bluuebunny/crossref_metadata_2025_split huggingface dataset:
STUDY OF A SPANISH FAMILY WITH INHERITED PROTEIN S DEFICIENCY
Authors: Fontcuberta J , de los Inocentes R M , Sala N , Borrell M , Félez J 
Published: June 2019

Protein S (PS) is a plasma glycoprotein that serves as a cofactor for activated protein C (PC) anticoagulant activity. Inherited PS deficiency has been found to be associated to thrombotic disease in several families. In the present study, we report on a Spanish family with type II PS deficiency.The propositus is a 40 year-old male that was referred to our center for study after having suffered from multiples thrombotic events since he was 20 year-old. After his first episode of deep vein thrombosis (DVT) he had 4 recurrences, three of them complicated with pulmonary embolism. It should be remarked that one of the episodes occured while the patient was under oral anticoagulant treatment. The basic screening of haemostasis and hepatic function were normal for a patient that was being treated with oral anticoagulants. Functional and antigenic levels of antithrombin III, protein C and plasminogen were also normal. When total and free protein S levels (method of Comp et al.) were measured using both an electroimmunoassay and an ELISA assay ,almost indetectable levels of free protein S (between 0 and 10%) and very low levels (20%) of total plasma PS, were found. These results were also confirmed by crossed-electriimnunophoretic studies.When the family of this patient was studied it was found that his two sons, aged 15 and 8 years, as well as one of his sisters, aged 35 years, and her daughter of 4 years, were also affected (free PS levels between 38-60% and total PS between 35 and 39%). All these members had been assymptomatic up to now and are not under oral anticoagulants.
CONCENTRATION DEPENDENCE OF ACTIVATION OF ACARBOXYPROTEIN C BY THE CONTORTRIX ACTIVATOR
Authors: Exner T 
Published: June 2019

The protein C activator in Southern Copperhead (Agkistrodon Contortrix Contortrix) venom was isolated by sequential chromatographies on SP�Sephadex, Con A Sepharose and hydroxylapatite. It was found to be a single chain glycoprotein with an apparent molecular weight of 36,000 and an enzymatic specificity on chromogenic substrates resembling kallikein.This "contortrix activator" was used in a solid-phase immunochromometric assay (ICMA) for functional protein C in which heterologous antibody against protein C was passively coated onto microtitre wells and used to immoblize protein C. This was then activated, easily freed of excess activator by washing and assessed by its subsequent overnight cleavage of chromogenic substrates sensitive to activated protein C.Correlation between protein C results obtained by ICMA and immunoradiometric assay (IRMA) on a variety of patient samples was excellent when relatively high concentrations of the venom activator was used. However with lower concentration of activator plasmas from patients deficient in vitamin K gave lower protein C values by ICMA then obtained by IRMA.Normal protein C and "acarboxy" protein C from a patient on oral anticoagulant therapy were immuno-immobilized and studied by the ICMA technique using varying concentrations of the venom activator. The acarboxy-protein C, although completely activatable by high concentrationa of activator, was found to activate much more slowly than normal protein C at low concentrations of the contortrix activator. Thus by reducing the intensity of the activation step, the ICMA protein C results were increased in their sensitivity for functional protein C.
Platelet Aggregation Induced by a Synthetase-Like Substance and Phospholipase-A.
Authors: Iatridis S. G. , Iatridis P. G. , Markidou S. G. , Ragatz B. H. 
Published: June 2019

