bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flow cytometric analysis of circulating platelet-monocyte aggregates in whole blood: Methodological considerations
Authors: Din Jehangir , Sarma Jaydeep , Jessop Alasdair , Weatherall Mark , Fox Keith , Newby David , Harding Scott 
Published: July 2007

SummaryPlatelet-monocyte aggregates are increasingly being used to quantify platelet activation.The variables that influence plateletmonocyte aggregates have not been well defined.We sought to determine the effect of blood collection, handling and processing techniques on detected levels of platelet-monocyte aggregates using a flow cytometric assay. Whole blood was labelled with anti-CD14-PE and anti-CD42a-FITC. Thereafter, samples were fixed and red cells lysed.Analysis was performed with the flow cytometer initially triggering on light scatter and then on FL-2 to identify CD14-PE positive monocytes. Platelet-monocyte aggregates were defined as monocytes positive for CD42a. The effect of collection, handling and processing techniques on this assay were assessed. Anticoagulation with heparin (20.1 ± 2.0%), PPACK (16.8 ± 1.9%), sodium citrate (12.3 ± 1.6%) and EDTA (9.5 ± 1.0%) resulted in markedly different levels of pla- gregation was higher in samples obtained from intravenous cannulae compared to those obtained by venepuncture (20.9 ± 3.9% vs.13.8 ± 2.4%,P=0.03).For every 10 minutes of delay prior to processing platelet-monocyte aggregates increased by 2.8% (P=0.0001) in PPACK anticoagulated blood and 1.7% (P=0.01) in citrate anticoagulated blood. Erythrocyte lysis together with fixation does not affect platelet-monocyte aggregation. Plateletmonocyte aggregates remained stable over 24 hours when fixed and stored at 4°C. Multiple handling and processing factors may affect platelet-monocyte aggregation. We recommend the measurement of platelet-monocyte aggregates on samples collected by direct venepuncture, using a direct thrombin inhibitor as the anticoagulant and minimising the time delay before sample fixation.
2B or not 2B? Disparate discrimination of functional VWF discordance using different assay panels or methodologies may lead to success or failure in the early identification of type 2B VWD
Authors: Bonar Roslyn , Meiring Muriel , Street Alison , Marsden Katherine , Favaloro Emmanuel ,   the RCPA QAP in Haematology
Published: July 2007

SummaryLaboratory proficiency in the identification of functional von Willebrand factor (VWF) discordance in type 2B von Willebrand disease (VWD) was assessed by external quality assurance surveys conducted by the RCPA Haematology QAP, and using six different type 2B VWD plasma samples (three historical and three previously unpublished) tested by up to 52 laboratories. For the three most recent samples, functional VWF discordance was either not identified in testing or by interpretation with misidentification as ‘normal’ or ‘type 1 VWD’, on average for 25.7% of test occasions when laboratories performed VWF:Ag and VWF:RCo as their primary VWF test panel, but somewhat fewer occasions (10.9%) for laboratories that incorporated VWF:CB as an additional functional VWF assay. VWF assay sub-methodologies also influenced the appropriate identification of samples as potentially type 2 VWD, and VWF functional discordance was more consistently identified when laboratories used (i) automated platelet agglutination for VWF:RCo compared to classical platelet aggregometry, (ii) inhouse VWF:CB assays compared to commercial kit methods, and (iii) automated LIA-based ‘VWF:Activity’ assays compared to ELISA based assays.We conclude that:(i) laboratories are generally proficient in tests for VWD but interpretative diagnostic errors do occur; (ii) correct diagnosis is more likely when test panels are more comprehensive and include the VWF:CB; (iii) sub-methodology influences the appropriate identification of VWF functional discordance. On the basis of these findings, we provide a series of recommendations to enable the appropriate laboratory identification of VWD, in particular type 2B VWD.
Fibrin clot structure in patients with end-stage renal disease
Authors: Sidelmann Johannes , Brabrand Mikkel , Pedersen Robert , Pedersen Jørgen , Esbensen Kim , Standeven Kristina , Ariëns Robert , Gram Jørgen , Sjøland Jonas 
Published: July 2007

