bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental characterisation of coaxial TSV transistor keep out zones
Authors: Adamshick Stephen , Northrup Steven , Liehr Michael
Published: July 2018

Three‐dimensional (3D) integration is an emerging technology that aims to achieve efficient packaging of the multifunctional silicon (Si) die within a single chip package. This system in package approach achieves connectivity between the individual Si die using through Si via (TSV) technology. Coaxial TSVs have emerged as the preferred 3D interconnect for high‐frequency packaging applications due to their superior high‐frequency electrical characteristics. The interconnect utilises a copper shield to prevent noise and unwanted signal coupling to occur within the Si substrate. However, a potential disadvantage of 3D integration is the large transistor keep‐out‐zones (KOZs) required to prevent transistor variability caused by thermally induced stress due to the copper‐based TSVs in the Si substrate. Currently, only analytical models exist that predict KOZs for various coaxial TSV configurations and determining the precise KOZ is critical to minimise interconnect footprint that results in increased costs due to reductions in Si die area for integrated circuit designers. For the first time, the work has characterised the thermomechanical behaviour of fabricated coaxial TSVs utilising the microRaman spectroscopy technique to define transistor KOZ for both analogue and digital circuital applications.
Agglomeration of the poly(butadiene‐styrene) latex triggered by CO2 bubbling and the preparation of poly(methyl methacrylate‐butadiene‐styrene) core/shell particles with a wide size distribution
Authors: Sun Jianwu , Jiang Yiming , Zhou Xiaoteng , Ning Bo , Qin He , Kan Chengyou
Published: July 2018

In order to meet the requirement of impact modifier, the agglomerated butadiene‐styrene rubber (a‐SBR) latexes were first prepared by bubbling CO2 into original butadiene‐styrene rubber latex with the diameter about 100 nm, and then the poly(methyl methacrylate‐butadiene‐styrene) latexes (a‐MBS) with a wide particle size distribution were fabricated via seeded emulsion copolymerisation of styrene and methyl methacrylate onto the a‐SBR seeds. It was found that the pH value of the system decreased slowly with the time of CO2 bubbling, while a‐SBR particles were not enlarged until the pH value reduced to about 8. In particular, when the pH value decreased to around 7, the size of a‐SBR particles enlarged dramatically and the agglomerated system should be adjusted immediately to alkaline condition with NaOH aqueous solution. Transmission electron microscopy observation indicated that the a‐MBS particles with a wide size distribution were successfully prepared. Moreover, both the shell thickness and grafting efficiency of the MBS particles decreased gradually with the increasing SBR particle size, while the rubber volume fraction of MBS particles increased. The whole process of agglomeration and grafting copolymerisation is mild, efficient and has great potential in the industrial application.
Prey herd behavior modeled by a generic non-differentiable functional response
Authors: Vilches Karina , González-Olivares Eduardo , Rojas-Palma Alejandro
Published: July 2018

Over the past decade, many works have studied an antipredator behavior (APB) namedprey herd behavior. Analyzes have been conducted by modifying the classical predator consumption rate to be dependent only on the prey population size assuming thesquare root functional response. This work focuses analyzing the dynamics of a Gause-type predator-prey model considering that social behavior of prey. However, we model this phenomenon using a Holling type II non-differentiable rational functional response, which is more general than that mentioned above. The studied model exhibits richer dynamics than those with differentiable functional responses, and one the main consequences of including this type of function is the existence of initial values for which the extinction of prey occurs within a finite time for all parameter conditions, which is a direct consequence of the non-uniqueness of the solutions over the vertical axes and of the existence of a separatrix curve dividing the phase plane. A discussion on what represents a well-posed problem from both the mathematical and the ecological points of view is presented. Additionally, the differences in other social behaviors of the prey are also established. Numerical simulations are provided to validate the mathematical results.
Step-Down Task Identifies Differences in Ankle Biomechanics Across Functional Activities
Authors: Donovan Luke , Miklovic Tyler , Feger Mark
Published: July 2018

Currently, there is no clinical exam to evaluate ankle frontal plane kinematics. The purpose of this study was to determine whether individuals identified as “lateral” landing during a video-recorded step-down task have differences in ankle inversion as measured with 3-dimensional motion capture during walking, step-down, and jump-landing tasks compared to individuals identified as “non-lateral”. Fifty-seven recreationally active adults completed the descriptive laboratory study. During walking, step-down, and jump-landing tasks, participants had their ankle frontal plane kinematics measured using a 3-dimensional motion capture system. In addition, during the step-down task, participants had a posterior view video of their foot recorded using a commercial camera. Following testing, a blinded-investigator scored the step-down video of all participants by classifying them as ”lateral” landing or ”non-lateral” landing. Ankle frontal plane kinematics during the walking, step-down, and jump-landing tasks were compared between the two groups (lateral (N=24) and non-lateral (N=33) using a binary logistic regression and time-series confidence interval analysis. During walking, stepping-down, and jump-landing, the lateral group had significantly more inversion at initial contact and during various other phases specific to each task. This study found that a clinical screening tool could identify individuals who have significantly more inversion during three tasks.
Synthesis of Fully Functionalized 3-Bromoazaspiro[4.5]trienones through Ugi Four-Component Reaction (Ugi-4CR) followed by ipso-Bromocyclization
Authors: Balalaie Saeed , Ghoroghaghaei Hadiseh , Alavijeh Nahid , Darvish Fatemeh , Rominger Frank , Bijanzadeh Hamid
Published: July 2018

