bluuebunny/crossref_metadata_2025 huggingface dataset:
Barlenses in the CALIFA survey: Combining photometric and stellar population analyses
Authors: Laurikainen E. , Salo H. , Laine J. , Janz J.
Published: July 2018

Aims: It is theoretically predicted that, at low galaxy inclinations, boxy/peanut bar components have a barlens appearance of a round central component embedded in the narrow bar. We investigate barlenses in the Calar Alto Legacy Integral Field Area (CALIFA) survey galaxies, studying their morphologies, stellar populations, and metallicities. We show that, when present, barlenses account for a significant portion of light of photometric bulges, i.e., the excess light on top of the disks, which highlights the importance of bars in accumulating central galaxy mass concentrations in the cosmic timescale.

Methods: We made multi-component decompositions for a sample of 46 barlens galaxies drawn from the CALIFA survey, whereM⋆/M⊙= 109.7− 1011.4andz= 0.005 − 0.03. Unsharp masks of the Sloan Digital Sky Survey (SDSS)r′-band mosaics were used to identify the boxy/peanut or X-shaped features. Barlenses are identified in the images using our simulation snapshots as an additional guide. Our decompositions with GALFIT include bulges, disks, and bars as well as barlenses as a separate component. For 26 of the decomposed galaxies the CALIFA DR2 V500 grating data cubes were used to explore stellar ages and metallicities at the regions of various structure components.

Results: We find that 25 ± 2% of the 1064 galaxies in the whole CALIFA sample show either X-shaped or barlens features. In the decomposed galaxies with barlenses, on average 13% ± 2% of the total galaxy light belongs to this component, leaving less than 10% for possible separate bulge components. Most importantly, bars and barlenses are found to have similar cumulative stellar age and metallicity distributions. The metallicities in barlenses are on average near solar, but exhibit a large range. In some of the galaxies barlenses and X-shaped features appear simultaneously, in which case the bar origin of the barlens is unambiguous.

Conclusion: This is the first time that a combined morphological and stellar population analysis is used to study barlenses. We show that their stars are accumulated in a prolonged time period concurrently with the evolution of the narrow bar.
Insights into the inner regions of the FU Orionis disc
Authors: Siwak Michał , Winiarski Maciej , Ogłoza Waldemar , Dróżdż Marek , Zoła Stanisław , Moffat Anthony F.J. , Stachowski Grzegorz , Rucinski Slavek M. , Cameron Chris , Matthews Jaymie M. , Weiss Werner W. , Kuschnig Rainer , Rowe Jason F. , Guenther David B. , Sasselov Dimitar
Published: July 2018

Context. We investigate small-amplitude light variations in FU Ori occurring in timescales of days and weeks.

Aims. We seek to determine the mechanisms that lead to these light changes.

Methods. The visual light curve of FU Ori gathered by the MOST satellite continuously for 55 d in the 2013–2014 winter season and simultaneously obtained ground-based multi-colour data were compared with the results from a disc and star light synthesis model.

Results. Hotspots on the star are not responsible for the majority of observed light variations. Instead, we found that the long periodic family of 10.5–11.4 d (presumably) quasi-periods showing light variations up to 0.07 mag may arise owing to the rotational revolution of disc inhomogeneities located between 16 and 20 R⊙. The same distance is obtained by assuming that these light variations arise because of a purely Keplerian revolution of these inhomogeneities for a stellar mass of 0.7 M⊙. The short-periodic (∼3 – 1.38 d) small amplitude (∼0.01 mag) light variations show a clear sign of period shortening, similar to what was discovered in the first MOST observations of FU Ori. Our data indicate that these short-periodic oscillations may arise because of changing visibility of plasma tongues (not included in our model), revolving in the magnetospheric gap and/or likely related hotspots as well.

Conclusions. Results obtained for the long-periodic 10–11 d family of light variations appear to be roughly in line with the colour-period relation, which assumes that longer periods are produced by more external and cooler parts of the disc. Coordinated observations in a broad spectral range are still necessary to fully understand the nature of the short-periodic 1–3 d family of light variations and their period changes.
A thermodynamically consistent model of a liquid-vapor fluid with a gas
Authors: Mathis Hélène
Published: July 2018

This work is devoted to the consistent modeling of a three-phase mixture of a gas, a liquid and its vapor. Since the gas and the vapor are miscible, the mixture is subjected to a non-symmetric constraint on the volume. Adopting the Gibbs formalism, the study of the extensive equilibrium entropy of the system allows to recover the Dalton’s law between the two gaseous phases. In addition, we distinguish whether phase transition occurs or not between the liquid and its vapor. The thermodynamical equilibria are described both in extensive and intensive variables. In the latter case, we focus on the geometrical properties of equilibrium entropy. The consistent characterization of the thermodynamics of the three-phase mixture is used to introduce two Homogeneous Equilibrium Models (HEM) depending on mass transfer is taking into account or not. Hyperbolicity is investigated while analyzing the entropy structure of the systems. Finally we propose two Homogeneous Relaxation Models (HRM) for the three-phase mixtures with and without phase transition. Supplementary equations on mass, volume and energy fractions are considered with appropriate source terms which model the relaxation towards the thermodynamical equilibrium, in agreement with entropy growth criterion.
Diagnostic Value of Cardiac Magnetic Resonance Strain Analysis for Detection of Cardiac Sarcoidosis
Authors: Dabir Darius , Meyer David , Kuetting Daniel , Luetkens Julian , Homsi Rami , Pizarro Carmen , Nadal Jennifer , Thomas Daniel
Published: July 2018

Purpose The aim of this study was to investigate the diagnostic value of cardiac magnetic resonance (CMR)-derived strain parameters in patients with sarcoidosis, and to compare results to standard CMR markers of sarcoidosis (edema/T2 ratio, early gadolinium enhancement, late gadolinium enhancement) for prediction of disease outcome.

