bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation Of The Dudley Clotting Test In Human Volunteers
Authors: O’Connell J , Rumaks A , Williams J L , Griggs T R 
Published: July 2018

We have evaluated four materials (polyurethane, silicone rubber, Teflon, and heparin-coated polyurethane) for compatibility with blood in six human volunteers. The test method employs a standard indwelling intravenous catheter (16 ga, 2 1/2") through which 100 cm lengths of small-bore (0.5 mm inner diameter) tubes made from the materials to be tested are passed. The tubes are filled with saline before they are inserted, and the distal end of the tube is immersed in sterile mineral oil. The rate and duration of flow through these tubes is determined by counting drops of blood as they emerge into the mineral oil. The four materials were tested in each of six volunteers, in random order during a single day.The testing produced no complications in the subjects. The average blood loss after 5 hours of testing was 25 ml.A safe and simple method for testing artificial materials for reactivity with native human blood is described. The major characteristics of the test are that the blood is in contact only with the test material and that multiple samples can be tested in a single subject on a single day.
Isolation, Pasteurization, And Lyophilization Of Human Plasma Fibronectin
Authors: Miekka Shirley I , Busby Thomas F , Ingham Kenneth C , Menache Doris 
Published: July 2018

The goal of this research is to develop a suitable method for purification of plasma fibronectin for potential replacement therapy in patients with acquired deficiencies. Using a modification of published affinity procedures, a simplified one-step method has been achieved. Plasma or cryoprecipitate is chromatographed on gelatin-agarose and the unadsorbed and loosely adsorbed proteins are removed by washing with pH 7.5 buffer (0.05 M Tris HC1, 0.05 M ∈-amino caproic acid, 0.02 M sodium citrate) followed by 1 M NaCl. The bound fibronectin is eluted simply by decreasing the buffer pH to 5.5 (0.02 M sodium citrate). The eluate can then be neutralized and further processed as desired. Sedimentation velocity measurements suggest that the elution may be related to a conformational change in the fibronectin molecule below pH 7.Studies of thermal stability have been initiated with the objective of defining conditions under which the protein can withstand pasteurization (10 h, 60°C) to minimize the risk of hepatitis. Using an increase in the fluorescence of added 1,8-anilinonaphthalene sulfonate to monitor thermal denaturation, a variety of potential stabilizers was tested. No protection was afforded by gelatin, heparin, citrate, phosphate, EDTA, CaCl2, glycine, glycerol, or PEG; however, neutral sugars increased the midpoint of the denaturation curve to well above 60°C. Lyophilization was found to have no detectable deleterious effect on fibronectin. Freeze-dried samples were readily soluble in water, showed no change in sedimentation behavior, and retained the ability to augment the uptake of gelatin-coated particles by rat liver slices.
Problems Raised By The Measurement Of Coagulation Factors On Chromogen Substrates By Automatic Methods
Authors: Droulle C , Lafaurie M , Remy M G , Florent B , Potron G 
Published: July 2018

The use of chromogen substrates has permitted a new approach of the factors responsible for the regulation and equilibrium of hemostasis.Automation has allowed to have access to the problems raised by enzymatic reactions in non-purified medium. The specificity and sensibility of substrates, the specificity of activators, the role of inhibitors and physiologic substrates in different technical conditions (pH, ionic forces, temperature, dilution) modifying the maximal velocity, have been studied for a standardizing approach of enzymatic kinetics in hemostasis. Measurements of antithrombin III and fast α2 antiplasmin, factor X, prekallikrein and plasminogen and heparinemies have been analyzed by an automatic apparatus (Kern O Mat 2-Coultronics) with different chromogen substrates (Kabi-Stago).Optimum technical conditions, units in which results are expressed, interpretation of normal and pathological values are systematically studied.
Isotopic And Immunological Half-Life Determination Of Antithrombin III In Various Types Of Antithrombin III Deficiency
Authors: Sas G , Kremmer T , Spät B , Pető I 
Published: July 2018

