bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of 5-Hydroxytryptamine [5-HT] Storing Organelles in Isolated Megakaryocytes
Authors: Seitz R. , Wesemann W.
Published: May 2019

Megakaryocytes were enriched from rat and guinea pig bone marrow by Percoll density gradient and/or Elutriator centrifugation, [3H]5-HT was incorporated into megakaryocytes by a time- and concentration dependent, saturable uptake mechanism comparable to 5-HT incorporation into human blood platelets. - Electron microscopy of megakaryocytes showed that the number of osmiophilic dense bodies is increased after incubation with 5-HT. These findings suggest that the osmiophilic dense organelles are the 5-HT storage sites within megakaryocytes and provide a mean to identify these organelles during their biogenesis.
Plasminogen Activity in Plasma and in Serum Before and After Venostasis
Authors: Soria C. , Rodriguez-Zeballos A. , Soria J. , Kartalis G.
Published: May 2019

When venostasis is applied in men for 10 minutes at a pressure half-way between diastolic and systolic, various results may be obtained as far as fibrinolysis is concerned, normally the euglobulin lysis time reduced from above 3 hours to less than one hour. In these conditions, after venostasis the estimation of plasminogen after activation by Streptokinase (S.K.) on synthetic substrate S2251, shows 20-80% greater activity in serum than in plasma. In some patients at high risks of thrombosis, the euglobulin lysis time 15 unchanged after venostasis. In these cases, the biological activity of plasminogen is slightly greater in plasma than in serum, as is observed before venostasis in all subjects.

In order to explain these observations, experiments were performed using placental or plasmatic (glu or lys) plasminogen ; these show that for the same antigen activity, the biological activity of placental plasminogen previously activated by S.K. is greater than that of plasmatic plasminogen. We suggest a modification of the structure of plasminogen in the presence of activators and of fibrin clots. Further experiments will be necessary to explain the modification of plasminogen structure
Automated Control of Coumarin Therapy by Chromogenic Factor X Assay
Authors: Mibashan R. S. , Scully M.F. , Birch A.J. , Thumpston J.K. , MacGregor I.R. , Kakkar V.V.
Published: May 2019

A fully automated chromogenic substrate method for measuring plasma factor X has been used to monitor patients attending an anticoagulant clinic. Thirty six patients already established on coumarin therapy were studied by taking four citrate plasma samples from each at monthly intervals. Factor X was assayed in 10 μl aliquots by an adaptation of the method of Aurell & Friberger (Kabi Diagnostica Information Sheet) in an LKB Mark II Analyser with pre-injection facility, allowing 60 s pre-incubation with RW before addition of the substrate S2222. Activity was measured as Δ OD 405/min. Calibration curves were prepared by dilution of lyophilyzed normal plasma, and six coumarin controls were interspersed, with values of 18% (1.09 SD) & 22.2%(1.50 SD) of normal. The F X levels in the 36 patients at each of the monthly clinics were 23.6%. (5.l SD), 23.1 (4.9), 23.1 (5.0) & 23.7% (4.8) of normal, corresponding to RVV/phospholipid coagulant assays of 22.3% (6.3 SD), 22.3 (6.3), 20.7 (5.8) & 21% (6.1) of normal respectively. The prothrombin activities ac each visit, expressed as prothrombin time ratios (PTR), averaged 2.64, 2.80, 2.64 & 2.56. Regression analysis of chromogenic F X values on individual PTR’s gave r=0.65, which led to no change in coumarin dosage when this was repeated blind. The results suggest that rapid, automated F X assays may be suitable clinically, technically & geographically in long-term coumarin control when apparatus & reagents become competitive with established coagulant procedures.
Treatment of Severe Pulmonary Embolism by Urokinase and Lysyl-Plasminogen
Authors: Sors H. , Venet A. , Reynaud P. , Safran D. , Cornu P. , Even P.
Published: May 2019

The effects of the heparin (H)-Urokinase (UK) treatment on pulmonary emboli (PE) are limited by the rapid disappearance of the plasminogen (Pig) contained in the clots. Two groups of patients with recent PE (less than 8 days) of equal severity (as judged by angiography) have been studied: Group I (15 patients) treated by H(500 IU/kg/24h) and UK (i.v. bolus 15,000 u. CTA/kg/20min) and Group II (15 patients) receiving H and a sequential treatment with a bolus of UK followed by Lysyl-Plg infusion (300 UI/kg/6h), then by a 2nd bolus of UK and finally by a Pig loading. Angiography and catheterization were performed before and 24 hours after the treatment. The vascular obstruction (VO%) was appreciated by the UPET method. In Group II, the values before treatment were : VO 57±11% ; mean pulmonary arterial pressure (PAP) : 30±5 torrs ; cardiac index (CI) ; 2.0±0.6 I/min/m2 ; pulmonary arterial resistances (PAR) 8.4±2.7 torrs/I/min/m2 ; PaO2 : 56±7 tors. The UK + Pig treatment elicited significant changes : 50% decrease in VO and PAR, 33% decrease in PAP and 30% increase in PaO2 and CI in 24 hours. One month later, hemodynamic was normal and the residual VO was less than 15%. In Croup I the initial hemodynamic values were similar but the 24 hours decrease in VO, PAP and FAR were respectively of 30, 22 and 29%, differing significantly of the Group II (F test). After one month, the residual VO was 25%. These observations suggest that Lys-Plg loading increases significantly the efficacy of thrombolytic treatment of massive and recent PE.
Synergism Between Adrenaline and Adenine Nucleotides in Producing Platelet Aggregation Responses
Authors: Oppenheim B. , Youdim M.B.H.
Published: May 2019