Platelets contain arachidonic acid-bearing phospholipids and phospholipase-A (Phl-A); it has been suggested that exposure of these substances to each other by stimuli, such as thrombin or adenosine diphosphate (ADP), would result in liberation of arachidonic acid (AA), which is the precursor of cyclic endoperoxide; a factor causing irreversible aggregation of platelets.By using a saline eluate of a polyurethane (SPU, -polyester elastomer of the thermoplastic type-, secured by exposing saline for two minutes to the inner surface of a polyurethane bag) we observed that platelet (human PRP) aggregation (second phase type, irreversible) could be induced by Phl-A plus SPU or AA plus SPU. These mixtures failed to aggregate aspirinized platelets. Aspirin, however, incubated for 10 minutes with SPU, Phl-A or AA did not inhibit platelet aggregation induced by the addition of the missing factor. In control experiments no aggregation was produced by SPU-saline, saline-Phl-A or saline-AA. SPU plus suboptimal concentrations of ADP or epinephrine induced an immediate in onset aggregation. Phl-A added in reversibly, by ADP, aggregated platelets produced a second phase of aggregation.The results show that AA which is the precursor of cyclic endoperoxide could be liberated by Phl-A. The results also provide evidence that at least two enzymes (synthetase-α and synthetase-β; α is inactive whereas β is active and can be blocked by apsirin) are involved in the process of AA activation and biosynthesis of cyclic endoperoxide.Supported by a grant from the U.S. Public Servie HL-15425.
Electroimmunoassay of Human Coagulation Factor IX in the Detection of Variants of Haemophilia B.
Authors: Orstavik K. , Osterud B. 
Published: June 2019

Factor IX was quantified by an electroimmunoassay (EIA, rocket Immunoelectrophoresis), using a rabbit antiserum against human factor IX. The EIA was performed on plasma samples from 38 healthy persons. The range was 65–150% relative to a standard plasma pool, and a positive correlation was found between determinations of factor IX antigen and factor IX activity.Seven patients with severe and six patients with moderate haemophilia B were tested for plasma cross-reacting material (CRM) by the EIA and by an antibody-neutralization test. Five of the seven patients with severe haemophilia had no detectable CRM by any of the two techniques whereas the remaining eight patients had CRM varying from low to normal values. The coefficient of correlation was 0.82 between the determinations of CRM by the two techniques.One of the patients with severe haemophilia and normal amounts of plasma CRM showed a prolonged prothrombin time using ox brain thromboplastin (haemophilia BM). As a group, the other patients had a significantly reduced prothrombin time when compared to 20 healthy males.Our results confirm that haemophilia B is a heterogeneous disorder and show that the EIA may be used to detect genetic variants of this disease.
Cyclical Variation in Factors VII and VIII Associated with Oral Contraception
Authors: Castaldi P. A. , McGrath K. M. 
Published: June 2019

Sequential studies of the levels of coagulation factors II, VII, VIII (activity and antigen), IX, X and fibrinogen, were carried out in three females using oral contraceptive agents, and two normal controls. A striking increase in the levels of factor VII activity was seen in the second half of the menstrual cycle in all test subjects. In two test subjects, a marked cyclic increase in factor VIII activity occurred and this did not have any fixed relationship to VIII antigen levels.The increase in factor VII activity was associated with shortening of the thrombotest in plasma tested after storage at –20 C. Activation of factor VII can be induced in vitro in 60% of oral contraceptive plasmas by incubation at 4 C for 16 hours. This cold promoted activity (CPA) also varies throughout a menstrual cycle, is independent of the prothrombin complex, being present in Al2OH3 adsorbed plasma, and is contained in the supernatant of the euglobulin fraction in CPA positive plasmas. It can induce activation of factor VII in normal plasma, but not in contact factor deficient plasma. The nature of this cold sensitive activity and its relationship to the cyclical increase seen in factor VII activity and to oestrogen induced clotting in vivo, remains to be determined.
Factor XIII Concentrate in the Long Term Management of Congenital Factor XIII Deficiency
Authors: Miloszewski K. , Losowsky M. S. 
Published: June 2019

Congenital Factor XIII deficiency causes a serious and disabling bleeding diathesis with a high risk of fatal intracranial haemorrhage. Blood levels of Factor XIII of a few percent of normal are sufficient to control bleeding and the in vivo half-life of Factor XIII is long, making permanent prophylaxis practicable.We have kept 5 patients with congenital Factor XIII deficiency free from bleeding manifestations for 3 to 10 years by regular plasma infusions. Their lives have been transformed. Plasma as a long term source of Factor XIII has disadvantages and a purified Factor XIII has been derived from human placenta (Hoechst), but its in vivo half-life was said to be only 70 hours. The only detailed report of the use of this preparation is of two injections in a single patient. We have used this preparation regularly for two years in two patients and we find that its half-life is similar to that of plasma Factor XIII i.e. 12–14 days. Both patients have remained free from bleeding manifestations or side effects.We conclude that long term prophylaxis for congenital Factor XIII deficiency is possible and the placental Factor XIII is preferable to plasma.
The Fibrinogen-Thrombin Reaction
Authors: Hogg D. H. , Blombäck B. 
Published: June 2019