Materials and Methods 61 patients with biopsy-proven sarcoidosis underwent CMR examination. According to CMR results, patients were divided into two different groups: patients with (CMR+; n = 23) and without (CMR–; n = 38) findings consistent with cardiac sarcoidosis. In addition, a group of healthy age-matched volunteers (controls; n = 22) served as controls. Left ventricular functional parameters as well as left ventricular longitudinal and circumferential strain were evaluated in all three groups.

Results Compared to controls, global longitudinal strain (GLS) was significantly impaired in patients with sarcoidosis, irrespective of cardiac involvement. No significant differences in GLS could be revealed between CMR+ and CMR– patients. Circumferential strain parameters were significantly impaired in CMR+ patients in comparison to CMR– patients and controls, while no significant differences could be revealed between CMR– patients and controls. GLS was significantly lower in patients with a negative outcome compared to controls. Compared to the rest of the CMR+ and CMR– patients, the GLS in patients with a negative outcome was further reduced but did not reach statistical significance.

Conclusion GLS is the only strain parameter detecting left ventricular functional impairment in sarcoidosis patients with otherwise unsuspicious CMR and controls. GLS is further reduced in patients with a negative outcome. Thus, GLS may have the potential to serve as a marker for early cardiac involvement in sarcoidosis.

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Die Hand im Fokus – Schnittstellen zwischen Chirurgie und Gefäßmedizin
Authors: Wahl Uwe , Klemenz Albrecht , Hirsch Tobias
Published: July 2018

Vibrationsbedingte Schädigungen an den Händen werden bei einer Reihe von Handwerksberufen, aber auch im Zusammenhang mit der Ausübung verschiedener Sportarten beobachtet. Knöcherne, neurogene, aber auch Gefäßläsionen können zu chronischen Beschwerden und einer dauerhaften funktionellen Beeinträchtigung führen. Aus gefäßmedizinischer Sicht sind das Hand-Arm-Vibrationssyndrom (HAVS) sowie das Hypothenar-/Thenar-Hammer-Syndrom (HHS, THS) von Interesse. Aus chirurgischer Sicht ergibt sich eine besondere Bedeutung aus der Tatsache, dass es sich bei beiden Syndromen um anerkannte Berufskrankheiten handelt (BK 2104 bzw. BK 2114), die auch im Rahmen der durchgangsärztlichen Versorgung sowie in der Begutachtung gewürdigt werden müssen. Das Hypothenar-/Thenar-Hammer-Syndrom wird ausgelöst durch wiederholte Krafteinwirkung im Bereich des Kleinfinger- oder Daumenballens und ist gekennzeichnet durch eine traumatische Läsion der A. ulnaris oder A. radialis, die zu ischämiebedingten Schmerzen im akralen Versorgungsgebiet der betroffenen Handarterien i. d. R. der dominanten Hand führt. Liegt eine erhöhte Kältesensibilität mit vasospastischen Durchblutungsstörungen infolge einer Exposition zu vibrierenden Werkzeugen und Maschinen vor, spricht man von einem Hand-Arm-Vibrationssyndrom. Die Arbeit stellt verschiedene klinische und funktionsdiagnostische Tests zur Diagnosestellung vor. Dabei kommt der doppler- und duplexsonografischen Exploration ein besonderer Stellenwert zu. Verschiedene radiologische Methoden können die Diagnostik ergänzen. Zur Behandlung der Symptome sind medikamentöse und auch physiotherapeutische Behandlungsansätze zu verfolgen, die über eine Stimulation der Vasodilatation eine Verbesserung der Perfusion bewirken sollen. Eine wirksame Kausaltherapie steht jedoch nicht zur Verfügung. Aus diesem Grund muss im Rahmen einer Begutachtung die besondere Aufmerksamkeit speziell der Anamneseerhebung mit einer zweifelsfreien Zuordnung von auslösender Noxe und Körperschaden gelten, da sich daraus für den Geschädigten sozialmedizinische bzw. rentenrelevante Konsequenzen ergeben können.
Knie-TEP-Verankerung bei Revision und schlechten Knochenverhältnissen. Knochen, Zement, Schaft, Sleeve, Konus?
Authors: Sentürk Ufuk , Perka Carsten
Published: July 2018

Nach aktuellen Registerdaten muss von einer erheblichen Steigerung von Revisionsoperationen in der Kniegelenksendoprothetik ausgegangen werden. Diese gehen häufig mit ausgeprägten knöchernen Defekten einher. Die stabile und korrekte Implantatverankerung ist und bleibt eine Herausforderung. Voraussetzung für langfristige und reproduzierbare Ergebnisse ist die Auswahl der korrekten Rekonstruktions- und Verankerungsstrategie unter Beachtung des vorliegenden Knochendefekts sowie der patientenspezifischen Anatomie.
Interventional Treatment of Acute Portal Vein Thrombosis
Authors: Wolter Karsten , Decker Georges , Kuetting Daniel , Trebicka Jonel , Manekeller Steffen , Meyer Carsten , Schild Hans , Thomas Daniel
Published: July 2018

Background Acute portal vein thrombosis is a potentially fatal condition. In symptomatic patients not responding to systemic anticoagulation, interventional procedures have emerged as an alternative to surgery. This study sought to retrospectively evaluate initial results of interventional treatment of acute portal vein thrombosis (aPVT) using a transjugular interventional approach.

Materials and Methods Between 2014 and 2016, 11 patients were treated because of aPVT (male: 7; female: 4; mean age: 41.06 years). All patients presented a rapid onset of symptoms without collateralization of portal flow as assessed by a CT scan at the time of admittance. The patients showed thrombotic occlusion of the main portal vein (11/11), the lienal vein (10/11) and the superior mesenteric vein (10/11). Different techniques for recanalization were employed: catheter thromboaspiration (1/9), AngioJet device (7/9), local-lysis-only (1/9) and TIPSS (7/9). Local lysis was administered using a dual (4/9) or single (5/9) catheter technique. The mean follow-up was 24.32 months.

