bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Fibrinogen Variant With Abnormal Gamma Chain : Fibrinogen Haifa
Authors: Soria J , Soria C , Palareti G , Tavori M , Samama M , Rimon A , Tatarsky I 
Published: May 2019

A congenital abnormal fibrinogen was detected in a 30 year old woman presenting several episodes of peripheral arterial thrombosis.The abnormality in fibrin formation is located in the fibrin monomers aggregation, since the fibrinopeptides release and the fibrin stabilization were normal.The SDS polyacrylamide gel electrophoresis of plasmic degradation products, obtained either in the presence or in the absence of calcium, revealed an absence of protective effect of calcium for plasmin degradation of Fibrinogen Haifa. Since, Ca++ protects against further plasmin degradation of the gamma chain, we suggest that the anomaly is located in this part of the fibrinogen molecule.Because the anomaly was discovered at Haifa, Israel, we suggest to call this abnormal fibrinogen : “Fibrinogen Haifa”.
Spontaneous Liver Rupture In Pregnancy Associated With Severe DIC: Management Of The Coagulation Disorder Prior To Surgery
Authors: Henny Ch P , Büller H R , ten Cate J W 
Published: May 2019

Spontaneous rupture of the liver is a severe com plication of pregnancy (maternal mortality: 59%, fetal mortality: 77%). The etiology is unknown, but it is commonly agreed that pre-ecclamptic toxaemia, and vascular damage of the liver play a definite role. Severe coagulation abnormalities which have been previously observed in these patients have as yet not been studied extensively. Recently we investigated two patients witn spontaneous liver rupture during pregnancy. Case 1: 34 year old multipara was presented with abdominal pain in the 37th wk of gestation. Suddenly a state of shock was observed. Surgery revealed hemoperi- toneum, subcapsular haematoma of the liver and ruptured capsule. The patient survived. Case 2: 30 year old primipara 37 wk of gestation was admitted with severe abdominal pain, jaundice and shock. Autopsy revealed a large subcapsular haematoma with ruptured capsule. Coagulation studies at admission revealed extensive DIC.Bleeding and DIC were succesfully controlled by the following transfusion regimen: 1) purified human AT III concentrates 2) prothrombin complex 3) cryoprecipitate 4) low dose heparin 5) platelets 6) Fresh Frozen Plasma 7) packed cells.Conclusively, maternal mortality might be reduced by early recognition of symptoms followed by prompt surgical intervention after correction of shock and coagulation defects.
Levels of platelet factor 3 in citrate plasma and in whole blood as determined by a chromogenic peptide substrate assay
Authors: Sandberg H , Gellerbring A.-K. , Andersson L.-O. 
Published: May 2019

A newly developed sensitive method for determination of platelet factor 3 (PF 3) using a chromogenic substrate (S 2238) (Sandberg and Andersson, Thromb. Res., in press) was used for comparison of the PF 3 levels in platelet-rich plasma (PRP) in citrate with the levels in PRP in the anticoagulant EDTA/citrate/PGE 1/theophylline. It was shown that in citrate PRP, release of PF 3 was started after about 20 minutes from blood sampling. Release of β-thromboglobulin (β-tg) was found to occur simultaneously with the release of PF 3. No release of PF 3 or β-tg could be detected within 3 hours from blood sampling in PRP in the EDTA/citrate/PGE 1/theophylline anticoagulant.The PF 3 level in whole blood was measured by a method which was a modification of the method used for plasma samples. It was found that, using the same donor, the PF 3 level of plasma and blood in the EDTA/citrate/PGE 1/theophylline anticoagulant was essentially the same. The levels of PF 3 found in blood upon standing in citrate or in EDTA/citrate/PGE 1/theophylline anticoagulant were in accordance with the levels found in plasma. Experiments with whole blood without any anticoagulant showed that release of PF 3 begin to occur simultaneously with release of β-tg, about 5 minutes before clotting. Thus the data show that PF 3 and β-tg are released in parallel.
Automated Microdensitometry And Protein Assays As Measures For Platelet Adhesion And Aggregation On Collagen Coated Slides Under Controlled Flow Conditions
Authors: Muggli R , Baumgartner H , Tschopp Th 
Published: May 2019

