bluuebunny/crossref_metadata_2025_split huggingface dataset:
A HEP ARINE-LIKE ANTICOAGULANT IN A PATIENT WITH WEGENER’S GRANULOMATOSIS
Authors: Chrobák L , Rozsíval V , Herout V 
Published: August 2018

In a 23-year-old man with Wegener’s granulomatosis and mild bleeding coagulation studies revealed a significant prolongation of the coagulation time (CT) prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), failure of TT and aPTT to correct in a 1:1 mixture with pooled normal plasma (PNP), correction of the prolonged TT with toluidine blue and correction of TT and aPTT both in vitro and in vivo^protamine sulphate (P.S.).All other coagulation tests, i.e.,bleeding time, platelet count? fibrinogen level, euglobulme lysis time were within normal limits. The patient did not receive heparine. TT after administration of 5ml of protamine sulphate i.v. to the patient became normal - 18,2 s (19,7 s).In summary a patient with Wegener s granulomatosis associated with an endogenous heparine-like anticoagulant is reported. The anticoagulant could be corrected both in vitro and in vivo by protamine sulphate.
ALTERED COAGULATION IN CEREBRAL ISCHEMIA PATIENTS
Authors: Fisher M , Francis R 
Published: August 2018

We investigated coagulation changes in a group of patients with cerebral ischemia, ranging from transient ischemic attacks to cerebral infarction. Patients were studied acutely (within 72 hours of onset of ischemia) and again approximately 2 months following the initial examination. We evaluated platelet activation, fibrin generation, and fibrinolysis by measuring plasma beta-thromboglobulin (BTG), fibrinopeptide A (FPA), and fibrinopeptide B-beta 1-42 (FPB), respectively. We compared measurements in cerebral ischemia patients with a group of age -and sex-matched neurological inpatients without vascular disease ("patient controls") and a similarly matched group of normal volunteers ("normal controls"). BTG levels for 90 patients studied acutely were not significantly different compared to 58 of the same patients studied 2 months later, 16.4 ± 11.3 ng/ml (mean ± SD) versus 17.5 ± 10.2 ng/ml. Both values were significantly increased (p< .05) compared to normal controls (12.2 ± 6.5 ng/ml, n = 44); patient controls (13.2 ± 7.6 ng/ml, n = 18) were not significantly different from normals. In contrast, FPA measurements were significantly increased in acute patients compared to normals (3.3 ± 5.8 versus 1.0 ± 1.7 ng/ml, p< .05) while FPA levels 2 months post-ischemia (0.6 ± 0.9 ng/ml) were no different than normals. FPB measurements were not significantly different among either acute patients (6.5 ± 2.4 pmol/ml) or patients 2 months post-ischemia (4.8 ± 1.5 pmol/ml) compared to normals (6.5 ± 1.8 pmol/ml).In summary, we have found, among cerebral ischemia patients, sustained increases in BTG, acute increases in FPA, and normal FPB. These findings are compatible with a model of cerebral ischemia consisting of acutely increased fibrin generation without concomitant increased fibrinolytic activity, superimposed on a background of increased platelet activation.
A NEW ASYMPTOMATIC TYPE III VARIANT OF ANTITHROMBIN III WITH DECREASE HEPARIN COFACTOR ACTIVITY : AT III AMIENS
Authors: ROUSSEL B , DIEVAL J , GROSS S , CLAISSE J F , DELOBEL J 
Published: August 2018

