bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interrelationships Between the Complement System and the Coagulation Kinin-Forming and Fibrinolytic Systems
Authors: Cooper Neil R. 
Published: May 2019

During contact activation, the coagulation, kinin-forming and fibrinolytic systems are initiated following the attachment of Factor XII to a surface by a complex series of protein-protein interactions that lead to the activation of serine proteases by limited proteolysis. The activation processes are modulated by protein cofactors and by inhibitors. These molecular processes are similar to those involved in triggering of the complement (C) system, another major plasma effector system. Multiple interrelationships of these four plasma effector systems that have been suggested will be summarized and their functional significance considered.We have begun a systematic investigation of such potential relationships employing highly purified proteins of the four systems. Initial efforts have been directed at determining whether plasma kallikrein, plasmin, thrombin or Factor Xa activate the first reacting component of the classical C pathway, Cl (C) is a calcium-dependent complex of three proteins: CIq , involved in binding ta antibody or other activators, generally on a surface; and Clr and Cls, zymogens of serine proteases. Both kallikrein and plasmin directly activate Clr and also Cls while thrombin and Factor Xa do not. Kallikrein and plasmin cleave the single polypeptide chain of Cls at a site near to or identical to that attacked by

and also cleave Cls at another, distant site. These evolving studies confirm and extend earlier work and indicate that the four plasma effector systems are closely interrelated.
Mechanism of Activation of Human Plasma Prekallikrein
Authors: Bouma Bonno N. , Vlooswijk Riek A.A. 
Published: May 2019

Human prekallikrein (PK) is in plasma complexed to High Moleculair Weight Kininogen (HMWK). The formation of a complex of PK with HMWK was demonstrated by cross-immunoelectrophoresis. Purified PK alone did not migrate upon electrophoresis, however when mixed with HMWK or Fletcher plasma, PK migrated with the same mobility as PK present in normal plasma. Also addition of PK to HMWK resulted in a reduction of the electrophoretic mobility of HMWK on cross-immunoelectrophoresis using anti-HMWK. Fitzgerald plasma which is deficient in HMWK has a PK clotting activity of 26% but no detectable PK-antigen level. Reconstitution with HMWK yielded PK-antigen levels corresponding to the PK-clotting activity. Addition of HMWK to normal plasma did not increase the PK-antigen levels.PK was activated by purified human (β-XIIa (28, 000 mol.wt) and by bovine α-XIIa (80, 000 mol.wt). Activation by αXIIa but not by by β-XII was enhanced by the presence of HMWK and dextran sulphate. After complete activation by α-XIIa in the presence of HMWK kallikrein remained complexed to HMWK. The generation of kallikrein activity paralelled the extent of proteolytic cleavage. SDS-polyacrylamide gel electrophoresis in the presence of reducing agents showed that both α-XIIa and β-XIIa generated fragments with apparent mol.wt’s of 52,000, 42,000 and 37,000. These fragments are initially held together by disulfide bonds, a second relatively slow cleavage generates fragments with similar mol. wt’s but observed on non reduced SDS-gels. This cleavage is not accompanied by a decrease in kallikrein activity.
Effect of pH on Platelet Aggregation and Leakage of β-Thromboglobulin from Platelets
Authors: Lloyd J.V. , Tunbridge L.J. , Rudzki Z. , Watts S.E. 
Published: May 2019

Experiments were carried out to determine whether there is a relationship between leakage of β-thromboglobulin (BTG)from platelets and changes in response to ADP occurring during storage or changes in pH. Blood or platelet rich plasma (PRP) collected in 0.1M citrate was incubated at 37°C and plasma BTG estimated by radioimmunoassay; further leakage of BTG was effectively prevented by adding PGE1 and cooling to 0-4°C.Plasma BTG concentration was 21ng/ml at venesection and 95ng/ml 60 minutes later when pH of PRP or whole blood was maintained at 7.35-7.50 by a 5% CO2 atmosphere. Further leakage was slight, plasma BTG being 123ng/ml at 120 minutes, but when pH was allowed to drift to 8.6 at 120 minutes after venesection plasma BTG was 325ng/ml (3.5% of total platelet BTG) and this was accompanied by liberation of 8.6% of H3'-serotonin from the platelets. Similar results were obtained when pH of whole blood was allowed to drift to 7.7. At pH 7.7-8.0 platelet aggregation was consistently enhanced.The experiments demonstrated leakage of BTG from platelets within 30 minutes of venesection and before deterioration of response to ADP. Further leakage of BTG and serotonin was induced by a shift in plasma pH and may be due to a pH related stimulus causing both changes in sensitivity to ADP and release of granule contents. Initial leakage after venesection may reflect small unavoidable changes in pH.
Enhanced Affinity of Fibrinogen and Factor XIII Induced by Limited Proteolysis
Authors: Chung S.I. , Folk J.E. , Finlayson J.S. 
Published: May 2019

