Search

The effect of fibrinolytic agents on platelet adhesion onto insolubilized collagen type I was evaluated. Normal human whole blood samples were incubated with agents and perfused over collagen-coated surfaces in a parallel-plate flow chamber. Platelet adhesion and aggregation were analyzed by video microscopy and image processing. When blood was perfused at 1500/s, both streptokinase and urokinase, each at 500 U/ml, caused a significantly less normalized platelet deposition, compared with controls. At 480/s, platelet deposition was not different between controls and test samples. Inhibition of platelet deposition at high flow rates was partly due to inhibition of platelet adhesion. Both ristocetin- and ADP-induced platelet aggregation were inhibited in test samples. The agents caused proteolytic degradation of plasma fibrinogen, but no degradation of platelet glycoproteins Ib and IIb-IIIa (GPIb and GPIIb-IIIa) and of plasma von Willebrand factor in test samples prior to perfusion. Post-perfusion von Willebrand factor degradation was not found. Plasmin may cause functional changes to plasma proteins and/or platelet receptors, altering their adhesive properties under flow. At high shear, fibrinogen degradation products may interfere with GPIIb-IIIa binding to insolubilized von Willebrand factor, leading to decreased platelet adhesion. Inhibition of platelet adhesion by thrombolytic agents could help maintain vessel patency after recanalization in stenosed arteries. Publishers.

Two adjective pairs in comparative form, more-less and taller-shorter, were tested with moderately mentally retarded (MR) and nonretarded children (NR) matched on verbal mental age (MA) and socioeconomic status (SES) in a “show” and an “act-out” experimental condition. The data indicated that all the main effects, the group, the experimental condition, and the unmarked-marked relational terms were significant and so were the interactions of the Group × Experimental Conditions, Group × Unmarked Versus Marked Relational Terms, and Group × Experimental Conditions and Unmarked Versus Marked Relational Terms. A logistic regression analysis (LRA) showed that the relational term shorter in the act-out condition best predicted classification membership for the subjects in either group, suggesting that the MR children were less able to self-regulate behavior. The error types, however, mainly observed in the act-out experimental condition were the same from a semantic point of view in either group. The effect of the unmarked versus marked distinction cannot be considered independent of the experimental conditions applied.

The present paper is related to a case study of an 8-year-old girl with Williams syndrome and mild intellectual disability. Initial informal assessments and standardized tests indicated that her reading ability was underdeveloped, as well as her phonological awareness. Hence, an intervention for the development of reading skills was designed according to the principles of the ‘top-down’ educational model, combining features from several teaching methods, such as ‘holistic approach’, ‘holisticanalytical method’, and ‘whole-word teaching’. The student’s progress was recorded in the researcher’s journal and evaluated through informal continuous assessment and standardized test. She managed to read 45 out of 65 words, which were included in the intervention, simple syllables with the consonant-vowel sequence and some simple two-syllable words without any complex content, not included in the intervention. The intervention proved to be effective, as the student indicated development in her reading skills, although to a certain degree. Finally, the results verified the influence of the phonological factor in reading and highlighted the holist approach as an appropriate way to develop reading and comprehension skills.

Systemic delivery of tissue-type plasminogen activator (t-PA) to dissolve a thrombus after a heart attack or stroke is accompanied by the risk of hemorrhage. A recent study shows the use of nanoaggregates to target t-PA to the thrombus in mouse models of mesenteric injury and pulmonary embolism.

The purpose of the present study was to identify the correlation between gender and reading preferences and reading strategies employed by 5th and 6th Grade students of primary school in Greece. The main objectives of the present study were (1) to identify possible differences between male and female students in employing cognitive and metacognitive strategies, (2) to record the difficulties encountered by males and females when reading and (3) to highlight possible differences between male and female students in reading preferences. 405 Greek students (206 boys and 199 girls, M=11.21 years old, SD.=0.47) participated in the study and were asked to fill in a questionnaire including questions related to reading preferences and attitudes. In addition, 32 students from the total sample were asked to choose their favourite text to read and think aloud about the processes they followed and the strategies they used. The questionnaire results indicated significant differences between male and female students in reading preferences, since the female students showed a greater preference for ‘human-interest’ stories and male ones preferred to read comics and action-stories. The verbal data revealed the female students’ flexibility in strategy use and their higher metacognitive awareness compared to male students. Reading, gender and social factors are discussed in the light of citizenship education.