A qualitative abnormality of AT III suggested by the discrepancy between a normal level of AT III antigen (0,33 g/1) and a decreased heparin cofactor activity (60 % of normal) was discovered in a 37 years old woman during a routine laboratory examination for oral contraceptive. The propositus was asymptomatic as she did not developpe any thrombo-embolic disease during three previous pregnancies. There was no familial history of thrombo-embolism. The AT III level measured by radial immuno-diffusion was within the normal range. The progressive anti factor lia and anti factor Xa activities (chromogenic substrates CBS 3 447 and CBS 3 139) were normal (92 % and 100 %). Plasma and serum crossed immunoelectrophoresis (CIE) showed a normal pattern. In the presence of heparin, anti factor Xa and anti factor Xa activities were decreased (60 % and 45 %); Plasma and serum crossed immunoelectrophoresis showed an abnormal slow moving peak exhibiting the inhability of the molecule to bind completely to heparin. CIE with various other glycosaminoglycans are on experiments.Familial study revealed that the daughter of the propositus was carrying the same molecular abnormality.We conclude that AT III Amiens is an hereditary type III variant.
DIURNAL VARIATION OF COMPONENTS OF THE FIBRINOLYTIC SYSTEM
Authors: Grimaudo V , Kruithof E K O , Hauert J , Bachmann F 
Published: August 2018

To elucidate the causes of the well known diurnal variations of the fibrinolytic activity we have studied severed parameters of the fibrinolytic system in 8 healthy male volunteers during a period of 24 h. Blood sanples were taken at 8, 10 and 12 a.m., 4 and 8 p.m. and at 8 a.m. next morning. Hie following parameters were analyzed: euglobulin clot lysis time (ECLT), fibrinolytic activity of euglobulins on fibrin plates (FPA), antigen concentrations of tissue-type plasminogen activator (t-PA) by ELISA and of urokinase (u-PA) and plasminogen activator inhibitor-1 (PAI-1) by RIA, the overall PA-inhibitor activity by the indirect chranogenic substrate assay (Verheijen et al; 1984) and the electrophoretic-zymogra-phic analysis of the euglobulins fraction.Global fibrinolytic activity increased from 1.0 ±0.3 U/ml at 8 a.m. to 2.5 ±1.1 U/ml at 8 p.m. (p <0.002) as measured by ECLT (U=300/lysis time in minutes) and from 2.3 ±0.4 IU/ml to 4.7 ±1.1 IU/ml (p <0.001) as determined by FPA. In contrast, t-PA antigen decreased from 5.1 ±0.8 ng/ml at 8 a.m. to 2.9 ±1.5 ng/ml at 8 p.m. (p<0.01) and u-PA antigen from 8.1 ±1.2 ng/ml to 7.1 ±0.7 ng/ml (p<0.05). Most pronounced was the decrease of PAI-1 antigen from 23.5 ± 7.6 ng/ml in the morning to 8.8 ±2.6 ng/ml at 8 p.m. (p <0.001), while PAI activity decreased from 8.8 ±3.6 U/ml to 5.5 ±1.8 U/ml at 4 p.m. (p <0.002). During the entire study period the electro-phoretic-zymographic analysis did not reveal any free t-PA; the latter was present throughout in the form of the 110 kD t-PA/PAI-1 ccnplex. During the day the intensity of the 110 kD band decreased progressively.These findings confirm the physiological diurnal fluctuation of the fibrinolytic activity. All components of the fibrinolytic system are involved in this fluctuation and participate in the modulation of fibrinolytic activity.Our study demonstrates that the diurnal increase of fibrinolytic activity is due principally to a marked decline of the PAI-1 concentration during the day and not to an increase of PA antigen levels.
COMPARISON OF SINGLE-CHAIN AND TWO-CHAIN RECOMBINANT TISSUE-PLAS-MINOGEN ACTIVATOR (t-PA) IN VITRO. TURNOVER OF SINGLE-CHAIN t-PA IN ANIMALS AND MAN
Authors: Nguyen G , Bara L , Samama M , Conard J , Van Dreden P , Desnoyers P , Bendetowicz A V 
Published: August 2018

