bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE PROTECTIVE EFFECT OF ACYLATI0N ON THE STABILITY OF EMINASE (APSAC) IN HUMAN PLASMA
Authors: Fears R , Ferres H , Standring R 
Published: August 2018

Clinical and animal studies indicate that APSAC (anisoylated plasminogen.streptokinase activator complex, Eminase) circulates longer in the bloodstream in an active form than the other thrombolytics. In the present studies in vitro u/e have found that functional activity of APSAC is maintained in human plasma longer than that of SK.plasmin(ogen): the relative stability half-lives are similar to the plasma clearance haif-lives in patients. Some of the loss of activity of SK at early times can be attributed to neutralisation by inhibitors. Thus, the survival of fibrinolytically-active SK was promoted in plasma depleted in α2-antiplasmin (α2AP) and α2AP-SK.plasmin complexes (detected by immunoblotting) formed rapidly in normal plasma. Corresponding studies with α2 macroglobulin-depleted plasma suggested a slight, late influence on SK activity but the inhibitor complex has not been detected unequivocally. In addition, loss of SK activity can be attributed, in part, to. rapid degradation to low molecular products. The degradation of SK in APSAC was much slower. In other comparative studies, the stability of APSAC was found to be similar to the stability of prourokinase and much superior to that of SK which is similar to UK; t-PA is intermediate in stability.Maintenance of fibrinolytic activity vivo depends on the stability of the thrombolytic, its rate of clearance and mode of administration. The protective effect of acylation, demonstrated in these experiments, explains why the objective of maintaining a high level of fibrinolytic activity after intravenous bolus injection of APSAC is less compromised by opposing inactivation processes.
A COMPARISON OF TOPICAL HAEMOSTATIC AGENTS IN EXPERIMENTAL LIVER RESECTION
Authors: Blaire S D , Backhouse C M , Matthews J L , McCollum C N 
Published: August 2018

Bleeding from lacerated paranchymal organs such as the liver and spleen may be profuse and difficult to control. The haemostatic agent, calcium alginate (Kaltostat), which acts as a source of chelateable calcium ions has been compared with oxidised cellulose (Surgicel) and porcine collagen (Medistat) in experimental liver resection.Under general anaesthesia, a standard 3cm2 piece of liver was excised in 42 NZW rabbits and the haemostatic agent immediately applied. Bleeding was assessed at 3-minute intervals and blood loss precisely measured by haemolysis and a haemoglobinometer. Macroscopic and histological examinations of the liver were performed at 2 and 6 weeks.Calcium alginate stopped bleeding within 3 minutes with minimal blood loss in every animal and was significantly better than the other materials by both criteria. At 2 weeks the macroscopic appearances were similar for the 3 implants with inflammation on microscopy. Oxidised cellulose had absorbed by 6 weeks with calcium alginate having only minimal residual material surrounded by a fibrous reaction. Porcine collagen remained intact with a vigorous foreign body reaction and granuloma formation.Calcium alginate is significantly more effective than the haemostatic materials currently used in surgical practice.
HAEMOSTASEOLOGICAL CHANGES IN DIABETIC CHILDREN (HUMAN INSULIN VERSUS PORCINE INSULIN
Authors: Nowak-Göttl U , Kreuz W D , John M , Krackhardt B , Grüttner H-P , Breddin H K , kollmann F 
Published: August 2018

Changes of haemostaseological parameters are involved in pathogenesis of diabetic angiopathy. However it is not yet clear whether they are cause or consequence of the endothelial damage. We investigated coagulation parameters in 84 children with type I diabetes mellitus without clinical signs of vascular disease.Compared to the control group no significant changes could be seen in fibrinogen, plasminogen, protein C, α 1 antichymotrypsin, β-thrombo-globulin and ristocetin - induced aggregation.Additionally we could observe significant differences in patients treated with human insulin to those treated with porcine insulin. Spontaneous platelet aggregation (PAT III) and factor VIII C correlated to the duration of diabetes. Also to the mean metabolic equilibrium (HBA1) correlations could be found. Spontaneous platelet aggregation seems to be a useful parameter to assess the onset of atherosclerotic diseases in diabetic children. High values of von Willebrand factor may indicate reversible and/or irreversible damage of vascular endothelium.
FUNCTIONAL CHANGES IN ANTITHROMBIN III IN INSULIN-DEPENDENT DIABETES MELLITUS
Authors: Sandbjerg Hansen M , Milner Jørgensen B 
Published: August 2018

