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C J Jen

Publications and source records attributed to C J Jen.

46 records · Page 3Linked to original sources
PubMed1987

Direct platelet-fibrin interaction that does not require platelet activation.

Interactions between platelets and fibrin are important in hemostasis but often confused with platelet-fibrinogen interactions. Fibrin solubilized in NaBr-acetic acid formed polymers in neutral pH buffers. A stirred mixture of solubilized fibrin and washed human platelets at neutral pH range showed drastic reduction in turbidity and concomitant platelet adhesion onto newly formed fibrin strands. Optimally, more than 99% of platelets could be associated with fibrin, whereas only 3% of erythrocytes were trapped in the fibrin network under similar conditions. This platelet-fibrin interaction was fibrin concentration dependent and polymerization stage dependent. It preceded any detectable platelet release of serotonin. Gly-Pro-Arg-Pro (250 times in excess) retarded the kinetics of fibrin polymerization as well as that of platelet-fibrin interaction. However, factors affecting platelet activation showed little effect on platelet-fibrin interaction. Our results support the existence of a platelet-fibrin interaction that does not require platelet activation.

Adenosine Diphosphate↗
PubMed1986

Platelet microtubules in clot structure formation and contractile force generation: investigation of a controversy.

Whether platelet microtubules are involved in clot retraction/contraction has been controversial. To address this question we have simultaneously measured two clotting parameters, clot structural rigidity and isometric contractile force, using a rheological technique. For recalcified PRP clots these two parameters began rising together at about 15 min after CaCl2 addition. In the concentration range affecting microtubule organization in platelets, colchicine, vinca alkaloids and taxol demonstrated insignificant effects on both clotting parameters of a recalcified PRP clot. For PRP clots induced by adding small amounts of exogenous thrombin, the kinetic curves of clot rigidity were biphasic and without a lag time. The first phase corresponded to a platelet-independent network forming process, while the second phase corresponded to a platelet-dependent process. These PRP clots began generating contractile force at the onset of the second phase. For both rigidity and force parameters, only the second phase of clotting kinetics was retarded by microtubule affecting reagents. When PRP samples were clotted by adding a mixture of CaCl2 and thrombin, the second phase clotting was accelerated and became superimposed on the first phase. The inhibitory effects of microtubule affecting reagents became less pronounced. Thrombin clotting of a two-component system (washed platelets/purified fibrinogen) was also biphasic, with the second phase being microtubule-dependent. In conclusion, platelet microtubules are important in PRP clotted with low concentrations of thrombin, during which fibrin network formation precedes platelet-fibrin interactions. On the other hand they are unimportant if a PRP clot is induced by recalcification, during which the fibrin network is constructed in the presence of platelet-fibrin interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1984

The gelation kinetics of platelet extracts.

The kinetics of the gelation process that occurs upon warming cold platelet extracts were studied using a sensitive rheometer. At micromolar or less free Ca2+ concentrations and in the presence of 1 mM ATP, the gel rigidity curves showed several peaks, indicating that platelet extract proteins went through network assembling/disassembling cycles during gelation. The gelation kinetics were accelerated by increasing the free Ca2+ concentration up to about 2 microM. At 4-15 microM free Ca2+, the gelation cycles were completely abolished except for the first peak. The gelation process became one of monotonically increasing elastic modulus at millimolar free Ca2+ concentrations. Trifluoperazine (50 microM), a calmodulin inhibitor, did not affect gelation at micromolar free Ca2+ concentrations. Except for the first gelation step, which was completed within 5 min after warming, the rest of the gelation process was found to be affected by K+, ATP, cytochalasin E and colchicine. K+ at concentrations higher than 10 mM retarded the gelation kinetics. Extracts prepared with low (0.1 mM) ATP content showed impaired gelation, and this was partially reversed by adding 1 mM ATP, but not 1 mM adenylylimidodiphosphate (p[NH]ppA). Both cytochalasin E (1 microM) and colchicine (1 mM) interfered with the gelation process.

Adenosine Triphosphate↗
PubMed1984

Characteristics of shear-induced aggregation in whole blood.

A cone-and-plate viscometer was used to study shear-induced aggregation in whole blood. Aggregate size distribution curves were measured from samples subjected to controlled shear rates for varying time intervals. Blood samples in heparin, but not in citrate, developed aggregates at shear rates below 500 sec-1. These aggregates disintegrated at 1000 to 2000 sec-1. There appears to be a donor-specific threshold shear rate, above which significant amounts of shear-induced aggregation were found. For normal donors this threshold is in the range of 2000 to 3000 sec-1 for exposure times of 1 min. The extent of aggregation and the stability of aggregates formed increased with both shear rate and the shear time. Above the threshold shear rate, less than 6 sec exposure time was sufficient to trigger aggregation. Aggregates generated by exposing blood to shear above these levels for 30 to 60 sec were stable for at least 5 min. Blood in heparin was more sensitive to shear than that in citrate. Whole blood was more sensitive to shear than platelet-rich plasma. An ADP-utilizing enzyme system, creatine phosphate/creatine phosphokinase, was effective in reducing both sensitivity to and stability of shear-induced aggregation. Creatine phosphate alone was partially effective, whereas creatine phosphokinase alone was ineffective. This indicates that ADP released from cellular components in blood plays a positive role in shear-induced aggregation.

