Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 32

Publication Record

Connections

Platelet-Based Drug Delivery for Cancer Applications.
Ortiz-Otero N, Mohamed Z, King MR
(2018) Adv Exp Med Biol 1092: 235-251
MeSH Terms: Blood Platelets, Drug Delivery Systems, Hemostasis, Humans, Male, Neoplasm Metastasis, Neoplasms
Show Abstract · Added April 15, 2019
Platelets can be considered as the "guardian of hemostasis" where their main function is to maintain vascular integrity. In pathological conditions, the hemostatic role of platelets may be hijacked to stimulate disease progression. In 1865, Armand Trousseau was a pioneer in establishing the platelet-cancer metastasis relationship, which he eventually termed as Trousseau's Syndrome to describe the deregulation of the hemostasis-associated pathways induced by cancer progression (Varki, Blood. 110(6):1723-9, 2007). Since these early studies, there has been an increase in experimental evidence not only to elucidate the role of platelets in cancer metastasis but also to create novel cancer therapies by targeting the platelet's impact in metastasis. In this chapter, we discuss the contribution of platelets in facilitating tumor cell transit from the primary tumor to distant metastatic sites as well as novel cancer therapies based on platelet interactions.
0 Communities
1 Members
0 Resources
7 MeSH Terms
α2β1 Integrin.
Madamanchi A, Santoro SA, Zutter MM
(2014) Adv Exp Med Biol 819: 41-60
MeSH Terms: Animals, Hemostasis, Humans, Immunity, Innate, Integrin alpha2beta1, Neovascularization, Physiologic, Protein Structure, Tertiary, Signal Transduction, Wound Healing
Show Abstract · Added February 12, 2015
The α2β1 integrin, also known as VLA-2, GPIa-IIa, CD49b, was first identified as an extracellular matrix receptor for collagens and/or laminins [55, 56]. It is now recognized that the α2β1 integrin serves as a receptor for many matrix and nonmatrix molecules [35, 79, 128]. Extensive analyses have clearly elucidated the α2 I domain structural motifs required for ligand binding, and also defined distinct conformations that lead to inactive, partially active or highly active ligand binding [3, 37, 66, 123, 136, 137, 140]. The mechanisms by which the α2β1 integrin plays a critical role in platelet function and homeostasis have been carefully defined via in vitro and in vivo experiments [76, 104, 117, 125]. Genetic and epidemiologic studies have confirmed human physiology and disease states mediated by this receptor in immunity, cancer, and development [6, 20, 21, 32, 43, 90]. The role of the α2β1 integrin in these multiple complex biologic processes will be discussed in the chapter.
1 Communities
1 Members
0 Resources
9 MeSH Terms
A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects.
Shameer K, Denny JC, Ding K, Jouni H, Crosslin DR, de Andrade M, Chute CG, Peissig P, Pacheco JA, Li R, Bastarache L, Kho AN, Ritchie MD, Masys DR, Chisholm RL, Larson EB, McCarty CA, Roden DM, Jarvik GP, Kullo IJ
(2014) Hum Genet 133: 95-109
MeSH Terms: Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Chromosomes, Human, Female, Genetic Loci, Genetic Pleiotropy, Genome-Wide Association Study, Hemostasis, Humans, Male, Mean Platelet Volume, Meta-Analysis as Topic, Middle Aged, Phenotype, Platelet Count, Polymorphism, Single Nucleotide, Thrombopoiesis
Show Abstract · Added March 7, 2014
Platelets are enucleated cell fragments derived from megakaryocytes that play key roles in hemostasis and in the pathogenesis of atherothrombosis and cancer. Platelet traits are highly heritable and identification of genetic variants associated with platelet traits and assessing their pleiotropic effects may help to understand the role of underlying biological pathways. We conducted an electronic medical record (EMR)-based study to identify common variants that influence inter-individual variation in the number of circulating platelets (PLT) and mean platelet volume (MPV), by performing a genome-wide association study (GWAS). We characterized genetic variants associated with MPV and PLT using functional, pathway and disease enrichment analyses; we assessed pleiotropic effects of such variants by performing a phenome-wide association study (PheWAS) with a wide range of EMR-derived phenotypes. A total of 13,582 participants in the electronic MEdical Records and GEnomic network had data for PLT and 6,291 participants had data for MPV. We identified five chromosomal regions associated with PLT and eight associated with MPV at genome-wide significance (P < 5E-8). In addition, we replicated 20 SNPs [out of 56 SNPs (α: 0.05/56 = 9E-4)] influencing PLT and 22 SNPs [out of 29 SNPs (α: 0.05/29 = 2E-3)] influencing MPV in a published meta-analysis of GWAS of PLT and MPV. While our GWAS did not find any new associations, our functional analyses revealed that genes in these regions influence thrombopoiesis and encode kinases, membrane proteins, proteins involved in cellular trafficking, transcription factors, proteasome complex subunits, proteins of signal transduction pathways, proteins involved in megakaryocyte development, and platelet production and hemostasis. PheWAS using a single-SNP Bonferroni correction for 1,368 diagnoses (0.05/1368 = 3.6E-5) revealed that several variants in these genes have pleiotropic associations with myocardial infarction, autoimmune, and hematologic disorders. We conclude that multiple genetic loci influence interindividual variation in platelet traits and also have significant pleiotropic effects; the related genes are in multiple functional pathways including those relevant to thrombopoiesis.
