disorders, chemo/radiotherapy-induced myelosuppression, trauma and surgery. Currently, these transfusions mostly use allogeneic platelet concentrates, while products like lyophilized platelets, cold-stored platelets and infusible platelet membranes are under investigation. These natural platelet-based products pose considerable risks of contamination, resulting in short shelf-life (3-5 days). Recent advances in pathogen reduction technologies have increased shelf-life to ~7 days. Furthermore, natural platelets are short in supply and also cause several biological side effects. Hence, there is significant clinical interest in platelet-mimetic synthetic analogs that can allow long storage-life and minimum side effects. Accordingly, several designs have been studied which decorate synthetic particles with motifs that promote platelet-mimetic adhesion or aggregation. Recent refinement in this design involves combining the adhesion and aggregation functionalities on a single particle platform. Further refinement is being focused on constructing particles that also mimic natural platelet's shape, size and elasticity, to influence margination and wall-interaction. The optimum design of a synthetic platelet analog would require efficient integration of platelet's physico-mechanical properties and biological functionalities. We present a comprehensive review of these approaches and provide our opinion regarding the future directions of this research. PMID:23092864

  9. Platelet activation risk index as a prognostic thrombosis indicator.

    PubMed

    Zlobina, K E; Guria, G Th

    2016-01-01

    Platelet activation in blood flow under high, overcritical shear rates is initiated by Von Willebrand factor. Despite the large amount of experimental data that have been obtained, the value of the critical shear rate, above which von Willebrand factor starts to activate platelets, is still controversial. Here, we recommend a theoretical approach to elucidate how the critical blood shear rate is dependent on von Willebrand factor size. We derived a diagram of platelet activation according to the shear rate and von Willebrand factor multimer size. We succeeded in deriving an explicit formula for the dependence of the critical shear rate on von Willebrand factor molecule size. The platelet activation risk index was introduced. This index is dependent on the flow conditions, number of monomers in von Willebrand factor, and platelet sensitivity. Probable medical applications of the platelet activation risk index as a universal prognostic index are discussed. PMID:27461235

  10. Platelet activation risk index as a prognostic thrombosis indicator

    PubMed Central

    Zlobina, K. E.; Guria, G. Th.

    2016-01-01

    Platelet activation in blood flow under high, overcritical shear rates is initiated by Von Willebrand factor. Despite the large amount of experimental data that have been obtained, the value of the critical shear rate, above which von Willebrand factor starts to activate platelets, is still controversial. Here, we recommend a theoretical approach to elucidate how the critical blood shear rate is dependent on von Willebrand factor size. We derived a diagram of platelet activation according to the shear rate and von Willebrand factor multimer size. We succeeded in deriving an explicit formula for the dependence of the critical shear rate on von Willebrand factor molecule size. The platelet activation risk index was introduced. This index is dependent on the flow conditions, number of monomers in von Willebrand factor, and platelet sensitivity. Probable medical applications of the platelet activation risk index as a universal prognostic index are discussed. PMID:27461235

  11. Calmodulin antagonists induce platelet apoptosis.

    PubMed

    Wang, Zhicheng; Li, Suping; Shi, Quanwei; Yan, Rong; Liu, Guanglei; Dai, Kesheng

    2010-04-01

    Calmodulin (CaM) antagonists induce apoptosis in various tumor models and inhibit tumor cell invasion and metastasis, thus some of which have been extensively used as anti-cancer agents. In platelets, CaM has been found to bind directly to the cytoplasmic domains of several platelet receptors. Incubation of platelets with CaM antagonists impairs the receptors-related platelet functions. However, it is still unknown whether CaM antagonists induce platelet apoptosis. Here we show that CaM antagonists N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W7), tamoxifen (TMX), and trifluoperazine (TFP) induce apoptotic events in human platelets, including depolarization of mitochondrial inner transmembrane potential, caspase-3 activation, and phosphatidylserine exposure. CaM antagonists did not incur platelet activation as detected by P-selectin surface expression and PAC-1 binding. However, ADP-, botrocetin-, and alpha-thrombin-induced platelet aggregation, platelet adhesion and spreading on von Willebrand factor surface were significantly reduced in platelets pre-treated with CaM antagonists. Furthermore, cytosolic Ca(2+) levels were obviously elevated by both W7 and TMX, and membrane-permeable Ca(2+) chelator BAPTA-AM significantly reduced apoptotic events in platelets induced by W7. Therefore, these findings indicate that CaM antagonists induce platelet apoptosis. The elevation of the cytosolic Ca(2+) levels may be involved in the regulation of CaM antagonists-induced platelet apoptosis. PMID:20172594

  12. Collection Development "Budget Decorating": Decorating Cents

    ERIC Educational Resources Information Center

    Kumaran, Maha

    2008-01-01

    Home decorating is a popular idea these days as seen in the rise of cable television channels like TLC and HGTV (Home & Garden Television) and TV shows like "Trading Spaces, Take This House and Sell It, Design on a Dime, Decorating Cents," and many others. Throughout history, humans have always expressed the desire to personalize and beautify…

  13. Platelet GpIbα Binding to von Willebrand Factor Under Fluid Shear: Contributions of the D'D3‐Domain, A1‐Domain Flanking Peptide and O‐Linked Glycans

    PubMed Central

    Madabhushi, Sri R.; Zhang, Changjie; Kelkar, Anju; Dayananda, Kannayakanahalli M.; Neelamegham, Sriram

    2014-01-01

    Background Von Willebrand Factor (VWF) A1‐domain binding to platelet receptor GpIbα is an important fluid‐shear dependent interaction that regulates both soluble VWF binding to platelets, and platelet tethering onto immobilized VWF. We evaluated the roles of different structural elements at the N‐terminus of the A1‐domain in regulating shear dependent platelet binding. Specifically, the focus was on the VWF D′D3‐domain, A1‐domain N‐terminal flanking peptide (NFP), and O‐glycans on this peptide. Methods and Results Full‐length dimeric VWF (ΔPro‐VWF), dimeric VWF lacking the D′D3 domain (ΔD′D3‐VWF), and ΔD′D3‐VWF variants lacking either the NFP (ΔD′D3NFP─‐VWF) or just O‐glycans on this peptide (ΔD′D3OG─‐VWF) were expressed. Monomeric VWF‐A1 and D′D3‐A1 were also produced. In ELISA, the apparent dissociation constant (KD) of soluble ΔPro‐VWF binding to immobilized GpIbα (KD≈100 nmol/L) was 50‐ to 100‐fold higher than other proteins lacking the D′D3 domain (KD~0.7 to 2.5 nmol/L). Additionally, in surface plasmon resonance studies, the on‐rate of D′D3‐A1 binding to immobilized GpIbα (kon=1.8±0.4×104 (mol/L)−1·s−1; KD=1.7 μmol/L) was reduced compared with the single VWF‐A1 domain (kon=5.1±0.4×104 (mol/L)−1·s−1; KD=1.2 μmol/L). Thus, VWF‐D′D3 primarily controls soluble VWF binding to GpIbα. In contrast, upon VWF immobilization, all molecular features regulated A1‐GpIbα binding. Here, in ELISA, the number of apparent A1‐domain sites available for binding GpIbα on ΔPro‐VWF was ≈50% that of the ΔD′D3‐VWF variants. In microfluidics based platelet adhesion measurements on immobilized VWF and thrombus formation assays on collagen, human platelet recruitment varied as ΔPro‐VWF<ΔD′D3‐VWF<ΔD′D3NFP─‐VWF<ΔD′D3OG─‐VWF. Conclusions Whereas VWF‐D′D3 is the major regulator of soluble VWF binding to platelet GpIbα, both the D′D3‐domain and N

  14. Basic Cake Decorating Workbook.

    ERIC Educational Resources Information Center

    Bogdany, Mel

    Included in this student workbook for basic cake decorating are the following: (1) Drawings of steps in a basic way to ice a layer cake, how to make a paper cone, various sizes of flower nails, various sizes and types of tin pastry tubes, and special rose tubes; (2) recipes for basic decorating icings (buttercream, rose paste, and royal icing);…

  15. Multiscale model of platelet translocation and collision

    NASA Astrophysics Data System (ADS)

    Wang, Weiwei; Mody, Nipa A.; King, Michael R.

    2013-07-01

    The tethering of platelets on the injured vessel surface mediated by glycoprotein Ibα (GPIbα) - Von Willebrand factor (vWF) bonds, as well as the interaction between flowing platelets and adherent platelets, are two key events that take place immediately following blood vessel injury. This early-stage platelet deposition and accumulation triggers the initiation of hemostasis, a self-defensive mechanism to prevent the body from excessive blood loss. To understand and predict this complex process, one must integrate experimentally determined information on the mechanics and biochemical kinetics of participating receptors over very small time frames (1-1000 μs) and length scales (10-100 nm), to collective phenomena occurring over seconds and tens of microns. In the present study, a unique three dimensional multiscale computational model, Platelet Adhesive Dynamics (PAD), was applied to elucidate the unique physics of (i) a non-spherical, disk-shaped platelet interacting and tethering onto the damaged vessel wall followed by (ii) collisional interactions between a flowing platelet with a downstream adherent platelet. By analyzing numerous simulations under different physiological conditions, we conclude that the platelet's unique spheroid-shape provides heterogeneous, orientation-dependent translocation (rolling) behavior which enhances cell-wall interactions. We also conclude that platelet-platelet near field interactions are critical for cell-cell communication during the initiation of microthrombi. The PAD model described here helps to identify the physical factors that control the initial stages of platelet capture during this process.

  16. New Horizons in Platelets Flow Cytometry

    PubMed Central

    Saboor, Muhammad; Moinuddin, Moinuddin; Ilyas, Samina

    2013-01-01

    Platelet flow cytometry is an emerging tool in diagnostic and therapeutic hematology. It is eminently suited to study the expression of platelet surface receptors both qualitatively as well as quantitatively. It can serve as a useful marker for the documentation of in vivo platelet activation, and thus, fore-warn the risk of thromboembolism in patients with diabetes mellitus, coronary syndromes, peripheral vascular diseases, and pre-eclampsia. This technique can also be extended to study and compare the effect of various antiplatelet drugs on the level of activation of platelets and to establish any dose-effect relationship of these drugs. Topographical localization of platelet granules and study of platelet-platelet and platelet-leukocyte interaction is also possible by this procedure. All these parameters serve as pointers towards the presence of activated platelets in the circulation with its thromboembolic consequences. This is a simple reliable and cost effective technique which has a wide application in the diagnosis of various inherited and acquired platelet disorders. Study of platelet cluster of differentiation (CD) markers in various inherited disorders i.e. Bernard Soulier’s disease, von Willebrand disease, Glanzman’s disease, and Grey platelet syndrome may help categories the molecular lesions in these oft under-studied disorders. PMID:23983579

  17. Platelet transport in microchannels

    NASA Astrophysics Data System (ADS)

    Reyssat, Mathilde; Le Goff, Anne; Blin, Antoine; Pujos, Justine; Magniez, Aurélie; Baruch, Dominique

    2013-11-01

    Blood platelets are small enucleated cells responsible for the arrest of bleeding. These cells have the ability to tether and translocate on injured vascular endothelium, thanks to a specific interaction between a receptor of their membrane and a protein expressed by the cells composing the inner wall of the vessel, the von Willebrand factor (VWF). Others cells have such abilities of rolling. Leucocytes, for example, translocate on surface due to a specific interaction between selectin molecules and their respective glycoprotein ligands. These kinds of cells present two modes of transport: they can either be advected by the flux, or translocate on surfaces due to specific ligand-receptor interactions. Our work consists first in studying experimentally the transport of platelets along a microchannel and then in modeling this particular cell transport. Due to these two modes of transport along a channel, platelets adhering to the surface are not equally distributed along the channel axis. We describe the evolution of the density of platelets with time and distance.

  18. Ceramics with decorative aspect

    NASA Astrophysics Data System (ADS)

    Voica, Cezara

    2009-08-01

    The last decades brought the development of bone china techniques used for producing the decorative articles. These products can be glazed with a transparent and thin glaze layer, even with more special (decorative) ones which gives new aesthetic aspect. The present article presents the results obtained after the studies performed for matte glazes for decorative bone china. As microcrystalization agent were used zinc oxide; the content of this oxide bring some changes of the basic glaze thus the chemical composition must be adjusted as the fluxes would present the desired properties after the heating process.

  19. Signaling during platelet adhesion and activation

    PubMed Central

    Li, Zhenyu; Delaney, M. Keegan; O’Brien, Kelly A.; Du, Xiaoping

    2011-01-01

    Upon vascular injury, platelets are activated by adhesion to adhesive proteins like von Willebrand factor and collagen, or by soluble platelet agonists like ADP, thrombin, and thromboxane A2. These adhesive proteins and soluble agonists induce signal transduction via their respective receptors. The various receptor-specific platelet activation signaling pathways converge into common signaling events, which stimulate platelet shape change, granule secretion, and ultimately induce the “inside-out” signaling process leading to activation of the ligand binding function of integrin αIIbβ3. Ligand binding to integrin αIIbβ3 mediates platelet adhesion and aggregation and triggers “outside-in” signaling, resulting in platelet spreading, additional granule secretion, stabilization of platelet adhesion and aggregation, and clot retraction. It has become increasingly evident that agonist-induced platelet activation signals also crosstalk with integrin “outside-in” signals to regulate platelet responses. Platelet activation involves a series of rapid positive feedback loops that greatly amplify initial activation signals, and enable robust platelet recruitment and thrombus stabilization. Recent studies have provided novel insight into the molecular mechanisms of these processes. PMID:21071698

  20. von Willebrand Disease

    PubMed Central

    Goodeve, Anne C.

    2013-01-01

    von Willebrand disease (VWD) is a common inherited bleeding disorder characterized by excessive mucocutaneous bleeding. Characteristic bleeding symptoms include epistaxis, easy bruising, oral cavity bleeding, menorrhagia, bleeding after dental extraction, surgery and/or childbirth and in severe cases, bleeding into joints and soft tissues. There are three subtypes: types 1 and 3 represent quantitative variants and type 2 is a group of four qualitative variants: 1) type 2A - characterized by defective von Willebrand factor (VWF) -dependent platelet adhesion because of decreased high molecular weight (HMW) VWF multimers, 2) type 2B - caused by pathologically increased VWF-platelet interactions, 3) type 2M - caused by decreased VWF-platelet interactions not based on the loss of HMW multimers and 4) type 2N - characterized by abnormal binding of VWF to FVIII. The diagnosis of VWD requires specialized assays of von Willebrand factor (VWF) and/or molecular genetic testing of VWF. Severe bleeding episodes can be prevented or controlled with intravenous infusions of virally-inactivated plasma-derived clotting factor concentrates containing both VWF and FVIII. Depending on the VWD type, mild bleeding episodes usually respond to intravenous or subcutaneous treatment with desmopressin, a vasopressin analog. Other treatments that can reduce symptoms include fibrinolytic inhibitors and hormones for menorrhagia. PMID:21289515

  1. PLATELET FORMATION

    PubMed Central

    Thon, Jonathan N.; Italiano, Joseph E.

    2010-01-01

    Thrombocytopenia is the underlying cause of a number of major clinical conditions and genetic disorders worldwide. While therapeutic agents that bind and stimulate the thrombopoietin receptor are currently available, the development of drugs that directly stimulate megakaryocytes to generate platelets has lagged behind. To improve the management of thrombocytopenia, we will need to define the cell biological pathways that drive the production of platelets from megakaryocytes. This review integrates the latest research of platelet biogenesis and focuses on the molecular pathways that power and regulate proplatelet production. PMID:20620432

  2. Platelet Count

    MedlinePlus

    ... rash Small purplish spots on the skin called purpura, caused by bleeding under the skin Testing may ... Idiopathic thrombocytopenia (ITP), also known as immune thrombocytopenic purpura, is the result of antibody production against platelets. ...

  3. Platelet count

    MedlinePlus

    ... reactions Cancer Certain medicines Bone marrow disease called polycythemia vera Bone marrow making too many platelets without a ... leukemia (CML) Hemolytic anemia Idiopathic thrombocytopenic purpura (ITP) Polycythemia vera Thrombocytopenia Patient Instructions Deep vein thrombosis - discharge Update ...

  4. Platelet aggregation test

    MedlinePlus

    The platelet aggregation blood test checks how well platelets , a part of blood, clump together and cause blood to clot. ... Decreased platelet aggregation may be due to: Autoimmune ... Fibrin degradation products Inherited platelet function defects ...

  5. Von Willebrand factor and von Willebrand disease.

    PubMed

    Budde, U; Schneppenheim, R

    2001-12-01

    von Willebrand disease (vWD) is caused by quantitative and/or qualitative defects of the von Willebrand factor (vWF), a multimeric high molecular weight glycoprotein. Typically, it affects the primary hemostatic system, which results in a mucocutaneous bleeding tendency simulating a platelet function defect. The vWF promotes its function in two ways: (i) by initiating platelet adhesion to the injured vessel wall under conditions of high shear forces, and (ii) by its carrier function for factor VIII in plasma. Accumulating knowledge of the different clinical phenotypes and the pathophysiological basis of the disease translated into a classification that differentiated between quantitative and qualitative defects by means of quantitative and functional parameters, and by analyzing the electrophoretic pattern of vWF multimers. The advent of molecular techniques provided the opportunity for conducting genotype-phenotype studies which have recently helped, not only to elucidate or confirm important functions of vWF and its steps in post-translational processing, but also many disease causing defects. Acquired von Willebrand syndrome (avWS) has gained more attention during the recent years. An international registry was published and recommendation by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis in 2000. It concluded that avWS, although not a frequent disease, is nevertheless probably underdiagnosed. This should be addressed in future prospective studies. The aim of treatment is the correction of the impaired hemostatic system of the patient, ideally including the defects of both primary and secondary hemostasis. Desmopressin is the treatment of choice in about 70% of patients, mostly with type 1, while the others merit treatment with concentrates containing vWF. PMID:11844133

  6. 12 CFR 264b.7 - Decorations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... wear a decoration tendered or awarded by a foreign government in recognition of active field service in... documentation. The recipient may retain the decoration pending action on the request. (b) Decorations...

  7. 7. WEST PORTAL. NOTE DECORATIVE ELEMENTS, INCLUDING DECORATIVE CAPS COVERING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. WEST PORTAL. NOTE DECORATIVE ELEMENTS, INCLUDING DECORATIVE CAPS COVERING COMPRESSION BLOCKS. NAME OF THE BRIDGE COMPANY WITH HERALDIC CARTOUCHE BEARING NAMES OF THREE COUNTY COMMISSIONERS BELOW, AND OPEN SCROLL WORK IN WROUGHT IRON. - Peevy Road Bridge, Peevy Road spanning Perkiomen Creek in Upper Hanover Township, East Greenville, Montgomery County, PA

  8. Preservation of hemostatic and structural properties of rehydrated lyophilized platelets: potential for long-term storage of dried platelets for transfusion.

    PubMed

    Read, M S; Reddick, R L; Bode, A P; Bellinger, D A; Nichols, T C; Taylor, K; Smith, S V; McMahon, D K; Griggs, T R; Brinkhous, K M

    1995-01-17

    Currently, therapeutic platelet concentrates can be stored for only 5 days. We have developed a procedure that permits long-term storage of fixed and lyophilized platelets that retain hemostatic properties after rehydration. These rehydrated lyophilized platelets (RL platelets) restore hemostasis in thrombocytopenic rats and become incorporated in the hemostatic plug of bleeding time wounds of normal dogs as well as von Willebrand disease dogs with partially replenished plasma von Willebrand factor. Ultrastructurally, these platelets are well preserved and are comparable to control normal washed platelets. Flow cytometry analysis shows that RL platelets react with antibodies to the major surface receptors, glycoprotein (GP)Ib and GPIIb/IIIa. These receptors are involved in platelet agglutination, aggregation, and adhesion. In vitro functional tests document the ability of RL platelets to adhere to denuded subendothelium and to spread on a foreign surface. Circulating RL platelets participated in carotid arterial thrombus formation induced in normal canine subjects. The participation of RL platelets in these vital hemostatic properties suggests that with further development they could become a stable platelet product for transfusion. PMID:7831298

  9. Platelet aggregation test

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003669.htm Platelet aggregation test To use the sharing features on this page, please enable JavaScript. The platelet aggregation blood test checks how well platelets , a ...

  10. 22 CFR 3.7 - Decorations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Decorations. 3.7 Section 3.7 Foreign Relations DEPARTMENT OF STATE GENERAL GIFTS AND DECORATIONS FROM FOREIGN GOVERNMENTS § 3.7 Decorations. (a) Decorations tendered in recognition of active field service in time of combat operations or awarded for...

  11. Analysis of aggregation of platelets in thrombosis

    NASA Astrophysics Data System (ADS)

    Ahuja, Suresh

    Platelets are key players in thrombus formation by first rolling over collagen bound von Willebrand factor followed by formation of a stable interaction with collagen. The first adhered platelets bind additional platelets until the whole injury is sealed off by a platelet aggregate. The coagulation system stabilizes the formed platelet plug by creating a tight fibrin network, and then wound contraction takes place because of morphological changes in platelets. Coagulation takes place by platelet activation and aggregation mainly through fibrinogen polymerization into fibrin fibers. The process includes multiple factors, such as thrombin, plasmin, and local shear-rate which regulate and control the process. Coagulation can be divided into two pathways: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is initiated by the exposure of a negatively charged. It is able to activate factor XII, using a complex reaction that includes prekallikrein and high-molecular-weight kininogen as cofactors.. Thrombin is the final enzyme that is needed to convert fibrinogen into fibrin. The extrinsic pathway starts with the exposure of tissue factor to the circulating blood, which is the major initiator of coagulation. There are several feedback loops that reinforce the coagulation cascade, resulting in large amounts of thrombin. It is dependent on the presence of pro-coagulant surfaces of cells expressing negatively charged phospholipids--which include phosphatidylserine (PS)--on their outer membrane. PS-bearing surfaces are able to increase the efficiency of the reactions by concentrating and co-localizing coagulation factors.. Aggregation of platelets are analyzed and compared to adhesion of platelet to erythrocyte and to endothelial cells. This abstract is replacing MAR16-2015-020003.

  12. Platelets deficient in glycoprotein I have normal Fc receptor expression.

    PubMed

    Pfueller, S L; de Rosbo, N K; Bilston, R A

    1984-04-01

    Platelet glycoprotein I (GPI) is known to be required for the interaction of platelets with ristocetin and factor VIII:von Willebrand factor (VIII:vWf). However, its role as Fc receptor is not clear. Some studies have shown that enzymatic removal of GPI destroys the ability of platelets to react with VIII:vWf but not their ability to bind Ig G (IgG). Others have shown that IgG immune complexes which block the Fc receptor also inhibit VIII:vWf interaction with platelets. This subject has been re-examined by testing the ability of platelets with reduced amounts of GPI to aggregate and undergo the release reaction in response to stimuli which act at the platelet Fc receptor. Platelets from two patients with Bernard-Soulier syndrome, congenitally deficient in GPI, both aggregated and released 14C-serotonin normally when exposed to latex particles coated with IgG. Levels of GPI were decreased experimentally in normal platelets by treating them with chymotrypsin. Platelets treated in this manner did not aggregate or release [14C]serotonin in response to ristocetin-VIII:vWf. They did, however, both aggregate and release when incubated with heat-aggregated IgG, antigen-antibody complexes or latex particles coated with IgG. Thus the presence of GPI is not a prerequisite for platelet stimulation via the Fc receptor. PMID:6231945

  13. Fire-Retardant, Decorative Inks

    NASA Technical Reports Server (NTRS)

    Kourtides, D.; Nir, Z.; Mikroyannidis, J.

    1987-01-01

    Effectiveness of fire-retardant additives evaluated. Fire retardance of decorative acrylic printing inks for aircraft interiors enhanced by certain commercial and experimental fire-retardant additives, according to study.