The kinetics of thrombin-catalyzed release of fibrinopeptides A and B is reported. The results suggest that the N-terminal disulphide knot (N-DSK) contains the structural elements of fibrinogen which are recognized by thrombin during release of the A-peptide. In contrast release of the B-peptide requires a structure larger than N-DSK. Further, it appears that most of the structural elements of N-DSK defining the specificity of action reside in an N-terminal portion of the Aγ chain.The mechanism of the fibrinogen-thrombin reaction is suggested as involving firstly release of the A-peptide with a consequent change in conformation in the substrate, possibly induced by polymerization, which then facilitates release of the B-peptide.
Kinetics of Homologous Urea-soluble 131I-Fibrin and 125I-Fibrinogen in Rabbits
Authors: Müller-Berghaus G. , Mahn I. , Kövecker G. 
Published: June 2019

In order to study the in vivo behaviour of soluble fibrin, purified rabbit 13I-fibrinogen was clotted in the presence of EDTA (0.005 M) and aprotinin (100 units/ml), the generated clot dissolved in buffered urea (3.0 M, pH 7.4), and the formed ureasoluble 131I-fibrin injected into rabbits. The behaviour of homologous 125I-fibrinogen was simultaneously studied in the same animals. Results: The distribution volume of 131I-fibrin (44 ml/kg) as well as that of 125I-fibrinogen (45 ml/kf) was nearly identical indicating that the injected soluble fibrin was homogenously distributed in the circulation immediately after injection. The elimination of soluble fibrin from the circulating blood did not represent a monophasic exponential decay. 84% (range: 77–94%) of the injected soluble fibrin disappeared from the circulation during the first 24 hours after injection, whereas only 54% (range: 41–72%) of the injected fibrinogen disappeared during that interval. Under these experimental conditions, the T/2 of fibrinogen was 46 hours. The clearance of urea-soluble fibrin did not influence the kinetics of 13I-fibrinogen. The disappearance of soluble fibrin could not be influenced by treating the animals with aprotinin for fibrinolysis inhibition. The experiments demonstrate that soluble fibrin can be traced in the circulation and cleared from the blood by a mechanism independent of the fibrinolytic system.(Supported by the Deutsche Forschungsgemeinschaft, Bad Godesberg, Germany.)
Immunological Cross Reaction Between Chains of Human Fibrinogen
Authors: Oårdlund B. 
Published: June 2019

Employing the crossed immunoelectrophoresis technique (CIE) the antigenic composition of fibrinogen chains and heterogeneity in their electrophoretic mobility was investigated.Highly purified chains of fibrinogen were prepared by chromatography on CM-cellulose (1). Antisera against chains were prepared by immunizing rabbits with Aα, Bβ and γ chains respectively. The CIE was performed on 10 × 10 glass plates with an 1 mm thick layer of 1% agarose in 0.04 M barbital buffer pH 8.6. The electrophoresis was run for 1 h with 12 V/cm. Four fifth of the gel was cut off and replaced with the same agarose solution containing antibodies. The second dimension electrophoresis was run for about 20 h with 2 V/cm.Using anti Bβ chain serum a partial immunological identity was revealed between the Bβ chain and the γ chain. The Bβ chain has except for the antigenic sites in common with the γ chain additional sites that are unique for the B β chain. The results were confirmed with the anti γ chain serum which gave a strong reaction with both the γ chain and the B β chain preparations. The Aα chain did not react with γ antiserum, nor did the γ chain react with anti Aα chain serum. The immunological relation between the Aα chain and the B β chain is under investigation.These experiments also concluded that the γ chain preparation is contaminated with a B β chain variant that has an electrophoretic mobility similar to that of the γ chain. Also the Bβ chain seemed to be impure due to contamination by an Aα chain derivative with higher electrophoretic mobility.(1) Murano, G., Wiman, B., Blomböck, B. and Blomböck, M. : Preparation and isolation of the S-carboxymethyl derivative chains of human fibrinogen. F.E.B.S. Letters: 14, 37, 1971.
Effect of Beta Blockers on Human Blood Plaletets in Vivo
Authors: Zawilska K. , Komarnicki M. , Manka B. 
Published: June 2019

