bluuebunny/crossref_metadata_2025_split huggingface dataset:
PROTEIN S AND ANTICARDIOLIPIN ANTIBODIES IN PATIENTS WITH LUPUS ANTICOAGULANT WITH OR WITHOUT THROMBOSIS
Authors: Panzer S , Pabinger I , Dudczak R , Schulz E , Wurz E , Lechner K , Lechner K 
Published: June 2019

Arterial and venous thrombosis frequently occur in patients with lupus anticoagulant. We investigated in patients with lupus anticoagulant the possible association between protein S:Ag deficiency and/or anticardiolipin antibodies and a history of thrombosis. In 27 patients (8 with and 19 without a history of thromboembolic disease) free protein S:Ag was determined with immunoelectrophoresis in PEG 8000 precipitated plasma. Anticardiolipin antibodies were measured in 22 patients (10 with thromboembolism) by means of a solid phase radioimmunoassay.Free plasma protein S:Ag was normal or elevated in 25 patients and slightly decreased (protein S:Ag 67%) in 2 patients without thromboembolism. 2-dimensional electrophoresis revealed a normal distribution of the free and of the complexed form of protein S:Ag. Anticardiolipin antibodies were found in 6 out of 10 patients with a history of thrombosis (5 of 7 with venous thrombosis, 1 of 1 with cerebral infarction , none of 2 with combined venous and arterial thromboembolism) and in 4 out of 12 patients without a history of thrombosis.We conclude 1. the thrombophilic state in patients with lupus anticoagulant cannot be explained by a reduction of protein S:Ag, and 2. there seems to be no correlation between the presence or absence of anticardiolipin antibodies and the development of thromboembolic disease.
THE EFFECT OF APROTININ ON EXPERIMENTAL PORCINE SEPTIC SHOCK
Authors: Svartholm E , Haglund U , Ljungberg J , Hedner U 
Published: June 2019

Septic shock induces pronounced haemodynamic changes resulting in pulmonary microemboliz., complement activ. and an activ. of the coag. and fibrinol. systems. Only minor effects on the sepsis-induced changes were found on pretreatment with a variety of platelet aggr. inhib. (Svartholm et al 1986). Aprotinin inhibits among other enzymes kallikrein. Endotoxin shock was induced in 12 pigs by i .v. inf. of E.coli, six of vdiich got Aprotinin i.v. (1000000 KIE) immediately before the E.coli infusion. Another 6 pigs were used as controls. Haemodynamic parameters, platelet counts, fibrinol. act., fibrinogen, ATIII, and ethanol gel. test were measured before the infusions, 8,60, 90-120, 150-180 min after. Ihe haemodynamic parameters stayed unchanged in the control pigs. In the E. coli-treated animals cardiac output and the mean art. pressure decreased signif. On the other hand, the mean pulm. art. blood pressure and the pulm. vase, resist, increased signif. Ihe increase of the pulm. resist, was less pronounced and reversible in the Aprotinin treated animals. Ihe pulm. vase, resist, in the E.coli group increased contin. from 2.8ଐ.2 mm Hg before to a max. of 23.4 mm Hg at the end of the obs. time and in the Apro-tinin-treated animals from 2.0ଐ.3 to 6.6଑.9 mm Hg (8 min after the inj.) being down to 4.4ଐ.2 at the end of theexp.The platelet decrease was less pronounced in the Aprotinin pretreated group, the ethanol gel test turned pos. in the E.coli group after 60 min but stayed neg. in both the contr. and the Aprotinin pretreated animals. Fibrinolytic act, was seen in all E. coli-treated animals but stayed neg. in the contr. Moderate changes were seen in ATIII and fib. gen in all E.coli-treated pigs. All animals treated with only E.coli died at the end of the obs. time but none in the control group and none in the Aprotinin pretreated groupIn conclusion Aprotinin seems to prevent the secondary fatal increase in pulm. resist, most probably caused by pulm. oedema and a gen. activ. of the coag. syst. (ethanol gel. test stayed neg.)
LOW PLASMA CONCENTRATIONS OF C4b-BINDING PROTEIN AND VITAMIN K-DEPENDENT PROTEIN S IN PRETERM INFANTS WITH DECREASED FORMATION OF PROTEIN S-C4b-BINDING PROTEIN COMPLEXES
Authors: Malm J , Bennhagen R , Holmberg L , Dahlbäck B 
Published: June 2019