  14. Tunable superconductivity in decorated graphene

    NASA Astrophysics Data System (ADS)

    Han, Zheng; Allain, Adrien; Marty, Laetitia; Bendiab, Nedjma; Toulemonde, Pierre; Strobel, Pierre; Coraux, Johann; Bouchiat, Vincent

    2013-03-01

    Graphene offers an exposed bidimensional gas of high mobility charge carriers with gate tunable density. Its chemical inertness offers an outstanding platform to explore exotic 2D superconductivity. Superconductivity can be induced in graphene by means of proximity effect (by depositing a set of superconducting metal clusters such as lead or tin nanoparticles). The influence of decoration material, density or particles and disorder of graphene will be discussed. In the case of disordered graphene, Tin decoration leads to a gate-tunable superconducting-to-insulator quantum phase transition. Superconductivity in graphene is also expected to occur under strong charge doping (induced either by gating or under chemical decoration, in analogy with graphite intercalated compounds). I will also show preliminary results showing the influence of Calcium intercalation of few layer graphene and progress toward the demonstration of intrinsic superconductivity in such systems. Work supported by EU GRANT FP7-NMP GRENADA.

  15. Clinical application of radiolabelled platelets

    SciTech Connect

    Kessler, C. )

    1990-01-01

    This book presents papers on the clinical applications of radiolabelled platelets. The papers are grouped into six sections on platelet labelling techniques, radiolabelled platelets in cardiology, monitoring of antiplatelet therapy, platelet scintigraphy in stroke patients, platelet scintigraphy in angiology, and platelet scintigraphy in hematology and other clinical applications, including renal transplant rejection.

  16. Acquired platelet function defect

    MedlinePlus

    ... dark black, or tarry bowel movements ; or vomiting blood or material that looks like coffee grounds Nosebleeds ... Tests that may done include: Bleeding time Platelet aggregation test Platelet count PT and PTT

  17. Decreased platelet function in aortic valve stenosis: high shear platelet activation then inactivation.

    PubMed Central

    O'Brien, J. R.; Etherington, M. D.; Brant, J.; Watkins, J.

    1995-01-01

    OBJECTIVE--To elucidate the mechanism of the bleeding tendency observed in patients with aortic valve stenosis. DESIGN--A prospective study of high and low shear platelet function tests in vitro in normal controls compared with that in patients with severe aortic valve stenosis with a mean (SD) systolic gradient by Doppler of 75 (18) mm Hg before and at least 4 months after aortic valve replacement. SETTING--District general hospital. RESULTS--The patients showed reduced retention in the high shear platelet function tests. (a) Platelet retention in the filter test was 53.6 (12.6)% in patients with aortic valve stenosis and 84.8 (9.6)% in the controls (P < 0.001). (b) Retention in the glass bead column test was 49.8 (19.2) in the patients and 87.4 (8.7) in the controls (P < 0.001). (c) The standard bleeding time was longer in the patients (P < 0.06). Results of the high shear tests (a, b, and c) after aortic valve replacement were within the normal range. The platelet count was low but within the normal range before surgery and increased postoperatively (P < 0.01). There were no differences in the results of standard clotting tests, plasma and intraplatelet von Willebrand's factor, or in 15 platelet aggregation tests using five agonists between patients with aortic valve stenosis and controls. CONCLUSIONS--The high shear haemodynamics of aortic valve stenosis modify platelet function in vivo predisposing to a bleeding tendency. This abnormality of platelet function is detectable only in vitro using high shear tests. The abnormal function is reversed by aortic valve replacement. High shear forces in vitro activate and then inactivate platelets. By the same mechanisms aortic valve stenosis seems to lead to high shear damage in vivo, resulting in a clinically important bleeding tendency in some patients. PMID:8541170

  18. Platelets and Infections – Complex Interactions with Bacteria

    PubMed Central

    Hamzeh-Cognasse, Hind; Damien, Pauline; Chabert, Adrien; Pozzetto, Bruno; Cognasse, Fabrice; Garraud, Olivier

    2015-01-01

    Platelets can be considered sentinels of vascular system due to their high number in the circulation and to the range of functional immunoreceptors they express. Platelets express a wide range of potential bacterial receptors, including complement receptors, FcγRII, Toll-like receptors but also integrins conventionally described in the hemostatic response, such as GPIIb–IIIa or GPIb. Bacteria bind these receptors either directly, or indirectly via fibrinogen, fibronectin, the first complement C1q, the von Willebrand Factor, etc. The fate of platelet-bound bacteria is questioned. Several studies reported the ability of activated platelets to internalize bacteria such as Staphylococcus aureus or Porphyromonas gingivalis, though there is no clue on what happens thereafter. Are they sheltered from the immune system in the cytoplasm of platelets or are they lysed? Indeed, while the presence of phagolysosome has not been demonstrated in platelets, they contain antimicrobial peptides that were shown to be efficient on S. aureus. Besides, the fact that bacteria can bind to platelets via receptors involved in hemostasis suggests that they may induce aggregation; this has indeed been described for Streptococcus sanguinis, S. epidermidis, or C. pneumoniae. On the other hand, platelets are able to display an inflammatory response to an infectious triggering. We, and others, have shown that platelet release soluble immunomodulatory factors upon stimulation by bacterial components. Moreover, interactions between bacteria and platelets are not limited to only these two partners. Indeed, platelets are also essential for the formation of neutrophil extracellular traps by neutrophils, resulting in bacterial clearance by trapping bacteria and concentrating antibacterial factors but in enhancing thrombosis. In conclusion, the platelet–bacteria interplay is a complex game; its fine analysis is complicated by the fact that the inflammatory component adds to the aggregation response

  19. The evolutionary ecology of decorating behaviour

    PubMed Central

    Ruxton, Graeme D.; Stevens, Martin

    2015-01-01

    Many animals decorate themselves through the accumulation of environmental material on their exterior. Decoration has been studied across a range of different taxa, but there are substantial limits to current understanding. Decoration in non-humans appears to function predominantly in defence against predators and parasites, although an adaptive function is often assumed rather than comprehensively demonstrated. It seems predominantly an aquatic phenomenon—presumably because buoyancy helps reduce energetic costs associated with carrying the decorative material. In terrestrial examples, decorating is relatively common in the larval stages of insects. Insects are small and thus able to generate the power to carry a greater mass of material relative to their own body weight. In adult forms, the need to be lightweight for flight probably rules out decoration. We emphasize that both benefits and costs to decoration are rarely quantified, and that costs should include those associated with collecting as well as carrying the material. PMID:26041868

  20. Rhesus monkey platelets

    SciTech Connect

    Harbury, C.B.

    1986-03-01

    The purpose of this abstract is to describe the adenine nucleotide metabolism of Rhesus monkey platelets. Nucleotides are labelled with /sup 14/C-adenine and extracted with EDTA-ethanol (EE) and perchlorate (P). Total platelet ATP and ADP (TATP, TADP) is measured in the Holmsen Luciferase assay, and expressed in nanomoles/10/sup 8/ platelets. TR=TATP/TADP. Human platelets release 70% of their TADP, with a ratio of released ATP/ADP of 0.7. Rhesus platelets release 82% of their TADP, with a ratio of released ATP/ADP of 0.33. Thus, monkey platelets contain more ADP than human platelets. Thin layer chromatography of EE gives a metabolic ratio of 11 in human platelets and 10.5 in monkey platelets. Perchlorate extracts metabolic and actin bound ADP. The human and monkey platelets ratios were 5, indicating they contain the same proportion of actin. Thus, the extra ADP contained in monkey platelets is located in the secretory granules.

  1. Platelets in Lung Biology

    PubMed Central

    Weyrich, Andrew S.; Zimmerman, Guy A.

    2013-01-01

    Platelets and the lungs have an intimate relationship. Platelets are anucleate mammalian blood cells that continuously circulate through pulmonary vessels and that have major effector activities in hemostasis and inflammation. The lungs are reservoirs for megakaryocytes, the requisite precursor cell in thrombopoiesis, which is the intricate process by which platelets are generated. Platelets contribute to basal barrier integrity of the alveolar capillaries, which selectively restricts the transfer of water, proteins, and red blood cells out of the vessels. Platelets also contribute to pulmonary vascular repair. Although platelets bolster hemostatic and inflammatory defense of the healthy lung, experimental evidence and clinical evidence indicate that these blood cells are effectors of injury in a variety of pulmonary disorders and syndromes. Newly discovered biological capacities of platelets are being explored in the context of lung defense, disease, and remodeling. PMID:23043249

  2. Platelet Interaction with Bacteria

    PubMed Central

    Clawson, C. C.

    1973-01-01

    The interaction of several common strains of bacteria with rabbit or human platelets in vitro has been examined sequentially with scanning and transmission electron microscopy. Bacteria were added to platelets in their native plasma or to washed platelets in a balanced salt solution at ratios of about 1:1 or at low bacteria to platelet ratios (down to 1:100). The platelet-bacterial interaction (PBI) was studied with recording nephelometry. Matched samples were fixed for microscopy at various points in the aggregation response. The results support these conclusions: a) Bacteria stimulate platelet aggregation by direct contact and adhesion with the platelet surface. b) Adhesion between the two cell types requires divalent cations, occurs through fusion of normal cell-surface coats and appears identical in the presence or absence of extracellular plasma protein. c) The morphologic transformation of platelets during PBI is identical to that produced by collagen. d) During PBI the bacteria are incorporated into the forming platelet aggregates and reside predominantly intercellularly. e) Phagocytosis of bacteria by a single platelet is very rare. f) Bacteria which have resided within platelet aggregates for one hour are unaltered morphologically. g) PBI occurs even at very low bacterial numbers and produces platelet-bacterial aggregates in small numbers without stimulating generalized platelet aggregation. Methods for concentration of thrombocytopenic plasma and washing human platelets are presented. ImagesFig 6Fig 7Fig 8Fig 9Fig 10Fig 11Fig 1Fig 2Fig 12Fig 13Fig 3Fig 14Fig 4Fig 5 PMID:4632008

  3. Platelet function and ageing.

    PubMed

    Jones, Chris I

    2016-08-01

    There are clear age-related changes in platelet count and function, driven by changes in hematopoietic tissue, the composition of the blood and vascular health. Platelet count remains relatively stable during middle age (25-60 years old) but falls in older people. The effect of age on platelet function is slightly less clear. The longstanding view is that platelet reactivity increases with age in an almost linear fashion. There are, however, serious limitations to the data supporting this dogma. We can conclude that platelet function increases during middle age, but little evidence exists on the changes in platelet responsiveness in old age (>75 years old). This change in platelet function is driven by differential mRNA and microRNA expression, an increase in oxidative stress and changes in platelet receptors. These age-related changes in platelets are particularly pertinent given that thrombotic disease and use of anti-platelet drugs is much more prevalent in the elderly population, yet the majority of platelet research is carried out in young to middle-aged (20-50 years old) human volunteers and young mice (2-6 months old). We know relatively little about exactly how platelets from people over 75 years old differ from those of middle-aged subjects, and we know even less about the mechanisms that drive these changes. Addressing these gaps in our knowledge will provide substantial understanding in how cell signalling changes during ageing and will enable the development of more precise anti-platelet therapies. PMID:27068925

  4. Surface decorated platinum carbonyl clusters

    NASA Astrophysics Data System (ADS)

    Ciabatti, Iacopo; Femoni, Cristina; Iapalucci, Maria Carmela; Longoni, Giuliano; Zacchini, Stefano; Zarra, Salvatore

    2012-06-01

    Four molecular Pt-carbonyl clusters decorated by Cd-Br fragments, i.e., [Pt13(CO)12{Cd5(μ-Br)5Br2(dmf)3}2]2- (1), [Pt19(CO)17{Cd5(μ-Br)5Br3(Me2CO)2}{Cd5(μ-Br)5Br(Me2CO)4}]2- (2), [H2Pt26(CO)20(CdBr)12]8- (3) and [H4Pt26(CO)20(CdBr)12(PtBr)x]6- (4) (x = 0-2), have been obtained from the reactions between [Pt3n(CO)6n]2- (n = 2-6) and CdBr2.H2O in dmf at 120 °C. The structures of these molecular clusters with diameters of 1.5-2 nm have been determined by X-ray crystallography. Both 1 and 2 are composed of icosahedral or bis-icosahedral Pt-CO cores decorated on the surface by Cd-Br motifs, whereas 3 and 4 display a cubic close packed Pt26Cd12 metal frame decorated by CO and Br ligands. An oversimplified and unifying approach to interpret the electron count of these surface decorated platinum carbonyl clusters is suggested, and extended to other low-valent organometallic clusters and Au-thiolate nanoclusters.Four molecular Pt-carbonyl clusters decorated by Cd-Br fragments, i.e., [Pt13(CO)12{Cd5(μ-Br)5Br2(dmf)3}2]2- (1), [Pt19(CO)17{Cd5(μ-Br)5Br3(Me2CO)2}{Cd5(μ-Br)5Br(Me2CO)4}]2- (2), [H2Pt26(CO)20(CdBr)12]8- (3) and [H4Pt26(CO)20(CdBr)12(PtBr)x]6- (4) (x = 0-2), have been obtained from the reactions between [Pt3n(CO)6n]2- (n = 2-6) and CdBr2.H2O in dmf at 120 °C. The structures of these molecular clusters with diameters of 1.5-2 nm have been determined by X-ray crystallography. Both 1 and 2 are composed of icosahedral or bis-icosahedral Pt-CO cores decorated on the surface by Cd-Br motifs, whereas 3 and 4 display a cubic close packed Pt26Cd12 metal frame decorated by CO and Br ligands. An oversimplified and unifying approach to interpret the electron count of these surface decorated platinum carbonyl clusters is suggested, and extended to other low-valent organometallic clusters and Au-thiolate nanoclusters. CCDC 867747 and 867748. For crystallographic data in CIF or other electronic format see DOI: 10.1039/c2nr30400g

  5. Effects of microgravity and hypergravity on platelet functions.

    PubMed

    Dai, Kesheng; Wang, Yuedan; Yan, Rong; Shi, Quanwei; Wang, Zhicheng; Yuan, Yanhong; Cheng, Hong; Li, Suping; Fan, Yubo; Zhuang, Fengyuan

    2009-05-01

    Many serious thrombotic and haemorrhagic diseases or fatalities have been documented in human being exposed to microgravity or hypergravity environments, such as crewmen in space, roller coaster riders, and aircrew subjected to high-G training. Some possible related organs have been examined to explore the mechanisms underlying these gravity change-related diseases. However, the role of platelets which are the primary players in both thrombosis and haemostasis is unknown. Here we show that platelet aggregation induced by ristocetin or collagen and platelet adhesion to von Willebrand factor (VWF) were significantly decreased after platelets were exposed to simulated microgravity. Conversely, these platelet functions were increased after platelets were exposed to hypergravity. The tail bleeding time in vivo was significantly shortened in mice exposed to high-G force, whereas, was prolonged in hindlimb unloaded mice. Furthermore, three of 23 mice died after 15 minutes of -8 Gx stress. Platelet thrombi disseminated in the heart ventricle and blood vessels in the brain, lung, and heart from the dead mice. Finally, glycoprotein (GP) Ibalpha surface expression and its association with the cytoskeleton were significantly decreased in platelets exposed to simulated microgravity, and obviously increased in hypergravity-exposed platelets. These data indicate that the platelet functions are inhibited in microgravity environments, and activated under high-G conditions, suggesting a novel mechanism for gravity change-related haemorrhagic and thrombotic diseases. This mechanism has important implications for preventing and treating gravity change-related diseases, and also suggests that special attentions should be paid to human actions under different gravity conditions. PMID:19404544

  6. Red Blood Cell Hematocrit Influences Platelet Adhesion Rate in a Microchannel

    NASA Astrophysics Data System (ADS)

    Spann, Andrew; Campbell, James; Fitzgibbon, Sean; Rodriguez, Armando; Shaqfeh, Eric

    2014-11-01

    The creation of a blood clot to stop bleeding involves platelets forming a plug at the site of injury. Red blood cells indirectly play a role in ensuring that the distribution of platelets across the height of the channel is not uniform - the contrast in deformability and size between platelets and red blood cells allows the platelets to preferentially marginate close to the walls. We perform 3D boundary integral simulations of a suspension of platelets and red blood cells in a periodic channel with a model that allows for platelet binding at the walls. The relative rate of platelet activity with varying hematocrit (volume fraction of red blood cells) is compared to experiments in which red blood cells and platelets flow through a channel coated with von Willebrand factor. In the simulations as well as the experiments, a decrease in hematocrit of red blood cells is found to reduce the rate at which platelets adhere to the channel wall in a manner that is both qualitatively and quantitatively similar. We conclude with a discussion of the tumbling and wobbling motions of platelets in 3D leading up to the time at which the platelets bind to the wall. Funded by Stanford Army High Performance Computing Research Center, experiments by US Army Institute of Surgical Research.

  7. Sources of variability in platelet accumulation on type 1 fibrillar collagen in microfluidic flow assays.

    PubMed

    Neeves, Keith B; Onasoga, Abimbola A; Hansen, Ryan R; Lilly, Jessica J; Venckunaite, Diana; Sumner, Meghan B; Irish, Andrew T; Brodsky, Gary; Manco-Johnson, Marilyn J; Di Paola, Jorge A

    2013-01-01

    Microfluidic flow assays (MFA) that measure shear dependent platelet function have potential clinical applications in the diagnosis and treatment of bleeding and thrombotic disorders. As a step towards clinical application, the objective of this study was to measure how phenotypic and genetic factors, as well as experimental conditions, affect the variability of platelet accumulation on type 1 collagen within a MFA. Whole blood was perfused over type 1 fibrillar collagen at wall shear rates of 150, 300, 750 and 1500 s⁻¹ through four independent channels with a height of 50 µm and a width of 500 µm. The accumulation of platelets was characterized by the lag time to 1% platelet surface coverage (Lag(T)), the rate of platelet accumulation (V(PLT)), and platelet surface coverage (SC). A cohort of normal donors was tested and the results were correlated to plasma von Willebrand factor (VWF) levels, platelet count, hematocrit, sex, and collagen receptors genotypes. VWF levels were the strongest determinant of platelet accumulation. VWF levels were positively correlated to V(PLT) and SC at all wall shear rates. A longer Lag(T) for platelet accumulation at arterial shear rates compared to venous shear rates was attributed to the time required for plasma proteins to adsorb to collagen. There was no association between platelet accumulation and hematocrit or platelet count. Individuals with the AG genotype of the GP6 gene had lower platelet accumulation than individuals with the AA genotype at 150 s⁻¹ and 300 s⁻¹. Recalcified blood collected into sodium citrate and corn trypsin inhibitor (CTI) resulted in diminished platelet accumulation compared to CTI alone, suggesting that citrate irreversibly diminishes platelet function. This study the largest association study of MFA in healthy donors (n = 104) and will likely set up the basis for the determination of the normal range of platelet responses in this type of assay. PMID:23355889

  8. Platelets enhance neutrophil transendothelial migration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Platelets are increasingly recognized as important mediators of inflammation in addition to thrombosis. While platelets have been shown to promote neutrophil (PMN) adhesion to endothelium in various inflammatory models, it is unclear whether platelets enhance neutrophil transmigration across inflame...

  9. Platelet Donation (Apheresis)

    MedlinePlus

    ... may be ideal for a simultaneous platelet and plasma donation. Anyone in need can receive your plasma, it is universal. Only 4% of the U.S. ... can donate up to 24 times per year. Plasma can be collected simultaneously with a platelet donation. ...

  10. Inherited platelet disorders.

    PubMed

    Sandrock-Lang, Kirstin; Wentzell, Rüdiger; Santoso, Sentot; Zieger, Barbara

    2016-08-01

    Inherited platelet disorders may be the cause of bleeding symptoms of varying severity as platelets fail to fulfil their haemostatic role after vessel injury. Platelet disorders may be difficult to diagnose (and are likely to be misdiagnosed) and raise problems in therapy and management. This review explores the clinical and molecular genetic phenotype of several inherited disorders. Inherited platelet disorders can be classified according to their platelet defects: receptor defects (adhesion or aggregation), secretion disorder, and cytoskeleton defects. The best characterized platelet receptor defects are Glanzmann thrombasthenia (integrin αIIbβ3 defect) and Bernard-Soulier syndrome (defect of GPIb/IX/V). Detailed case reports of patients suffering from Glanzmann thrombasthenia (GT) or Bernard-Soulier syndrome (BSS) showing the bleeding diathesis as well as investigation of platelet aggregation/agglutination and platelet receptor expression will complement this review. In addition, Hermansky-Pudlak syndrome (HPS) as an important defect of δ-granule secretion is extensively described together with a case report of a patient suffering from HPS type 1. PMID:25707719

  11. Platelet Function Tests

    MedlinePlus

    ... of the clotting process in the body ( in vivo ). A person with normal platelet function test results may still experience excessive bleeding or inappropriate clotting during and after a surgery. Most samples for platelet function testing are only stable for a very short period ...

  12. The Role of Decorative Pictures in Learning

    ERIC Educational Resources Information Center

    Lenzner, Alwine; Schnotz, Wolfgang; Müller, Andreas

    2013-01-01

    Three experiments with students from 7th and 8th grade were performed to investigate the effects of decorative pictures in learning as compared to instructional pictures. Pictures were considered as instructional, when they were primarily informative, and as decorative, when they were primarily aesthetically appealing. The experiments…

  13. Painter and Decorator. Occupational Analyses Series.

    ERIC Educational Resources Information Center

    Chapman, Mike; MacCallum, Marilyn; Maddocks, Christopher

    This analysis covers tasks performed by a painter and decorator, an occupational title some provinces and territories of Canada have also identified as painter and painter and decorator--commercial and residential. A guide to analysis discusses development, structure, and validation method; scope of the occupation; trends; and safety. To…

  14. Platelet dysfunction-eosinophilia syndrome in parasitized Venezuelan children.

    PubMed

    Ruiz-Sáez, Arlette; Sifontes, Luz Núñez; Feijoo, Rosa; Certad, Gabriela; Arenas-Pinto, Alejandro; Pocaterra, Leonor; Ferrara, Guiseppe; Giménez, Rita; Torres, Obdulita; Goldstein, Carlos; Bosch, Norma

    2005-08-01

    Platelet dysfunction was detected in six children with purpura and eosinophilia. We conducted clinical evaluations, hematologic and platelet function tests, clotting studies (bleeding time, prothrombin time, partial thromboplastin time, thrombin time, factor XIII, factor VIII, and von Willebrand factor), assays for IgG and IgM antibodies to platelets, and a search for stool parasites. Mild bleeding phenomena (ecchymoses, petechiae, epistaxis, and gingival) were transient. All children showed intestinal parasites and marked eosinophilia (mean count = 2,615.2 cells/muL, 95% confidence interval = 1,259.6-5,429.8). Main abnormalities included prolonged bleeding times (50%) and defective aggregation with collagen (100%) adrenaline (66%), or ADP (66%). Antibodies to platelets were not detected. Anti-parasite therapy reversed the hemorrhagic manifestations and normalized eosinophil counts and platelet alterations. No relationship could be established between excess eosinophils, intensity of bleeding, or type and degree of platelet abnormalities. Thrombocytopathic features mimicked the intrinsic defect of storage pool disease. The possible pathogenic roles of eosinophilia and parasitism are reviewed. This is the first report of this pathologic combination in Latin American children. PMID:16103609

  15. Platelet adhesion signalling and the regulation of thrombus formation.

    PubMed

    Gibbins, Jonathan M

    2004-07-15

    Platelets perform a central role in haemostasis and thrombosis. They adhere to subendothelial collagens exposed at sites of blood vessel injury via the glycoprotein (GP) Ib-V-IX receptor complex, GPVI and integrin alpha(2)beta(1). These receptors perform distinct functions in the regulation of cell signalling involving non-receptor tyrosine kinases (e.g. Src, Fyn, Lyn, Syk and Btk), adaptor proteins, phospholipase C and lipid kinases such as phosphoinositide 3-kinase. They are also coupled to an increase in cytosolic calcium levels and protein kinase C activation, leading to the secretion of paracrine/autocrine platelet factors and an increase in integrin receptor affinities. Through the binding of plasma fibrinogen and von Willebrand Factor to integrin alpha(IIb)beta(3), a platelet thrombus is formed. Although increasing evidence indicates that each of the adhesion receptors GPIb-V-IX and GPVI and integrins alpha(2)beta(1) and alpha(IIb)beta(3) contribute to the signalling that regulates this process, the individual roles of each are only beginning to be dissected. By contrast, adhesion receptor signalling through platelet endothelial cell adhesion molecule 1 (PECAM-1) is implicated in the inhibition of platelet function and thrombus formation in the healthy circulation. Recent studies indicate that understanding of platelet adhesion signalling mechanisms might enable the development of new strategies to treat and prevent thrombosis. PMID:15252124

  16. Decoration Increases the Conspicuousness of Raptor Nests

    PubMed Central

    Canal, David; Mulero-Pázmány, Margarita; Negro, Juan José; Sergio, Fabrizio

    2016-01-01

    Avian nests are frequently concealed or camouflaged, but a number of species builds noticeable nests or use conspicuous materials for nest decoration. In most cases, nest decoration has a role in mate choice or provides thermoregulatory or antiparasitic benefits. In territorial species however, decorations may serve additional or complementary functions, such as extended phenotypic signaling of nest-site occupancy and social status to potential intruders. The latter may benefit both signaler and receiver by minimizing the risk of aggressive interactions, especially in organisms with dangerous weaponry. Support for this hypothesis was recently found in a population of black kites (Milvus migrans), a territorial raptor that decorates its nest with white artificial materials. However, the crucial assumption that nest decorations increased nest-site visibility to conspecifics was not assessed, a key aspect given that black kite nests may be well concealed within the canopy. Here, we used an unmanned aircraft system to take pictures of black kite nests, with and without an experimentally placed decoration, from different altitudes and distances simulating the perspective of a flying and approaching, prospecting intruder. The pictures were shown to human volunteers through a standardized routine to determine whether detection rates varied according the nest decoration status and distance. Decorated nests consistently showed a higher detection frequency and a lower detection-latency, compared to undecorated versions of the same nests. Our results confirm that nest decoration in this species may act as a signaling medium that enhances nest visibility for aerial receivers, even at large distances. This finding complements previous work on this communication system, which showed that nest decoration was a threat informing trespassing conspecifics on the social dominance, territory quality and fighting capabilities of the signaler. PMID:27455066

  17. Decoration Increases the Conspicuousness of Raptor Nests.

    PubMed

    Canal, David; Mulero-Pázmány, Margarita; Negro, Juan José; Sergio, Fabrizio

    2016-01-01

    Avian nests are frequently concealed or camouflaged, but a number of species builds noticeable nests or use conspicuous materials for nest decoration. In most cases, nest decoration has a role in mate choice or provides thermoregulatory or antiparasitic benefits. In territorial species however, decorations may serve additional or complementary functions, such as extended phenotypic signaling of nest-site occupancy and social status to potential intruders. The latter may benefit both signaler and receiver by minimizing the risk of aggressive interactions, especially in organisms with dangerous weaponry. Support for this hypothesis was recently found in a population of black kites (Milvus migrans), a territorial raptor that decorates its nest with white artificial materials. However, the crucial assumption that nest decorations increased nest-site visibility to conspecifics was not assessed, a key aspect given that black kite nests may be well concealed within the canopy. Here, we used an unmanned aircraft system to take pictures of black kite nests, with and without an experimentally placed decoration, from different altitudes and distances simulating the perspective of a flying and approaching, prospecting intruder. The pictures were shown to human volunteers through a standardized routine to determine whether detection rates varied according the nest decoration status and distance. Decorated nests consistently showed a higher detection frequency and a lower detection-latency, compared to undecorated versions of the same nests. Our results confirm that nest decoration in this species may act as a signaling medium that enhances nest visibility for aerial receivers, even at large distances. This finding complements previous work on this communication system, which showed that nest decoration was a threat informing trespassing conspecifics on the social dominance, territory quality and fighting capabilities of the signaler. PMID:27455066

  18. Taurine and platelet aggregation

    SciTech Connect

    Nauss-Karol, C.; VanderWende, C.; Gaut, Z.N.

