Age-Dependent Control of Collagen-Dependent Platelet Responses by Thrombospondin-1-Comparative Analysis of Platelets from Neonates, Children, Adolescents, and Adults.

Platelet function is developmentally regulated. Healthy neonates do not spontaneously bleed, but their platelets are hypo-reactive to several agonists. The mechanisms underlying immature platelet function in neonates are incompletely understood.

Integrin-mediated cell adhesion requires extracellular disulfide exchange regulated by protein disulfide isomerase.

Cell adhesion to extracellular matrix, mediated by integrin receptors, is crucial for cell survival. Receptor-ligand interaction involves conformational changes in the integrin by a mechanism not fully elucidated. In addition to several direct evidence that there is disulfide re-arrangement of integrins, we previously demonstrated a role for extracellular thiols and protein disulfide isomerase (PDI) in integrin-mediated functions using platelets as model system.

Evaluating platelet function disorders in children with bleeding tendency - A single center study.

Platelet function disorders (PFDs) are a common cause of mild bleeding tendency. However, they cannot be recognized by standard screening studies. The gold standard test for PFD is platelet aggregation, performed by light transmission aggregometry (LTA).

The role of protein disulfide isomerase in the post-ligation phase of β3 integrin-dependent cell adhesion.

Introduction: Protein disulfide isomerase (PDI) catalyzes disulfide bond exchange. It is crucial for integrin-mediated platelet adhesion and aggregation and disulfide bond exchange is necessary for αIIbβ3 and αvβ3 activation. However, the role of disulfide bond exchange and PDI in the post-ligation phase of αIIbβ3 and αvβ3 mediated cell adhesion has yet to be determined.

Disulfide bond exchanges in integrins αIIbβ3 and αvβ3 are required for activation and post-ligation signaling during clot retraction.

Background: Integrin αIIbβ3 mediates platelet adhesion, aggregation and fibrin clot retraction. These processes require activation of αIIbβ3 and post-ligation signaling. Disulfide bond exchanges are involved in αIIbβ3 and αvβ3 activation.

Factor XIII improves platelet adhesion to fibrinogen by protein disulfide isomerase-mediated activity.

Background: Factor XIII (FXIII), a plasma pro-transglutaminase, consists of two A subunits and two B subunits (FXIIIA2B2). Following activation by thrombin, it cross-links fibrin chains at the final step of coagulation. We previously reported that FXIII subunit A (FXIIIA) serves as a protein disulfide isomerase (PDI), and that PDI promotes platelet adhesion and aggregation.

Staphylococcal extracellular adherence protein induces platelet activation by stimulation of thiol isomerases.

Objective: Staphylococcus aureus can induce platelet aggregation. The rapidity and degree of this correlates with the severity of disseminated intravascular coagulation, and depends on platelet peptidoglycans. Surface-located thiol isomerases play an important role in platelet activation.

[Laboratory evaluation of lupus anticoagulant in Israel].

Lupus anticoagulants (LAC) are antibodies which are detected by a prolongation of phospholipid-dependent coagulation assays, and are associated with thrombotic events and pregnancy complications in patients with the antiphospholipid syndrome. The antiphospholipid syndrome is defined by arterial or venous thrombosis and/or pregnancy morbidity and by laboratory diagnosis of antiphospholipid antibodies. The laboratory diagnosis is based on LAC and/or anticardiolipin and/or anti-beta2-glycoprotein I antibodies present in plasma, on two or more occasions at least 12 weeks apart.

Effect of imatinib on the signal transduction cascade regulating telomerase activity in K562 (BCR-ABL-positive) cells sensitive and resistant to imatinib.

Objective: Imatinib mesylate (IM) is a tyrosine kinase inhibitor selective for BCR-ABL and indicated for the treatment of chronic myeloid leukemia. It has recently been demonstrated that IM also targets other cellular components. Considering the significant role of telomerase in malignant transformation, we studied the effect of IM on telomerase activity (TA) and regulation in BCR-ABL-positive and -negative cells, sensitive and resistant to IM.

Coagulation factor XIII serves as protein disulfide isomerase.

Tissue transglutaminase was reported to act as protein disulfide isomerase (PDI). We studied whether plasma transglutaminase - coagulation factor XIII (FXIII) - has PDI activity as well. PDI activity was measured by determining the ability to renature reduced-denatured RNase (rdRNase).

Specific cysteines in beta3 are involved in disulfide bond exchange-dependent and -independent activation of alphaIIbbeta3.

Disulfide bond exchange among cysteine residues in epidermal growth factor (EGF)-like domains of beta3 was suggested to be involved in activation of alphaIIbbeta3. To investigate the role of specific beta3 cysteines in alphaIIbbeta3 expression and activation, we expressed in baby hamster kidney cells normal alphaIIb with normal beta3 or beta3 with single or double cysteine substitutions of nine disulfide bonds in EGF-3, EGF-4, and beta-tail domains and assessed alphaIIbbeta3 surface expression and activation state by flow cytometry using P2 or PAC-1 antibodies, respectively. Most mutants displayed reduced surface expression of alphaIIbbeta3.