SummaryFibrin clots with reduced permeability, increased clot stiffness and reduced fibrinolysis susceptibility may predispose to cardiovascular disease (CVD). Little is known, however, about the structure of fibrin clots in patients with end-stage renal disease (ESRD).These patients suffer from a high risk of CVD in addition to their chronic low-grade inflammation. Using permeability, compaction and turbidity studies in 22 ESRD patients and 24 healthy controls, fibrin clots made from patient plasma were found to be less permeable (p<0.001), less compactable (p<0.001), and less susceptible to fibrinolysis (p<0.001) than clots from controls.The maximum rate of turbidity increase was also higher for the patients than controls (p<0.001), and scan-ning electron microscopy revealed higher clot density of fibrin fibers in clots from patients than clots from controls (p<0.001). Patients had higher plasma concentrations of fibrinogen, C-reative protein and interleukin 6 than controls.These plasma markers of inflammation correlated significantly with most of the fibrin structure characteristics observed in the patients. In contrast, plasma markers of azothemia showed no such correlations. The results suggest that in ESRD patients fibrin clots are significantly different from healthy controls, and that the fibrin structure characteristics in the patients are associated primarily with the inflammatory plasma milieu rather than with level of azothemia.
Reduction of painful vaso-occlusive crisis of sickle cell anaemia by tinzaparin in a double-blind randomized trial
Authors: Qari Mohamad Hasan , Aljaouni Soad Khalil , Alardawi Mohamad Salleh , Fatani Huda , Alsayes Fatin Mohamad , Zografos Panagiotis , Alsaigh Mohamad , Alalfi Adnan , Alamin Mohamad , Gadi Abdulilah , Mousa Shaker 
Published: July 2007

SummaryA randomized double-blind clinical trial was performed to test the safety and efficacy of a low-molecular-weight heparin, tinzaparin (Innohep®), for the management of acute painful vasoocclusive crisis characteristic of sickle cell anemia (SCA). We studied 253 patients with acute painful crisis but with no other complications of SCA, randomized to treatment or control groups. In the treatment group, 127 patients received tinzaparin at 175 IU/kg, subcutaneous once daily, along with supportive care including morphine analgesia; in the control group, 126 patients received placebo and the same supportive care.The maxi- mal experimental treatment period was seven days. Analysis revealed a statistically significant reduction in number of days with the severest pain score, overall duration of painful crisis, and duration of hospitalization (p <0.05 for each comparison of tinzaparin vs. placebo).The decline in pain intensity was sharper for tinzaparin-treated patients, and complications consisted of two minor bleeding events that were reported and treated by cessation of tinzaparin.This investigation demonstrated that tinzaparin, administered at its approved treatment regimen, reduced the severity and duration of acute crisis of SCA.
Platelet dysfunction after normothermic cardiopulmonary bypass in children: Effect of high-dose aprotinin
Authors: Flaujac Claire , Pouard Philippe , Boutouyrie Pierre , Emmerich Joseph , Bachelot-Loza Christilla , Lasne Dominique 
Published: July 2007

SummaryPlatelet dysfunction after cardiopulmonary bypass (CPB) can contribute to excessive post-operative bleeding. Most trials of the protective effect of aprotinin in this setting have involved hypothermic CPB, which is more deleterious for platelets than normothermic CPB.Here we investigated the effect of aprotinin on platelet function during normothermic CPB in pediatric patients. Twenty patients (9 newborns [<1 month old] and 11 infants [<36 month old]),weighting less than 15 kg and undergoing normothermic CPB (35–36°C) were randomly assigned to two equal groups,one of which received high-dose aprotinin.Platelet function was assessed by flow cytometry just before CPB and 5 minutes after heparin neutralization. F1+2 fragments were measured by ELISA before and 5 minutes after CPB. Platelet activation marker expression (CD62P and activated αIIbβ3) induced by ADP or TRAP was lower after CPB than before CPB, suggesting a deleterious effect of normothermic CPB on platelet function. Prothrombin fragment F1+2 levels increased after CPB. Aprotinin administration did not influence the level of prothrombin fragments or platelet marker expression measured in basal condition. However, after CPB, the capacity for platelet activation was higher in the aprotinin group, as shown by measuring CD62P expression afterTRAP activation (p=0.05).This study suggests that pediatric normothermic CPB causes platelet dysfunction, and that high-dose aprotinin has a protective effect.
Effect of low-molecular-weight heparin on survival in patients with advanced pancreatic adenocarcinoma
Authors: Ayvaz Muhammed , Wagenpfeil Stefan , Eckel Florian , Schmid Roland , Lersch Christian , Delius Stefan von 
Published: July 2007