Recently we have shown that 5′-adenylylimidodiphosphate (AIP), a structural analogue of ATP, causes a transient aggregation of human blood platelets similar to that produced by 5-hydroxytryptamine (5-HT) (Brit. J. Pharmacol. 1979, in press). In addition AIP strongly inhibits the second phase of aggregation induced by adrenaline (A), noradrenaline, ADP and irreversible 5-HT when such a response is obtained. However, it does not affect collagen response, indicating that AIP is an inhibitor of release I (i.e. release is reversible. Like 5-HT, the aggregation to AIP can be enhanced by pretreatment (30-60 sec.) with low (0.1-0.5 μM) non-aggregating concentrations of A, but without exhibiting a second phase of aggregation. The synergistic effect of A (but not isoproterenol, 10-100 μM) was also observed with ATP and ADP. ATP by itself does not produce an aggregation response but it causes a 5-HT like response after preincubation with A. The potentiating effects of A on aggregation responses are selectively prevented by phentolamine (10 μM) but not by proparanolol (10 μM). The results suggest an α-adrenergic mediated effect.
Adhesiveness of 51Cr-Labelled Platelets
Authors: Dale J. , Myhre E.
Published: May 2019

The procedure of labelling platelets may disturb their reactivity, and methods based on measurements of radioactivity may therefore not reflect the survival of representative platelets. To study this, nine patients with prosthetic heart valves were chosen because platelet adhesiveness is reduced to a varying degree after valve replacement. Autologous platelets were labelled by incubation of PRP from 120 ml of ACD-blood with 250 μci 51CrO4 for one hour, and then reinjected. After 16 hours, platelet retention was estimated according to Hellem’s modified glass bead method, in parallel samples, the retention of radioactivity was measured. Labelled and non-labelled platelets were retained in the glass-bead columns to the same degree, indicating that the Labelling procedure did not permanently disturb platelet adhesiveness.
Effect of Dextran on the Posttraumatic Fibrinolysis Inhibition
Authors: Carlin G. , Karlström G. , Modig J. , Saldeen T.
Published: May 2019

Increased fibrinolysis inhibition activity (PIA) in the blood is seen in patients with postoperative thromboembolic complications and has been suggested to be of importance in the pathogenesis of these conditions. Infusion of dextran (500 ml 6 %) to patients 3 days after total hip replacement surgery, when PIA was maximal, strongly decreased FIA of plasma measured by a clot lysis assay. Plasma antiplasmin (chromogenic substrate assay) and immunologically determined levels of the primary fibrinolysis inhibitor (PFI, α2-antiplasmin), α2-macroglobulin, α1-antitrypsin and plasminogen were not changed after the infusion of dextran. The effect of dextran on plasminogen activation by urokinase and fibrin degradation was studied in clotted plasma. The presence of dextran accelerated both the fibrinolysis and the uptake of labelled plasmin on fibrin. This effect of dextran was not seen in experiments where the clot was made of purified fibrinogen (containing plasminogen) instead of plasma. The FIA-decreasing effect of dextran is also dependent on the presence of physiological plasmin inhibitors and fibrin. The results indicate that the activation of plasminogen is enhanced by dextran provided that fibrin and inhibitors are present.
Function of Previously Unrecognized Plasma Protein M in Thrombin Generation
Authors: Seegers Walter H. , Ghosh Abha , Wu Van-Yu
Published: May 2019

Purified prethrombin 1 converts to thrombin in the presence of purified Ac-globulin, purified Factor Xa, phospholipid and calcium ions (Baker and Seegers, Thromb. Diath. Haemorrh. 17: 205-213 (1967)). The yields are, however, low. By adding a protein fraction isolated from bovine prothrombin complex the yield becomes maximum. This fraction we call Protein M. It is obtained by fractionating bovine prothrombin complex (McCoy and Seegers, Thromb. Res. 1: 451-472 (1972)) using a DEAE-Sephadex A-50 column 1.5 χ 15 cm as previously described (Novoa, Seegers and Hassouna, Prep. Biochem, 6: 307-338 (1975)). Prothrombin and Factor IX are eluted with 0.25M sodium chloride followed by Protein M at 0.30M sodium chloride. Protein M is obtained as a single component from a Sephadex G-100 column (2.5 χ 180 cm). Until now we have not been able to identify Protein M with any previously known coagulation factor. Protein M is a single chain protein with an apparent molecular weight near 60,000 as determined by Polyacrylamide gel electrophoresis. Litte prethrombin 1, highly purified bovine prothrombin also requires Protein M for maximum thrombin production in the presence of purified Ac-globulin, purified Factor xa, phospholipid and calcium ions. In relatively large amounts Protein M shortened the prothrombin time Of normal bovine plasma as well as plasma samples drawn during Coumadin administration.
Immunoradiometric Assay for VIII:CAg BASED on Two Non-Haemophilic Antibodies
Authors: Holmberg L.
Published: May 2019

Antihaemophilic-factor-A-antibodies, which had spontaneously arisen in two patients, were used to develop an imtiunoradiometric method for measurement of antihasnophilic factor A antigen (VIII:CAg). One of the antibodies was used for ooating plastic tubes. A seaond antibody formed a stable high molecular weight complex with a factor VIII-concentrate and could conveniently be isolated in labelled form. This antibody, which seated to be bound to only one immunologie site of VIII:CAg, was used for detecting the VIII. CAg fixed to the tubes by the first antibody.

