bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Different Forms of Antithrombin III in Serum
Authors: Pepper D. S , Banhegyi D , Cash J. D 
Published: July 2018

SummaryAntithrombin III (AT III) complexes were isolated from human serum by affinity chromatography and gel filtration. In the first step of the preparation, using heparin-agarose chromatography, we observed that the complexed form of AT III bound less strongly to the gel than the free form and that about half of the AT III was free. With further purification a 2.5 × 105 molecular weight complex was isolated. Using 125I labelled human thrombin, this complex was radioactive indicating the presence of thrombin. Only in a synthetic thrombin-AT III system was a 9 × 104 molecular weight complex detected, but not in serum. These facts suggest that in serum AT III complexes may exist in a polymeric form. Also, an AT III antigen derived from the original AT III molecule, but not complexed, was isolated which may be a degradation product.Abbreviations used: AT-III, antithrombin III. Hepes, N-2-Hydroxyethylpiperazine-N-2-Ethanesulphonic acid.
The Aspirin Tolerance Test in von Willebrand’s Disease
Authors: Barbui Tiziano , Rodeghiero Francesco , Dini Enrico 
Published: July 2018

SummaryOpinions about the clinical value of aspirin tolerance test proposed by Quick in von Willebrand’s disease are conflicting.The results of the present study seem to support the view that a platelet defect, induced by aspirin, causes a significant lengthening of bleeding time only in the cases with severe von Willebrand factor deficiency.
Fibrin and Fibrinogen Proteolysis Products: Comparison between Gel Filtration and SDS Polyacrylamide Electrophoresis Analysis
Authors: Alkjaersig Norma , Davies Andrew , Fletcher Anthony 
Published: July 2018

SummaryThe proteolysis of purified human fibrinogen, stabilized and non-stabilized fibrin by plasmin were investigated by gel filtration analysis and SDS polyacrylamide electrophoresis of the reaction products. Plasmin proteolysis of fibrinogen followed the sequential steps previously reported and the two analytical methods yielded concordant results. Large molecular weight proteolysis products, of substantially greater molecular weight than native fibrinogen, were identified by gel filtration analysis following dissolution of stabilized and non-stabilized fibrin clots; with further incubation with plasmin, these proteolysis products gradually diminished in size. On the other hand, SDS polyacrylamide electrophoresis of these fibrin digests demonstrated that while non-stabilized fibrin yielded breakdown products similar in size to those obtained after proteolysis of fibrinogen, stabilized fibrin digests showed moieties of greater molecular size estimated to be of molecular weight 400,000 to 800,000. The final breakdown products of stabilized fibrin differed from those of fibrinogen and nonstabilized fibrin in that fragment D was present in the “double D” cross-linked form.
Alteration in Second Phase Platelet Aggregation Associated with an Emotionally Stressful Activity
Authors: Arkel Yale S. , Haft Jacob I. , Kreutner William , Sherwood Joseph , Williams Rae 
Published: July 2018

Summary23 healthy house staff officers were studied for platelet aggregation changes immediately prior to, immediately after and at a 7 to 11 day interval after their presenting a case before the Medical Mortality Conference. In 12 of the 23 with epinephrine (2.5 × 10−6M) and 11 of the 23 with ADP (2.0 × 10−6M) an absence of second phase aggregation was noted. A total of 19 of the 23 with epinephrine (2.5 × 10−6M) either had absent second phase or had a decreased slope of second phase aggregation. In all subjects except two a return to normal pattern was noted in the recovery samples 7 to 11 days later.In 5 subjects who had absent second phase aggregation with epinephrine (2.5 × 10-6M) immediately after presentation, one had a return toward normal at 24 hours while the others were resistant to higher concentrations of epinephrine (2.5 × 10−5M and 2.5 × 10−4M). One subject in the immediate post presentation period had a slight improvement in second phase aggregation with 2.5 × 10−4M epinephrine.Platelet counts increased in 5 of 6 subjects in the immediate post presentation period and did not necessarily correlate with the absence of second phase aggregation.ADP/ATP platelet content increased in the post presentation samples.We can conclude that during and immediately after an activity associated with stress, platelet changes can occur characterized by a decreased second phase aggregation with epinephrine or ADP. These changes last for at least 24 hours and are resistant to higher concentrations of epinephrine.
Fibrinogen, Fibrinogen Degradation Products and Erythrocyte Flexibility
Authors: Rampling Michael W. , Sirs John A. 
Published: July 2018