SummaryThis retrospective analysis aimed to identify whether low-molecular- weight heparins (LMWH) might improve survival in patients receiving chemotherapeutic treatment for advanced pancreatic adenocarcinoma.Two hundred forty-three patients who had received chemotherapy for advanced pancreatic adenocarcinoma were identified from a prospectively maintained database. Of these, 30 patients had to be excluded from analysis due to insufficient documentation. Of the remaining 213 patients 94 patients had been treated with LMWH, whereas 119 patients served as controls. Outcome was assessed in relation to overall survival, which was calculated from the date of initiation of chemotherapy to the date of death.There was no significant difference (hazard ratio, 0.8; 95% confidence interval (CI), 0.6 to 1.1; P=0,2) between the two groups in terms of overall survival. The median survival was 7.1 months (95% CI,5.8–8.4 months) in the LMWH group and 5.9 months (95% CI, 5.1–6.7 months) in the non-LMWH group. A positive effect of LMWH was seen in patients with metastatic disease (hazard ratio for LMWH vs. non-LMWH, 0,6; 95% CI, 0,4 to 0,8; P=0,006) in contrast to those without metastatic disease (hazard ratio for LMWH vs. non-LMWH, 1; 95% CI, 0.6 to 1.7; P=0,96).The median survival of patients with metastatic disease was 6,6 months (95% CI, 5–8,2 months) and 3.8 months (95% CI, 2.5–5.1 months) for the LMWH group and the non-LMWH group, respectively. In conclusion, we found for metastatic pancreatic adenocarcinoma a survival advantage for patients receiving LMWH. Nevertheless, our observations need confirmation by prospective randomized studies.
Identification of tissue factor and platelet-derived particles on leukocytes during cardiopulmonary bypass by flow cytometry and immunoelectron microscopy
Authors: Chung Jihwa , Suzuki Hidenori , Tabuchi Noriyuki , Sato Kengo , Shibamiya Aya , Koyama Takatoshi 
Published: July 2007

SummaryThe extrinsic coagulation system initiated by tissue factor (TF) appears to be a major procoagulant stimulus during cardiopulmonary bypass (CPB), although the precise mechanisms remain to be revealed.We recently reported the appearance ofTF-bearing leukocytes during CPB and described their role in promoting coagulation. In this study, we visually identified the in-vivo appearance ofTF-bearing leukocytes and platelet-derived particles on leukocytes in the pericardial blood during cardiac surgery with CPB, by flow cytometry and immunoelectron microscopy. Preliminary flow cytometric experiments showed that the proportion of TF-positive or both TF- and platelet antigen CD41a-positive leukocytes was increased markedly in pericardial blood obtained during CPB,compared with the proportions in preoperative circulating blood. Immunoelectron microscopic analysis revealed that both monocytes and polymorphonuclear leukocytes in the pericardial blood express TF. On the surfaces of these cells, CD41a-positive or both CD41a- and TF-positive platelet-derived particles were observed. Platelet-derived particles include not only microparticles, but also platelets themselves. Leukocytes from preoperative circulating blood contained far fewer of these particles. Our results demonstrate the in-vivo appearance of TF-bearing platelet-derived particles on leukocytes during cardiac surgery with CPB.These findings may be important for the development of strategies to control procoagulant activities during and after cardiac surgery.
Tyrosine phosphorylation / dephosphorylation balance is involved in thrombin-evoked microtubular reorganisation in human platelets
Authors: Bouaziz Aicha , Amor Nidhal Ben , Woodard Geoffrey , Zibidi Hanen , López José , Bartegi Ahgleb , Salido Ginés , Rosado Juan 
Published: July 2007