Two preparations of recombinant t-PA obtained from mammalian cells (Boehringer Ingelheim) containing mainly single-chain forms t-PA (sct-PA > 95%) or two-chain forms t-PA (tct-PA > 70%) were compared in vitro for their thrombolytic and fibrinogeno-lytic properties.Thrombolytic activities studied on human hanging clots were similar for both preparations, at plasma concentrations ranging from 62.5 to 1,000 IU/ml. Fibrinogenolysis appeared for both preparations at concentrations higher than 500 IU/ml, after a 90 min incubation at 37°C. For higher concentrations, fibrinogenolysis was dose-dependent, and- there was a trend with sct-PA to provoke less fibrinogenolysis.The turnover of sct-PA was studied in rabbits and cats. After an intravenous bolus injection of 0.2 mg/kg, t-PA activity and antigen showed a double decay disappearance curve. Initial and secondary phases had similar t.1/2 for the activity and the antigen, as well as in both species, which were respectively estimated about 2 min and 20 min.Although the biological and immunological clearance rates were not significantly different, sct-PA antigen values were much higher than the activity.Sct-PA clearance rate was also measured in patients with acute myocardial infarction, treated with intravenous infusion of sct-PA, 100 mg over 3 hours, of which 60 mg during the first hour (n=4). t-PA antigen was regularly measured within 20 min after the end of the first hour infusion.A biphasic disappearance curve was observed, the first phase was extremely rapid with a t.1/2 of 3.2 ± 1.2 min, and the secondary phase had a t.1/2 of 10.4 ± 2.6 min.
Kinetics of piasminogen-activation. Effects of ligands binding to the AH-site of plasminogen
Authors: Christensen Ulla 
Published: August 2018

Detailed kinetic studies of the urokinase catalysed conversion of Lys-77- and Val-440-plasminogens in the presence and absence of ligands binding to the AH-site of the plasminogens shows that the effects of such ligand-binding correspond with a model of the activation reaction in which the effective Km and kc decreases, but kc/Km increases when the ligands bind. Apparently plasminogen with a free AH-site is a less specific substrate for urokinase, than is plasminogen with an AH-site-bound ligand.The AH-site is a weak lysine binding site of plasminogen located in the mini plasminogen part (Val-440-Asn-790) of plasminogen and is suggested to participate in the binding of the plasminogens to undegraded fibrin.
FIBRINOLYTIC RESPONSE AFTER VENOUS OCCLUSION AND DDAVP IN PATIENTS WITH DEEP VENOUS THROMBOSIS
Authors: Kozak M , Keber D 
Published: August 2018

After prolonged stimulation venous endothelium becomes refractory to otherwise efficacious stimuli for tissue plasminogen activator (t-PA) release. When the stimulus is removed, the restitution of the response is observed. The distention of the veins distally from the occlusion site in deep venous thrombosis (DVT) could represent such a chronic stimulus. We studied t-PA release in patients with DVT during 20-min venous occlusion (VO) and DDAVP infusion (0,4 ug/kg b.w. in 10 min). t-PA release was estimated as the difference in euglobulin clot lysis time (ECLT in U) and fibrin plates (FP in mm2) before and after VO (fibrinolytic potential). Two groups of patients were studied: 15 recumbent patients with oneside iliofemoral DVT, and 15 patients with oneside postthrombotic syndrome.In both groups the response of legs was lower than that of arms. The comparison of the healthy and the affected leg in postthrombotic group showed no difference in t-PA release after VO. A higher release of t-PA was seen in the acute DVT group in all three tested limbs, explainable by a restitution of fibrinolytic potential due to the reduction of hydrostatic stimulus. However, the response was slightly lower in the diseased leg. In 5 patients from the acute DVT group DDAVP infusion induced higher t-PA release after VO in both legs compared to VO before DDAVP. We can conclude that hydrostatic pressure in upright position is such a strong stimulus that an additional decrease of t-PA release due to chronic venous stasis cannot be expressed. In recumbent patients DVT hinders the restitution of the response to V0 in the diseased leg. DDAVP seems to act independently of hydrostatic pressure and venous stasis.
EFFECT OF DEXTRAN ON PLASMINOGEN ACTIVATOR INHIBITOR (PAI)
Authors: Saldeen T , Moalli R , Hasan F M , Carvalho A , Eriksson M 
Published: August 2018