    1986-03-01

    Taurine is a putative neurotransmitter or neuromodulator. The endogenous taurine concentration in human platelets, determined by amino acid analysis, is 15 ..mu..M/g. In spite of this high level, taurine is actively accumulated. Uptake is saturable, Na/sup +/ and temperature dependent, and suppressed by metabolic inhibitors, structural analogues, and several classes of centrally active substances. High, medium and low affinity transport processes have been characterized, and the platelet may represent a model system for taurine transport in the CNS. When platelets were incubated with /sup 14/C-taurine for 30 minutes, then resuspended in fresh medium and reincubated for one hour, essentially all of the taurine was retained within the cells. Taurine, at concentrations ranging from 10-1000 ..mu..M, had no effect on platelet aggregation induced by ADP or epinephrine. However, taurine may have a role in platelet aggregation since 35-39% of the taurine taken up by human platelets appears to be secreted during the release reaction induced by low concentrations of either epinephrine or ADP, respectively. This release phenomenon would imply that part of the taurine taken up is stored directly in the dense bodies of the platelet.

  19. Platelet Adhesion under Flow

    PubMed Central

    Ruggeri, Zaverio M.

    2011-01-01

    Platelet adhesive mechanisms play a well-defined role in hemostasis and thrombosis, but evidence continues to emerge for a relevant contribution to other pathophysiological processes including inflammation, immune-mediated responses to microbial and viral pathogens, and cancer metastasis. Hemostasis and thrombosis are related aspects of the response to vascular injury, but the former protects from bleeding after trauma while the latter is a disease mechanism. In either situation, adhesive interactions mediated by specific membrane receptors support the initial attachment of single platelets to cellular and extracellular matrix constituents of the vessel wall and tissues. In the subsequent steps of thrombus growth and stabilization, adhesive interactions mediate platelet to platelet cohesion (aggregation) and anchoring to the fibrin clot. A key functional aspect of platelets is their ability to circulate in a quiescent state surveying the integrity of the inner vascular surface, coupled to a prompt reaction wherever alterations are detected. In many respects, therefore, platelet adhesion to vascular wall structures, to one another or to other blood cells are facets of the same fundamental biological process. The adaptation of platelet adhesive functions to the effects of blood flow is the main focus of this review. PMID:19191170

  20. 10 CFR 1050.203 - Acceptance of decorations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Acceptance of decorations. 1050.203 Section 1050.203 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) FOREIGN GIFTS AND DECORATIONS Guidelines for Acceptance of Foreign Gifts or Decorations § 1050.203 Acceptance of decorations. (a) An employee may...

  1. von Willebrand Factor Test

    MedlinePlus

    ... Platelet Count , Platelet Function Tests , Complete Blood Count , Coagulation Factor VIII , PT , PTT At a Glance Test ... a protein , one of several components of the coagulation system that work together to stop bleeding and ...

  2. Platelet kinetics with indium-111 platelets: comparison with chromium-51 platelets.

    PubMed

    Peters, A M; Lavender, J P

    1983-04-01

    The application of 111In-oxine to platelet labeling has contributed to the understanding of platelet kinetics along three lines: 1. It allows the measurement of new parameters of splenic function, such as the intrasplenic platelet transit time, which has shed new light on the physiology of splenic blood cell handling. 2. It facilitates the measurement of platelet life span in conditions, such as ITP, in which 51Cr may undergo undesirable elution from the platelet as a result of platelet-antibody interaction. 3. It allows the determination of the fate of platelets, that is, the site of platelet destruction in conditions in which reduced platelet life span is associated with abnormal platelet consumption, as a result of either premature destruction of "abnormal" platelets by the RE system, or the consumption (or destruction) of normal platelets after their interaction with an abnormal vasculature. Future research using 111In platelets may yield further valuable information on the control as well as the significance of intrasplenic platelet pooling, on the role of platelets in the development of chronic vascular lesions, and on the sites of platelet destruction in ITP. With regard to the latter, methods will have to be developed for harvesting sufficient platelets representative of the total circulating platelet population from severely thrombocytopenic patients for autologous platelet labeling. This would avoid the use of homologous platelets, which is likely to be responsible for some of the contradictory data relating to the use of radiolabeled platelet studies for the prediction of the response of patients with ITP to splenectomy. PMID:6346489

  3. Lack of multimer organization of von Willebrand factor in an acquired von Willebrand syndrome.

    PubMed

    Casonato, A; Pontara, E; Doria, A; Bertomoro, A; Cattini, M G; Gambari, P F; Girolami, A

    2002-03-01

    We report a case of acquired von Willebrand syndrome (AVWS) in a 20-year-old-woman with systemic lupus erythematosus, in whom severe bleeding complications followed kidney biopsy. Coagulation studies demonstrated undetectable levels of ristocetin-induced platelet aggregation (RIPA), von Willebrand factor antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:RCo), associated with significantly prolonged bleeding time; unlike type 3 von Willebrand disease (VWD), platelet VWF was reduced but not undetectable. The plasma VWF multimer pattern was characterized by the presence of only two bands, one of low molecular weight (MW) running as the protomer of plasma VWF in normals, the other of abnormally high MW without detectable intermediate multimers; this pattern resembles that of VWF present in endothelial cells. A search for an anti-VWF antibody demonstrated the presence of an inhibitor at high titre. This anti-VWF antibody did not interfere in the interaction of VWF with platelet glycoprotein (GP) Ib through the A1 domain, and did not react with the A2 domain of VWF; instead, it seemed to modify the relative representation of high and low MW VWF multimers released by normal human umbilical vein endothelial cells (HUVEC). After Azathioprine and corticosteroid treatment, the anti-VWF antibody disappeared and the patient's haemostatic profile normalized, except for the platelet VWF content which still remained decreased. We suggest that the anti-VWF antibody present in the AVWS described compromised both circulating VWF levels and their multimeric organization, inducing the maintenance of the multimer structure that VWF normally has before or in the early phase after secretion from endothelial cells. PMID:11886398

  4. Nanotechnology: Platelet mimicry

    NASA Astrophysics Data System (ADS)

    Farokhzad, Omid C.

    2015-10-01

    Cloaking drug-loaded nanoparticles with platelet membranes enhances the drugs' abilities to target desired cells and tissues. This technology might improve treatments for cardiovascular and infectious diseases. See Letter p.118

  5. Platelet-delivered therapeutics.

    PubMed

    Lyde, R; Sabatino, D; Sullivan, S K; Poncz, M

    2015-06-01

    We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to sights of vascular injury. Ectopic expression of proteins within α-granules prior to platelet activation has been achieved for several proteins, including urokinase, factor (F) VIII, and partially for FIX. Potential uses of platelet-directed therapeutics will be discussed, focusing on targeted delivery of urokinase as a thromboprophylactic agent and FVIII for the treatment of hemophilia A patients with intractable inhibitors. This presentation will discuss new strategies that may be useful in the care of patients with vascular injury as well as remaining challenges and limitations of these approaches. PMID:26149015

  6. Platelet associated antibodies

    MedlinePlus

    ... of the following: For unknown reasons (idiopathic thrombocytopenic purpura, or ITP ) Side effect of certain drugs such ... 2012:chap 134. Read More Antibody Idiopathic thrombocytopenic purpura (ITP) Platelet count Serum globulin electrophoresis Thrombocytopenia Update ...

  7. Dependence of plasmin-mediated degradation of platelet adhesive receptors on temperature and Ca sup 2+

    SciTech Connect

    Winters, K.J.; Eisenberg, P.R.; Jaffe, A.S.; Santoro, S.A. )

    1990-10-15

    The effects of activation of plasminogen by streptokinase and tissue-type-plasminogen activator on platelet activation and the membrane glycoproteins (GPs) that mediate platelet adhesion and aggregation are not yet fully defined. To clarify effects on platelets during activation of plasminogen in vitro, we used monoclonal antibodies (MoAbs), flow cytometry, and platelets surface-labeled with {sup 125}I to characterize changes in receptors for fibrinogen (GPIIb-IIIa), von Willebrand factor (GPIb), and collagen (GPIa-IIa). Activation of plasminogen in plasma with pharmacologic concentrations of plasminogen activators did not degrade GPIIb-IIIa or GPIb, and caused only a modest decrease in GPIa. In washed platelets GPIIb-IIIa was extensively degraded by plasmin at 37{degrees}C in the absence of exogenous Ca{sup 2+}, conditions that destabilize the IIb-IIIa complex. Degradation of GPIb in washed platelets displayed a similar although less-marked dependence on temperature and the absence of Ca{sup 2+}. The binding of activation-specific MoAbs did not increase during activation of plasminogen in plasma. We conclude that during pharmacologic fibrinolysis, reported inhibition of platelet function in plasma is not due to degradation of platelet-adhesive receptors. In addition, platelet activation observed during thrombolytic therapy does not appear to be a direct consequence of plasminogen activation.

  8. Platelets and diabetes mellitus.

    PubMed

    Santilli, Francesca; Simeone, Paola; Liani, Rossella; Davì, Giovanni

    2015-07-01

    Platelet activation plays a key role in atherothrombosis in type 2 diabetes mellitus (T2DM) and increased in vivo platelet activation with enhanced thromboxane (TX) biosynthesis has been reported in patients with impairment of glucose metabolism even in the earlier stages of disease and in the preclinical phases. In this regards, platelets appear as addresses and players carrying and transducing metabolic derangement into vascular injury. The present review critically addresses key pathophysiological aspects including (i) hyperglycemia, glycemic variability and insulin resistance as determinants and predictors of platelet activation, (ii) inflammatory mediators derived from platelets, such as soluble CD40 ligand, soluble CD36, Dickkopf-1 and probably soluble receptor for advanced glycation-end-products (sRAGE), which expand the functional repertoire of platelets from players of hemostasis and thrombosis to powerful amplifiers of inflammation by promoting the release of cytokines and chemokines, cell activation, and cell-cell interactions; (iii) molecular mechanisms underpinning the less-than-expected antithrombotic protection by aspirin (ASA), despite regular antiplatelet prophylaxis at the standard dosing regimen, and (iv) stratification of patients deserving different antiplatelet strategies, based on the metabolic phenotype. Taken together, these pathophysiological aspects may contribute to the development of promising mechanism-based therapeutic strategies to reduce the progression of atherothrombosis in diabetic subjects. PMID:25986598

  9. Biosynthesis of von Willebrand protein by human megakaryocytes.

    PubMed Central

    Sporn, L A; Chavin, S I; Marder, V J; Wagner, D D

    1985-01-01

    Immunofluorescence staining of buffy coat smears from a patient with chronic myelogenous leukemia in accelerated phase showed that approximately 13% of all nucleated cells contained von Willebrand protein and, therefore, appeared to be of megakaryocytic origin. This was confirmed by positive staining with antisera against platelet factor 4 and platelet glycoproteins. Short-term cultures of the buffy coat, which lacked endothelial cells, were metabolically labeled with [35S]methionine, and von Willebrand protein was immunopurified from cell lysates and culture medium. Cultures from this patient synthesized and secreted von Willebrand protein, in contrast with cultures from other patients with leukemia, who lacked circulating megakaryocytes, and from normal volunteers. The subunit composition of the megakaryocytic von Willebrand protein was very similar to that of human umbilical vein endothelial cells. The size of the processed subunit (220 kD) and of the cellular (260 kD) and secreted (275 kD) precursors from the two cell types were indistinguishable by gel electrophoresis. Furthermore, the ratio of precursor to processed subunit and the pattern of cellular and secreted nonreduced multimers were very similar. It appears, therefore, that the processing steps in biosynthesis of von Willebrand protein used by the megakaryocytes are very similar to those of umbilical vein endothelial cells. Images PMID:2413071

  10. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Wernher von Braun with Dr. Eberhard Rees and R.W. Cook at a press conference concerning Dr. Von Braun's assignment to NASA headquarters and Dr. Rees' subsequent assignment as Marshall Center director.

  11. Platelet preservation: agitation and containers.

    PubMed

    van der Meer, Pieter F; de Korte, Dirk

    2011-06-01

    For platelets to maintain their in vitro quality and in vivo effectiveness, they need to be stored at room temperature with gentle agitation in gas-permeable containers. The mode of agitation affects the quality of the platelets, and a gentle method of agitation, either a circular or a flat bed movement, provides the best results. Tumblers or elliptical agitators induce platelet activation and subsequent damage. As long as the platelets remain in suspension, the agitation speed is not important. Agitation of the platelet concentrates ensures that the platelets are continuously oxygenated, that sufficient oxygen can enter the storage container and that excess carbon dioxide can be expelled. During transportation of platelet concentrates, nowadays over long distances where they are held without controlled agitation, platelets may tolerate a certain period without agitation. However, evidence is accumulating that during the time without agitation, local hypoxia surrounding the platelets may induce irreversible harm to the platelets. Over the decades, more gas-permeable plastics have been used to manufacture platelet containers. The use of different plastics and their influence on the platelet quality both in vitro and in vivo is discussed. The improved gas-permeability has allowed the extension of platelet storage from 3 days in the early 1980s, to currently at least 7 days. In the light of new developments, particularly the introduction of pathogen reduction techniques, the use of platelet additive solutions and the availability of improved automated separators, further (renewed) research in this area is warranted. PMID:21514232

  12. The mechanism of VWF-mediated platelet GPIbalpha binding.

    PubMed

    Auton, Matthew; Zhu, Cheng; Cruz, Miguel A

    2010-08-01

    The binding of Von Willebrand Factor to platelets is dependent on the conformation of the A1 domain which binds to platelet GPIbalpha. This interaction initiates the adherence of platelets to the subendothelial vasculature under the high shear that occurs in pathological thrombosis. We have developed a thermodynamic strategy that defines the A1:GPIbalpha interaction in terms of the free energies (DeltaG values) of A1 unfolding from the native to intermediate state and the binding of these conformational states to GPIbalpha. We have isolated the intermediate conformation of A1 under nondenaturing conditions by reduction and carboxyamidation of the disulfide bond. The circular dichroism spectrum of reduction and carboxyamidation A1 indicates that the intermediate has approximately 10% less alpha-helical structure that the native conformation. The loss of alpha-helical secondary structure increases the GPIbalpha binding affinity of the A1 domain approximately 20-fold relative to the native conformation. Knowledge of these DeltaG values illustrates that the A1:GPIbalpha complex exists in equilibrium between these two thermodynamically distinct conformations. Using this thermodynamic foundation, we have developed a quantitative allosteric model of the force-dependent catch-to-slip bonding that occurs between Von Willebrand Factor and platelets under elevated shear stress. Forced dissociation of GPIbalpha from A1 shifts the equilibrium from the low affinity native conformation to the high affinity intermediate conformation. Our results demonstrate that A1 binding to GPIbalpha is thermodynamically coupled to A1 unfolding and catch-to-slip bonding is a manifestation of this coupling. Our analysis unites thermodynamics of protein unfolding and conformation-specific binding with the force dependence of biological catch bonds and it encompasses the effects of two subtypes of mutations that cause Von Willebrand Disease. PMID:20713003

  13. Clinical uses of radiolabeled platelets

    SciTech Connect

    Datz, F.L.; Christian, P.E.; Baker, W.J.

    1985-12-01

    Platelets were first successfully radiolabeled in 1953. At that time, investigators were primarily interested in developing a technique to accurately measure platelet life span in both normal and thrombocytopenic patients. Studies using platelets labeled with /sup 51/Cr have shown shortened platelet survival times in a number of diseases including idiopathic thrombocytopenic purpura, coronary artery disease, and diabetes mellitus. More recently, labels such as /sup 111/In have been developed that allow in vivo imaging of platelets. Indium-111 platelets are being used to better understand the pathophysiology of atherosclerosis, thrombophlebitis, pulmonary embolism and clotting disorders, and to improve the clinical diagnosis of these diseases.

  14. Polyphosphate, Platelets, and Coagulation

    PubMed Central

    Travers, Richard J.; Smith, Stephanie A.; Morrissey, James H.

    2015-01-01

    While we have understood the basic outline of the enzymes and reactions that make up the traditional blood coagulation cascade for many years, recently our appreciation of the complexity of these interactions has greatly increased. This has resulted in unofficial “revisions” of the coagulation cascade to include new amplification pathways and connections between the standard coagulation cascade enzymes, as well as the identification of extensive connections between the immune system and the coagulation cascade. The discovery that polyphosphate is stored in platelet dense granules and is secreted during platelet activation has resulted in a recent burst of interest in the role of this ancient molecule in human biology. Here we review the increasingly complex role of platelet polyphosphate in hemostasis, thrombosis, and inflammation that has been uncovered in recent years, as well as novel therapeutics centered on modulating polyphosphate’s roles in coagulation and inflammation. PMID:25976958

  15. Development and evaluation of decorated aceclofenac nanocrystals.

    PubMed

    Park, Jeong-Joo; Meghani, Nilesh; Choi, Jin-Seok; Lee, Beom-Jin

    2016-07-01

    This study was aimed at achieving enhanced solubility of aceclofenac (ACF) in nanocrystaline forms (ACF-NC) and evaluating the effects of ACF-NC on cell viability. Decorated ACF-NC were prepared by nano-precipitation with stabilizers. Three kinds of stabilizers were investigated: Tween 80, Poloxamer 407, and PEG 6000. The crystal structure and morphology of ACF-NC were characterized by field emission scanning electron microscopy (FE-SEM) and differential scanning calorimetry (DSC). The solubility of ACF-NC and ACF (pure) was evaluated in different media (pH 1.2 and pH 6.8 buffers and distilled water [DW]). A drug release study was performed in PBS for 24h. Cell viability was evaluated for 24h using a human colon cancer cell-line (HCT-116) and a human breast cancer cell-line (MCF-7). Decorated ACF-NC with a mean size of 725nm were successfully prepared. The solubility of the decorated ACF-NC were 4-7 times higher than that of ACF in DW and pH 6.8 buffer. A peak shift from 153.1°C to 150.5-151.0°C was observed in the DSC thermogram of decorated ACF-NC versus ACF. In terms of drug release, there was an initial burst in decorated ACF-NC within 1h followed by slow release for up to 4h. Decorated ACF-NC exhibited viability approximately 63.9% of HCT-116 cells and also showed viability in 58.3% of MCF-7 cells at 15μg/mL of drug concentration. In conclusion, decorated ACF-NC proved to be a promising approach for enhancing drug solubility and cytotoxicity. PMID:27011350

  16. Platelet storage in PAS-2 or autologous plasma: impact on functional parameters.

    PubMed

    Bunescu, A; Hild, M; Lundahl, J; Egberg, N

    2001-04-01

    Currently, several platelet additive solutions for long-term platelet storage have been introduced. The aim of this study was to compare the deterioration of functional status of platelets stored for up to 5 days in autologous plasma (AP) only, with platelet stored in PAS-2, a salt solution containing acetate, citrate and sodium chloride. Change in platelet adhesion, aggregation and activation was measured by flow cytometric technique. In addition, beta-Thromboglobulin (beta-TG), lactate and glucose were determined. After 5 days of storage, the expression of P-Selectin was significantly higher, the production of lactate and the consumption of glucose were significantly lower, in platelets stored in PAS-2 than in autologous plasma. No significant differences were detected on day 5 between the two groups with regard to fibrinogen, von Willebrand factor binding capacity, or to beta-TG release. It can be concluded that neither storage medium was consistently better for the parameters tested. However, it must be emphasized that platelets stored in autologous plasma exhibited less lesion, in terms of P-Selectin expression compared with platelets stored in PAS-2. PMID:11299027

  17. Dietary α-linolenic acid increases the platelet count in ApoE-/- mice by reducing clearance.

    PubMed

    Stivala, Simona; Reiner, Martin F; Lohmann, Christine; Lüscher, Thomas F; Matter, Christian M; Beer, Juerg H

    2013-08-01

    Previously we reported that dietary intake of alpha-linolenic acid (ALA) reduces atherogenesis and inhibits arterial thrombosis. Here, we analyze the substantial increase in platelet count induced by ALA and the mechanisms of reduced platelet clearance. Eight-week-old male apolipoprotein E knockout (ApoE(-/-)) mice were fed a 0.21g% cholesterol diet complemented by either a high- (7.3g%) or low-ALA (0.03g%) content. Platelet counts doubled after 16 weeks of ALA feeding, whereas the bleeding time remained similar. Plasma glycocalicin and glycocalicin index were reduced, while reticulated platelets, thrombopoietin, and bone marrow megakaryocyte colony-forming units remained unchanged. Platelet contents of liver and spleen were substantially reduced, without affecting macrophage function and number. Glycoprotein Ib (GPIb) shedding, exposure of P-selectin, and activated integrin αIIbβ3 upon activation with thrombin were reduced. Dietary ALA increased the platelet count by reducing platelet clearance in the reticulo-endothelial system. The latter appears to be mediated by reduced cleavage of GPIb by tumor necrosis factor-α-converting enzyme and reduced platelet activation/expression of procoagulant signaling. Ex vivo, there was less adhesion of human platelets to von Willebrand factor under high shear conditions after ALA treatment. Thus, ALA may be a promising tool in transfusion medicine and in high turnover/high activation platelet disorders. PMID:23801636

  18. The caspase-3 inhibitor (peptide Z-DEVD-FMK) affects the survival and function of platelets in platelet concentrate during storage

    PubMed Central

    Shiri, Reza; Ahmadinejad, Minoo; Vaeli, Shahram; Tabatabaei, Mohammad Reza

    2014-01-01

    Background Although apoptosis occurs in nucleated cells, studies show that this event also occurs in some anucleated cells such as platelets. During storage of platelets, the viability of platelets decreased, storage lesions were observed, and cells underwent apoptosis. We investigated the effects of caspase-3 inhibitor on the survival and function of platelets after different periods of storage. Methods Platelet concentrates were obtained from the Iranian Blood Transfusion Organization in plastic blood bags. Caspase-3 inhibitor (Z-DEVD-FMK) was added to the bags. These bags along with control bags to which no inhibitor was added were stored in a shaking incubator at 22℃ for 7 days. The effects of Z-DEVD-FMK on the functionality of platelets were analyzed by assessing their ability to bind to von Willebrand factor (vWF) and to aggregate in the presence of arachidonic acid and ristocetin. Cell survival was surveyed by MTT assay. Results At day 4 of storage, ristocetin-induced platelet aggregation was significantly higher in the inhibitor-treated (test) than in control samples; the difference was not significant at day 7. There was no significant difference in arachidonic acid-induced platelet aggregation between test and control samples. However, at day 7 of storage, the binding of platelets to vWF was significantly higher in test than in control samples. The MTT assay revealed significantly higher viability in test than in control samples at both days of study. Conclusion Treatment of platelets with caspase-3 inhibitor could increase their functionality and survival. PMID:24724067

  19. [Molecular biology of von Willebrand disease].