Previous studies have shown that tissue transglutaminase has strong affinity for fibrinogen. In this study, the binding of protransglutaminase, i.e., plasma Factor XIII(a2b2) and platelet Factor XIII (a2), to fibrinogen was examined by ultracentrifugation, exclusion and affinity chromatography, Immunoelectrophoresis, and salt precipitation. Affinity was detected only by salting out and affinity chromatography. Limited proteolysis to form Factor XIIIa (a′2b2 and a′2) enhanced the affinity for fibrinogen. Limited proteolysis of fibrinogen by thrombin or ancrod enhanced affinity for both a2b2 and a2. Fibrin also bound a′2b2 and a′2. The b2 subunit exhibited no affinity for fibrinogen or fibrin. Thus, in the presence of fibrin(ogen), a′2b2 gave rise to a fibrin(ogen)-a′2 complex, and the b2 subunit was liberated.The enhanced affinity for fibrinogen induced by limited proteolysis of Factor XIII suggests that fibrinogen could serve to adsorb active transglutaminase(s) released or generated in the circulation.
Modifications of the Freeze-Cleaved Circulating Platelets Membrane in Hypercholesterolemic Rabbits, Prevented by AD6.
Authors: Weber G. , Bianciardi G. , Pierli C. , Toti P. 
Published: May 2019

Circulating platelets present on their membrane some protuberances, placed among the plasma-membrane particles, when examined with F.E. technique. Statistic tests have shown a significant increase in the average number of such protuberances in the platelets of hypercholesterolemic (15 and 45 days) rabbits.After i.v. administration of AD6, (8-mono-chloro carbochromen, a substance with a supposed anti-aggregating action) the number of the protuberances of circulating platelets in the hypercholesterolemic rabbits approaches to the average values of the normocholesterolemic ones.
Acquired Thrombasthenia in Non Hodgkin’S Lymphoma
Authors: Colvin B.T. , Lloyd M.J. , Mills M.J. , Bainbridge D.R. , Bateman S. , Turnbull A.L. 
Published: May 2019

A patient with non-Hodgkin’s lymphoma developed a typical thrombasthenic defect confirmed by platelet aggregation. The patient’s plasma was capable of inducing an identical defect in normal platelets. Patient’s platelets were found to be coated with IgGK and IgAK when studied by immunofluorescent techniques. Immunoglobulin of similar specificity was demonstrated in tumour at autopsy. IgAK specific antibody to normal platelets was found in the plasma.The finding of this autoantibody mirrors the observation of Levy-Toledano et al (1978) Blood, 51, 1065 in which a similar isoantibody was demonstrated in a multitransfused thrombasthenic patient.
Platelets Cross-Linked with Dimethyl Adipimidate Hydrochloride (DMA) Used in Ristocetin Assay For F VIII: Rcof.
Authors: Qazzaz M. , Podolsak B. , Wenzel E. 
Published: May 2019

When PRP or washed platelets are incubated with dimethyl adipimidate (DMA)(final concentration 2 mg/ml, 30 - 60 min.), the aggregation of the platelets by ADP, collagen or thrombin is clearly reduced. Aggregation by ristocetin plus F VIII: Rcof is however not affected.DMA is a bifunctional imidoester which acts as a cross-linking reagent. SDS Polyacrylamide gel electrophoresis of platelet membranes shows a different pattern for membrane glycoproteins from the platelet treated with DMA when compared to untreated platelets. This different pattern is due to cross-linking of the glycoproteins.The DMA - treated platelets can be stored for at least three weeks at 4° without losing their ability to aggregate in the ristocetin F VIII: Rcof test system. Both freshly -treated and stored DMA - treated platelets could be used to assay F VIII: Rcof reproducible in normal pooled plasma and in defective plasma (von Willebrand’s disease patients; N = 8). The preparation of DMA-fixed platelets takes less than two hours.
Purification and Properties of a Porcine Tissue Plasminogen Activator and its Comparison with Activators from Human Uterine Tissue, Blood and Urine
Authors: Kok P. 
Published: May 2019