The thrombin neutralizing activity of Antithrombin III (AT) was measured in a group of patients with insulin-dependent diabetes mellitus. All patients evaluated had diabetes of several years duration. Their blood glucose control was unsatisfactory as evidenced by relative concentrations of glycated hemoglobin (HbA1c) of 9.6-14.0% determined by polyacrylamide gel electrophoresis. The plasma AT-activity was estimated as thrombin neutralizing activity using the chromogenic substrate Th-1.The group of diabetic patients had a higher AT-activity than a reference group, but normal AT-concentrations by electro-immunoassay. The treatment of the patient samples with neuraminidase caused a greater fall in the AT-activity than did the treatment of normal samples. The patient samples had a slower mobility in crossed affino-immunoelectrophoresis using immobilized helix pomatia lectin in the first dimension and specific antibodies against AT in the second dimension. The mobility of patient AT, also in complex with thrombin, was indistinguishable from normal AT in crossed immunoelectrophoresis in the presence or absence of heparin.It is concluded that long-term dysregulation of diabetes mellitus may induce functional changes in the plasma antithrombin activity.
CLINICAL RELEVANCE OF PLASMA FIBRIN DEGRADATION PRODUCTS DETERMINATION IN PATIENTS WITH DEEP VEIN THROMBOSIS (DVT)
Authors: Aillaud M F , Roul C , Elias A , Bouvier J L , Serradimigni A , Juhan-Vague I 
Published: August 2018

We have studied fibrin degradation products, D-dimer, in citrated plasma with an ELISA assay using monoclonal antibodies (Asserachrom D-Di Stago).35 patients with DVT< 7 days were studied at day O (DO) that is upon admission before treatment with streptokinase (n=6), heparin (n=5) or LMWH CY222 Choay (n=24). Phlebographies were scored by Marder’s index (MI).At DO, MI = 24.28 ± 10.85 (m ± SD), the mean (± SD) of D-dimer was : 4056 ± 5545 ng/ml (range 950-19000) (normal values < 500 ng/ml). No correlation was found between D-dimer and MI and between D-dimer and clinical delay of DVT.The evolution of D-dimer was studied during 7 days in patients treated with heparin or LMWH (n=29). Blood sampling was undertaken at DO and at 8 h AM, 1 hour before injection at Dl, D3, D5, D7. The evolution of thrombolysis was evaluated by comparing MI at DO and D7. Among patients with MI at DO < 10 (n=25) two groups were compared : - successful group : 8 patients with decrease of MI at D7 < 80% ; - failure group : 11 patients with decrease of MI at D7< 20% : D-dimer at DO were higher in successful group (p< 0.05) ; these results could be explained by better endogenous thrombolysis in this group. The percentages of the decrease of D-dimer at D3 and at D7 compared to DO were higher in the successful group : Successful group versus Failure group (m ± SD) = % decrease at D3 : 46.4 ± 29.2/ 13.4 ± 11 (p< 0.05) ; % decrease at D7 : 52.3 ± 31.5/ 24.2 ± 26.3 (p<0.05) (in agreement with Soria and al, -IX th International Congress of Phlebology, September 1986, Kyoto) ; these results could be explained by a smaller clot mass to be lysed in successful group.In conclusion the level of D-dimer at DO and the intensity of the decrease of D-dimer during 7 days (as from D3) may have a predictive value for in vivo thrombolysis.
MONITORING OF DEEP VEIN THROMBOSIS BY D DIMER DETERMINATION. INFLUENCE OF HEPARIN REGIMEN
Authors: Soria C , Mirshahi Mc , Soria J , Mirshahi M , Faivre R , Neuhart D , Kieffer Y , Maurat J P , Caen J P 
Published: August 2018

In 49 patients the level of plasma fibrin degradation products (FbDP) was measured during the first ten days of deep vein thrombosis (DVT) in order to determine whether FbDP may be used as a non invasive marker to follow the evolution of DVT. Plasma FbDP was measured precisely and reliably by Elisa using a personal anti D neo monoclonal antibody. Thrombus size was determined angiographically on day 0 and day 10 and expressed according to Marder score. Patients were treated by standard or by a very low molecular weight heparin (CY 222 from Choay Laboratory, Paris France).It is shown that before treatment, in 45 cases of DVT the level of FbDP was dramatically increased as compared to control and remained normal or slightly elevated in 4 cases of DVT. The correlation between thrombus size and FbDP level at day 0 was poor (p = 0.3). During the 10 days of treatment, FbDP determination may give some informations about the evolution of DVT. Three groups were defined :1 There was no reduction of thrombus size in patients who presented a normal or only slightly elevated FbDP level, leading to the evidence that thrombolysis was almost inexistant in these patients.2 Thrombolysis was almost complete in 10 days in patients presented both a high FbDP level before treatment and a dramatic decrease of FbDP after 10 days treatment. Taking into account the half life of FbDP, the decrease in FbDP level is related to the reduction in thrombus size.3 A partial or absence of recanalization was evidenced in patients presenting a high FbDP level throughout the 10 days on therapy. In cases without recanalization we have to assume that thrombolysis evidenced by plasma FbDP level was continuously counteract by a clotting process.Similar results were observed in patient treated by standard and CY 222.
PRQOOAGULANT ACTIVITY OF HUMAN T LYMPHOCYTES IN INTRINSIC AND EXTRINSIC SYSTEMS
Authors: Barrowcliffe T W , Marshall D A , Trickett L P , Hubbard A R , Thorpe R 
Published: August 2018