    PubMed

    Melo-Nava, Brenda; Peñaloza, Rosenda

    2007-01-01

    Von Willebrand Factor (VWF) is a large multimeric glycoprotein expressed in the megakaryocytes and endothelial cells of all vertebrates. It participates fundamentally in the primary and secondary hemostasis because it induces the adhesion of platelets to vascular subendothelium and promotes aggregation of platelets when blood vessels and capillaries are damaged. In addition, VWF links to factor VIII which avoids its proteolysis. The deficiency or the inadequate synthesis of the VWF causes von Willebrand disease (VWD), which is the most common hereditary bleeding disorder in humans principally from mucous and cutaneous sites. VWD is difficult to detect with accuracy due to interrelation among VWF with different components of hemostasis, although it is performed by different tests of haemostatic system, and the basic mechanisms in VWD are herein emphasized. The diagnosis of VWD is difficult due to the heterogeneous manifestation of the disease, which also complicates its classification. This article focuses on the molecular aspects of the disease and discusses their possible clinical implications. PMID:18268896

  20. Misfolding of vWF to pathologically disordered conformations impacts the severity of von Willebrand disease.

    PubMed

    Tischer, Alexander; Madde, Pranathi; Moon-Tasson, Laurie; Auton, Matthew

    2014-09-01

    The primary hemostatic von Willebrand factor (vWF) functions to sequester platelets from rheological blood flow and mediates their adhesion to damaged subendothelium at sites of vascular injury. We have surveyed the effect of 16 disease-causing mutations identified in patients diagnosed with the bleeding diathesis disorder, von Willebrand disease (vWD), on the structure and rheology of vWF A1 domain adhesiveness to the platelet GPIbα receptor. These mutations have a dynamic phenotypical range of bleeding from lack of platelet adhesion to severe thrombocytopenia. Using new rheological tools in combination with classical thermodynamic, biophysical, and spectroscopic metrics, we establish a high propensity of the A1 domain to misfold to pathological molten globule conformations that differentially alter the strength of platelet adhesion under shear flow. Rheodynamic analysis establishes a quantitative rank order between shear-rate-dependent platelet-translocation pause times that linearly correlate with clinically reported measures of patient platelet counts and the severity of thrombocytopenia. These results suggest that specific secondary structure elements remaining in these pathological conformations of the A1 domain regulate GPIbα binding and the strength of vWF-platelet interactions, which affects the vWD functional phenotype and the severity of thrombocytopenia. PMID:25185554

  1. Effects of platelet inhibitors on propyl gallate-induced platelet aggregation, protein tyrosine phosphorylation, and platelet factor 3 activation.

    PubMed

    Xiao, Hongyan; Kovics, Richard; Jackson, Van; Remick, Daniel G

    2004-04-01

    Propyl gallate (PG) is a platelet agonist characterized by inducing platelet aggregation, protein tyrosine phosphorylation, and platelet factor 3 activity. The mechanisms of platelet activation following PG stimulation were examined by pre-incubating platelets with well-defined platelet inhibitors using platelet aggregation, protein tyrosine phosphorylation, activated plasma clotting time, and annexin V binding by flow cytometry. PG-induced platelet aggregation and tyrosine phosphorylation of multiple proteins were substantially abolished by aspirin, apyrase, and abciximab (c7E3), suggesting that PG is associated with activation of platelet cyclooxygenase 1, adenosine phosphate receptors, and glycoprotein IIb/IIIa, respectively. The phosphorylation of the cytoskeletal enzyme pp60(c-src) increased following PG stimulation, but was blunted by pre-incubation of platelets with aspirin, apyrase, and c7E3, suggesting that tyrosine kinase is important for the signal transduction of platelet aggregation. Propyl gallate also activates platelet factor 3 by decreasing the platelet coagulation time and increasing platelet annexin V binding. Platelet incubation with aspirin, apyrase, and c7E3 did not alter PG-induced platelet coagulation and annexin V binding. The results suggest that platelet factor 3 activation and membrane phosphotidylserine expression were not involved with activation of platelet cyclooxygenase, adenosine phosphate receptors, and glycoprotein IIb/IIIa. PG is unique in its ability to stimulate platelet aggregation and coagulation simultaneously, and platelet inhibitors in this study affect only platelet aggregation but not platelet coagulation. PMID:15060414

  2. Functional responses and molecular mechanisms involved in histone-mediated platelet activation.

    PubMed

    Carestia, A; Rivadeneyra, L; Romaniuk, M A; Fondevila, C; Negrotto, S; Schattner, M

    2013-11-01

    Histones are highly alkaline proteins found in cell nuclei and they can be released by either dying or inflammatory cells. The recent observations that histones are major components of neutrophil extracellular traps and promote platelet aggregation and platelet-dependent thrombin generation have shown that these proteins are potent prothrombotic molecules. Because the mechanism(s) of platelet activation by histones are not completely understood, we explored the ability of individual recombinant human histones H1, H2A, H2B, H3 and H4 to induce platelet activation as well as the possible molecular mechanisms involved. All histones were substrates for platelet adhesion and spreading and triggered fibrinogen binding, aggregation, von Willebrand factor release, P-selectin and phosphatidylserine (PS) exposure and the formation of platelet-leukocyte aggregates; however, H4 was the most potent. Histone-mediated fibrinogen binding, P-selectin and PS exposure and the formation of mixed aggregates were potentiated by thrombin. Histones induced the activation of ERK, Akt, p38 and NFκB. Accordingly, histone-induced platelet activation was significantly impaired by pretreatment of platelets with inhibitors of ERK (U 0126), PI3K/Akt (Ly 294002), p38 (SB 203580) and NFκB (BAY 11-7082 and Ro 106-9920). Preincubation of platelets with either aspirin or dexamethasone markedly decreased fibrinogen binding and the adhesion mediated by histones without affecting P-selectin exposure. Functional platelet responses induced by H3 and H4, but not H1, H2A and H2B, were partially mediated through interaction with Toll-like receptors -2 and -4. Our data identify histones as important triggers of haemostatic and proinflammatory platelet responses, and only haemostatic responses are partially inhibited by anti-inflammatory drugs. PMID:23965842

  3. 5. EAST ELEVATION (OFFICE BLOCK), DETAIL SHOWING DECORATIVE PILASTERS AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. EAST ELEVATION (OFFICE BLOCK), DETAIL SHOWING DECORATIVE PILASTERS AND STYLIZED EGG-AND-DART DECORATION AROUND WINDOWS OF UPPER FLOORS - Delaware, Lackawanna & Western Railroad & Ferry Terminal, Hudson Place, Hoboken, Hudson County, NJ

  4. ABO blood group as a model for platelet glycan modification in arterial thrombosis

    PubMed Central

    Zhong, Ming; Zhang, Hanrui; Reilly, John P.; Chrisitie, Jason D.; Ishihara, Mayumi; Kumagai, Tadahiro; Azadi, Parastoo; Reilly, Muredach P.

    2015-01-01

    ABO blood groups have long been associated with cardiovascular disease, thrombosis and acute coronary syndromes. Many studies over the years have shown type O blood group to be associated with lower risk of cardiovascular disease compared to non-type O blood groups. However, the mechanisms underlying this association remain unclear. Although ABO blood group is associated with variations in concentrations of circulating von Willebrand Factor and other endothelial cell adhesion molecules, ABO antigens are also present on several platelet surface glycoproteins and glycosphingolipids. As we highlight in this platelet-centric review, these glycomic modifications may impact platelet function in arterial thrombosis. More broadly, improving our understanding of the role of platelet glycan modifications in acute coronary syndromes may inform future diagnostics and therapeutics for cardiovascular diseases. PMID:26044584

  5. von Willebrand disease: a laboratory approach.

    PubMed

    Trasi, Sucheta; Ghosh, Kanjaksha; Shetty, Shrimati; Mohanty, Dipika

    2005-01-01

    von Willebrand disease (VWD) is a common inherited bleeding disorder. Accurate diagnosis and classification of VWD is crucial for clinical management. A detailed clinical history, including that of bleeding, is required. A family and drug history are also important. Genetic factors such as blood group, and environmental factors such as stress, trauma, pregnancy and inflammation should also be considered. The age, ethnic group and hormonal status could also affect the von Willebrand factor (VWF) levels. No single test is robust enough to detect all variants of VWD. In view of the heterogeneity of the disease and limitations in assays, a battery of tests should be performed before a final diagnosis can be reached. These include the screening coagulation tests, factor VIII:C assay, VWF antigen assay, assessment of functional VWF which includes VWF ristocetin cofactor assays, VWF collagen binding assay, ristocetin-induced platelet aggregation and VWF multimer analysis. The newer ELISA techniques based on VWF binding with factor VIII glycoprotein (Gp) 1b and cerebrosides have also helped in determining certain unusual forms of VWD. The advent of new systems such as platelet function analysers (PFA), thromboelastography (TEG) and clot signature analysers (CSA), which are designed to assess either the primary platelet function or as a global haemostasis screen, have facilitated and simplified the diagnosis. However, few centres all over the world can perform all these expensive tests to provide a final diagnosis of VWD. We reviewed the laboratory investigations required for a diagnosis of VWD. Apart from congenital VWD, the possibility of acquired VWD should be considered in those with a negative past history of bleeding or in the presence of an underlying disease. PMID:15981443

  6. von Willebrand factor antigen as a therapeutic target of portal hypertension in cirrhosis

    PubMed Central

    Kalambokis, Georgios N; Baltayiannis, Gerasimos; Christodoulou, Dimitrios

    2016-01-01

    Increased thrombotic potential within the liver sinusoids due to local endothelial production of von Willebrand factor antigen macromolecules could represent an additional therapeutic target of portal hypertension in patients with cirrhosis. In this case, anti-inflammatory and antithrombotic drugs could modulate portal pressure by preventing the formation of intrahepatic platelet-induced microthrombi. PMID:27217711

  7. Diagnosis of von Willebrand disease.

    PubMed

    Ingerslev, J; Gürsel, T

    1999-05-01

    The haemorrhagic diathesis in von Willebrand disease (vWD) is caused by a quantitative deficiency or a qualitative defect in the von Willebrand factor (vWF) in plasma and/or platelets causing insufficient primary haemostasis. Since vWF binds and protects factor VIII (FVIII) towards random proteolysis, coagulation may also be impaired in patients with a low plasma level of vWF, and in instances where vWF displays insufficient binding capacity to FVIII. The entity of vWD displays a vast heterogeneity. Apart from rarely occurring acquired cases, vWD is an inherited disorder of autosomal linkage. The major clinical hallmark in vWD is an increased tendency to mucocutaneous bleeding that rarely reach life-threatening proportions, unless vWF is severely reduced or completely absent. Increased bleeding may also occur in sites such as muscles and joints when the level of FVIII is particularly low. Significant progress has recently been achieved through extensive molecular genetic exploration of various forms of vWD. In order to guide treatment and to form a platform for genetic investigation, however, accuracy in diagnosis and phenotypic characterization is important. By means of various laboratory methods, major subclasses of vWD can be differentiated, as presented in another article of this series. Whereas most of the cases of vWD can quite easily be diagnosed and classified using today's diagnostic methods, the most frequently occurring bleeding disorder of all, vWd type 1 of mild degree, continues to challenge clinicians and diagnostic laboratories. The aim of this paper is to review the laboratory methods most commonly used in diagnostic investigation of the patient suspected of vWD. PMID:23401900

  8. Dietary manipulation of platelet function.

    PubMed

    Bachmair, E M; Ostertag, L M; Zhang, X; de Roos, B

    2014-11-01

    Activated platelets contribute to plaque formation within blood vessels in the early and late stages of atherogenesis, and therefore they have been proposed as risk factor for cardiovascular disease. Anti-platelet drugs, such as aspirin, are now the most prescribed pharmacological treatment in Europe. Certain dietary bioactives also beneficially affect platelet function, and with less side effects, albeit that effects are generally more subtle. Therefore, consumption of dietary bioactives could play a role in the prevention of atherothrombotic vascular disease. Here we review the efficacy of dietary treatment strategies, especially those involving certain dietary fatty acids and polyphenols, to modulate platelet function in healthy subjects or in patients with cardiovascular disease. Variation in study populations, small study sizes and lack of comparability between methods to assess platelet function currently limit robust evidence on the efficacy of dietary bioactives in healthy subjects or specific patient groups. Also, limited knowledge of the metabolism of dietary bioactives, and therefore of the bioavailability of bioactive ingredients, restricts our ability to identify the most effective dietary regimes to improve platelet function. Implementation of uniform point-of-care tests to assess platelet function, and enhanced knowledge of the efficacy by which specific dietary compounds and their metabolites affect platelet function, may enable the identification of functional anti-platelet ingredients that are eligible for a health claim, or combined treatment strategies, including both pharmacological anti-platelet treatment as well as dietary intervention, to tackle atherothrombotic vascular disease. PMID:24858060

  9. Platelet satellitism: an ultrastructural study.

    PubMed Central

    Payne, C. M.

    1981-01-01

    The ultrastructural morphology of platelet-polymorph (platelet-polymorphonuclear leukocyte) rosettes was investigated in EDTA-anticoagulated blood obtained from two patients who exhibited the phenomenon of platelet satellitism. Most of the platelet profiles were attached to the polymorph surface by broad areas of contact. Examination of these broad areas of contact at high magnification revealed an intercellular material of low electron density. This material appeared to form strands, which bridged the intercellular space and spanned the entire area formed by the apposing plasma membranes. Phagocytosis of entire platelets was only observed in 1 case. The platelet profiles that participated in rosette formation revealed a large number of glycogen particles, compared with unattached platelets. Ultrastructural examination of "stress" platelets obtained from five normal subjects treated with steroids similarly showed a large number of glycogen particles, although no rosette formation or phagocytosis of platelets was observed. The etiology of platelet satellitism is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7223859

  10. Up to date concepts about Von Willebrand disease and the diagnose of this hemostatic disorder

    PubMed Central

    Buga-Corbu, I; Arion, C

    2014-01-01

    Abstract The authors review the current data in literature regarding the recent knowledge about hemostase, coagulation and clinical and laboratory diagnostic algorithms of hemostatic disorders. They also present the pathological classification of bleeding disorders - the basis to clinical approach of these diseases. Abbreviations: AD=autosomal dominant; Ag=antigen; DNA=deoxyribonucleic acid; ADAMTS13=serum metalloproteinase; AR=autosomal recessive; Arg=arginine; RNA=ribonucleic acid; VWD=von Willebrand disease; Cys=cysteine; C1—C9=factors of the seric complement; ELISA=enzyme linked immuno assay; FI---FXIII=plasmatic factors of coagulation; Glu=glutamines; Pg=platelet glycoprotein; HMW=high molecular weight; IL=interleukin; SLE=systemic lupus erythematosus; Met=methionine; PFA=automated study test of platelets aggregation; RCo=ristocetin cofactor; RI PA=ristocetin induced platelet aggregation; Tyr=tyrosine; VWF= von Willebrand factor PMID:25408749

  11. PECAM-1 negatively regulates GPIb/V/IX signaling in murine platelets.

    PubMed

    Rathore, Vipul; Stapleton, Michelle A; Hillery, Cheryl A; Montgomery, Robert R; Nichols, Timothy C; Merricks, Elizabeth P; Newman, Debra K; Newman, Peter J

    2003-11-15

    Platelet adhesion at sites of vascular injury is mediated, in part, by interaction of the platelet plasma membrane glycoprotein (GP) Ib/V/IX complex with von Willebrand Factor (VWF) presented on collagen-exposed surfaces. Recent studies indicate that GPIb/V/IX may be functionally coupled with the Fc receptor gamma (FcR gamma)-chain, which, by virtue of its cytoplasmic immunoreceptor tyrosine-based activation motif, sends activation signals into the cell. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is an inhibitory receptor that has previously been shown to negatively regulate platelet responses to collagen, which transduces activation signals via the GPVI/FcR gamma-chain complex. To determine whether PECAM-1 might similarly regulate signals emanating from GPIb/FcR gamma, we compared activation and aggregation responses to VWF of PECAM-1-positive and PECAM-1-deficient murine platelets. PECAM-1 and the FcR gamma-chain became rapidly tyrosine phosphorylated in platelets following botrocetin-induced VWF binding, but FcR gamma-chain tyrosine phosphorylation was delayed in PECAM-1-positive, versus PECAM-1-deficient, platelets. PECAM-1-deficient platelets were hyperaggregable to VWF, exhibited enhanced spreading and, under conditions of arterial flow, formed markedly larger thrombi on immobilized VWF than did wild-type platelets. Taken together, these data support the notion that engagement of the GPIb complex, in addition to sending activation signals, also initiates a negative feedback loop involving PECAM-1 that controls the rate and extent of platelet activation. PMID:12893757

  12. Simulation of the Effect of Red Blood Cell Collisions on Platelet Adsorption

    NASA Astrophysics Data System (ADS)

    Fitzgibbon, Sean; Zhao, Hong; Shaqfeh, Eric

    2012-11-01

    The adsorption of platelets to the endothelial wall is an important first step in the clotting process, which is critical to stopping blood loss after trauma. Initial platelet arrest is controlled by very short range interaction between two proteins, von Willibrand Factor and GPIb, so the rate of platelet adsorption is expected to be strongly dependent on the rate at which the platelets sample the wall. With Peclet numbers in the range (103 - 105) , simple diffusive arguments are not sufficient to explain the high rates of platelet adsorption. Using Stokes flow simulations, we show that the platelets' wall sampling rate is significantly increased by interactions with red blood cells. Our simulation models platelets as rigid bodies suspended in a Stokesian linear shear flow. We solve for the flow using standard boundary integral techniques with the appropriate single wall bounded Green's function. Receptor-ligand interactions are represented as Hookean springs with characteristic lifetimes, sizes, and stiffness coefficients. Drag forces are calculated with the reciprocal theorem, and RBC collisions are modelled as AR processes extracted from the large scale suspension simulations of Zhao et al.

  13. 10 Ways to...Decorate Your Classroom

    ERIC Educational Resources Information Center

    Prescott, Jennifer

    2005-01-01

    Recruit the best decorating corps you have for this year's classroom makeover--your students! Not only does involving kids save money and effort on your part, teachers agree that it increases kids' sense of involvement and respect. In this article, the author presents 10 teacher-tested ideas for a classroom that shines with color and learning: (1)…

  14. Platelet Immobilization on Supported Phospholipid Bilayers for Single Platelet Studies.

    PubMed

    Uhl, Eva; Donati, Alessia; Reviakine, Ilya

    2016-08-23

    The worldwide cardiovascular disease (CVD) epidemic is of grave concern. A major role in the etiology of CVDs is played by the platelets (thrombocytes). Platelets are anuclear cell fragments circulating in the blood. Their primary function is to catalyze clot formation, limiting traumatic blood loss in the case of injury. The same process leads to thrombosis in the case of CVDs, which are commonly managed with antiplatelet therapy. Platelets also have other, nonhemostatic functions in wound healing, inflammation, and tissue regeneration. They play a role in the early stages of atherosclerosis and the spread of cancer through metastases. Much remains to be learned about the regulation of these diverse platelet functions under physiological and pathological conditions. Breakthroughs in this regard are expected to come from single platelet studies and systems approaches. The immobilization of platelets at surfaces is advantageous for developing such approaches, but platelets are activated when they come in contact with foreign surfaces. In this work, we develop and validate a protocol for immobilizing platelets on supported lipid bilayers without activation due to immobilization. Our protocol can therefore be used for studying platelets with a wide variety of surface-sensitive techniques. PMID:27438059

  15. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Wernher Von Braun (left) and Fred W. Kelley examine a ST-100 Stellar Instrument Platform in the astrionics lab. Dr. Von Braun, then deputy associate administrator for planning, NASA, was visiting on the anniversary of the establishment of the Marshall Space Flight Center.

  16. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1968-01-01

    Dr. Wernher Von Braun, stands in front of a Saturn IB Launch Vehicle at Kennedy Space Center (KSC). Dr. Von Braun was Marshall's first Center Director (1960-1970). Under his leadership Marshall was responsible for the development of the Saturn rockets, the Skylab project and getting the United States into Space and landing on the moon with the Apollo missions.

  17. Platelets in Inflammation and Atherogenesis

    PubMed Central

    Nording, Henry M.; Seizer, Peter; Langer, Harald F.

    2015-01-01

    Platelets contribute to processes beyond thrombus formation and may play a so far underestimated role as an immune cell in various circumstances. This review outlines immune functions of platelets in host defense, but also how they may contribute to mechanisms of infectious diseases. A particular emphasis is placed on the interaction of platelets with other immune cells. Furthermore, this article outlines the features of atherosclerosis as an inflammatory vascular disease highlighting the role of platelet crosstalk with cellular and soluble factors involved in atheroprogression. Understanding, how platelets influence these processes of vascular remodeling will shed light on their role for tissue homeostasis beyond intravascular thrombosis. Finally, translational implications of platelet-mediated inflammation in atherosclerosis are discussed. PMID:25798138

  18. Dr. Wernher von Braun

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Dr. von Braun is looking out from a 10th floor window of building 4200 at the Marshall Space Flight Center (MSFC). He was the first Center Director and served as the Director from July 1960 through February 1970. Following World War II, Dr. von Braun and his German colleagues arrived in the United States under the Project Paperclip (American acquisition of German rocket experts) to continue their rocket development work. In 1950, von Braun and his German Rocket Team (also called the Peenemuende Team) were transferred from Ft. Bliss, Texas to Huntsville, Alabama to work for the Army's rocket program at Redstone Arsenal and later, NASA's Marshall Space Flight Center (MSFC). Under Dr. von Braun's leadership, MSFC developed the Saturn V launch vehicle, which placed the first men, two American astronauts, on the Moon. Wernher von Braun's life was dedicated to expanding man's knowledge through the exploration of space.

  19. Human blood platelets at microgravity

    NASA Technical Reports Server (NTRS)

    Surgenor, D. MACN.; Ausprunk, D.; Blevins, D.; Chao, F. C.; Curby, W.

    1987-01-01

    A set of freshly collected and separated human platelet suspensions were transported, in three types of plastic containers, on a 6 day, 2 hr mission of the orbiter Columbia to study the effect of prolonged exposure of human blood cells to microgravity. A controlled environment at a temperature of 22 + or - 1 deg with air flow was provided and another set of samples held on the ground acted as controls. Paired comparisons of platelets at ug versus controls at lxg revealed superior platelet survival at microgravity. When viewed in terms of plastic type, ug platelets in containers fabricated from PVC-TOTM displayed the best overall postflight viability.