0 Communities
2 Members
0 Resources
19 MeSH Terms
Intraoperative use of low-dose recombinant activated factor VII during thoracic aortic operations.
Andersen ND, Bhattacharya SD, Williams JB, Fosbol EL, Lockhart EL, Patel MB, Gaca JG, Welsby IJ, Hughes GC
(2012) Ann Thorac Surg 93: 1921-8; discussion 1928-9
MeSH Terms: Aged, Aorta, Thoracic, Blood Coagulation Tests, Blood Transfusion, Blood Vessel Prosthesis Implantation, Cardiopulmonary Bypass, Cohort Studies, Critical Pathways, Dose-Response Relationship, Drug, Factor VIIa, Female, Heart Arrest, Induced, Hemostasis, Surgical, Hospital Costs, Humans, Intraoperative Period, Male, Matched-Pair Analysis, Middle Aged, Postoperative Hemorrhage, Propensity Score, Recombinant Proteins
Show Abstract · Added June 14, 2016
BACKGROUND - Numerous studies have supported the effectiveness of recombinant activated factor VII (rFVIIa) for the control of bleeding after cardiac procedures; however safety concerns persist. Here we report the novel use of intraoperative low-dose rFVIIa in thoracic aortic operations, a strategy intended to improve safety by minimizing rFVIIa exposure.
METHODS - Between July 2005 and December 2010, 425 consecutive patients at a single referral center underwent thoracic aortic operations with cardiopulmonary bypass (CPB); 77 of these patients received intraoperative low-dose rFVIIa (≤60 μg/kg) for severe coagulopathy after CPB. Propensity matching produced a cohort of 88 patients (44 received intraoperative low-dose rFVIIa and 44 controls) for comparison.
RESULTS - Matched patients receiving intraoperative low-dose rFVIIa got an initial median dose of 32 μg/kg (interquartile range [IQR], 16-43 μg/kg) rFVIIa given 51 minutes (42-67 minutes) after separation from CPB. Patients receiving intraoperative low-dose rFVIIa demonstrated improved postoperative coagulation measurements (partial thromboplastin time 28.6 versus 31.5 seconds; p=0.05; international normalized ratio, 0.8 versus 1.2; p<0.0001) and received 50% fewer postoperative blood product transfusions (2.5 versus 5.0 units; p=0.05) compared with control patients. No patient receiving intraoperative low-dose rFVIIa required postoperative rFVIIa administration or reexploration for bleeding. Rates of stroke, thromboembolism, myocardial infarction, and other adverse events were equivalent between groups.
CONCLUSIONS - Intraoperative low-dose rFVIIa led to improved postoperative hemostasis with no apparent increase in adverse events. Intraoperative rFVIIa administration in appropriately selected patients may correct coagulopathy early in the course of refractory blood loss and lead to improved safety through the use of smaller rFVIIa doses. Appropriately powered randomized studies are necessary to confirm the safety and efficacy of this approach.
Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
22 MeSH Terms
Multiple biomarkers and risk of clinical and subclinical vascular brain injury: the Framingham Offspring Study.