SummaryAn investigation has been made of the effect of fibrinogen concentration and fibrinogen degradation products on the flexibility of erythrocytes. The measurements were made using the blood of 2 donors, one representative of the normal population, the other representative of the 1. 5% of the normal population whose flexibility is more than three standard deviations from the total population mean. A linear relationship between erythrocyte flexibility and fibrinogen concentration was found in both cases. However, while the normal control had only a slow packing rate at zero fibrinogen concentration, the fast-packing cells retained a high degree of flexibility. Digestion of fibrinogen for sufficient time to form the larger degradation fragments X and Y indicated that they have similar effects to the native fibrinogen. The smaller fragments D and E, do not affect the flexibility nor do they inhibit or modify the effect of fibrinogen.
Heparin Neutralizing Activity (HNA) and Antithrombin III in Coronary Artery Disease
Authors: Cella G , Russo R 
Published: July 2018

SummaryPlasma from 14 patients with severe and diffuse coronary atherosclerosis has been compared with that obtained from a normal control group. While a decreased he parin-thrombin clotting time was demonstrated in the patient group, suggesting an increased level of circulating platelet factor 4, there was no significant alteration in plasma antithrombin III level. These results do not support a recent suggestion of a mild chronic intravascular coagulation in atherosclerosis.
Studies on the Neutralization of Rabbit Antibodies to Human Factor VIII
Authors: Kernoff P. B. A , Kaelin A. C 
Published: July 2018

SummaryThe capacity of normal and haemophilic cryoprecipitates to neutralize the anticoagulant effect of rabbit antibodies to human factor VIII (anti-VIII) was assessed using a quantitative estimation of antibody. About 4 times as much anti-VIII could be neutralized by normal factor VIII as was required to neutralize clotting activity. This suggests that there are probably several antigenic sites intimately associated with factor VIII clotting activity, quite apart from any antigenic sites which may be detected using antibodies directed against other components of the factor VIII complex. The neutralizing capacity of factor VIII was only slightly greater for the rabbit antibodies employed in this study than has been previously reported for antibodies of human origin, thus indicating only minor differences in specificities. Additional evidence in support of this concept was the finding that cryoprecipitates prepared from haemophilic plasmas previously recognized as either lacking or possessing the capacity to neutralize antibodies of human origin neutralized least or most quantities of rabbit antibodies, respectively.
A) Coagulation Proteins and Inhibitors: Cold-Insoluble Globulin (Clg), a Circulating Cell Surface Protein
Authors: Mosesson Michael W. 
Published: July 2018

SummaryThe history of the discovery and characterization of the cold-insoluble globulin of plasma (Clg) is reviewed. Subsequent growth of knowledge relating to its structure and function in plasma, in tissues, and on cell surfaces is examined.
Serine Protease Specificity for Peptide Chromogenic Substrates
Authors: Mattler L. E , Bang N. U 
Published: July 2018

SummaryRates of hydrolysis of the newly developed peptide chromogenic substrates S-2160 (N-Bz-Phe-Val-Arg-pNA, HCl), S-2238 (H-D-Phe-Pip-Arg-pNA, 2HC1), S-2222 (N-Bz-Ile-Glu-Gly-Arg-pNA, HC1), and S-2251 (H-D-Val-Leu-Lys-pNA, 2HC1) from AB Kabi Peptide Research and Chromozym TH (Z-Gly-Pro-Arg-pNA, HC1) from Pentapharm Limited were tested against highly purified preparations of human plasmin, bovine trypsin, human alpha thrombin, and bovine factor Xa.S-2160, S-2238, and Chromozym TH are sensitive to thrombin, Chromozym TH and S-2238 exhibiting a substantially greater sensitivity than S-2160. All 3 substrates are insensitive to factor Xa but hydrolyzed to varying degrees by plasmin and trypsin. In contrast, S-2222 is sensitive to Xa and insensitive to thrombin. S-2251 is relatively plasmin-specific, being resistant to the clotting enzymes thrombin and Xa. S-2251 exhibits even greater sensitivity to the SK-plasmin complex than to plasmin. In addition, the substrate Chromozym PK (N-Bz-Pro-Phe-Arg-pNA, HC1) was evaluated and found to be relatively specific for plasma kallikrein. Assays for antithrombin III and heparin using S-2222 as the substrate and factor Xa as the enzyme, plasma plasminogen and plasmin inhibitors using S-2251 as the substrate, and plasma prekallikrein and kallikrein inhibitors using Chromozym PK as the substrate have been developed. Synthetic peptides mimicking amino acid sequences adjacent to proteolytic activation cleavage of plasma serine protease precursors appear to be sensitive and relatively specific tools applicable to kinetical and clinical studies of these enzymes and their inhibitors.
Plasma Antithrombin III and Factor VIII Antigen in Relation to Angiographic Findings, Angina and Blood Groups in Middle-Aged Men
Authors: Stormorken Helge , Erikssen Jan 
Published: July 2018