Adult respiratory distress syndrome (ARDS) is often associated with impaired fibrinolysis and appearance of microemboli in the lung. Increased production of PAI, associated with acute lung injury, may contribute to this process. In patients at risk of developing microembolic complications, aeteinistration of dextran reduced the incidence of ARDS. Accordingly, we studied the effect of dextran adninistration on plasma PAI levels in a rabbit model of endotoxin-induced lung injury and in patients. E coli endotoxin (500 μg/kg bw, infused over 5 min) was administrered to three groups of anesthetized, ventilated rabbits; 10 rabbits were pretreated and maintained with a 10% dextran-40 infusion (20 ml/kg bw), 6 received a 3% albunin solution (20 ml/kg bw) and 8 control rabbits received saline. Plasma PAI levels were measured by chrcmogenic assay. By 180 minutes after endotoxin infusion, PAI levels increased from 28 ± 6 to 155 ± 7 U/ml in the saline group, to 152 ± 10 U/ml in the albumin group and to 85 ± 8 U/ml in the dextran group.24 surgical patients were given 500 ml Dextran 70 (Macrodex) and PAI and t-PA were determined before, during and after dextran. PAI levels decreased 6 ± 8 U/ml during dextran infusion and 11 ±11 U/ml (26 per cent) after dextran, and was significantly decreased after correction for hemodilution. t-PA antigen levels were not changed due to dextran. Dextran thus has an effect on PAI levels which is not due to release of t-PA. Dextran by decreasing PAI levels may have unique salutary effects on fibrinolysis which may be important in the prevention of thrombotic disorders.
PREPARATION AND CHARACTERIZATION OF MONOCLONAL ANTIBODIES TO PROTEASE NEXIN
Authors: Steven I , Wagner L , van Nostrand W E , Cunningham D D 
Published: August 2018

Protease nexin I (PN-1) is a cell-secreted protease inhibitor which modulates the activity of certain serine proteases in the extracellular environment. To probe PN-1 functions, we prepared a panel of monoclonal antibodies (mAbs) against it and studied their effects on a variety of PN-1 activities. Three highly potent inhibitors of PN-1 activity have been characterized. MAbs pl-6 and pl-9 stoichiometri-cally block PN-l-mediated anti-thrombin and anti-urokinase activity. These mAbs block PN-l-mediated anti-trypsin activity less effectively. MAb pl-18 stoichiometrically blocks all PN-1 antiprotease activities tested including anti-trypsin activity and therefore appears to bind at the reactive center of PN-1. Heparin, which greatly accelerates PN-1 anti-thrombin activity, does not compete with the binding of these blocking mAbs. None of these blocking mAbs could bind to thrombin-PN-1 complexes. A mAb (pl-1) which did not block PN-1 activity was capable of binding to these complexes.
MAbs pl-9 and pl-18 were used to immunopurify two forms of PN-1 which have different affinities for heparin-Sepharose. These have been referred to as the low heparin affinity and high heparin affinity forms of PN-1 (Scott et al., J. Biol. Chem. 260,7029-7034 [1985]). MAb pl-18 binds only to the high heparin affinity form while mAb pl-9 binds to both forms. Preliminary characterization of this low heparin affinity form reveals no major differences between it and the well characterized high heparin affinity form.
OCCURRENCE OF PAI-2 IN MEN AND NON-PREGNANT WOMEN
Authors: Lecander I , Åstedt B 
Published: August 2018