Creatine Kinase↗
PubMed1982

The structural properties and contractile force of a clot.

When citrated plasma is recalcified, it forms a viscoelastic gel--a clot. The relationship between platelet contractility and clot rigidity was studied by using a rheological technique which simultaneously measured both the dynamic rigidity modulus and the contractile force during gel formation with platelet rich plasma (PRP). Protein network formation in a clot was accompanied by a contractile force throughout the clotting process. PRP demonstrated a maximum elastic modulus of 6,000 dynes/cm2 and a maximum contractile force/area of 1,500 dynes/cm2. The values of these parameters for a platelet-free clot (PFP) were 700 dynes/cm2 and less than 100 dynes/cm2 respectively. Sonicated control PRP and PRP from a Glanzmann thrombasthenia patient both clotted in a manner similar to PFP. Metabolic inhibitors, 2-deoxy-D-glucose and KCN (5 mM each), retarded the clotting curves of PRP. Cytochalasin B and E suppressed both structural rigidity and force generation in a concentration-dependent manner similar to their inhibitory effect on actin polymerization in platelets. Colchicine (2.5 mM) or vinblastine (0.11 mM) did not affect these clotting curves. Thrombin-activated, fixed platelets did not generate any force, nor did they significantly increase clot rigidity. Streptokinase induced a concurrent decrease of both rigidity and force in PRP clots. The elastic modulus of a PFP clot could be increased to 2,500 dynes/cm2 by externally straining the network with an axial force/area of 1,500 dynes/cm2. Our results indicate that clot structure formation in PRP is strongly coupled to the contractile force generated by the platelet microfilament system and that this force modulates clot rigidity.

Blood Coagulation↗
PubMedDate not supplied

The various effects of fractionated oxidized low density lipoproteins on the growth of smooth muscle cells in culture.

The effects of fractionated oxidized low density lipoproteins (oxidized LDL) on the growth of vascular smooth muscle cells (VSMC) and their relationship to the formation of lysophosphatidylcholine (lyso-PC) as well as the activation of protein kinase C (PKC) were studied. VSMC were isolated from porcine aorta by explant culture. LDL was isolated from porcine blood by sequential ultracentrifugation and oxidized LDL was obtained by incubating LDL with 5 microM CuSO(4) at 37 degrees C for various lengths of time. Our results showed that LDL oxidized for 12 h and eluted from fast protein liquid chromatography at 43 min inhibited the growth of VSMC, and that LDL oxidized for longer than 48 h and eluted at 48 min stimulated the growth of VSMC. The formation of lyso-PC in the oxidized LDL correlated well with its stimulatory effect, suggesting that lyso-PC is responsible for the mitogenic effect of oxidized LDL. This stimulatory effect of oxidized LDL was inhibited by staurosporine, a PKC inhibitor. Treatment with oxidized LDL increased the activity of membrane PKC, but it decreased that of cytosolic PKC, suggesting the translocation of PKC from cytosol to the membrane in the presence of oxidized LDL. These results suggested that the oxidized LDL-stimulated VSMC growth was mediated by the formation of lyso-PC and the activation of PKC.

Animals↗
PubMedDate not supplied

Platelet adhesion onto the wall of a flow chamber with an obstacle.

In the present study, the data of the initial adhesion of platelets onto the wall of a flow chamber with an obstacle in steady human blood flows were obtained. The flowfields and the distribution of stress-related factors were simulated numerically by a finite volume method and the fluid dynamic effect on the platelet adhesion is discussed. In addition to the wall shear effect, the normal stress effect was also taken into account. A parameter Vn/[Vt] was devised to assess the combined effect of both shear and normal forces in platelet adhesion. It was found that the peak adhesion occurred next to, but not on, the impingement point on the obstacle where the value of Vn/[Vt] was negative. In these regions, direct impact played a major role in platelet adhesion. On the other hand, near the separation point before the obstacle where Vn/[Vt] was insignificant, the mechanism was believed to be different from that in the direct impact region. Denser adhesion there might be caused by the accumulation and frequent collision of particles due to flow retardation and/or detour of the flow path. Interestingly, relatively low adhesion was found inside the recirculation regions. These results show that the normal stress effect (impingement) should be considered in platelet adhesion in addition to the shear effect.

Blood Flow Velocity↗