Thirteen patients with severe haancphilia A had VIII:CAg below the limit of detection (0.01 U/ml). Patients with moderate and mild haemophilia A either had VTII:CAg roughly equal to factor VIII clotting activity (VIII:C) or a not detectable VTII. CAg, suggesting two different molecular mechanisms in moderate and mild hasrophilia. VIII:CAg oould be detected in serum but in lower amounts than in plasma. In two patients with von Willebrand’s disease VIII:CAg equalled VIII.C. The post-transfusional retarded increase of VIII :C in a patient with von Willebrand’s disease was accompanied by a slight increase in VIII. CAg. Fetal plasma contained measurable amounts of VIII. CAo.
Platelet Abnormalities in Experimental Diabetes
Authors: Johnson M. , Harrison H.E. , Hawker R. , Hawker L.
Published: May 2019

Many abnormalities of platelet function occur in patients with diabetes mellitus, partioularly those with angiopathy. We have previously demonstrated that prostacyclin (PGI2) is decreased in streptozotocin-diabetic rats, and have now investigated platelet reactivity in these animals. Responsiveness to ADP and arachidonlc acid was increased, and platelet cyclo-oxygenase and thromboxane synthetase activities were significantly elevated (p<0.05) in diabetic animals (5.5±0.7 and 5.9±0.9 arbitrary units/109 platelets) when compared with control animals (J.0±0.4 and 3.9±0.3 arbitrary units/109 platelets). Malondialdehyde synthesis was 1,5 and 0.9 n moles per 108 platelets in diabetic and control rats respectively. Diabetic platelets were also less sensitive to the anti-aggregating effects of PGI2 (IC50: diabetic, 2.3 ng/ml; control, 1.3 ng/ml. Survival of illindium-labelled autologous platelets was significantly reduced, indicating that platelet function is abnormal in vivo, in diabetic animals. Platelet hyper-reactivity, possibly associated with depressed PGI2, could be related to the vascular complications of diabetes.
Predictive Value of Tests of Haemostatic Function in Ischaemic Heart Disease
Authors: Meade T.W.
Published: May 2019

The Northwick Park Heart Study (NPHS) has recruited 5,500 participants since it began in 1973. Follow-up examinations began in 1978. The chief objective is to obtain prospective data on the association of results of tests of haemostatic function with the subsequent incidence of clinically manifest ischaemic heart disease (IHD). Levels of factors V, VII and VIII, fibrinogen, anti-thrombin III, and fibrinolytic activity, platelet adhesiveness and platelet count have been measured routinely on all participants. Prospective data are also being obtained from plasma aliquote stored in liquid nitrogen at recruit-pent, but only analysed, on a case-comparison basis, as new events of IHD occur; ristocetin co-factor is one variable being assayed in this way. In addition, the follow-up round of examinations is being used to carry out full dose-response related platelet aggregation to ADP and adrenaline in about half the participants, and to investigate the feasibility of measuring relevant prostaglandin derivatives, particularly thromboxane, on large numhers. Assays of factors II and X have also been introduced. However, nrospective findings on adequate numbers of different types of new IHD events (i.e. “sudden death”, infarction, angina) are still some years away. Meanwhile, analyses of data from those who had already had IHD at the time of recruitment, and of the general epidemiology nf the variables concerned are providing evidence of the haemostatic system’s involvement in the pathogenesis of IHD.
Biophysical Factors of Thrombosis
Authors: Stoltz J.F.
Published: May 2019

In addition to patiental anf blood factors, Virckow’s classical trial includes stasis which combined with one of the others factors, may cause venous or arterial thrombosis. The author successively consider hempdynamic biophysical factors and rheological factors related to blood.

With regard to hemodynamic factors attention is drawn to the incidence of thrombosis from local modifications of blood flow. The type of flow should also be considered and the risk of thrombosis increases in presence of turbulence, areas of recirculation or Vortex. With record to blood factors, hyperviscosity must be taken into account and particular attention should be paid to increase of haematocrit, intravascular aggregation of bloos cells (sludge) globular factors (membrane elasticity and internal viscosity) and interaction of blood cells on platelets.

Atheromatous deposits on white thrombi may also obey certain rheological parameters (irregularities in the vascullar wall, changes in the juxtaparietal layer, microturbulence, stanating areas...) Lastly, with regard to vascular wall, in addition to biochemical and haemotologic changes, account must be taken of parietal viscoelasticity, electrial charge of the vascular wall...

This work was supported by DRET (Biological department) Grant 78 34.097.00.480.01
Possible Mode of Action of Ticlopidine: A Novel Inhibitor of Platelet Aggregation
Authors: Johnson H. , Heywood J. B.
Published: May 2019

Ticlopidine (T) is weakly active in vitro, but is a potent inhibitor of platelet aggregation induced by ADP, collagen, thrombin, adrenaline, arachidonic acid, prostaglandin (PG) endoperoxide and thromboxane A2 with a sustained effect, when administered to a variety of animal species, including man. Platelets from treated animals were normal in ultrastructure and 14C-ADP binding was not modified by T. Basal PG synthesis was unaffected, whereas aspirin (A) had a marked inhibitory effect. Platelet cyclo-oxygenase and thromboxane synthetase activities were 90.6±12.9 and 96.1±5.3% of control following T treatment. In contrast to A, T had no effect on vascularprostacyclin (PGI2) synthesis, this being 1.4±0.1, 0.5±0.1 and 1.3±0. 3ng/mg wet weight aorta in T and A-treated and control animals respectively. Platelets from T-treated rats were significantly more responsive to inhibition by exogenous PGI2 (0.2-4 ng/ml) and PGE1 (4- 20 ng/ml). when compared with controls. T administration (30-300 mg/kg) resulted in a dose-dependent inhibition of ADP-induced platelet aggregation (26.0- 87. 5%) and enhancement of platelet reactivity to PGI2 (37.0-159.8%). There was a good correlation between these parameters (r=+0.994). T is a potent inhibitor of platelet aggregati on with a novel mode of action. It is not aspirin-like, but may act to potentiate endogenous PGI2 in vivo, possibly through an effect on platelet adenylate cyclase.
Interactions Between Acrosin and the Coagulation System
Authors: Bang N. U. , Mattler L.E. , Burck P.J. , marks C. A. , Zimmerman R.E.
Published: May 2019