Second-order mental state attribution in two groups of children with non-specific intellectual disability and Down syndrome was investigated. The children were compared to overall mental age-matched group of typically developing children. The aim of the present study was to determine the specificity of the theory of mind deficit to different groups of children with intellectual disability. The results clearly showed that children with Down syndrome performed more poorly than the children with non-specific intellectual disability, and that typically developing children perform significantly better than do other groups. The findings are discussed in terms of the specificity of the etiology-related profiles of intellectually disabled groups. Several critical issues related to intervention strategies in the field of intellectual disability are also discussed, considering the educational practices.

The mitochondrial network is dynamic with conformations that vary between a tubular continuum and a fragmented state. The equilibrium between mitochondrial fusion/fission, as well as the organelle motility, determine network morphology and ultimately mitochondrial/cell function. Network morphology has been linked with the energy state in different cell types. In this study, we examined how bioenergetic factors affect mitochondrial dynamics/motility in cultured vascular endothelial cells (ECs). ECs were transduced with mitochondria-targeted green fluorescent protein (mito-GFP) and exposed to inhibitors of oxidative phosphorylation (OXPHOS) or ATP synthesis. Time-lapse fluorescence videos were acquired and a mathematical program that calculates size and speed of each mitochondrial object at each time frame was developed. Our data showed that inner mitochondrial membrane potential (ΔΨ(m)), ATP produced by glycolysis, and, to a lesser degree, ATP produced by mitochondria are critical for maintaining the mitochondrial network, and different metabolic stresses induce distinct morphological patterns (e.g., mitochondrial depolarization is necessary for "donut" formation). Mitochondrial movement, characterized by Brownian diffusion with occasional bursts in displacement magnitude, was inhibited under the same conditions that resulted in increased fission. Hence, imaging/mathematical analysis shed light on the relationship between bioenergetics and mitochondrial network morphology; the latter may determine EC survival under metabolic stress.

Ischemia (I)/reperfusion (RP)-induced endothelial cell (EC) injury is thought to occur due to mitochondrial reactive oxygen species (mtROS) production. MtROS have been implicated in mitochondrial fission. We determined whether cultured EC exposure to simulated I/RP causes morphological changes in the mitochondrial network, and the mechanisms behind those changes. Since shear stress results in nitric oxide (NO)-mediated endothelial mtROS generation, we simulated I/RP as hypoxia (H) followed by oxygenated flow over the ECs (shear stress of 10 dyne/cm2). By exposing ECs to shear stress, H, H/reoxygenation (RO) or simulated I/RP and employing mitotracker staining, the differential effects of changes in mechanical forces and/or O2 levels on the mitochondrial network were assessed. Static or sheared ECs maintained their mitochondrial network. H- or H/RO-exposed ECs underwent changes, but mitochondrial fission was significantly less compared to that in ECs exposed to I/RP. I/RP-induced fission was partially inhibited by antioxidants, a NO synthase inhibitor or an inhibitor of the fission protein dynamin-related protein 1 (Drp1), and was accompanied by Drp1 oligomerization and phosphorylation (Ser616). Hence, shear-induced NO, ROS (including mtROS), and Drp1 activation are responsible for mitochondrial fission in I/RP-exposed ECs, and excessive fission may be an underlying cause of EC dysfunction in postischemic hearts.

Two likely mechanisms for the initiation of arterial platelet thrombus formation under conditions of elevated fluid shear stresses are: (1) excessive adhesion and aggregation of platelets from rapidly flowing blood onto the exposed sub-endothelium of injured, atherosclerotic arteries; or (2) direct, fluid shear stress-induced aggregation of platelets in constricted arteries with intact endothelial cells. Mechanism (1) was simulated using a parallel plate flow chamber, fibrillar collagen type I-coated slides, and mepacrine-labeled (fluorescent) platelets in whole blood anticoagulated with citrate, hirudin, unfractionated porcine heparin, or low molecular weight heparin flowing for 1 to 2 minutes at wall shear rates of 100 to 3,000 seconds-1 (4 to 120 dynes/cm2). The precise sequence of interactions among von Willebrand factor (vWF), glycoprotein (GP)Ib, and GPIIb-IIIa during platelet adhesion and subsequent aggregation were resolved by direct real-time observation using a computerized epifluorescence video microscopy system. Adhesion at high shear rates was the result of the adsorption of large vWF multimers onto collagen and the binding of platelet GPIb to the insolubilized vWF. Aggregation occurred subsequently and required the binding of ligands, including vWF via its RGD binding domain, to GPIIb-IIIa. Mechanism (2) was modeled by producing shear stresses of 90 to 180 dynes/cm2 in a rotational cone and plate viscometer, which aggregates platelets from platelet-rich- plasma (PRP) anti-coagulated with citrate, hirudin, or either type of heparin in reactions that require large vWF multimers, Ca2+, adenosine diphosphate, and both GPIb and GPIIb-IIIa. Both vWF-mediated shear- aggregation in PRP and platelet-collagen adhesion in flowing whole blood (anticoagulated with citrate and hirudin) are inhibited by two potentially useful anti-arterial thrombotic agents: polymeric aurin tricarboxylic acid (ATA; 28.5 to 114 micrograms/mL), which binds to vWF and inhibits its attachment of GPIb, and a recombinant vWF fragment (rvWF445–733; 30 to 200 micrograms/mL) that binds to platelet GPIb (in the absence of any modulator) and blocks attachment of vWF multimers. Unfractionated heparin, but not low molecular weight heparin, apparently binds to rvWF445–733 and counteracts the inhibitory effects of the vWF fragment in vitro on shear-aggregation and platelet-collagen adhesion.

