bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Vitamin K1 and Warfarin on Prothrombin Expression in Human Hepatoblastoma (HepG2) Cells
Authors: Jamison C Scott , Burkey Bryan F , Degen Sandra J Friezner 
Published: July 2018

SummaryCultures of human hepatoblastoma (HepG2) cells were treated with vitamin K1 or warfarin and prothrombin antigen and mRNA levels were determined. With 3 and 6 h of 10 µg vitamin K1 treatment secreted prothrombin antigen levels, relative to total secreted protein levels, were increased 1.5-fold and 2.1-fold, respectively, over ethanol-treated control levels as determined by an enzyme-linked immunosorbent assay. Dose-response analysis with 3 h of 25 µg/ml vitamin K1 treatment demonstrated a maximal increase of 2.0-fold in secreted prothrombin antigen levels, relative to total secreted protein levels, over ethanol-treated control levels. Pulse-chase analysis with 35S-methionine and immunoprecipitation of 35S-labelled prothrombin demonstrated that, with vitamin K1 treatment (25 µg/ml, 3 h), the rate of prothrombin secretion increased approximately 2-fold and the total amount (intra- and extracellular) of prothrombin synthesized increased approximately 50% over ethanol-treated control levels. Warfarin treatment (1, 5, or 10 µg/ml, 24 h) resulted in decreases in secreted prothrombin antigen levels, relative to total protein levels to approximately 85%, 87% or 81% of ethanol-treated control levels. Analysis of total RNA isolated from these cultures by Northern and solution hybridization techniques demonstrated that prothrombin mRNA was approximately 2.1 kb and that neither vitamin K1 nor warfarin treatment affected the quantity of prothrombin mRNA (ranging from 240–350 prothrombin mRNA molecules per cell). These results demonstrate that vitamin K1 and warfarin, in addition to effects on γ-carboxylation, affect prothrombin synthesis post-transcriptionally, perhaps influencing translation, post-translational processing and/or secretion mechanisms.
Comparison of Recombinant Tissue Factor Pathway Inhibitors Expressed in Human SK Hepatoma, Mouse C127, Baby Hamster Kidney, and Chinese Hamster Ovary Cells
Authors: Wun Tze-Chein , Kretzmer Kuniko K , Palmier Mark O , Day Kathleen C , Huang Margaret D , Welsch Dean J , Lewis Charles , Wolfe Richard A , Zobel James F , Lange Gary W , Frazier Ronald B , Bild Gary S , Peel Michelle A , Shell Robert E , Horn Nancy A , Junger Kurt D , Foy Barbara A , Gustafson Mark E , Leimgruber Richard M , Novotny William F , Broze George J , Pyla Yvonne E , Hippenmeyer Paul J , Warren Thomas G 
Published: July 2018

SummaryRecombinant tissue factor pathway inhibitor (rTFPI) has been expressed in four mammalian expression systems using human SK hepatoma, mouse C127, baby hamster kidney (BHK), and Chinese hamster ovary (CHO) cells as hosts. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the immunoaffinity purified rTFPIs all show broad bands and the mean molecular weight of SK hepatoma and C127 rTFPIs (M
r ~ 38,000) appear larger than those of BHK and CHO rTFPIs (M
r ~ 35,000). All these proteins inhibit factor Xa and appear to bind factor Xa with 1:1 stoichiometry. The ability of these proteins to inhibit tissue factor-induced coagulation in plasma was examined using a prothrombin time assay. The relative activities of SK rTFPI:C127 rTFPI:BHK rTFPI:CHO rTFPI were found to be 28:15:2.1:1. By Western blot using specific antisera against the amino- and carboxy-termini of TFPI as probes, it is found that all the immunoaffinity purified rTFPIs possess approximately equal amounts of the amino terminus, but the C127 and BHK rTFPIs are deficient in carboxy terminus and the CHO rTFPI is essentially devoid of this region of the protein. Mono S chromatography allowed separation of the full-length and the truncated molecules with high and low anticoagulant activities, respectively. The above results suggest that proteolysis of the carboxy terminus of TFPI occurs to different extent when TFPI is expressed in different cells and that the carboxy terminal region of the TFPI molecule is important for the inhibition of tissue factor-induced coagulation. Recombinant and non-recombinant SK hepatoma cells appear to produce TFPI with the least amount of proteolysis compared with other cell systems tested and SK TFPI functionally resembles TFPI circulating in the blood.
Peritoneal Fluid and Plasma Fibrinolytic Activity in Women with Pelvic Inflammatory Disease
Authors: Dörr P J , Brommer E J P , Dooijewaard G , Vemer H M 
Published: July 2018