Highly purified acrosin (A), the serine protease of the acrosome; which facilitates penetration of sperm through the zona pellucida, rapidly hydrolyzes tri- and tetrapeptide synthetic substrates relatively specific for thrombin (T) (S2238, chromozym TH, S2160) and factor Xa (Xa) (S2222) but only minimally hydrolyzes plasmin and plasma kallikrein substrates. A shares other biological properties with T and Xa. A slowly converts highly purified fibrinogen to fibrin and rapidly converts purified bovine prothrombin into T in a factor V or phospholipid-independent fashion. A, like T and Xa, is inhibited by antithrombin Ill; the inhibition is enhanced by heparin. A, like T, is inhibited by the pancreatic secretory trypsin inhibitor of Kazal but not by the Kunitz-Northrop trypsin inhibitor. A, unlike T, is not inhibited by hirudin and does not aggregate platelets. As has been reported for T and other serine proteases, A stimulates the growth of cultured fibroblasts in a concentration-dependent fashion. In T3T mouse fib,Vblasts only A stimulated DNA synthesis; T, plasmin and trypsin had no effect. Although the evolutionary and physiologic implications of similarities between A and clotting serine proteases remain unclear, the observed effect of A on cell proliferation may assign a new role for this enzyme in early embryogenesis.
Platelet Survival Half-Life in Diabetes Mellitus with and without Peripheral Arterial Occlusive Disease
Authors: Kazmier F.J. , Fuster V. , Chesebro J.H. , O’Fallon W. M. , Palumbo P.J.
Published: May 2019

A role for the platelet has been suggested in the pathogenesis and complications of atherosclerosis and diabetes mellitus. Accordingly, as part of a large prospective study on diabetes mellitus, platelet consumption was estimated by 51Cr platelet survival halflife in 4 groups of subjects over age of 50: (1) in 20 control apparently normal individuals free of known risk factors for atherosclerotic disease, (2) in 25 patients (pts) with diabetes, (3) in 29 pts with clinical and objective evidence (by transcutaneous Doppler ultrasound studies) of peripheral arterial occlusive disease (PAOD), and (4) in 28 pts with both diabetes and PAOD.

vs. control:* = 0.03, # p = 0.02, ** p < 0.001

In conclusion, platelet survival was significantly short in 3 groups of pts:in those with diabetes mellitus alone, in those with PAOD and in those with diabetes mellitus associated with PAOD. This data further supports the role of platelets in the pathogenesis and complications of atherosclerosis and diabetes mellitus.
Tissue Culture Urokinase Thrombolytic Treatment in the Management of Massive Pulmonary Embolism (14 patients).
Authors: Brochier Mireille , Griguer P.
Published: May 2019

In 1978, 14 patients with massive or sub-massive pulmonary embolism (PE) were treated in the Intensive Care Unit of this hospital with a tissue culture Urokinase (TCUK). The total dose administered was 2,700,000 IU over 24 hours; Heparin was given concomitantly, at a dose controlled by coagulation tests. Diagnosis was established by angiography which was repeated 24 hours after treatment. Early resolution of the vascular obstructions was 40.6% - 21.2 of the total filling defect. Three recurrent PE were observed. In vivo fibrinolytic activity was confirmed the following parameters .- a fall in plasminogen level from 104.5% ± 1.4 to 51.4% ± 1.4, and increase in unheated fibrin plate lysis from 3.27 mm±0.4 to 33.42 mm ± 19 at 24 hours post treatment. Tolerance of TCUK was excellent and only two cases of mild bleeding were observed. One patient died the death was related neither to the TCUK treatment nor to the PE. when comparing the results from this group of patients with those obtained in a series of 97 patients treated over the last 4 gears with urinary Urokinase, no difference can be detected in the clinical efficacy or in the in vivo fibrinolytic activity of these two types of Urokinase. The authors conclude that tissue culture Uroxinase is a safe and effective treatment in the management of pulmonary embolism.
Localization of the α-Chain Cross-Linking Sites in Human Fibrinogen
Authors: Hessel B. , Savidge G. , Blombäck B.
Published: May 2019

Antisera were raised in rabbits against the fragments Hi2-DSK and N-DSK obtained from cyanogen bromide treatment of human fibrinogen. Sensitive radioimmunoassay techniques were developed to quantitate substances sharing the same antigenic determinants as these fragments. We have found that the cross-linking process in fibrin formation involves the Hi2-DSK region which has its origin in the Aα-chain of fibrinogen. This relationship is based upon the following experimental data: - Fibrin samples produced in the presence and absence of Factor Xllla and Ca++ and thus cross-Linked and non cross-linked respectively were treated with cyanogen bromide. The resulting degradation products were chroraatographed on Sephadex G-100, and radioimmunoassays for Hi2-DSK and N-DSK were performed on the eluates. The elution profiles of Hi2-DSK and N-DSK antigenic determinants demonstrated that Hi2-DSK eluated after N-DSK in non cross-linked fibrin samples but in the cross-linked samples Hi2-DSK eluated before N-DSK. These results demonstrate that the Hi2-DSK region is involved in the cross-linking process in the presence of Factor XIIIa and calcium ions. Fibrin samples produced in the coagulation of whole blood showed a similar cross-linking profile.