Two likely mechanisms for the initiation of arterial platelet thrombus formation under conditions of elevated fluid shear stresses are: (1) excessive adhesion and aggregation of platelets from rapidly flowing blood onto the exposed sub-endothelium of injured, atherosclerotic arteries; or (2) direct, fluid shear stress-induced aggregation of platelets in constricted arteries with intact endothelial cells. Mechanism (1) was simulated using a parallel plate flow chamber, fibrillar collagen type I-coated slides, and mepacrine-labeled (fluorescent) platelets in whole blood anticoagulated with citrate, hirudin, unfractionated porcine heparin, or low molecular weight heparin flowing for 1 to 2 minutes at wall shear rates of 100 to 3,000 seconds-1 (4 to 120 dynes/cm2). The precise sequence of interactions among von Willebrand factor (vWF), glycoprotein (GP)Ib, and GPIIb-IIIa during platelet adhesion and subsequent aggregation were resolved by direct real-time observation using a computerized epifluorescence video microscopy system. Adhesion at high shear rates was the result of the adsorption of large vWF multimers onto collagen and the binding of platelet GPIb to the insolubilized vWF. Aggregation occurred subsequently and required the binding of ligands, including vWF via its RGD binding domain, to GPIIb-IIIa. Mechanism (2) was modeled by producing shear stresses of 90 to 180 dynes/cm2 in a rotational cone and plate viscometer, which aggregates platelets from platelet-rich- plasma (PRP) anti-coagulated with citrate, hirudin, or either type of heparin in reactions that require large vWF multimers, Ca2+, adenosine diphosphate, and both GPIb and GPIIb-IIIa. Both vWF-mediated shear- aggregation in PRP and platelet-collagen adhesion in flowing whole blood (anticoagulated with citrate and hirudin) are inhibited by two potentially useful anti-arterial thrombotic agents: polymeric aurin tricarboxylic acid (ATA; 28.5 to 114 micrograms/mL), which binds to vWF and inhibits its attachment of GPIb, and a recombinant vWF fragment (rvWF445–733; 30 to 200 micrograms/mL) that binds to platelet GPIb (in the absence of any modulator) and blocks attachment of vWF multimers. Unfractionated heparin, but not low molecular weight heparin, apparently binds to rvWF445–733 and counteracts the inhibitory effects of the vWF fragment in vitro on shear-aggregation and platelet-collagen adhesion.

The effect of flow-induced shear stress on membrane K+ permeability was investigated by measuring86Rb+ efflux in cultured calf pulmonary artery endothelial cells. Cells were subjected to step changes in shear stress from 1 dyn/cm2 to 2.4, 4.8, or 10 dyn/cm2 in a parallel-plate flow chamber. Increasing shear stress produced a graded, transient increase in86Rb+ efflux which peaked within 1 min and subsequently declined rapidly toward pre-stimulus levels. Upon returning shear stress to 1 dyn/cm2,86Rb+ efflux initially decreased, but returned slowly to basal values. In contrast, application of bradykinin at a constant shear stress of 1 dyn/cm2 produced a transient increase in86Rb+ efflux that was followed by a sustained elevated phase during which time efflux gradually returned to pre-stimulus levels. In order to exclude the possibility that the transient increase in86Rb+ efflux with shear stress simply reflects a flow-dependent change in the washout of radiotracer, the transient convection-diffusion equation was solved using finite element simulation. When the flux of86Rb+ from the cell monolayer was assumed to be constant with time, the mathematical model predicted an increase in efflux rate coefficients upon step increases in flow that were only 7–19% of that observed experimentally. The numerical predictions correlated well with the experimentally obtained peaks when the flux of86Rb+ from the cell monolayer was simultaneously increased with flow to a new steady value. These simulations however, could not predict the transient nature of the response to increased shear stress. The results from the computer modeling suggest that the transient increase in86Rb+ efflux does not reflect a washout phenomenon and supports the hypothesis that shear stress produces a graded, transient increase in the K+ permeability of vascular endothelial cells.

