bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic and Therapeutic Problems in a Patient with Factor VIII Inhibitor
Authors: Sas G. , Petö I. , Csörgö M. , Köves Á , Kun L. 
Published: May 2019

An old man was admitted to our hospital with the suspicion of acute abdomen. Sonography was used to visualize the psoas haematoma which accounted for the severe abdominal pain and made it possible to avoid an explorative laparotomy. We found a circulating anticoagulant against factor VIII /4 Bethesda units per ml plasma/. The antibody belonged to the IgG class. The patient was treated repeatedly by transfusions of fresh blood, large doses of cryoprecipitate and prednisolone. The improvement of the haemorrhagic symptoms was slow and a long term imtnuno - suppressive therapy was introduced. After a symptom-free year a massive bleeding occured in the thigh and in the psoas muscle. FEIBA therapy was introduced /plus prednisolone & azathioprine/. At first 15 units of FEIBA/kg were administered but the long clotting time did not change. In the following days the quantity of the FEIBA was gradually increased up to 60 units/kg but the coagulation time did not shorten significantly. The PTT became longer, the antithrombin III level decreased. At the same time a definite clinical improvement was observed.In our case sonography has proved a very useful tool in the diagnosis of psoas haematoma. However, the value of therapy applied could not be judged just as unequivocally.
An in Vivo Model for the Study of Antithrombotic Drugs
Authors: Strachan C.J. L. , Hawker R.J. , Fejfar J. 
Published: May 2019

A series of experimental animal models have been developed (a) to produce a model for double blind crossover assessment of new and existing antithrombotic drugs, and (b) to investigate the nature of the initiating factor in venous thrombosis. The following table describes results from 4 models in 80 dogs and 8 baboons.Types I, II, III involved bilateral femoral vein dissection but type IV was unilateral, jugular and femoral and allowed crossover studies. The 2.5 milliamps for 10 minutes was standard but if no current passed in Type IV with jugular electrodes in situ, no thrombus was produced in the femoral vein indicating a third factor is required i.e. circulatory, as in Virchow’s triad. Partial thromboplastin time, euglobulin lysis, white blood count, haematocrit, platelet count, fibrinogen and fibrinogen turnover were followed for 7 days and reflected the clinical response. Low dose heparin prevented and an anti-factor XIII inhibited, thrombus formation. A series of anti-platelet drugs had little or no effect on thrombogenesis. We conclude that Types III and IV models reproduce the 3 factors in Virchow’s triad with minimal trauma.
Prostaglandin Endoperoxides and Thromboxanes: Role in Platelets
Authors: Samuelsson Bengt 
Published: May 2019

Two groups of unstable (t1/2=5 min) endoperoxides, PGG and PGH compounds, have been isolated and shown to be precursors of the prostaglandins. The endoperoxides cause platelet aggregation and contract vascular and air-way smooth muscle.A new group of compounds(thromboxanes) derived from the endoperoxides has been discovered. A highly unstable(t1/2=30-40 sec) intermediate, thromboxane A2, between the endoperoxides and thromboxane B2 has been detected. Structural work indicates that it has a bicyclic oxane-oxetane structure. Thromboxane A2 is a potent aggregating agent with pronounced effects on vascular smooth muscle. Studies on the mechanisms of actions of the endoperoxides and thromboxanes in human platelets will be discussed.
Inhibition of Fibrinolysis, Associated with Oncogenic Transformation, by Normal and Antiplasmin-Depleted Human Plasma
Authors: Collen D. , Billiau A. , Edy J. , Somer De P. 
Published: May 2019

When mixed cultures of mouse fibroblasts and mouse fibroblasts transformed with Kirsten murine sarcoma virus (Arch. ges .Virusforsch. 43, 345, 1973) were grown in petri dishes and overlayed with plasminogen-enriched casein, they showed foci of caseinolysis induced by plasminogen activator secreted by the transformed cells. Caseinolysis was inhibited by the addition of human plasma or bovine pancreatic trypsin inhibitor (BPTI) to the overlay, I ml of plasma being equivalent to 67 ± 18 (mean ± S.E.), kallikrein inhibitor (Kl) units of BPTI.The culture fluid from a human melanoma line (gift of Dr. G. Barlow, Abbott Labs, III..), induced lysis of a fibrin clot, I ml of cuIture fluid being equivalent to 25 CTA units of urokinase . Fibrinolysis was inhibited by addition of human plasma or BPTI, I ml of plasma being equivalent to 94 ± 34 Kl units of BPTI.Specific removal of antiplasmin, the fast-reacting plasmin inhibitor from plasma, by immuno-absorption, completely abolished its inhibitory activity on caseinolysis and on fibrinolysis. This depleted plasma still contained normal levels of the known plasma protease inhibitors. It is conduced that antiplasmin is the only protein in human plasma capable of inhibiting the fibrinolysis associated with oncogenic transformation or neoplasia. Whether this effect is exclusively due to inhibition of formed plasmin or also to interference with plasminogen activation remains unsettled.
Blood Coagulation in High Altitude Pulmonary Oedema
Authors: Singh I. , Chohan I.S. 
Published: May 2019