SummaryIn a prospective study on latent coronary heart disease (CHD) in 2,014 presumably healthy men aged 40–59 years, 115 had strong clinical evidence of CHD never diagnosed nor suspected prior to the survey. Coronary angiography was performed in 105 of these. In 80 of them – whereof 57 were angiopositive and 23 angionegative – AT III and factor VIII Ag were assayed as well as in 35 normals from the same material. The results showed that:1. AT III was significantly lower in the angiopositive than in the normal controls.2. Subdivision of the angiopositive into those with and those without angina pectoris revealed significantly lower level of AT III in the former.3. Within blood group A only did the angiopositive subjects have significantly lower AT III than the remaining subjects in the group, and this was entirely due to the low values in those with angina pectoris.4. Blood group 0 individuals had significantly lower factor VIII Ag level than all other blood groups.The significance of these findings for the possible relation to development of atheromatosis is briefly discussed.
Measurement of Nucleotide Pools in Platelets Using High Pressure Liquid Chromatography
Authors: D’Souza Leo , Glueck Helen I. 
Published: July 2018

SummaryWe have devised an improved high pressure liquid chromatographic technique whereby serotonin, nucleosides, cyclic nucleotides, namely cAMP and cGMP, and 5’ mono-, 5’ di-, and 5’ tri-nucleotides can be analyzed. The cyclic nucleotides have been measured in pico molar quantities. All nucleotides can be quantitated in a single step separation in 75 min using a 0.0015 M phosphoric acids vs. 1 M pH 4.8 ammonium phosphate gradient. 5/10 ml of platelet-rich plasma furnishes an adequate sample for complete analysis. Nucleotide levels in platelets from 16 normal donors expressed in 1011 platelets are as follows: cAMP, 6.32 (4.15) nanomoles and AMP, 0.32(0.14); ADP, 2.48 (0.67); ATP 3.78 (0.68); GDP 0.38 (0.07) and GTP, 0.45 (0.07) micromoles. ADP and ATP values are lower than those previously published. However, the total nucleotide level approaches published values.Upon aggregation with thrombin, approximately 50% of ADP and 40 % ATP is released. Release is complete by 2 min. Thrombin is the most potent releasing agent with collagen and ADP occupying an intermediate role and epinephrine being the least effective. Upon aggregation cyclic AMP levels diminish along with other nucleotides. Patients with asthma showed depression of ADP, ATP, GDP and GTP levels.
The Role of Platelets in Myocardial Infarction, Ischemic Heart Disease, Cerebrovascular Disease, Thromboembolic Disorders and Acute Idiopathic Pericarditis
Authors: Zahavi J 
Published: July 2018