A plasminogen activator was prepared from porcine ovaries by a simple procedure described earlier (Kok and Astrup, Biochemistry 8:79, 1969) and further purified by ion exchange chromatography on SE- or SP-Sepharose and affinity chromatography on Sepharose-lysine.The preparation was homogeneous by gel electrophoresis at pH 3.5 and SDS-polyacrylamide electrophoresis(PAGE). The specific activity was about 4.5 x 106 A and A tissue activator units per mg protein (one tissue activator unit is comparable to 0.1 CTA urokinase unit in a fibrinolytic assay under specified conditions). The molecular size estimated by SDSPAGE corresponded to a Mw of 67000 dalton. After reduction with dithiothreitol the activator produced a single band corresponding to a Mw of 33500 dalton, indicating cleavage into two chains of equal size. Isoelectric focusing revealed several bands, which were active and with an isoelectric pH range of 7-8.An activator from human uterine tissue and an activator in the euglobulin fraction from human plasma were similar to the porcine tissue activator in molecular size, estimated by gel filtration, and immunochemically. The porcine tissue activator differed from the activator from human urine in reactivity, molecular size and immunochemically.(This work was supported by USPHS Grant HL-05020, NIH, National Heart and Lung Institute, to dr. Tage Astrup and by the Swedish Medical Research Council (project no. 13X 03906 07A).)
Purification of Porcine and Human Tissue Activator
Authors: Wallen P , Rånby M , Bergsdorf N , Kok P 
Published: May 2019

Tissue activator from pig heart: A highly purified activator preparation from pig heart has been prepared, essentially using two affinity adsorbtion steps. 1) Affinity adsorbtion to fibrin and elution with potassium thiocyanate. 2) Affinity chromatography on Sepharose-arginine. The final product, which is obtained by gel filtration on Sephacryl S-200 contains according to SDS-polyacrylamide gel electrophoresis one main band with Mw 64000. Reduced samples still appear as one component but with Mw 31000. The specific activity is about 500000 IU/mg (WHO Reference Preparation for Urokinase) and the yield 15-25 %.
Tissue activator from human uterus: A highly purified preparation of human tissue activator has been prepared from uterus by an immunosorbent technique using antibodies produced in goats against the porcine tissue activator and coupled to Sepharose. A crude preparation from 1 kg uterus tissue and containing about 100000 IU tissue activator was adsorbed on 30 g of the immunosorbent. The activity was eluted with a KSCN-gradient. Further purification was obtained by affinity chromatography on Sepharose-arginine. The yield in the active fraction was 30-35 % and the specific activity 200000 to 300000 IU/mg. SDS-polyacrylamide gel electrophoresis showed one main band and 1-2 additional trace components.
Familial Deficiency of a Plasma Factor Stimulating Vascular Prostacyclin (PGI2) Activity
Authors: Remuzzi G. , Marchesi D. , Misiani R. , Mecca G. , de Gaetano G. , Donati M.B. 
Published: May 2019

We previously reported successful treatment with plasma in patients with thrombotic micro angiopathy and defective vascular PGI2 activity and suggested that a defect in a plasma factor stimulating PGI2 synthesis might be implicated in the pathogenesis. We report here that in one of these patients the plasma defect was still detectable 1 year after clinical remission (without recurrencies). Two of this patient’s 4 children had a simile,though less severe, plasma defect. The proposita is a 54-year-old woman admitted with a clinical and laboratory picture of haemolytic uraemic syndrome. Unlike normal plasma, the patient’s plasma had a low capacity to stimulate PGI2 production by rat aortic rings (previously washed until their endogenous PGI2 activity was exhausted). After plasma treatment the patient’s plasma behaved normally in this respect, but again appeared deficient at outpatient follow-up. PGI2 stimulating activity was normal in 2 daughters but consistently low (20-60% of control) in both patient’s sons. None of them had any history or clinical signs of microangiopathic disorders. Detection of this plasma defect in apparently healthy subjects and in patients who have recovered from thrombotic microangiopathic episodes could have clinical implications. Our observations support previous suggestions that some people have a congenital (or hereditary) predisposition to thrombotic microangiopathy.(Supported by Ass. Berg. Mal. Ren. and Italian CNR, Rare disease Project).
Fibrinolytic Activity of the Arterial Wall in Occluded Arteries With Thrombi
Authors: Donner L. , Klener P. , Vodáková L. 
Published: May 2019