Blood coagulation studies were undertaken in patients of high altitude pulmonary oedema at 3,700 m, comparable controls, and sea level subjects to determine the possible causal connection between changes in fibrinolytic activity, blood coagulation factors, and formation of thrombi within the alveolar capillaries, venules and some branches of pulmonary arteries. The following changes have been observed: Fibrinolytic activity was reduced. Plasma fibrinogen and factor VIII were increased. Factor XII was decreased. Platelet adhesiveness and platelet factor 3 were increased and electrophoretic mobility of platelets reduced. The integrity of platelet plasma membrane, capacity of pseudopodia formation, and ability of degranulation remained intact. Both arterial and venous adenosine-5′-diphosphate (ADP) levels were low and there was evidence of excessive utilisation of ADP in the pulmonary bed. The findings suggest that sludging of RBCs and formation of thrombi possibly result from these changes, impede the pulmonary blood flow, and aggravate the disease.Apart from inducing diuresis and reducing pulmonary blood volume, within 30 minutes of its administration intravenously, furosemide enhances fibrinolytic activity, decreases factors V, VIII and X and thrombotest activity, increases factor XII, reduces platelet factor 3 and adhesiveness, and improves clot retraction. It seems imoediments to blood flow at capillary and venuiar level, which occur on account or the hypercoagulable state, are removed and pulmonary oedema is relieved.
Vasoactive Substances in Pulmonary Embolism
Authors: Todd M.H. , Forrest J.B. , Hirsh J. 
Published: May 2019

Embolisation of the pulmonary vasculature with microspheres releases prostaglandin-1ike substances, PGLS (Piper and Vane, N.Y. Acad. Sei. 180: 363, 1971) but the capacity of autologous blood clots (ABC) to release pulmonary vasoactive substances is disputed. Ten normal mongrel dogs were anesthetised with pentobarbitone sodium and instrumented. Pulmonary venous blood was continuously superfused over isolated tissues for bioassay and then returned to the animal. Injection of ABC into the right atrium increased pulmonary artery pressure from 21 ± 6.5 mm Hg to 38 ± 15 mm Hg (mean ± S.D.), increased arterial pCO2 and decreased arterial pO2. No significant changes in heart rate, systemic arterial blood pressure or cardiac output occurred. In three animals contractions of the blood superfused assay tissues occurred following embolism. This effect was produced in normal assay tissues and those pretreated with antagonists of ACh, Serotonin, Histamine and Catecholamines and could therefore be attributed to PGLS. No cardiovascular or assay tissue tension changes were observed when equivalent volumes of saline or clot lysate were injected into the right atrium.Therefore, pulmonary embolism with ABC can release PGLS which may contribute to the pulmonary artery pressure rise. Vasoactive substances may normally be inactivated in the lung but in some animals appear in pulmonary venous blood.(Supported by the Ontario Heart Foundation)
On the pathogenesis of “disseminated intravascular coagulation.”
Authors: Spaet Theodore H. 
Published: May 2019

The following remarks introduce an alternative hypothesis to those conventionally held concerning the hemostatic changes of “disseminated intravascular coagulation (DIC).”The concept that coagulant materials may enter the blood with sufficient rapidity to produce clotting within the vessels and reduction of various blood coagulation factors, particularly fibrinogen, has long been with us. In early animal experiments intravenous tissue factor or thrombin was administered; when these were given at sublethal rates, typical coagulopathies were observedoThe next step was to identify experimental situations or clinical conditions in which blood changes resembled those produced in coagulant-injected animals. These were readily found, and many tests were developed to achieve increased sensitivity in diagnosis of the process. In general, the most widely used have been those which demonstrate loss of certain clotting factors, and those which identify fibrinogen or fibrin fragments.“DIC” is now a generally accepted syndrome»Some neglected observations suggest an alternative interpretation of the blood changes in “DIC.”These raise the possibility that in some, if not many or even most of these syndromes, the source of the blood changes is extravascular processing of the clotting factors. Products may return to the circulation via lymphatics. It is proposed that present methodology cannot resolve this alternative.Supported by UoS. Public Health Service, NIH Grant #HL 16387.
Changes in Platelet Function, Ultrastructure and Plasma Membrane-Associated Proteins (Actin and Tubulin) in Thrombocythemia
Authors: Podolsak B. , Wenzel E. , Morgenstern E. , Meiser R.J. 
Published: May 2019