Cells of the monocyte/macrophage series develop thromboplastin procoagulant activity (PCA) when activated. This activity may be enhanced by T lymphocytes, but there have been few studies of the PCA of T lymphocytes themselves. In the present study, we have measured the PCA of four T lymphoma cell lines (JURKAT, CEM, HSB2 and MQLT4) as well as normal peripheral blood T lymphocytes, before and after stimulation with phyto-haemag-glutinin (PHA), using clotting and amidolytic methods.Of the four cell lines only one, JURKAT, gave enhanced PCA. after stimulation with PHA., with recalcification times in plastic tubes being shortened from 200 secs, to 90 secs, at a cell concentration of 4 × 106 ml. This activity was shown to be thromboplastin-like by its dependence on Factor VII in plasma and in an amidolytic assay with purified Factors VII and × . JURKAT was also the only one of the four cell lines to secrete interleukin-2. All four cell lines promoted the generation of large amounts of thrombin in platelet-free plasma in glass tubes; the peak thrombin concentration of 25 iu/ml was equivalent to that generated by a procoagulant phospholipid reagent. This activity was dependent on the presence of plasma Factor VIII, and was shown to be due to phospholipids in the cell membranes by its inhibition with phospholipase A2 and C and its activity in a purified system with Factors VIII, IXa and X. Normal T lynphocytes generated similar thromboplastin PCA to JURKAT after PHA stimulation, but their intrinsic PCA in the thrombin generation test was only 15% of that of the lymphoma cells.These results show that some T lymphocytes can develop PCA in both intrinsic and extrinsic systems and this should be taken into account in studies of the PCA of mixed leucocyte populations. The difference in intrinsic PCA between normal and lymphoma cells could be an interesting marker for malignant transformation.
IN VIVO CHANGES IN SYSTEMIC PCO2 AND PO2 INFLUENCE THE THROMBOEMBOLIC REACTION FOLLOWING WALL PUNCTURE IN VENULES BUT NOT IN ARTERIOLES
Authors: oude Egbrink Mirjam G A , Jan Tangelder Geert , Slaaf Dick W , Reneman Robert S 
Published: August 2018

Changes in pH and PCO2 influence the aggregation of blood platelets in response to various agents in vitro. In the present study intravital video-microscopy was used to investigate whether changes in systemic blood gas values influence the thromboembolic reaction in vivo as induced by vessel wall injury.The microtrauma was induced by puncturing the walls of microvessels in the rabbit mesentery (diameter range: 20-40 μm) with glass micropipets (tip diameters: 6-8 μm). The thromboembolic reactions were compared in two groups of anesthetized rabbits. The control group was ventilated to keep the blood gas values within normal ranges (means: pH=7.40, pCO2=32.9 mmHg, pO2=104.7 mmHg). The experimental group breathed spontaneously (mean blood gas values: pH=7.34, pCO2=50.5 mmHg, pO2=48.1 mmHg). The pCO2 and pO2 values were significantly different between both groups.In arterioles and venules of both groups bleeding and thrombus formation started immediately following wall puncture. Bleeding times were short (medians between 1.0 and 2.6 s). Parts of the thrombi started to embolize between 11.4 and 18.2 s following wall puncture (medians). In the control group embolization continued for 101 s in the arterioles and 17 s in the venules; during these periods 6 and 1 emboli were produced, respectively (all median values). In the experimental group the duration of embolization in the arterioles was 143 s in which period 7.5 emboli were produced, values not significantly different from control. In the venules of the experimental group embolization and hence platelet reaction went on uninhibited during the whole observation period of 600 s and 30 emboli were produced. Fluid dynamic factors cannot explain the differences in thromboembolic reaction between the control and experimental venules; vessel diameters and red blood cell velocities were not significantly different between both groups. Therefore, it is likely that the change in thromboembolic reaction in the venules results from the changes in systemic PCO2 and/or pO2. The different reactions in arterioles and venules in response to the altered systemic blood gas values might arise from different reactions in the vessel walls.
IDENTIFICATION AND PURIFICATION OF AN INHIBITOR TO PLASMINOGEN ACTIVATORS FROM PROSTATE ADENOCARCINOMA CELLS
Authors: Gargan P E , Ploplis V A 
Published: August 2018