Microscope slides were homogeneously coated over a length of 2 cm with a mixture of soluble and fibrillar collagen and exposed at 37°C and under laminar flow to citrated whole rabbit blood at a flow-rate of 100 ml/min. Surface coverage with platelets (adhesion) and platelet accumulations higher than about 5 μm in height (aggregation) were determined by automated microdensitometry of fuchsine stained ‘en face’ preparations. The platelet mass per unit surface was measured with a modified Lowry technique whose sensitivity was equivalent to 5×l05platelets. Platelet number, amount of protein and surface coverage with platelet accumulations correlated. After a perfusion time of 10 min thrombi up to 30 μm in height and oriented in the direction of flow had developed on the collagen coated area. Surface coverage with platelets was 75% and the amount of deposited protein 1.4 μg/mm2(2×l06platelets/mm2). On the uncoated surface single platelets predominated; the surface coverage was 20% and the density of platelets 8×104/mm2. Acetyl- salicylic acid at 100 μm decreased platelet aggregation by about 80% without affecting adhesion.The new parallel plate perfusion system offers rapid quantitation of platelet-surface and platelet-platelet interaction after exposure to flowing blood and iftay also be diagnostically useful.
Isolation of Fibrinogen Protomer by Partial Reduction of Disulfide Bonds in Concentrated Urea
Authors: Albert A , Cacho F , Saiz J 
Published: May 2019

Partial reduction of human and bovine fibrinogen (F). recently dissolved in 6 and 8M deionized urea, with different amounts of dithioeritritol (DTE) (10 to 60:100 DTE:F, w/w) has been carried out in nitrogen atmosphere. Disc gel electrophoresis in 0.1% SDS shows changing amounts of six molecular species depending on the reaction time and DTE:F ratio. Three bands are identical with those obtained by total reduction of fibrinogen, one with unreduced material, the remaining two show mobilities corresponding to molecular weights of 170.000-190.000 (band H, with yields up to 40-50%) and 130.000-140.000 (band N).Total reduction of the isolated species H shows identical composition in fibrinogen chains as the original material. Stabilization by alkylation of this soecies is only successful in 0.1% SDS. Comparative ultracentrifugation studies show sedimentation coefficients of 6.8 S for fibrinogen incubated with SDS and 4.1 S for the H Species, which agree with a ratio 2:1 for their molecular weights.These results confirm the existence of two protomer entities easily cleaved by partial reduction but the need of high concentration of urea to separate the protomer, suggests the existence of additional strong non-covalent interactions between the two hemimolecules.
Red Cell Deformability and Risk Factors in One Hundred Patients with Cerebrovascular Thrombosis
Authors: Boisseau M , Lorient M , Bricaud H 
Published: May 2019

The rheological importance of red cell deformability on thrombotic states has recently been established. The aim of the present study was to demonstrate the relationship between the loss of erythrocyte flexibility and vascular risk factors in one hundred patients presenting with cerebrovascular accidents (CVA).Erythrocyte deformability measured by Nucleopore filtration method was significantly (p 0.001) decreased in patients with CVA (filtration time (FT) = 57 ± 28 s. x ml-1) compared with two hundred heathly subjects (FT = 33 ± 6 s. x ml-1). Among the risk factors erythrocyte deformability mainly depended upon the gravity of Hypertension (FT = 77 ± 35 s. x ml-1; p 0.001). Additionnal risk factors such as hyperlipemia, diabetes were less effective.In all cases high FT were observed in patients with widespread atherosclerotic lesions (carotid stenosis, arteritis).Finally in thrombotic states, as CVA, the decrease of red cell deformability appears to be strongly correlated to vascular diseases and risk factors.
Thrombin-Induced Changes in Phosphatidic ACID (PA) and Phosphoinositides
Authors: Leung N. L. , Kinlough-Rathbone R. L. , Mustard J. F. 
Published: May 2019

Thrombin-induced changes in PA, monophosphoinositide (MPI) , diphosphoinositide (DPI) and triphosphoinositide (TPI) of washed rabbit platelets have been examined. Platelets prelabeled by incubation with 32P-orthophosphate, 3H-glycerol, 3H-inositol or 14C-arachidonate were exposed to 0.33 u/ml thrombin for one minute, and the phospholipids extracted and separated by thin layer chromatography. Measurement of absolute amounts of PA and MPI by phosphorus assay showed that PA increased by 180% while MPI decreased by 15%.The changes in MPI with 3H-G, 3H-I and 14C-AA and in 1,2-diacyl glycerol (DG) indicate that some MPI may be converted to PA via DG. Changes in the 3H-G and 3H-I labeling of DPI and TPI suggest that the changes observed with 32P-Iabeled platelets are a result of the turnover of the phosphorylinositol moiety. The increase in AA with 14C-AA indicates that some of the decrease in MPI may be due to the formation of lyso MPI and free fatty acid. These results indicate that thrombin stimulation of platelets may affect inositol phospholipid metabolism through three pathways: (1) involving PA, DG and MPI; (2) the cleavage of free fatty acids from MPI; (3) turnover of the ester phosphates on DPI and TPI.
Relation of Growth Hormone and Von Willebrand Factor Activity
Authors: Sarji K. E. , Schraibman H. B. , Levine J. H. , Barnes M. , Nair R. M. G. , Sagel J. , Colwell J. A. 
Published: May 2019

