bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Molecular Weight Heparin in Haemodialysis for Chronic Renal Failure: Dose Finding Study of CY222
Authors: Ireland H , Lane D A , Flynn A , Pegrum A C , Curtis J R 
Published: May 2018

SummaryA dose finding study of the very low molecular weight heparin CY222 (MW 2500) in patients (n = 8) with chronic renal failure undergoing dialysis has been carried out to (i) establish an effective dose and (ii) determine the relationship between ex vivo anti-factor Xa levels in plasma and the anticoagulant effect (in vivo suppression of FPA levels). Doses of CY222 were compared to a dose (5000 iu bolus + 1500 iu/hr) of unfractionated heparin (UFH) that has been shown to suppress FPA levels during prolonged (>5 hr) dialysis (Ireland et ah, J Lab Clin Med 103, 643, 1984). CY222 given iv in increasing doses produced a dose related increase in anti-factor Xa levels (measured as Institute Choay u/ml, with CY222 itself as standard) and suppression of FPA levels. When given in its highest dose, 20,000 Institute Choay u bolus + 1500 Institute Choay u/hr, there was little effect upon KCCT, FPA levels were statistically indistinguishable from those of the UFH regime (indicating comparable anticoagulant effect), but anti-factor Xa levels (expressed in Institute Choay u/ ml) were 2-3 times those of UFH (expressed in iu/ml). All samples were also assayed for anti-factor Xa level against the proposed low MW Heparin Standard. Plasma levels of CY222 were then found to be 2.78 times lower, so that the anti-factor Xa levels of CY222 required to produce comparable anticoagulant effect were then indistinguishable from those of UFH. Clinically, doses of CY222 exceeding 10,000 Institute Choay u bolus were effective, although increasing amounts of fibrin were visible in the drip chamber of the dialyser circuit with decreasing dose. These results indicate that CY222 is an effective anticoagulant for haemodialysis that can be monitored by its anti-factor Xa level in plasma (in conjunction with the appropriate standard). For prolonged dialysis a dose of 20,000 Institute Choay u bolus + 1500 Institute Choay u/hr is effective at suppressing fibrin formation, while the maintenance infusion may be unnecessary for short frequent dialyses.
The Application of the Biotin/Avidin System to the von Willebrand Factor Antigen Immunoassay
Authors: Taylor L D 
Published: May 2018

SummaryA vWf: Ag ELISA which uses biotinylated anti-vWf: Ag IgG and an avidin/biotinylated peroxidase (ABP) complex detection system has been developed. The sensitivity of the ELISA for vWf: Ag was 4 × 10-5 U/ml which is approximately 10-fold lower than previously reported vWf: Ag ELISA’s. The avidin used for the preparation of the ABP complex was glutaraldehyde-treated. This treatment increased the reactivity 2-3-fold as compared to ABP complex prepared using untreated avidin. The reactivity of two commercial detection reagents was also tested.The effect of the reduction of the total assay time to 3.5 h is also described. In this form the detection limit for vWf: Ag was 2 × 10-4 U/ml, the intra-assay precision at vWf: Ag concentrations of 0.01 and 0.0025 U/ml was 3.8% and 4.9% respectively and ELISA results for normal individuals still correlated well with those obtained using electro-immunodiffusion (r = 0.93).
Pharmacokinetics of Dermatan Sulfate in the Rabbit After Intravenous Injection
Authors: Dol F , Houin G , Dupouy D , Cadroy Y , Caranobe C , Gabaig A M , Mardiguian J , Sie P , Boneu B 
Published: May 2018