Results In 9 patients transhepatic access was successful. Initially reduction of thrombus load and recanalization were achieved in all 9 cases with residual thrombi in PV (n = 3), SMV (n = 7), and IL (n = 5). In the collective undergoing interventional procedures (n = 9) rethrombosis and continuous abdominal pain were seen in one patient, and thrombus progression after successful recanalization was seen in another. Freedom from symptoms could be achieved in 6 patients. One patient developed peritoneal and pleural effusion, respiratory insufficiency and portosystemic collaterals. Both patients who could not undergo an interventional procedure developed a cavernous transformation of the portal vein. One of them also had continuous intermittent abdominal pain.

Conclusion Interventional percutaneous approaches are able to improve patient outcome in patients with aPVT. It appears to be of utmost importance to not only remove/reduce the thrombotic material but to establish sufficient inflow and outflow by TIPS and simultaneous multi-catheter thrombolysis.

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Stellungnahme
Authors: Baur Eva-Maria , Nitto Agnese , Loizides Alexander , Gruber Hannes
Published: July 2018

von Dr. Nitto auf den Leserbrief von Prof. Dr. Staub und Mitar. bzgl. ihrer Arbeit Nitt A, Baur EM, Gruber H, Löscher W, Loizides A, Mattesich M, Pülzl P.
Betreffend der Wrist-to-Forearm-Ratio des N. medianus ist die Sonographie zur Verlaufskontrolle nach Operation eines Karpaltunnelsyndroms ungeeignet.
Handchir Mikrochir Plast Chir 2018; 50: 14-18.
Interaction Study between Org 10172, a Low Molecular Weight Heparinoid, and Acetylsalicylic Acid in Healthy Male Volunteers
Authors: de Boer A , Danhof M , Cohen A F , Magnani H N , Breimer D D
Published: July 2018

Potential interactions between Org 10172 (Lomoparan®; i. v. bolus injection of 3,250 anti-Xa units followed by 750 units twice daily s. c. for 8 days) and acetylsalicylic acid (ASA) (500 mg orally 14 and 2 h before i. v. Org 10172 administration) were studied in eight healthy male volunteers using an open, randomised three-way cross-over design. Except for moderate bruising at venepuncture and s.c. injection sites which were equally distributed over all three treatments (Org 10172 alone, ASA alone, Org 10172 and ASA combined), no side effects were observed. The effects of the separate drugs on several haemostatic parameters were as expected, although the prolongations in bleeding time after ASA were highly variable and tended to be somewhat more pronounced after the combination (p >0.05). Org 10172 did not influence the inhibiting effects of ASA on platelet function nor the functional recovery afterwards, as evaluated by thromboxane A2 (TXA2) generation and collagen-induced platelet aggregation. Furthermore, no important interactions were observed with regard to the coagulation tests and plasma anti-Xa activity. Although this study did not entirely exclude small interactions between Org 10172 and ASA in this relatively small group of subjects, these effects are probably without clinical significance.
Dexamethasone and Phorbol Ester, but not Cytokines, Increase the Production of Plasminogen Activator Inhibitor Type-2 in the PL-21 Human Promyelocytic Leukemia Cell Line
Authors: Niiya Kenji , Takeuchi Tetsuo , Kobayashi Makoto , Miyoshi Isao , Hayashi Tomohiro , Sakuragawa Nobuo
Published: July 2018

PL-21 is a promyelocytic leukemia cell line that produces plasminogen activator inhibitor 2 (PAI-2). Differentiation-linked expression of PAI-2 was investigated by adding cell-differentiation promoting agents [such as phorbol myristate acetate (PMA), retinoic acid (RA), dexamethasone (Dex), and recombinant cytokines, including tumor necrosis factor-α (TNF-a), transforming growth factor-β (TGF-β), granulocyte-colony stimulating factor (G-CSF), and interleukin-6 (IL-6)] into the culture medium of PL-21 cells. PAI-1 and PAI-2 antigens were measured by an enzyme-linked immunoassay. The PAI-1 antigen, however, became detectable only after stimulation. The presence of PAI-2 antigen was further verified by immunoblotting using a monoclonal antibody against PAI-2 purified from a PL-21 culture medium. PAI activity both in the culture medium and in the cell lysate increased approximately 70-fold after exposure to PMA. Both PAI-1 and PAI-2 antigens increased, but the amount of the latter in the culture medium and in the cell lysate was approximately 10 times and 2,500 times, as much, respectively, as that of the former. Dex also increased the intracellular PAI activity approximately 6-fold, parallel with PAI-2 antigen. PAI-1 antigen increased only slightly in the culture medium but not in the cell lysate after Dex-stimulation. As with the case of PMA, TNF-a and IL-6 induced PL-21 cells to macrophage-like cells, but did not affect the PAI activity. Thus, the increase of the PAI-2 production by PMA may not necessarily depend on differentiation into macrophages. Other cytokines examined did not increase the PAI activity. Glucocorticoid has various effects on the fibrinolytic system because it has been also shown that the mRNA of PAI-2 in a human fibrosarcoma cell line decreases in response to Dex.
Normal ADP-Induced Aggregation and Absence of Dissociation of the Membrane GP IIb-IIIa Complex of Intact Rat Platelets Pretreated with EDTA
Authors: Gachet Christian , Stierlé Anita , Ohlmann Philippe , Lanza François , Hanau Daniel , Cazenave Jean-Pierre
Published: July 2018