Five patients with thrombocythemia (two primary hemorrhagic cases and three symptomatic cases, one with generalised amyloidosis and two with splenectomies after hemoblastosis or hepatosplenomegaly) showed the following pathological platelet functions: platelet count, 8 × 105 - 1.4 × 106/μ1; bleeding time 4 min, 50 sec. - 20 min; adhesiveness (Hellem II) 1.5 - 27%; significantly decreased aggregation with collagen and ADP and decreased platelet spreading capacity.In two patients, clot-retraction was less than normal. The distribution of platelet volumes was normal in all cases. Electron microscopic studies on platelets from these patients showed an increase in microtubular structures and a decrease in electron dense hyaloplasma.Analyses of the platelet membrane proteins from each patients, by SDS-PAGE and staining showed a band at ca. 50,000 daltons (probably tubulin) which was stronger, while in only three cases there was a significant decrease in membrane-associated actin, as compared to normal platelet membranes. In the other patients, the decrease was smaller. In two patients, there was a discrete decrease in the bands corresponding to heavy myosin chains. No essential changes were found in membrane glycoproteins. The changes in the relation between the different cytosoeletal elements could partially explain the impaired platelet function in thrombocythemia.
Platelet Antibodies and Circulating Immune Complexes in Thrombocytopenic Purpura
Authors: Wautier J.L. , Kadeva H. , Wautier M.P. , Boizard B. , Caen J.P. 
Published: May 2019

Forty five patients with thrombocytopenia (Platelet count below 105/ul) have been studied. Platelet associated IgG (Plat IgG) was determined by the method of Dixon et al (Normal range 38 ± 16 × 10-16g). Circulating immune complexes were detected by the [3H] Clq precipitation and the PEG precipitation techniques.The sera were also tested for their thrombo-agglutinating activity (Aggl.). The results were:The [3H] Clq test and the PEG test were significantly more frequently positive in patients with high level of Plat IgG.The thramboagglutination seems to be independant of the level of Plat IgG. It could be correlated with the presence of circulating immune complexes in the serum.
Molecular Characterization of Human Foetal Fibrinogen
Authors: Witt Irene , Tesch Rudolf 
Published: May 2019

Until eiqht days after birth, the human newborn synthesizes a molecular variant of fibrinogen. This foetal fibrinogen is characterized by several biochemical and functional properties.Previous results led to the assumption that the peculiarities of the foetal protein are caused by a special sequence of amino acids.Comparison of the tryptic peptide maps showed the identity of foetal and adult Bβ- and γ-chains, whereas the Aα-chain tryptic peptides and cyanogen bromide fragments are different. By thin layer chromatographic and sequence analyses the special amino acid sequence of the foetal Aα-chain can be localized in the amino acid sections 50 - 250 and/or 500 - 620. Because it could be ruled out that posttranslational constituents of the molecule are the cause of the “foetal” features it is quite probable that the foetal fibrinogen is genetically determined.
Histochemical and Ultrastructural study of the Platelet-Arterial Subendothelium Interaction
Authors: Legrand Y.J. , Bariety J. , Birembaut P. , Michel H. , Fauvel F. , Caen J.P. 
Published: May 2019

In order to characterize the subendothelial macromolecules able to interact with platelets rabbit aortas were de-endothelialized and incubated either with chymotrypsin (24 h at 37° C), with a highly purified bacterial collagenase (2 h at 37° C), or with chymotrypsin followed by collagenase or the reverse. Histochemical ultrastructural studies were performed before and after blood perfusion, using three different staining procedures: tannic acid (for the microfibrillar structures and elastin), ruthenium red (for the polyanions) and two peroxidase-labelled lectins (concanavalin A and ricinus communis (for the detection of saccharidic determinants)). After chymotrypsin, the tannic acid +ve, ruthenium red +ve and lectin +ve microfibrils had been digested; platelet adherence to the remaining sparse collagen fibrils persisted. After collagenase, these microfibrils are preserved, collagen has been digested, but the platelets can still adhere. After combined incubation with both enzymes, elastin is the only remaining constituent and no platelet adhesion can be observed.These results show that in the rabbit aorta subendothelium besides collagen, microfibrillar glycoproteins are able to interact with human platelets.
Heparin Catabolism Under Extracorporeal Circulation in Cardiac Surgery: Experimental Study
Authors: Simonuff M. , Doutremepuich Ch. , Chauve A. , Nicod J. , Fontan F. 
Published: May 2019