The plasminogen activator in 117 specimen of 20 coronary and 20 pulmonary arteries completely occluded by thrombi, or emboli was studied within the adventitia and intima using Todd s histochenncal method. 39 cadavers were used, 1-18 hours post mortem from subjects aged 45 to 88 years.In occluded arteries both coronary and pulmonary the plasminogen activator activity was decreased in comparison of patent normal and atherosclerotic coronary and pulmonary arteries. In arterial thrombi a low grade focal activity of plasminogen activator was detected. It is suggested that the decrease of plasminogen activator in occluded human arteries might be due to the impaired oxygen supply of the vessel wall and to the consumption of plasminogen activator for lysis of the thrombus. These mechanisms must probable influence the plasminogen activator for a certain and prolonged time, since there were no changes of fibrinolysis within the vessel wall of arteria carotis of rats where a peracute thrombosis by means of an electric current was provoked.
A Study of Intravascular Platelet Aggregation in the Rat
Authors: Duncan G. G. , Smith G. M. 
Published: May 2019

Intravascular platelet aggregation can be studied by measuring the fall in the circulating platelet count induced by aggregating agents in anaesthetized animals. The Technicon Auto-counter was modified and connected via a double cannula to an anaesthetized rat to give a continuous count of the number of circulating platelets (1). Adenosine diphosphate (ADP), Collagen, Arachidonic acid (AA) and 5-Hydroxytryptamine (5-HT) were given at 15 minute intervals over a period of 2-3 hours. Aspirin (10 mg/Kg IV ) and Indomethacin (1-8 mg/Kg IV) partially inhibited collagen-induced aggregation and Indomethacin (2 mg/Kg IV) completely inhibited AA-induced aggregation. Adenosine (0.25 mg/min) inhibited the ADP-induced aggregation but did not inhibit aggregation produced by collagen or the residual response to collagen that remains after the addition of indomethacin.Reproducible responses to ADP and collagen were obtained but responses to AA and 5-HT were not reliable. Collagen-induced aggregation is thought to be mediated by the liberation of ADP, 5-HT and the formation of prostaglandin (PG ) endoperoxides and thromboxane A2. This study has shown that collagen-induced aggregation is reduced by inhibition of PG synthesis but the involvement of ADP or 5-HT could not be shown.
Hemorrhagic Complications of Heparin Therapy in Elderly People
Authors: Kher A. , Hervy M.P. , Henry J.F. , Forette F. , Berthaux P. 
Published: May 2019

The most important side effect of heparin therapy is bleeding. The reported incidence has varied widely and the relationship of bleeding to dose, route of administration, age, sex, underlying haemostatic defect and hypertension has been suggested. A review of one years experience with subcutaneous heparin in 113 elderly patients is presented in this paper. They are divided into three groups : Group I without laboratory control, Group II - dosage of heparin being controlled with recalcification plasma test, and Group III-heparin requirement controlled by thrombo-elastography. Group I - 24 women (average age 82.1 years) receiving 5000 I.U. every 8 or 12 hours, mean duration of treatment 24 days ± 13.3 : one fatal retroperitoneal haemorrhage. Group II - 35 females, 10 males (average age 81.3 years), mean daily dose of heparin 13.250 I.U.(TID), duration of treatment 30.3 ± 24 days, 10 patients sustained bleeding complications. Group III -38 females, 6 males (average age 81.6 years), average daily heparin requirement 12.250 I.U. (TID), mean duration of treatment 42.2±55.5, 4 patients developed minor bleeding.The relationship between age, sex, control of heparin dosage and existence of hypertension will be discussed in detail.
Plasma Concentrations of Platelet Specific Proteins Correlated with Platelet Survival
Authors: Doyle D.J. , Chesterman C.N. , Cade J.F. , Morgan F.J. 
Published: May 2019

Relationships between platelet survival (51Cr) and plasma concentrations (radioimmunoassay) of β-thromboglobulin (βTC) and platelet factor 4 (PF4) were analysed in 91 studies of patients prior to and after coronary artery bypass surgery. Platelet lifespans were calculated using the linear, exponential, weighted mean (WM) and multiple hit (MH) models. The values obtained approximated normal distributions and all the indices correlated, r values ranging from 0.69 to 6 (p<0,001 in all cases).βTC had significant negative correlations with all indices of platelet survival, the most significant being with MH (r = -0.39, p<0.001). Of interest was the correlation of βTG with the number of hits (n) in MH (r = -0.29, p<0.01). PF4 correlated with all indices of platelet survival except n, the most significant correlation was with WM (r = 0.33, p<0.01). BTC and PF4 were highly correlated (r = 0.62, p<0.001), however no benefit was obtained by combining measurements of the two proteins in any regression with platelet lifespan.The results suggest that shortened platelet survival in vascular disease is associated with platelet release of BTG and PF4 and that these platelet specific proteins are comparable as markers of platelet activation in vivo.
Coumarin Anticoagulation and Experimental Metastases
Authors: Hilgard P. 
Published: May 2019