Biologically attractive azaspiro[4.5]trienones have been prepared via Ugi four-component reaction (Ugi-4CR) followed by bromine-mediated ipso-cyclization. This allows a straightforward synthetic route to a diverse collection of fully functionalized 3-bromoaza­spiro[4,5]trienones in moderate to good yields that can be used as templates for further modifications.
Platelet Behaviour in Normal Pregnancy, Pregnancy Complicated by Essential Hypertension and Pregnancy-Induced Hypertension
Authors: Morrison R , Crawford J , MacPherson M , Heptinstall S
Published: July 2018

Platelet behaviour was studied throughout pregnancy in a group of women who remained normotensive and a group with essential hypertension (EHT). Women who developed pregnancy-induced hypertension (PIH) were also studied together with a group of non-pregnant female controls. We determined the sensitivity of platelets to arachidonic acid (AA) and determined the effects of dazoxiben, a thromboxane synthetase inhibitor, on AA-induced platelet behaviour.

A marked increase in platelet reactivity was evident in all three groups throughout pregnancy; platelets became more sensitive to AA and less sensitive to the inhibitory effects of dazoxiben. The change was apparent as early as 16 weeks gestation. In normotensive pregnancy and in EHT platelet behaviour had returned to normal six weeks after delivery. Platelets from women who developed PIH were more sensitive to AA than those from the other pregnant women and platelet reactivity had not returned to normal six weeks after delivery.

The results indicate that alterations in platelet behaviour may contribute to the vascular complications that are known to be associated with pregnancy and with PIH in particular.
One Year Follow-Up Study of T-Cell Subsets and Incidence of Seropositivity for HTLV-I and HTLV-III Antibodies in Patients Treated “On Demand” or Sporadically with Clotting Concentrates
Authors: Rodeghiero F , Castaman G C , Chisesi T , De Rossi A , Dalla Gassa O , Del Mistro A , Dini E , Castronovo S , Pornaro E , Chieco-Bianchi L
Published: July 2018

A 1-year follow-up study of the T-cell subset abnormalities was carried out in 16 severe haemophilia A patients, treated “on demand” with an average amount of 500 U/kg/yr of factor VIII concentrate (group A) and in 15 mild haemophiliacs or von Willebrand patients treated only sporadically with less than 3000 U of factor VIII and no longer exposed to any other blood component in the 2 years preceding the beginning of the study (group B).

In group A, 50% and 70% of patients showed a reduced or inverted T 4/T 8 ratio, respectively, at the beginning and at the end of follow-up. These values were of 30% and 20% in patients of group B, suggesting a long-lasting effect of concentrate therapy on T-cell subsets. The low T 4/T 8 ratio was mainly due to an increase of suppressor cells. None of the patients was found positive for anti HTLV-I, whereas 3 patients, all belonging to the group A, showed antibodies against HTLV-III. Thus, in these patients, HTLV-III seems not to be the only cause of low T 4/T 8 ratio.
Assay of Human Tissue-Type Plasminogen Activator (t-PA) with an Enzyme-Linked Immunosorbent Assay (ELISA) Based on Three Murine Monoclonal Antibodies to t-PA
Authors: Holvoet Paul , Cleemput Hugo , Collen Désiré
Published: July 2018

An enzyme-linked immunosorbent assay (ELISA) for the measurement of human tissue-type plasminogen activator (t-PA) was developed. Microtiter plates were coated with a mixture of two monoclonal antibodies and bound t-PA was quantitated with a third monoclonal antibody linked to peroxidase. The lower limit of sensitivity of the assay was 0.2 ng of t-PA per ml. The concentration of antigen in citrated plasma of human subjects was found to be 3.4 ± 0.8 ng/ml. The assay had a good reproducibility with values of 3.8, 6.5 and 4.9 percent respectively for the intra-, inter-assay and inter-dilution variation coefficients. The results of the ELISA assay on plasma samples from patients during thrombolytic therapy with t-PA correlated very well, over a wide concentration range, with those obtained with a previously described two-site immuno-radiometric assay (r = 0.96). This ELISA with monoclonal antibodies constitutes a stable and reproducible set of reagents for the measurement of t-PA antigen in biological fluids, avoiding the disadvantages of the use of radioisotopes and of polyclonal antibodies.
Epidemiological Study on Factor VII, Factor VIII and Fibrinogen in an Industrial Population - II. Baseline Data on the Relation to Blood Pressure, Blood Glucose, Uric Acid, and Lipid Fractions
Authors: Balleisen L , Assmann G , Bailey J , Epping P-H , Schulte H , van de Loo J
Published: July 2018

In a preceding paper the baseline data in the Munster Arteriosclerosis Study (PROCAM study) of the levels of fibrinogen, factor VIIc and factor VIIIc were described, and their correlation of age, body weight, smoking, alcohol, pill-using and menopause discussed. In this part the relationship of these coagulation factors to blood pressure, blood glucose, uric acid and lipid parameters, which were examined in 4186 apparently healthy individuals, is presented. The correlations are described using two different statistical models, first the Pearson correlation coefficients after allowing each clotting factor for the effects of age, cigarette and alcohol consumption, body weight, menopausal state, pill using and the other clotting factors, and secondly by a multiple regression analysis. The data suggest that there are multiple interrelationships between hemostatic factors and the variables under consideration. The most striking positive correlations were found for factor VII c to blood glucose and triglycerides in men and women and to HDDcholesterol in women.
The Influence of Molsidomine and Its Active Metabolite SIN-1 on Fibrinolysis and Platelet Aggregation
Authors: Basista M , Grodzińska L , święs J
Published: July 2018

Molsidomine and its active metabolite SIN-1 were examined in humans and animals for platelet suppressant and fibrinolytic activities.