ADP-induced platelet aggregation requires the presence of external calcium and fibrinogen. When human platelets are incubated for 30 min at 37° C with 5mM EDTA and then resuspended in a calcium containing medium, they lose their ability to bind fibrinogen and to aggregate in response to ADP stimulation. Under these conditions, the effect of EDTA is irreversible and accompanied by dissociation of the glycoprotein (GP) IIb-IIIa complex into its free subunits, GP IIb and GP IIIa. We studied the effect of incubation of intact rat platelets with 5 mM EDTA at 37° C from 30 to 120 min. EDTA treated rat platelets showed normal aggregation in response to 5 εM ADP in the presence of added purified rat fibrinogen and bound 125I-labeled rat fibrinogen at the same rate and magnitude after stimulation with 5 εM ADP as untreated platelets. Control and EDTA treated rat platelets, labeled or not with 125I and solubilized in Triton X-100, had a similar pattern of immunoprecipitates after crossed immunoelectrophoresis (CIE) analysis. The rat GP IIb-IIIa arc was located by incorporation of an 125I-labeled polyclonal anti-human GP IIb-IIIa antibody. In contrast, in experiments using rat platelet lysates, we demonstrated that the rat GP IIb-IIIa is a Ca2+-dependent heterodimer as it was dissociated by EDTA. Using SDS-PAGE and two-dimensional SDS-PAGE, the rat GP IIb-IIIa complex was found to have characteristics similar to the human complex with the exception that the light chain of the rat GP IIb was undetectable after 125I surface labeling. Small structural particularities of rat GP IIb-IIIa might still explain the functional differences observed between intact rat and human platelets treated with EDTA.
Factor IXa Inhibition Contributes to the Heparin Effect
Authors: Béguin Suzette , Dol Frédérique , Hemker H Coenraad
Published: July 2018

We investigated whether the inactivation of factor IXa contributes to the partial inhibition of thrombin formation that is observed at therapeutic concentrations of heparin. The action of standard unfractionated heparin (0.05 U/ml) on thrombin formation in the intrinsic system was compared to that of a mixture of dermatan sulfate (DS) and a synthetic pentasaccharide (PS). DS enhances the action of heparin cofactor II which inhibits thrombin only. PS specifically enhances the anti-factor Xa activity of antithrombin III (AT III). The concentrations of DS and PS were chosen so as to obtain equal anti-thrombin and anti-factor Xa activities as in 0.05 U/ml heparin. An extra inhibitory effect of heparin over the mixture is observed in situations where free factor IXa, not bound to factor VIIIa and phospholipid, limits the rate of thrombin formation, notably in contact activated plasma. We conclude that the inactivation of free factor IXa by heparin contributes importantly to the inhibition of thrombin formation in the intrinsic system such as e.g. measured in the activated partial thromboplastin time.
Dipyridamole Potentiates Platelet Inhibition by Nitric Oxide
Authors: Bult Hidde , Fret Hermine R L , Jordaens François H , Herman Arnold G
Published: July 2018

In a placebo-controlled double blind cross-over experiment the adenosine uptake inhibitor dipyridamole (400 mg/day) did not affect ex vivo platelet aggregation induced by collagen or adenosine-diphosphate (ADP) in an electronic whole blood aggregometer (WBA). Dipyridamole was also inactive in vitro, unless red blood cell injury was deliberately enhanced, thereby increasing the level of free adenine nucleotides. Since dipyridamole also inhibits cyclic guanosine monophosphate (GMP) phosphodiesterase (PDE), we used platelet rich plasma (PRP) to study its interaction with authentic and endothelium-derived nitric oxide (NO). The latter inhibits platelets by increasing cyclic GMP. Dipyridamole (1 to 30 εM), either alone or in combination with a subthreshold concentration of prostacyclin (PGI2), was inactive. However, when combined with a subthreshold concentration of NO, dipyridamole caused a concentration-dependent platelet suppression, which became more pronounced when PGI2 was present as well. It is concluded that dipyridamole could reduce the threshold for platelet suppression by NO through inhibition of cyclic GMP PDE.
Characterization of Epitheloid Cells from Human Omentum: Comparison with Endothelial Cells from Umbilical Veins
Authors: Latron Y , Alessi M C , George F , Anfosso F , Poncelet P , Juhan-Vague I
Published: July 2018

Capillary cells represent 95% of the vascular bed, and cells from large and micro-vessels do not express identical functions. In order to study the hormonal regulation of plasminogen activator inhibitor 1 (PAI-1) secretion by human capillary cells we used epithelial cells from omental tissue (HOTMEC). As their endothelial origin is subject to controversy, we attempted to determine their characteristics by comparing them to human umbilical vein endothelial cells (HUVEC). Morphological and biological criteria were studied. By phase contrast microscopy HOTMEC elicited a cobblestone pattern similar to HUVEC. Weibel-Palade bodies were not found in the cytoplasm with electron microscopy. Fluorescence microscopy studies indicated that HOTMEC took up acetylated-LDL more intensely than HUVEC, and showed no staining for von Willebrand factor. The phenotype of HOTMEC was studied by flow cytometry using monoclonal antibodies (mo Ab) directed against epitopes either specific for endothelial cells or for mesothelial cells. We showed that in our preparations only 10% of cells reacted with mo Ab specific for endothelial cells. About 60% of the HOTMEC were labelled with an antibody directed against mesothelial cells. HOTMEC expressed fibrinolytic factors. Tissue plasminogen activator (t-PA) levels in HOTMEC conditioned medium were 50 fold higher than those of HUVEC, and the PAI-1 secretions were identical in both cell types. Insulin which is known to increase PAI-1 synthesis by hepatocytes did not enhance the PAI-1 level either in HOTMEC or in HUVEC conditioned media. Our results suggested that morphological and functional methods did not allow discrimination between the cell types present in the omentum tissue. They also showed that the population obtained from the omental tissue by collagenase digestion is heterogeneous, with few cells expressing endothelial markers.
Are Admission Plasma Fibrinogen Levels Useful in the Characterization of Risk Groups after Myocardial Infarction Treated with Fibrinolysis?
Authors: Pollak Hans , Fischer Michael , Fritsch Stephan , Enenkel Wolfgang
Published: July 2018