Under experimental conditions oral anticoagulants of the coumarin type retard primary tumour growth and drastically reduce the incidence of distant metastases from rodent tumours. Employing different dose schedules it was found that satisfactory therapeutic anticoagulation and long-term treatment are pre-requisites for the anti-tumour activity. The equivocal effects of other anticoagulants, such as snake venoms, heparin and “antiplatelet” drugs on tumour growth and dissemination suggest a unique mechanism of coumarin derivatives. There is experimental evidence that the anti-tumour action is not a direct drug effect on malignant cells but specifically mediated by the vitamin K antagonism of the coumarins. Altered blood coagulability appears not to be the sole mechanism by which oral anticoagulants exert their anti-metastatic effect.There is a theoretical role for vitamin K dependent γ-carboxyglutamic acid containing proteins in interactions between tumour and host. Vitamin K deficiency increases tne phagocytic activity of peritoneal macrophages after nonspecific immunostimulation; this might be an important factor in controlling tumour growth. The synthesis of serine proteases with clot promoting activity by tumour cells is partly vitamin K dependent; these proteases could also nave considerable implications for the metastatic potential of blood borne cancer cells.
Platelet Survival Half-Life in Coronary Disease Patients under and over age 50
Authors: Chesebro J.H. , Fuster V. , Byrne J.H. , Olson D.A. , Kazmier F.J. 
Published: May 2019

Coronary disease (CAD) is usually severe when t he first symptoms appear. Thus identification of CAD patients (PTS) prior to symptom on set would be desirable for future preventive interventions. Since we found that cigarette smoking ≥10 pack-years (S) and family history of CAD at a young age (FH) are the 2 most important risk factors in CAD, and since platelet deposition to damaged endothelium appears important in the pathogeneais of atherosclerosis, platelet consumption was estimated by 51Cr platelet survival half-life (PS) in 3 groups of subjects:(1) in 49 accarentlv normal individuals without the risk factors (AN, no RF), (2) in 36 apparently normal individuals with the risk factors (AN, with RF), and (3) in 114 symptomatic PTS with angiographically proven CAD.There Is (1) a probable role of platelets in CAD as suoported bv the shortened PS, (2) a possibility that S or FH when associated with short PS (≤92 hrs) might identify the AN individual ≤ age 50 who is developing CAD, (3) a lower percent of CAD PTS >age 50 with a shortened PS and perhaps lesser probability of identifying asymptomatic CAD PTS >-age 50.
Increased Plasma Fibrinogen and Platelet-Aggregates in Type II Hyperlipoproteinaemia
Authors: Third J.L.H.C. , Lowe G.D.O. , Drummond M.M. , Bremner W.F. , Lawrie T.D.V. , Prentice C.R.M. 
Published: May 2019

Plasma-fibrinogen and circulating platelet-aggregates (method of Wu and Hoak1) were measured in 21 patients with Type II hyperlipoproteinaeima and 21 matched control subjects. Patients with hyperlipoproteinaemia had increased levels of fibrinogen (3.5 g/l ± SEM 0.2 vs. 2.5 g/l±0.1, p(0.01) and platelet-aggregates (platelet aggregate ratio 0.71 vs. 0.65, p(0.01). Young patients with hyperlipoproteinaemia had prematurely high fibrinogen levels, and the normal fibrinogen rise durina adult life was abolished. There were no significant correlations between fibrinogen, platelet-aggregates, and plasma lipids (cholesterol, cholesterol fractions, or triglyceride). High librinogen and platelet-aggregate levels may play a part in the development of the premature arterial disease associated with Type II hyperlipoproteinaemia, or may be markers of arterial injury.
1Wu, K.K., Hoak, J.C.Lancet, 1974, ii, 924.
Coagulation Studies During Operative Surgery
Authors: Sandilands D G D , Poller L 
Published: May 2019

The rate of thrombin induced platelet aggregation using the Chandler’s Tube technique, has been compared with changes in ‘intrinsic’ clotting and ADP - induced aggregation. Some of the results from operations with a high risk of developing venous thromboses provide suggestive evidence of circulating tissue thromboplastin activity. The significance of this in relation to heparin prophylaxis and its laboratory monitoring is discussed.* National (UK) Reference Laboratory for Anticoagulant Reagents and Control