Supported by The Bank of Sweden Tercentenary Foundation.
Fibrinogen Bβ Chain Proteolysis by Thrombin and Plasmin - A Regulatory Mechanism in Hemostasis and Thrombosis
Authors: Nossel H.L. , Canfield R. , Kaplan K. , Kernoff P. , LaGamma K. , Owen J. , Wasser J. , Yudelman I.
Published: May 2019

Thrombin cleaves fibrinogen in two steps producing fibrin I and fibrinopeptide A(FPA) and then fibrin II and fibrinopeptide B(FPB). Plasmin cleaves the Aα chain and the N-terminal Bβ chain to form fragment X. Radioiimminoassay of plasma FPA reflects fibrin I formation. A modified FPB assay detects plasm in-produced Bβ1-42, reflecting fragment X formation. Sequential changes have been studied in saline abortion and in venous thrombosis. Following intra-uterine infusion of hypertonic saline to interrupt pregnancy, FPA levels rose immediately from 1 to 18 pmol/ml in 60 minutes, and after 2 hours began to slowly decline to the baseline level. Bβ1-42 levels rose rapidly after the first hour to reach 67 pmol/ml at 4 hours. Thus fibrin I was formed and then fragment X. In post-surgical patients FPA levels rose and exceeded Bβ1-42 levels for several days preceding thrombosis indicated by 125I-fibrinogen scanning and confirmed by venography. These results suggest that following injury thrombin forms fibrin I. Each fibrin I molecule is then either cleaved by thrombin to form fibrin II or by plasmin to form fragment X. The balance between thrombin and plasmin proteolysis of the N-terminal Bβ chain may be critical. Normally sufficient fibrin II formation occurs for effective hemostasis. Thrombosis occurs with excessive thrombin action and fibrin II formation. Slow thrombin formation as in hemophilia results in preferential formation of fragment X and ineffective hemostasis.
Contribution of Sialic Acid to the Heterogeneity of Human Fibrinogen Polypeptide Chains
Authors: Kuyas C. , Haeberli A. , Straub P.W
Published: May 2019

Human fibrinogen, isolated from single donor or from pooled plasma, shows a heterogeneity of the Bऔ- and the γ-polypeptide chains on CM-cellulose chromatography. In order to find out whether this heterogeneity is due to the observed differences in sialic acid content of the variants (2 and 1 residue per chain; Gati et al., J.Biol.Chem.253:1315,1978) pooled or single donor fibrinogen (clottability 93-95%) was incubated 24 hrs with either vibrio cholerae sialidase or buffer. The asialofibrinogen (10% of original sialic acid) was compared with intact fibrinogen. After dithiothreitol reduction and alkylation the chains were separated on CM Sepharose. The individual homogeneous Bऔ- and γ-chains were rechromatographed on CM-cellulose. The γ-chain heterogeneity of normal fibrinogen was absent in asialofibrinogen whereas the Bऔ-chain heterogeneity appeared unaffected. Although the variants were indistinguishable on SOS-PAGE, isoelectric focusing in presence of urea demonstrated heterogeneities of both Bऔ- and γ-chains even in asialofibrinogen. Thus, the differences in sialic acid content of the main polypeptide chain variants of pooled as wel l as single donor human fibrinogen can only explain a small part of the polypeptide chain heterogeneity.
Interaction of Activators, Inhibitors and Plasminogen with Each other and with Fibrin
Authors: Wallén P , Rånby M
Published: May 2019

Fibrin seems to have an important regulating function for both activating and inhibiting processes. Both plasminogen and plasminogen activators are specifically adsorbed to fibrin. This is in particular the case for the tissue plasminogen activator (TA). which is very strongly adsorbed to fibrin. Fibrin in complex with plasminogen and TA greatly enhances
the activation. Thus the rate of activation is increased about 40-fold in the presence of a soluble fibrin polymer whereas fibrinogen only has a weak effect. Fibrin prepared from fragment X lacking the C-terminal parts of both α-chains has significantly lower stimulating power than native fibrin. This is in accordance with the finding that a fragment with affinity for TA has been isolated from the C-terminal part of the A-chain. If native plasminogen is replaced by low Mw-plasminogen obtained by elastase cleavage the stimulating activity of fibrin disappears indicating that the lysine binding sites in the N-terminal part of plasminogen are of functional importance for the TA-induced fibrinolysis. Recent studies indicate that fibrin competes with α2 -antiplasmin for lysine binding sites and the active site in plasmin (Wiman and Collen, Nature 272, 549, 1978). Thus plasmin occupied with fibrin degradation would largely be unaccessible for α2-antiplasmin whereas free plasmin is very rapidly inactivated.
Sex Differences in Platelet Response to Aspirin
Authors: Coppe D. , Harris W.H. , Ransil B.J. , Salzman E.W.
Published: May 2019

To understand the reported (NEJM 297:1246; 299:53) sex difference in antithrombotic effectiveness of aspirin (ASA), we studied ASA pharmacokinetics and ASA’s effect on hemostasis and platelet function in patients undergoing totai hip replacement who received either 1.2 gm or 3.6 gm daily. Platelets from women aggregated more with epinephrine and collagen than did those from men, and, although ASA inhibited aggregation in both sexes, the sex difference persisted after ASA. The response did not correlate with ASA dosage. Serotonin release was initially greater with platelets from females but was abolished by ASA in both sexes. Platelet counts were higher in women (p<0.05). There was no sex difference in platelet malondialdehyde production or its inhibition by ASA or in basal values or ASA’S effect on bleeding time or fibrinolytic activity in whole blood. Serum ASA esterase activity was similar in the two sexes. Plasma salicylate levels were higher in women.