Growth hormone (GH) has been implicated in the pathogenesis of diabetic angiopathy although the exact mechanism remains unknown, von Willebrand factor activity (vWF) is significantly higher in diabetic than in normal plasma (p<.001). In view of this, we have investigated the relationship of radioimmunoassayable GH and vWF activity, as measured in a bioassay using washed normal human platelets and ristocetin. Samples were obtained after an overnight fast, during oral glucose tolerance tests, and during sleep. A significant positive correlation was seen between GH over a range of 0.46 to 12.2 ng/ml and vWF activity over a range of 1 to 470% (p<.01). vWF activity was suppressed by oral glucose in normals and diabetics, with the amount of suppression related to the degree of glucose intolerance. Maximal suppression of vWF activity was coincident with maximal GH suppression. Samples from 4 normal subjects drawn through an indwelling catheter at 30-minute intervals during sleep showed peaks of plasma GH and vWF activity with GH peaks preceding vWF peaks by an hour or less. Two patients with panhypopituitarism and one patient with isolated GH deficiency were similarly studied. GH levels were low in these patients, but vWF levels were normal; both GH and vWF showed little sleep-related change.A single intramuscular injection of GH produced a marked increase of vWF activity in all 3 patients within 30 minutes and a later increase after 5–6 hours. We conclude that a regulator of glucose metabolism, possibly GH, is involved in regulation of vWF activity.
Activation of Hageman Factor (HF, Factor XII) by Sephadex-Ellagic Acid Mixtures
Authors: Ratnoff O. D. , Saito H. 
Published: May 2019

In the intrinsic pathway of clotting, PTA (Factor XI) is activated by activated HF. Whether activation of HF requires the presence of prekallikrein (Fletcher factor) and high M. W.(HMW) kininogen (Fitzgerald factor), or whether these agents act after activation of HF is disputed. Purified HF activates PTA in the absence of prekallikrein, but this may reflect molecular changes in HF during purification.Sephadex G10 or G15 was mixed with ellagic acid and freed of excess ellagic acid by washing. A mixture of normal plasma, or plasma deficient in HF, prekallikrein, HMW kininogen or PTA, and Sephadex-ellagic acid was centrifuged at 31000 xg. Each supernatant plasma except that deficient in HF shortened the abnormally long partial thromboplastin time (PTT) of HF-deficient plasma. Plasma simultaneously depleted of HMW kininogen, prekallikrein and PTA also shortened the PTT of HF-deficient plasma and of plasma depleted of HF and prekallikrein (albeit minimal clotting times were reached more slowly in the latter case) but had virtually no procoagulant effect upon the PTT of plasma depleted of HF and HMW kin inogen.Thus, exposure of HF in plasma to Sephadex-ellagic acid generated a clot-promoting form of HF in the absence of other clotting factors, but its full expression requited the presence of HMW kininogen.
Effects of Pyrazolone Drugs on Synthesis of Prostaglandin D2 and Thromboxane B2 by Platelets
Authors: Ali M. , Zamecnik J. , McDonald J. W. D. 
Published: May 2019

The principle products of arachidonic acid (AA) in platelets are hydroxylated fatty acids and thromboxane B2(TXB2). Prostaglandin D2(PGD2) has been considered to be a nonenzymatic degradation product of prostaglandin H2 formed in the presence of plasma albumin. Using 14C AA as substrate and thin layer and silicic acid chromatography, we have demonstrated PGD2 synthesis by washed (albumin-free) human platelets. The identity of PGD2 was confirmed by gas chromatography-mass spectrometry. In platelets lysed by freezing and thawing synthesis of TXB2 and PGD2 was approximately equal and equally inhibited by pyrazolones.Synthesis of PGD2 by platelets is enzymatic and may contribute to bronchoconstrictor, vasomotor, and inflammatory effects induced by platelet aggregation. Pyrazolones appear to inhibit cyclooxygenase activity rather than the breakdown of cyclic endoperoxides as previously postulated.
Fluorogenic Substrates for the Determination of Plasminogen Activators and Plasmin
Authors: Nieuwenhuizen W. , Wijngaards G. , Groeneveld E. 
Published: May 2019