Following oral administration of molsidomine at doses of 6 or 15 mg/kg to rabbits, their blood platelets in PRP ex vivo required higher threshold concentrations of ADP, AA and thrombin to be aggregated. Unlike molsidomine, SIN-1 when infused (10 and 20 μg/kg i.v.) into anaesthetized cats caused a release of a substance disaggregating platelet clumps which had adhered to blood superfused collagen strip. The appearance of this unstable disaggregating substance was prevented by the pretreatment of cats with aspirin (50 mg/kg i.v.). It is suggested that SIN-1 may promote formation of a PGI2-like substance.

In humans shortening of euglobulin clot lysis time was observed 60 min after a single ingestion of 2 mg of molsidomine. This fibrinolytic effect of molsidomine was not abolished by the pretreatment of patients with aspirin. Neither molsidomine nor SIN-1 activated fibrinolysis in preformed euglobulin clots in vitro.
Evidence for Glycoprotein Abnormality in Platelets from Patients with May-Hegglin Anomaly
Authors: Ricci Giorgio , Manservigi Roberto , Albonici Loredana , Zavagli Giorgio , Cassai Enzo
Published: July 2018

In the present research protein analysis on SDS-polyacry-lamide gel electrophoresis (PAGE) has been used to study the glycoprotein pattern of the blood platelets of four members from a family affected by May-Hegglin anomaly. In order to characterize the glycoprotein fractions, lactoperoxidase-iodination and immunoprecipitation procedures were used.

N,N’diallyltartardiamide (DATD) cross-linked gel electrophoresis was shown to improve the glycoprotein pattern resolution, although with the lactoperoxidase-iodination the glycoprotein characterization of May-Hegglin platelets overlapped the normal. On the other hand with the immunoprecipitation the specific antiserum precipitated all the five major fractions of normal membrane glycoproteins, but it was shown to react quite poorly with the component V of the May-Hegglin glycoprotein pattern.
Experimental Studies on Venous Thrombosis: Effect of Coagulants, Procoagulants and Vessel Contusion
Authors: Aronson David L , Thomas Duncan P
Published: July 2018

We have examined the relative contribution of stasis, activated coagulants, procoagulants and vessel wall damage in the pathogenesis of experimental venous thrombosis. Using a Wessler stasis model in rabbits, we found an inverse correlation between duration of stasis and the amount of Contact Factor and Factor Xa required to produce a stasis thrombus. However, the slope of the dose-response curve for producing thrombi was different with these two coagulants. The infusion of Factor IX complex was also thrombogenic in this model despite prolonged circulation prior to stasis, implying that high levels of multiple procoagulants may be thrombogenic. In contrast, Factor VIII concentrates or a purified Factor IX preparation did not give thrombi under these conditions.

When the vessel wall was crushed mechanically, followed by restored blood flow and subsequent stasis, there was essentially no formation of thrombi over the time course of the experiments. Scanning electron microscopy demonstrated that although the endothelium was swollen and damaged, there was usually no exposure of sub-endothelium and no adherence platelets. Where there was definite disruption of the endothelium, activated platelets could be seen adhering to the vessel wall. However, the blood in the segments remained fluid over a period of 30 min, despite the presence of adherent platelets.

Our experiments demonstrated that the combination of vessel wall damage and stasis was relatively ineffective in producing venous thrombosis. In contrast, high levels of zymogens or small amounts of activated clotting factors, combined with local stasis, is a very effective thrombogenic stimulus in the venous system.
Antithrombin III Determination by Rate (Kinetic) Nephelometry
Authors: Balla G , Misz M , Karmazsin L , Rák K
Published: July 2018

Rate nephelometry immunological antithrombin III determination was elaborated with Beckman Immunochemistry System. The measuring can be carried out within 60 sec from 20 μl plasma. The results show a close correlation with those of gained by the radial immunodiffusion method (r = 0.91) and by Coatest (Kabi-Ortho) (r = 0.77). Both laser-nephelometric and usual non-nephelometric anti-antithrombin III serum (Behring) may be applied.
A Double-Blind Trial of Intramuscular Stanozolol in the Prevention of Postoperative Deep Vein Thrombosis Following Elective Abdominal Surgery
Authors: Blarney S L , McArdle B M , Burns P , Carter D C , Lowe G D O , Forbes C D
Published: July 2018

Fibrinolytic shutdown may be important in the development of postoperative deep vein thrombosis (DVT). We have previously shown that stanozolol 50 mg, given intramuscularly 24 hr before surgery, prevents the decrease in plasminogen activator activity (PA) seen on the first postoperative day in patients at high risk of DVT. To investigate the role of fibrinolytic shutdown in causation of DVT, sixty patients were randomised in a double-blind controlled trial to receive stanozolol or placebo intramuscularly, and DVT was detected by leg scanning and confirmed by venography. Scan positive DVT occurred in IT of 31 placebo patients (35%) and 12 of 29 who received stanozolol (41%). A significant decrease in PA was confirmed in the placebo group, while stanozolol caused a significant increase in PA on the first postoperative day. Patients in either group who did not develop DVT showed minimal changes in PA. We conclude that prevention of fibrinolytic shutdown by this regimen of stanozolol does not prevent postoperative DVT, and that further studies are required to clarify the relationships of postoperative fibrinolysis and DVT.
Selective PF4 Release In Vitro Induced by Heparin and Related Glycosaminoglycans (GAGs) - Correlation with β-TG Release and Platelet Aggregation
Authors: Cofrancesco E , Colombi M , Cristoforetti G , Pogliani E M
Published: July 2018

