bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism Of Proteinase-Binding To α2-Macroglobulin
Authors: Sottrup-Jensen L , Hansen H F , Mortensen S B , Petersen T E , Magnusson S , Jörnvall H 
Published: May 2019

Peptide-bond cleavage in the bait-region of the α2M polypeptide chains, associated with proteinase-α2M complex formation was shown to occur in the sequence: GLRVGFYESDVMGRG HARLVH (part of the 298-residue “middle” segment) such that plasmin, thrombin and trypsin cleave the Arg-Leu (RL) bond, elastase mainly the Val-Gly (VG) and partly the Gly-Phe (GF) bonds. Thus, in the first step of complex formation the proteinase active site binds to the bait region of α2M.J.B. Howard found that heat inactivation of α2M causes cleavage of a Glu-Glx bond, and inactivation with CH3NH2 leads to incorporation of CH3NH2 on the γ-carboxyl of the same Glx-residue. We have found that reaction of α2M with trypsin or elastase but not trypsinogen causes the 2:1 stoichiometric appearance of up to 4 SH-/tetrameric α2M for up to 2 trypsin/2 elastase bound. The -SH was found to be the Cys-SH of thiol-ester-containing PYGCGEZNM sequence. Inactivation of native α2M (by CH3NH2, heating, dissolving in 2 M guanidine or 1.6% SDS at 50°C) also led to the appearance of up to 4 SH for 4 CH3NH2 incorporated per tet- rameric α2M. Competition between trypsin and CH3NH2 for the thiol-ester site proved that trypsin binds to the same Glx- γ-carboxyl that incorporates CH3NH2. Thus, the second step of complex formation involves the thiol-ester site γ-carboxyl of α2M and a proteinase-site other than its active- site (since the complex is active against small substrates). Other compounds with nucleophiles, e.g. putrescine or insulin, when added with trypsin, were also incorporated into α2M. The thiol-ester mechanism may be associated with the rapid elimination of proteinase α2M-complexes, particularly since the recent finding by B.F. Tack that complement factor C3 has an identical thiol-ester-containing sequence, points to at least one common function of these proteins.
Objective Assessment Of Late Results Of Treatment Of Deep Vein Thrombosis
Authors: Kakkar V V , Lawrence D 
Published: May 2019

There have been few prospective clinical studies where the haemodynamic status of the deep venous system has been assessed objectively following an episode of deep vein thrombosis (DVT). Recently, a foot plethysmograph has been developed in Sweden which allows haemodynamic changes in the venous system to be measured accurately. The purpose of this prospective study was to investigate the haemodynamic changes that may occur following treatment of DVT using heparin or thrombolytic therapy.113 Patients were included in this prospective study. None of these had suffered previous DVT or had signs and symptoms of the post-phlebitic limb at the time of initial treatment. In each case the diagnosis was established by ascending phlebography. In 79 of these patients, thrombus (>5 cm) was confined to the calf veins only. Initial treatment in these patients consisted of heparin in therapeutic anticoagulant dosage (adjusted according to APTT) for 7 days. Oral anticoagulation with Warfarin was commenced on the 5th day of treatment and continued for a minimum of 3 months. The remaining 34 patients had extensive thrombosis involving femoral, popliteal and iliac veins; in 32 of these calf veins were also involved. They received streptokinase therapy for a period of 5 days; the loading dose of 500,000 IU of SK was followed by a maintenance dose of 100,000 units per hour. Thrombolytic therapy was followed by heparin for 3 days and concurrent anticoagulation with Warfarin, the latter being given for a minimum of 6 months. In both groups, ascending phlebography was repeated on the 6th or 7th day to assess the extent of lysis or propagation of the thrombus. Haemodynamic assessment by foot volumetry was performed at 6,12 and 24 months following the initial episode of DVT. 77% Of 34 patients who sustained major DVT and received SK and 16% of 79 patients with calf vein thrombosis treated with heparin had evidence of severe haemodynamic impairment equivalent to that seen in the established post phlebitic syndro.
Treatment Of Neonatal Renal Vein Thrombosis (RVT) With Urokinase (UK)
Authors: Pavon A Fernandez , Chacon J L Fernandez , Cuesta M V , Ruza J 
Published: May 2019