The rat prostate adencarcinoma cell line (PA-III), derived from qerm-free Lobund Wistar rats has served as a unique model for prostatic cancer. The supernatant from confluent cultures of the cell line was shown by zymographic analysis to contain three molecular forms of plasminogen activator. One of the activators was characterized in a previous study and has been classified as a tissue type plasminogen activator(Mr=30,000). In the same study the activator with a Mr=45,000 was shown to be of the urokinase class. The high molecular weight(Mr=120, 000) activator, which has not been described previously, was identified as a complex between the tissue plasminogen activator and an inhibitor. Dissociation of the activator and its inhibitor was achieved by incubation of the complex with ammonium hydroxide (1.5M) in the presence of NaDodGO4 (2%). Treatment with NaDodSO4 alone did not dissociate the complex but did however enhance its fibrinolytic activity, suggesting disruption of hydropnotic interactions leading to exposure of the activators active site.A scheme for the purification of the two plasminogen activators, the activator-inhibitor complex, and the free inhibitor was developed. The various components were purified approximately 1000 fold by hydrophobic interaction chromatography on Phenyl-Sepharose, affinity chromatography on Con A Sepharose and by gel filtration on Sephacryl S-200. The purified inhibitor was capable of inhibiting the fibrinolytic activity of both the urokinase type and tissue type plasminogen activators produced by the PAIII cells.
INTERFERENCE OF MONOCLONAL IMMUNOGLOBULINS ON PLATELETS AND WHOLE BLOOD AGGREGATION
Authors: Schinco P C , Fusaro A , Bazzan M , Pannocchia A , Pileri A , Tamponi G 
Published: August 2018

We studied 31 patients with monoclonal gammopathy (MG), 10 of them secreting monoclonal antibodies (MoAb) of the G class, 13 of them IgM and 8 IgA. We also studied 15 healthy age- and sex-matched control subjects. On each subject we evaluated whole blood aggregation (WBA) in response to ADP, collagen, epinephrine and arachidonic acid in parallel with PRP aggregation according to the method of Born. We wondered whether WBA could provide us further information on the interference of MoAb on platelet function. Agonists and concentrations which yielded statistically significant results in comparison with controls will be reported.IgM MG: Increased WBA to epinephrine 5 and 10 μM (p < 0.01) and ADP 4 and 6 μM (p < 0.001). Increased PRP aggregation to ADP 1 μM (p < 0.001) and collagen 1 μg/ml (p < 0.001).IgA MG: increased WBA to ADP 1 μM (p < 0.001). No difference in PRP aggregation.IgG MG: no difference in WBA. Reduced PRP aggregation in response to ADP 1 μM (p < 0.01) and arachidonic acid 0.5 mM (p < 0.01).We conclude that high molecular weight Ig (IgM pentamers and IgA dimers) seem to play a role in WBA, causing an increased aggregatory response when measured as impedance variation; on the other hand, low molecular weight Ig (IgG) seem to interfere directly with platelet function, causing a decreased aggregation. The mechanism underlying this phenomenon is still unclear.Supported by Grant n° 13 by Regione Piemonte.
PLATELET MEMBRANE GLYCOPROTEINS ABNORMALITIES IN PATIENTS WITH ACUTE LEUKEMIAS AND MALIGNANT LYMPHOMAS
Authors: Gorski J , Van Hove L , Vanlangendonck F , Boogaerts M A , Verwilghen R L , Vermylen J 
Published: August 2018