SummaryPrevious studies have shown that the fibrinolytic activity of peritoneum is depressed in local inflammation. We measured fibrinolytic parameters in peritoneal fluid and in plasma of 10 women with pelvic inflammatory disease (PID). Nine women, in whom laparoscopy for sterilisation was performed, served as a control group.In the peritoneal fluid of women with PID, PAI-Ag, t-PA-Ag and u-PA-Ag were many times higher than in the control group. In contrast to the antigens which may be present in inert complexes, the potentially active compounds, measured as t-PA activity and plasmin-activable scu-PA, were not significantly different in the two groups, and in none of the samples was the active enzyme tcu-PA detectable. Nevertheless, the mean peritoneal fluid TDP and FbDP concentrations were about twenty times higher in the PID group than in the control group. In plasma of PID patients, none of the parameters except u-PA-Ag differed from those in the control group. The difference between control and patient plasma u-PA-Ag was statistically significant, but too small to attach any relevance to the observation.Our data suggest that, in contrast to the classical concept of decreased fibrinolytic activity as a cause of adhesion formation, intraperitoneal fibrinolysis is enhanced in peritoneal inflammation through stimulation of the local production of t-PA and u-PA. Despite concomitant production of PAI, fibrinolysis occurs at a high rate, resulting in high levels of fibrin degradation products. Since this activated fibrinolysis does not meet the demand, therapeutic enhancement should be considered to prevent adhesions.
High Level Expression of Active Human Prothrombin in a Vaccina Virus Expression System
Authors: Falkner F G , Turecek P L , MacGillivray R T A , Bodemer W , Scheiflinger F , Kandels S , Mitterer A , Kistner O , Barrett N , Eibl J , Dorner F 
Published: July 2018

SummaryWe have worked out an efficient and time saving procedure for the expression of recombinant human prothrombin. The glycoprotein was expressed in the vaccinia virus expression system in several mammalian cell lines. The kidney cell lines Vero and BHK and the human cell line Hela were found to efficiently secrete prothrombin. Expression levels of 3–4 µg of factor II per 106 cells per day corresponding to 18–23 mU per 106 cells per day were achieved. Since the expression levels obtained with the vaccinia virus/Vero cell system were comparable to those obtained in amplified transformed CHO cells it provides an alternative system for the efficient expression of human prothrombin and may allow to further elucidate structure-function relationships of (pro)thrombin and its various effectors.
Insights on Monoclonal Antibodies to Kininogens' Heavy Chain Which Influence Kininogens' Binding to Platelets
Authors: Jiang Yongping , Nawarawong Weerasak , Meloni Frank J , Schmaier Alvin H 
Published: July 2018

SummaryPurified domains of low molecular weight kininogen (LK) can be used directly to determine the epitopes of monoclonal antibodies (mAbs) that have been shown to influence kininogen function. LK, purified from plasma by carboxymethyl-papain-Sepharose 4B affinity chromatography and kaolin adsorption, was digested by trypsin and chymotrypsin. The domains of LK were then separated by gel filtration followed by carboxymethyl-papain-Sepharose 4B affinity chromatography. Using the purified domains of LK’s heavy chain, the regions on kininogens' heavy chain which various monoclonal antibodies are directed to were determined by enzyme-linked immunosorbent assay and immunoblotting. MAb 2B5 which neutralized kininogens' ability to inhibit calpain cross-reacted with domains 2 and 3. MAb HKH8 which reacted with kininogens' domain 1 and 2 was found to inhibit 125I-HK binding to platelets. At two-fold molar excess, mAb HKH8 was a better inhibitor of 125I-HK binding to platelets than higher concentrations, where the antibody was shown to cause increased binding to platelets. Alternatively, HKH8 F(ab')2 completely inhibited 125I-HK binding to platelets even at high concentrations of antibody. These studies indicate that purified domains of kininogens' heavy chain can be used to rapidly localize epitopes for antibodies. Further, mAb HKH8 should be a valuable probe to understand the mechanisms of kininogens' binding to platelets.
Standardisation of Factor VIII – V. Calibration of the 2nd International Standard for Factor VIII and von Willebrand Factor Activities in Plasma
Authors: Heath A B , Barrowcliffe T W 
Published: July 2018

