bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vivo Release of Tissue-Type Plasminogen Activator across the Human Forearm during Mental Stress
Authors: Jern Christina , Selin Lena , Jern Sverker 
Published: July 2018

SummaryWe have previously shown that plasma levels of endothelium-derived tissue-type plasminogen activator (t-PA) increase during mental stress. The aim of the study was to investigate in vivo release in an intact human muscle vascular bed. Eleven healthy young males (22-36 yrs) were studied at rest and during 10 min of mental stress (forced arithmetic). Net release or uptake were assessed by arterio-venous (AV) concentration gradients across the forearm of t-PA antigen and t-PA activity, and plasminogen activator inhibitor antigen type 1 (PAI-1). Forearm blood flow was measured by venous occlusion plethysmography. At rest, there was a positive AV-difference of t-PA activity across the forearm indicating a net release of t-PA activity of approximately 3.7 fmol × min−1 × 100 ml−1 (Wilcoxon’s signed rank test vs 0, p = 0.01). However, t-PA antigen showed a variable release pattern. On the average, there was a net release of 0.17 ng × min−1 × 100 ml−1 after 60 min of rest (Wilcoxon vs 0, p = 0.07). PAI-1 antigen showed net release at rest. In response to stress, forearm blood flow increased from 1.9 to 2.9 ml × min−1 × 100 ml−1 (ANOVA, p = 0.007), and net release of t-PA activity increased to 9.8 fmol × min-1 × 100 ml −1 (ANOVA, p = 0.01 compared with rest). Arterial and venous plasma t-PA levels also increased significantly during stress (ANOVA, p < 0.01). t-PA antigen showed a similar but less pronounced release pattern during stress. PAI-1 antigen was unaffected by stress. During i. a. infusion of norepinephrine (6-1,200 ng/min), forearm blood flow decreased from 2.1 till 1.0 ml × min-1 × 100 ml−1 (ANOVA, p = 0.002), while net release of t-PA activity increased from 2.7 till 10.1 fmol × min-1 × 100 ml−1 (ANOVA, p = 0.002). The study demonstrates a net release of t-PA activity across forearm tissues at rest. Net release of t-PA activity increases in response to mental stress and i. a. infusion of norepinephrine, despite disparate effects on blood flow.
Platelet Activation Induced by lnterleukin-6: Evidence for a Mechanism Involving Arachidonic Acid Metabolism
Authors: Oleksowicz Leslie , Mrowlec Zbignelw , Zuckerman Dina , Isaacs Randi , Dutcher Janice , Puszkin Elena 
Published: July 2018

SummaryThe effect of IL-6 on in vitro platelet function was investigated. Platelet-rich plasma (PRP) incubated with IL-6 showed a dose dependent enhancement of agonist induced maximum aggregation (AIMA) and secretion of thromboxane B2 (TXB2) as measured by RIA, in short term incubations. Dazoxiben (0.2 to 160 (µM) pretreated PRP incubated with IL-6 and aggregated with ionophore A23187, showed a dose dependent inhibition of TXB2 secretion concomitant with a dose dependent abrogation of IL-6’s enhancement of AIMA. A similar abrogation of AIMA was observed when these experiments were repeated using indomethacin. Further, PRP incubated with IL-6 showed a dose dependent increase in TXB2 and BTG secretion as measured by RIA and an increased incorporation of actin binding protein, talin, and myosin into the cytoskeletal core (triton insoluble residue) as shown by SDS-PAGE. The integrin glycoprotein Ilia (GPIIIa) was also observed to be retained into the cytoskeleton by immunoblot. These results suggest that IL-6 activates platelets in vitro and enhances AIMA via a mechanism involving arachidonic acid metabolism.
The Antiaggregating Activity of Clopidogrel Is due to a Metabolic Activation by the Hepatic Cytochrome P450-1A
Authors: Savi P , Combalbert J , Gaich C , Rouchon M-C , Maffrand J-P , Berger Y , Herbert J-M 
Published: July 2018