Pikula A, Beiser AS, DeCarli C, Himali JJ, Debette S, Au R, Selhub J, Toffler GH, Wang TJ, Meigs JB, Kelly-Hayes M, Kase CS, Wolf PA, Vasan RS, Seshadri S
(2012) Circulation 125: 2100-7
MeSH Terms: Aged, Albuminuria, Biomarkers, Blood Proteins, Brain, Brain Injuries, Cohort Studies, Creatinine, Endothelium, Vascular, Female, Hemostasis, Homocysteine, Hormones, Humans, Incidence, Inflammation, Ischemic Attack, Transient, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Prospective Studies, Risk, Stroke, United States
Show Abstract · Added April 15, 2014
BACKGROUND - Several biomarkers have been individually associated with vascular brain injury, but no prior study has explored the simultaneous association of a biologically plausible panel of biomarkers with the incidence of stroke/transient ischemic attack and the prevalence of subclinical brain injury.
METHODS AND RESULTS - In 3127 stroke-free Framingham offspring (age, 59±10 years; 54% female), we related a panel of 8 biomarkers assessing inflammation (C-reactive protein), hemostasis (D-dimer and plasminogen activator inhibitor-1), neurohormonal activity (aldosterone-to-renin ratio, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptides), and endothelial function (homocysteine and urinary albumin/creatinine ratio) measured at the sixth examination (1995-1998) to risk of incident stroke/transient ischemic attack. In a subset of 1901 participants with available brain magnetic resonance imaging (1999-2005), we further related these biomarkers to total cerebral brain volume, covert brain infarcts, and large white-matter hyperintensity volume. During a median follow-up of 9.2 years, 130 participants experienced incident stroke/transient ischemic attack. In multivariable analyses adjusted for stroke risk factors, the biomarker panel was associated with incident stroke/transient ischemic attack and with total cerebral brain volume (P<0.05 for both) but not with covert brain infarcts or white-matter hyperintensity volume (P>0.05). In backward elimination analyses, higher log-B-type natriuretic peptide (hazard ratio, 1.39 per 1-SD increment; P=0.002) and log-urinary albumin/creatinine ratio (hazard ratio, 1.31 per 1-SD increment; P=0.004) were associated with increased risk of stroke/transient ischemic attack and improved risk prediction compared with the Framingham Stroke Risk Profile alone; when the <5%, 5% to 15%, or >15% 10-year risk category was used, the net reclassification index was 0.109 (P=0.037). Higher C-reactive protein (β=-0.21 per 1-SD increment; P=0.008), D-dimer (β=-0.18 per 1-SD increment; P=0.041), total homocysteine (β=-0.21 per 1-SD increment; P=0.005), and urinary albumin/creatinine ratio (β=-0.15 per 1-SD increment; P=0.042) were associated with lower total cerebral brain volume.
CONCLUSION - In a middle-aged community sample, we identified multiple biomarkers that were associated with clinical and subclinical vascular brain injury and could improve risk stratification.
0 Communities
1 Members
0 Resources
25 MeSH Terms
Selective depletion of plasma prekallikrein or coagulation factor XII inhibits thrombosis in mice without increased risk of bleeding.
Revenko AS, Gao D, Crosby JR, Bhattacharjee G, Zhao C, May C, Gailani D, Monia BP, MacLeod AR
(2011) Blood 118: 5302-11
MeSH Terms: Animals, Disease Models, Animal, Factor XII, Factor XII Deficiency, Gene Knockdown Techniques, Hemorrhage, Hemostasis, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Oligonucleotides, Antisense, Prekallikrein, RNA, Messenger, Risk Factors, Thrombosis
Show Abstract · Added May 19, 2014
Recent studies indicate that the plasma contact system plays an important role in thrombosis, despite being dispensable for hemostasis. For example, mice deficient in coagulation factor XII (fXII) are protected from arterial thrombosis and cerebral ischemia-reperfusion injury. We demonstrate that selective reduction of prekallikrein (PKK), another member of the contact system, using antisense oligonucleotide (ASO) technology results in an antithrombotic phenotype in mice. The effects of PKK deficiency were compared with those of fXII deficiency produced by specific ASO-mediated reduction of fXII. Mice with reduced PKK had ∼ 3-fold higher plasma levels of fXII, and reduced levels of fXIIa-serpin complexes, consistent with fXII being a substrate for activated PKK in vivo. PKK or fXII deficiency reduced thrombus formation in both arterial and venous thrombosis models, without an apparent effect on hemostasis. The amount of reduction of PKK and fXII required to produce an antithrombotic effect differed between venous and arterial models, suggesting that these factors may regulate thrombus formation by distinct mechanisms. Our results support the concept that fXII and PKK play important and perhaps nonredundant roles in pathogenic thrombus propagation, and highlight a novel, specific and safe pharmaceutical approach to target these contact system proteases.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Factor XI and XII as antithrombotic targets.