  20. Overview of platelet physiology and laboratory evaluation of platelet function.

    PubMed

    Rodgers, G M

    1999-06-01

    Appropriate laboratory testing for the platelet-type bleeding disorders hinges on an adequate assessment in the history and physical examination. Patients with histories and screening laboratory results consistent with coagulation disorders (hemophilia, disseminated intravascular coagulation) are not appropriate candidates for platelet function testing. In contrast, patients with a lifelong history of platelet-type bleeding symptoms and perhaps a positive family history of bleeding would be appropriate for testing. Figure 6 depicts one strategy to evaluate these patients. Platelet morphology can easily be evaluated to screen for two uncommon qualitative platelet disorders: Bernard-Soulier syndrome (associated with giant platelets) and gray platelet syndrome, a subtype of storage pool disorder in which platelet granulation is morphologically abnormal by light microscopy. If the bleeding disorder occurred later in life (no bleeding with surgery or trauma early in life), the focus should be on acquired disorders of platelet function. For those patients thought to have an inherited disorder, testing for vWD should be done initially because approximately 1% of the population has vWD. The complete vWD panel (factor VIII coagulant activity, vWf antigen, ristocetin cofactor activity) should be performed because many patients will have abnormalities of only one particular panel component. Patients diagnosed with vWD should be classified using multimeric analysis to identify the type 1 vWD patients likely to respond to DDAVP. If vWD studies are normal, platelet aggregation testing should be performed, ensuring that no antiplatelet medications have been ingested at least 1 week before testing. If platelet aggregation tests are normal and if suspicion for an inherited disorder remains high, vWD testing should be repeated. The evaluation of thrombocytopenia may require bone marrow examination to exclude primary hematologic disorders. If future studies with thrombopoietin assays

  1. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury

    PubMed Central

    Sugiyama, Michael G.; Gamage, Asela; Zyla, Roman; Armstrong, Susan M.; Advani, Suzanne; Advani, Andrew; Wang, Changsen

    2015-01-01

    ABSTRACT Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza. IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza

  2. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    PubMed

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2016-02-01

    Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have

  3. Subpopulations in purified platelets adhering on glass.

    PubMed

    Donati, Alessia; Gupta, Swati; Reviakine, Ilya

    2016-01-01

    Understanding how platelet activation is regulated is important in the context of cardiovascular disorders and their management with antiplatelet therapy. Recent evidence points to different platelet subpopulations performing different functions. In particular, procoagulant and aggregating subpopulations have been reported in the literature in platelets treated with the GPVI agonists. How the formation of platelet subpopulations upon activation is regulated remains unclear. Here, it is shown that procoagulant and aggregating platelet subpopulations arise spontaneously upon adhesion of purified platelets on clean glass surfaces. Calcium ionophore treatment of the adhering platelets resulted in one platelet population expressing both the procoagulant and the adherent population markers phosphatidylserine and the activated form of GPIIb/IIIa, while all of the platelets expressed CD62P independently of the ionophore treatment. Therefore, all platelets have the capacity to express all three activation markers. It is concluded that platelet subpopulations observed in various studies reflect the dynamics of the platelet activation process. PMID:27338300

  4. [Von Willebrand factor and ADAMTS13 balancing primary haemostasis].

    PubMed

    Schneppenheim, R; Budde, U

    2011-11-01

    Von Willebrand factor (VWF) is an adhesive, multi-functional huge multimerized protein with multiple domains harboring binding sites for collagen, platelet glycoprotein receptors and coagulation factor VIII (FVIII). The functional domains enable VWF to bind to the injured vessel wall, to recruit platelets to the site of injury by adhesion and aggregation and to bind and protect FVIII, an important cofactor of the coagulation cascade. VWF function in primary haemostasis is located in particular in the arterial and micro-circulation. This environment is exposed to high shear forces with hydrodynamic shear rates ranging over several orders of magnitude from 10⁻¹ to 10⁵ s-1 and requires particular mechanisms to enable platelet adhesion and aggregation under these variable conditions. The respective VWF function is strictly correlating with its multimer size. Lack or reduction of large VWF multimers is seen in patients with von Willebrand disease (VWD) type 2A which correlates with reduction of both VWF:platelet GPIb-binding and VWF:collagen binding and a bleeding phenotype. To prevent unlimited platelet adhesion and aggregation which is the cause of the microangiopathic disorder thrombotic thrombocytopenic purpura (TTP), VWF function is regulated by its specific protease ADAMTS13. Whereas a particular susceptibility of VWF to ADAMTS13 proteolysis is the cause of a frequent VWD type 2A phenotype, lack or dysfunction of ADAMTS13, either acquired by ADAMTS13 antibodies or by inherited ADAMTS13 deficiency (Upshaw-Schulman Syndrome), causes TTP. Therefore VWD and TTP represent the opposite manifestations of VWF related disorders, tightly linked to each other. PMID:21792464

  5. [STRUCTURAL CHARACTERIZATION OF PLATELETS AND PLATELET-DERIVED MICROVESICLES].

    PubMed

    Ponomareva, A A; Nevzorova, T A; Mordakhanova, E R; Andrianova, I A; Litvinov, R I

    2016-01-01

    Platelets are the anucleated blood cells, wich together with the fibrin stop bleeding (hemostasis). Cellular microvesicles are membrane-surrounded microparticles released into extracellular space upon activation and/or apoptosis of various cells. Platelet-derived macrovesicles from the major population of circulating blood microparticles that play an important role in hemostasis and thrombosis. Despite numerous studies on the pathophysiology of platelet-derived macrovesicles, mechanisms of their formation and structural details remain poorly understood. Here we investigated the ultrastructure of parental platelets and platelet-derived microvesicles formed in vitro by quiescent cells as well as by cells stimulated with one of the following activators: arachidonic acid, ADP, thrombin, calcium ionophore A23187. Using transmission electron microscopy of human platelets and isolated microvesicles, we analyzed the intracellular origin, steps of formation, structural diversity, and size distributions of the subcellular particles. We have revealed that thrombin, unlike other stimuli, not only induced vesiculation of the plasma membrane but also caused break-up of the cells followed by formation of microparticles that are comparable with microvesicles by size. A fraction of these microparticles contained cellular organelles surrounded by a thin membrane. The size of platelet-derived macrovesicles varied from 30 nm to 500 nm, however, the size distributions depended on the nature of a cell-activating stimulus. The results obtained provide new information about the formation of platelet-derived macrovesicles and their structural diversity, wich is important to understand their multiple functions in normal and disease states. PMID:27228656

  6. [Diagnosis of inherited diseases of platelet function. Interdisciplinary S2K guideline of the Permanent Paediatric Committee of the Society of Thrombosis and Haemostasis Research (GTH e. V.)].

    PubMed

    Knöfler, R; Eberl, W; Schulze, H; Bakchoul, T; Bergmann, F; Gehrisch, S; Geisen, C; Gottstein, S; Halimeh, S; Harbrecht, U; Kappert, G; Kirchmaier, C; Kehrel, B; Lösche, W; Krause, M; Mahnel, R; Meyer, O; Pilgrimm, A K; Pillitteri, D; Rott, H; Santoso, S; Siegemund, A; Schambeck, C; Scheer, M; Schmugge, M; Scholl, T; Strauss, G; Zieger, B; Zotz, R; Hermann, M; Streif, W

    2014-01-01

    Congenital disorders of platelet function are a heterogeneous group of disorders that are often not detected until bleeding occurs. In clinical settings only a few methods have proven to be useful for identification and classification of inherited platelet disorders. For a rational diagnostic approach, a stepwise algorithm is recommended. Patient history and clinical investigation are mandatory. Von Willebrand disease and other coagulation disorders should always be ruled out prior to specific platelet testing. Platelet count, size, volume (MPV) and morphology may guide further investigations. The PFA-100® CT is suited for screening for severe platelet defects. Platelet aggregometry allows assessment of multiple aspects of platelet function. Flow cytometry enables diagnosis of thrombasthenia Glanzmann, Bernard-Soulier syndrome and storage pool defects. Molecular genetics may confirm a putative diagnosis or pave the way for identifying new defects. We present an unabridged version of the interdisciplinary guideline. PMID:24903476

  7. Genomics of platelet disorders.

    PubMed

    Westbury, S K; Mumford, A D

    2016-07-01

    Genetic diagnosis in families with inherited platelet disorders (IPD) is not performed widely because of the genetic heterogeneity of this group of disorders and because in most cases, it is not possible to select single candidate genes for analysis using clinical and laboratory phenotypes. Next-generation sequencing (NGS) technology has revolutionized the scale and cost-effectiveness of genetic testing, and has emerged as a valuable tool for IPD. This review examines the potential utility of NGS as a diagnostic tool to streamline detection of causal variants in known IPD genes and as a vehicle for new gene discovery. PMID:27405671

  8. von Willebrand factor, Jedi knight of the bloodstream.

    PubMed

    Springer, Timothy A

    2014-08-28

    When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use "the Force" to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned. PMID:24928861

  9. von Willebrand factor, Jedi knight of the bloodstream

    PubMed Central

    2014-01-01

    When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use “the Force” to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned. PMID:24928861

  10. Biologic nanoparticles and platelet reactivity

    PubMed Central

    Miller, Virginia M; Hunter, Larry W; Chu, Kevin; Kaul, Vivasvat; Squillace, Phillip D; Lieske, John C; Jayachandran, Muthuvel

    2009-01-01

    Aim Nanosized particles (NPs) enriched in hydroxyapatite and protein isolated from calcified human tissue accelerate occlusion of endothelium-denuded arteries when injected intravenously into rabbits. Since platelet aggregation and secretory processes participate in normal hemostasis, thrombosis and vascular remodeling, experiments were designed to determine if these biologic NPs alter specific platelet functions in vitro. Methods Platelet-rich plasma was prepared from citrate anticoagulated human blood. Platelet aggregation and ATP secretion were monitored in response to thrombin receptor agonists peptide (10 μM) or convulxin (50 μg/ml) prior to and following 15 min incubation with either control solution, human-derived NPs, bovine-derived NPs or crystals of hydroxyapatite at concentrations of 50 and 150 nephelometric turbidity units. Results Incubation of platelets for 15 min with either human- or bovine-derived NPs reduced aggregation induced by thrombin receptor activator peptide and convulxin in a concentration-dependent manner. Hydroxyapatite caused a greater inhibition than either of the biologically derived NPs. Human-derived NPs increased ATP secretion by unstimulated platelets during the 15 min incubation period. Conclusion Effects of bovine-derived and hydroxyapatite NPs on basal release of ATP were both time and concentration dependent. These results suggest that biologic NPs modulate both platelet aggregation and secretion. Biologically derived NPs could modify platelet responses within the vasculature, thereby reducing blood coagulability and the vascular response to injury. PMID:19839809

  11. Platelets: production, morphology and ultrastructure.

    PubMed

    Thon, Jonathan N; Italiano, Joseph E

    2012-01-01

    Platelets are anucleate, discoid cells, roughly 2-3 μm in diameter that function primarily as regulators of hemostasis, but also play secondary roles in angiogensis and innate immunity. Although human adults contain nearly one trillion platelets in circulation that are turned over every 8-10 days, our understanding of the mechanisms involved in platelet production is still incomplete. Platelets stem from large (30-100 μm) nucleated cells called megakaryocytes that reside primarily in the bone marrow. During maturation megakaryocytes extend long proplatelet elongations into sinusoidal blood vessels from which platelets ultimately release. During this process, platelets develop a number of distinguishable structural elements including: a delimited plasma membrane; invaginations of the surface membrane that form the open canalicular system (OCS); a closed-channel network of residual endoplasmic reticulum that form the dense tubular system (DTS); a spectrin-based membrane skeleton; an actin-based cytoskeletal network; a peripheral band of microtubules; and numerous organelles including α-granules, dense-granules, peroxisomes, lysosomes, and mitochondria. Proplatelet elongation and platelet production is an elaborate and complex process that defines the morphology and ultrastructure of circulating platelets, and is critical in understanding their increasingly numerous and varied biological functions. PMID:22918725

  12. Platelet abnormalities in nephrotic syndrome.

    PubMed

    Eneman, Benedicte; Levtchenko, Elena; van den Heuvel, Bert; Van Geet, Chris; Freson, Kathleen

    2016-08-01

    Nephrotic syndrome (NS) is a common kidney disease associated with a significantly increased risk of thrombotic events. Alterations in plasma levels of pro- and anti-coagulant factors are involved in the pathophysiology of venous thrombosis in NS. However, the fact that the risk of both venous and arterial thrombosis is elevated in NS points to an additional role for blood platelets. Increased platelet counts and platelet hyperactivity have been observed in nephrotic children. Platelet hyperaggregability, increased release of active substances, and elevated surface expression of activation-dependent platelet markers have been documented. The mechanisms underlying those platelet alterations are multifactorial and are probably due to changes in plasma levels of platelet-interfering proteins and lipid changes, as a consequence of nephrosis. The causal relationship between platelet alterations seen in NS and the occurrence of thromboembolic phenomena remains unclear. Moreover, the efficiency of prophylactic treatment using antiplatelet agents for the prevention of thrombotic complications in nephrotic patients is also unknown. Thus, antiplatelet medication is currently not generally recommended for routine prophylactic therapy. PMID:26267676

  13. Platelet adhesiveness in diabetes mellitus

    PubMed Central

    Shaw, S.; Pegrum, G. D.; Wolff, Sylvia; Ashton, W. L.

    1967-01-01

    Platelet adhesiveness has been assessed on whole blood from a series of 34 diabetics and 50 control subjects using adenosine diphosphate (A.D.P.) and by adherence to glass microspherules (ballotini). Using both techniques it was possible to demonstrate a significant increase in platelet adhesiveness in the diabetic patients. PMID:5614070

  14. Platelet-derived VWF is not essential for normal thrombosis and hemostasis but fosters ischemic stroke injury in mice.

    PubMed

    Verhenne, Sebastien; Denorme, Frederik; Libbrecht, Sarah; Vandenbulcke, Aline; Pareyn, Inge; Deckmyn, Hans; Lambrecht, Antoon; Nieswandt, Bernhard; Kleinschnitz, Christoph; Vanhoorelbeke, Karen; De Meyer, Simon F

    2015-10-01

    Von Willebrand factor (VWF) is a key hemostatic protein synthesized in both endothelial cells and megakaryocytes. Megakaryocyte-derived VWF is stored in α-granules of platelets and is enriched in hyperactive "ultra-large" VWF multimers. To elucidate the specific contribution of platelet VWF in hemostasis and thrombosis, we performed crossed bone marrow transplantations between C57BL/6J and Vwf(-/-) mice to generate chimeric mice. Chimeric mice specifically lacking platelet VWF showed normal tail bleeding and carotid artery thrombosis, similar to wild-type mice. Chimeric mice with VWF present only in platelets were not able to support normal thrombosis and hemostasis. However, using a mouse model of transient middle cerebral artery occlusion, we observed that cerebral infarct sizes and fibrin(ogen) deposition in chimeric mice with only platelet VWF were significantly increased compared with Vwf(-/-) mice (P < .01). Blocking of the platelet VWF-glycoprotein (GP)Ib interaction abrogated this platelet VWF-mediated injury. These data suggest that whereas platelet-derived VWF does not play a crucial role in hemostasis and arterial thrombosis, it aggravates thrombo-inflammatory diseases such as stroke via a GPIb-dependent mechanism. PMID:26209660

  15. Interactions of von Willebrand factor and ADAMTS13 in von Willebrand disease and thrombotic thrombocytopenic purpura.

    PubMed

    Budde, U; Schneppenheim, R

    2014-01-01

    The function of von Willebrand factor (VWF), a huge multimeric protein and a key factor in platelet dependent primary haemostasis, is regulated by its specific protease ADAMTS13. The ADAMTS13 dependent degradation of VWF to its proteolytic fragments can be visualized as a characteristic so-called triplet structure of individual VWF oligomers by multimer analysis. Lack of VWF high molecular weight multimers (VWF-HMWM) or their pathologically enhanced degradation underlies a particular type of von Willebrand disease, VWD type 2A with a significant bleeding tendency, and may also be observed in acquired von Willebrand syndrome due to cardiovascular disease. In these conditions multimer analysis is an obligatory and powerful tool for diagnosis of VWD. The opposite condition, the persistence of ultralarge VWF (UL-VWF) multimers may cause the microangiopathic life-threatening disorder thrombotic thrombocytopenic purpura (TTP). During the course of active TTP, UL-VWF is consumed in the hyaline thrombi formed in the microvasculature which will ultimately result in the loss of UL-VWF and VWF-HMWM. Therefore, VWF multimer analysis is not a valid tool to diagnose TTP in the active phase of disease but may be helpful for the diagnosis of TTP patients in remission. PMID:25010251

  16. First principle study of sodium decorated graphyne

    NASA Astrophysics Data System (ADS)

    Sarkar, Utpal; Bhattacharya, Barnali; Seriani, Nicola

    2015-11-01

    We present first-principles calculations of the electronic properties of Na-decorated graphyne. This structure of the graphyne family is a direct band gap semiconductor with a band gap of 0.44 eV in absence of sodium, but Na-decorated graphyne compounds are metallic, and can then be employed as carbon-based conductors. Metallization is due to charge donation from sodium to carbon. Pristine graphyne is more stable than Na-decorated graphyne, therefore is seems probable that, if this material should be employed as electrode in Na-ion batteries, it would lead to the formation of metallic sodium rather than well dispersed sodium ions. On the other side, this property might be useful if graphyne is employed in water desalination. Finally, the abrupt change from a semiconducting to a metallic state in presence of a small amount of sodium might be exploited in electronics, e.g. for the production of smooth metal-semiconductor interfaces through spatially selective deposition of sodium.

  17. Generalized transformation for decorated spin models

    NASA Astrophysics Data System (ADS)

    Rojas, Onofre; Valverde, J. S.; de Souza, S. M.

    2009-04-01

    The paper discusses the transformation of decorated Ising models into an effective undecorated spin model, using the most general Hamiltonian for interacting Ising models including a long range and high order interactions. The inverse of a Vandermonde matrix with equidistant nodes [-s,s] is used to obtain an analytical expression of the transformation. This kind of transformation is very useful to obtain the partition function of decorated systems. The method presented by Fisher is also extended, in order to obtain the correlation functions of the decorated Ising models transforming into an effective undecorated Ising model. We apply this transformation to a particular mixed spin-(1/2, 1) and (1/2, 2) square lattice with only nearest site interaction. This model could be transformed into an effective uniform spin- S square lattice with nearest and next-nearest interaction, furthermore the effective Hamiltonian also includes combinations of three-body and four-body interactions; in particular we considered spin 1 and 2.

  18. Platelet-Rich Plasma

    PubMed Central

    Cole, Brian J.; Seroyer, Shane T.; Filardo, Giuseppe; Bajaj, Sarvottam; Fortier, Lisa A.

    2010-01-01

    Context: Platelet-rich plasma (PRP) may affect soft tissue healing via growth factors released after platelet degranulation. Because of this potential benefit, clinicians have begun to inject PRP for the treatment of tendon, ligament, muscle, and cartilage injuries and early osteoarthritis. Evidence Acquisition: A PubMed search was performed for studies relating to PRP, growth factors, and soft tissue injuries from 1990 to 2010. Relevant references from these studies were also retrieved. Results: Soft tissue injury is a major source of disability that may often be complicated by prolonged and incomplete recovery. Numerous growth factors may potentiate the healing and regeneration of tendons and ligaments. The potential benefits of biologically enhanced healing processes have led to a recent interest in the use of PRP in orthopaedic sports medicine. There has been widespread anecdotal use of PRP for muscle strains, tendinopathy, and ligament injuries and as a surgical adjuvant to rotator cuff repair, anterior cruciate ligament reconstruction, and meniscal or labral repairs. Although the fascination with this emerging technology has led to a dramatic increase in its use, scientific data supporting this use are still in their infancy. Conclusions: The literature is replete with studies on the basic science of growth factors and their relation to the maintenance, proliferation, and regeneration of various tissues and tissue-derived cells. Despite the promising results of several animal studies, well-controlled human studies are lacking. PMID:23015939

  19. [Raman and EDXRF Study on Overglaze Decorations of Jingdezhen Ceramics].

    PubMed

    Wu, Juan; Zhang, Mao-lin; Wu, Jun-ming; Li, Qi-jiang; Cao, Jian-wen; Li, Qing-hui; Zhao, Hong-xia

    2015-05-01

    Overglaze decoration porcelain is an important category of ancient Chinese ceramics, which has significant artistic value and scientific value. Nondestructive analysis methods such as Raman spectroscopy and EDXRF were used to analyze the overglaze decorations on the Jingdezhen ceramic samples of Yuan, Ming and Qing Dynasty. The recipe and color mechanism of the overglaze pigments were discussed according to the chemical composition and phase composition analysis. The study found that dark red overglaze decorations of ancient Honglvcai, Wucai and famille rose in Jingdezhen are colored by hematite, yellow color is lead tin yellow, carmine decoration is colored by gold less than 0. 1 % in concentration, and green decorations are colored by bivalent copper ion. The result also indicates that the effective combination of Raman spectroscopy and EDXRF can play an important role in the deep research on ceramic artifacts, especially for the overglaze decoration pigments which are interveined each other. PMID:26415441

  20. Platelet-Rich Plasma and Platelet Gel: A Review

    PubMed Central

    Everts, Peter A.M.; Knape, Johannes T.A.; Weibrich, Gernot; Schönberger, Jacques P.A.M.; Hoffmann, Johannes; Overdevest, Eddy P.; Box, Henk A.M.; van Zundert, André

    2006-01-01

    Abstract: Strategies to reduce blood loss and transfusion of allogeneic blood products during surgical procedures are important in modern times. The most important and well-known autologous techniques are preoperative autologous predonation, hemodilution, perioperative red cell salvage, postoperative wound blood autotransfusion, and pharmacologic modulation of the hemostatic process. At present, new developments in the preparation of preoperative autologous blood component therapy by whole blood platelet-rich plasma (PRP) and platelet-poor plasma (PPP) sequestration have evolved. This technique has been proven to reduce the number of allogeneic blood transfusions during open heart surgery and orthopedic operations. Moreover, platelet gel and fibrin sealant derived from PRP and PPP mixed with thrombin, respectively, can be exogenously applied to tissues to promote wound healing, bone growth, and tissue sealing. However, to our disappointment, not many well-designed scientific studies are available, and many anecdotic stories exist, whereas questions remain to be answered. We therefore decided to study perioperative blood management in more detail with emphasis on the application and production of autologous platelet gel and the use of fibrin sealant. This review addresses a large variety of aspects relevant to platelets, platelet-rich plasma, and the application of platelet gel. In addition, an overview of recent animal and human studies is presented. PMID:16921694

  1. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Wernher Von Braun (right), Deputy Associate Administrator for planning, National Aeronautics and Space Administration, inspects the mockup of the Saturn Workshop during a visit marking the 10th anniversary of the Marshall Center. Shown with Dr. Von Braun, from left to right, are Karl Heimburg, Director of the astronautics lab; Herman K. Weidner, Director of Science and Engineering, and George Hardy of the Astronautics lab.

  2. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Wernher Von Braun (right), Deputy Associate Administrator for Planning, National Aeronautics and Space Administration, inspects the mockup of the Saturn Workshop during a visit marking the 10th anniversary of the Marshall Center. Shown with Dr. Von Braun, from left to right, are Karl Heimburg, Director of the Astronautics Lab; Herman K. Weidner, Director of Science and Engineering, and George Hardy of the Astronautics Lab.

  3. Mediators and molecular pathways involved in the regulation of neutrophil extracellular trap formation mediated by activated platelets.