Protein S is a vitamin K-dependent plasmaprotein functioning as a non-enzymatic cofactor to the activated form of protein C in the degradation of coagulationfactors Va and VIIa. In the circulation approximately 60% of protein S is complexed to the complement protein C4b-binding protein (C4BP). Only the remaining, free fraction exhibits protein Ca cofactor activity.The plasma concentrations of protein S and C4BP were determined in 25 term and 26 preterm infants. Both proteins werequantified with radioimmunoassays. The free, functionally active form of proteinS and the total protein S concentration were determined separately. The level ofC4BP in preterm infants was found to be very low (mean 6% of the adult level). In term infants the level had increased to a mean of 18%. Also the total concentration of protein S was decreased in preterm as well as in term infants; 18% and 31% of the adult level, respectively. Free protein S was the predominant form in plasma representing 83 % of total protein S in preterm and 68 % in term infants. This was probably due to the very low C4BP levels. In adult controls the corresponding value was 34%. The plasma concentration of free protein S in preterm and term infants, when compared to the adult level, was 44% and 66%, respectively. These results demonstrate that although the total protein S concentration in preterm and term infants was very low when compared to adult levels, the difference in the concentration of free, functionally active protein S between infants and adults was less pronounced.
ANTENATAL DIAGNOSIS OF THROMBOPATHY
Authors: Wautier J L , Gruel Y , Boizard B , Caen J P , Daffos F , Forestier F 
Published: June 2019

We previously determined platelet antigens and glycoproteins in the human fetus after 19 weeks of intrauterine life (Blood 68, 488-92,1986). These results obtained in fetuses with normal platelets allowed us to do the first attempt of antenatal diagnosis in Glanzmann thrombasthenia. The fetal propositus was tested with monoclonal (AP2, AP3) or polyclonalantibodies (IgGL) directed against GPIIbllla or platelets antigen (PLA1, Leka). The foetus was found to be heterozygous for GT and similar results were foundafter his birth.Grey platelet syndrome is a rare congenital platelet defect caracterized by an alpha granule deficiency and is transmitted on the dominant feature. To be able to detect this abnormality before birth we have measured the platelet content of alpha granules.The amount of Beta thromboglobulin (gTG) at 18 weeks of intrauterine life was32±4.3 mg/109 platelets in normal platelets (adults 60 mg/10^ platelets). The foetus of the mother with grey platelet syndrome was sampled at 19 weeks when the mother was under platelet transfusion and the platelets were studied by electron microscopy and for their BTG content. The platelet morphologyshowed the presence of alpha granules and the $TG content was in the range of the control fetuses (42mg/109 platelets). The baby was born after artificial delivery under platelet transfusion. These results showed that the antenatal diagnosis of thrombopathies is feasible and can permit a therapy to avoid dramatic haemorrhage during pregnancy or delivery.
PROTEIN C AND PROTEIN S IN MILD AND MODERATE PREECLAMPSIA
Authors: Hopmeier P , Halbmayer M , Schwarz H P , Heuss F , Fischer M 
Published: June 2019

In normal pregnancy, total protein S antigen and activity have been reported to be markedly reduced, whereas protein C level was found unaltered. In contrast, in severe preeclampsia protein C antigen was found to be considerably reduced. The presentstudy was done to clarify whether similar changes in protein Cwould alsobe observed for the mildand moderatepreeclamptic state andwhether there would be any effects on the level ofprotein S, since nodata on this cofactor in preeclampsia have been reported to date. 4-0 women in the 3rd trimester of pregnancy - 20 with uncomplicated pregnancies and 20 who had developed a mild (n = 14-) or moderate (n = 6) preeclamptic condition - were included in the study. All groups were well matched in age and gestational age. In addition, 20 healthynon-pregnant women served as controls. All probands had normal liver (SGOT, SGPT) and kidney (BUN, creatinine) values and no other medication than oral vitamins was used. Classification of preeclampsia was done according to a modification of the gestosis index of Goecke using an 11 gradeindex system (0 - 11). ProteinC antigen was measured by an enzyme-linkedimmunosorbent assay and protein S by the Laurell rocket technique.For statistics, the Wilcoxon rank sum test was appliedWe conclude that in comparison tonormal pregnancies, protein S is found elevated at least in the moderate, and protein C in the moderateas well as in the mild preeclamptic state
DEFECTS OF VITAMIN K-DEPENDENT FACTORS IN CA(11)-STABILI ZED STRUCTURE
Authors: Poort S R , Krommenhoek-van Es C , van der Linden I K , van Tilburg N H , Bertina R M 
Published: June 2019