SummaryClopidogrel and ticlopidine are two well known selective anti-ADP agents which are inactive in vitro and must be administered in vivo to fully exhibit their antiaggregating and antithrombotic effects. Since previous studies have clearly demonstrated that the activation steps take place in the liver, we examined the effect of specific induction or inhibition of cytochrome P450 subfamilies on the antiaggregating activity of clopidogrel. SKF 525-A, a global cytochrome P450 inhibitor, dramatically decreased the antiaggregating effect of clopidogrel, therefore indicating that cytochrome P450 enzymes are involved in the hepatic activation of clopidogrel. The efficacy of clopidogrel was increased in animals pretreated with 3-methylcholanthrene and (3-naphthoflavone, indicating that the cytochrome P450-1A subfamily pathway was mainly involved in the activating metabolism of clopidogrel. The use of specific antibodies directed against the various cytochrome P450 subfamilies ascertained this observation.
Gel Filtration Properties of Factors II, VII, IX, IXa, and X
Authors: Østerud Bjarne , Schiffman Sandra 
Published: July 2018

SummaryThe following gel filtration properties of the vitamin ढ dependent clotting factors have been established :1. The elution patterns of factors II, VII, IX, and X in 0.5 M NaCl are the same in factor XII deficient native plasma, anticoagulated plasma, and BaSO4 eluates.2. In 0.01 M Tris buffer pH 7.3 or 0.5 M NaCl, plasma factors II, IX, and X elute together; factor VII élûtes later as a smaller molecule. All 4 plasma activities elute as larger molecules in 0.01 M Tris buffer and smaller ones in 0.5 M NaCl.3. In 0.01 M Tris - 0.005 M EDTA peak factor II activity elutes first, followed by factor IX, factor X, and then factor VII.4. Activation decreases the apparent size of factor IX.
Studies on Activator Formation in Human Plasma with Streptokinase
Authors: Martin M ,   with the technical assistance of Frau R. Albrecht
Published: July 2018

SummaryThe activator concentrations developing during a streptokinase infusion treatment were measured on a quantitative basis. The reference value (100 per cent activator) selected for this purpose was the activator effectiveness resulting from a mixture of 20,000 units of streptokinase and 1 millilitre of citrate plasma. The streptokinase treatment regimens used for our study consisted either of a continuous streptokinase infusion treatment extended over three days or of intermittent streptokinase infusions with a 16-hour streptokinase-free interval. The highest activator concentrations measured had developed between 1 and 24 hours after the streptokinase treatment had started, the values being in the order of 0.4 per cent. When treatment was continued, the activator concentrations dropped below that level. Under the intermittent streptokinase regimen, the activator concentrations measured during the second series of infusions were always lower than those measured during the first series. The activator concentration levels and the plasminogen values measured simultaneously acted in a reciprocal manner, i.e. a plasminogen decrease corresponded to an activator increase and vice versa. Seen under the aspect of the obtainable maximum of activator effectiveness, the intermittent streptokinase infusion regimen offers no advantage as against the continuous treatment form. It would certainly be desirable to achieve higher activator levels through modifications in the streptokinase dosage.
The Effect of Phospholipase C on Platelet Factor 3 in Human Blood Platelets
Authors: Otnaess A-B , Prydz H 
Published: July 2018

SummaryIntact human platelets isolated by gel filtration have been treated with purified phospholipase C. The effect of the enzyme on available and total platelet factor 3 has been tested.The available procoagulant platelet factor 3 was very low. A further small reduction was observed after incubation with phospholipase C when the enzyme was washed away before testing.External attack on platelets by phospholipase C led to a marked inactivation of total platelet factor 3.
A Comparison of Coagulation Factor Replacement with and without Prednisolone in the Treatment of Haematuria in Haemophilia and Christmas Disease
Authors: Rizza C. R , Kernoff P. B. A , Matthews J. M , McLennan C. R , Rainsford S. G 
Published: July 2018

SummaryA double-blind controlled study was carried out to investigate the effectiveness of treatment with factor VIII or factor IX concentrate and a reducing dose of prednisolone in controlling haematuria in patients with haemophilia and Christmas disease.41 episodes of haematuria were studied in 30 different patients. No appreciable benefit was observed in the treated, as compared with the control group and this is at variance with the results of the few studies reported elsewhere.
Apparent Similarity of Mechanisms of Platelet Adhesion and Aggregation
Authors: Mason R. G. , Read M. S. , Saba S. R. , Shekmek R. W. 
Published: July 2018