Using the modified crossed immunoelectrophoresis technique (Heparin in agarose), different patterns were obtained characterizing the various types of antithrombin III (AT-III) deficiency. 125J labelled and purified commercial (KABI, Stockholm) AT-III preparates were administered to patients of different types in order to determine the biological half-life of AT-III. Various methods, including crossed immunoelectrophoresis and disc electrophoresis as well as heparin-Sepharose 4B chromatography were applied for the characterization of the AT-III administered.These techniques revealed the molecular heterogeneity of AT-III preparates, especially those labelled by 125J. In the light of these observations it became obvious that among the AT-III determinations the most reliable and most specific method is the quantitative measurement of the fast migrating AT-III component (I-AT-III1) obtained by the modified method of crossed immunoelectrophoresis. This component corresponds to the “natural” AT-III of fresh normal plasma.Applying this technique, one of our propositi (B.I.) displayed a significant shortening of the biological half-life of AT-III (26 hrs) while the two others (M.L. and B.J.) had approximately normal time courses (55 and 52 hrs, respectively). The different biological half-life times of AT-III in these patients also support the assumption of the heterogeneity of the congenital AT-III deficiency.
Antithrombin III (At III) In Acute Liver Failure (ALF): Experimental Data After Intoxications Of Dogs
Authors: Heirnburger N , Ronneberger H , Hein B 
Published: July 2018

Vogel, G., Bottermann, P. et al. [Verh. Dtsch. Ges. inn. Med. 85, 477 (1979)] observed a benefit therapeutical effect of AT III in patients with ALF. With respect to the fact that AT III has been used as one drug in a combination therapy the effect of AT III itself had still to be proven.ALF was induced in Beagle-dogs by intoxications with carbon tetrachloride (CCl4, 0.4 ml/kg, given orally over 2 days) and Galactosamine (Gain, 200 mg/kg, i. v.). First toxic symptoms were observed after 24 h: Elevated transaminases (GOT, GPT), alkaline phosphatase, serum bilirubin; the dogs developed severe coagulation disorders triggered by a DIC characterized by a fall of platelet counts and clotting factors AT III included. After Gain 5 of 6 untreated dogs died between 48 and 72 h. AT III concentrate prepared from human plasma (Behringwerke) and given i. v. in 3 different concentrations over a period of 3 days following intoxication reduced the toxicity: Associated with an inhibition of the consumption reaction there was a reduction of the death rate. The minimal effective dose was determined to be 3 × 50 U AT III/kg.From the experimental data it can be concluded that AT III has a benefit effect on ALF. The results are in good agreement with the clinical observations by Vogel, Bottermann et al.
The Effect of Partial Splenectomy on Platelet Production in Mice
Authors: Bessler H , Notti I , Djaldetti M 
Published: July 2018

SummaryThe effect of total and partial splenectomy on the number and production of circulating platelets was studied in mice. Five days after total and partial splenectomy the number of the peripheral blood platelets increased by 87% and 60%, respectively and the incorporation of 75selenium methionine (75Se-Met) into platelets was enhanced indicating that the thrombocytosis was due to increased platelet production. The results obtained by the two operative procedures were compared.Since previous work from our laboratory has shown that a factor produced by splenic lymphocytes affects the platelet number in mice, it is suggested that the differences in the number of circulating platelets observed in animals after total and partial splenectomy may reflect a difference in the number of spleen lymphocytes removed.
Effect of Long-Term Aspirin Treatment on Platelet Adhesion to Chronically Damaged Canine Pulmonary Arteries
Authors: Schaub Robert G , Rawlings Clarence A , Keith James C 
Published: July 2018

SummaryThe effect of aspirin on platelet adhesion to chronically damaged pulmonary arteries was studied in 18 dogs. Chronic injury was produced in all dogs by infection with the canine heartwonn Dirofilaria immitis(DI). Ten dogs were subjected to 4 days of chronic injury. Eight dogs were subjected to 30 days of chronic injury. Five of the 4 day injury and 4 of the 30 day injury dogs received aspirin daily (325 mg/day orally). Aspirin was started 3 days prior to infection with DI. Pulmonary arteries were perfusion fixed in situ at physiologic pressure. The damaged pulmonary arteries were located by Evan’s blue staining (2ml/kg of 1% dye glven one hr prior to perfusion) and prepared for scanning electron microscopy. Both groups of dogs with 4 day DI infection had monolayers of platelets adhered to exposed subendothelium. Aspirin treated dogs had enhanced platelet adhesion to damaged arteries. Aspirin treatment for 33 days reduced platelet adhesion. The damaged arteries of treated dogs infected with DI for 30 days had very few platelets adhering to the damaged surface. However, non-treated dogs subjected to 30 days of infection had platelet adhesion equivalent to the 4 day non-treated infection group. These results suggest that although aspirin is ineffective in preventing platelet adhesion in short term therapy it is effective when given for longer time periods. This inhibitory effect may occur due to platelet membrane changes rather than because of aspirin inhibition of cyclooxygenase.
Factors Affecting the Size of Platelet Aggregates in Blood
Authors: Kennedy P S , Ware J , Horak J K , Solis R 
Published: July 2018