We studied human platelet aggregation and β-TG/PF4 release induced by heparin and related GAGs in vitro both in normal PRP and in PRP after aspirin. In our experimental conditions, heparin and related GAGs always caused PF4 release in vitro from normal platelets, whether or not there was measurable platelet aggregation in the aggregometer. Significant β-TG release was induced only by the mucosal heparin preparation (which also induced platelet aggregation in some citrated PRP). Therefore, while β-TG release in vitro seems to correlate with platelet aggregating activity of heparin, the selective PF4 release, caused by heparin and related GAGs also in conditions in which neither platelet aggregation nor β-TG are measurable, is probably associated with the high affinity of PF4 for heparin. The degree of affinity of GAGs for PF4 (heparin > DeS > HS) seems to correlate with PF4 release. Moreover, the significant reduction in PF4 release in vitro after aspirin suggests that GAGs-induced PF4 release is related to a cyclooxygenase-dependent activation process.
Dysfibrinogenemia (Fibrinogen Dusard) Associated with Impaired Fibrin-Enhanced Plasminogen Activation
Authors: Lijnen H R , Soria J , Soria C , Collen D , Caen J P
Published: July 2018

The fibrin-mediated enhancement of the activation of plasminogen by tissue-type plasminogen activator observed with normal fibrin, is strongly decreased with fibrin Dusard, although the binding of tissue-type plasminogen activator to this fibrin is normal. This impaired fibrin-mediated plasminogen activation is most likely related to the history of recurrent thrombosis and pulmonary embolism observed in this family.
Effects of Tris on Responses of Human and Rabbit Platelets to Aggregating Agents
Authors: Packham M A , Guccione M A , Nina M , Kinlough-Rathbone R L , Mustard J F
Published: July 2018

Despite reports that Tris [tris(hydroxymethyl)aminomethane] affects platelets, it is often used to buffer suspending media. Human or rabbit platelets were washed and resuspended in Tyrode solution containing apyrase and 0.35% albumin. Addition of 15 mM Tris partially inhibited primary aggregation induced by 10 μM ADP and inhibited aggregation and release of 14C- serotonin from prelabelled platelets stimulated with low concentrations of thrombin (0.05-0.2 U/mL), or collagen. Platelets resuspended in 15 mM Tris, 0.15 M NaCl, 0.35% albumin, pH 7.5, did not aggregate in response to 10 μM ADP whereas platelets in Tyrode-albumin aggregated extensively. Ca2+ (5 mM) did not overcome the inhibition of thrombin-induced aggregation. Tris (15 or 1.5 mM) potentiated aggregation and release induced by sodium arachidonate (20-50 μM) or the ionophore A23187 (0.6-1 μM). Pretreatment of platelets with aspirin did not prevent potentiation by A23187, indicating that it is not mediated through activation of the arachidonate pathway. The inhibitory and potentiating effects of Tris are similar to those of amino sugars, lysine, arginine and primary amines such as methylamine and cadaverine, and may represent general effects of amines on platelets. Potentiation of the effects of some aggregating agents and inhibition of others re-emphasizes the concept that there are several different mechanisms through which aggregation can occur. Tris-based buffers are unsuitable for platelet suspending media and their use as solvents for aggregating agents or inhibitors should be limited.
Comparison Between Vascular Plasminogen Activator Activity and Changes in Blood Flow in the Renal Cortex in Pigs
Authors: Smokovitis Athanasios , Maier Manfred , Binder Bernd R
Published: July 2018

Patterns of vascular plasminogen activator activity (PAA) and of blood flow were compared in the renal cortex of pigs. The comparison was made in pigs with or without induction of hemorrhagic hypotension and continuous infusion of indomethacin (prostaglandin synthetase inhibitor) or saralasin (competitive inhibitor of angiotensin II). Blood flow was measured by radiolabelled microspheres. A significant decrease in the vascular PAA was observed only in saralasin treated animals (15% in not hemorrhaged pigs and 30% in the inner and 45% in the outer half of the renal cortex in hemorrhaged pigs). Changes in plasmin inhibitor activity in the renal cortex were not noted. No correlation could be seen between vascular PAA and changes in blood flow in the renal cortex or changes in the mean arterial blood pressure. The vascular fibrinolytic response to saralasin should be due to an effect of saralasin independent of the changes in blood flow induced by this agent.
Mass Action Effects on Competitive Adsorption of Fibrinogen from Hemoglobin Solutions and from Plasma
Authors: Horbett Thomas A
Published: July 2018

The strong effect of protein adsorption on blood and tissue compatibility is well known. Little is presently known about the mechanisms which control the composition of the adsorbed protein layer which forms upon exposure of surfaces to mixtures of proteins. Reexamination of the ability of hemoglobin to inhibit the adsorption of 125I fibrinogen to polyethylene revealed that the inhibition was strongly dependent on the fibrinogen concentration. These results suggested that fibrinogen adsorption from more complex mixtures such as plasma should also be strongly dependent on total concentration. Fibrinogen adsorption from plasma was found to be maximal at intermediate plasma concentrations, and was reduced at both low and high plasma concentrations. The plasma concentration at which this maximum occurred was 10% for polytetrafluoroethylene, 1% for polyethylene, and 0.1% for glass. The unusual concentration dependence is attributed to mass action effects on the competitive adsorption of proteins, specifically that competitive effectiveness is expected to increase as unoccupied surface adsorptive sites become less frequent. Analogous effects of adsorption time on competitive adsorption are also predicted due to the changing concentration at the interface as the buffer is gradually replaced by protein solution. These mass action effects are very similar to previous qualitative observations by Vroman and are therefore dubbed the “Vroman effect”.
Selective Increases of Procoagulant Activity in Rabbit Lymphoid Populations In Vitro Following Stimulation with Endotoxin: Dependence on Anatomic Source
Authors: McGee Maria P , Rothberger Henry , Lee Tung-Kuang
Published: July 2018