The aim of our study was to prove or disprove the independent prognostic importance of fibrinogen after myocardial infarction. Plasma fibrinogen levels were determined on admission in 135 patients with an acute myocardial infarction and symptoms up to 4 h (mean: 1.8 h) immediately before starting fibrinolytic treatment with 1.5 mio U. streptokinase i.v. All patients were free from other diseases which are known to cause elevated fibrinogen levels. Coronary angiography was carried out in 87%. During a mean follow-up period of 26.2 months 31 coronary events could be observed in 26 patients: 18 reinfarctions, 6 cases of sudden death, and 7 coronary artery bypass graft surgeries because of new symptoms. While plasma fibrinogen levels were higher in smokers than in non-smokers (3.30 vs 2.94 g/l p = 0.011) and correlated with the number of involved coronary arteries (p = 0.08), values were similar in patients with and without coronary events during follow-up (3.07 vs 3.16 g/l, p = 0.70). This applied as well to univariate analysis as to multivariate Cox's regression model. We conclude that plasma fibrinogen levels determined very early in patients with acute myocardial infarction do correlate with other important prognostic variables, but have no independent prognostic importance.
Characterization of Genetic Defects of Hemophilia B of Chinese Origin
Authors: Lin Shu-Wha , Shen Ming-Ching
Published: July 2018

To define the precise genetic defects of hemophilia B of Chinese origin, we have used the polymerase chain reaction (PCR) combined with direct sequencing to analyze the amplified DNA fragments containing the entire coding regions and their flanking introns of the factor IX gene from 6 affected individuals. Among these patients, two are siblings with normal factor IX antigen level (CRM+) yet reduced factor IX clotting activity (28%). Analysis of their factor IX genes revealed a G to A transition at nucleotide residue 10394, which causes substitution of an arginine for a glycine at amino acid residue 48. This is a novel mutation which resides in the first EGF-like domain of factor IX. Studies of two other hemophilia B patients with CRMr phenotypes (factor IX antigen level <35%, and clotting activity <1%), demonstrated a distinct mutation in each individual's factor IX gene. In one case, a guanine to adenine (residue 6365) transition results in replacement of arginine by glutamine at the –4 codon of the propeptide of factor IX. In the other, thymine at 6442 was mutated to cytosine which causes an arginine for cysteine substitution at residue 23. We have also characterized 2 discrete CRM- patients. Both exhibited an identical mutation at nucleotide residue 6460 which generates a translation termination codon (CGA to TGA) at the 29th amino acid. The mutation created a new NlaIII restriction enzyme site which could be used to identify this variant.
Comparative Fibrinolytic Properties of Staphylokinase and Streptokinase in Animal Models of Venous Thrombosis
Authors: Lijnen H R , Stassen J M , Vanlinthout I , Fukao H , Okada K , Matsuo O , Collen D
Published: July 2018

The thrombolytic and pharmacokinetic properties of staphylokinase were compared with those of streptokinase in hamsters with a pulmonary embolus produced from human plasma or from hamster plasma, and in rabbits with a jugular vein blood clot produced from rabbit blood. In both models, a continuous intravenous infusion of staphylokinase and streptokinase over 60 min in hamsters or over 4 h in rabbits, induced dose-dependent progressive clot lysis in the absence of significant systemic activation of the fibrinolytic system. The results of thrombolytic potency (clot lysis at 30 min after the end of the infusion, in percent, versus dose administered, in mg/kg) were fitted with an exponentially transformed sigmoidal function and the maximal percent clot lysis (c), the maximal rate of lysis (z = ¼ac · e
b
) and the dose at which the maximal rate of lysis is achieved (b) were determined. In hamsters with a pulmonary embolus produced from human plasma, streptokinase had a somewhat higher thrombolytic potency than staphylokinase, as revealed by a higher z value (2,100 ± 1,100% lysis per mg/kg streptokinase administered versus 1,100 ± 330% lysis per mg/kg for staphylokinase). In hamsters with a pulmonary embolus produced from hamster plasma, staphylokinase had a somewhat higher thrombolytic potency than streptokinase (z = 1,600 ± 440 versus 1,200 ± 370% lysis per mg/kg). Staphylokinase had a higher thrombolytic potency than streptokinase in rabbits, as revealed by a higher z-value (950 ± 350% lysis per mg/kg staphylokinase administered versus 330 ± 39% lysis per mg/kg for streptokinase) and a lower b-value (0.035 ± 0.010 mg/kg staphylokinase versus 0.091 ± 0.008 mg/kg for streptokinase). The plasma clearance following bolus injection of staphylokinase or streptokinase in hamsters or rabbits was comparably rapid (1.1 to 1.4 ml/min in hamsters and 14 to 15 ml/min in rabbits) as a result of a short initial half-life (1.8 to 1.9 min in hamsters and 1.7 to 2.0 min in rabbits). These results in two quantitative rodent models of thrombolysis suggest that staphylokinase is a potent thrombolytic agent with an in vivo thrombolytic potency that is comparable to that of streptokinase. Further investigation of the thrombolytic potential of staphylokinase seems to be warranted.
Ascorbic Acid Increases the Thrombogenicity of Cellular Matrices
Authors: Hindriks Georg A , Sixma Jan J , de Groot Philip G
Published: July 2018