Increased thromboembolic events after lung transplantation.

Background: Lung transplantation is a good therapeutic option for end-stage lung disease. Data on thromboembolic complications following lung transplantation are scarce.

Study Objectives: To evaluate the incidence of thromboembolic events following lung transplantation, and to determine their possible association with hypercoagulable state.

Antiphospholipid antibodies may be a new prognostic parameter in aggressive non-Hodgkin's lymphoma.

Objectives: Patients with malignancies have an increased prevalence of antiphospholipid antibodies (APA). The aim of this study was to determine the prevalence of IgG, IgM, and IgA anticardiolipin antibodies (aCL) and anti-beta-2 glycoprotein I antibodies (anti-beta2-GPI) in patients with non-Hodgkin's lymphoma (NHL), and to investigate their clinical and prognostic significance.

Methods: The study group included 86 patients with NHL.

Molecular characterization of a human monoclonal antibody that interacts with a sulfated tyrosine-containing epitope of the GPIb receptor and inhibits platelet functions.

Modification of tyrosine residues in extracellular proteins by a sulfate moity plays an important role in many ligand/receptors interactions. In the present work, we describe a unique human monoclonal antibody, termed Y1-scFv, that is specific for a sulfated epitope in the platelat receptor GPIb. The Y1-scFv single chain antibody (scFv) competes with von Willebrand factor (vWF) for binding to human platelets and thus effectively inhibits platelet aggregation.

Effect of urinary versus recombinant follicle-stimulating hormone on platelet function and other hemostatic variables in controlled ovarian hyperstimulation.

Objective: To determine the effect of urinary versus recombinant FSH on platelet function and hemostatic variables in women undergoing controlled ovarian hyperstimulation cycles.

Design: Randomized clinical study.

Setting: Major university-based infertility and in vitro fertilization unit and hemostasis laboratory.

Central venous line thrombosis in children and young adults with thalassemia major.

High doses of intravenous deferoxamine via central venous line (CVL) has recently been shown to improve survival in patients with noncompliant thalassemia major (TM). The aim of this retrospective study was to evaluate the extent of CVL-related thrombosis and to determine the presence of prothrombotic factors in children and young patients with TM on such a regimen. Twenty-three patients (median age 13, range 5-25 years) with TM in whom a tunneled CVL was inserted for intensification of iron chelation were evaluated for signs and symptoms of thrombosis and for inherited and acquired risk factors of thrombosis.

Administration of eptifibatide to acute coronary syndrome patients receiving enoxaparin or unfractionated heparin: effect on platelet function and thrombus formation.

Objectives: The goal of this study was to compare the antithrombotic effects of enoxaparin versus unfractionated heparin (UFH) when combined with eptifibatide in acute coronary syndrome (ACS) patients.

Background: An increasing number of high-risk ACS patients are treated with low-molecular-weight heparin and a glycoprotein (GP) IIb/IIIa inhibitor. There is a paucity of data regarding the antithrombotic properties of such a combination as compared with UFH and GP IIb/IIIa inhibitors.

Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin alpha2beta1.

Integrin alpha2beta1 is the principal adhesive receptor for collagen but platelets also adhere through glycoprotein VI (GPVI). Integrin alphaIIbbeta3 may augment platelet adhesion. We have shown that disulfide exchange is necessary for platelet adhesion to fibrinogen, fibronectin, and collagen.

Sustained integrin ligation involves extracellular free sulfhydryls and enzymatically catalyzed disulfide exchange.

Studies have suggested a pivotal role for free sulfhydryls in platelet integrin function, and enzyme-mediated reduction of disulfide bonds on platelets has been implicated. The platelet fibrinogen receptor alpha(IIb)beta(3) is the best-studied platelet integrin and serves as a model system for studying the structure-function relation in this family of adhesion receptors. The demonstration of free sulfhydryls on the exofacial domain of purified alpha(IIb)beta(3), specifically in its activated conformation, prompted us to explore the potential for activation-dependent, enzymatically catalyzed thiol expression on intact platelets and the possible role of surface-associated protein disulfide isomerase (PDI) in alpha(IIb)beta(3) ligation.

Impaired platelet aggregation in melanoma patients treated with interferon-alpha-2b adjuvant therapy.

Background: High-dose interferon (INF)- alpha-2b is the only Food and Drug Administration-approved adjuvant treatment for patients with melanoma who are at high risk of recurrence. Although circumstantial evidence points to a potentially harmful effect of INF-alpha-2b on platelet function, to the authors' knowledge this has never been studied in humans.

Methods: The study group was comprised of patients who had undergone surgery for melanoma and were free of disease but at a high risk of recurrence.