No difference was observed in ASA’s effect in the two sexes. The sex difference in the antithrombotic efficacy of aspirin may relate to ASA’s failure to eliminate the preexistent sex difference in platelet count and aggregability.
Blood Fibrinolysis in Subjects with Risk Factors and in Patients with Peripheral Atherosclerotic Arterial Disease
Authors: Steqnar H. , Accetto B.
Published: May 2019

Depressed fibrinolysis is common in subjects with risk factors for atherosclerosis as well as in patients with peripheral atherosclerotic arterial disease (PAAD). In order to establish changes in fibrinolysis related either to risk factors alone or to PAAD, separate components of the fibrinolytic enzyme system were studied in the plasma of 13 young males, in 11 males with risk factors and in 34 natlents with PAAD, arranged into 3 qro-ups according to the progression of the disease.

Results show lower plasminogen activator activity, higher antiurokinase activity, higher fibrinogen and flbrinogen/fIbrin degradation product concentrations in risk and PAAD groups compared to the healthv controlsFurther significant changes in PAAD rtroups were observed in fibrinogen, total antlplasmln and alpha-1-antitrypsin activity, beina most pronounced in th. most advanced PAAD group.

From the results we concluded that fibrinolysis in PAAD is depressed due to elevated levels of plasmin Inhibitors in addition to chances already observed in subjects with risk factors. High concentration of fibrinogen probably favours progression of the disease.
Platelet Prostaglandin F2α(PFG2α) in Atherosclerosis
Authors: Gürsoy Ayla , Alev Ozbllen , Ulutin Orhan N.
Published: May 2019

This study was done with the clinically evaluated atherosclerotic cases that showed hyperaggregability, hypersecretion and increased adhesion of platelets, as well as platelet phospholipid changes. Using radio immunoassay (RIA) we have measured PGF2α which was formed by human platelet in response to collagen. Synthesis of PGF2α by freeze-thawed platelets and in platelet rich plasma (PRP) incubated with different amounts of collagen were also investigated.

Incubation of atherosclerotic patients’ PRP with collagen at 37°C for 5 minutes showed an increase in the amount of PGF2α compared to normal controls.
Affinity Labeling of Human Thrombins with Extended Benzamidine Sulfonylfluoride Exo-Site Reagents
Authors: Bing D.H. , Fenton J.W. , Sonders S.
Published: May 2019

The reagent m[o-(2-chloro-5-fluorosulfonylphenylureido)phenoxybutoxy]benzamidine [mCP(PBA)-F] is an exo-site affinity labeling reagent for human thrombins. To delineate the sites of the reacticn of mCP(PBA)-F on thrombin (Th), experiments were done with three structurally related variants of mCP(PBA)-F in which the distijnce from the cationic amidino portion to the reactive sulfonylfluoride was varied by 5-6 A. In clotting inhibition assays the reagent m[o-(2-chloro-5-fluorosulfonylphenylamido)phenoxypropoxy]benzamidine (t½ = 99.4 ± 7.8 sec, klst = 6970 ± 550 × 106 sec-l n=5) was 2-fold more inhibitory than mCP(PBA)-F (t½ = 200 ± 10.1 sec, klst = 3460 ± 150 x 12-6 sec-1 n=5). Minimal energy models of the compounds show the optimum length is 14-17 Å. In other experiments hirudin (9600 μ/mg, gift F. Markwardt) mixed with 13.1 μM α (clotting) or 12.1 ±M γ/β (nonclotting) Th in 1- to 3-fold molar excess did not prevent incorporation of [3H]mCP( PBA)-F (0.961-0.794 mole label/mole Th) but did inhibit [3H]diisopropylfluorophosphate (iPr2P-F) uptake (.096-.005 mole label/mole Th). mCP(PBA)-Th had reduced binding for proflavin (Kd ≈ 9-fold that of Th) but not as low as iPr2P-Th (Kd : 38-fold that of Th) and further suggests that mCP(PBA)-F is attached to Th at points distal to the catalytic site. These new data show that mCP(PBA)-F reacts at nonclotting related but specific secondary sites on Th and that mCP(PBA)-F can be used to identify the structural features associated with the uniq.ue proteolytic specificity of thrombin. (Supported by NIH and AHA)
Role of α2Plasmin Inhibitor in Fibrinolytic Therapy by Urokinase and the Optimal Urokinase Dosage
Authors: Hayashi S. , Yamada K.
Published: May 2019