SummaryA correlation between effects of a series of compounds on platelet adhesion, aggregation, and retraction of the clot, and their effects on platelet electrophoretic mobility, ecto-ATPase activities, and AChE activity has been sought. Compounds which inhibited aggregation induced by ADP or epinephrine also inhibited platelet adhesion to glass. Six compounds which inhibited adhesion and aggregation did not inhibit clot retraction. The data suggest that the effect of thrombin on platelet electrophoretic mobility and ecto-ATPase activities may have less influence on platelet function than was formerly believed. However, the effects of test compounds on platelet AChE activity suggest that this enzyme may play a role in aggregation and adhesion. Platelet adhesion and aggregation may operate by similar mechanisms.
Fibrinogen Metabolism in Healthy Dogs and in Dogs with CCI4-Induced Liver Damage and with Portal Vein Occlusion
Authors: Tytgat G. N. , Collen D. , Oei L. S. , Van Damme B. 
Published: July 2018

SummaryThe metabolism of dog fibrinogen, labelled with radioactive iodine was studied in 16 healthy dogs on 28 occasions, in 12 dogs with CCl4-induced chronic liver damage and in 5 dogs with interruption of the hepatoportal blood flow by occlusion of the portal vein.Results in healthy control dogs were: plasma volume 48±12 ml/kg ; plasma fibrinogen concentration 316±102 mg%; total plasma fibrinogen pool 168±42 mg/kg, representing 0.72±0.08 of the total body pool; fibrinogen half-life 2.54±0.23 day; fractional catabolic rate 0.39±0.05 of the plasma pool per day; absolute catabolic rate 58±25 mg/kg per day.Results in dogs with CCl4-induced liver damage were: plasma volume 46 ± 12 ml/kg ; plasma fibrinogen concentration 334±97 mg%; total plasma fibrinogen pool 152±55 mg/kg, representing 0.70±0.04 of the total body pool; fibrinogen half-life 2.15±0.26 days; fractional catabolic rate 0.47±0.06 of the plasma pool per day; absolute catabolic rate 71±21 mg/kg per day.Results in dogs with longstanding portal vein occlusion were: plasma volume 41 ±8 ml/kg; plasma fibrinogen concentration 330±23 mg%; total plasma fibrinogen pool 142±36 mg/kg, representing 0.70±0.06 of the total body pool; fibrinogen half-life 2.60 ±0.36 days; fractional catabolic rate 0.40 ±0.04 of the plasma pool per day; absolute catabolic rate 56±14 mg/kg per day.A significant difference between control dogs and dogs with liver disease was observed for the fibrinogen half-life and the fractional catabolic rate. All fibrinogen turnover data in dogs with portal vein occlusion were comparable to control values.Heparinization did not influence the fibrinogen half-life in most of the control dogs and in the dogs with portal vein occlusion ; however in 2 control dogs, a prolongation of their rather short fibrinogen survival occurred during anticoagulation. In contrast, a general trend towards prolongation and occasionally normalization of the fibrinogen life span during heparinization was observed in the dogs with liver damage, supporting the concept of accelerated fibrinogen consumption by a process of disseminated intravascular coagulation in liver disease.
Schwere serogene hämolytische Anämie verursacht durch ein Anti-D im Faktor-VIII-Konzentrat
Authors: Schkickeb K. Th , Schrenk K. H 
Published: July 2018

ZusammenfassungEs wird über eine schwere serogene hämolytische Anämie berichtet, die unter der Therapie mit antihämophilem Globulin bzw. Cohnscher Fraktion aufgetreten ist und durch einen Rh-Antikörper (Anti-D) hervorgerufen wurde. Da eine Sensibilisierung durch Bluttransfusionen und eine echte autoimmunhämolytische Anämie als ursächliche Faktoren der Hämolyse ausgeschlossen werden konnten, muß das Anti-D im antihämophilen Globulin oder der Cohnschen Fraktion enthalten gewesen sein. Der Patient besaß das Antigen D, so daß der direkt mit dem Konzentrat zugeführte Rh- Antikörper (Anti-D) eine schwere hämolytische Reaktion auslöste.
Etude en Microscopie électronique de différentes Etapes de la Fibrinoformation
Authors: Pouit L , Marcille G , Suscillon M , Hollard D 
Published: July 2018

RésuméNous avons étudié en microscopie électronique par la technique de coloration négative : la molécule de fibrinogène, les étapes intermédiaires de la fibrinoformation et la fibre de fibrine. Nous avons constaté que la molécule de fibrinogène se présentait sous forme d’éléments globulaires, à pH 8,3 et pour une force ionique de 0,2, le diamètre moyen mesure 240 Â. L’observation des molécules de taille variable (entre 180 Å et 420 Å) et de filaments très minces nous a conduit à émettre l’hypothèse d’une molécule capable de se dérouler sous certaines conditions physiques. L’ensemble des clichés observés suggère qu’au cours de l’organisation périodique de la fibre, le matériel protéique change de structure. Ce phénomène se manifeste par une diminution des éléments globulaires qui constituent les bandes transversales (de 280 Å à 30 Å) et le développement à partir de ces éléments d’un réseau de filaments longitudinaux, très denses, porteurs de fins granules dont l’alignement forment des sous striations transversales. Il se produit aussi une diminution de la période qui passe de 300 Å à 230 Å.
Platelet Aggregation by Staphylococcal Toxins
Authors: Jeljaszewicz J , Niewiarowski S , Popławski A , Bławat L 
Published: July 2018