PAI-2 is a specific plasminogen activator inhibitor most likely produced in the trophoblasts of placenta but presumably also in certain macrophages. It occurs in two molecular froms of 48 and 60 kDa. From placenta homogenates mainly the LMW-form can be isolated. During pregnancy mainly the HMW-form increases in the blood and disappears after delivery.We examined blood samples from 120 male blood donors (females excluded to avoid unknown pregnancies) and 20 staff members, 4 males and 16 females for the presence of PAI-2.PAI-2 antigen levels were measured with a sandwich ELISA using a polyclonal and a monoclonal antibody. The concentration was given in per cent of that in pooled term plasma.PAI-2 antigen was detected in 5 of the blood donors 9, 12, 22, 31 and 60 %. In one male staff member the antigen concentration was 9 % and in one female 72 %. Repeated analyzes of this last member for six months resulted in values between 30-90 %. Immunoblotting using a monoclonal antibody against PAI-2 showed a HMW-band of about 80 kDa.
PLASMINOGEN ACTIVATOR INHIBITORS OF TYPE 1 (PAI-1) AND TYPE 2 (PAI-2) ARE PRESENT IN ASCITIC FLUID FROM PATIENTS WITH OVARIAN CARCINOMA
Authors: Lecander I , Martinsson G , Nielsen L S , Andreasen P A , Danø K , Åstedt B 
Published: August 2018

The fast acting specific plasminogen activator inhibitor PAI-1 produced in endothelial cells and present in plasma and thrombocytes is known also to be released from certain tumour cell lines. The specific plasminogen activator inhibitor PAI-2 of placental type and present in pregnancy plasma is also released from a histocytoma cell line.We examined ascitic fluid for the presence of PAI-1 and PAI-2 in five patients with advanced ovarian carcinoma. The antigen levels of PAI-1 and PAI-2 were assayed with sandwich ELISAs using a combination of monoclonal and polyclonal antibodies and the activity of PAI-1 was in addition measured by an activity assay (BioPool). The antigen level of PAI-1 ranged between 110 and 800 ug/1 (mean 315 μg/1) and the activity between 5 and 16 U/ml (mean 12 U/ml). Antigen levels of PAI-2 ranged from 10 to 62 ug/1 (mean 30 μg/ml), i.e. approximately 35 (12-72) % of the concentration of PAI-2 in term plasma. In blood samples obtained from three of the patients during surgery from veins draining the tumors, the concentration of PAI-2 was 0, 7 and 12 μg/1, respectively. PAI-2 could not be detected in the peripheral blood.
NONENZYMATIC GLYCATI0N OF HUMAN BLOOD PLATELET PROTEINS
Authors: Cohen I , Burk D , Fullertone R J , Veis A , Green D 
Published: August 2018

Atherothrombotic events are common in diabetics, and enhanced platelet function is thought to be partly responsible. Since excessive glycation occurs in many proteins of diabetic subjects, we decided to evaluate glycation of diabetic platelet proteins, and especially those proteins known to be involved in platelet aggregation. We believe this is the first report of nonenzy-matic glycation of platelet proteins from patients with poorly-controlled diabetes mellitus. Overall glycation was assessed by the extent of incorporation of [3H]BH4 into fructosyl lysine separated from whole platelet proteins following protein hydrolysis. We studied 12 diabetic patients, all of whom had severe atherothrombotic disease, and 13 normal controls. Fructosyl lysine eluted in the first major radioactive peak and represented 5.7 ± 1.0 S.D. of the total radioactivity in the normal whole platelet samples. Five of the 12 diabetics showed increased radioactive labeling of fructosyl lysine, without a clear pattern of correlation with the levels of glycation of hemoglobin and albumin (r = 0.33 and 0.17, respectively for hemoglobin and albumin). The pattern of glycation of the various platelet proteins in whole platelets, as determined by the incorporation of [3H]BH4 in proteins electrophoretically separated, does not clearly show a selectivity, although myosin and glycoproteins IIb and IIIa have relatively increased levels of [3H]BH4 incorporation. Artificially glycated platelet membranes exhibit glycation mainly in proteins corresponding to the electrophoretic mobility of myosin, glycoproteins IIb and IIIa and actin.Whether this glycation results in enhanced platelet function and specific loss of these platelets in vascular thrombi is still unclear. Trapping of highly glycated platelets in thrombi may be responsible for the poor correlation between the extent of platelet glycation and the elevated levels of glycated hemoglobin and albumin. (Supported in part by Grant AM13921-26 to A.V.)
ROLE OF PLATELETS IN EXPERIMENTAL THROMBOSIS INDUCED BY VENOUS STASIS
Authors: Bernat A , Vallée E , Maffrand J P , Gordon J 
Published: August 2018