Vitamin K-dependent (anti)coagulation factors (factor II, VII, IX, X protein C and S) undergo a conformational transition upon binding of Ca(II), which is a prerequisite for their normal function. Abnormalities in these properties occur during vitamin K deficiency or treatment with anti vitamin K drugs and in some genetic variants of coagulation factors. Immunological assays utilizing antibodies against the Ca(II)-stabilized structure are useful to detect such abnormalities.Starting from specific rabbit antisera antibody populations specific for the Ca(II)-dependent conformation of factor II, VII, IX, X and protein C and S were isolated using immuno-affinity procedures. Subsequently immunoradiometric assays specific for the Ca(II)-dependent (Ca(II)Ag) and Ca(II)-independent (NonCa(II)Ag) conformations of the different proteins were developed. These assays were used for the analysis of plasmas of patients stably treated with oral anticoagulants; Ca(II)Ag, NonCa(II)Ag and their ratio were measured as function of the intensity of the treatment (INR 2.4 to 4.8). The same parameters were measured in plasmas of patients with hereditary coagulation disorders. After treatment with oral anticoagulation with an antivitamin K drug reduced ratios of Ca(II)Ag/-NonCa(II)Ag were observed for factor II, VII, IX, protein C and protein S. However, the actual degree of reduction and its dependence on the intensity of treatment varied for the different vitamin K-dependent proteins. In general Ca(II)Ag levels correspond nicely with the procoagulant activity of the concerning proteins. These data provide indirect evidence for the existence of abnormal (non and/or subcarboxylated) forms of the vitamin K-dependent proteins during oral anticoagulant treatment.Genetic variants with a mutation in one of the sites involved in the formation of the Ca(II)-s tab i1ized structure could be detected for factor IX, factor VII and factor II. However, the extent of reduction of the ratio Ca(II)Ag/-NonCa(II)Ag differed considerably in those variants.
Pathobiology of Human Fibrinogen. Binding site for Staphylococci on Aα and Bβ chains of Fibrinogen Molecule
Authors: Hawiger J. , Hammond D. K. , Timmons S. 
Published: June 2019

The ability of human fibrinogen to interact with some staphylococci to cause a non-enzymatic clumping reaction has been used to detect fibrinogen and its derivates in blood and body fluids. We studied localization of the binding site for staphylococci on human fibrinogen using 125I-fibrinogen after reduction and alkylation of polypeptide chains, CNBr-treatment, and limited plasmin digestion. This combined approach revealed that the staphylococci-binding site is located on Aα and B β chains involving C-terminal portion but not N-terminal disulfide knot, γ chain has no binding site for staphylococci. Abnormal fibrinogens with defects in the N-terminal portion interacted normally with staphylococci. The degree of binding paralleled the extent of clumping reaction between staphylococci and 125I-fibrinogen or its plasminderived fragments. However, monomeric Scarboxymethyl Aα and B β chains showed a high degree of binding without concomitant clumping suggesting requirement for dimeric form of polypeptide chains for clumping. Conclusion: Aα and Bβ chains but not γ chain have homologous regions in terms of staphylococci-binding site on C-terminal portion responsible for clumping reaction. Thus, staphylococci can be used to measure abnormal fibrinogens with defects in the N-terminal region.(Supported by NIH Grants and VA.)
Effect of Acetyl Salicylic Acid on Platelet Function in Yivo
Authors: Hassanein A. A. , Afifi N. , Badr M. 
Published: June 2019

The ingestion of a single dose of 300 mg. acetyl salicylic acid (ASA) cause after two hours, significant diminution in ADP-induced platelet aggregation and increase in platelet disaggregation. The calcium-induced platelet aggregation test, a turbidimetric modification of the Chandler tube technique, showed significant prolongation in the onset of aggregation and in the clotting time. A test based on the contact product forming activity of platelets showed inhibition after ASA intake.It is suggested that acetyl salicylic acid in addition to its inhibitory effect on platelet release reaction, also affects primary aggregation by ADP and possibly interferes with the ability of platelets to activate the contact system of the intrinsic blood coagulation pathway.
Daunomycin and Platelet Function
Authors: Whaun J. M. , Dundas J. E. , Clarke H. 
Published: June 2019