We have studied the influence of ascorbate on extracellular matrix formation in cultured human endothelial cells, smooth muscle cells and fibroblasts and measured the influence of the changed composition of their isolated extracellular matrices on their affinity for platelets. When endothelial cells were grown for a week in the presence of ascorbate, no influence on proline incorporation in their extracellular matrix was found. In accordance, no influence on platelet adhesion or aggregate formation on these matrices was detected. When smooth muscle cells were cultured in the presence of ascorbate, a strong increase in the amount of collagen types I and III in the extracellular matrix was found. When these matrices were perfused with whole blood, a significant enhanced increase in aggregate formation was observed. No influence was seen on the total coverage of the matrix with platelets. When fibroblasts were grown in the presence of ascorbate, no significant increase in proline incorporation in their matrix was measured. However, an increased adhesion of platelets was seen to the matrices at lower shear rates. We conclude that ascorbate feeding has a significant effect on endogenous deposited matrices of smooth muscle cells and fibroblasts, and that the changed composition had profound effects on platelet interaction with these matrices.
α2-Antiplasmin, Plasminogen Activator Inhibitor (PAI) and Dilute Blood Clot Lysis Time in Selected Disease States
Authors: Cucuianu Mircea , Knauer Oliver , Roman Stefan
Published: July 2018

This paper is an attempt to assess the relevance of the inhibitors of fibrinolysis for clot lysis in selected disease states and to discuss the mechanisms leading to acquired abnormal levels of such inhibitors. When compared to 20 control subjects the 30 hypertriglyceridemic patients (14 with type IIb and 16 with type IV) displayed significantly (p <0.001) increased plasma plasminogen activator inhibitor (PAI) activity (221 ± 88% and 290 ± 104% respectively; mean ± SD), moderately (p <0.01) increased α2 antiplasmin (α2AP) level (112 ± 11% and 115 ± 16%) and accordingly an obviously prolonged dilute blood clot lysis time (DBCLT). Neither PAI activity and α2AP level nor DBCLT were significantly different from controls in the 10 patients with hyperlipoproteinemia type IIa. The 18 patients with severe hepatic cirrhosis had low α2AP level (59 ± 19.7%) and accelerated clot lysis, while mean PAI activity (160 ± 87%) was slightly (p <0.05) increased. In the 17 nephrotic patients α2AP was increased (115 ±12%) while PAI activity was similar to controls and DBCLT rather shorter. Two liver secretion enzymes, namely serum Cholinesterase and plasma protein C, were found to be decreased in cirrhotic patients, similar to control values in hyperlipoproteinemia type Ha and obviously increased in nephrotic patients as well as in hypertriglyceridemic subjects. The relevance of PAI and α2AP for clot lysis was considered in relation to data in the literature concerning the behaviour of t-PA and factor XIII. Enhanced hepatic synthesis of protease inhibitors and factor XIII as a possible cause of delayed clot lysis in hypertriglyceridemia was envisaged.
Thrombosis: A Study of Coagulation Parameters and Mechanisms during Allograft Rejection
Authors: Mandel Stanley R , Shermer Richard , Clark Richard , Staab Edward V , Webster William P
Published: July 2018

Thrombosis of the microvasculature has been recognized as the end product of organ rejection, but the exact biological pathway through which this occurs has not been clarified. Normal, factor VII deficient and heterozygous hemophilic (factor VIII) dogs were grouped to study the intrinsic and extrinsic clotting and platelet mechanisms during unmodified renal allograft rejection. The observed alterations of the hemostatic mechanisms are related to the changes observed in the microvasculature. Six groups of donor-recipient animals were studied: Group I - autografts (control); Group II - normal to normal allografts with bilateral nephrectomy; Group III - heterozygotes for factor VIII deficiency; Group IV - normal to normal allografts with unilateral nephrectomy; Group V - normal to factor VII deficiency without nephrectomy; and Group VI - normal to normal allografts with unilateral nephrectomy and dipyridamole. Each engrafted animal was followed pre- and posttransplantation for change in the blood clotting factors, fibrin split products, platelets, white blood cells, renal function and microvasculature. The animals with factor VII deficiency rejected in a similar fashion as the control animals. The group with impaired factor VIII synthesis and platelet function had longer survival times. These data suggest that the intrinsic clotting pathway and platelets are the primary mechanism through which thrombosis occurs secondary to immune injury.
Separation of Fibrinogen Degradation Products (FDP) by Means of Adsorption to Insolubilized Fibrinmonomer (FM-ag)
Authors: Heene D L , Matthias F R , Wegrzynowicz Z , Hocke G
Published: July 2018

The phenomenon of complex formation between fibrinmonomer and fibrinogen degradation products was investigated by means of adsorption of FDP to insolubilized thrombin- modified fibrinogen (FM-ag). Since it could be demonstrated that there are different adsorption characteristics for early FDP and late FDP, the possibility of separation of FDP by means of affinity chromatography on FM-ag columns was evaluated using plasmic digests of 3H-Ac-labelled fibrinogen. The identification of FDP was performed by disc-electrophoresis. The results indicate that the adsorption of early FDP is comparable to the behaviour of fibrinogen, whereas late FDP show essential difference in the affinity towards FM-ag, evident by the result that fragment E adsorbs only to a minimal extent. Fragments D and E derived from fibrinogen as well as from non-crosslinked fibrin, revealed identical adsorption characteristics. Under specified conditions the procedure is suitable as a preparative method for the separation of fragments D and E.
Cancer Procoagulant in Acute Non Lymphoid Leukemia: Relationship of Enzyme Detection to Disease Activity
Authors: Donati M B , Falanga A , Consonni R , Alessio M G , Bassan R , Buelli M , Borin L , Catani L G , Pogliani E , Gugliotta L , Masera G , Barbui T
Published: July 2018