    PubMed

    Carestia, Agostina; Kaufman, Tomás; Rivadeneyra, Leonardo; Landoni, Verónica Inés; Pozner, Roberto Gabriel; Negrotto, Soledad; D'Atri, Lina Paola; Gómez, Ricardo Martín; Schattner, Mirta

    2016-01-01

    In addition to being key elements in hemostasis and thrombosis, platelets amplify neutrophil function. We aimed to gain further insight into the stimuli, mediators, molecular pathways, and regulation of neutrophil extracellular trap formation mediated by human platelets. Platelets stimulated by lipopolysaccharide, a wall component of gram-negative bacteria, Pam3-cysteine-serine-lysine 4, a mimetic of lipopeptide from gram-positive bacteria, Escherichia coli, Staphylococcus aureus, or physiologic platelet agonists promoting neutrophil extracellular trap formation and myeloperoxidase-associated DNA activity under static and flow conditions. Although P-selectin or glycoprotein IIb/IIIa were not involved, platelet glycoprotein Ib, neutrophil cluster of differentiation 18, and the release of von Willebrand factor and platelet factor 4 seemed to be critical for the formation of neutrophil extracellular traps. The secretion of these molecules depended on thromboxane A(2) production triggered by lipopolysaccharide or Pam3-cysteine-serine-lysine 4 but not on high concentrations of thrombin. Accordingly, aspirin selectively inhibited platelet-mediated neutrophil extracellular trap generation. Signaling through extracellular signal-regulated kinase, phosphatidylinositol 3-kinase, and Src kinases, but not p38 or reduced nicotinamide adenine dinucleotide phosphate oxidase, was involved in platelet-triggered neutrophil extracellular trap release. Platelet-mediated neutrophil extracellular trap formation was inhibited by prostacyclin. Our results support a role for stimulated platelets in promoting neutrophil extracellular trap formation, reveal that an endothelium-derived molecule contributes to limiting neutrophil extracellular trap formation, and highlight platelet inhibition as a potential target for controlling neutrophil extracellular trap cell death. PMID:26320263

  4. Holiday Decorating Contest - A Way to Meet Fellow Employees | Poster

    Cancer.gov

    The trolls from “Frozen,” a North Pole tunnel, and a Christmas tree­–shaped periodic table of elements were just a few of the decorations on display during the second annual Holiday Decorating Contest in December. The contest, sponsored by the R&W Club Frederick, awarded prizes to three groups and two individuals whose decorations were judged based on visual impact, creativity, and craftsmanship.

  5. Synthesis of polymer latex particles decorated with organically-modified laponite clay platelets via emulsion polymerization.

    PubMed

    Herrera, Norma Negrete; Persoz, Stéphanie; Putaux, Jean-Luc; David, Laurent; Bourgeat-Lami, Elodie

    2006-02-01

    We report a new route to colloidal nanocomposites consisting of polymer latex particles covered with Laponite clay nanoplatelets. These composite particles are prepared by seeded emulsion (co)polymerization of styrene and butyl acrylate from Laponite clay suspensions previously functionalized by ion exchange using either a free radical initiator: 2,2-azobis (2-methylpropionamidine) hydrochloride (AIBA) or a cationic vinyl monomer: 2-(methacryloyloxy) ethyl trimethyl ammonium chloride (MADQUAT). The successful intercalation of the cationic reactive molecules was confirmed by elemental analysis, FTIR, 13C solid-state NMR and WAXD. The organically-modified clays were dispersed into water with the help of tetrasodium pyrophosphate and an anionic surfactant. stable latexes, produced under different experimental conditions, were successfully obtained from the clay suspensions. Cryo-TEM images of the resulting latexes showed spherical composite particles with diameters in the 50-250 nm range with clay sheets located on their surface. This paper reports on the effect of the processing conditions on the particle morphology and latex stability, and describes the mechanism of formation of the nanocomposite particles. PMID:16573041

  6. Platelet storage media.

    PubMed

    Gulliksson, H

    2014-10-01

    Present platelet storage media often designated platelet additive solutions (PAS) basically contain acetate, citrate and phosphate and recently also potassium and magnesium. However, there seems to be an increasing interest in developing PASs that can be used also after further reduction of residual plasma content below 15-20% plasma. Inclusion of glucose but also calcium and bicarbonate in such solutions have been suggested to improve platelet (PLT) storage, especially when plasma content is reduced to very low levels. Results from a limited number of studies using novel PAS alternatives have been presented during the last years, such as InterSol-G, PAS-5, M-sol, PAS-G and SAS. Most of them are experimental solutions. The combined results presented in those studies suggest that presence of glucose may be necessary during PLT storage, primarily to maintain ATP at acceptable levels. At plasma inclusion below 15-20%, the content of glucose will generally be too low to support PLT metabolism for more than a few days making glucose addition in PAS necessary. Significant effects associated with presence of calcium was observed in PLTs stored in PAS with 5% inclusion but not with 20-35% plasma inclusion, suggesting that the content of plasma could be of importance. Bicarbonate only seems to be of importance for pH regulation, primarily when plasma inclusion is reduced to about 5%. Reduction in rate of glycolysis was observed in some PAS alternatives containing potassium and magnesium but not in others. Differences in pH or in concentrations of the various compounds included in PAS may be possible explanations. Additionally, novel PAS containing glucose, calcium and bicarbonate does not seem to be associated with improved in vitro results as compared to SSP+ or CompoSol when PLTs are stored with 35% plasma inclusion. The results would then also suggest that excess of glucose in novel PAS environment may not be associated with additional positive effects on PLT metabolism

  7. Shiga toxin binds to activated platelets.

    PubMed

    Ghosh, S A; Polanowska-Grabowska, R K; Fujii, J; Obrig, T; Gear, A R L

    2004-03-01

    Hemolytic uremic syndrome (HUS) is associated with acute renal failure in children and can be caused by Shiga toxin (Stx)-producing Escherichia coli. Thrombocytopenia and formation of renal thrombi are characteristic of HUS, suggesting that platelet activation is involved in its pathogenesis. However, whether Shiga toxin directly activates platelets is controversial. The present study evaluates if potential platelet sensitization during isolation by different procedures influences platelet interaction with Shiga toxin. Platelets isolated from sodium citrate anticoagulated blood were exposed during washing to EDTA and higher g forces than platelets prepared from acid-citrate-dextrose (ACD) plasma. Platelet binding of Stx was significantly higher in EDTA-washed preparations relative to ACD-derived platelets. Binding of Stx was also increased with ACD-derived platelets when activated with thrombin (1 U mL-1) and exposure of the Gb3 Stx receptor was detected only on platelets subjected to EDTA, higher g forces or thrombin. EDTA-exposed platelets lost their normal discoid shape and were larger. P-selectin (CD62P) exposure was significantly increased in EDTA-washed preparations relative to ACD-derived platelets, suggesting platelet activation. Taken together, these results suggest that direct binding of Stx occurs only on 'activated' platelets rather than on resting platelets. The ability of Stx to interact with previously activated platelets may be an important element in understanding the pathogenesis of HUS. PMID:15009469

  8. Platelet Interaction with Innate Immune Cells

    PubMed Central

    Kral, Julia Barbara; Schrottmaier, Waltraud Cornelia; Salzmann, Manuel; Assinger, Alice

    2016-01-01

    Summary Beyond their traditional role in haemostasis and thrombosis, platelets are increasingly recognised as immune modulatory cells. Activated platelets and platelet-derived microparticles can bind to leukocytes, which stimulates mutual activation and results in rapid, local release of platelet-derived cytokines. Thereby platelets modulate leukocyte effector functions and contribute to inflammatory and immune responses to injury or infection. Platelets enhance leukocyte extravasation, differentiation and cytokine release. Platelet-neutrophil interactions boost oxidative burst, neutrophil extracellular trap formation and phagocytosis and play an important role in host defence. Platelet interactions with monocytes propagate their differentiation into macrophages, modulate cytokine release and attenuate macrophage functions. Depending on the underlying pathology, platelets can enhance or diminish leukocyte cytokine production, indicating that platelet-leukocyte interactions represent a fine balanced system to restrict excessive inflammation during infection. In atherosclerosis, platelet interaction with neutrophils, monocytes and dendritic cells accelerates key steps of atherogenesis by promoting leukocyte extravasation and foam cell formation. Platelet-leukocyte interactions at sites of atherosclerotic lesions destabilise atherosclerotic plaques and promote plaque rupture. Leukocytes in turn also modulate platelet function and production, which either results in enhanced platelet destruction or increased platelet production. This review aims to summarise the key effects of platelet-leukocyte interactions in inflammation, infection and atherosclerosis. PMID:27226790

  9. Platelet Interaction with Innate Immune Cells.

    PubMed

    Kral, Julia Barbara; Schrottmaier, Waltraud Cornelia; Salzmann, Manuel; Assinger, Alice

    2016-03-01

    Beyond their traditional role in haemostasis and thrombosis, platelets are increasingly recognised as immune modulatory cells. Activated platelets and platelet-derived microparticles can bind to leukocytes, which stimulates mutual activation and results in rapid, local release of platelet-derived cytokines. Thereby platelets modulate leukocyte effector functions and contribute to inflammatory and immune responses to injury or infection. Platelets enhance leukocyte extravasation, differentiation and cytokine release. Platelet-neutrophil interactions boost oxidative burst, neutrophil extracellular trap formation and phagocytosis and play an important role in host defence. Platelet interactions with monocytes propagate their differentiation into macrophages, modulate cytokine release and attenuate macrophage functions. Depending on the underlying pathology, platelets can enhance or diminish leukocyte cytokine production, indicating that platelet-leukocyte interactions represent a fine balanced system to restrict excessive inflammation during infection. In atherosclerosis, platelet interaction with neutrophils, monocytes and dendritic cells accelerates key steps of atherogenesis by promoting leukocyte extravasation and foam cell formation. Platelet-leukocyte interactions at sites of atherosclerotic lesions destabilise atherosclerotic plaques and promote plaque rupture. Leukocytes in turn also modulate platelet function and production, which either results in enhanced platelet destruction or increased platelet production. This review aims to summarise the key effects of platelet-leukocyte interactions in inflammation, infection and atherosclerosis. PMID:27226790

  10. Radioimmune assay of human platelet prostaglandin synthetase

    SciTech Connect

    Roth, G.J.; Machuga, E.T.

    1982-02-01

    Normal platelet function depends, in part, on platelet PG synthesis. PG synthetase (cyclo-oxygenase) catalyzes the first step in PG synthesis, the formation of PGH/sub 2/ from arachidonic acid. Inhibition of the enzyme by ASA results in an abnormality in the platelet release reaction. Patients with pparent congenital abnormalities in the enzyme have been described, and the effects have been referred to as ''aspirin-like'' defects of the platelet function. These patients lack platelet PG synthetase activity, but the actual content of PG synthetase protein in these individuals' platelets is unknown. Therefore an RIA for human platelet PG synthetase would provide new information, useful in assessing the aspirin-like defects of platelet function. An RIA for human platelet PG synthetase is described. The assay utilizes a rabbit antibody directed against the enzyme and (/sup 125/I)-labelled sheep PG synthetase as antigen. The human platelet enzyme is assayed by its ability to inhibit precipitation of the (/sup 125/I)antigen. The assay is sensitive to 1 ng of enzyme. By the immune assay, human platelets contain approximately 1200 ng of PG synethetase protein per 1.5 mg of platelet protein (approximately 10/sup 9/ platelets). This content corresponds to 10,000 enzyme molecules per platelet. The assay provides a rapid and convenient assay for the human platelet enzyme, and it can be applied to the assessment of patients with apparent platelet PG synthetase (cyclo-oxygenase) deficiency.

  11. Nucleation of platelets with bloodborne pathogens on Kupffer cell precedes other innate immunity and contributes to bacterial clearance

    PubMed Central

    Wong, Connie H. Y.; Jenne, Craig N.; Petri, Björn; Chrobok, Navina L.; Kubes, Paul

    2016-01-01

    Using intravital imaging of the liver, we unveil a collaborative role for platelets with Kupffer cells (KCs) in eradicating bloodborne bacterial infections. Under basal conditions, platelets via glycoprotein Ib (GPIb) formed transient “touch-and-go” interactions with von Willebrand factor (vWF) constitutively expressed on KCs. Bacteria, such as Bacillus cereus and Methicillin-resistant Staphylococcus aureus (MRSA), were rapidly caught by KCs and triggered platelets to switch from “touch-and-go” to sustained GPIIb-mediated adhesion on the KC surface to encase the bacterium. Infected GpIbα−/− mice demonstrated increased endothelial and KC damage, leading to increased fluid leakage, significant polycythemia and rapid mortality. This study identifies a novel surveillance mechanism of intravascular macrophage by platelets that rapidly converts to a critical host response against bloodborne bacteria. PMID:23770641

  12. Acquired von Willebrand syndrome with a type 2B phenotype: diagnostic and therapeutic dilemmas.

    PubMed

    Scepansky, Ellen; Othman, Maha; Smith, Hedy

    2014-01-01

    In this report, we provide evidence of an acquired von Willebrand syndrome (AVWS) with a type 2B phenotype rather than the expected type 1 or 2A. The patient was referred prior to surgical removal of a fibrous mass within the maxillary sinus. His first bleeding 7 years earlier following a retinal tear had been complicated by monocular blindness. Several mucocutanous bleedings followed. Hematological investigations revealed von Willebrand factor (VWF):Ag 91 IU/ml, factor VIII 86 IU/ml, VWF:RCo 34 IU/ml and profound thrombocytopenia with platelet clumping. VWF multimer analysis showed a loss of high-molecular-weight multimers and his plasma aggregated normal platelets under low ristocetin concentration, consistent with type 2B von Willebrand disease (VWD). Sequencing of VWF exon 28 and of the platelet GP1BA gene to investigate the possibility of platelet-type VWD failed to reveal mutations. Serum protein electrophoresis showed a monoclonal IgG protein and led to the diagnosis of monoclonal gammopathy of unknown significance (MGUS), raising suspicion of an AVWS. Over 2 years, he experienced severe gingival bleedings and traumatic intracerebral hemorrhage. Following debridement of the sinus mass, the patient required 20 units of packed red blood cells, despite high-dose Humate-P, continuous Amicar and twice-daily platelet transfusions. Bleeding finally ceased following infusion of activated factor VIIa. A history of prior uncomplicated vasectomy and tendon laceration, no family history of bleeding, the inability to identify a causative mutation in either exon 28 VWF or platelet GP1BA and the MGUS led to diagnosis of AVWS with a type 2B phenotype. This case highlights the difficulties in assigning a diagnosis and the management of bleeding in a patient with an atypical presentation of AVWS. PMID:24296552

  13. Hormonal contraception and platelet function.

    PubMed

    Saleh, A A; Ginsburg, K A; Duchon, T A; Dorey, L G; Hirata, J; Alshameeri, R S; Dombrowski, M P; Mammen, E F

    1995-05-15

    73 healthy women (29 controls, 25 using OCs, and 19 using Norplant) were selected from the clinic population at North Oakland Medical Center for inclusion in this study after obtaining informed consent. Age, race, height, weight, blood pressure, and cigarette smoking were recorded for each subject. 12 patients were on monophasic OCs while 13 were on triphasic preparations. Both hormonal contraceptive groups had used their particular contraceptive for at least 3 months prior to blood drawing. Platelet tests were performed within 2 hours of sample collection: platelet counts (PLC) and mean platelet volume (MPV) were determined on an Automated Platelet Counter (Baker 810 Platelet Analyzer). Whole blood aggregation was performed on a platelet aggregometer (Chrono-Log, Model 550) using both ADP (ADP, 5 mM) and collagen (COLL, 2 mcg/ml) as inducing agents. Demographic differences were not significant (p 0.05) among the 3 treatment groups, whose average age was 25.3-25.8 years old. Furthermore, no significant differences (p 0.05) in platelet function were detected among controls or subjects receiving either oral contraceptives or Norplant, compared to control patients. The mean platelet counts (X 10/9/L) were 223 for OC users, 231 for Norplant users, and 232 for controls. The respective platelet aggregation (ADP, ohms) values were 12.5, 18.0, and 19.2 as well as (COLL, ohms) 35.6, 40.7, and 39.0. These results demonstrated that there is no evidence for altered platelet function, with the testing methods employed, in women using either Norplant or combination low dose oral contraceptives. To date, several studies have examined this issue, with contradictory reports about the effects of hormonal contraceptives in platelet function. After controlling for differences between various steroid preparations and other such confounding variables, some of these conflicting conclusions could be the result of a lack of uniformity among the methods used to evaluate platelet aggregation

  14. A monoclonal antibody directed against a granule membrane glycoprotein (GMP-140/PADGEM, P-selectin, CD62P) inhibits ristocetin-induced platelet aggregation.

    PubMed

    Boukerche, H; Ruchaud-Sparagano, M H; Rouen, C; Brochier, J; Kaplan, C; McGregor, J L

    1996-02-01

    P-selectin (also called CD62, GMP-140, PADGEM, CD62P) is a recently described member of a family of vascular adhesion receptors expressed by activated platelets and endothelial cells that are involved in leucocyte cell adhesion. The aim of this study was to characterize a new monoclonal antibody (LYP7) directed against activated human blood platelets that inhibits ristocetin-induced platelet aggregation. Immunoadsorbent affinity chromatography and immunoprecipitation studies showed that LYP7 (IgG1) bound a surface-labelled glycoprotein (GP) which changed its apparent molecular mass (M(r)) on reduction from 138 kD (situated below GPIIb) to 148 kD (above GPIIb alpha). LYP7 and S12, a monoclonal antibody directed against P-selectin immunoprecipitated the same band. Using ELISA assay, purified P-selectin was shown to bind LYP7 and S12 monoclonal antibodies. Binding sites of 125I-labelled LYP7, which was greatly increased on thrombin-stimulated (2 U/ml) washed platelets (10825 +/- 2886, mean +/- SD) Kd = 1.5 +/- 0.5 nM) compared to resting platelets (2801 +/- 1278, mean +/- SD) (Kd = 1.5 +/- 0.6 nM), was found to be normal on thrombin-stimulated platelets taken from a patient with grey platelet syndrome or a patient with Glanzmann thrombasthenia. LYP7 (IgG1, F(ab')2 or Fab fragments) inhibited ristocetin-induced platelet aggregation of platelets in a dose-dependent fashion without affecting the binding of von Willebrand (vWf) factor. However, agglutination of formaldehyde-fixed platelets induced by ristocetin was not affected by monoclonal antibody LYP7. In addition, the binding of thrombin-activated platelets to neutrophils was inhibited by monoclonal antibody LYP7. These results strongly suggest that P-selectin, by promoting cell-cell contact, may play an active role in platelet-platelet interactions. PMID:8603015

  15. Glycans and the platelet life cycle.

    PubMed

    Li, Renhao; Hoffmeister, Karin M; Falet, Hervé

    2016-09-01

    Platelet numbers are intricately regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. The growth factor thrombopoietin (TPO) drives platelet biogenesis by inducing megakaryocyte production. A recent study in mice identified a feedback mechanism by which clearance of aged, desialylated platelets stimulates TPO synthesis by hepatocytes. This new finding generated renewed interest in platelet clearance mechanisms. Here, different established and emerging mechanisms of platelet senescence and clearance will be reviewed with specific emphasis on the role of posttranslational modifications. PMID:27135356

  16. Systemic lupus erythematosus complicated by acquired von Willebrand's syndrome.

    PubMed

    Hong, Sc; Lee, Jh; Chi, Hs; Lee, Ck; Nah, Ss; Kim, Yg; Oh, Js; Moon, Hb; Yoo, B

    2008-09-01

    Haematological abnormalities are common in systemic lupus erythematosus (SLE). In some cases of acquired von Willebrand syndrome (AvWS), von Willebrand disease (vWD) is associated with autoimmune or lymphoproliferative disorders. In this study, we describe a 36-year-old woman with SLE and AvWS. The patient was referred to our hospital because of easy bruisability and recurrent vaginal bleeding. She had no history of bleeding tendency and no family history of bleeding diathesis, but she had a history of recurrent arthralgia, photosensitivity and sicca symptoms. Tests for antinuclear, anti-double stranded DNA, anticardiolipin and anti-beta2-glycoprotein I antibodies were all positive. Analysis of haemostatic parameters showed complete absence of von Willebrand factor ristocetin cofactor (vWF:Rco), von Willebrand antigen (vWF:Ag) and ristocetin-induced platelet aggregation (RIPA). Electrophoretic analysis of plasma showed a complete absence of high-molecular weight vWF multimer. The presence of antibody to vWF was detected by enzyme linked immunosorbent assay (ELISA). Treatment with corticosteroids improved SLE symptoms and corrected bleeding diasthesis. Also, the multimeric patterns of vWF became normalised and anti-vWF antibody disappeared. These findings indicated that this patient had SLE associated with AvWS, which was ameliorated by corticosteroid treatment. PMID:18755868

  17. Holiday Door Decorating Contest Brings Cheer | Poster

    Cancer.gov

    By Carolynne Keenan, Contributing Writer Other than the time of year, what do the following have in common: the leg lamp from the movie “A Christmas Story,” a compilation of silly holiday jokes, a gingerbread house, and Santa on a motorcycle? All four were among the individual door winners for the Holiday Door Decorating Contest, held at NCI at Frederick in December. Employees dressed up their office doors, hallways, and even stairwells to participate. Entries for the contest included individual office doors as well as groups. Some employees even “decked the halls” of whole office buildings to participate.

  18. Comparison between von Willebrand factor (VWF) and VWF antigen II in normal individuals and patients with von Willebrand disease.

    PubMed

    de Romeuf, C; Mazurier, C

    1998-07-01

    Von Willebrand disease is characterised by a quantitative (type 1) or qualitative (type 2) decrease in von Willebrand factor (vWF) a multimeric glycoprotein involved in primary haemostasis. The propeptide of von Willebrand, also named vWF antigen II (vWF:AgII), is released from platelets and endothelial cells and circulates in plasma as a glycoprotein of 100 kD. In the present study, we attempted to determine whether vWF:AgII level may provide information on the synthesis of vWF, specially in patients with von Willebrand disease (vWD). To elucidate that point, we developed an ELISA and quantify the vWF:AgII in normal individuals and in various vWD patients. The propeptide molar concentration was found to be 5 nM as compared to 31 nM for mature vWF. In normal individuals, the level of vWF:AgII was significantly decreased in females from O and A blood groups. In type 2 vWD patients the level of plasma vWF:AgII appears normal in the patients with normal level of platelet vWF. In type 2 B vWD characterised by increased affinity of mature vWF for platelet glycoprotein Ib, the vWF:AgII in contrast to the vWF antigen (vWF:Ag) was not decreased. In type 2A vWD patients the level of vWF:AgII was decreased in patients with absence of high molecular weight vWF in platelets and plasma but normal in patients with increased sensitivity to proteolysis. Finally, in type 1 vWD, some studied patients have a parallel decrease in vWF:AgII and vWF:Ag whereas in others, the vWF:Ag levels were much more affected than corresponding vWF:AgII levels, as observed in some type 2 vWD patients. Thus, in contrast to that already described, the plasma vWF:AgII level cannot discriminate type 1 from type 2 vWD patients. We conclude that the vWF:AgII measurement provides additional information on the mechanisms responsible for vWD and might also contribute to the classification of vWD patients. PMID:9684782

  19. Platelet aggregability and in vivo platelet deposition in patients with ischemic cerebrovascular disease--evaluation by indium-111-platelet scintigraphy

    SciTech Connect

    Isaka, Y.; Kimura, K.; Uehara, A.; Hashikawa, K.; Mieno, M.; Matsumoto, M.; Handa, N.; Nakabayashi, S.; Imaizumi, M.; Kamada, T. )

    1989-12-15

    In ischemic cerebrovascular disease, it is not clear whether platelet function in vitro actually reflects the situation in vivo. Using indium-111 platelet scintigraphy as a method for detecting platelet activation in vivo, we tried to elucidate this problem. Twenty eight patients with chronic stage of ischemic cerebrovascular disease (CVD) and 17 control subjects were examined. Platelet scintigrams were positive in 9 of 28 patients in CVD, while all were negative in control. A comparison of the results obtained from qualitative platelet imaging and platelet aggregability was performed to evaluate whether threshold aggregation concentration (TAC) grade differed across the three groups (control, CVD patients without platelet deposition and CVD patients with platelet deposition). CVD patients with platelet deposition showed a higher TAC than those patients who did not show platelet deposition (P less than 0.05) or control subjects without platelet deposition (P less than 0.05). These results suggest that some patients in chronic stages of CVD may have active platelet deposition on carotid atheromatous lesions, and presence of platelet deposition in vivo could contribute to reduce platelet reactivity in peripheral blood.

  20. Platelet aggregability and in vivo platelet deposition in patients with ischemic cerebrovascular disease--evaluation by indium-111-platelet scintigraphy.