Membrane glycoproteins are implicated in platelet functions.In myeloproliferative disorders some of the platelet functions are known to be perturbated and an abnormal glycoproteins pattern was demonstrated ear-lier.In this study flow cytometry analysis of human platelet membrane glycoproteins IIa and IIIa in patients with acute leukemias and malignant lymphomas has been performed using monoclonal antibodies against these glycoproteins.A reduction in number of glycoproteins receptors on platelet membrane was demonstrated in patients with acute leukemias and malignant lymphomas in comparison with platelets of healthy donors.In patients with leukemias the positive correlation of percentage of platelets recovered in various density receptor regions to bleeding time and negative correlation to platelet number for both glycoproteins have been found.The study demonstrated that flow cytometry can be a useful method of analysis of platelet membrane glycoproteins, and that the patients with acute leukemias and malignant lymphomas have the number of glycoproteins reduced.
MODIFICATIONS OF BIOLOGICAL PARAMETERS DURING TREATMENT OF PULMONARY EMBOLISM BY A VERY LOW MOLECULAR HEPARIN FRAGMENT (CY 222)
Authors: DELAHOUSSE B , GRUEL Y , MOALIC P , QUILLIET L , TOULEMONDE F , LEROY J 
Published: August 2018

45 patients with pulmonary embolism (PE) were treated by a very low molecular weight heparin fragment (CY 222, Institut CHOAY - France) in an open range dose study. Patients were included into three groups (I, II and III) and received respectively 500, 750 or 1000 IC (Institut Choay) antiXa units/ kg/day by continuous intravenous infusion for ten days. The laboratory screen carried out at Day 0 and at 2 - 8 - 12 - 24 - 36, 48 hours and then every day until Day 10, included : Platelet count, Thromboelastography (TEG) on platelet rich plasma (PRP), Amidolytic assays for anti Xa (CBS 3139 STAGO) and anti Ila (S2238 KABI) activities (Calibration with Hepanorm STAGO), Heptest (Diamed, France), Amidolytic assay for tissue plasminogen activator (t-PA) and its inhibitor (PAI, Verheijen's method). Results showed no modification of platelet count and t-PA or PAI levels; An hypocoagulabi 1 ity was demonstrated with TEG on PRP (r+k > 35 mm) in 20 cases (3 patients from group III with haemorrhagic manifestations and 17 cases from groups II and III without complication). Anti-IIa activities were always lower than 0.15 U/ml. Anti-Xa activities and Heptest (Control adult values = 12.75 sec + 1.15) were (Mean + SD):Any significant biological difference between patients who have good or poor clinical results was observed, excepted for 1 patient who had a high level of PAI at Day 0 and recurrence of PE.
MODIFICATION OF COAGULATION AND FIBRINOLYSIS DURING TRANSLUMINAL ANGIOPLASTY IN PATIENTS RECEIVING HEPARIN OR PENTOSAN POLYSULFATE (HEMOCLAR)
Authors: Bel Lakhal N , Pernes J M , Lichtenstein D , Roncato M , Gaux J C , Nieuwenhuizen W , Aiach M 
Published: August 2018

Twenty patients with high stenosis of iliac or femoral artery were randomely allocated to receive by intra arterial route (IA) either 5,000 IU heparin or 50 mg Hemoclar immediately before starting the angioplasty. Those receiving Hemoclar were given a second IA 50 mg bolus at the end of the dilatation.Two blood samples were obtained by venous punction 1) after an initial 30 min resting (V1), 2) at the end of the procedure (V2)- Arterial punction by the dilatation catheter was also performed immediately before and after the dilatation leading to two other samples A1 and A2
The coagulation studies include activated partial thromboplastin time (APTT), thrombin time (TT), hep test (Hemachem, St-Louis, USA), anti Xa activity (Stachrom heparin, Diagnostica-Stago Asnieres, France). There was a significant increase in APTT, TT, and hep test between A1 and A2 as well as V1 and V2 in both groups of patients. However, the prolongation was significantly higher for heparin. Anti Xa activity significantly increased only in heparin group.Fibrinolysis was studied by measuring tPA by the SOFIA assay described by Angles-Cano (Anal. Biochem. 1985, 153, 201), euglobulin lysis time (ELT) and a new plasma ELISA assay specific for fibrinogen degradation products (FDPs) using monoclonal antibody described at the Gaubius Institute (Blood 1985, 66, 503). A significant increase in tPA was observed during the dilatation (A2/A1) and V2/V1) only in the patients receiving Hemoclar. The slight increase of the fibrinolytic activity was further corroborated by a significant increase in FDPs (A2/A1). In both groups, but only in the venous samples (V2/V1), ELT was shortened (p<0.05) and fibrinogen was decreased (p<0.05)No thrombotic complications were observed during the procedure in both groupsConclusion: This study confirms that Hemoclar has an inhibiting effect on coagulation by inhibiting thrombin and thrombin generation, but no anti Xa activity. However, the anticoagulant potency is much reduced when compared to heparin. The profibrinolytic effect seems to be related to the release of free tPA.