SummaryWe have investigated the intracellular mechanisms involved in microtubular remodelling by thrombin and its possible involvement in platelet aggregation and secretion. Platelet stimulation with thrombin induces a time- and concentration-dependent regulation of the microtubular content, which was found to be maximally effective at the concentration 0.1 U/ml. Thrombin (0.1 U/ml) evoked an initial decrease in the microtubule content detectable at 5 seconds (sec) and reached a minimum 10 sec after stimulation.The microtubular content then increased, exceeding basal levels again approximately 30 sec after stimulation. Inhibition of tyrosine phosphatases using vanadate abolished thrombin-induced microtubular depolymerisation while inhibition of tyrosine kinases by methyl-2,5-dihydroxycinnamate prevented microtubule polymerisation.Thrombin activates the cytosolic Brutons tyrosine kinase (Btk) and Src proteins. Inhibition of Btk or Src by LFM-A13 or PP1, respectively, abolished thrombin-induced microtubular polymerisation, while maintaining intact its ability to induce initial depolymerisation. Microtubular disruption by colchicine significantly reduced thrombin induced platelet aggregation and ATP secretion. Similar results were observed after inhibition of microtubular disassembly by paclitaxel.These findings indicate that thrombin induces microtubular remodelling by modifying the balance between protein tyrosine phosphorylation and dephosphorylation. The former seems to be required for microtubular polymerisation, while tyrosine dephosphorylation is required for microtubular depolymerisation. Both, initial microtubular disassembly and subsequent polymerisation are required for thrombin-induced platelet aggregation and secretion in human platelets.
Regulation of endothelial progenitor cell homing after arterial injury
Authors: Hristov Mihail , Zernecke Alma , Liehn Elisa , Weber Christian 
Published: July 2007

SummaryAdult bone marrow and peripheral blood contain sub-populations of vascular precursor cells, which can differentiate into mature endothelial cells and have therefore been commonly termed endothelial progenitor cells (EPCs). Although EPCs encompass rather heterogeneous cell sub-populations of multiple origins and localization, these cells were basically characterized by expression of progenitor markers and by the development of colony-forming units and late endothelial outgrowth with terminal differentiation into mature endothelial cells. Notably, functional studies in vivo have implied the contribution of EPCs to therapeutic reendothelialization and inhibition of neointimal growth following endothelial injury. In the context of this regenerative arterial remodeling, an adequate homing of EPCs plays a central role. This multi-step process of EPC mobilization, recruitment and firm adhesion is regulated by key angiogenic chemokines (CCL2, CXCL1, CXCL7, CXCL12) and their respective receptors (CCR2, CXCR2, CXCR4). Furthermore, the recruitment of circulating EPCs to sites of arterial injury is synchronized by activated platelets and adhesion molecules of the selectin and integrin family. Thus, translating this molecular knowledge to interventional cardiovascular medicine,such a detailed understanding in the complex regulation of EPC homing may be helpful for more effectively preventing “in-stent” stenosis by facilitating stent endothelialization.
Regulation of vascular endothelial permeability by junctional adhesion molecules (JAM)
Authors: Orlova Valeria , Chavakis Triantafyllos 
Published: July 2007

SummaryThe vascular endothelium forms a barrier between the circulation and the interstitium, and changes in vascular permeability are very important during vascular repair and inflammatory conditions. The regulation of the endothelial barrier depends on actomyosin- related cell contractility as well as the integrity of cellcell junctions, such as tight and adherens junctions.The present review will introduce the basic pathways involved in the regulation of the endothelial barrier as well as important participating signaling players, such as the small GTPases RhoA, Rac and Rap1. In this context, we will attempt to analyze and interpret the recent evidence pointing to the role of the family of junctional adhesion molecules (JAMs) in modulating the pathways involved in the regulation of the endothelial barrier.
Lymphangiogenesis in development and disease
Authors: Liersch Ruediger , Detmar Michael 
Published: July 2007