SummaryThe proposed 2nd International Standard for Factor VIII and von Willebrand Factor activities in plasma, NIBSC code 87/718, was assayed against the 1st IRP, 80/511, and against fresh normal plasma, in 21 laboratories. There were no significant differences between the various assay methods for factor VIII antigen, von Willebrand factor antigen, and von Willebrand factor ristocetin co-factor activity. For factor VIII clotting activity there was a significant difference between the results of one-stage and two-stage assays. Plasma 87/718 has now been established by the WHO Expert Committee on Biological Standardisation as the 2nd IS for factor VIII and vWF in plasma with the following potencies: VIII:C 0.60 IU/ampoule; VIII:Ag 0.91 IU/ampoule; vWF:Ag 0.91 IU/ampoule; vWF/RCo 0.84 IU/ampoule.
Unexpected Effects of Aurin Tricarboxylic Acid on Human Platelets
Authors: Kinlough-Rathbone Raelene L , Packham Marian A 
Published: July 2018

SummaryAurin tricarboxylic acid (ATA) is a potent inhibitor of ristocetin-mediated platelet agglutination and of shear-induced, von Willebrand factor (vWf)-mediated platelet aggregation, probably via inhibition of vWf interaction with glycoprotein Ib (GPIb). We examined the effects of ATA (both the sodium salt and a solution of ATA in ethanol) on platelet functions in citrated plasma (PRP) and in suspensions of washed platelets in Tyrode-albumin solution (contains 2 mM Ca2+). ATA (42–211 µg/ml) blocked aggregation and release of granule contents induced by thrombin (0.15 U/ml in PRP; 0.03 U/ml in platelet suspension). Responses to higher concentrations of thrombin were not inhibited. ATA also prolonged thrombin-induced clotting of fibrinogen. Since ATA had no effect on fibrinogen-induced responses of chymotrypsin-treated platelets, ATA probably acts on thrombin rather than on fibrinogen.In PRP and platelet suspensions, ATA (acid form 106 µg/ml; sodium salt 122 µg/ml) had little effect on ADP-induced platelet aggregation. The sodium salt of ATA (61–122 µg/ml) enhanced collagen-induced aggregation and release by platelets in citrated plasma and by washed platelets; the enhancement was extensively inhibited by aspirin. With platelet suspensions, ATA significantly enhanced aggregation and release caused by low concentrations of sodium arachidonate (15–50 µM); aggregation and release caused by higher concentrations of arachidonate were somewhat inhibited by ATA. Arachidonate-induced aggregation and release were also enhanced by ATA in PRP. ATA enhanced aggregation and release induced by the calcium ionophore A23187; aspirin had little effect on the enhancement. ATA also enhanced aggregation and release caused by the thromboxane A2 mimetic, U46619 (0.1–.4 µM) or platelet-activating factor (PAF) (5 ng/ ml), but enhancement was never as extensive as when these platelet responses were caused by arachidonate or A23187; aspirin partially inhibited these enhancements. Thus, although ATA may interfere with the interaction of GPIb with large vWf multimers and inhibit the activity of thrombin, thereby having antithrombotic properties, it has potentiating effects on some other agonists; these effects should be considered if it is used as an antithrombotic agent.
The Ex Vivo Effect of Preadsorbed Vitronectin on Platelet Activation
Authors: Fabrizius-Homan D J , Cooper S L , Mosher D F 
Published: July 2018

SummaryThe activation of ex vivo canine platelets by preadsorbed vitronectin (VN) was sensitive not only to the polymer substrate utilized but also to the adsorption conditions employed. Lower levels of maximal platelet deposition were obtained for VN-coated silicone rubber (SR) than for other VN-coated substrates with comparable levels of adsorbed VN, but this effect was diminished with increased residence time of VN on the SR surface. Submonolayer and monolayer surface concentrations of VN elicited similar maximal levels of platelet deposition at both short (<3 h) and long (>12 h) residence times, but thrombi were larger and more dense for the submonolayer surface concentrations. VN was also more effective in forming thrombi when adsorbed sequentially before albumin instead of after albumin. To further examine these differences in the nature of adsorbed VN between substrates and adsorption conditions, sodium dodecyl sulfate (SDS) elutability measurements and Fourier transform infrared spectroscopy with attenuated total reflectance optics (FTIR-ATR) evaluations of the adsorbed protein were performed. An SDS solution was able to remove a greater percentage of the VN which was adsorbed to a submonolayer than a monolayer surface concentration when SDS displacement was initiated immediately after adsorption was terminated. However, if the adsorbed protein was allowed to reside on the surface for a length of time before the introduction of the SDS displacing media, a greater percentage of the monolayer surface concentration was removed. The submonolayer surface concentration may be better able to increase its strength of contact with the surface during the added residence time than the monolayer surface concentration. FTIR-ATR spectra of VN showed less structural alterations when it was adsorbing to SR than to a segmented polyurethane, a more thrombogenic material when coated with VN. Thus, the ability of VN to stimulate thrombus formation appeared to correlate with the percentage of VN which was nonelutable by SDS and the amount of structural alterations observed by FTIR-ATR, both of which are indications of its extent of contact with the surface.
Faktor VIII:C aus Tiermaterial
Authors: Jones P. 
Published: July 2018