SummaryInitial white thrombus formation, has been attributed to platelet interaction with damaged vessel wall at sites of vascular injury or atherosclerotic plaques in the process of platelet aggregation (PA) and adhesion. Enhancement of PA seems to be an important factor in the development of thrombosis in the coronary and cerebral blood vessels and in embolization of platelet microthrombi to the microcirculation of the vessels. This latter event in turn might lead to serious or fatal arrhythmias or to paroxysms of cerebral ischemia.We have found enhanced PA in 66 patients with acute myocardial infarction (MI) and ischemic heart disease (IHD) which was specifically indicated by 4 distinct abnormalities: a) increased rate and extent of aggregation to 11,1 μM of adenosine diphosphate (ADP). b) Increased platelet responsiveness to 1,11 μM of ADP. c) Spontaneous aggregation which appeared in 95% of the patients compared to less than 5% of controls, d) Prolonged aggregation time indicated by parameter τ, τ = -[dt/dln(T–T ∞ ≤)], In addition, enhanced and occasionally more pronounced PA on the day of discharge from hospital, has been recently observed. The abnormal platelet behaviour was also detected in 10 thromboembolic disorder (TED), 28 acute cerebrovascular accident (CVA) and 24 acute infectious disease (AI) patients. It was, however, more pronounced in MI compared to TED and CVA patients. In AI the curves returned to normal some time after their subsidence, but remained abnormal for up to 2 years in IHD patients. In 10 patients with acute benign idiopathic pericarditis, which were included in the AI patients, PA proved to be a rehable indicator of the course of the disease and its treatment. Early reduction of corticosteroid dosage in the patients, was followed by increased abnormalities in the PA curves.The enhanced PA in these patients is most probably an indicator of a thrombogenic state and seems to be an important contributory factor in the pathogenesis of coronary and cerebrovascular diseases. Preliminary reports of anti-aggregating drugs, wether beneficial or adverse, in these vascular disorders are controversial and further research is needed.
The Effect of Insulin Treatment on the Balance between Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Type 2 Diabetic Patients
Authors: Vukovich Thomas , Proidl Sylvia , Knöbl Paul , Teufelsbauer Harald , Schnack Christoph , Schernthaner Guntram 
Published: July 2018

SummaryBeside hypercoagulation and hyperactivated platelets disturbances of the fibrinolytic system towards hypofibrinolysis have been reported to be associated with both glycemic and lipidemic derangement in diabetic patients. In the present prospective follow-up study the effect of 16 weeks insulin treatment and glycemic regulation on plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), the main regulators of fibrinolysis, was investigated in 19 type-2 diabetic patients with secondary failure to sulphonylureas. A similar glycemic regulation was obtained in a control group of 10 type 2 diabetic patients with sufficient metabolic response to strict dietary treatment and continuation of sulphonylurea treatment. Compared to 27 healthy subjects levels of tPA and PAI-1 were not significantly increased in type 2 diabetic patients before metabolic intervention. Although a hypofibrinolytic state due to an increase of PAI-1 levels was previously reported in obese hyperinsulinemic patients, no effect of insulin treatment on both tPA- and PAI-1 levels was observed in the present study including patients with only slightly increased body mass index (median 26.0 kg/m2). By correlation analysis PAI-1 levels were significantly related to serum cholesterol (R = 0.52) and glycemic control (glucose R = 0.41) in the whole group of diabetic patients at entry and in both subgroups after 16 weeks of treatment (insulin group: cholesterol R = 0.46, HbA1c R = 0.51; sulphonylurea group: cholesterol R = 0.59, HbA1c R = 0.58). In healthy subjects tPA and PAI-1 was correlated to serum insulin (R = 0.54, R = 0.56) and triglycerides (R = 0.46, R = 0.40). In conclusion, our results indicate that insulin treatment associated with metabolic improvement has no adverse effect to fibrinolysis in type 2 diabetic patients.
A Comparison of Methods for the Measurement of Activated Factor VII
Authors: Kitchen S , Malia R G , Preston F E 
Published: July 2018

SummaryA number of different methods are available for the measurement of factor VIIa. Almost all of these employ ratios of two different measurements of factor VII. In order to determine which is the most sensitive to activated factor VII we have compared currently available methods in the following groups: two patients with haemophilia A following treatment with activated recombinant factor VII (rVII a); 6 normal plasmas during cold promoted activation of factor VII; normal individuals (n = 23); and patients with unequivocal disseminated intravascular coagulation (DIC, n = 19). Factor VII was measured in an amidolytic assay (VII: Amid) and an antigen assay (VII:Ag). Clotting activity was measured using rabbit (VII:C Rab), human (VII:C Hum) and bovine (VII:C Bov) thromboplastin.Of the clotting assays the most sensitive to the presence of factor VIIa was that which utilised bovine thromboplastin. Amidolytic and immunological measurements were unaffected by the activity state of factor VII. The ratios VII:C Rab/VII: Ag and VII:C Rab/VII:Amid were insensitive to activated factor VII. The ratios most sensitive to the presence of factor VII a were VII:C Bov/VII: Amid and VII: C Bov/VII:Ag. The ratios VII:C Bov/VII:C Rab and VII:C Bov/VII:C Hum are less sensitive but have the advantage for epidemiological studies of narrower reference ranges.
Tissue Plasminogen Activator Release in Chronic Venous Hypertension due to Heart Failure
Authors: Keber Irena , Keber Dušan , Stegnar Mojca , Vene Nina 
Published: July 2018