Klinefelter syndrome (KS) is a genetic disorder in males characterized by the presence of an extra X chromosome. Its most consistent endocrinological manifestations include lower testosterone production and impaired spermatogenesis. KS individuals have a general typical appearance with taller stature, and they demonstrate a characteristic cognitive phenotype involving weaknesses in verbal processing. Anomalous cerebral lateralization involves the inverse or weak dominance of hand, language, and visuospatial abilities and has been associated with the cognitive deficits of KS individuals. This article summarizes the ongoing research in this field, discusses the main findings, and attempts to provide a thorough description of the cause of the observed functional and anatomical cerebral asymmetries associated with the syndrome. Nonetheless, efforts have been directed to incorporate evidence for and against theoretical accounts that explain the experimental findings, to discuss issues involving the implications of the chosen methodology, and present key research areas for future empirical research.

Study of the mechanisms of monocyte adhesion initiating atheroslerotic lesions has engaged investigators for decades. Single-phase computational fluid dynamics (CFD) analyses fail to account for particulate migration. Consequently, inconsistencies arise when correlating adhesion with wall shear stress (WSS). The purpose of this paper is to present, to our knowledge, the first computational analysis of in vitro U937 monocyte-like human cell adhesion data using a coupled multiphase CFD-population balance adhesion model. The CFD model incorporates multiphase non-Newtonian hemodynamic models to compute the spatial distributions of freely flowing monocytes and WSSs in control volumes adjacent to the wall. Measurements of monocyte adhesion onto an E-selectin-coated flow model that included an idealized stenosis and an abrupt expansion were available from the literature. In this study, we develop a new monolayer population balance adhesion model, based on the widely accepted mechanism of ligand-receptor binding, coupled to the CFD results. The monolayer population balance model accounts for the interactions of freely flowing, rolling, and adhering monocytes with surfaces via first-order reactions, transport of rolling cells in the monolayer, and the concept of a WSS detachment threshold, clearly evident in the adhesion experiments. The new paradigm of coupling the multiphase hemodynamic CFD model with the proposed adhesion model is illustrated by determining and interpreting the model parameters for experimental datasets having Reynolds numbers of 100 and 140. The coupled multiphase CFD adhesion model is able to simultaneously predict the spatial variations in freely flowing monocytes, their adherent number density, and carrier fluid WSSs adjacent to ligand-coated flow cell surfaces.

Cultured vascular endothelial cell (EC) exposure to steady laminar shear stress results in peroxynitrite (ONOO−) formation intramitochondrially and inactivation of the electron transport chain. We examined whether the “hyperoxic state” of 21% O2, compared with more physiological O2tensions (Po2), increases the shear-induced nitric oxide (NO) synthesis and mitochondrial superoxide (O2·−) generation leading to ONOO−formation and suppression of respiration. Electron paramagnetic resonance oximetry was used to measure O2consumption rates of bovine aortic ECs sheared (10 dyn/cm2, 30 min) at 5%, 10%, or 21% O2or left static at 5% or 21% O2. Respiration was inhibited to a greater extent when ECs were sheared at 21% O2than at lower Po2or left static at different Po2. Flow in the presence of an endothelial NO synthase (eNOS) inhibitor or a ONOO−scavenger abolished the inhibitory effect. EC transfection with an adenovirus that expresses manganese superoxide dismutase in mitochondria, and not a control virus, blocked the inhibitory effect. Intracellular and mitochondrial O2·−production was higher in ECs sheared at 21% than at 5% O2, as determined by dihydroethidium and MitoSOX red fluorescence, respectively, and the latter was, at least in part, NO-dependent. Accumulation of NO metabolites in media of ECs sheared at 21% O2was modestly increased compared with ECs sheared at lower Po2, suggesting that eNOS activity may be higher at 21% O2. Hence, the hyperoxia of in vitro EC flow studies, via increased NO and mitochondrial O2·−production, leads to enhanced ONOO−formation intramitochondrially and suppression of respiration.