Extracorporeal circulation E. C. C. was performed on 13 Beagle dogs to deter mine heparin catabolism. Three types of heparin were used: a cold heparin and two radio-active(R. A.) heparins (S-35 and H-3) The E.C.C. was performed for 70 minutes (mn.) in all dogs, at a temperature of 37°C. in 4 dogs, 28°C in 4 and 20°C. in 5, (duration of hypothermia: 30 mn.).1) Plasmatic heparin elimination was related to the E. C. C. temperature: 42.6% at 37°C., 30 7% at 28 ° C. and 14.6% at 20°C. The biological half-lives were respectively 60 + 10 mn, 80 + 10 mn, and 200 + 20 mn.2) Urinary heparin elimination was delayed with respect to the E. C. C. temperature and independant of the type of heparin used. At the same time, the relation of heparin in plasmatic R.A, to urinary R.A. was constant(≈ 10) during the entire E. C. C.3) The study of the gastric fluid in 8 dogs showed an heparin elimination increased to a maximum at the end of the E.C.C.; at that time, the plasmatic R. A. to gastric R.A.heparin relation, in 5 dogs, was equal to 1.The study indicates that a)there is a correlation between the dosage made, try classical and radta-active melhods, b) the lowering of E. C. C. temperature diminfshes the catabolism of heparin, and c) a gastric heparin elimination during E. C. C.
Platelet Collagen Activation by Basement Membrane Collagens
Authors: Balleisen L. , Rauterberg J. 
Published: May 2019

The collagen component of the vessel intima consists of collagen type I, III and basement membrane collagens. For type III a particularly potent platelet aggregation activity was found earlier.Three different basement membrane collagens were isolated from call placenta. Occurence of type IV and V(A/B collagen) in the intimal and medial layer of vessel walls has been shown by chemical and immunhistological means(1). The third basement membrane collagen is probably isentical with the 55000 molecular weight component described by CHUNG et al. (2).Platelets from normal subjects were tested for aggregation and spreading on Zaponlack with type IV, V, the separated A and B chains of type V and the short chain collagen. Complete aggregation was obtained only with native type V collagen. Spreading of platelets was induced only by collagen type IV, the A chain of type V and the short chain collagen.The data indicate that all basement membrane collagens activate platelets but in different respects.1. Rauterberg J. et al.: Coll. Int. Cent. Nat. Rech. Sc. 287:220(1978)2. Chung E. et al.: Bioehem. Biophys. Res. Comm. 71: 1167(1976)
Rapid binding of ADP to a small population of platelet receptor sites
Authors: Legrand C. , Bauvois B. , Dubernard V. , Caen J.P. 
Published: May 2019

By studying binding of ADP to isolated human plasma membranes, we have found that ADP binds with different affinities and/or different kinetics to several types of receptor sites whose nature and localization have been assessed by subjecting the membranes to various treatments such as proteolytic digestion or alkaline extraction. From kinetic results, two populations of receptor sites were distinguished, with t 1/2 = IE-30 secor (approximately 20 % of the sites) and with t 1/2 = 4-6 minutes (80 % of the sites). The binding of AMP was studied to determine whether, as expected from its inhibition of ADP-induced platelet shape change and aggregation, it could react with ADP receptor sit We found that AMP bound rapidly to the platelet membrane (t 1/2 =15-30 seconds) ; up to approximately 100 picomoles of AMP could bind to One milligram of membrane protein, which represented 20-30% of the total ADP binding capacity, with an affinity constat (Ka =0.6 × 106M-1) higher than that of ADP (Ka=0.4 × 106M-1). AMP partially and conspectitively inhibited the binding of ADP. It was shown mainly to inhibit those molecules of ADP which bind to the platelet membrane during the first 90 seconds of incubation and which represent approximately 20 - 30 % of the total ADP binding.From this study, it is concluded that a population of receptor sites showirg high react vity towards ADP and AMP is present on the platelet membrane.
Abnormalities in Fibrin Formation in Hepatic Disease. Consequences of Acquired Dysfibrinogenemia on Fibrin Formation and on Platelet Aggregation Cofactor Activity
Authors: Soria J. , Soria C. , Ryckewaert J.J. , Samama M. 
Published: May 2019