The renal vein thrombosis represents an etiologic and therapeutic problem in neonatal pathology. In our milieu RVT is more frequent than is reported in current bibliography. This high incidence is accompanied by a high mortality and by the development of chronic renal failure among survivors.This fact led us to try a thrombolytic treatment that could be effective with respect to life and renal function.In our study we describe seven newborn patients with radiologically checked RVT. All cases were secondary to hypernatremic dehydration syndrome due to hyperconcentrated feeding. Five patients were submitted to thrombolytic treatment with UK, one patient was treated with heparin and one patient died before any treatment could be tried.Among the five patients treated with UK, four showed a complete recanalization of the RVT, with recovery of their renal function without sequelae. One of the patients, in whom an intracraneal haemorrhage was clinically suspected, died during treatment.The dosage of UK during treatment was 1000 U/Kg/hour.The duration of treatment was individualized according to renal evolution.The description of treated cases will be done individually.
Clotting Abnormalities During The Course Of Immune Type Glomerulonephritis Induced By HgCl2 In The Brown Norway(BN) Rat
Authors: Michaud A , Sapin C , Aiach M , Druet P , Forestier F 
Published: May 2019

This work was undertaken in order to study the clotting process during the course of a biphasic immune type glomerulonephritis(GN) induced by HgCl2 in the Brown Norway (BN) rat. This toxic agent induced, in a first stage, the formation of antiglomerular basement membrane (GBM) antibodies and in a second stage an immune complex type GN.Antithrombin III (AT III), fibrinogen degradation products (FDP) were evaluated by electroimmunodiffusion using specific antisera. The other classical methods were performed using commercial reagents. The albumin platelet content was evaluated by a radioimmunoassay. The soluble fibrin monomer complexes (FM) were searched for by a chromatographic technic.Transient clotting proteins variations related to nephrotic syndrome were observed (low AT III level, low factor XII activity, increased factor V activity, and increased fibrinogen level). Disseminated intravascular coagulation (DIC) was suggested by low platelet counts, rise in FDP, and presence of FM. Fibrin thrombi in the glomerular capillaries were observed by immunofluorescence in the rats presenting evidence for DIC and in rats which died during the first phase of the disease. The animals presenting DIC syndrome were the most severy ill.The hypothesis of an activation of the haemostasis system was supported by a low albumin platelet content and by the existence of high molecular weight fibrinogen derivatives. Complement activation, immune complexes, endothelial lesion might trigger DIC : the mechanism responsable for initiation of DIC are under study.According to this results, it can be concluded that DIC which is responsable for the death of several animals, plays a major pathogenic role in this experimental autoimmune disease.
Cyclic Nucleotides And PlateLet-Leukocyte Aggregates In Patients With Occlusive Arterial Disease
Authors: Kiersnowska-Rogowska B , Bielawiec M , Rogowski F , Bodzenta A , Giedrojć J 
Published: May 2019

The aim of the work was to study plasma cyclic nucleotides level /cyclic-AMP and cyclic-GMP/ and platelet-leukocyte aggregates in patients with obliterative arteriosclerosis of the lower limbs. The following parameters were investigated: cyclic-AMP and GMP radioimmunochemically by the use of a cyclic-AMP and cyclic-GMP assay kit, platelet leukocyte aggregates by the method of Silbergleit in our modification.The remainder were hospital deaths, five within the first 48 hours, 8 between 2-14 days, and 4 between 14 and 94 days. Five cases showed subendocardial infarction (SI). Four of these occuring out of hospital. The remaining 18 cases were transmural infarctions (TI). Sixteen of 17 hospital deaths exhibited TI.Significant decrease in cyclic-AMP level was found in arteriosclerotic patients in comparison to the control group. No significant changes in cyclic-GMP level were observed. The number of platelet-leukocyte aggregates was significantly higher in these patients.The influence of Hydroxy-ethyl-rutosides /HR/ on investigated parameters was also studie.The significant decrease in the level of cyclic-GMP in plasma was observed in patients after intravenously injection of 1000 mg of HR whereas no changes were found in cyclic-AMP level. The significant decrease in the number of platelet-leukocytes aggregates in the blood obtained after HR injection was also observed.Our results have shown the disturbances of plasma cyclic nucleotides balance and function of platelets and leukocyte in arteriosclerotic patients. This study also suggests that HR may be a modulating agent of these parameters.
Experience with an Amidolytic Heparin Assay Method
Authors: Teien A. N. , Abildgaard U. , Gjesdal K. , Holm A. H. 
Published: May 2019