SummaryTo investigate the pharmacokinetic properties of dermatan sulfate (DS), a new potential antithrombotic agent, two different approaches were used. In the first one, DS was derivatized with 3-4 hydroxyphenyl propionic acid N hydroxysuccinimide ester (SHPP) and iodinated. The labelled derivative was injected by IV route to rabbits with increasing doses of unlabelled compound ranging from 20 to 4000 μg/kg. The disappearance of DS from plasma was characterized by measuring both the circulating radioactivity and the biological activity using an original assay based upon the catalysis of heparin cofactor II – thrombin formation. The radioactivity data indicated that the volume of distribution, the clearance and the half life of the tracer were independent of the dose of DS injected. DS concentrations measured by the bioassay indicated that more than 90% were cleared with half lives close to those calculated from the radioactivity data; the remaining biological activity was cleared at a slower rate. Experiments performed with bi-nephrectomized animals indicated that the kidneys play a major role in the elimination of DS or of its metabolites which may have a residual biological activity. In the second set of experiments, unlabelled DS was delivered under continuous intravenous infusion for 5 hours at 5 increasing doses ranging from 160 to 4200 μg/kg/h. The biological activities were used to measure the plateau concentration of DS: there was a linear relationship between the dose delivered and the plasma concentration. These data indicate that the pharmacokinetic profile of DS is very close to that of low molecular weight heparin, and quite different from that of SH.
Cytomegalovirus Alters the von Willebrand Factor Content in Human Endothelial Cells
Authors: Bruggeman C A , Debie W H M , Muller A D , Schutte B , Dam-Mieras M CE van 
Published: May 2018

SummaryCultured human endothelial cells were infected with human cytomegalovirus AD 169 and Kerr. The infection resulted in the appearance of viral antigens in the nuclei of about 10% of the endothelial cells and in the concomittant disappearance of vWF from the infected cells. No differences were observed between endothelial cells from different sources (umbilical cord veins or arteries, adult veins).
Standard Heparin Enhances the Antithrombotic Activity of Dermatan Sulfate in the Rabbit but CY 216 Does Not
Authors: Cadroy Y , Dol F , Caranobe C , Petitou M , Lormeau J C , Sié P , Choay J , Boneu B 
Published: May 2018

SummaryStandard heparin (SH) and dermatan sulfate (DS) two gly- cosaminoglycans with different pharmacological targets are effective antithrombotic agents in the rabbit. We have investigated the antithrombotic activity of the association DS plus SH. It was found that doses as low as 25 µg/kg for DS and 10 µg/kg for SH were ineffective when injected separately but generated a high and significant antithrombotic activity when injected together. These results were confirmed when higher doses of each compound were delivered in association. Further experiments were performed to determine if the enhancement of the antithrombotic activity of DS by HS resulted from its anti-factor Ha or antifactor Xa activity or from its moiety without affinity to AT III. A low molecular weight heparin (CY 216) with an anti-factor Xa/ anti-factor Ha ratio of 5, the synthetic pentasaccharide bearing the minimum binding sequence to antithrombin III, and a low affinity fraction of SH to AT III did not increase the antithrombotic activity of DS; in contrast a high affinity fraction of SH to AT III had the same effect than SH. We conclude that the enhancement of the antithrombotic activity of DS by SH mainly results from its anti-factor IIa activity.
Fibrinolysis in Normal Subjects - Comparison Between Plasminogen Activator Inhibitor and Other Components of the Fibrinolytic System
Authors: Nicoloso Grazia , Hauert Jacques , Kruithof Egbert K O , Melle Guy Van , Bachmann Fedor 
Published: May 2018

SummaryWe analyzed fibrinolytic parameters in 20 healthy men and 20 healthy women, aged from 25 to 59, before and after 10 and 20 min venous occlusion. The 10 min post-occlusion fibrinolytic activity measured directly in diluted unfractionated plasma by a highly sensitive 125I-fibrin plate assay correlated well with the activity of euglobulins determined by the classical fibrin plate assay (r = 0.729), but pre-stasis activities determined with these two methods did not correlate (r = 0.084). The enhancement of fibrinolytic activity after venous occlusion was mainly due to an increase of t-PA in the occluded vessels (4-fold increase t-PA antigen after 10 min and 8-fold after 20 min venous occlusion). Plasminogen activator inhibitor (PAI) activity and plasminogen activator inhibitor 1 (PAI-1)1 antigen levels at rest showed considerable dispersion ranging from 1.9 to 12.4 U/ml, respectively 6.9 to 77 ng/ml. A significant increase of PAI-1 antigen levels was observed after 10 and 20 min venous occlusion. At rest no correlation was found between PAI activity or PAI-1 antigen levels and the fibrinolytic activity measured by 125I-FPA. However, a high level of PAI-1 at rest was associated with a high prestasis antigen level of t-PA and a low fibrinolytic response after 10 min of venous stasis. Since the fibrinolytic response inversely correlated with PAI activity at rest, we conclude that its degree depends mainly on the presence of free PAI.
Comparison of the Platelet Aggregation Induced by Three Thrombin-Like Enzymes of Snake Venoms and Thrombin
Authors: Teng Che-Ming , Ko Feng-Nien 
Published: May 2018