Müller F, Gailani D, Renné T
(2011) Curr Opin Hematol 18: 349-55
MeSH Terms: Animals, Anticoagulants, Blood Coagulation, Factor XI, Factor XI Deficiency, Factor XII, Factor XII Deficiency, Hemostasis, Humans, Thrombosis
Show Abstract · Added May 19, 2014
PURPOSE OF REVIEW - Arterial and venous thrombosis are major causes of morbidity and mortality, and the incidence of thromboembolic diseases increases as a population ages. Thrombi are formed by activated platelets and fibrin. The latter is a product of the plasma coagulation system. Currently available anticoagulants such as heparins, vitamin K antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for terminating blood loss at sites of vascular injury. As a result, anticoagulants currently in clinical use increase the risk of bleeding, partially offsetting the benefits of reduced thrombosis. This review focuses on new targets for anticoagulation that are associated with minimal or no therapy-associated increased bleeding.
RECENT FINDINGS - Data from experimental models using mice and clinical studies of patients with hereditary deficiencies of coagulation factors XI or XII have shown that both of these clotting factors are important for thrombosis, while having minor or no apparent roles in processes that terminate blood loss (hemostasis).
SUMMARY - Hereditary deficiency of factor XII (Hageman factor) or factor XI, plasma proteases that initiate the intrinsic pathway of coagulation, impairs thrombus formation and provides protection from vascular occlusive events, while having a minimal impact on hemostasis. As the factor XII-factor XI pathway contributes to thrombus formation to a greater extent than to normal hemostasis, pharmacological inhibition of these coagulation factors may offer the exciting possibility of anticoagulation therapies with minimal or no bleeding risk.
0 Communities
1 Members
0 Resources
10 MeSH Terms
Prospective comparison of four laparoscopic vessel ligation devices.
Lamberton GR, Hsi RS, Jin DH, Lindler TU, Jellison FC, Baldwin DD
(2008) J Endourol 22: 2307-12
MeSH Terms: Animals, Cattle, Hemostasis, Surgical, Laparoscopes, Ligation, Photometry, Pressure, Prospective Studies, Vascular Surgical Procedures
Show Abstract · Added January 16, 2018
PURPOSE - The merits of laparoscopic sealing devices have been poorly characterized. The purpose of this study was to compare two bipolar sealing devices [LigaSure V (LS) and Gyrus PK (GP)], an ultrasonic device [Harmonic Scalpel ACE (HS)] and a novel device using nanotechnology [EnSeal PTC (ES)].
MATERIALS AND METHODS - The ability of all four 5 mm devices to seal 5 mm bovine arteries was tested under controlled temperature and humidity in accordance with manufacturer specifications. Study endpoints included lateral thermal spread, time to seal, burst pressure, smoke production and subjective (blinded review of video clips) and objective (measured using an aerosol monitor) effect upon visibility.
RESULTS - The HS demonstrated the least thermal spread. The LS (10.0 secs) and GP (11.1 secs) had the fastest sealing times (p<0.001 for both) when compared to ES (19.2 sec) and HS (14.3 sec). Mean burst pressure values were: LS 385 mm Hg, GP 290 mm Hg, ES 255 mm Hg and HS 204 mm Hg. The HS had the best subjective visibility score and the lowest objective smoke production (2.88 ppm) compared to the GP (74.1 ppm), ES (21.6 ppm) and LS (12.5 ppm), (p<0.01 for all).
CONCLUSIONS - The LS has the highest burst pressure and fastest sealing time and was the highest rated overall. The HS produced the lowest thermal spread and smoke but had the lowest mean burst pressure. The GP had the highest smoke production, and variable burst pressures. Despite employing nanotechnology, the ES device was the slowest and had variable burst pressures.