    PubMed

    Isaka, Y; Kimura, K; Uehara, A; Hashikawa, K; Mieno, M; Matsumoto, M; Handa, N; Nakabayashi, S; Imaizumi, M; Kamada, T

    1989-12-15

    In ischemic cerebrovascular disease, it is not clear whether platelet function in vitro actually reflects the situation in vivo. Using indium-111 platelet scintigraphy as a method for detecting platelet activation in vivo, we tried to elucidate this problem. Twenty eight patients with chronic stage of ischemic cerebrovascular disease (CVD) and 17 control subjects were examined. Platelet scintigrams were positive in 9 of 28 patients in CVD, while all were negative in control. A comparison of the results obtained from qualitative platelet imaging and platelet aggregability was performed to evaluate whether threshold aggregation concentration (TAC) grade differed across the three groups (control, CVD patients without platelet deposition and CVD patients with platelet deposition). CVD patients with platelet deposition showed a higher TAC than those patients who did not show platelet deposition (P less than 0.05) or control subjects without platelet deposition (P less than 0.05). These results suggest that some patients in chronic stages of CVD may have active platelet deposition on carotid atheromatous lesions, and presence of platelet deposition in vivo could contribute to reduce platelet reactivity in peripheral blood. PMID:2633402

  1. Myeloperoxidase induces the priming of platelets.

    PubMed

    Kolarova, H; Klinke, A; Kremserova, S; Adam, M; Pekarova, M; Baldus, S; Eiserich, J P; Kubala, L

    2013-08-01

    The release of myeloperoxidase (MPO) from polymorphonuclear neutrophils is a hallmark of vascular inflammation and contributes to the pathogenesis of vascular inflammatory processes. However, the effects of MPO on platelets as a contributory mechanism in vascular inflammatory diseases remain unknown. Thus, MPO interaction with platelets and its effects on platelet function were examined. First, dose-dependent binding of MPO (between 1.7 and 13.8nM) to both human and mouse platelets was observed. This was in direct contrast to the absence of MPO in megakaryocytes. MPO was localized both on the surface of and inside platelets. Cytoskeleton inhibition did not prevent MPO localization inside the three-dimensional platelet structure. MPO peroxidase activity was preserved upon the MPO binding to platelets. MPO sequestered in platelets catabolized NO, documented by the decreased production of NO (on average, an approximately 2-fold decrease). MPO treatment did not affect the viability of platelets during short incubations; however, it decreased platelet viability after long-term storage for 7 days (an approximately 2-fold decrease). The activation of platelets by MPO was documented by an MPO-mediated increase in the expression of surface platelet receptors P-selectin and PECAM-1 (of about 5 to 20%) and the increased formation of reactive oxygen species (of about 15 to 200%). However, the activation was only partial, as MPO did not induce the aggregation of platelets nor potentiate platelet response to classical activators. Nor did MPO induce a significant release of the content of granules. The activation of platelets by MPO was connected with increased MPO-treated platelet interaction with polymorphonuclear leukocytes (an approximately 1.2-fold increase) in vitro. In conclusion, it can be suggested that MPO can interact with and activate platelets, which can induce priming of platelets, rather than the classical robust activation of platelets. This can contribute to the

  2. 21 CFR 109.16 - Ornamental and decorative ceramicware.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-PACKAGING MATERIAL General Provisions § 109.16 Ornamental and decorative ceramicware. (a) Lead is a toxic... food may result in the leaching of lead from the glaze or decoration into the food. The provisions of... Food Use. May Poison Food,” “Not for Food Use. Glaze contains lead. Food Use May Result in...

  3. 21 CFR 109.16 - Ornamental and decorative ceramicware.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-PACKAGING MATERIAL General Provisions § 109.16 Ornamental and decorative ceramicware. (a) Lead is a toxic... food may result in the leaching of lead from the glaze or decoration into the food. The provisions of... Food Use. May Poison Food,” “Not for Food Use. Glaze contains lead. Food Use May Result in...

  4. 21 CFR 109.16 - Ornamental and decorative ceramicware.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-PACKAGING MATERIAL General Provisions § 109.16 Ornamental and decorative ceramicware. (a) Lead is a toxic... food may result in the leaching of lead from the glaze or decoration into the food. The provisions of... Food Use. May Poison Food,” “Not for Food Use. Glaze contains lead. Food Use May Result in...

  5. 21 CFR 109.16 - Ornamental and decorative ceramicware.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-PACKAGING MATERIAL General Provisions § 109.16 Ornamental and decorative ceramicware. (a) Lead is a toxic... food may result in the leaching of lead from the glaze or decoration into the food. The provisions of... Food Use. May Poison Food,” “Not for Food Use. Glaze contains lead. Food Use May Result in...

  6. Geometric and Electronic Properties of Edge-decorated Graphene Nanoribbons

    PubMed Central

    Chang, Shen-Lin; Lin, Shih-Yang; Lin, Shih-Kang; Lee, Chi-Hsuan; Lin, Ming-Fa

    2014-01-01

    Edge-decorated graphene nanoribbons are investigated with the density functional theory; they reveal three stable geometric structures. The first type is a tubular structure formed by the covalent bonds of decorating boron or nitrogen atoms. The second one consists of curved nanoribbons created by the dipole-dipole interactions between two edges when decorated with Be, Mg, or Al atoms. The final structure is a flat nanoribbon produced due to the repulsive force between two edges; most decorated structures belong to this type. Various decorating atoms, different curvature angles, and the zigzag edge structure are reflected in the electronic properties, magnetic properties, and bonding configurations. Most of the resulting structures are conductors with relatively high free carrier densities, whereas a few are semiconductors due to the zigzag-edge-induced anti-ferromagnetism. PMID:25123103

  7. [Acquired von Willebrand syndrome].

    PubMed

    Franchini, Massimo

    2006-01-01

    Acquired von Willebrand syndrome (aVWS) is a rare, but probably underestimated, bleeding disorder that mimics the congenital form of von Willebrand disease (VWD) in terms of laboratory findings and clinical presentation. However, unlike congenital VWD, it arises in individuals with no personal or family history of bleeding. AVWS occurs in association with a variety of underlying disorders, including lymphoproliferative disorders, myeloproliferative disorders and cardiovascular diseases. The main pathogenic, clinical, laboratory and therapeutic aspects of this syndrome are concisely reported in this review. PMID:16913181

  8. Adsorption of anaphylatoxins and platelet-specific proteins by filtration of platelet concentrates with a polyester leukocyte reduction filter.

    PubMed

    Shimizu, T; Uchigiri, C; Mizuno, S; Kamiya, T; Kokubo, Y

    1994-01-01

    Anaphylatoxins generated during storage of platelet concentrates (PCs) may potentially have side effects on platelet transfusion. We evaluated the anaphylatoxin-scavenging abilities of white blood cell reduction filters. Among the commercially available filters for PCs, one made with polyester fiber (PL50) dramatically adsorbed C3a and C4a anaphylatoxins to the respective mean level of 1,721-208 ng/ml and 1,240-141 ng/ml in 3-day-old PCs. C3a and C4a were measured as the native and des Arg form of each complement by radioimmunoassay. C3a and C4a anaphylatoxins in the supernatant plasma fraction from 3-day-old PC again decreased from 1,136 to 114 ng/ml and from 1,086 to 65 ng/ml, respectively. The filter also adsorbed 85% of platelet factor 4 (PF4) and 31% of beta-thromboglobulin (beta-TG), which had been released from platelets into the plasma during storage. The plasma levels of adhesive proteins such as fibronectin, fibrinogen, and von Willebrand factor, and plasma lactate dehydrogenase activity did not decrease after filtration. Another polyester filter (PL5A), on the other hand, significantly increased C3a and C4a levels with filtration. In addition, there was no PF4 adsorption ability during the filtration. The filters for red cells (RC50, BPF4, and R500A) had no anaphylatoxin adsorption capabilities. The observed specific adsorption of anaphylatoxins might be attributed to the electrostatic force between the positively charged anaphylatoxins with high pI and the possibly negatively charged filter membranes. Since PF4 and beta-TG have positively charged moieties in the C-terminal position, the same adsorption mechanism might operate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8036783

  9. Platelet function defects in chronic alcoholism.

    PubMed Central

    Mikhailidis, D P; Jenkins, W J; Barradas, M A; Jeremy, J Y; Dandona, P

    1986-01-01

    Platelet function in alcoholic patients was assessed on admission and during abstinence in hospital. On admission platelets from these patients were significantly less responsive (percentage aggregation and thromboxane A2 release) to conventional in vitro aggregating agents (adrenaline, adenosine diphosphate, and collagen) than platelets from healthy, moderate drinkers. Initially, platelet counts in platelet rich plasma tended to be low and the Simplate II bleeding times frequently prolonged. Platelet aggregation and thromboxane A2 release, however, were inhibited even in patients with normal platelet counts on admission. Platelet aggregation and thromboxane A2 release returned to normal or became hyper-responsive during two to three weeks of abstinence. Platelet counts rose during this period, the largest responses occurring in those patients with the lowest counts on admission. Bleeding times reverted to normal during abstinence and correlated significantly with changes in platelet aggregation, thromboxane A2 release, and platelet count and with the estimated ethanol consumption during the week before admission. Chronic, heavy alcohol ingestion evidently exerts an inhibitory effect on platelet function even in the absence of alcohol in the blood, and this phenomenon is reversible on abstaining. The impaired platelet function, together with the reduced platelet count, may contribute to the bleeding diathesis associated with chronic alcoholism and to the increased incidence and recurrence of gastrointestinal haemorrhage associated with excessive alcohol intake. PMID:3094624

  10. von Willebrand Disease

    MedlinePlus

    ... have vWD, talk with your doctor before taking medicine for pain or fever. Don't take aspirin and ibuprofen ... bleeding. It's usually OK to take acetaminophen for pain or fever, since it has no effect on platelet function. Medicines for vWD Some people with more serious vWD ...

  11. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    A camerman catches Dr. Wernher Von Braun, Director of the Marshall Space Flight Center, his son, Peter, and daughter, Martgrit, as they arrive at the employee picnic held to celebrate man's first landing on the moon 6 days earlier. In the foreground is David R. Newby, Director of Administration and Technical Services at the Marshall Space Flight Center.

  12. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Shown viewing the Apollo telescope mockup are, from left to right, Charles Donlan, deputy associate administrator for manned space flight; Dr. Wernher Von Braun, Marshall Space Flight Center director; William Horton, astrionics lab; Dr. Thomas Paine, NASA deputy administrator; Warner Kuers, director of the ME lab.

  13. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Marshall Space Flight Center director Wernher Von Braun and his family were honored with a series of events prior to his relocation to Washington, D.C. where he was assigned duties at NASA headquarters as deputy associate administrator for planning. Here he is shown with General Richard Drury and Hazel Toftoy, widow of General H.N. Toftoy.

  14. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1968-01-01

    Dr. Wernher von Braun, Director of the Marshall Space Flight Center, explains the purpose of a thermal curtain in the mockup of a Saturn I workshop to U.S. Representative Armistead Seldon of Alabama. The Congressman visited the Marshall Center on March 2, 1968 to tour the workshop and to visit Marshall Center facilities.

  15. Dr. Wernher Von Braun

    NASA Technical Reports Server (NTRS)

    1968-01-01

    U.S. Representative Armistead Seldon (D.-Al) inspects the food preparation area of the Saturn I workshop mockup during a visit to the Marshall Space Flight Center. Explaining the operation of the food preparation area to the congressman is Dr. Wernher Von Braun, Marshall Space Flight Center director.

  16. Analytik von Lebensmittelallergenen

    NASA Astrophysics Data System (ADS)

    Demmel, Anja; Hahn, Alexandra

    Ansonsten harmlose Lebensmittel oder deren Bestandteile können bei von Lebensmittelallergien betroffenen Personen Überempfindlichkeitsreaktionen auslösen. Hierbei kann es sich um immunvermittelte Lebensmittelallergien oder um Intoleranzen gegenüber bestimmten Lebensmittelbestandteilen handeln. Ein Beispiel für Letzteres ist die Laktoseintoleranz, welche durch einen Enzymdefekt hervorgerufen wird [1]. Im Gegensatz hierzu handelt es sich bei Lebensmittelallergien um Sofortreaktionen, die durch IgE-Antikörper gegen Antigene aus den Lebensmitteln hervorgerufen werden und zu verschiedenen körperlichen Beschwerden führen können. Bei den Antigenen, welche von den von Allergikern produzierten IgE-Antikörpern erkannt werden, handelt es sich vor allem um Proteine [2]. Symptome IgE-vermittelter Reaktionen können zum Beispiel Hautausschlag, eine Schwellung der Schleimhäute oder das sogenannte orale Allergiesyndrom mit allergischen Reaktionen an der Mundschleimhaut und im Magen-Darm-Trakt sein [3]. Die hierbei auftretenden Beschwerden reichen von einem Brennen im Mund und einer Schwellung der Lippen und der Zunge bis zu Atemnot verursachenden Schwellungen im Kehlkopfbereich. In besonders schlimmen Fällen können allergische Reaktionen zu einem anaphylaktischen Schock und zum Tod durch Kreislaufversagen führen [4]. Während klassische Nahrungsallergene häufig komplexe Reaktionen zur Folge haben, ist bei Pollen-assoziierten Nahrungsmittelallergien das orale Allergiesyndrom vorherrschend.

  17. Acquired von Willebrand disease.

    PubMed

    Petrini, P

    1999-05-01

    Acquired von Willebrand disease (AvWD) is a syndrome that has clinical and laboratory features similar to hereditary vWD. In contrast to the latter it occurs in patients without a family history of previous bleeding tendency. PMID:23401904

  18. Dynamic light scattering can determine platelet function

    NASA Astrophysics Data System (ADS)

    Lee, Nathan

    2011-10-01

    Platelet transfusions are life-saving procedures for patients who are bleeding or undergoing chemotherapy. The effectiveness of transfusions depends on the number of platelets transfused and the platelet function. Platelet function correlates with proportion of discoid to activated platelets, morphology response to temperature stress, and inversely correlates with microparticle content. ThromboLUX is a novel device that determines platelet function by measuring all of these characteristics using dynamic light scattering (DLS). During periods of stress, such as decreased temperature, cytoskeletal rearrangements will cause normal, discoid platelets to activate and become spiny spheres. The formation of pseudopods of various lengths facilitates the clotting cascade and also increases the apparent size of platelets. ThromboLUX uses a 37-20-37 C temperature cycle that mimics the bleeding, storage, and transfusion process. As the temperature fluctuates, DLS will measure the changing platelet hydrodynamic radius and the size of any microparticles present. ThromboLUX analysis of platelet concentrates in vitro would allow determination of high platelet function units before transfusion and would therefore improve transfusion outcomes and patient safety. This study examined how DLS is able to distinguish between discoid and activated platelets as well as measure the parameters that contribute to high platelet function.

  19. Platelet function tests: a comparative review

    PubMed Central

    Paniccia, Rita; Priora, Raffaella; Alessandrello Liotta, Agatina; Abbate, Rosanna

    2015-01-01

    In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation – adhesion, shape change, release reaction, and aggregation – have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT) dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]). POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well-tried and innovative platelet function tests and their methodological features and clinical applications are considered. PMID:25733843

  20. 41 CFR 102-42.85 - What gifts or decorations must we report to GSA?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... decorations must we report to GSA? 102-42.85 Section 102-42.85 Public Contracts and Property Management... 42-UTILIZATION, DONATION, AND DISPOSAL OF FOREIGN GIFTS AND DECORATIONS Utilization of Foreign Gifts and Decorations § 102-42.85 What gifts or decorations must we report to GSA? You must report to...

  1. 41 CFR 102-42.85 - What gifts or decorations must we report to GSA?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... decorations must we report to GSA? 102-42.85 Section 102-42.85 Public Contracts and Property Management... 42-UTILIZATION, DONATION, AND DISPOSAL OF FOREIGN GIFTS AND DECORATIONS Utilization of Foreign Gifts and Decorations § 102-42.85 What gifts or decorations must we report to GSA? You must report to...

  2. 41 CFR 102-42.85 - What gifts or decorations must we report to GSA?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... decorations must we report to GSA? 102-42.85 Section 102-42.85 Public Contracts and Property Management... 42-UTILIZATION, DONATION, AND DISPOSAL OF FOREIGN GIFTS AND DECORATIONS Utilization of Foreign Gifts and Decorations § 102-42.85 What gifts or decorations must we report to GSA? You must report to...

  3. 41 CFR 102-42.85 - What gifts or decorations must we report to GSA?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... decorations must we report to GSA? 102-42.85 Section 102-42.85 Public Contracts and Property Management... 42-UTILIZATION, DONATION, AND DISPOSAL OF FOREIGN GIFTS AND DECORATIONS Utilization of Foreign Gifts and Decorations § 102-42.85 What gifts or decorations must we report to GSA? You must report to...

  4. 41 CFR 102-42.85 - What gifts or decorations must we report to GSA?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... decorations must we report to GSA? 102-42.85 Section 102-42.85 Public Contracts and Property Management... 42-UTILIZATION, DONATION, AND DISPOSAL OF FOREIGN GIFTS AND DECORATIONS Utilization of Foreign Gifts and Decorations § 102-42.85 What gifts or decorations must we report to GSA? You must report to...

  5. Desmopressin in vitro effects on platelet function, monitored with Multiplate, ROTEM and Sonoclot.

    PubMed

    Pearson, Kevin; Jensen, Hanna; Kander, Thomas; Schött, Ulf

    2016-07-01

    Background and aims The vasopressin analogue desmopressin has demonstrated efficacy in decreasing bleeding time by increasing the circulating levels of coagulation factor VIII and von Willebrand factor, but also by direct effects on platelets. Previous studies have demonstrated contrasting results regarding the effect of desmopressin on platelets in vitro. The aim of this study was to investigate the dose-response effects of in vitro desmopressin in whole blood. Our hypothesis was that desmopressin could increase platelet function in anticoagulated whole blood being stored up to 4 hours. Methods Desmopressin was administered with up to four different concentrations to venous whole blood, sampled with standard vacutainer tubes from 10 healthy volunteers after consent. Platelet function was analyzed with three different point-of-care techniques: Multiplate platelet aggregometry with adenosine diphosphate, collagen, thrombin receptor activating peptide-6, ristocetin and arachidonic acid agonists, tissue factor-activated thromboelastometry and Sonoclot glass bead viscoelastic coagulation tests at baseline and 4 hours later using different activator reagents. Results Thromboelastometry and Sonoclot did not show any significant change between baseline and 4 h later. A significant decrease in area under curve (AUC) could be seen with the Multiplate between baseline and after 4 h. Desmopressin did not improve any of these tests at baseline or during a 4 h storage and incubation period. Conclusion In vitro administered desmopressin could not increase normal platelet function or coagulation being measured with thromboelastometry and Sonoclot. Multiplate indicated decreased platelet aggregation over time, without any effect of in vitro added desmopressin. PMID:26923171

  6. Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate.

    PubMed Central

    Weiss, H J; Hawiger, J; Ruggeri, Z M; Turitto, V T; Thiagarajan, P; Hoffmann, T

    1989-01-01

    Platelet adhesion and thrombus formation on subendothelium, studied at a shear rate of 2,600 s-1, were inhibited by two synthetic peptides known to interact with GPIIb-IIIa. One peptide (HHLGGAKQAGDV) corresponds to the carboxyl terminal segment of the fibrinogen gamma-chain (gamma 400-411) and the other (RGDS) contains the amino acid sequence Arg-Gly-Asp (RGD) common to fibronectin, von Willebrand factor, vitronectin and the alpha-chain of fibrinogen. Neither platelet adhesion nor thrombus formation were decreased in a patient with severe congenital fibrinogen deficiency and this was equally true when his blood was further depleted of the small amounts of fibrinogen present utilizing an anti-fibrinogen antibody. In normal subjects, adhesion and thrombus formation were inhibited by the Fab' fragments of a monoclonal anti-GPIIb-IIIa antibody (LJ-CP8), which interferes with the interaction of platelets with all four adhesive proteins in both the fluid and solid phase. However, another anti-GPIIb-IIIa antibody (LJ-P5) that had minimal effects on the interaction of platelets with fibrinogen, but inhibited to varying degrees platelet interaction with other adhesive proteins, was equally effective. The findings demonstrate that, at a shear rate of 2,600 s-1, adhesive proteins other than fibrinogen are involved in GPIIb-IIIa-mediated platelet adhesion and thrombus formation on subendothelium. In addition, since LJ-P5 inhibited the binding of soluble von Willebrand factor and vitronectin, these adhesive proteins may be involved in platelet thrombus formation. In contrast to the results obtained at a shear rate of 2,600 s-1, fibrinogen could play a role in mediating platelet-platelet interactions with weak agonists or lower shear rates. PMID:2910912

  7. Characterization of aberrant splicing of von Willebrand factor in von Willebrand disease: an underrecognized mechanism.

    PubMed

    Hawke, Lindsey; Bowman, Mackenzie L; Poon, Man-Chiu; Scully, Mary-Frances; Rivard, Georges-Etienne; James, Paula D

    2016-07-28

    Approximately 10% of von Willebrand factor (VWF) gene mutations are thought to alter messenger RNA (mRNA) splicing through disruption of consensus splice sites. This mechanism is likely underrecognized and affected by mutations outside consensus splice sites. During VWF synthesis, splicing abnormalities lead to qualitative defects or quantitative deficiencies in VWF. This study investigated the pathologic mechanism acting in 3 von Willebrand disease (VWD) families with putative splicing mutations using patient-derived blood outgrowth endothelial cells (BOECs) and a heterologous human embryonic kidney (HEK 293(T)) cell model. The exonic mutation c.3538G>A causes 3 in-frame splicing variants (23del, 26del, and 23/26del) which cannot bind platelets, blood coagulation factor VIII, or collagen, causing VWD through dominant-negative intracellular retention of coexpressed wild-type (WT) VWF, and increased trafficking to lysosomes. Individuals heterozygous for the c.5842+1G>C mutation produce exon 33 skipping, exons 33-34 skipping, and WT VWF transcripts. Pathogenic intracellular retention of VWF lacking exons 33-34 causes their VWD. The branch site mutation c.6599-20A>T causes type 1 VWD through mRNA degradation of exon 38 skipping transcripts. Splicing ratios of aberrant transcripts and coexpressed WT were altered in the BOECs with exposure to shear stress. This study provides evidence of mutations outside consensus splice sites disrupting splicing and introduces the concept that VWF splicing is affected by shear stress on endothelial cells. PMID:27317792

  8. CD8(+) T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia.

    PubMed

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming

    2016-01-01

    In addition to antiplatelet autoantibodies, CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8(+) T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8(+) T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8(+) T cells than those without cytotoxicity and controls. In vitro, CD8(+) T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8(+) splenocytes were used. Platelets co-cultured with these CD8(+) splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8(+) splenocytes. These findings suggest that CD8(+) T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  9. CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia

    PubMed Central

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming

    2016-01-01

    In addition to antiplatelet autoantibodies, CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8+ T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8+ T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8+ T cells than those without cytotoxicity and controls. In vitro, CD8+ T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8+ splenocytes were used. Platelets co-cultured with these CD8+ splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8+ splenocytes. These findings suggest that CD8+ T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  10. Genetics Home Reference: gray platelet syndrome

    MedlinePlus

    ... to play a role in the formation of alpha-granules, which are sacs inside platelets that contain ... injury that causes bleeding, the proteins stored in alpha-granules help platelets stick to one another to ...

  11. [Assessment of platelet function in man].

    PubMed

    Gaussem, Pascale

    2006-01-01

    Assessment of platelet function was primarily designed to explore patients with hemostatic disorders, but is becoming important for the monitoring of anti platelet agents, mostly aspirin and clopidogrel. Beside platelet counting, morphological analysis and bleeding time, a number of dedicated platelet function instruments are now available, generally allowing a rapid evaluation of platelet function in whole blood. The other tests including aggregometry and ELISA measurement of activation markers are generally restricted to specialized laboratories. Although aggregometry is still considered as the "gold standard", the recently developed flow cytometric-based platelet function analysis provides a wide choice of tests that assess the number of surface receptors, the measure of secretion and aggregation, the quantification of microparticules and leukocyte-platelet aggregates. It also allows the measure of the function of the ADP receptor P2Y12 by the phosphorylation level of the VASP protein, method currently under evaluation to monitor the platelet response to clopidogrel treatment. PMID:17243268

  12. Effect of photodynamic therapy on mouse platelets

    NASA Astrophysics Data System (ADS)

    Zhou, Chuannong; Chi, Shunji; Deng, Jinsheng; Zhang, Hua; Liang, Junlin; Ha, Xian-wen

    1993-06-01

    Normal mice received hematoporphyrin derivative (HpD) i.v. prior to red light irradiation and the platelet-rich plasma was prepared and irradiated by red light. The platelets were processed for EM examination and stereological analysis. It was shown the 16 hrs after irradiation almost all platelets were necrotized; 8 hours after irradiation about one fourth of the platelets were necrotized and the remaining were considerably damaged. Immediately after irradiation a small number of platelets became necrotic and most other platelets were swollen and deformated, showing significantly increased mean area, perimeter and short axis, and mean cell volume and cell surface area. The findings indicate that platelets are highly sensitive to PDT action and can be directly and rapidly damaged by PDT even in the absence of vascular endothelial cells. The early platelet photoactivation may play an important role in the initiation of early vascular damage and microcirculatory alterations induced by PDT in vivo.