Exposure of vascular endothelial cells (ECs) to steady laminar shear stress activates the NF-E2-related factor 2 (Nrf2) which binds to the antioxidant response element (ARE) and upregulates the expression of several genes. The onset of shear is known to increase the EC reactive oxygen species (ROS) production, and oxidative stress can activate the ARE. ARE-regulated genes include phase 2 enzymes, such as glutathione-S-transferase (GST) and NAD(P)Hquinone oxidoreductase 1 (NQO1), and antioxidants, such as glutathione reductase (GR), glutathione peroxidase (GPx) and catalase. We examined how shear stress affects the antioxidant/phase 2 enzyme activities and whether ROS mediate these effects. ROS production, measured by dichlorofluorescin fluorescence, depended on level and time of shear exposure and EC origin, and was inhibited by either an endothelial nitric oxide synthase (eNOS) inhibitor or a superoxide dismutase (SOD) mimetic and peroxynitrite (ONOO-) scavenger. Shear stress (10 dynes/cm2, 16 h) significantly increased the NQO1 activity, did not change significantly the glutathione (GSH) content, and significantly decreased the GR, GPx, GST and catalase activities in human umbilical vein ECs. Either eNOS inhibition or superoxide radical (O 2 •- )/ONOO- scavenging differentially modulated the shear effects on enzyme activities suggesting that the intracellular redox status coordinates the shear-induced expression of cytoprotective genes. © Biomedical Engineering Society 2007.

There is evidence that nitric oxide (NO), superoxide (O2•−), and their associated reactive nitrogen species (RNS) produced by vascular endothelial cells (ECs) in response to hemodynamic forces play a role in cell signaling. NO is known to impair mitochondrial respiration. We sought to determine whether exposure of human umbilical vein ECs (HUVECs) to steady laminar shear stress and the resultant NO production modulate electron transport chain (ETC) enzymatic activities. The activities of respiratory complexes I, II/III, and IV were dependent on the presence of serum and growth factor supplement in the medium. EC exposure to steady laminar shear stress (10 dyn/cm2) resulted in a gradual inhibition of each of the complexes starting as early as 5 min from the flow onset and lasting up to 16 h. Ramp flow resulted in inhibition of the complexes similar to that of step flow. When ECs were sheared in the presence of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 100 μM), the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO; 100 μM), or the peroxynitrite (ONOO−) scavenger uric acid (UA; 50 μM), the flow-inhibitory effect on mitochondrial complexes was attenuated. In particular, l-NAME and UA abolished the flow effect on complex IV. Increased tyrosine nitration was observed in the mitochondria of sheared ECs, and UA blocked the shear-induced nitrotyrosine staining. In summary, shear stress induces mitochondrial RNS formation that inhibits the electron flux of the ETC at multiple sites. This may be a critical mechanism by which shear stress modulates EC signaling and function.

Antibody-mediated rejection is characterized by deposits of complement (C) C4 and C3 split products on endothelial cells (ECs). C3 split products are critical mechanistically and diagnostically because they are deposited in amplified quantities, bind covalently to ECs and act as ligands for leukocytes. This study was designed to determine whether cultured vascular human ECs could clear covalently bound C3 split products from their surface. An immunoglobulin M (IgM) antibody against beta(2)-microglobulin of major histocompatibility complex class I antigens was used to activate C in human serum. Some cells were exposed to hypoxia/reoxygenation and/or interleukin 1beta (IL-1beta) prior to incubation with antibody. C3b/iC3b and C3d deposition on the cell surface was measured by flow cytometry. Incubation with antibody followed by human serum caused a dose-dependent deposition of C3b/iC3b and C3d. Over half of deposited C3b/iC3b and one-third of C3d were cleared from the cell surface during a 3-7-h incubation period with human serum. Neither hypoxia/reoxygenation nor IL-1beta further increased the deposition of C3b/iC3b and C3d, and only slightly modulated their rates of clearance. In summary, human ECs rapidly clear iC3b and C3d from their surface. This finding may have important diagnostic and mechanistic implications to transplantation because C3d is used as a marker of antibody-mediated rejection.

when flowing blood leukocytes interact with activated endothelium, the initial rolling event is mediated by selectins, which bind to their carbohydrate-based ligands, and the later firm adhesion event is mediated by integrins, which bind to cell adhesion molecules (CAMs). Specifically, neutrophils