A novel plasmin inhibitor, namely α2plasmin inhibitor (α2PI), was found to be more efficient than other plasmin inhibitors but its clinical role in fibrinolytic therapy by urokinase (UK) was not examined. We injected UK into 9 patients with thrombotic diseases at several different doses (2-180×l04 IU/day) in order to estimate the optimal dosage inducing fibrinolysis, ahd to evaluate the role of α2PI in fibrinolysis during UK administration. The correlation coefficients(CE) between UK/day and α2PI, plasminogen (PIg), ulantitrypsin (UIAT) and α2macroglobulin(α2MC) were-0.75, -0.54, 0.39 and -0.37, respectively. Above50×104 of UK/day, the α2PI level fell below 60%, and above 150×10 4 IU of UK/day it fell below 30%. The CE between lysis area on fibrin plate (FPL) and α2PI, α2AT, α2MC, UK/day and PIg were -0.69, 0.51, -0.31, 0.30 and -0.26, respectively. When the level of α2PI fell below 60%, EPL was observed in 13 of 20 samples (65%) , whereas above 60% of α2PI it was observed in only 4 of 35 samples (11%). The above results suggest that α2PI is most important in regUlating fibrinolysis during UK administration and about 50xl0 4IU/day of UK should be infused in order to lower the level of α2PI to below 60%, so inducing prominent fibrinolysis.
On the Euler characteristic of a relative hypersurface
Authors: Fullwood James , Helmer Martin
Published: May 2019

We derive a general formula for the Euler characteristic of a fibration of projective hypersurfaces in terms of invariants of an arbitrary base variety. When the general fiber is an elliptic curve, such formulas have appeared in the physics literature in the context of calculating D-brane charge for M-/F-theory and type-IIB compactifications of string vacua. While there are various methods for computing Euler characteristics of algebraic varieties, we prove a base-independent pushforward formula which reduces the computation of the Euler characteristic of relative hypersurfaces to simple algebraic manipulations of rational expressions determined by its divisor class in a projective bundle. We illustrate our methods by applying them to an explicit family of relative hypersurfaces whose fibers are of arbitrary dimension and degree.
The close connection between the definition and construction of raised and decreased coherent states with the inverse generators in the algebraic description of quantum confined systems
Authors: Aleixo A. N. F. , Balantekin A. B.
Published: May 2019

Using an expanded algebraic formalism with the inclusion of inverse operators, we construct raised and decreased coherent states for a set of exactly solvable quantum confined systems. We assume in this procedure both the ladder-operator and the displacement-operator methods, showing the equivalence between the two approaches. For each coherent state defined, we present its expansion in the Hilbert eigenstate space Hes, eigenvalue equation, overcompleteness relation, as well as other intrinsic properties. Whenever possible, we present an interpretation based on nonlinear deformation models for these new forms of coherent states. We evaluate the relevance of the new coherent states in quantum entanglement and squeezing by taking, as an example, the case of a coupled system.
Structure resonance crossing in space charge dominated beams
Authors: Liu Zhicong , Li Chao , Qin Qing
Published: May 2019

As an extension of a previous theoretical study on the coherent structure resonance due to space charge effects [C. Li and R. A. Jameson, Phys. Rev. Accel. Beams 21, 024204 (2018)], this paper aims to demonstrate how the beam is spontaneously affected when the predicted mixed coherent 2nd/4th order structure resonance stop band around 90° phase advance is crossed. The beam characteristics during the structure resonance crossing as rms emittance growth and the appearance of a 2-fold/4-fold structure in phase space are well explained by the mixture characteristic of different orders of structure resonances. The related “attracting” and “repulsive” effects in the structure resonance stop band from below and above crossing are considered as a natural beam reaction to the structure resonance that the beam spontaneously moves to a structure resonance free region and then the space charge takes a weaker importance. In the paritlce-in-cell simulation, it is found that the emittance growth is positively related to the time the beam spends inside the structure resonance stop band. As a potential candidate mechanism, the incoherent particle-core resonance also has been checked. The incoherent particle-core resonance might lead to phase space distortion, emittance growth, or beam halo formation only on a long-time scale. This clarity of the discrepancies between coherent and incoherent resonance mechanisms will lead to a better understanding of the numerical and experimental research studies.
Long time aging effect on Be-implanted GaN epitaxial layer
Authors: Chen J. L. , Peng Y. , Zhang X. , Wei W. W. , Zhong S. K. , He K. Y. , Wang L. S. , Zhang J. C. , Chen Z. Q. , Sun W. H.
Published: May 2019

Be-implanted GaN thin films grown by low-pressure Metalorganic Chemical Vapor Deposition (LP-MOCVD), the postimplantation rapid thermal annealing (RTA) samples and the postimplantation RTA samples after 18 years’ room temperature (RT) aging were investigated by Resonant Raman scattering (RRS). It was observed that the Resonant Raman scattering intensity is most enhanced in the 4th order A1 (LO) mode in the after aging sample rather than both the 4th and 5th order A1(LO) mode at different temperatures in the postimplantation RTA sample, which is attributed to a different prominent laser excited emission involved in the RRS processes in the sample before and after aging. A jump step of the intensities of RRS modes was observed at 170 K. Based on the temperature dependent and power dependent RRS spectra, we estimate quantitatively the properties of the optical emission participated in RRS processes below and above this temperature, with the assumption that the intensity of the RRS modes is linearly proportional to the intensity of the optical emission involved in it. We obtained the activation energy of 65 meV and 85 meV for two emissions, respectively, and confirmed both emissions are not band edge related emission with power density dependent RRS spectra. We proposed the dominant optical emission changed from band edge emission to dopant related emission after aging. This study provides an evidence of evolution of optical properties and microstructures in postimplantation RTA GaN epilayers over long time RT aging, which could be a benefit to studying reliability control of devices based on this material.
Symmetry in a space of conceptual variables
Authors: Helland Inge S.
Published: May 2019