  13. Luminescence properties of lustre decorated majolica

    NASA Astrophysics Data System (ADS)

    Galli, A.; Martini, M.; Sibilia, E.; Padeletti, G.; Fermo, P.

    Luminescence measurements have been performed on several Italian Renaissance ceramic shards produced in central Italy, as well as on some others from Hispano-Moresque and Fatimid periods. The aim of this study was the characterisation of the raw materials used to manufacture lustre decorated majolica. At first, the thermoluminescence (TL) dating of all ceramic bodies was performed, because the shards lacked sure chronological attribution, having been provided by private collectors, or found during emergency restoration works or archaeological surveys. To characterise the defects and the recombination centers of the different components of the ceramics (ceramic body, glaze, glaze, and lustre), radioluminescence (RL) measurements have been performed on samples representative of each historical period. The dating results are reported, as well as the preliminary RL results.

  14. William Cowper and his decorated copperplate initials.

    PubMed

    Sanders, Mark A

    2005-01-01

    William Cowper was an 18th-century London surgeon/anatomist who made important contributions to several medical disciplines. He achieved lasting fame for describing the bulbourethral glands and lasting infamy for pirating plates for his anatomical atlas, the Anatomy of Humane Bodies. Cowper wrote the books and papers that taught the forerunners of today's surgeons and anatomists. His most famous pupil, the great surgeon William Cheselden, was one of the teachers of John Hunter, the founder of modern surgery. Cowper's magnificent atlas of human myology, the Myotomia Reformata, is a showcase for exquisitely rendered illustrations of muscles and bones. Cowper populated his masterwork with dozens of delightfully decorated initial letters depicting anatomical scenes. This article introduces readers to the long-forgotten William Cowper and exhibits his stunning historiated letters in all their glory. PMID:15672355

  15. Decorating Cutting as New Approach to Machine Tool System Dynamics

    NASA Astrophysics Data System (ADS)

    Murcinkova, Zuzana; Vasilko, Karol

    2014-12-01

    The paper presents so called decorating cutting focused on turning. It uses self-excited vibrations that are typical for turning and other types of cutting operations. The decorating turning do not utilize setting of unstable technological conditions of cutting process but it actively use the acting of cutting force on machine tool without generation of unwanted chatter vibrations. The special tool fixture was developed to utilize self-excited vibrations invoked by periodical changeability of cutting force by cutting process itself. Thus the typical texture of surface appears. The various macro/micro-textures of surfaces can be applied either for decorating purpose or for better holding of oil film.

  16. New treatment for low platelets.

    PubMed

    Grodeck, B

    1995-01-01

    The Food and Drug Administration (FDA) recently approved WinRho SD, a new treatment for immune thrombocytopenic purpura (ITP). A clinical trial in children with acute ITP found that WinRho SD is as effective as IVIG or prednisone, but less expensive and dramatically easier to administer. WinRho SD is the first polyclonal antibody product shown to increase platelets in ITP patients. Platelets usually rise within one to two days and peak within seven to fourteen days after initial therapy. On average, platelet levels are maintained for approximately thirty days. Each year, 50,000 people nationally suffer from ITP as a complication of HIV infection, while another 18,000 manifest the disease as a primary condition. PMID:11362579

  17. Mutational Constraints on Local Unfolding Inhibit the Rheological Adaptation of von Willebrand Factor.

    PubMed

    Tischer, Alexander; Campbell, James C; Machha, Venkata R; Moon-Tasson, Laurie; Benson, Linda M; Sankaran, Banumathi; Kim, Choel; Auton, Matthew

    2016-02-19

    Unusually large von Willebrand factor (VWF), the first responder to vascular injury in primary hemostasis, is designed to capture platelets under the high shear stress of rheological blood flow. In type 2M von Willebrand disease, two rare mutations (G1324A and G1324S) within the platelet GPIbα binding interface of the VWF A1 domain impair the hemostatic function of VWF. We investigate structural and conformational effects of these mutations on the A1 domain's efficacy to bind collagen and adhere platelets under shear flow. These mutations enhance the thermodynamic stability, reduce the rate of unfolding, and enhance the A1 domain's resistance to limited proteolysis. Collagen binding affinity is not significantly affected indicating that the primary stabilizing effect of these mutations is to diminish the platelet binding efficiency under shear flow. The enhanced stability stems from the steric consequences of adding a side chain (G1324A) and additionally a hydrogen bond (G1324S) to His(1322) across the β2-β3 hairpin in the GPIbα binding interface, which restrains the conformational degrees of freedom and the overall flexibility of the native state. These studies reveal a novel rheological strategy in which the incorporation of a single glycine within the GPIbα binding interface of normal VWF enhances the probability of local unfolding that enables the A1 domain to conformationally adapt to shear flow while maintaining its overall native structure. PMID:26677223

  18. Megakaryocyte rupture for acute platelet needs

    PubMed Central

    Stritt, Simon

    2015-01-01

    Circulating platelets were thought to arise solely from the protrusion and fragmentation of megakaryocyte cytoplasm. Now, Nishimura et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201410052) show that platelet release from megakaryocytes can be induced by interleukin-1α (IL-1α) via a new rupture mechanism, which yields higher platelet numbers, occurs independently of the key regulator of megakaryopoiesis thrombopoietin, and may occur during situations of acute platelet need. PMID:25963815

  19. Megakaryocyte rupture for acute platelet needs.

    PubMed

    Nieswandt, Bernhard; Stritt, Simon

    2015-05-11

    Circulating platelets were thought to arise solely from the protrusion and fragmentation of megakaryocyte cytoplasm. Now, Nishimura et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201410052) show that platelet release from megakaryocytes can be induced by interleukin-1α (IL-1α) via a new rupture mechanism, which yields higher platelet numbers, occurs independently of the key regulator of megakaryopoiesis thrombopoietin, and may occur during situations of acute platelet need. PMID:25963815

  20. Platelet Activation: The Mechanisms and Potential Biomarkers

    PubMed Central

    Yun, Seong-Hoon; Sim, Eun-Hye; Goh, Ri-Young; Park, Joo-In

    2016-01-01

    Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, mediating inflammatory and immunomodulatory activities. Our knowledge about how platelets modulate inflammatory and immunity has greatly improved in recent years. In this review, we discuss recent advances in the pathways of platelet activation and potential application of platelet activation biomarkers to diagnosis and prediction of disease states. PMID:27403440

  1. Antiplatelet drugs in patients with enhanced platelet turnover: biomarkers versus platelet function testing.

    PubMed

    Freynhofer, Matthias K; Gruber, Susanne C; Grove, Erik L; Weiss, Thomas W; Wojta, Johann; Huber, Kurt

    2015-08-31

    Platelets are key players in atherothrombosis. Antiplatelet therapy comprising aspirin alone or with P2Y12-inhibitors are effective for prevention of atherothrombotic complications. However, there is interindividual variability in the response to antiplatelet drugs, leaving some patients at increased risk of recurrent atherothrombotic events. Several risk factors associated with high on-treatment platelet reactivity (HTPR), including elevated platelet turnover, have been identified. Platelet turnover is adequately estimated from the fraction of reticulated platelets. Reticulated platelets are young platelets, characterised by residual messenger RNA. They are larger, haemostatically more active and there is evidence that platelet turnover is a causal and prognostic factor in atherothrombotic disease. Whether platelet turnover per se represents a key factor in pathogenesis, progression and prognosis of atherothrombotic diseases (with focus on acute coronary syndromes) or whether it merely facilitates insufficient platelet inhibition will be discussed in this state-of-the art review. PMID:26272640

  2. Dr. von Braun at 'Wernher von Braun Day' Celebration

    NASA Technical Reports Server (NTRS)

    1970-01-01

    In 1970 Marshall Space Flight Center (MSFC) Director Dr. Wernher von Braun (right) was reassigned to NASA Headquarters to serve as Deputy Associate Administrator for Plarning. Prior to his transfer, Dr. von Braun was honored for his career in Huntsville, Alabama, with the celebration of 'Wernher von Braun Day.' Among those participating were Alabama Governor Albert Brewer (left) and Alabama Senator John Sparkman (center). (Courtesy of Huntsville/Madison County Public library)

  3. Von Willebrand factor in patients on mechanical circulatory support – a double-edged sword between bleeding and thrombosis

    PubMed Central

    Kaczmarski, Jacek; Pacholewicz, Jerzy; Zakliczynski, Michal; Gasior, Mariusz; Zembala, Marian

    2015-01-01

    Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF. PMID:26702279

  4. Chitosan scaffold enhances growth factor release in wound healing in von Willebrand disease

    PubMed Central

    Periayah, Mercy Halleluyah; Halim, Ahmad Sukari; Saad, Arman Zaharil Mat; Yaacob, Nik Soriani; Hussein, Abdul Rahim; Karim, Faraizah Abdul; Rashid, Ahmad Hazri Abdul; Ujang, Zanariah

    2015-01-01

    Chitosan-derived biomaterials have been reported to adhere when in contact with blood by encouraging platelets to adhere, activate and aggregate at the sites of vascular injury, thus enhanced wound healing capacity. This study investigated platelet morphology changes and the expression level of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor-AB (PDGF-AB) in the adherence of two different types of chitosans in von Willebrand disease (vWD): N,O-carboxymethylchitosan (NO-CMC) and oligo-chitosan (O-C). Fourteen vWD voluntary subjects were recruited, and they provided written informed consent. Scanning electron microscopy and enzyme-linked immunosorbent assay test procedures were employed to achieve the objective of the study. The results suggest that the O-C group showed dramatic changes in the platelet’s behaviors. Platelets extended filopodia and generated lamellipodia, leading to the formation of grape-like shaped aggregation. The platelet aggregation occurred depending on the severity of vWD. O-C was bound to platelets on approximately 90% of the surface membrane in vWD type 1; there was 70% and 50% coverage in vWD type II and III, respectively. The O-C chitosan group showed an elevated expression level of TGF-β1 and PDGF-AB. This finding suggests that O-C stimulates these mediators from the activated platelets to the early stage of restoring the damaged cells and tissues. This study demonstrated that the greater expression level of O-C assists in mediating the cytokine complex networks of TGF-β1 and PDGF-AB and induces platelet activities towards wound healing in vWD. With a better understanding of chitosan’s mechanisms of action, researchers are able to accurately develop novel therapies to prevent hemorrhage. PMID:26629055

  5. Exploratory studies of extended storage of apheresis platelets in a platelet additive solution (PAS).

    PubMed

    Slichter, Sherrill J; Corson, Jill; Jones, Mary Kay; Christoffel, Todd; Pellham, Esther; Bailey, S Lawrence; Bolgiano, Doug

    2014-01-01

    To evaluate the poststorage viability of apheresis platelets stored for up to 18 days in 80% platelet additive solution (PAS)/20% plasma, 117 healthy subjects donated platelets using the Haemonetics MCS+, COBE Spectra (Spectra), or Trima Accel (Trima) systems. Control platelets from the same subjects were compared with their stored test PAS platelets by radiolabeling their stored and control platelets with either (51)chromium or (111)indium. Trima platelets met Food and Drug Administration poststorage platelet viability criteria for only 7 days vs almost 13 days for Haemonetics platelets; ie, platelet recoveries after these storage times averaged 44 ± 3% vs 49 ± 3% and survivals were 5.4 ± 0.3 vs 4.6 ± 0.3 days, respectively. The differences in storage duration are likely related to both the collection system and the storage bag. The Spectra and Trima platelets were hyperconcentrated during collection, and PAS was added, whereas the Haemonetics platelets were elutriated with PAS, which may have resulted in less collection injury. When Spectra and Trima platelets were stored in Haemonetics' bags, poststorage viability was significantly improved. Platelet viability is better maintained in vitro than in vivo, allowing substantial increases in platelet storage times. However, implementation will require resolution of potential bacterial overgrowth during storage. PMID:24258816

  6. Detail view of the decorative arched concrete railing with bushhammered ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail view of the decorative arched concrete railing with bush-hammered inset panels - Pamelia Creek Bridge, Spanning Pamelia Creek at Milepoint 62.78 on North Santiam Highway (OR22), Marion Forks, Linn County, OR

  7. Detail of front west entry showing telescoping pilasters and decorative ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of front west entry showing telescoping pilasters and decorative crawl space vents, facing east. - Albrook Air Force Station, Dispensary, East side of Canfield Avenue, Balboa, Former Panama Canal Zone, CZ

  8. Transport properties of zigzag graphene nanoribbon decorated with copper clusters

    SciTech Connect

    Berahman, M.; Sheikhi, M. H.

    2014-09-07

    Using non-equilibrium green function with density functional theory, the present study investigates the transport properties of decorated zigzag graphene nanoribbon with a copper cluster. We have represented the decoration of zigzag graphene nanoribbon with single copper atom and cluster containing two and three copper atoms. In all the cases, copper atoms tend to occupy the edge state. In addition, we have shown that copper can alter the current-voltage characteristic of zigzag graphene nanoribbon and create new fluctuations and negative differential resistance. These alternations are made due to discontinuity in the combination of orbitals along the graphene nanoribbon. Decoration alters these discontinuities and creates more visible fluctuations. However, in low bias voltages, the changes are similar in all the cases. The study demonstrates that in the decorated zigzag graphene nanoribbon, the edge states are the main states for transporting electron from one electrode to another.

  9. 11. BASRELIEF DECORATION, 'REGENERATION,' MURAL COMMEMORATING THE REBUILDING OF CHICAGO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. BAS-RELIEF DECORATION, 'REGENERATION,' MURAL COMMEMORATING THE REBUILDING OF CHICAGO AFTER THE GREAT FIRE - Chicago River Bascule Bridge, Michigan Avenue, Spanning Chicago River at North Michigan Avenue, Chicago, Cook County, IL

  10. 'Colored' and Decorative Contact Lenses: A Prescription Is a Must

    MedlinePlus

    ... labeling. (See additional information about cleaning solutions with hydrogen peroxide on the FDA website.) See your eye ... For More Information Decorative Contact Lenses Contact Lenses Hydrogen Peroxide Solution Related Consumer Updates Focusing on Contact ...

  11. Detail view of the Ten Mile Creek Bridge decorative concrete ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail view of the Ten Mile Creek Bridge decorative concrete arched balustrade at southeast corner of bridge, view looking east. - Ten Mile Creek Bridge, Spanning Ten Mile Creek on Oregon Coast Highway, Yachats, Lincoln County, OR

  12. Detail of decorative panel featuring a monkey at Ten Mile ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of decorative panel featuring a monkey at Ten Mile River Playground comfort station, looking northwest. - Henry Hudson Parkway, Extending 11.2 miles from West 72nd Street to Bronx-Westchester border, New York County, NY

  13. Detail view of the decorative element at the peak of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail view of the decorative element at the peak of the gabled dormer of the northwest corner bay of the west façade - Oregon State Fairgrounds Grandstand, 2330 Seventeenth Avenue, Northeast, Salem, Marion, OR

  14. 42. DETAIL OF TRIPLE WINDOW ELEMENT WITH DECORATIVE BRICK SURROUND, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    42. DETAIL OF TRIPLE WINDOW ELEMENT WITH DECORATIVE BRICK SURROUND, ON EAST SIDE OF 1931 SECTION, TAKEN FROM THE EAST. - James Russell Lowell Elementary School, 4501 Crittenden Drive, Louisville, Jefferson County, KY

  15. 36. DETAIL OF WINDOW ELEMENT WITH DECORATIVE BRICK PATTERN ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    36. DETAIL OF WINDOW ELEMENT WITH DECORATIVE BRICK PATTERN ON MAIN FRONT OF 1931 SECTION, TAKEN FROM THE NORTH. - James Russell Lowell Elementary School, 4501 Crittenden Drive, Louisville, Jefferson County, KY

  16. 9. BASRELIEF DECORATION, 'DEFENSE', MURAL COMMEMORATING THE DEFENSE OF FORT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. BAS-RELIEF DECORATION, 'DEFENSE', MURAL COMMEMORATING THE DEFENSE OF FORT DEARBORN - Chicago River Bascule Bridge, Michigan Avenue, Spanning Chicago River at North Michigan Avenue, Chicago, Cook County, IL

  17. 8. BASRELIEF DECORATION, 'THE DISCOVERS', MURAL COMMEMORATING JOLLIET, FATHER MARQUETTE, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. BAS-RELIEF DECORATION, 'THE DISCOVERS', MURAL COMMEMORATING JOLLIET, FATHER MARQUETTE, LASALLE AND TONTY - Chicago River Bascule Bridge, Michigan Avenue, Spanning Chicago River at North Michigan Avenue, Chicago, Cook County, IL

  18. Stable parabolic Higgs bundles as asymptotically stable decorated swamps

    NASA Astrophysics Data System (ADS)

    Beck, Nikolai

    2016-06-01

    Parabolic Higgs bundles can be described in terms of decorated swamps, which we studied in a recent paper. This description induces a notion of stability of parabolic Higgs bundles depending on a parameter, and we construct their moduli space inside the moduli space of decorated swamps. We then introduce asymptotic stability of decorated swamps in order to study the behaviour of the stability condition as one parameter approaches infinity. The main result is the existence of a constant, such that stability with respect to parameters greater than this constant is equivalent to asymptotic stability. This implies boundedness of all decorated swamps which are semistable with respect to some parameter. Finally, we recover the usual stability condition of parabolic Higgs bundles as asymptotic stability.

  19. Heteroatom substituted and decorated graphene: preparation and applications.

    PubMed

    Chen, Nan; Huang, Xianke; Qu, Liangti

    2015-12-28

    Graphenes have attracted increasing attention in a variety of scientific fields. By modification with foreign elements such as boron, sulfur, and fluorine, their unique electronic and spin structures can be effectively tuned and the substituted or decorated graphenes as promising materials have been successfully employed in electrical, optical, and catalytic fields. In this review, we summarize the recent advances of these newly derived heteroatom substituted or decorated graphenes with an emphasis on the preparation methods, applications and the mechanisms of action. We are hopeful for future developments of heteroatom substituted or decorated graphenes in precisely controlled substitution methods, and finding wide applications of heteroatom substituted or decorated graphenes in many different fields. PMID:26465923

  20. DETAIL OF FRONT ENTRY. SHOWING THE KNEE BRACES AND DECORATIVE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF FRONT ENTRY. SHOWING THE KNEE BRACES AND DECORATIVE CUT RAFTER TAILS. VIEW FACING EAST. - Hickam Field, Fort Kamehameha Officers' Housing Type Z, 19 Worchester Avenue, Honolulu, Honolulu County, HI

  1. DETAIL OF FRONT ENTRY. SHOWING KNEE BRACES AND DECORATIVE CUT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF FRONT ENTRY. SHOWING KNEE BRACES AND DECORATIVE CUT RAFTERS. PILASTERS, AND LAVA ROCK CHEEK CHEEK WALLS. VIEW FACING NORTH. - Hickam Field, Fort Kamehameha Officers' Housing Type Y, 27 Worchester Avenue, Honolulu, Honolulu County, HI

  2. DETAIL VIEW OF END OF TRUSS SHOWING CONNECTION OF DECORATIVE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL VIEW OF END OF TRUSS SHOWING CONNECTION OF DECORATIVE "KNEE", RAILING ENDPOST AND UPPER AND LOWER CHORDS - Scarlets Mill Bridge, Spanning former Reading Railroad, Scarlets Mill, Berks County, PA

  3. ZnO nanorods decorated with ZnS nanoparticles

    SciTech Connect

    Joicy, S.; Sivakumar, P.; Thangadurai, P.; Ponpandian, N.

    2015-06-24

    In this study, ZnO nanorods (NRs) and ZnS nanoparticles decorated ZnO-NRs were prepared by a combination of hydrothermal and hydrolysis method. Structural and optical properties of the samples were studied by XRD, FE-SEM, UV-Vis DRS and photoluminescence spectroscopy. Microscopy analysis revealed that the diameter of ZnO-NRs was ∼500 nm and the length was ranging from a few hundred nm to several micrometers and their surface was decorated with ZnS nanoparticles. UV-Vis DRS showed the absorption of ZnS decorated ZnO-NRs was blue shifted with respect to pure ZnO-NRs which enhanced the separation of electron-hole pairs. PL spectrum of ZnS decorated ZnO-NRs showed a decrease in intensity of UV and green emissions with the appearance of blue emission at 436 nm.

  4. 4. Photocopy of photograph, date unknown DETAIL, DECORATIVE SWAG OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Photocopy of photograph, date unknown DETAIL, DECORATIVE SWAG OF EARS OF CORN - Thomas Asylum for Orphan & Destitute Indians, Dining Hall, Route 438, Cattaraugas Reservation, Irving, Chautauqua County, NY

  5. Perspective view of the front elevation (note: decorative details such ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Perspective view of the front elevation (note: decorative details such as the brackets underpinning the deep cornice on the porch and house) - Philip T. Berry House, 1402 Thirty-first Street, Northwest, Washington, District of Columbia, DC

  6. 4. DETAIL OF TERRA COTTA DECORATION AT TOP OF EXPRESSED ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. DETAIL OF TERRA COTTA DECORATION AT TOP OF EXPRESSED COLUMN, JUST ABOVE FOURTH FLOOR WINDOWS ON SOUTH FRONT FACADE - John D. Van Allen & Son Store, South Fifth Avenue & Second Street, Clinton, Clinton County, IA

  7. 3. DETAIL OF TERRA COTTA DECORATION ON LOWER END OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. DETAIL OF TERRA COTTA DECORATION ON LOWER END OF EXPRESSED COLUMN, JUST BELOW SECOND FLOOR ON SOUTH FRONT FACADE - John D. Van Allen & Son Store, South Fifth Avenue & Second Street, Clinton, Clinton County, IA

  8. Calcium decorated and doped phosphorene for gas adsorption

    NASA Astrophysics Data System (ADS)

    Lalitha, Murugan; Nataraj, Yuvarani; Lakshmipathi, Senthilkumar

    2016-07-01

    In this paper, we present the results from first-principles study based on the electronic structure and adsorption characteristics of CH4, CO2, H2 and NH3 adsorbed on Ca decorated/doped phosphorene. Our study finds that phosphorene exhibits n-type behaviour on decorating calcium, and p-type on doping calcium. Gas molecules are physisorbed on both pristine and calcium-mediated phosphorene, visible through their lower binding energy and charge transfer values. Ca decorated phosphorene is suitable for hydrogen storage due to its higher binding energy for H2. Ca doped structures shows increased binding affinity towards CH4 and NH3 in zigzag1 direction and armchair directions respectively. The extracts of our study implies that Ca doped phosphorene possess increased binding affinity towards gas molecules, and the results are highly helpful for gas adsorption and to design gas sensors based on calcium doped or decorated phosphorene.

  9. 72. 451 MADISON AVENUE, GRAND STAIR, ZODIAC CLOCK WITH DECORATIVE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    72. 451 MADISON AVENUE, GRAND STAIR, ZODIAC CLOCK WITH DECORATIVE CARVING BY STANFORD WHITE AND AUGUSTUS SAINT-GAUDENS - Villard Houses, 451-457 Madison Avenue & 24 East Fifty-first Street, New York County, NY

  10. 11. DETAIL OF TERRACOTTA DECORATION, SHOWING SCROLL CONSOLE, WAVE ORNAMENT, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. DETAIL OF TERRACOTTA DECORATION, SHOWING SCROLL CONSOLE, WAVE ORNAMENT, EGG-AND-DART, NYMPH HEADS AND FOLIATE PATTERN AROUND WINDOWS - City Hall, Atlantic & Tennessee Avenues, Atlantic City, Atlantic County, NJ