Different causes of abnormal fibrin formation can be identified in severe hepatic diseases.A decrease in the level of Aα band of isolated fibrinogen can be related to increased fibrinolysis.Soluble complexes detected by the haemagglutination assay of red blood cells sensitized with fibrin monomers are present in cases with associated intravascular coagulation. An abnormal fibrin monomers aggregation can be due either to a plasma inhibitor or to dysfibrinogenemia. The anomaly is only present in plasma in the former case and in both plasma and isolated fibrinogen in the latter case.In acquired dysfibrinogenemia an increase in sialic acid content in the fibrinogen molecule can be demonstrated and is associated with an increase of ADP platelet aggregation cofactor activity. The effect of desialidation was also studied. These results are in good correlation with the hypothesis that oreviously isolated fibrinogen glycopeptides might play an important, roie in platelet aggregation.
Advantages of a Sequential Compression Device in Prevention of Deep Vein Thrombosis
Authors: Nicolaides A.N. , Fernandas J. , Pollock A.V. 
Published: May 2019

A sequential compression device (SCD) (6 chambers) compressing the ankle, calf end thigh sequentially at 35, 30 and 20 mm Hg for 12 seconds in every minute produced a 240% increase in peak velocity in the femoral vein. A non-sequential device (NSD) inflated to 25 mm Hg with a similar time cycle produced only an 180% increase in blood velocity.The two devices were tested clinically; 250 surgical patients were randomised to 3 groups scanned with the 125 I-fibrinogen test. Group A: 7 days subcutaneous heparin. Group B: NSD for 24 hours. Group C: SCD for 24 hours. The SCD was found to be as effective as heparin during the period it was used and more effective than NSD in preventing deep vein thrombosis proximal to the calf.
Structure-Function Studies on Native and Synthetic Permeability Increasing Peptide Derived from Fibrinogen or Fibrin
Authors: Belew M. , Gerdin B. , Larsson L.-E. , Lindberg G. , Porath J. , Ragnarsson U. , Saldeen T. , Wallin R. 
Published: May 2019

Vasoactive peptides liberated from fibrin microemboli have been suggested to be responsible for the increased microvascular permeability in the delayed microembolism syndrome. Two such peptides were isolated from fibrin or fibrinogen lysate after chromatography on Bio Gel P-6 and column zone electrophoresis. These peptides designated as 6A and 6D show a strong effect on microvascular permeability in the rat skin after injection of as little as 5 μg. Amino acid sequence: Ala-Arg-Pro-Ala-Lys for 6A and Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys for 6D. Synthetic counterparts were achieved by the Merrifield solid phase method. Structure-function studies revealed 1) Removal of the C-terminal Lys by carboxypeptidase B resulted in complete loss of activity. 2) Replacement of the C-terminal Lys with Arg in the pentapeptide did not affect its potency whereas substitution of the N-terminal Ala with a propionyl group resulted in an inactive product. 3) Cleavage of 6D with trypsin gave two inactive fragments. 4) Formylation of the Trp-residue in 6D gava product which was about 50% more active than the parent moleculeThese studies show that the N-terminal amino-group, the C-terminal Lys (or Arg) as well as Trp (in 6D) are apparently essential for the permeability increasing effect of these peptides.
Synthesis of an Arginine Analog of the Fragment 56-68 of Human Platelet Factor 4 Having Significant Antiheparin Activity
Authors: Bajusz S. , Fauszt I. , Barabáa É. , Bagdy D. 
Published: May 2019

Of the 70-residue polypeptide human platelet factor 4, which binds heparin stoichiometrlcally, the C-terminal fragment 50-70 /Tc-3/ showed a reduction of the heparin induced prolongation of thrombin time /Deuel et al., Proc. Natl. Acad. Sei. USA., 74:2256, 1977/.The arginine analog of the fragment 58-68 of Tc-3, which comprises the unique lysine rich region /Lys-Lys-Ile-Ile-Lys-Lys/, was prepared; Pro-Leu-Tyr-Arg-Arg-Ile-Ile-Arg-Arg-Leu-Leu-NH2. The aim of replacing of lyslne residues of the native molecule by arginine was to increase the interactions between the basic side chains of the peptide and SO3
- and/or COO- groups of heparin by introducing additional H-bridges and strengthening the ionic bonds. The new undecapeptide was synthesized by the standard solid phase method using Boc amino acids and dicyclo-hexylcarbodiimide condensation.1 nmole /1.8/ug/ of synthetic peptide completely inhibits the action of 0.3 units of heparin which corresponde a heparin/peptide molecular ration of about 1:6.