Daunomycin, an antimetabolite antibiotic used in the treatment of acute leukemia, is highly cytotoxic to both normal and malignant cells. Thrombocytopenia occasionally noted with its use, has usually been attributed to its toxic effect on the bone marrow. Citrated platelet-rich plasma (PRP) from normal volunteers was tested in vitro in the aggregometer after addition of either aggregating agent, collagen, (0.083 mg/ml PRP), or varying concentrations of daunomycin, or both. Other aliquots were exposed to daunomycin or saline for 90 seconds before fixing in glutaraldehyde. The remainder, labelled with 0.5 μM 2−14C-5-hydroxytryptamine binoxalate (14C-5-HT), 27.5 c/mole for 15 minutes, was tested for 14C-5-HT release before and after exposure (90 sees. 37° C) to collagen of final concentration 0.04 mg/ml.At a concentration 0.001 mg/ml PRP, daunomycin was associated with decreased response of platelets to collagen with decreased 14C-5-HT release. At 0.02–0.04 mg/ml daunomycin was associated with vacuole formation, loss of dense bodies as well as platelet lysis as well as liberation of newly absorbed 14C-5-HT. Electron micrographs of platelets exposed to higher doses of daunomycin showed platelet swelling, vacuole formation, swollen mitochondria and granules and interruption of the trilaminar membrane.
Platelet Dysfunction Induced by Parenteral Administration of Carbenicillin and Ticarcillin
Authors: Johnson G.J. , White J. G. 
Published: June 2019

Carbenicillin treatment of humans has resulted in impaired platelet function occasionally accompanied by hemorrhage. Because of their therapeutic potential as anti-thrombotic agents, we have studied carbenicillin (CARB) and ticarcillin (a-carboxy-3-thienylmethyl penicillin) (TIC) effects on platelet function in the dog. Studies of platelet aggregation (AGG), adhesiveness (ADS), factor 3 availability (PF3), bleeding time (BT), electron microscopy (EM), and serotonin (5HT) and adenine nucleotide (AN) content were performed sequentially in dogs given CARB or TIC. Progessive impairment of platelet function was observed with increasing doses from 250 to > 1250 mg/kg/day. Doses of 250 to 750 mg/kg/day resulted in mild to marked impairment of ADP induced AGG, markedly decreased ADS, and moderately prolonged PF 3 clotting times. Collagen induced AGG was impaired and the BT was prolonged only at doses > 750 mg/kg/day. Platelet dysfunction was evident at 4 hr., significant at 24 hr., and maximal at 72 to 96 hr. with little further progression up to 14 days despite continued treatment. At equivalent doses CARB was slightly more inhibitory than TIC. EM, 5HT, and AN did not change significantly. Platelet function was significantly improved 24 hr. after treatment was discontinued, and progressive improvement continued for 5 to 14 days.These studies demonstrate that CARB and TIC induce a dose-related impairment of platelet function. They suggest that these drugs interfere with the platelet release reaction. They indicate that CARB and TIC are promising anti-thrombotic agents which merit further study.
Prevention of Ischemic Cerebro Vascular Accident; A Long Term Clinical Trial with Vasodilator an dAntiaggregatin Drugs
Authors: Guiraud B. , David J. , Géraud G. , Boneu B. , Biermé R. , Rascol A. 
Published: June 2019

The purpose of this study is to determine whether antiaggregating drugs are more effective than vasodilators in the prevention of ischemic cerebrovascular accidents.To date, 350 patients are randomly divided into 3 groups and treated as follows: group 1 – hydergin alone (4.5 mg/day); group 2 – hydergin (4.5 mg/day) plus aspirin (1 g/day); group 3 – hydergin (4.5 mg/day) plus aspirin (1 g/day) plus dipyridamole (15 Omg/day).Only those patients with a history of transient ischemic attacks or a regressive stroke with minimal sequellae are included. Patients with coagulopathy, long term anticoagulant or anti-inflammatory treatment, valvulopathy or peptic ulcus are excluded. Cerebral angiography is performed only when indicated. All patients are clinically examined three times a year with platelet aggregation performed at each visit to control correct drug intake.This study, begun on the june 1st 1973, will be followed for a three years period once a total sample population of 400 patients is reached.A preliminary interpretation of the data will be completed.
Defibrinogenation Procedures for Antithrombin III (AT-III) Biological Assay
Authors: Tonolli M. C. , Donati M. B. 
Published: June 2019