Rabbit mononuclear leukocytes isolated from a variety of anatomic sites were examined for ability to generate procoagulant activity in vitro. Marrow, blood and spleen mononuclear cell populations were found to differ functionally from lymph node, thymus and alveolar populations by having much greater ability to increase in tissue factor activity in response to an endotoxin stimulus. Thus, after incubation in the presence of endotoxin, leukocytes obtained from marrow, blood, and spleen were found to increase in procoagulant activity characterized as tissue factor by 832, 1942 and 12.6 fold, respectively. In contrast, pulmonary alveolar macrophages increased in tissue factor activity only by 2.8 fold, and lymph node and thymus mononuclear cells showed little or no increases. These functional differences, demonstrated by exposing the six cell populations to endotoxin under controlled conditions in vitro, likely explain the similar pattern of anatomic selectivity of leukocyte tissue factor increases reported to occur in vivo during endotoxemia and Shwartzman reactions (1).
A Comparison of Human Pulmonary Arterial and Venous Prostacyclin and Thromboxane Synthesis- Effect of a Thromboxane Synthase Inhibitor
Authors: Carter A J , Bevan J A , Hanley S P , Morgan W E , Turner D R
Published: July 2018

The amounts of 6-keto-prostaglandin F1α (6-keto-PGF1α) and thromboxane B2 (TxB2) produced by the endothelial surfaces of paired samples of human pulmonary arteries and veins, obtained from patients undergoing thoracic surgery, were measured. The amounts of 6-keto-PGF1α and TxB2 produced by arteries compared with veins were not different. However, both arteries and veins produced more 6-keto-PGFlα than TxB2, the ratio being approximately 7.5:1 for both. 6-keto-PGFlα synthesis by arteries was significantly correlated with that produced by veins but the relative amounts of TxB2 were not correlated. 6-keto-PGFlα synthesis was correlated with TxB2 synthesis for veins but not for arteries. 8 of the 12 arterial samples exhibited some degree of intimal fibrosis.

Incubation with the thromboxane synthase inhibitor, dazoxiben, caused a significant inhibition of vascular TxB2 synthesis and a significant increase in 6-keto-PGFlα synthesis. In 3 of the 5 cases the increase in 6-keto-PGFlα was too large to be explained by the fall in TxB2.
Influence of Vitamin E on Plasma Malondialdehyde- Like Material in Man
Authors: Cordova C , Musca A , Violi F , Alessandri C , Ghiselli A , Iuliano L , Balsano F
Published: July 2018

The behaviour of plasma malondialdehyde-like material (MDA-LM) was evaluated in 13 healthy subjects by a single-blind study that consisted of placebo (30 days), vitamin E treatment (300 mg/day) (30 days) and placebo (30 days). The study demonstrated that MDA-LM did not change during placebo treatment while it significantly decreased after vitamin E administration.
Evidence for the Occurrence of a Fast-Acting Inhibitor for Tissue-Type Plasminogen Activator in Human Plasma
Authors: Verheijen J H , Chang G T G , Kluft C
Published: July 2018

Human plasma contains a fast-acting t-PA inhibitor, which is not identical with α2-antiplasmin or α2-macroglobulin. The concentration of this inhibitor in normal plasma is highly variable, much lower than that of known plasma protease inhibitors, and in the range of physiologically occurring plasma concentrations of t- PA (0-2 IU/ml).

The inhibitor binds to concanavalin A-Sepharose, is rather stable when heated, is not precipitated in euglobulin fractions and probably does not originate from platelets. The inhibitor seems to form a 190 Kd complex with t-PA. The relation between this plasma inhibitor and the recently discovered endothelial cell inhibitor is not yet clear.
Pressure-Induced Metabolic Activation of Platelets Demonstrated In Vitro by Determination of Malondialdehyde Formation
Authors: Torsellini Alessandro , Doni Luca , Palinski Wulf , Guidi Giovanni , Lombardi Valeriano
Published: July 2018

Platelet rich plasma (PRP) exposed in vitro to 200 mm Hg above atmospheric pressure showed a significant increase in malondialdehyde (MDA) formation compared to PRP at atmospheric pressure. This difference is also evident when platelets are incubated with arachidonic acid.

The increase of MDA demonstrates that the increased beta- thromboglobulin and platelet factor 4 in plasma and the shape changes of platelets after pressure stimulation in vitro that were described in a previous paper result from the release reaction.

Pressure-induced effects in vivo are discussed
Prothrombin Evaluation as Obtained by Kinetics Studies of Antigen-Antibody Reaction in a Laser Nephelometer
Authors: Girolami A , Sticchi A , Melizzi R , Saggin L , Ruzza G
Published: July 2018