SummaryThe lymphatic vascular system plays an important role in the maintenance of fluid homeostasis, in the afferent immune response, in the intestinal lipid uptake and in the metastatic spread of malignant cells. The recent discovery of specific markers and growth factors for lymphatic endothelium and the establishment of genetic mouse models with impairment of lymphatic function have provided novel insights into the molecular control of the lymphatic system in physiology and in embryonic development. They have also identified molecular pathways whose mutational inactivation leads to human diseases associated with lymphedema. Moreover, the lymphatic system plays a major role in chronic inflammatory diseases and in transplant rejection. Importantly, malignant tumors can directly promote lymphangiogenesis within the primary tumor and in draining lymph nodes, leading to enhanced cancer metastasis to lymph nodes and beyond. Based upon these findings, novel therapeutic strategies are currently being developed that aim at inhibiting or promoting the formation and function of lymphatic vessels in disease.
Natural Order or Divine Will: Maimonides on Cosmogony and Prophecy
Authors: Weiss Roslyn 
Published: July 2007

AbstractIn Guide 2.32 Maimonides notes that just as there are three opinions concerning prophecy (as discussed earlier in 2:13), so are there three opinions concerning cosmogony. Scholars have tended to assume that Maimonides, despite what he says, must have seen some more important correspondence between the two sets of opinions than their number. I argue that although for Maimonides what the two sets of opinions have in common is indeed their number, what he wishes to direct the careful reader's attention to is that the number of opinions in both cases is actually two rather than three.
Nucleolin is a receptor that mediates antiangiogenic and antitumor activity of endostatin
Authors: Shi Hubing , Huang Yujie , Zhou Hao , Song Xiaomin , Yuan Shaopeng , Fu Yan , Luo Yongzhang 
Published: July 2007

AbstractThe exact molecular mechanism of how endostatin inhibits angiogenesis and tumor growth remains uncharacterized. Here, we report that endostatin specifically binds to the cell surface nucleolin with high affinity. Blockage of nucleolin by a neutralizing antibody or knockdown of nucleolin by the RNA interference results in loss of antiendothelial activities of endostatin. Importantly, a neutralizing antinucleolin antibody abrogates the antiangiogenic and antitumor activities of endostatin in vivo. Nucleolin and endostatin are colocalized on the cell surface of endothelial cells of angiogenic blood vessels in the tumor environment. Finally, we found that endostatin is internalized and transported into cell nuclei of endothelial cell via nucleolin. In the nucleus, the phosphorylation of nucleolin, which is critical for cell proliferation, can be inhibited by endostatin. Our studies demonstrate that nucleolin is a novel functional receptor for endostatin, and mediates the antiangiogenic and antitumor activities of endostatin. These findings also provide mechanistic insights of how endostatin specifically inhibits proliferating endothelial cell growth and angiogenesis.
The molecular signature of MDS stem cells supports a stem-cell origin of 5q− myelodysplastic syndromes
Authors: Nilsson Lars , Edén Patrik , Olsson Eleonor , Månsson Robert , Åstrand-Grundström Ingbritt , Strömbeck Bodil , Theilgaard-Mönch Kim , Anderson Kristina , Hast Robert , Hellström-Lindberg Eva , Samuelsson Jan , Bergh Gösta , Nerlov Claus , Johansson Bertil , Sigvardsson Mikael , Borg Åke , Jacobsen Sten Eirik W. 
Published: July 2007

Abstract
Global gene expression profiling of highly purified 5q-deleted CD34+CD38−Thy1+ cells in 5q− myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34+CD38−Thy1+ hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cells. Expression of BMI1, encoding a critical regulator of self-renewal, was up-regulated in 5q− stem cells. Whereas multiple previous MDS genetic screens failed to identify altered expression of the gene encoding the myeloid transcription factor CEBPA, stage-specific and extensive down-regulation of CEBPA was specifically observed in MDS progenitors. These studies establish the importance of molecular characterization of distinct stages of cancer stem and progenitor cells to enhance the resolution of stage-specific dysregulated gene expression.