SummaryPlatelet aggregation induced by three thrombin-like enzymes of snake venoms was compared with that by thrombin. Acutin was isolated from Agkistrodon acutus venom and thrombocytin and batroxobin were from Bothrops atrox venom. The fibrinogenclotting activities were 700,170 and 7 U/mg for batroxobin, acutin and thrombocytin, respectively. They induced aggregation and ATP release of washed rabbit platelets. The aggregating activity of thrombin was 102, 104 and 105 times more potent than those of thrombocytin, acutin and batroxobin, respectively. Plateletactivating potency of the thrombin-like enzymes was correlated with their effectiveness on the retractility and elasticity of the clots. Platelet aggregation induced by thrombin or thrombocytin could be inhibited by heparin with antithrombin III while that by acutin or batroxobin could not. Indomethacin showed weak inhibition on the aggregation while the ADP-scavenging system, creatine phosphate/creatine phosphokinase, inhibited the aggregation induced by the three thrombin-like enzymes but not that by thrombin. Platelet aggregation induced by the thrombin-like enzymes could not be inhibited by PAF antagonists-BN 52021, kadsurenone or L-652,731. In the presence of EGTA, only thrombin could induce ATP release from platelets. Thrombin-like enzymes and low concentration of thrombin did not form thromboxane B2. Nitroprusside and prostaglandin E1 completely inhibited the aggregation, mepacrine and imipramine showed marked inhibition while verapamil had only weak inhibition. It is concluded that the aggregation induced by the thrombin-like enzymes is different from that of thrombin and mainly due to ADP released from platelets.
A Monoclonal Antibody-Based Enzyme Immunoassay for Fibrin Degradation Products in Plasma
Authors: Koppert P W , Hoegee-de Nobel E , Nieuwenhuizen W 
Published: May 2018

SummaryWe have developed a sandwich-type enzyme immunoassay (EIA) for the quantitation of fibrin degradation products (FbDP) in plasma with a time-to-result of only 45 minutes.* The assay is based on the combination of the specificities of two monoclonal antibodies (FDP-14 and DD-13), developed in our institute. FDP-14, the capture antibody, binds both fibrinogen degradation products (FbgDP) and FbDP, but does not react with the parent fibrin(ogen) molecules. It has its epitope in the E-domain of the fibrinogen molecule on the Bβ-chain between amino acids 54-118. Antibody DD-13 was raised using D-dimer as antigen and is used as a tagging antibody, conjugated with horse-radish peroxidase. A strong positive reaction is obtained with a whole blood clot lysate (lysis induced by tissue-type plasminogen activator) which is used as a standard. The EIA does virtually not detect FbgDP i. e. purified fragments X, Y, or FbgDP generated in vitro in plasma by streptokinase treatment. This indicates that the assay is specific for fibrin degradation products.We have successfully applied this assay to the plasma of patients with a variety of diseased states. In combination with the assay previously developed by us for FbgDP and for the total amount of FbgDP + FbDP (TDP) in plasma, we are now able to study the composition of TDP in patients plasma in terms of FbgDP and FbDP.
Mid-Term Clinical Outcome and Reconstruction of Posterior Tibial Slope after UKA
Authors: Franz Alois , Boese Christoph , Matthies Andrej , Leffler Jörg , Ries Christian 
Published: May 2018