Blast cell extracts from patients with acute non lymphoid leukemia (ANLL) express cancer procoagulant (cp). Thii factor X (FX) activator is distinct from tissue factor (TF) in that it does not require factor VII (FVII) to trigger blood coagulation, it acts as a cysteine proteinase and is not present in normal mononuclear cells. Tb assess whether there is any relationship between the presence of CP and the status of the disease, ANLL patients have been studied at diagnosis, during remission, at relapse. The procoagulant activity in either the presence or absence of F VII and sensitivity to cysteine proteinaie inhibitors were tested on cell extracts. Immunoreactivity was explored with an anti-cP polyclonal antibody. Data obtained in gL newlydiagnosed ANLL patients (subtypes M1 to M5, EAB classification) confirmed the presence of cp in M1- to M4 groups (mean + sE Fvll-independent activity: M1 = 2.1 ± 0.7 unit/mg; M2 = 5.7 ± 1.7 unit/mg; M3 = 31.5 ± 8 unit/mg M4 = 1.6 ± 1.2 unit/mg; CP was absent in the M5 type. In eight patients analy zedin a subsequent phase of partial remission, specific activity had dropped from 26.9 ± 7.8 to 10.5 ± 4.0 unit/mg. Activiiy was virtually absent (0−0.05 unit/mg) in the bone marrow of 37 patients studied at complete remission. Bone marrow samples from six subjects tested at different intervals after complete remission were repeatedly negative for CP but became positive 2 to 5 months before relapse. Upon relapse, the FVII indbpendent activity rose to 24.2 ± 8.2 unit/mg.

These results suggest that CP activity may be closely associated with the presence of myeloid malignant cells in the bone marrow, a finding of potential relevance not only to the coagulation disorders of acute leukemia, but also to the early deteition of blast cells in ANLL.
Coagulation, Fibrinolytic and Platelet Function in Patients on Long-Term Therapy with Aspirin 300 mg or 1200 mg Daily Compared with Placebo
Authors: Hampton K K , Cerletti C , Loizou L A , Bucchi F , Donati M B , Davies J A , de Gaetanox G , Prentice C R M
Published: July 2018

Aspirin has been shown to be beneficial in the prophylaxis of arterial thromboembolic disease. The rationale for its use as an antithrombotic drug lies in its inhibition of thromboxane A2- dependent platelet function. However, the effect of aspirin on coagulation and fibrinolysis during chronic therapy has not been studied. We have measured a range of haemostatic and platelet functions in 49 patients with transient ischaemic attacks randomly allocated to aspirin 300 mg a day, aspirin 1,200 mg a day or placebo. All had been taking their allocated treatment for between 9 months and 4 years prior to investigation. Bleeding time was prolonged, serum thromboxane diminished and platelet aggregation to arachidonic acid but not ADP was abolished by both 300 mg and 1,200 mg aspirin, in a non-dose dependent fashion. Serum salicylate increased with the dose of aspirin ingested. No effect was seen with either dose of aspirin on urinary thromboxane and 6-keto-PGF1α excretion, or on coagulation. Patients taking 1,200 mg aspirin a day had a lower haemoglobin and packed cell volume, lower resting fibrinopeptide A concentration and lower basal plasminogen activator activity than those on placebo. Response to venous occlusion was norrnal in all groups. The results suggest 300 mg and 1,200 mg aspirin have an equivalent platelet inhibitory effect but 1,200 mg aspirin causes greater gastro-intestinal blood loss.
Characterization of Domain Deletion and/or Duplication Mutants of a Recombinant Chimera of Tissue-Type Plasminogen Activator and Urokinase-Type Plasminogen Activator (rt-PA/u-PAI)
Authors: Nelles L , Lijnen H R , Van Nuffelen A , Demarsin E , Collen D
Published: July 2018

Chimeric molecules comprising the A-chain of tissue-type plasminogen activator (t-PA) and the catalytic domain of urokinase-type plasminogen activator (u-PA) have intact enzymatic characteristics of u-PA, but only partial fibrin-binding properties of t-PA (Nelles et al., J Biol Chem 1987; 262: 10855–62). The following domain deletion and/or duplication mutants of such a t-PA/u-PA chimera were constructed, purified and charactertzed: rt-PA-ΔFE∇/u-PA, with deletion of the finger-like (F) and epidermal growth factor-like (E) domains, rt-PA-ΔK1∇K2/u-PA, with kringle 1 (K1) replaced by a second copy of kringle 2 (K2), and rt-PA-ΔFEK1∇K2/u-PA, with F and E domain deletions in rt-PAΔK1∇K2/u-PA.

The specific activities on fibrin plates of the single-chain (sc) chimeras ranged between 68,000 IU/mg for rt-PA-ΔK1∇K2/scu-PA and 200,000 IU/mg for rt-PA-ΔFEK1∇K2/scu-PA, as compared to L20,000 IU/mg for rscu-PA. The specific activities of their plasmin-generated two-chain (tc) derivatives ranged between 120,000 IU/mg for rt-PA-ΔK1∇K2/tcu-PA and 240,000 IU/mg for rt-PA-ΔFEK1∇K2/tcu-PA, as compared to 100,000 IU/mg for rtcu-PA. All two-chain chimeras activated plasminogen following Michaelis-Menten kinetics, with catalytic efficiencies between 0.072 μM−1s−1 for rt-PA-ΔK1∇K2/tcu-pA and 0.081 pM−1 s−1 for rt-PA-ΔFEK1∇K2/tcu-PA, as compared to 0.088 μM−1 s−1 for rtcu-PA. CNBr-digested fibrinogen enhanced the initial rate of plasminogen activation by a factor 2.2 to 6.2, as compared to 4.9 for rtcu-PA. The fibrin-affinity of the chimeras decreased in the order rt-PA > rt-PA-ΔK1∇K2/u-PA > u-PA and that for lysine in the order rt-PA-ΔFEK1∇K2/u-PA > > t-PA/u-PA ⩽ st-PA > rt-PA-ΔFE/u-PA > u-PA. All single-chain plasminogen activators caused a time and concentration-dependent clot lysis in an in vitro plasma clot lysis system, with equi-effective doses (causin g 50% clot lysis in 2 h) ranging between 0.53 and 0.90 μg/ml, as compared to 1 .7 μg/ml for rscu-PA, and were associated with comparable residual fibrinogen levels of approximately 80%.