A sharp increase in shear stress followed by steady laminar shear stress (step flow) imposed on the surface of macrovascular endothelial cells (ECs) causes changes to the metabolism, gene expression, protein synthesis, as well as to the reactive oxygen species (ROS) production. In this study, we monitored the shear-induced cytosolic ROS production in human umbilical vein ECs (HUVECs) and in human dermal microvascular ECs (HMVECs) using the oxidant-sensitive fluorescent probe 2,7-dichlorodihydrofluorescein diacetate (DCF-DA). HMVECs increased their ROS levels in response to shear stress in a time- and dose-dependent manner, when the shear stress was in the range of those encountered in postcapillary venules (2 or 4 dynes/cm/sup 2/). whereas HUVECs responded only to a higher shear stress tested (10 dynes/cm/sup 2/). It is known that many oxidants induce DCF-DA oxidation (hydra peroxides, ONOO/sup -/, NO/sub 2/ radical). In agreement to that, either an ecNOS inhibitor or a ONOO scavenger/SOD mimetic inhibited the shear-induced DCF signal. We are currently establishing a method to monitor lipid peroxidation (formation of lipid hydroperoxides) in the membranes of sheared ECs. Our plan is to investigate the contribution of cytosolic ROS to membranous lipid peroxidation and to intracellular shear-induced signaling.

Adhesion of platelets to the exposed extracellular matrix proteins at sites of vascular injury is partly regulated by the local fluid shear stress. Because the Leu33Pro (Pl(A)) polymorphism of integrin beta(3) confers only a modest increase in adhesion under static conditions, we used CHO and 293 cells expressing the Leu33 or Pro33 isoform of beta(3) in flow chamber experiments to test whether shear forces would alter the Pl(A) adhesive phenotype. We found that shear force augmented the Pro33-mediated enhanced adhesion to fibrinogen. This Pro33-dependent enhancement was aspirin-sensitive and was also observed on immobilized von Willebrand factor and cryoprecipitate, but not fibronectin. Thus, shear stress enhances the adhesive phenotype of the Pro33 cells to multiple physiologic substrates.

The presence of platelets increases the fibrinolytic resistance of thrombi. When activated, platelets secrete PAI-1 and /spl alpha//sub 2/-antiplasmin and induce clot retraction. The search for potent antiplatelet agents has led to inhibitors of the platelet receptor GP IIb/IIIa, one of which is ReoPro (c7E3 Fab; abciximab). The effect of ReoPro on rt-PA-induced fibrinolysis was studied using an in vitro whole blood reperfusion model. When ReoPro was administered simultaneously with rt-PA at a wall shear rate of 500 s/sup -1/, it had no effect on the rate of fibrinolysis. rt-PA was found to lyse preformed gel-filtered platelet-fibrin substrates containing fixed platelets quicker than those containing normal platelets. ReoPro was shown to block platelet-fibrin interactions under arterial flow. Hence, the authors hypothesized (and are currently testing) that a combination of a GP IIb/IIIa inhibitor preincubated with the substrate, and a fibrinolytic drug injected with the flow, may hasten lysis of platelet-fibrin substrates under well-defined hemodynamic conditions. ReoPro may prove a necessary adjunctive treatment during thrombolytic therapy of platelet-rich thrombi.

A model of tissue-type plasminogen activator (t-PA) mediated mural clot lysis has been developed. The model treats the clot as a porous two-phase mixture, and includes mechanisms of kinetics and fluid transport of chemical species, and mechanical property degradation as the fibrin dissolves. The model is consistent with experimental lysis of platelet-fibrin substrates in an in vitro whole blood reperfusion model. Lysis time is predicted to decrease with increasing wall shear stress, and increase with increasing plasminogen activator inhibitor (PAI)-1 concentration.

The Parkinson's disease questionnaire (PDQ-39) is a well-validated British scale for the assessment of health-related quality of life (HQoL) in Parkinson's disease (PD). The PDQ-39 has been translated into Greek and it was applied to 119 Greek PD patients. These patients were classified in stages according to the Hoehn and Yahr (HY) scale and their motor disability was assessed by means of the Unified Parkinson's disease rating scale (UPDRS) as well as the Schwab and England activities of daily living scale (ADL). The Beck depression inventory (BDI) was applied for the evaluation of depression. The translated version of PDQ-39, designated PDQ-39GrV, was validated as follows: (1) Cronbach's alpha coefficient and item-total Spearman's rank-order correlations were calculated in order to estimate the internal consistency of PDQ-39GrV scales. (2) Validity of the PDQ-39GrV was examined in terms of agreement with the clinical assessment parameters (stage, UPDRS. ADL and BDI scores). (3) Sixty one PD patients were re-evaluated 3-7 days later in order to check test-retest reliability. The results showed the following: (1) The PDQ-39GrV demonstrated very good internal consistency (alpha 0.71-0.94). Item-total correlations were statistically significant (r: 0.52-0.93). Test-retest measurements correlated significantly (p = 0.001). (2) Clinically obtained motor parameters correlated well with PDQ-39GrV scales influenced by physical aspects of the disease, while emotionally and socially influenced ones correlated with depression. Our findings indicate that PDQ-39 GrV is a reliable, easy to administer scale for the assessment of HQoL in Greek PD patients.