Laser nephelometry is a technique which allows the evaluation of the concentration of several serum proteins and clotting factors. By means of this technique it is also possible to study the kinetics of the reaction between antigen and antibody. We studied the kinetics of the reaction between prothrombin and an antiprothrombin antiserum using several prothrombins namely: Prothrombin Padua, prothrombin Molise, which are two congenital dysprothrombinemias, cirrhotic, coumarin or normal prothrombins. Different behaviors in the kinetics of the reactions were shown even when the concentration of prothrombins was about the same in all plasma tested. These differences were analyzed by means of a computer (Apple II 48 RAM) programmed to solve four unknown equations (Rodbard’s equation). From the data so obtained one can see that when voltages at the beginning and at the end of the reaction are in all cases about the same, a clear difference in the time required to reach half the maximum value of the voltage can still be demonstrated. This parameter, which is expressed in minutes, is longer in coumarin and prothrombin Molise than in controls. On the contrary it is shorter in prothrombin Padua and has about the same value of controls in the cirrhotic patient. Moreover the time at which the maximum rate is obtained is longer in coumarin and prothrombin Molise than in controls and shorter in liver cirrhosis and prothrombin Padua. In conclusion data obtained show that coumarin prothrombin behaves in a different way from cirrhotic prothrombin and also that there is a different behaviour between the two congenital dysprothrombinemias.
Inhibitor to Factor VIII in Mild Haemophilia
Authors: Kesteven P J , Holland L J , Lawrie A S , Savidge G F
Published: July 2018

Factor VIII inhibitors in mild haemophilia are uncommon and the management of such patients is controversial. The development of a persistently high responding F VIII inhibitor in a mild haemophiliac is reported and the behaviour of the inhibitor discussed in the context of the various therapeutic regimes employed for symptomatic management. When inhibitor titres were low, endogenous F VIII stimulation, by DDAVP, was less immunogenic than the administration of exogenous F VIII concentrates. This inhibitor displayed characteristics of an autoantibody, and was characterised as an immunoglobulin of IgG subtype.
The Effect of Dietary Cholesterol on Platelet Survival in the Rabbit – A Study Using 14C-Serotonin and 51Chromium Double-Labelled Platelets
Authors: Wanless Ian R
Published: July 2018

Hypercholesterolemic men and monkeys have shortened platelet survival but attempts to demonstrate this in rabbits have been unsuccessful. The present study examines platelet survival in cholesterol-fed rabbits. Platelets were double-labelled in vitro with 51Cr and 14C-serotonin or in vivo by intravenous injection of 14C-serotonin.

In the double-label experiments 51Cr survival was always shorter than 14C survival but changes in survival of one label were accompanied by similar changes in the other label. Survival was shortened after 4 and 7 weeks of cholesterol feeding. This was demonstrated when the donor platelets were from normal rabbits for both cholesterol and control recipients but no shortening was demonstrated when cholesterol-rich platelets were injected into cholesterol-fed recipients and normal platelets were injected into the control rabbits. When 14C-serotonin was injected intravenously 14C survival was the same as when platelets were labelled ex vivo prior to injection and 14C survival was shortened in rabbits fed cholesterol for 1,2, and 6 weeks.

These results indicate that cholesterol-feeding shortens platelet survival. This effect may be masked if the test platelets are not identical in both test and control groups.
Impaired Fibrinolytic Capacity Predisposes for Recurrence of Venous Thrombosis
Authors: Korninger C , Lechner K , Niessner H , Gössinger H , Kundi M
Published: July 2018

The fibrinolytic capacity of 121 patients with a history of venous thrombosis and/or pulmonary embolism was studied by venous occlusion technique, at earliest 3 months after the last thromboembolic episode. After discontinuation of oral anticoagulation treatment the clinical course of the patients was followed and new thromboembolic episodes were noted. During the observation period of 56 ± 18.8 months 45 of 121 patients experienced recurrence of thrombosis. The recurrence-rate was significantly lower in patients with a post-occlusion ELT shorter than 60 min (4.8%/year) than in patients with an ELT longer than 60 min (10.3%/year). It is concluded that the fibrinolytic capacity is a useful parameter for determining the risk of recurrence in patients with venous thrombosis.
Association Between Bleeding Time and Platelet Adherence to Artery Subendothelium
Authors: Sakariassen K S , Bolhuis P A , Blombäck Margaretha , Thorell L , Blombäck Birger , Sixma J J
Published: July 2018

The efficacy of five different factor VUI-von Willebrand factor (FVIII-VWF) preparations in mediating adherence of blood platelets to damaged vessel walls was tested in an annular perfusion chamber utilizing human arteries and reconstituted blood.

FVIII-VWF-purified by Sepharose CL-4B chromatography and von Willebrand factor prepared from this preparation by dissociation with 0.25 M CaCl2 followed by Sepharose CL-6B chromatography were equally effective in mediating platelet adherence as FVIII-VWF in cryoprecipitate and in plasma from normal subjects. A commercial concentrate of FVIII-VWF (Hemofil, Hyland) used for the treatment of haemophiliacs did not mediate platelet adherence at normal levels of FVIII-VWF related properties. A recently developed high-purity FVIII-VWF preparation (Concentrate II) containing multimers of high molecular weight normalized the platelet adherence. Platelet adherence in plasma obtained from two patients with von Willebrand’s disease (VWD) was impaired, but plasma samples obtained following treatment with Concentrate II mediated normal platelet adherence. The normalization of platelet adherence paralleled the normalization of the bleeding time.