SummaryAggregation by some staphylococcal toxins resulted in the following observations. Staphylocoagulase in lower concentrations causes aggregation in a similar way as thrombin, whereas in higher concentrations, clotting occurs which is always preceded by quick platelet aggregation. Alpha-hemolysin aggregates human and rabbit platelets, whereas sheep platelets are not affected. Preincubation of susceptible platelets with this toxin, results in their lysis. Betahemolysin causes also aggregation. Leukocidin is inactive. All these phenomena are well visible visually and in the phase contrast microscope. Staphylocoagulase and alpha-hemolysin, when added to the platelet-rich plasma simultaneously with the adenosine diphosphate, interfere and the platelet aggregation is partly inhibited. Pathological aggregation of platelets by bacterial products and its possible significance is discussed.
Effects of Soy Bean Trypsin Inhibitor on Fibrin Clot Lysis
Authors: Egeblad K 
Published: July 2018

SummaryThe effect of soy bean trypsin inhibitor (SBTI) on fibrinolysis and blood coagulation was investigated. Clot lysis was recorded by means of thrombelastography. SBTI delays fibrinolysis induced by plasmin and by activators of plasminogen (SK-activator and urokinase). Activator-induced lysis is delayed by a combined effect on activator and plasmin. There appears to exist an equilibrium between highly dissociated compounds of inhibitor with the active agents. The inhibitory effect of SBTI is relatively decreased in clots containing human plasma probably caused by an equilibrium with inhibitory agents in the plasma. SBTI delays thrombin generation in recalcified plasma as well as the effect of thromboplastin, but the effect is weak and requires a concentration 70-100 fold the antifibrinolytic active. The effect on thrombosis is even weaker.
Orgaran (Org 10172) or Heparin for Preventing Venous Thrombosis after Elective Surgery for Malignant Disease? A Double-Blind, Randomised, Multicentre Comparison
Authors: Gallus A , Cade J , Ockelford P , Hepburn S , Maas M , Magnani H , Bucknall T , Stevens J , Porteous F ,   (ANZ-Organon Investigators’Group)
Published: July 2018

SummaryThis double-blind, randomised, multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis (VT) prophylaxis using 750 anti-factor Xa units of Orgaran (a mixture of low molecular weight heparinoids) given subcutaneously (sc) twice-daily with that of twice-daily injections of 5,000 units Standard heparin. The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning, and the onset of clinically significant venous thromboembolism or bleeding. “Intent to treat” analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis (10.4%) than after heparin (14.9%) and there was no difference in bleeding complications between the two study groups. Results remained similar if only patients who completed the intended course of therapy (“compliant patients”) were analysed. Other trials have shown that Orgaran prevents VT after hip surgery and stroke. We now show it is also safe and effective in patients having major surgery for cancer.
The Coagulant Active Phospholipid(Pl) Content Of Prothrombin Complex Concentrates(Pcc) Is A Critical Determinant Of Their In Vivo Thrombogenicity
Authors: Giles A R , Nesheim M E , Tracy P B , Hoogendoorn H , Mann K G 
Published: July 2018