Monocyte adhesion to the endothelium depends on concentrations of receptors/ligands, local concentrations of chemoattractants, monocyte transport to the endothelial surface and hemodynamic forces. Monocyte adhesion to the inert surface of a three-dimensional perfusion model was shown to correlate inversely with wall shear stress, but was also affected by flow patterns which influenced the near-wall cell availability. We hypothesized that (a) under the same flow conditions, insolubilized E-selectin on the model's surface may mediate adhesive interactions at higher wall shear stresses, compared to an uncoated model, and (b) pulsatile flow may modify the adhesion profile obtained under steady flow. An axisymmetric flow model with a stenosis and a sudden expansion produced a range of wall shear stresses and a separated flow with recirculation and reattachment. Pre-activated U937 cells were perfused through the model under either steady ( Re =100, 140) or pulsatile ( Re mean =107) flow. The velocity field was characterized through computational fluid dynamics and validated by inert particle tracking. Surface E-selectin greatly increased cell adhesion in all regions at Re =100 and 140, compared to an uncoated model under the same flow conditions. In regions where the cells near the wall were abundant (taper and stenosis), adhesion to E-selectin correlated with the reciprocal of local wall shear stress when flow was steady. Pulsatile flow distributed the adherent cells more evenly throughout the coated model. Hence, characterizing both the local hemodynamics and the biological activity on the vessel wall is important in leukocyte adhesion.

The Test of Nonverbal Intelligence (TONI-2; L. Brown, R. J. Sherbenou, & S. Johnsen, 1990) and Raven's Colored Progressive Matrices (RCPM; J. C. Raven, 1965) are defined as language-free measures of cognitive ability. The purpose of the present study was to investigate the relation between the RCPM and the TONI-2 for samples of patients with Parkinson's disease (n = 75) and controls (n = 47). A regression equation was computed to evaluate the relation of the RCPM scores to the TONI-2 quotient. Regression equation results indicate that there is a significant overlapping linear variance between the two measures in both patients and controls.

Although the Fab fragment of the mouse-human chimeric anti-alphaIIbbeta3 (GP IIb/IIIa) monoclonal antibody (MoAb) c7E3 facilitates recombinant tissue-type plasminogen activator (rt-PA)-mediated thrombolysis, it is not clear whether this is due to inhibition of new clot formation and/or a direct effect on the lysis rate. We employed an in vitro flow (re)circulation model to investigate how c7E3 Fab affected (a) platelet adhesion to clotted fibrin substrates under laminar flow at wall shear rates of 100 or 500 s(-1) and (b) rt-PA-induced lysis of preformed mural platelet-fibrin substrates at 500 s(-1). c7E3 Fab dose-dependently (0.5-5 microg/ml) inhibited platelet adhesion from flowing whole blood onto fibrin substrates ( approximately 14 microm thick) at each wall shear rate. When at 5 min after the onset of flow, c7E3 Fab (0.1-10 microg/ml) and rt-PA (1 microg/ml) were coinjected in flowing blood, it was found that modest fibrinolysis caused major platelet release from fibrin substrates and there was no difference in the lysis rate in the presence of rt-PA + c7E3 Fab compared to rt-PA alone. Platelet pretreatment with c7E3 Fab (10 microg/ml) had no effect on the lysis rate of thin ( approximately 40 microm), and slightly delayed the lysis rate of thick (< 250 microm), platelet-fibrin substrates containing evenly dispersed platelets (10(9)/ml). When the platelets within thick platelet-fibrin substrates were organized in platelet-rich regions ("residual thrombi"), these substrates followed a nonuniform lysis pattern, where fibrin between the thrombi lysed first and the residual thrombi lysed at a slower rate. Platelet pretreatment with c7E3 Fab (10 microg/ml) abolished the formation of the lytic-resistant residual thrombi and the associated platelet-protected fibrin zones. Hence, treatment with c7E3 Fab has no direct effect on the rate of rt-PA-mediated lysis, but is expected to block platelet-fibrin interactions that lead to clot retraction, thus maintaining a fibrin architecture that is more susceptible to lysis.