ADP and collagen-induced platelet aggregations are diminished one hour after propanolol administration to normal subjects while adrenalin-induced aggregation and platelet factor 3 availability are not influenced. This effect of propanolol in vivo is very different from its in vitro action and is possibly related to the interaction adrenalin-ADP and collagen-ADP. Intermediary products of propanolol metabolism may also be involved in this effect.The administration of practololol to a second group of normal subjects had no effect on platelet aggregation and on platelet factor 3 availability.
In Vivo Activity of Tieclopidine, a New Drug with Platelet Aggregation Inhibiting, Antisludge and Antithrombotic Properties
Authors: Ferrand J. C. , Aubert D. , Lacaze B. , Pepin O. , Thebault J. J. 
Published: June 2019

Tieclopidine (53–32 C) belongs to a new series of synthetic compounds which have proved to inhibit significantly blood platelet aggregation in animals. Administered orally to rats, it reduces markedly the plate let aggregation induced by ADP and collagen. The activity appears 2 to 6 hours after a single dose and persists for 24 hours.The sludge and blood stasis induced in rats by protamin sulfate injections disappear completely in five minutes after an intravenous administration of Thieclopidine. Animals pretreated orally with this compound failed to show any sludge formation.The antithrombotic activity of Tieclopidine was demonstrated in rats carrying a dental broach implanted in the abdominal aorta. White thrombideveloped locally in the control animals, but were absent or much less severe in pretreated animals.In man the first clinical approach has shown that at a daily dose of 1 g the inhibitory effect of Tieclopidine on ADP induced aggregation requires 24 to 48 hrs to become significant and reaches a plateau after 5 or 6 days of treatment.
Fitzgerald Factor and Surface-Mediated Reactions
Authors: Saito H. , Ratnoff O. D. , Waldmann R. , Abraham J. P. 
Published: June 2019

The kaolin-activated partial thromboplastin time (PTT) was abnormally long in an asymptomatic 71 year old man whose plasma contained normal amounts of recognized clotting factors except Fletcher factor, the titer of which was 10–15% of normal. Prolonged incubation with kaolin before recalcification did not shorten the PTT. The defect resided after activation of Hageman factor (F XII) and Fletcher factor and before participation of activated PTA (F XI). Other surface-mediated reactions – generation of kinins, evolution of PF/Dil, augmentation of Factor VII activity and generation of fibrinolytic activity in acidified, diluted plasma exposed to kaolin – were all impaired, the last despite the presence of adequate amounts of urokinase-activable plasminogen and HF-cofactor. A corrective fraction of normal plasma was partially purified by chromatography on QAE-Sephadex, SP-Sephadex and Sephadex G-150; a similar fraction of the patient’s plasma was inert. The correction fraction had a sedimentation constant of 5.0 and an apparent MW by gel filtration of 160,000. The corrective agent – named Fitzgerald factor after the patient’s surname – shortened the patient’s PTT and, in small amounts, induced partial correction of impaired kaolin-induced fibrinolysis. The site of origin of Fitzgerald factor is not known, but its titer was diminished in hepatic cirrhosis, but not in coumadin-treated cases, renal failure or rheumatoid arthritis. Low titers were observed in patients undergoing disseminated intravascular coagulation. The hereditary nature of Fitzgerald trait is not yet established.Activation of PTA and augmentation of Factor VII activity require the presence of activated HF and Fletcher factor, but additional factor or factors are needed. The studies described suggest that one additional factor needed for surface-mediated reactions is Fitzgerald factor.
The Treatment of Asphyxiated Newborn with Dic by an Alpha Blocking Agent
Authors: Yamada K. , Shirahata A. , Meguro T. 
Published: June 2019