It has generally been assumed that the thrombogenicity of PCC relates to their invariable contamination by activated products of their component clotting factors. In earlier studies we demonstrated a lack of correlation between the activated clotting factor content ᶓ in vivo thrombogenicity of some PCC. In contrast, in vitro measurement of coagulant active PL content appeared to be a more reliable determinant of subsequent in vivo activity. In recent studies we have confirmed the presence of PL of known coagulant activity in PCC ᶓ studied its activity both in vitro ᶓ in vivo after its extraction from the parent PCC.PCCs were obtained from various agencies or prepared in our laboratory to a standard protocol either from fresh frozen plasma or plasma obtained from outdated platelet concentrates. Each was assayed for Xa (S-2222) ᶓ PL (thrombin generation assay with DAPA) ᶓ an index of thrombogenicity in vivo determined in a stasis model in rabbits. There was a significant correlation between the latter ᶓ PL (r=0.8727 p<0.01) but not Xa. Thin layer chromatography of an ethanol ether extract of the most thrombogenic PCC showed the presence of PL known to be coagulant active including Phospho- tidylserine ᶓ -choline. This extract retained full PL replacing activity in the DAPA assay in vitro but was non- thrombogenic in vivo. When, however, a highly purified preparation of Xa was added, in the same relative proportions as in the parent PCC, thrombogenicity in vivo was restored.It is concluded that the content of coagulant active PL is a critical determinant of the potential thrombogenicity of PCC in vivo. It appears to act in concert with Xa ᶓ conceivably, other serine proteases perhaps by protecting them from inactivation by AT III. This may explain why relatively “non-activated” PCCs may still be associated with thromboembolic complications.
Declining Mortality From Pulmonary Embolism In Surgical Patients
Authors: Dismuke S E 
Published: July 2018

The frequency and clinical characteristics of autopsied surgical patients dying with pulmonary embolism (PE) were studied at a University hospital from 1966-1976. During this period a standard autopsy protocol was in use. All patients in whom PE occluded the equivalent of at least one lobar artery were studied. Information collected in all adult deaths confirmed the year to year similarity of patient characteristics and likelihood of autopsy. In order to assess the role of PE in a patient’s death, cases were grouped separately by 2 criteria:	1) according to size of PE (3 groups: greater than 2/3 of pulmonary vasculature occluded, 1/2 - 2/3 occluded, less than 1/2 occluded); 2) weighing competing causes of death by having 3 physicians (randomly selected from a pool of 25) judge the likelihood of death after 1 month had PE been prevented (classifying them as primary PE death, contributory PE death, and death from competing causes). Sixty percent (900/1489) of surgical deaths were autopsied and 7.7% (69) had large emboli. The percentage of deaths from PE, using either criteria, has declined significantly (p<0.01) over time (1966-71 vs 1972-76): 10.5% to 4.5% for all cases studied and 5.5% to 2.1% in those where PE was the primary or a contributory cause of death. PE was the primary or a contributory cause of death in 3.9% (34 cases) of these autopsies. The clinical diagnosis of PE was considered in only 17% (6) of these cases but 63% (22) had no symptoms suggestive of PE prior to death. An infiltrate or effusion, however, was present in 60% (21) of cases and 80% (28) had 2 or more major risk factors for PE. In contrast to previous studies, this study demonstrates an impressive decline in surgical deaths from PE from 1966-1976 despite no routine use of prophylactic anticoagulation.
Purification, Characterization And Radioimmunoassay Of A New Antiheparin Protein Secreted By Rabbit Platelets
Authors: Muggli R , Glatthaar B , Mittelholzer E , Tschopp T B 
Published: July 2018

We isolated a platelet specific protein from rabbits for studying the usefulness of such proteins as marker for in vivo platelet activation in animals.The protein was purified by chromatography on heparin-agarose and on Sephadex G75 from the soluble release products of thrombin aggregated washed rabbit platelets. On heparin- agarose the protein eluted in front of rabbit PF4 at a salt concentration of about 0.9 M NaCl, and had a MW of about 20,000 dalton as judged by gel filtration. The purified protein migrated in SDS PAGE in the presence or absence of mercaptoethanol as a single band with a MW of <12,000 dalton. It had a heparin-neutralizing activity of 0.16 mg Polybrene/ mg and a pI of >9.5.A radioimmunoassay with second antibody precipitation was developed. Antisera were produced in goats. Plasma and serum levels were 26 ± 6 ng/ml (n = 16, x ± SD) and 2900 ± 960 ng/ ml (n = 8), respectively. Washed platelets contained 2.0 ng of the protein per 106 platelets. The protein was released in parallel to platelet aggregation induced by collagen. Plasma levels rose from 26 ± 8 ng/ml (n = 6) to 72 ± 29 ng/ml 30 s after i.v. injection of collagen into rabbits. After injection of the iodinated protein into rabbits (n = 4) the disappearance of radioactivity followed two-compartment kinetics with half-lives of 3.8 min and 137 min for the fast and slow component, respectively. No increase of plasma radioactivity was recorded after injection of 500 U heparin per rabbit after 3 hrs. At that time 51 ± 13 % of the injected radioactivity was recovered in the urine.This new rabbit platelet secretory protein shows similar but not identical biochemical and in vivo behaviour as human βTG.