ZusammenfassungFaktor VIII:C vom Schwein bietetsich al seine brauchbare Alternative zu menschlichen Konzentraten bei bestimmten Patienten an. Der Autor hat Erfathrung mit dem alten Material, das routinemäßig für die Prophylaxe während chirurgischer Eingriffe oder beischweren Blutungen bei Fehlen einer hinreichenden Menge an menschlichem Material angewendet wurde. Es war schwer löslich, verursachte Fieberreaktionen und, besonders bei hoher Dosierung, eine Thrombozytopenie. Seine Wirksamkeit war auf 8–10 Tage beschränkt, so daϐ dann Rinderoder menschliches Konzentrat substituiert warden muϐte, bis die Wundheilung vollständing war. Abgesehen von diesen Einschränkungen verdanken viele Hämophile ihr Leben der Verwendung doeses Materials.Das neue über Polyelektrolyte hergestellte Schweinematerial (Hyate: C) hat verschiedene wichtige Vorteile. Das PAF-Problem scheint gelöst zusein, schwere Reaktionen sind selten (sollten aber immer als möglich angesehen warden), es ist leicht löslich und, was das Wichtigste von allem ist, seine Antigenität scheint viel geringer zu sein als jene des alten Prodluktes. Patienten wurden erfolgreich über mehr als 10 Tage behandelt und wiederholte Behandlungszyklen wurden nicht von anaphylaktischen Reaktionen begleitet.Hyate: C bietet eine alternative und wahrscheinlich sicherere Methode der Therapie für Patienten mit Antikörpern (besonders solchen, die eine hohe anamnestische Reaktion aufweisen) als aktivierte Prothrombin-Komplex-Produkte. Die Verwendung dieses Produktes sollte immer erwogen warden, wenn Schweineantikörper fehlen oder in niedriger Konzentrationtion vorhanden sind. Es bleibt jedoch Vorsicht bei der Anwendung erforderlich. Das Material muϐ nach Ansicht des Autors noch immer als ein experimentelles Produkt betrachtet warden.
Perioperative, Single-Surgeon Experience in Cerebrovascular Bypass Procedures at Academic Medical Center and Community Hospital
Authors: Nissman Kathleen W. , Zomorodi Ali R. , Gupta Dhanesh K. , Dhakal Ishwori , Li Yi-Ju , James Michael L. 
Published: July 2018

Abstract
Background Little evidence exists for superiority of neurosurgical outcomes from care subspecialization. Outcomes of a single neurosurgeon after complex vascular neurosurgery in an academic medical center were compared against those in a community hospital.
Methods In this retrospective analysis of extracranial-intracranial vascular bypass operations performed between July 1, 2013 and February 1, 2015, cases were identified by cross-referencing the electronic medical record with the surgeon's own records. Pre-, intra-, and postoperative variables were abstracted from cases performed at a tertiary center and a community hospital. Dichotomous postoperative data recorded included extubation in the operating room (OR), readmission, and survival to discharge, and length of stay was also analyzed. Due to small sample size and low readmission rate, Firth's penalized likelihood tests were incorporated in the logistic regression model for parameter estimation and testing.
Results A total of 28 hemispheres in 26 patients were included: 18 hemispheres in 16 patients at the tertiary center and 10 hemispheres in 9 patients at the community hospital. Differences were found in operative time (tertiary mean: 7.21 + 2.5 hours, community mean: 5.19 + 0.9 hours, p = 0.0074) and readmission to the tertiary center (p = 0.078). However, significant difference was observed only for anesthetic type (more likely to include remifentanil and propofol at the tertiary center, p = 0.0104).
Conclusion Subspecialty care alone may be insufficient to enhance outcome after complex neurosurgical procedures.
Auf der Suche nach dem Glück – ein Exkurs zu einigen wissenschaftlichen Grundlagen
Authors: Jordan Wolfgang 
Published: July 2018