The alpha blocking agent was used in the cases of newborn infants with respiratory distress syndrome (RDS) in which DIC developed. The cases of RDS included idiopathic respiratory distress syndrome, massive aspiration syndrome, atelectasis, etc. To those infants, 1 mg per kg of phenoxybenzamine (POB) was infused every 24 hours. In some of the cases, the exchange transfusion was combined with the administration of POB. After the infusion of POB, almost all of abnormal findings in coagulation studies improved remarkably as did the clinical conditions of DIC, except for the cases of sever stage.In order to analyse our clinical results, a set of animal experiment was carried out. In this study, the rabbits which were rendered asphyxic were infused with POB and the pharmacological effects of this agent on asphyxia were examined from the aspects of coagulation and platelet functions.
ICSH-ISTH International Anticoagulant Control Study. I. Background and Co-ordination
Authors: Schmidt R. M. 
Published: June 2019

Numerous thromboplastins and control plasmas are now available for prothrombin time tests in the control of oral anticoagulants. Quality Control schemes are running in various countries, and a number of attempts are being made to standardize reagents. In addition, the National Institute for Biological Standards and Control (NIBS & C), London, holds for distribution five lyophylized thromboplastins which could serve as a primary and four secondary reference materials. Broadly-based data on the relative performance of the more widely-used reagents are therefore urgently needed, and the International Committee for Standards in Haematology, co-sponsored by the International Society on Thrombosis and Haemostasis, has established an Expert Panel on Oral Anticoagulant Control. An international collaborative study was conducted in the autumn of 1974 involving some 180 laboratories in 24 countries; 10 widely used thromboplastins, the NIBS & C materials and three series of lyophylized control plasmas representing different degrees of anticoagulant effect were tested in parallel with local working thromboplastins and fresh plasma samples from patients on anticoagulant treatment.The background, purpose and conduct of the trial will be described.
Progress in Proficiency Testing of the One-Stage Prothrombin time in the Federal Republic of Germany
Authors: Beeser H. , Fischer J. , Merten R 
Published: June 2019

With regard to the small range of the therapeutic prothrombin complex levels the treatment with oral anticoagulants needs reliable laboratory controls. The results of the one-stage prothrombin time generally used as control method are however known to be poorly comparable between different laboratories. This difficulty arises particularly from the use of numerous types of thromboplastins, insufficient reference materials and calibration curves.In the Federal Republic of Germany we three times a year conduct quality control trials of the one-stage prothrombin time according to the Bundesärztekammer (BAK) directions on external quality control of clinical laboratory methods. Participating laboratories are asked to determine prothrombin times of normal and abnormal freeze dried plasma samples using their own thromboplastin reagents and methods. For reasons remarked above a uniform evaluation of the results of all laboratories is impossible.We can state: 1. Wide variation of the seconds for prothrombin times, even if identical thromboplastins are used. But the increasing use of mechanical devices brings along an obvious improvement. 2. The variability of the percentage results tends to decrease probably due to better calibration of the methods. 3. Prothrombin time ratios show a good comparability for each type of thromboplastin. Grouping of qualitively similiar thromboplastins has proved to be practicable. 4. There is found an increasing conformity of all mentioned parameters between expert labs and other labs.
Factor XIII, Fibrin and Collagen
Authors: Nyman D. , Duckert F. 
Published: June 2019

The significance of factor XIII (fibrin stabilizing factor) in hemostasis and wound healing is well known. The significance of fibrincrosslinking has, however, not been unequivocally demonstrated. As an additional hypothesis we postulated that factor XIII could bind fibrin to collagen by transamidination. To test this hypothesis:1) Normal plasma or F XIII deficient plasma, collagen or buffer, Ca++ and thrombin were incubated at 37°. The clots were washed and dissolved in SDS, urea and 2-mercap-thanol. Electrophoresis on 7% SDS-polyacrylamide showed disappearance of the γ-dimer in the clot of normal plasma in presence of collagen. N-acetylation of the collagen abolished the disappearance of the γ-dimer.2) To normal plasma, F XIII free plasma or normal plasma with EDTA, 125I-fibrinogen was added. The plasma-collagen mixtures were incubated with thrombin and Ca++, without Ca++ for the normal EDTA-plasma. The clots were solubilized as described. After extensive washing the radioactivity retained on the collagen was measured. The collagen from F XIII free clots had 23-47% and that from normal EDTA-plasma 23-46% of the radioactivity of the collagen from normal recalcified plasma clots.These results are interpreted as demonstration of binding of fibrin to collagen by F XIII catalyzed transamidination. The importance of this binding for normal hemostasis and wound healing is emphasized.