Venous stasis in the rat, induced by ligature of the vena cava, provokes thrombosis. This venous thrombosis was initially believed to be platelet-independent because severe thrombocytopenia (95 % reduction in platelet count), aspirin and dipyridamole had little effect. However, the model responded to other platelet anti-aggregators, such as Ticlopidine and its analogue PCR 4099, although these compounds had no effect on coagulation, fibrinolysis or leucocyte functions (Thromb. Res. 37, 279-285, 1985). Both these drugs are known to exert their main antiplatelet effect against aggregation induced by ADP.The aim of the present study was to re-evaluate the role of platelets in this model of venous thrombosis. We have been able to show that :1) complete thrombocytopenia (99 %), achieved with an antiplatelet anti-serum, dramatically inhibited thrombus formation (by 84 % ; p < 0.01).2) partial transfusion of platelets (23 %) from control animals to these thrombocytopenic rats re-established the thrombosis.3) transfusion (under identical conditions) of platelets from rats treated with PCR 4099 had no effect.4) vena cava ligature in Fawn Hooded rats (deficient in platelet dense granules) induced less thrombosis (64 % of control ; p < 0.05).We conclude that this venous stasis model is platelet-dependent. Furthermore, because thrombus formation was reduced in normal rats treated with anti-aggregants acting selectively against ADP, and in rats lacking ADP in their platelet dense granules, it appears that ADP plays a major role in this model of thrombosis.
A ROLE OF DIACYLGLYCEROL KINASE IN STIMULUS-SECRET I ON COUPLING OF HUMAN PLATELETS -DISSOCIATION OF SEROTONIN SECRETION FROM Ca2+ MOBILIZATION-
Authors: TOHMATSU T , NAKASHIMA S , HATTORI H , SUGANUMA A , NOZAWA Y 
Published: August 2018

Diacylglycerol (DG) kinase catalyzes the reaction: DG + ATP phosphatidic acid + ADP and it is widely distributed in animal tissues. The enzyme seems to play a pivotal role in removing a second messenger, DG, which activates protein kinase C. DG kinase inhibitor, R 59 022 (6-[2-[4-[(4-fluorophenyl)pheny1- methylene] -1-piperidinyl] ethyl] -7-methyl-5H-thiazolo [3,2-a] -pirimidin-5-one) has recently been developed. In order to gain further insight into the role of DG in the secretory response, effects of the DG kinase inhibitor on secretory responses and Ca2+ mobilization were investigated in human platelets.The addition of the DG kinase inhibitor (10 μM) potentiated thrombin-induced accumulation of [3H]radioactivity of DG in platelets loaded with [3H] arachidonate. Thrombin-induced release of [3H] arachidonic acid and its metabolites was not affected by the inhibitor. The inhibitor did not cause significant secretion of [14C] serotonin by itself. However, the pretreatment with this agent potentiated the level of secretion in thrombin-stimulated platelets. When l-oleoyl-2-acetylglycerol(OAG) was added to [32pjpi-iabeled platelets in the presence of the DG kinase inhibitor, the formation of [32P] l-oleoyl-2-acetylphosphatidic acid was greatly prevented. The pretreatment with the inhibitor also potentiated OAG-induced serotonin secretion. With the view that Ca2+ is thought to be another important second messenger, we investigated the effect of the DG kinase inhibitor on Ca2+ mobilization. Two types of Ca2+ indicators, Quin2 and aequorin were used to measure cytosolic free Ca2+ concentration ([Ca2+]i). The inhibitor alone did not affect [Ca2+]i. Interestingly, thrombin-induced increase in [Ca2+]i was suppressed by the pretreatment with this agent both in the Quin2-loaded and aequorin-loaded platelets.These results indicate that diacylglycerol kinase may operate as an attenuator in the signal transduction system involving protein kinase C and that Ca2+ mobilization may not be tightly coupled to serotonin secretion.