ZusammenfassungAusgehend von dem Märchen „Hans im Glück“ werden einige wissenschaftliche Erkenntnisse zur Sozialökonomie, zur Neurobiologie, zur Psychologie, zur Psychiatrie und zur Philosophie des Glücks erläutert und in einer persönlichen Betrachtung einer moralischen, einer ästhetischen, einer geistigen und einer spirituellen Dimension als Grundlage des menschlichen Zusammenlebens zugeordnet.
Zum Glück in der Forensik
Authors: von Schönfeld Carl-Ernst 
Published: July 2018

ZusammenfassungGlück in der Forensik kann für Patienten eine gute Behandlung, für die Gesellschaft Sicherheit und für die Behandler eine sehr befriedigende Arbeit bedeuten. Forensische Behandlung braucht eine Grundhaltung, die auf eine würdevolle positive Identität abzielt und eine Fachlichkeit, die sich an den Risk-Need-Responsivity (RNR)-Prinzipien sowie den persönlichen Zielen der Patienten orientiert. Die jüngsten Gesetzesreformen werden zu kürzeren Verweildauern im Maßregelvollzug führen und erfordern eine intensive und gut vernetzte Nachsorge. Rückfallgefahr ist keine reine Glückssache, sondern kann kalkuliert und reduziert werden.
Convergent beam electron holography for analysis of van der Waals heterostructures
Authors: Latychevskaia Tatiana , Woods Colin Robert , Wang Yi Bo , Holwill Matthew , Prestat Eric , Haigh Sarah J. , Novoselov Kostya S. 
Published: July 2018

Significance
Assembling 2D materials into vertically stacked heterostructures allows an unprecedented control over their properties. The interaction between the individual crystals plays the crucial role here; thus, the information about the local atomic stacking is of great importance. Still, there are no techniques which would allow investigation of the stacking between such crystals with any reasonable throughput. We present the use of convergent beam electron diffraction (CBED) to investigate the quality of the interface in such heterostructures. We demonstrate that defects such as misorientation, strain, ripples, and others can be visualized, and quantitative information about such structures can be easily extracted. Furthermore, CBED images can be treated as holograms; thus their reconstruction gives 3D profiles of the heterostructures over a large area.
In-House Manufacture of Sterilizable, Scaled, Patient-Specific 3D-Printed Models for Rhinoplasty
Authors: Bekisz Jonathan M , Liss Hannah A , Maliha Samantha G , Witek Lukasz , Coelho Paulo G , Flores Roberto L 
Published: July 2018

Abstract

Background
Rhinoplasty relies on clear patient communication and precise execution of a three-dimensional (3D) plan to achieve optimal results. As 3D imaging and printing continue to grow in popularity within the medical field, rhinoplasty surgeons have begun to leverage these resources as an aid to preoperative planning, patient communication, and the technical performance of this challenging operation.

Objectives
Utilizing departmentally available resources and open-access 3D imaging platforms, we have developed an affordable, reproducible protocol for rapid in-house virtual surgical planning (VSP) and subsequent manufacture of 3D-printed rhinoplasty models.

Methods
Preoperative 3D photographic images underwent virtual rhinoplasty using a freely available 3D imaging and sculpting program (BlenderTM [Version 2.78, Amsterdam, The Netherlands]). Once the ideal postoperative result was digitally achieved, scaled, sterilizable, and patient-specific 3D models of the preoperative and ideal postoperative result were manufactured in-house using a departmentally owned 3D printer.

Results
3D-printed models have successfully been manufactured and employed for 12 patients undergoing rhinoplasty. The average time to prepare a set of pre- and postoperative models was 3 hours, while the printing process required 18 to 24 hours per model. Each set of surgical models can be manufactured at a total materials cost of approximately $5.00.

Conclusions
We describe an affordable means to construct sterilizable, scaled, patient-specific 3D-printed models for rhinoplasty. This technique may become of increasing interest to academic and cosmetic centers as hardware costs of 3D printers continue to fall.

Level of Evidence: 4