A conceptual variable is any variable defined by a person or by a group of persons. Such variables may be inaccessible, meaning that they cannot be measured with arbitrary accuracy on the physical system under consideration at any given time. An example may be the spin vector of a particle; another example may be the vector (position and momentum). In this paper, a space of inaccessible conceptual variables is defined, and group actions are defined on this space. Accessible functions are then defined on the same space. Assuming this structure, the basic Hilbert space structure of quantum theory is derived: Operators on a Hilbert space corresponding to the accessible variables are introduced; when these operators have a discrete spectrum, a natural model reduction implies a new model in which the values of the accessible variables are the eigenvalues of the operator. The principle behind this model reduction demands that a group action may also be defined also on the accessible variables; this is possible if the corresponding functions are permissible, a term that is precisely defined. The following recent principle from statistics is assumed: every model reduction should be to an orbit or to a set of orbits of the group. From this derivation, a new interpretation of quantum theory is briefly discussed: I argue that a state vector may be interpreted as connected to a focused question posed to nature together with a definite answer to this question. Further discussion of these topics is provided in a recent book published by the author of this paper.
Magnetothermodynamics: An experimental study of the equations of state applicable to a magnetized plasma
Authors: Kaur M. , Brown M. R. , Light A. D.
Published: May 2019

Measuring the equations of state of a compressed magnetized plasma is important for both advancing fusion experiments and understanding natural systems such as stellar winds. In this paper, we present results from our experiments on the thermodynamics of compressed magnetized plasmas; we call these studies “magnetothermodynamics.” In these experiments, we generate parcels of relaxed, magnetized plasma at one end of the linear Swarthmore Spheromak eXperimental device and observe their compression in a closed conducting boundary installed at the other end. Plasma parameters are measured during compression. Instances of ion heating during compression are identified by constructing a pressure-volume diagram using the measured density, temperature, and volume of the magnetized plasma. An axial scan of the ion temperature at upstream locations suggests that the increase in ion temperature arises due to the compression of the magnetized plasma in the conducting boundary. The theoretically predicted magnetohydrodynamic (MHD) and double adiabatic equations of state are compared with experimental measurements to estimate the adiabatic nature of the compressed plasma. The equilibrium of our magnetized plasmas is well-described by magnetohydrodynamics; however, we find that the MHD equation of state is not supported by our data. Our results are more consistent with the parallel Chew-Goldberger-Low equation of state, suggesting that there is significant anisotropy in the ion distribution function.
Separation induced low-frequency unsteadiness in a supersonic combustor with single-side expansion
Authors: Chen Chongpei , Gao Tianyun , Liang Jianhan
Published: May 2019

Systematic studies on separation induced low-frequency unsteadiness in a canonical supersonic combustor are implemented through wind tunnel experiment and numerical simulation. With an inflow Mach number of 3, cold flow analysis has been carried out to focus on the key impact factor of flow instability. Dynamic flow features are captured by high-frequency pressure signals, and three-dimensional Reynolds-Averaged Navier-Stokes simulation is performed to represent the typical unsteady movement of the shock train. The separated flowfield shows an intrinsic instability, whose feature is the large-amplitude and low-frequency streamwise movement of the oblique shock train. The oscillation of shock train is in a broadband frequency range, and pressure signals obtained from different streamwise regions behave various features. The intermittent region and the backpressure-affected region are two major resources of oscillation energy. Numerical results represent variable-speed shock train motions with multiple amplitudes, and broadband behaviors in experiments are captured. The autocorrelation analysis shows that the broadband behavior of the unsteadiness is not caused by the white noise. From the coherence analysis, it is found that two kinds of oscillation modes (independent and synchronous) exist in the flowfield. The independent mode exists extensively in the unstable flow, while the synchronous mode only appears occasionally and is always suppressed in the very-low-frequency band (below 80 Hz). Repeated experiments indicate that signals from these two oscillation modes superpose randomly. The phase analysis reveals that the backpressure is the original source of this complicated unstable separated flow.
An echelon-based single shot optical and terahertz Kerr effect spectrometer
Authors: Mead Griffin , Katayama Ikufumi , Takeda Jun , Blake Geoffrey A.
Published: May 2019

We report on the design and performance of an echelon-based single shot visible/near-infrared spectrometer with adequate sensitivity to measure the nonlinear optical and terahertz Kerr effects in neat molecular liquids at room temperature. Useful molecular information spanning tens of picoseconds can be measured in just a few milliseconds, and the signal-to-noise performance scales favorably with respect to the standard stage scan technique. These results demonstrate the viability of stage-free nonlinear Kerr effect measurements and provide a route for improvements to the speed of future multidimensional Kerr effect studies.
First-principles study on sum-frequency generation spectroscopy of methanol adsorbed on TiO2(110) surface: Effects of substrate and molecular coverages
Authors: Shen Zhitao , Lin Chih-Kai , Zhu Chaoyuan , Lin Sheng Hsien
Published: May 2019

In this work, starting from the general theory of sum-frequency generation (SFG), we proposed a computational strategy utilizing density functional theory with periodic boundary conditions to simulate the vibrational SFG of molecules/solid surface adsorption system. The method has been applied to the CH3OH/TiO2(110) system successfully. Compared with the isolated molecule model, our theoretical calculations showed that the TiO2 substrate can significantly alter the second-order susceptibilities of a methanol molecule which is directly related to the SFG intensity. In addition, the SFG spectra have obvious changes while the methanol coverage increases, especially for the OH vibration peaks. Our theoretical spectra agree reasonably well with experimental measurements at 1 ML coverage, and an interesting peak which is absent in the theoretical spectra is tentatively assigned to some CH3 stretch vibration of methanol adsorbed on the oxygen vacancy of TiO2.