This platelet adherence assay offers an inexpensive and efficient in vitro tool to test the efficacy of FVIII-VWF preparations designed for VWD patients. Preparations such as cryoprecipitate and Concentrate II mediated the platelet adherence and normalized the bleeding time. The commercial preparation did not mediate platelet adherence and had no effect on the bleeding time.
Haemostasis in Normal Pregnancy
Authors: Stirling Yvonne , Woolf Linda , North W R S , Seghatchian M J , Meade T W
Published: July 2018

A study has been undertaken in 72 women to provide systematic information on the changes that occur in a wide range of haemostatic variables during and after pregnancy. Factors VII, VIII :C, VIIIR:Ag, X, fibrinogen and α1 antitrypsin, rose markedly throughout pregnancy. Factors II and V and α2 macroglobulin all rose early on but then decreased steadily. Antithrombin III: C and Ag fell slightly. There was a marked decrease in fibrinolytic activity from 11-15 weeks onwards. Levels of fibrin degradation products rose from 21-25 weeks onwards. The rise in coagulation factors that occurs could be due to increased synthesis or increased activation by thrombin, or to both. The findings are consistent with a mild degree of local intravascular coagulation from early on in pregnancy in some women.
Influence of Some Plasma Fatty Acids on the Phospholipid Fatty Acid Pattern of Human Platelets – An “Ex Vivo” Experience
Authors: Vallés Juana , Aznar Justo , Santos M Teresa
Published: July 2018

Some correlations between plasma and platelet fatty acids (FA) were evaluated “ex vivo” in 94 normal subjects.

The highest relationships between total FA from plasma and platelets were found for 18:1 (r = 0.74) and 18:2 (r = 0.67). Low correlations were obtained for free fatty acids (FFA). The most significant correlations between fatty acids esterifying plasma and platelet phospholipids were found for the 18:1 (r = 0.66); 18:2 (r = 0.74) and 20:5 (r = 0.66).

Our results suggest that the platelet phospholipid FA could be more easily modified by plasma variation in the FA composition of phospholipids than by variations in the plasma FA composition of the FFA fraction. In addition, the incorporation of FA from plasma into the platelet phospholipids “in vivo” may take place through an acylation-deacylation process and also by the incorporation of whole plasma phospholipid molecules into the platelets, probably through an exchange of plasma lipoproteins and platelets. Finally, arachidonic acid seems to have a different and selective way of incorporation into platelet phospholipids.
Fibrinogen, Factor VIII Related Antigen, Antithrombin III and α2-Antiplasmin in Peripheral Arterial Disease
Authors: Christe M , Delley A , Marbet G A , Biland L , Duckert F
Published: July 2018

In 306 subjects, 217 without and 89 with peripheral arterial disease (PAD), VIIIR:Ag and α2-antiplasmin are significantly higher in PAD (p < 0.01). In the PAD negative group the ratio α2-antiplasmin/antithrombin III activity is significantly higher 1.11 ± 0.3 in the patients with an abnormal exercise ECG typical of coronary disease than in normal subjects 1.02 ± 0.2 (p < 0.05). In the PAD positive group antithrombin III concentration is higher in patients with a normal exercise ECG than in patients with abnormal exercise ECG (p < 0.05). The same is true for α2- antiplasmin but not for the antithrombin III activity. Fibrinogen and VIIIR:Ag are higher in patients with a previous myocardial infarction, however, the age is also significantly different as compared to the group without previous myocardial infarction. Disturbance of the cerebral arterial circulation is characterized by an elevation of VIIIR:Ag and of α2-antiplasmin as comapred to the values obtained in patients without this complication. There is a general tendency towards higher α2-antiplasmin values with the extension of the arterial disease.
Protein C Antigen Is Not an Acute Phase Reactant and Is often High in Ischemic Heart Disease and Diabetes
Authors: Viganò S , Mannucci P M , D’Angelo A , Gelfi C , Gensini G F , Rostagno C , Serneri G G Neri
Published: July 2018

Protein C, an antithrombotic protein, was measured immunologically in 299 patients with clinical conditions associated with a high frequency of venous or arterial thromboembolism. The mean protein C antigen (PC: Ag) level was high for 48 patients with ischemic heart disease and, to a lesser extent, for 95 diabetics. In 28 patients with thrombotic strokes, 48 patients with proximal deep-vein thrombosis and in 80 patients with localized or metastatic tumors, mean PC: Ag was normal. Comparison of the pattern of changes of PC: Ag levels with those of fibrinogen, orosomucoid and prothrombin in 21 patients during the postoperative period and in 20 patients with active rheumatoid arthritis ruled out the possibility that high PC: Ag is non-specific, acute-phase reaction to inflammation, tissue injury or neoplastic growth. Therefore, high PC:Ag might be specifically related to the thrombotic tendency of these patients, but the mechanism of such a relationship remains to be clarified.
Quantitation by Radioimmunoassay of Thrombospondin Synthesised and Secreted by Human Endothelial Cells
Authors: Hunter N R , Dawes J , MacGregor I R , Pepper D S
Published: July 2018

Synthesis and secretion of thrombospondin by cultured human endothelial cells was quantified using a sensitive radioimmunoassay. Two endothelial lines were examined; those from umbilical veins and those from saphenous veins. The foetal line secreted ̴17 μg/106 cells of the antigen at 24 hr, whereas the saphenous line secreted five times less in the same period. Intracellular values were similar in both lines.

Thrombin and calcium ionophore A23187 were added to umbilical vein endothelial cultures. In contrast to platelets where both agents cause a rapid release reaction, no such thrombospondin release was observed in endothelial cells.
Exercise-Induced Platelet Activation in Myocardial Infarction Survivors with Normal Coronary Arteriogram
Authors: Douste-Blazy Ph , Sié P , Boneu B , Marco J , Eche N , Bernadet P
Published: July 2018