SummaryFactors affecting the size distribution of platelet aggregates formed in whole blood were measured using an electronic particle counter. Lysis of red cells after dilution of blood for analysis allows detection of smaller aggregates without altering aggregate measurement. Differences in platelet response to increasing concentrations of ADP are detected by an increase in the mean size of platelet aggregates while the total volume of aggregates varies linearly with the volume of available platelets (r = .99). The mean aggregate size varies directly with the total volume of aggregates formed (r = .99). Mean aggregate size is inversely related to the packed red cell volume. As the reactivity of platelets is reduced by incubation with aggregation inhibitors at increasing concentrations, the mean size of aggregates becomes smaller, followed by a decrease in the total volume of aggregates. The total volume and mean size of aggregates formed after incubation with collagen and epinephrine, but not ADP, increases with time after venepuncture.
Prevention by a Glucocorticoid of the Thrombotic and Hemorrhagic Tendencies Consecutive to Shock and Surgical Intervention in Rat
Authors: Renaud S , Latouk J. G 
Published: July 2018

SummaryRats pretreated with acenocoumarin present a high incidence of hemorrhages from one to three days after an endotoxemic shock or a surgical intervention. The onset of hemorrhages is concomitant with a marked decrease in the platelet count and a considerable increase in the prothrombin time and the plasma clotting time. These hemorrhages as well as the changes in the parameters examined could be completely prevented by administration of triamcinolone at high doses (4 mg/kg), 2 hrs before and 2 hrs after the shock or the intervention.Three days after the induction of a traumatic shock in hyperlipemic rats the count and adhesiveness of blood platelets was markedly increased. At this time, the intravenous injection of an endotoxin (S. typhosa lipopolysaccharide) induced a much higher incidence of large phlebothromboses in these traumatized rats than in the control animals. Here again, administration of high doses of triamcinolone could completely block the consequences of the traumatic shock, namely the changes in the platelet count and adhesiveness and the increased thrombotic tendency.
Thrombolytic Treatment with Tissue-type Plasminogen Activator (t-PA) Containing Liposomes in Rabbits: a Comparison with Free t-PA
Authors: Heeremans J L M , Prevost R , Bekkers M E A , Los P , Emeis J J , Kluft C , Crommelin D J A 
Published: July 2018

SummaryIn this study, we aimed at improving the therapeutic index of tissue- type Plasminogen Activator (t-PA) as thrombolytic agent in the treatment of myocardial infarction. Liposome-encapsulated t-PA was tested in a rabbit jugular vein thrombosis model: administration of free t-PA (t-PA) as a bolus injection in the ear vein was compared to a similar administration of liposomal t-PA (t-PA-lip), liposomal t-PA in plasminogen-coated liposomes (Plg-t-PA-lip), a mixture of free t-PA and empty liposomes (t-PA+empty lip) and a saline-blank (blank) in terms of thrombolytic activity and side effects.Liposomal t-PA (t-PA-lip/Plg-t-PA-lip) showed a significantly better thrombolysis efficiency than equimolar doses of free t-PA (t-PA/ t-PA+ empty lip): about 0.24 mg/kg of liposomal t-PA practically equalled the lysis-activity of a dose of free t-PA of 1.0 mg/kg (t-PAlmg/kg). On the other hand, liposome encapsulation did not affect the systemic activation of alpha2-antiplasmin and plasminogen by t-PA.We conclude that for this model an improvement in thrombolytic efficacy of t-PA is achieved by liposome encapsulation of t-PA. As t-PA-lip and Plg-t-PA-lip -treatment induced similar results, targeting of liposomal t-PA by coupled glu-Plg remains a topic to be optimized in future studies.
Calcium Ion-Dependent Monoclonal Antibody Against Human Fibrinogen: Preparation, Characterization, and Application to Fibrinogen Purification
Authors: Takebe Mikihiro , Soe Gilbu , Kohno Isao , Sugo Teruko , Matsuda Michio 
Published: July 2018