AbstractUnicompartmental knee arthroplasty (UKA) has gained growing popularity over the last decades. The posterior tibial slope (PTS) has been shown to play a significant role for knee biomechanics and is thought to be crucial for clinical function of the UKA. We evaluated the clinical outcome at mid-term follow-up after UKA. Furthermore, the reconstruction of the individual PTS was analyzed. A total of 91 consecutive patients undergoing medial UKA for osteoarthritis were included. Patients were contacted by telephone for a survival analysis at a minimum of 30 months after surgery. Patient-oriented questionnaires and Knee Osteoarthritis Outcome Score (KOOS) were obtained. A retrospective chart review and radiological analysis of component alignment were performed for all patients before and at 6 weeks after surgery. Of 91 patients (93 knees) undergoing UKA, 69 patients (70 knees) were available for clinical follow-up after a mean of 56.0 (range 31–81) months post-surgery. The clinical results of the examined patients in the present study showed mean subscale scores of the KOOS and Western Ontario and McMaster Universities Osteoarthritis Index between 71 and 91%. Overall 7 of 91 patients were revised during the course of follow-up period and underwent total knee arthroplasty. A Kaplan–Meier analysis showed a survival rate for UKA of 90.5% after 48 months. Calculated implant survival was 75.9 months (95% confidence interval 72.3–79.6) at the mean. The radiographic analysis of pre- and postoperative PTS showed no differences (p = 0.113).UKA for osteoarthritis of the medial knee compartment shows encouraging clinical results at mid-term follow-up. The individual PTS could be reconstructed within acceptable ranges. This is a retrospective therapeutic study with Level IV.
Prevotella melaninogenica Meningitis and Abscess: A Complication of the Removal of a Midline Dermoid Cyst
Authors: Garcia Megan B. , Kunz Anjali N. 
Published: May 2018

Abstract
Prevotella species are gram-negative anaerobic commensal bacteria of the oropharynx, which frequently cause periodontal disease but are otherwise rarely implicated in serious bacterial infections. Cranial dermoid cysts are benign neoplasms that grow along the planes of the embryonic neural tube closure. In infants, they most commonly present in frontal locations, including periorbital, nasal, and within the anterior fontanelle. Although dermoid cysts are slow growing, usually uncomplicated, and easily treated definitively with surgical excision, cranial cysts located on the midline are associated with a higher risk for persistent dermal sinus tract with intracranial extension of the tumor. We describe a case of a 10-month-old male patient with an occipital midline dermoid cyst with intracranial extension, infected with Prevotella melaninogenica, and complicated by intracranial abscess formation and meningitis.This case highlights two unusual disease entities: the uncommon occipital location of a dermoid cyst, and complications of that cyst caused by a serious bacterial infection with a normal oral flora. We discuss the recommendation for neuroimaging prior to surgical excision of a midline dermoid cyst, given the risk for dermal sinus tract with intracranial communication. We also discuss potential mechanisms for bacterial inoculation of this cyst with Prevotella melaninogenica. This pathogen has not previously been reported as a complication of dermoid cysts.
Hamartin regulates cessation of mouse nephrogenesis independently of Mtor
Authors: Volovelsky Oded , Nguyen Thi , Jarmas Alison E. , Combes Alexander N. , Wilson Sean B. , Little Melissa H. , Witte David P. , Brunskill Eric W. , Kopan Raphael 
Published: May 2018

Significance
Mammals form the final numbers of nephrons, the functional units of their kidneys, before or within a few days after birth. This initial endowment declines throughout life without the ability to replace nephrons lost to injury. Therefore, humans with low nephron numbers (such as premature infants) have higher rates of kidney disease in adulthood. Here we report that partial reduction in hamartin activity within mouse renal progenitors can lead to a significant increase in nephron numbers in newborns. Nephrogenesis was prolonged by at least a day and correlated with higher engraftment rates in the developing niche in a stem cell engraftment assay. We provide evidence that this phenotype is independent of the inhibitory effect of hamartin on the Mtor complex.
Distributed and dynamic intracellular organization of extracellular information
Authors: Granados Alejandro A. , Pietsch Julian M. J. , Cepeda-Humerez Sarah A. , Farquhar Iseabail L. , Tkačik Gašper , Swain Peter S. 
Published: May 2018

Significance
To thrive in diverse environments, cells must represent extracellular change intracellularly despite stochastic biochemistry. Here, we introduce a quantitative framework for investigating the organization of information within a cell. Combining single-cell measurements of intracellular dynamics with a scalable methodology for estimating mutual information between time series and a discrete input, we demonstrate that extracellular information is encoded in the dynamics of the nuclear localization of transcription factors and that information is lost with alternative static statistics. Any one transcription factor is usually insufficient, but the collective dynamics of multiple transcription factors can represent complex extracellular change. We therefore show that a cell’s internal representation of its environment can be both distributed across diverse proteins and dynamically encoded.
Global patterns of protection of elevational gradients in mountain ranges
Authors: Elsen Paul R. , Monahan William B. , Merenlender Adina M. 
Published: May 2018