Platelet activation may participate in the pathophysiology of myocardial infarction occurring in patients with normal coronary arteriogram. We investigated this possibility in a series of 9 such patients (group A) during a standardized bicycle excercise test as myocardial infarction had occurred in all of them during or soon after strong physical exercise. Twelve patients with effort-induced angina and coronary atherosclerosis (group B) and eleven healthy subjects (group C) served as test groups. Peripheral venous blood was collected by separate venipuncture before, at peak exercise and during recovery. As a sensitive index of activation, the shape of the circulating platelets was examined with a phase contrast microscope after instantaneous fixation of the whole blood. The percentage of non strictly disc-shaped platelets with one or more thin pseudopods was determined. Simultaneously, the plasma levels of platelet factor 4 (PF4) and of beta-thromboglobulin (β-TG) were measured. At rest, there was no significant difference in the platelet morphology nor in the plasma levels of platelet specific proteins between the three groups. During exercise, a significant change in platelet shape occurred in group A and B patients and not in the healthy subjects. This platelet activation was not related to myocardial ischemia since it occurred to a similar extent in group B patients who developed electrocardiographic changes and in group A patients who did not. There was no detectable release of platelet proteins during exercise in any group.
Urinary Excretion Rate of Antithrombin III Related Antigen in Cerebral Stroke
Authors: Matsuo T , Shinomiya K , Okuno S , Matsuo C , Matsuo O
Published: July 2018

The urinary excretion rate of antithrombin III related antigen (AT III RA) was examined in cerebral stroke. The excretion rate of AT III RA in cerebral hemorrhage (CH) was 12.33 ± 1.61 × 10-4 ml/min. The patients with CH were further classified into two groups: in group CH-I, whose consciousness state was stupor or further deteriorated including coma on admission, the excretion rate of AT III RA was 18.08 ± 2.50 × 10-4 ml/min. In group CH-II, whose consciousness state was clear on admission, the excretion rate of AT III RA was significantly lower than that in CH-I (6.20 ± 1.56 × 10-4 ml/min). The excretion rate in cerebral thrombosis (CT) was 1.96 ± 0.25 × 10-4 ml/min, which was significantly lower than that in CH. The excretion rate of AT III RA in both CH and CT was significantly higher than that in the healthy control group (0.29 ± 0.04 × 10-4 ml/min). Thus, AT III may change dynamically in cerebral stroke.
Effect of Anti-Thrombospondin Antibodies on the Hemagglutination Activities of the Endogenous Platelet Lectin and Thrombospondin
Authors: Gartner T Kent , Doyle Mary Jean , Mosher Deane F
Published: July 2018

The proposal that thrombospondin is the endogenous platelet lectin was evaluated using antisera and monoclonal antibodies to thrombospondin. The platelet-bound hemagglutinin activity of human platelets stimulated with A23187 was inhibited by rabbit anti-thrombospondin sera and by a monoclonal anti-thrombospondin IgG. A second monoclonal IgG did not inhibit platelet- bound agglutinin activity. Preparations of purified platelet thrombospondin differed in their hemagglutination activities. The hemagglutination activity of an active preparation of thrombospondin was inhibited by the monoclonal antibody that inhibited platelet-bound lectin activity. The hemagglutination activity of an almost inactive preparation of thrombospondin was enhanced by the anti-thrombospondin monoclonal antibody that did not block platelet-bound lectin activity. The results demonstrate that expression of the platelet-bound form of the endogenous lectin is thrombospondin-dependent and suggest that thrombospondin must become part of a larger complex, either by binding to the platelet surface or by becoming aggregated in solution, before hemagglutination activity can be expressed.
Urine Beta-Thromboglobulin Concentration or Beta-Thromboglobulin/Creatinine Ratio in Single Voided Urine Samples Cannot Be Reliably Used to Estimate Quantitative Beta-Thromboglobulin Excretion
Authors: Musumeci V , Rosa S , Caruso A , Zappacosta B , Tutinelli F , Zuppi C
Published: July 2018

Different procedures are currently used in the urine beta-thromboglobulin (BTG) assay. We investigated the reliability of limited urine collections and of different expressions of urine BTG results (concentration, urine BTG/creatinine ratio) for the measurement of hourly or daily BTG excretion rates. BTG was measured by a sensitive RIA method in various urine collections of normal subjects (n.80) and patients (n.120) with miscellaneous diseases where an enhanced in-vivo platelet activation could be expected. The BTG concentration in a 6-hour urine collection appeared to change in relation to the urine flow rate (r = -0.53 in normals, r = 0.27 in patients, p <0.01) and urine osmolality (r = 0.46 in normals, r = 0.31 in patients, p <0.01). In both normals and patients not a very good correlation was observed between the urine BTG/creatinine ratio and the BTG excretion rate (r = 0.54 and r = 0.48; p <0.001, respectively). Variable coefficients of correlation (r = 0.83-0.34) were observed between the BTG excretion rate of single voidings of the morning, afternoon-evening and night and the daily BTG excretion both in normals and patients. Reliable measurements of the BTG in urine should be expressed as the hourly excretion rate in a given period of the day for limited urine collections or as the daily excretion for 24-hour urine collections.
Hemostatic Parameters in Newborn - II. Sequential Study During the First Four Weeks of Life
Authors: Kolindewala J K , Dube B , Bhargava V , Dube R K , Kota V L N , Das B K
Published: July 2018

A sequential study of kaolin cephalin clotting time (KCCT), prothrombin time (PT), thrombin time (TT), plasma fibrinogen and serum FDP was conducted during the first four weeks of life on term and preterm babies. A “physiological dip” of PT and TT was noted inappropriate for gestational age (AGA) babies both term and preterm; in case of KCCT, the dip was significant in term AGA babies only. At the end of four weeks, PT and TT had moderately improved in term babies but showed little improvement in preterm ones; KCCT reached almost an adult value in all babies except in preterm AGA and term LGA (large for gestational age) ones. Plasma fibrinogen showed no “physiological dip” and reached adult level in two to four weeks. Serum FDP levels were appreciably raised in preterm AGA babies only at birth and there too normalised by 72 h.