SummaryIn order to study the effects of chronic venous hypertension due to heart failure on blood fibrinolytic activity, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) antigen, t-PA activity and PAI activity were measured before and after venous occlusion of the arm for 20 min in 15 patients with right-sided heart failure, 15 patients with left-sided heart failure, and 30 control healthy subjects. Central venous pressure, measured by observing the jugular veins, was above 15 cm of the blood column in all patients with right-sided heart failure, and normal (below 8 cm) in all patients with left-sided heart failure and control subjects. There was no difference in the basal concentrations of t-PA (11.0, 10.2 and 10.8 ng/ml; all values medians) and PAI-1 antigens and their activities between right and left-sided heart failure and the control subjects. After the occlusion, t-PA antigen increased significantly less in right-sided heart failure (28.6 ng/ml) than in left-sided heart failure and the control subjects (54.5 and 45.9 ng/ml, respectively). It was concluded that the poor increase in fibrinolytic activity that had already been reported in patients with heart failure, was due to low t-PA release during occlusion and not to a high basal PAI level. It was limited to the patients with right-sided heart failure and was probably the consequence of chronic systemic venous hypertension.
Mass Contents of Inositol 1,4,5-Trisphosphate and 1,2-Diacylglycerol in Human Platelets Stimulated with a Thromboxane Analogue and Thrombin
Authors: Suganuma A , Nakashima S , Okano Y , Nozawa Y 
Published: July 2018

SummaryMass contents of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DG) were measured in U46619-stimulated human platelets. 1 µM of U46619 induced maximum responses in aggregation, 5-hydroxytryptamine (5HT) secretion and increase in intracellular free Ca2+ concentration ([Ca2+]i). Aggregation was almost comparable to that induced by maximal dose (1 U/ml) of thrombin, while 5HT release was almost half. The initial [Ca2+]i peak in response to U46619 was about half of thrombin stimulation. Production of IP3 and DG was, however, less than one tenth of that seen in thrombin stimulation. The profile (time course and concentration-dependency) of IP3 formation did not correlate with that of [Ca2+]i, suggesting that U46619 stimulates IPs-dependent and -independent Ca2+ mobilization. DG production was small but sustained for more than 5 min. These findings support the recent hypothesis that aggregation is regulated by a delayed accumulation of DG. The low level of 5HT secretion could be explained by the low production of second messengers, IP3 and DG.
On the Significance of Different Aequorin Loading Techniques on Intracellular Aequorin Discharge, Baseline Calcium, Platelet Aggregation and Aequorin-Indicated Ca2+-Transients
Authors: Malmgren R , Grunfelt S , Joseph Rajiv 
Published: July 2018

SummaryThe study compares the decay of intracellular luminescence activity (L
max), the levels of basal [Ca2+]i in resting platelets, and agonist-induced peak [Ca2+]i-signals in platelets loaded with aequorin using the EGTA-, DMSO- and hypoosmotic shock treatment (HOST)-techniques. The highest load of intracellular aequorin with almost unchanged luminescence activity during 4 h was achieved with HOST. L
max decreased linearly in EGTA- and HOST-platelets, but the decay rate and the levels of basal [Ca2+]i were significantly lower in HOST-platelets. Platelet aggregation and aequorin-indicated [Ca2+]i-rise induced by thrombin and collagen were similar in EGTA- and HOST-platelets. In HOST-platelets, ADP-induced platelet aggregation was always accompanied by aequorin-signals, while at a similar time point, aequorin-signals were absent in 3 of 5 cases in EGTA-platelets. The initial aequorin loading was highest in DMSO-platelets, but L
max described an exponential decay, which was most pronounced when DMSO-platelets were maintained in Ca2+-free buffer (R
2 = 0.86). Agonist-induced platelet aggregation was significantly reduced in DMSO-platelets: thrombin-stimulation was accompanied by a significantly lower and delayed [Ca2+]i-rise and no aequorin-signal was obtained in response to ADP in 3 of 5 cases. The study shows that in addition of being a rapid loading-technique, the criteria of high intracellular aequorin load with low luminescence consumption, low basal [Ca2+]i and completely preserved platelet functions are most convincingly met by the HOST-method.