Plasminogen activator activities in biological fluids are low and specific for plasminogen. Highly sensitive and accurate assays are needed for direct quantification and for kinetic studies. We therefore, synthesized tripeptide amides i. e., t. BOC. val. gly. arg β-NA (l) and val. gly. arg β-NA (II) from which the fluorescent group β-naphtylamine (β-NA) is released upon enzymatic hydrolysis.Kinetic parameters found for the hydrolysis of these substrates by plasmin, urokinase and tissue plasminogen activator are:*in nmol/CU/min; **in pmol/CTA/minStrikingly, tissue activator is not active on substrate II, allowing discrimination between this activator and other proteases.The sensitivity of the assay is at least ten times higher than that observed for other synthetic substrates available. Moreover, substrates I and II can be used in enzyme histochemistry.
Immunological Characterisation of A∝ Chain Fragments of Human Fibrinogen
Authors: Conkie J. A. , Davidson J. F. 
Published: May 2019

In an investigation of the early cleavage fragments resulting from fibrin(ogen)olysis, we have examined the nature of small peptides arising from the C-terminal part of the Aα chain of human fibrinogen.Antiserum to the carboxymethylated Aα chain of human fibrinogen has been prepared, and used to study the Aα-related antigens from (i) a plasmin digest of human fibrinogen, (ii) human serum, obtained from urokinase-treated normal plasma, and (iii) normal human serum. Using immunodiffusion and immunoelectrophoresis with anti-Aα antiserum, along with Polyacrylamide gel electrophoresis, at least two non-identical Aα -related antigens have been detected in a final plasmin digest of human fibrinogen. The largest of these antigens (MW 26,000) has been isolated and named Aα.-RA (26,000). This may be similar to the previously-described fragments, Hi2-Ala, fragment A or fragment H. Aα -related antigen has been produced by in vitro fibrinogenolysis in plasma and has been detected in the serum. In addition, small quantities of Aα -related antigen have been found in untreated normal human serum.These results suggest that anti-Aα antiserum is likely to be a useful reagent for the study of the early plasmin-derived fragments of fibrin(ogen)olysis in vitro and in vivo.
Incorporation of3H-Glycerol into Phospholipids of Normal and abnormal Platelets
Authors: Hutton R. A. , Hardisty R. M. , Deykin D. 
Published: May 2019

Glycerol-2-3H uptake into phospholipids separated by unidirectional chromatography on silica gel H plates, was measured in normal platelets and those from patients with Glanzman’s thrombasthenia (GT), Bernard-Soulier syndrome (B-S), Storage pool deficiency (SPD) or aspirinlike release defect . The results were compared with the release of adenine nucleotides (AN) and with changes in platelet factor 3 availability (PF3a). In normal platelets, secondary aggregation induced by adenosine diphosphate (ADP), Epinephrine (EPI) , Collagen (COL) or Ristocetin (RI) led to a marked stimulation of glycerol uptake over a 60 minute period of incubation, the most striking increase being in the phosphatidyl inositol (PI) fraction.No quantitative differences in phospholipid distribution were noted in any of the patients tested. In all cases, the uptake of glycerol was proportional to the degree of platelet aggregation, being minimal where no aggregation was observed (GT platelets mixed with ADP or EPI) , of intermediate level where primary aggregation alone occurred (SPD platelets with all agents or with GT platelets with RI), and similar to normal where secondary aggregation was induced (B-S platelets stirred with ADP or EPI). The results suggest that the defective 3H-glycerol uptake by abnormal platelets is a consequence rather than a cause of the decrease in platelet aggregation. Enhanced PI turnover most probably reflects the cells response to membrane damage or distortion incurred during aggregation and the release reaction.
Dihomo-γ-Linolenic Acid Metabolism in Man:Its Relevance to Platelet Function
Authors: Stone K. J. , Willis A. L. , Hart M. , Marples P. 
Published: May 2019