The Wisconsin Card Sorting Test, a standard test for the assessment of executive function and free of a motor component, was employed for the assessment of 37 nondemented patients with idiopathic Parkinson's Disease and 37 matched normal controls. The symptoms of the patients were clinically assessed by means of the Unified Parkinson's Disease Rating Scale, which yielded scores for the cardinal symptoms of the disease as well as a total motor score. The Wisconsin Card Sorting Test was administered in all subjects in its original form (128 cards), and it was scored to yield 16 measures according to the instruction of the Wisconsin Card Sorting Test revised manual. Patients with Parkinson's Disease had significantly lower scores on the following test variables: number of trials administered, perseverative responses, percent perseverative responses, and failure to maintain set. The correlations between the last three variables and total motor score were statistically significant. Of the four cardinal symptoms of the disease, only rigidity correlated significantly with the number of perseverative responses and percent perseverative responses. These findings provide a clue that the lower performance of these patients on certain variables of the Wisconsin Card Sorting Test may be related to the process of the disease.

Seventy-three subjects with mild and moderate intellectual disability (ID) of an unknown/idiopathic nature, who had no record of specific deficits in motor control, and 73 normal controls, matched for chronological age and sex, underwent evaluation of handedness. The results confirmed the previously reported excess of non-right handedness among subjects with ID, and suggested that this finding might be indicative of a deviant cerebral organization or atypical lateralization of cerebral representation of function in this group. However, it was noted that further research is needed to clarify how far this is a function of level of motor skill and how far is a syndrome-specific pathological phenomenon.

We report on effects of pulsatile flow on monocytic cell adhesion to the surface of a model in which flow characteristics thought to be important in atherogenesis are simulated. The surface was coated with E-selectin, and adhesion of activated monocytes was investigated under pulsatile flow conditions and compared with uncoated models and steady flow experiments. Coating the model with E-selectin increased the adhesion of cells in all regions in the vertical model. However, pulsatile flow with the same mean Reynolds number as for steady flow significantly reduced the number of adherent cells throughout the model.

Two adjective pairs in comparative form, more-less and taller-shorter, were tested with moderately mentally retarded (MR) and nonretarded children (NR) matched on verbal mental age (MA) and socioeconomic status (SES) in a "show" and an "act-out" experimental condition. The data indicated that all the main effects, the group, the experimental condition, and the unmarked-marked relational terms were significant and so were the interactions of the Group x Experimental Conditions, Group x Unmarked Versus Marked Relational Terms, and Group x Experimental Conditions and Unmarked Versus Marked Relational Terms. A logistic regression analysis (LRA) showed that the relational term shorter in the act-out condition best predicted classification membership for the subjects in either group, suggesting that the MR children were less able to self-regulate behavior. The error types, however, mainly observed in the act-out experimental condition were the same from a semantic point of view in either group. The effect of the unmarked versus marked distinction cannot be considered independent of the experimental conditions applied.

Visuospatial discrimination was evaluated longitudinally in 45 patients with idiopathic Parkinson's disease. 47 normal matched subjects served as controls. Visuospatial discrimination was assessed by means of a picture test with complex superimposed objects (Poppelreuter's test) at the beginning of the study as well as three years later. At initial evaluation the group with Parkinson's disease identified fewer objects than the control group and made more errors. Relations between performance on the visuospatial discrimination task and the main parameters of the disease were not statistically significant. At reevaluation, three years later on the same task, performance by the group with Parkinson's disease deteriorated. Longitudinal assessment of motor symptoms showed that disease progressed during the study period in 35 patients. Comparison of motor deterioration with performance on the visuospatial discrimination task showed no statistically significant relationship.

In the present study, fifty-four subjects were tested; twenty-seven with idiopathic Parkinson's disease and twenty-seven normal controls matched in age, education, verbal ability, level of depression, sex and socio-economic status. The subjects were tested on eight tasks. Five of the tasks were the classic deductive reasoning syllogisms, modus ponens, modus tollendo tollens, affirming the consequent, denying the antecedent and three-term series problems phrased in a factual context (brief scripts). Three of the tasks were inductive reasoning, including logical inferences, metaphors and similes. All tasks were presented to subjects in a multiple choice format. The results, overall, have shown nonsignificant differences between the two groups in deductive and inductive reasoning, an ability traditionally associated with frontal lobes involvement. Of the comparisons performed between subgroups of the patients and normal controls concerning disease duration, disease onset and predominant involvement of the left and/or right hemisphere, significant differences were found between patients with earlier disease onset and normal controls and between bilaterally affected patients and normal controls, demonstrating an additive effect of lateralization to reasoning ability.