Thus, substitution of K1 by a second copy of K2 in the chimeric protein t-PA/u-PA enhances the affinity for both fibrin and lysine significantly and improves the fibrinolytic potency in an in vitro clot lysis system marginally.
Lack of Platelet Response to Collagen Associated with an Autoantibody against Glycoprotein Ia: A Novel Cause of Acquired Qualitative Platelet Dysfunction
Authors: Deckmyn Hans , Chew Shern L , Vermylen Jos
Published: July 2018

Platelets from a patient with an acquired hemorrhagic disorder had a severely impaired response to collagen, whereas platelet aggregation to other agonists and coagulations tests were normal. No abnormalities of the patient’s platelet membrane glycoproteins (GP) were seen.

Tleatment of the patient with immunosuppressive agents temporarily improved both the bleeding tendency and the collagen responsiveness of the platelets. An IgG was found to be present in the plasma, directed against a protein comigrating with GPIa, and coadsorbing with GPIa to insoluble collagen fibers in a Mg+2-dependent manner. Furtherrnore, GPIa was recognized by the patient’s antibody when affinity-purified GPIa-IIa was used as antigen. Finally, the GPIa-IIa complex was immunoprecipitated from a platelet lysate by patient’s plasma.

In addition, purified platelet specific IgG’s from the patient inhibited aggregation of normal platelets induced by collagen or by wheat germ agglutinin. We conclude that the lack of response to collagen of the patient’s platelets may well be due to the presence of an autoantibody against GPIa.
1-Desamino-8-D-Arginine Vasopressin (DDAVP) Infusion in Type IIB von Willebrand’s Disease: Shortening of Bleeding Time and Induction of a Variable Pseudothrombocytopenia
Authors: Casonato Alessandra , Teresa Sartori M , de Marco Luigi , Girolami Antonio
Published: July 2018

We have investigated the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) infusion on platelet count and bleeding time in 4 patients with type IIB von Willebrand’s disease (vWd). Three of four patients showed a normalization of the bleeding time within 1 h after the infusion, while bleeding time was not modified in the fourth. In accordance with the literature, thrombocytopenia was observed after DDAVP infusion, but this thrombocytopenia was due to the anticoagulants used for blood collection. In two patients (F. I., G. F.) no thrombocytopenia was observed when platelets were counted by fingerstick method but there was a 20% platelet decrease in blood samples collected in sodium citrate and a 50% decrease in samples collected in EDTA. Dramatic falls in platelet counts (70–95%) were observed in the additional two patients (C. A., D.Z.) after DDAVP infusion, when both sodium citrate or EDTA were used as anticoagulants. In the latter two patients there was also a 50% decrease in platelet count when the fingerstick method was used. The decrease in the patient’s platelet count in EDTA samples after DDAVP infusion could be prevented, in part, by the previous additions of an anti GPIb monoclonal antibody and an anti GPIIb-IIIa monoclonal antibody.

Thus, the thrombocytopenia observed in the four IIB vWd patients studied after DDAVP infusion seems to be, at least partially, a pseudothrombocytopenia depending on the calcium concentration in the blood samples and the availability of GPIb and GPIIb-IIIa receptors. These findings and the normalization of the bleeding time observed in three of the four patients has led us to reconsider the possible use of DDAVP in the treatment of our IIB vWd patients.
Does Increased Platelet Aggregation Have a Prognostic Value in the Deterioration of Background Diabetic Retinopathy?
Authors: Plu G , Lecrubier C , Scarabin P Y , Baudoin C , Samama M ,   on behalf of the Damad Study Group
Published: July 2018

Many case-control studies have suggested that increased platelet aggregation (PA) could be involved in the pathogenesis of diabetic microangiopathy. However, longitudinal data are needed to support this hypothesis. We consider here such an approach in the placebo group (93 diabetic patients) of a controlled clinical trial on the effect of PA inhibitors in the treatment of diabetic retinopathy (Damad program). We have measured spontaneous PA and PA induced by ADP, collagen and arachidonic acid before treatment and yearly during a 3-year period. The assessment of retinopathy was based on the changes in the number of microaneurysms present in the macular field as seen on fluorescein angiograms during follow-up. PA was estimated by maximal decrease in optical density. The lowest ADP concentration still able to induce irreversible aggregation was also determined. No significant correlations between any baseline PA measurements and end point criterion were found (all correlation coefficients lower than 0.20). No significant changes in mean PA were observed during follow-up. Within-subject variation of PA was markedly large accounting for 61% to 98% of the total variance of various measurements. Allowances for the main characteristics of diabetes made no substantial difference to the results. These negative findings can be partly attributed to the lack of reliability of PA tests. In our study, we conclude that PA tests are not useful measures for the prediction of evolution of background diabetic retinopathy.
Antibody to Hepatitis G Mrus after a Vapour-Heated Factor Vlll Goncentrate
Authors: Mannucci P M , Zanetti A R , Colombo M , Chistolini A , De Biasi R , Musso R , Tamponi G ,   the Study Group of the Fondazione deii–Emofilia
Published: July 2018

To evaluate whether or not clotting factor concentrates
exposed to virucidal procedures transmitted hepatitis C, sera obtained in 1984–1986 from 27 previously untreated hemophiliacs infused with a vapour-heated factor VIII concentrate were tested retrospectively for the antibody to the hepatitis C virus (anti- HCV). A 2-year-old hemophiliac, negative for anti-HCV before administration of concentrate, seroconverted at week 12 and remained anti-HCV positive thereafter. Both his parents were anti-HCV negative and he had no other household contact. The patient had also become HBsAg positive at week 8 and had at the same time a marked elevation of alanine aminotransferase. His double infection with the hepatitis B and C viruses indicates that hot vapour was not completely effective in inactivating these viruses.