Prostaglandin (PG) metabolites of dihomo-γ-linolenic acid (DELA) inhibit platelet aggregation (Kernoff et al, this meeting). In vivo, antithrombotic effects of DHLA might be limited by its rate of Δ5-desaturation to arachidonic acid (AA), which enhances platelet aggregation when administered to man. In the rat and mouse desaturation is particularly active but in the guinea-pig, cat and rabbit it appears insignificant*. We now report on the metaholism of single oral doses of DHLA in 3 human volunteers. Lipids were extracted from blood fractions and separated into different lipid classes before estimation of fatty acid composition by gas-liquid chromatographys P.G.’s, generated from platelets by maximal stimulation with thrombin, were isolated by argentation chromatography and estimated by bioassay. Maximal plasma DHLA/AA ratios (0.2-0.5) occurred at 3–4 hrs when the DHLA/AA ratio in triglycerides had increased 9–12 fold. Between 5-24 hrs DHLA accumulated in phosphatidyl choline. There were no consistent increases in the AA content of blood lipids and no increases in platelet production of its metabolite PGE2. Small increases in platelet PGE1 synthesis occurred, indicating that orally-administered DHLA reaches PG precursor pools in man. These results support our hypothesis that chronically-administered DHLA may be of therapeutic value as an antithrombotic agent.*Willis, Stone, et al (1977). In: Prostaglandins in platelets and other blood cells, Ed. Silver, Smith and Kocsis, Spectrum Publications, Holliswood, N. Y.
Isolation of an Apparently Abnormal Von Willebrand Factor: Comparison with Plasma and Serum Von Willebrand Factor
Authors: Baugh R. F. , Burnand C. , Hougie C. 
Published: May 2019

A patient with an extremely high level of von Willebrand factor (8X normal) failed to show any response to ristocetin with her platelet-rich plasma. The patient also had a long bleeding time and a large amount of a paraprotein. Using a washed platelet assay system and dilutions of her platelet-poor plasma, ristocetin-induced platelet aggregation activity could be recovered to 40% of normal. Purification of the von Willebrand factor from the patient’s plasma resulted in an increase in ristocetin-induced platelet aggregating activity associated with the von Willebrand factor. Electrophoretic comparison by SDS disc gel electrophoresis and crossed immunoelectrophoresis showed no differences between this patient’s von Willebrand factor and either purified normal plasma or serum von Willebrand factor. The patient’s plasma, following removal of the von Willebrand factor, inhibited ristocetin-induced platelet aggregation in normal platelet-rich plasma and in a washed platelet system using purified normal von Willebrand factor. These observations indicate the presence of an abnormal plasma protein which binds ristocetin and thereby inhibits platelet aggregation. Furthermore, the abnormal protein must interfere with the in vivo functions of the von Willebrand factor as witnessed by the increased bleeding time presented by the patient. This behavior is explained by a model system in which ristocetin mimics a structural component found in the lining of the vessel walls which is exposed by tissue injury. The abnormal plasma protein competes with the von Willebrand factor and interferes with von Willebrand dependent platelet adhesion.Supported by an NIH Research Career Development Award and the American Heart Association.
Difference in Thrombolytic Effect between Higher and Lower Molecular Weight Forms of Urokinase
Authors: Suyama T. , Nishida M. , Iga Y. , Naito R. 
Published: May 2019

Urokinase (UK) from human urine has been widely used for thrombolytic therapy in Japan. However, commercially available preparations are not identical but consist of mainly two forms of UK with higher and lower molecular weight (H-UK and L-UK) . An attempt was made in this report to compare thrombolytic activity of H-UK with that of L-UK on artificial thrombi produced from human blood by a modification of Chandler’s loop method, which was somehow comparable to the situation in vivo. Two active forms of UK were purified from crude preparation by gel filtration. The approximate molecular weight of the H-UK was 54,000 and of the L-UK 34,000. The potency of UK was determined by “two-stage lysis time method” and expressed by International unit(lU). Thrombolytic activity measured by Chandler’s method was calculated as % lysis of the control thrombus that was formed in the abscence of UK.As a result, thrombus-dissolution time of H-UK was much shorter than that of L-UK. Furthermore, concentration of H-UK (IU/ml blood) necessary to induce 50% lysis was approximately one half lower than that of L-UK. The similiar results were obtained on artificial thrombi from the blood of dog, rat and rabbit. The data suggest that H-UK seems to be more effective on treatment of thromboembolicdisorders as compared to L-UK in terms of the same IU basis.