0 Communities
1 Members
0 Resources
9 MeSH Terms
Characterization of Novel Forms of Coagulation Factor XIa: independence of factor XIa subunits in factor IX activation.
Smith SB, Verhamme IM, Sun MF, Bock PE, Gailani D
(2008) J Biol Chem 283: 6696-705
MeSH Terms: Arginine, Binding Sites, Biochemistry, Catalysis, Catalytic Domain, Dimerization, Factor IX, Factor XIa, Hemostasis, Humans, Hydrolysis, Kinetics, Models, Biological, Peptides, Recombinant Proteins
Show Abstract · Added May 19, 2014
Factor XI is the zymogen of a dimeric plasma protease, factor XIa, with two active sites. In solution, and during contact activation in plasma, conversion of factor XI to factor XIa proceeds through an intermediate with one active site (1/2-FXIa). Factor XIa and 1/2-FXIa activate the substrate factor IX, with similar kinetic parameters in purified and plasma systems. During hemostasis, factor IX is activated by factors XIa or VIIa, by cleavage of the peptide bonds after Arg145 and Arg180. Factor VIIa cleaves these bonds sequentially, with accumulation of factor IX alpha, an intermediate cleaved after Arg145. Factor XIa also cleaves factor IX preferentially after Arg145, but little intermediate is detected. It has been postulated that the two factor XIa active sites cleave both factor IX peptide bonds prior to releasing factor IX abeta. To test this, we examined cleavage of factor IX by four single active site factor XIa proteases. Little intermediate formation was detected with 1/2-FXIa, factor XIa with one inhibited active site, or a recombinant factor XIa monomer. However, factor IX alpha accumulated during activation by the factor XIa catalytic domain, demonstrating the importance of the factor XIa heavy chain. Fluorescence titration of active site-labeled factor XIa revealed a binding stoichiometry of 1.9 +/- 0.4 mol of factor IX/mol of factor XIa (Kd = 70 +/- 40 nm). The results indicate that two forms of activated factor XI are generated during coagulation, and that each half of a factor XIa dimer behaves as an independent enzyme with respect to factor IX.
0 Communities
2 Members
0 Resources
15 MeSH Terms
Mechanisms of hemostatic failure during laparoscopic nephrectomy: review of Food and Drug Administration database.
Hsi RS, Saint-Elie DT, Zimmerman GJ, Baldwin DD
(2007) Urology 70: 888-92
MeSH Terms: Hemostasis, Surgical, Humans, Laparoscopy, Ligation, Nephrectomy, Retrospective Studies, Surgical Staplers, Treatment Failure, United States, United States Food and Drug Administration
Show Abstract · Added January 16, 2018
OBJECTIVES - To compare the complications with endovascular stapling devices, nonlocking titanium clips, and nonabsorbable polymer ligating (Hem-o-lok) clips during laparoscopic nephrectomy.
METHODS - The Food and Drug Administration Manufacturer and User Facility Device Experience Database was retrospectively reviewed for reports dated from January 1992 to March 2006 using the key words "nephrectomy" and "kidney." All episodes of pure and hand-assisted laparoscopic nephrectomy were evaluated.
RESULTS - Of 2172 total nephrectomy or kidney-related reports, 352 reported failure using laparoscopic hemostatic devices to secure the renal vasculature, and 223 complications (63%) resulted during the use of endovascular stapling devices, 111 (33%) from nonlocking titanium clips and 18 (5%) from locking clips. The leading causes of failure reported in stapling devices were staple line malformation (47%) and locking up (29%). In titanium clips, jamming/feeding difficulties (27%) and trouble closing or "scissoring" clips (26%) were the most common. In locking clips, dislodgement (44%) was most frequently reported. Three, one, and three deaths were reported after the use of the stapling device, titanium clip, and locking clip device, respectively.
CONCLUSIONS - All three methods used to secure the renal hilum in laparoscopic nephrectomy can result in malfunction. Because the overall denominator of use is not known, it would be inappropriate to conclude that one device is safer than another. When they occurred, these device malfunctions were potentially serious. Knowledge of the possible mechanisms of failure seen with each device could allow surgeons to anticipate potential complications and, therefore, perform laparoscopic surgery more safely.
0 Communities
1 Members
0 Resources
10 MeSH Terms