The amidolytic method using Xa, purified antithrombin III(At-III) and the chromogenic substrate Bz-Ile-Glu-Gly-Arg-pNA(S-2222 from KABI, Stockholm, Sweden) measures heparin down to a concentration of 0.010 U/ml plasma. The accuracy of the method was evaluated by adding heparin to plasma samples from 10 normals and 10 patients, to concentrations of 0.05 and 0.5 U/ml. The results indicated that the content was assayed more accurately than by existing clotting assays. The precision was 5 and 2 per cent of the mean value at the two heparin concentrations, respectively. The concentrations of platelet factor 4 and At-III in test plasma had some influence on the result at low heparin concentrations. The “error” due to At-III, however, may be corrected by a simple formula. Heparinized plasma(containing less than about 15 000 platelets/μl) could be kept at 0 – 4 °c for 24 hours before assay, kept frozen and thawed repeatedly without significant loss of heparin activity.In plasma from patients on heparin prophylaxis with 5 000 U twice daily, heparin was detected in 98 per cent of the samples (range 0.010 – 0.241 U/ml).The present assay method reflects heparin concentration more directly than the activated partial thromboplastin time test and the thrombin clotting time test. In order to investigate to what extent these three tests mirror the clinical effects of heparin (therapeutic response and bleeding complications) a collaborative study involving 14 hospitals has been started.
Localization of Factor VIII Antigen in Platelets and Megakaryocytes of Normal and Von Willebrand Patients.(Electron Microscopy Studies with Peroxidase Labelled Antibodies)
Authors: Jeanneau C. , Sultan Y. , Savariau E. , Caen J. 
Published: May 2019

Using peroxidase coupled antibodies to human factor VIII, factor VIII related antigen (F VIIIRA) was localized in platelets and megakaryocytes of normal and Von Willebrand’s patients.Megakaryocytes and washed platelets were fixed either in glutaraldehyde alone or in a mixture of tannic acid, paraformaldehyde and glutaraldehyde and then incubated with the peroxidase coupled antibodies. In normal platelets, the peroxidase was found in two locations, on the plasma membrane and surface connecting system (S.C.S.) and in the cytoplasm associated with the membrane complex and dense tubular system.The plasma membrane of the megakaryocyte and the demarcating membrane system were not labelled. Antigen was localized in the perinuclear space, in smooth reticulum and clear vesicles, known to be the future platelet S. C.S.In homozygotes with severe forms of Von Willebrand’s disease (VWd) no F VIIIRA was detected around or in the platelete either before of after transfusion of normal cryo or after incubation of their washed platelets in normal plasma. In less severe forms, with detectable F VIIIRA in the plasma there is no such clear correlation between plasma and platelet F VIIIRA. Some have antigen in all platelets with a low plasma level. Others have two populations of platelets some with and others totally lacking antigen. In genetic variants of the disease all the platelets are normally labelled.
A New Primary Fibrinolysin from Mammalian Bile
Authors: King J. B. 
Published: May 2019

This primary fibrinolysin, termed cholelysin, has been found in the bile of all mammalian species tested so far. 0x bile has been studied in detail. This was freed of bile salts by adsorption on DEAE sephadex or the anion exchange resin Ag 1-X8, precipitated by ammonium sulphate, redissolved, and eluted off a Whatmans DE 32 column. A further stage of purification on sephadex G 75 was sometimes added, followed by freeze drying.This purified product gave one or two bands following sodium dodecyl Polyacrylamide gel electrophoresis. These bands contained sharply delimited lytic activity when tested on a standard fibrin plate. Molecular weights were estimated at 10 000 and 20 000 respectively, suggesting the presence of two polymers. Fibrin split products differed from those produced by plasmin.Cholelysin was actively fibrinolytic on a fibrin plate that had been heated to 80° for 30 minutes, caseinolytic, and active against synthetic substrates such as benzoyl arginine methyl ester. It was inhibited by a substance present at the inter-alpha anti-trypsin position in both human and rat serum. Using a rat model originally developed to test the anticoagulant activity of arvin, intravenous cholelysin was shown to have significant anticoagulant activity.
Familial Primary Fibrinolysis
Authors: Currimbhoy Z. 
Published: May 2019