SummaryWe have produced a high-affinity monoclonal antibody classified as IgG1 with K-type light chains that recognizes the calcium ion(Ca2+)- dependent conformation of the D-domain of human fibrinogen. Binding of fibrinogen in solution to the insolubilized antibody increased in the presence of increasing concentrations of up to 2 mM Ca2+, the half-maximal binding being reached at 130 μM Ca2+. The dissociation constant was estimated to be 1.6 × 10-8 M at 2 mM Ca2+. The antibody was found also to be dependent on other divalent metal ions including Zn2+, Mn2+, Co2+ and Cu2+, but not Ba2+, Mg2+ or Sr2+. The synthetic Gly-Pro-Arg-Pro-amide peptide, which has recently been shown to bind to close proximity to the calcium binding site in the D-domain, was unable to elicit the conformation for the antigen to be recognized by this antibody. This antibody was found to be a suitable ligand for the immunoaffinity chromatography of normal and abnormal fibrinogens directly from citrated plasma depleted of the vitamin K-dependent proteins or heparinized plasma by eliminating the precipitation procedure widely adopted in conventional techniques of fibrinogen purification. Indeed, fibrinogen Marburg I with the Aa chains depleted of the carboxy-terminal Aα(461-610) residue segment has been purified by this technique, although this dysfibrinogen was difficult to purify by conventional precipitation techniques.
Über einen Fall kongenitaler Hypoprokonvertinämie (Faktor VII – Mangel)
Authors: Rák K , Waltner K 
Published: July 2018

ZusammenfassungAls Ursache für die Bluterkrankheit eines 16jährigen Mädchens konnte kongenitale Hypoprokonvertinämie festgestellt werden. Die ähnlich schwere Blutungsneigung ihrer Schwester läßt familiäres Vorkommen vermuten. Es werden neben dem ausführlichen Hämostatus der Kranken auf mildere Gerinnungsstörungen der Eltern hinweisende Angaben mitgeteilt. Im Laufe der kurzen Besprechung des Falles wird hingewiesen:1. auf diagnostische Fragen,2. auf die Rolle des fehlenden Serumfaktors im Geritmungssystem,3. auf die Notwendigkeit der Differenzierung von dem sog. Stuart-Faktor,4. auf die wenigen von der Literatur akzeptierten echten Hypoprokonvertin-ämiefälle,5. auf die Rolle des Prokonvertins in der Hämostase,6. auf die Frage einer Möglichkeit zur Hebung des Faktor-VII-Spiegels bei der Behandlung der Krankheit mit Bluttransfusionen, sowie auf die Vitamin-K-Resistenz und endlich7. auf die Vererbungsverhältnisse des Leidens.
Abdomino-perineal Resection of the Rectum in a Haemophilic
Authors: Christie T. H , Graham-Stewart C. W , Ingram G. I. C 
Published: July 2018

SummaryA moderately affected haemophilic aged 69 years, with about 10% of the normal plasma level of AHG, underwent abdomino-perineal resection of the rectum for carcinoma, under cover of bovine and porcine AHG.The post-operative course was complicated by the necessity of plugging the perineal wound to arrest operative haemorrhage from a vessel in the prostatic capsule; and considerable bleeding occurred on two occasions when the packs were removed. Otherwise, there was no abnormal bleeding.The management of the case is described, and technical details are discussed from the points of view of the surgeon, the anaesthetist and the haematologist.The Biggs’ AHG assay procedure was slightly modified to save time and stock haemophilic plasma. The importance of frequent assays is stressed.The anaesthetist remained responsible for the intravenous drips throughout the post-operative course.
Recombinant Polypeptides Derived from the Fibrin Binding Domain of Fibronectin Are Potential Agents for the Imaging of Blood Clots
Authors: Ezov N , Nimrod A , Parizada B , Werber M M , Goldlust A , Greenstein L A , Vogel T , Drizlich N , Levanon A , Reich S , Gorecki M , Panet A 
Published: July 2018

SummaryThrombus formation in the circulation is accompanied by covalent linkage of fibronectin (FN) through transglutamination of glutamine no. 3 in the fibrin binding amino terminal domain (FBD) of FN. We have exploited this phenomenon for thrombus detection by the employment of radioactively-labelled recombinant polypeptide molecules derived from the 5-finger FBD of human FN. Three recombinant FBD polypeptides, 12 kDa (“2 fingers”), 18.5 kDa (“3 fingers”) and 31 kDa FBD (“5 fingers”), were prepared and compared to native FN-derived 31 kDa-FBD with respect to their ability to attach to fibrin clots in vitro and in vivo. The accessibility of Gln-3 in these molecules was demonstrated by the incorporation of stoichiometric amounts of 14C- putrescine in the presence of plasma transglutaminase. Competitive binding experiments to fibrin have indicated that, although the binding affinities of the FBD molecules are lower than that of FN, substantial covalent linkage was obtained in the presence of transglutaminase, and even in the presence of excess FN or heparin. The biological clearance rates of radioactively labelled FBD molecules in rats and rabbits were much higher than those of FN and fibrinogen, thus indicating their potential advantage for use as a diagnostic imaging tool. Of the three molecules, the 12 kDa FBD exhibited the highest rate of clearance. The potential of the 12 kDa and 31 kDa FBDs as imaging agents was examined in a stainless steel coil-induced thrombus model in rats and in a jugular vein thrombus model in rabbits, using either [125I] or [111ln]-labelled materials. At 24 h, clot-to-blood ratios ranged between 10 and 22 for [125I]-12 kDa FBD and 40 and 60 for [luIn]-12 kDa FBD. In the rat model, heparin did not inhibit the uptake of FBD. Taken together, the results indicate that recombinant 12 kDa FBD is a good candidate for the diagnosis of venous thrombosis.
Location on the Human Genetic Linkage Map of 26 Genes Involved in Blood Coagulation
Authors: Koeleman Bobby P C , Reitsma Pieter H , Bakker Egbert , Bertina Rogier M 
Published: July 2018