Since fibrinogen has itself an antithrombin activity, defibrinogenation of the sample is a prerequisite for AT-III determination. Five different defibrinogenation procedures were tested: heat precipitation for either 3 or 10 minutes, ristocetin precipitation, clotting with either Reptilase-R or Botropase-R. AT-III was measured as biological activity according to Howie et al. (Br. J. Haemat. 25, 101, 1973) and assayed immunologically by radial immunodiffusion. Defibrinogenation was complete with all the procedures used (< 16 μg/ml F. R.-antigen being left). In the samples defibrinogenated by ristocetin, the biological assay could not be performed, since some ristocetin remained in the supernatant and provoked a rapid precipitation of the substrate fibrinogen used for the assay. The possibility that Botropase-R or Reptilase-R had themselves some antithrombin activity was preliminarly ruled out. In samples definbriogenated by heating (3 min), Reptilase-R or Botropase-R the same biological AT-III activity was found; in addition, no differences in immunological reactivity of the protein were observed as compared with the corresponding-plasma before defibrinogenation. In contrast, a statistically significant (P < 0.001) reduction of both biological and immunological AT-III activity was found in the samples defibrinogenated by heating (10 min), as compared with the other 3 procedures. These results indicate that Reptilase-R and Boropase-R are suitable reagents for defibrinogenation of plasma prior to AT-III assay; heat precipitation can also be used, provided the duration of the incubation period is accurately controlled.(Supported by Grant N. 73.00400.04 of the Italian Research Council (C. N. R.).)
Modification of the Hyperacute Reaction in the Rat by Sulphinpyrazone
Authors: Jamieson S. W. 
Published: June 2019

It has been found that guinea-pig hearts are rejected in hyperacute fashion by the rat. By using inbred strains this model has been found to be markedly reproducible. Electron microscopic studies show that the platelet plays a critical role in the rejection process. An important point is that endothelial cell damage morphologically occurs subsequent to platelet contraction.Flow studies demonstrate that flow through the coronary arteries ceases abruptly between 2 and 3 minutes; this co-inciding with platelet aggregation in the vessels. The heart continues to beat for 10–12 minutes, and then suffers an ischaemic death.30 transplants were performed as controls to fully monitor flow, E. C. G. and microscopic events during the reaction.Ten transplants were performed in rats pre-treated with 150 mgs/kg. Sulphinpyrazone orally daily for 6 days and then transplanted, and ten were performed in rats transplanted and then given 400 mgs/kg sulphinpyrazone I–V before release of the clamps preventing revasularisation of the heart.It was found that rejection time was not significantly changed from the controls (12–14 minutes), but flow studies showed that the coronary circulation remained patent for 5–6 minutes, i.e. twice the time of the control studies, with subsequent delay of E. C. G. changes.
A Radioimmunoassay for Human Platelet β-Thromboglobulin
Authors: Ludlam C. A. , Bolton A. E. 
Published: June 2019

β-thromboglobulin (βtg) is a protein recently isolated from human platelets. A radioimmunoassay for βtg has been established.Using this assay, conditions have been defined for the preparation of platelet poor plasma, so as to minimise the liberation of βtg during manipulations in vitro. Platelet poor plasma prepared from whole blood, collected in EDTA, prostaglandin E9, and theophylline, and centrifuged at 0°C., contained 0.019±0.0075 μg ml−1 (mean±l SD). Serum prepared from clotted whole blood (in which platelets had undergone the release reaction) had a concentration of 17.4±6.3 μg ml−1, while plasma from platelet transfusion concentrates contained 247.0±120.3 μg ml−1. There was no increase in βtg concentration when platelet poor plasma was clotted by the addition of calcium. The presence of a 1000-fold difference between plasma and serum concentrations, the observed release following collagen induced platelet aggregation in vitro, and the observations that other human tissues contained only trace amounts suggests that βtg is unique to platelets.Preliminary clinical studies have shown that patients with acute arterial thrombosis and others with prosthetic heart valves have raised plasma concentrations. It is possible, therefore, that this assay has potential uses for studying the platelet release reaction in vitro, and also the identification of individuals with excessive platelet sequestration in vivo.