This study reports on a unique family with primary fibrinolysis. A 31-year-old female had hematuria of one month’s duration. She had a previous episode of hematuria lasting 3 weeks and a hysterectomy for menorrhagia. Her 10-year-old daughter bled from the gums at the age of 9 months for one week. All clotting factors (including Factors VIII, V and XIII) were normal, except Fibrinogen. The mother’s Fibrinogen varied from 110 to 165 mg%, and the daughter’s from 90 to 146 mg%. The diluted Thrombin Time and Reptilase times were normal. The most striking and constant defect was in the fibrinolytic system. These studies were performed over a 4 month period. Euglobulin clot lysis, done on the mother repeatedly and on the daughter twice, were abnormally short, varying from 60 to 100 minutes, with FSP>10 and <40 ug/ml or <10 ug/ml. Active lysis was present on fibrin plates. α2 macroglobulin, α1 antitrypsin and Antithrombin III were normal, as was plasminogen immunologically. Platelet count and functions were normal. The maternal grandmother bled profusely twice after two gynecological procedures and once needed a blood transfusion. She was then put on birth control pills. Work-up on the pill revealed a Fibrinogen of 217 mg%, but no clot formed when attempting to evaluate euglobulin lysis. Off the pill, Fibrinogen was 167 mg%, euglobulin clot lysis 30 mins,, and there was a zone of lysis on the fibrin plate.The congenital loss of an inhibitor to plasminogen activator could explain these results.
Multiple Molecular Forms of Factor VIII Antigen in Normal Individuals and Von Willebrand’s Disease Patients
Authors: Zimmerman T. S. , Kimball J. R. , Edgington T. S. , Abildgaard C. F. 
Published: May 2019

Factor VIII antigen is present in normal individuals in multiple molecular forms which can be separated according to size. The intermediate and larger forms preferentially bind to platelets in the presence of ristocetin. In order to evaluate the possibility that Factor VIII antigen forms of large size may be an artifact of in vitro aggregation, we have ultracentrifuged plasma on a 20% sucrose cushion at 37°C for 10 min at 254,000 xg (peak). The rate of clearing of Factor VIII antigen was compared to that of IgM, fibrinogen, IgG, α1-antitrypsin and the S rate calculated to be between 15 and 18. These results indicate that Factor VIII-related antigen forms of high S exist even when plasma is maintained at physiological temperature and analyzed with minimal delay, suggesting that these large molecular forms also exist as such in vivo.Two types of von Willebrand’s disease (vWd) have been identified according to size of Factor VIII antigen forms present in plasma. In Type I all forms of Factor VIII antigen are present but are decreased in quantity. In Type II large forms are missing and smaller forms are present in normal or increased quantities. Factor VIII antigen was isolated from plasma of one patient with Type I and two patients with Type II vWd by counter Immunoelectrophoresis. The Factor VIII antigen was then reduced and electrophoresed on SDS-containing polyacrylamide gels. The presence of carbohydrate was evaluated by staining with perchloric acid-Schiff’s reagent (PAS). The 210,000 MW Factor VIII antigen subunit from each patient was PAS-positive. Though subtle changes in carbohydrate content or composition could not be evaluated by this technique, a total defect of glycosylation is unlikely in this small sample of vWd patients.
The von Willebrand Pig as a Model for Atherosclerosis Research
Authors: Fuster V. , Bowie E. J. W. , Lewis J. C. 
Published: May 2019

The aortas of 11 pigs with homozygous von Willebrand’s disease (vWd) were compared with those of 11 normal pigs, all aged 1 to 3 years. Six of the controls exhibited multiple arteriosclerotic plaques over 2 mm. in diameter with intimal thickenings of 63 to 130 microns. In contrast, none of the vWd pigs had multiple plaques; one had a single lesion over 2 mm. in diameter.Ten additional pigs, 5 controls and 5 with homozygous vWd, were placed on a 2% cholesterol diet for 6 months, beginning at the age of 3 months. Four of the controls developed aortic arteriosclerotic lesions exceeding 7.5% of the entire surface. Intimal thickness ranged up to 370 microns. In contrast, 4 of the vWd pigs developed lesions not exceeding 0.5% of the aortic surface; the fifth vWd pig had arteriosclerotic lesions involving 7.3% of the aortic surface.The aortas of the vWd pigs did stain with Evans blue dye injected antemortem, and they exhibited fatty infiltration in the intima. By electron microscopy, severe endothelial damage was apparent, but there was no intimal proliferation.The vWd pig seems to be an ideal model for arteriosclerosis research and the possible relationship of our findings may be related to impaired platelet-arterial wall interaction in vWd.
Antibodies as a Cause for Platelet Functional Defects
Authors: Caen J. P. , Levy-Toledano S. , Tobelem C. , Michel H. , Nurden A. T. , Legrand C. , Degos L. 
Published: May 2019