SummarySeveral human genetic linkage maps have been constructed as part of the Human Genome Project. These maps show the positional order of closely linked, highly informative AC-repeat polymorphisms on each human chromosome, and are extremely useful in genetic linkage analysis of inheritable diseases. For a candidate gene approach the current linkage maps are less useful, since they consist mainly of anonymous markers rather than of specific genes. This situation also applies for inheritable disorders of blood coagulation. Numerous genes are involved in the blood coagulation cascade and its regulation, and can be considered as candidate genes for unexplained haemophilia and thrombophilia. We have selected 29 candidate genes that seem to be the ones most likely to be involved in thrombophilia. For 19 genes genotype data were already present in the CEPH database (version 7.0). We typed 7 additional genes in the CEPH reference families, i.e. the factor V, factor XII, protein C, protein S, prothrombin, thrombomodulin, and heparin cofactor II gene. The genotype data were used to integrate these 26 genes in the current genetic linkage map, and to identify closely linked AC-repeat polymorphisms. This information will benefit the investigation of inheritable disorders of blood coagulation, especially thrombophilia.
Early Platelet-Collagen Interactions in Whole Blood and Their Modifications by Aspirin and Dipyridamole Evaluated by a New Method (Basic Wave)
Authors: Pérez-Requejo José Luís , Aznar Justo , Santos M Teresa , Vallés Juana 
Published: July 2018

SummaryIt is shown that the supernatant of unstirred whole blood at 37° C, stimulated by 1 μg/ml of collagen for 10 sec, produces a rapid generation of pro and antiaggregatory compounds with a final proaggregatory activity which can be detected for more than 60 min on a platelet rich plasma (PRP) by turbidometric aggregometry. A reversible aggregation wave that we have called BASIC wave (for Blood Aggregation Stimulatory and Inhibitory Compounds) is recorded. The collagen stimulation of unstirred PRP produces a similar but smaller BASIC wave. BASIC’s intensity increases if erythrocytes are added to PRP but decreases if white blood cells are added instead. Aspirin abolishes “ex vivo” the ability of whole blood and PRP to generate BASIC waves and dipyridamole “in vitro” significantly reduces BASIC’s intensity in whole blood in every tested sample, but shows little effect in PRP.
In Vitro Effects of the Acylated StreptokinasePlasminogen Activator Complex BRL 33 575 Incubated with Normal Human Plasma
Authors: Lämmle B , Noll G , Tran T H , Lohri A , Duckert F 
Published: July 2018

SummaryThrombolysis with acylated streptokinase-plasminogen complexes is aimed to achieve fibrinolysis without systemic fibrinogenolysis. The p-aminobenzoyl-streptokinase-(Lys)-plasminogen-complex (BRL 33 575) should be particularly useful due to its slow deacylation rate. Unexpectedly, repeated doses of 10 mg of BRL 33 575 (corresponding to 310'000 streptokinase equivalent units) induced systemic effects in patients though less than streptokinase alone. In vitro incubation of normal human plasma with BRL 33 575 at concentrations used in patients resulted in nearly complete consumption of α2-antiplasmin and plasminogen and significant fibrinogenolysis within 3 hr. This demonstrates that - despite of slow deacylation of BRL 33 575 - the small amounts of activator generated are highly efficacious in activating plasma plasminogen under conditions in which no physiological clearance of the free activator takes place. Simulating the calculated activator release from BRL 33 575 by infusing equivalent amounts of streptokinase into plasma resulted in less pronounced effects. This is probably explained by anti-streptokinase antibodies which will neutralize the initially infused streptokinase but will be bound by BRL 33 575.Our in vitro experiments indicate that further clinical studies should be done with lower doses of BRL 33 575 or prolonged dosage intervals.