The Luc. antibody occurring in a polytransfused thrombasthenic patient is an IgG which agglutinates all human platelets except thrombasthenic ones. At sub-agglutinating doses, ADP, Adrenaline, Collagen, Thrombin and arachidonic acid-induced aggregations but not ristocetin and bovine factor VIII mediated platelet aggregations are inhibited. It does not modify ADP binding to normal human platelet membranes. The antibody strongly reduced thrombus formation on rabbit aorta subendothelium. Its activity is consumed after incubation with normal human platelet membranes but not with thrombasthenic ones. It inhibits thromboxane formation with all inducers but not with arachidonic acid and PGG2. This antibody reacts with a component present on human platelet membranes 120.000 MW.The Por. antibody occurring in a polytransfused Bernard-Soulier patient is an IgG which agglutinates all human platelets except those of Bernard-Soulier and thrombasthenia. The activity is consumed after incubation with normal and thrombasthenic platelet membranes but not with platelet membranes of Bernard-Soulier patients. At sub-agglutinating doses only ristocetin, bovine factor VIII aggregation and adhesion of human platelets to rabbit aorta subendothelium are inhibited. Purified neuraminidase, chymotrypsin or trypsin destroy the reaction of normal platelets with this antibody. This IgG reacts with a component of human platelet membrane 155.000 MW.
The Biphasic Effect of Sulfinpyrazone on Platelet Function
Authors: Buchanan M. R. , Rosenfeld J. , Hirsh J. 
Published: May 2019

Experiments performed in vitro have shown that the effect of sulfinpyrazone (SUL) on platelet function is associated with inhibition of platelet prostaglandin synthesis. We have studied platelet aggregation in vivo, plasma-drug levels and platelet MDA production in rabbits after treatment with SUL. At a dose of 100mg/kg, collagen-induced platelet aggregation in vivo was inhibited by 44% at ½ hr, 20% at 4 hr and then increased to a maximum inhibition of 57% at 18hr. This latter effect was achieved when there was no detectable SUL in the plasma (<0.5ug/ml). Platelets prepared from rabbits given 100mg/kg SUL either 2 or 8 hr beforehand were washed, labelled with 51Cr and injected into normal rabbits and platelet aggregation in vivo was measured. The response to collagen of platelets exposed for 2 hr to SUL was normal, whereas the response of platelets exposed for 18 hr to SUL was inhibited by 32%. MDA production by platelets incubated for 60 min in PPP prepared from rabbits which had been treated with either 10mg/ kg 1 hr beforehand or 100mg/kg 18 hr beforehand, was measured.(The SUL levels of the former and the latter plasmas were 4.4 and <0.5ug/ml respectively.) Platelet MDA production was inhibited 15% after incubation in the 10mg/kg-l hr PPP and 32% after incubation in the 100mg/kg-18 hr PPP (p<0.0001).It is concluded that SUL has a biphasic effect on collagen-induced platelet aggregation in vivo. Both effects are associated with inhibition of MDA production but the initial effect is reversible with washing and less marked than the secondary effect which is irreversible and could be due to a metabolite still present in the plasma at 18 hr.
vWAgII: A New von Willebrand’s Disease Antigen
Authors: Montgomery R. R. , Zimmerman T. S. 
Published: May 2019

Factor VIII-related antigen (vWAg I) is a protein of high molecular weight which co-purifies with Factor VIII procoagulant activity and von Wiflebrand Factor under a variety of conditions. It is decreased or absent in most cases of von Willebrand’s disease (vWD). We now report the existence of a second antigen (vWAgII) which is absent from the plasma of individuals (3/3) with severe vWD but present in normal amounts in the plasmas of individuals (8/8) with moderate or variant vWD. vWAgII is present in normal platelets and is released from them during clotting. However, it is also present in platelet-free plasma from normal individuals which has been collected in a variety of protease inhibitors including benzamidine, heparin, Trasylol, PMSF and soybean trypsin inhibitor suggesting that it circulates in plasma in vivo. The plasma from a patient with intravascular coagulation was found to have increased vWAgII.vWAgII is detected by antisera raised against void volume fractions of American Red Cross Factor VIII concentrates subjected to agarose gel chromatography. Antisera raised against highly purified vWAgI do not detect vWAgII. Crossed immunoelectrophoretic analysis shows vWAgII to have a more anodic mobility than vWAg I. II exhibits no immunologic cross-reactivity with intact vWAgI nor with vWAg I fragments produced by plasmin, a-chymotrypsin, trypsin or elastase. Though the absence of both antigens from the plasma of individuals with severe vWD suggests a biologic linkage, immunologic evidence for the origin of these two species from a common precursor has not been demonstrated.