Significance
Mountain ranges constitute biodiversity hotspots, and montane species are shifting their ranges in elevation in response to climate change. Protecting elevational gradients can help fully capture montane biodiversity patterns and facilitate species range shifts. We map the protection of elevational gradients for mountain ranges worldwide to reveal where elevational protection is needed and may be optimized. Most of the world’s mountain ranges are narrowly protected and lack elevational distributions needed to preserve biodiversity. This could undermine the effectiveness of protected areas (PAs) under climate change. Strategic planning is required to prioritize elevational gradients in future PA establishment; otherwise, protecting roughly half of all mountainous area will be required to protect just 17% of land across nearly all elevational gradients.
Synergy between Fe and Ni in the optimal performance of (Ni,Fe)OOH catalysts for the oxygen evolution reaction
Authors: Xiao Hai , Shin Hyeyoung , Goddard William A. 
Published: May 2018

Significance
The oxygen evolution reaction (OER) is a key component to applications of electrochemistry in energy and environment, but the reaction mechanism for OER on a best-performing catalyst, the Fe-doped NiOOH [(Ni,Fe)OOH], is under debate. Using advanced quantum mechanics (QM) methods, we find that the (Ni,Fe)OOH systems feature synergy between Fe and Ni, in which the two components assume the two different key functionalities needed for OER, forming an active O radical and catalyzing the O–O coupling, respectively. It is this synergy that delivers the optimal performance of (Ni,Fe)OOH for driving the OER. This suggests a strategy to further improve the (Ni,Fe)OOH-type OER catalysts, i.e., separately screening for the best component for each key functionality.
Extant fold-switching proteins are widespread
Authors: Porter Lauren L. , Looger Loren L. 
Published: May 2018

Significance
It is commonly thought that each globular protein has a single 3D structure, or fold, that fosters its function. In contrast, recent studies have identified several fold-switching proteins whose secondary structures can be remodeled in response to cellular stimuli. Although thought to be rare, we found 96 literature-validated fold-switching proteins by exhaustively searching the database of protein structures [Protein Data Bank (PDB)]. Characterizing these proteins led us to hypothesize that their abundance may be underrepresented in the PDB. Thus, we developed a computational method that identifies fold-switching proteins and used it to estimate that 0.5–4% of PDB proteins switch folds. These results suggest that proteins switch folds with significant frequency, which has implications for cell biology, genomics, and human health.
PaleoceneIpomoea(Convolvulaceae) from India with implications for an East Gondwana origin of Convolvulaceae
Authors: Srivastava Gaurav , Mehrotra Rakesh C. , Dilcher David L. 
Published: May 2018

SignificanceThe origin of the worldwide-distributed morning glory family (Convolvulaceae) has been a matter of debate. The fossil record from late Eocene sediments of North America argues for a Laurasian origin that is in contrast to a molecular phylogenetic study that favors an East Gondwana origin. This report of fossilIpomoeafrom the late Paleocene of India supports the current molecular phylogenetic conclusions of an East Gondwana origin for Convolvulaceae.
Abrupt global-ocean anoxia during the Late Ordovician–early Silurian detected using uranium isotopes of marine carbonates
Authors: Bartlett Rick , Elrick Maya , Wheeley James R. , Polyak Victor , Desrochers André , Asmerom Yemane 
Published: May 2018

SignificanceThe Late Ordovician mass extinction (LOME) terminated one of the greatest biodiversity radiations in Earth history eliminating ∼85% of marine animals, and it is coincident with the first major glaciation of the Phanerozoic. To evaluate LOME origins, we use uranium isotopes from marine limestones as a proxy for global-ocean redox conditions. Our results provide evidence of an abrupt global-ocean anoxic event coincident with the LOME onset and its continuation after the biologic recovery, through peak glaciation, and the following early Silurian deglaciation. These results also provide evidence for widespread ocean anoxia initiating and continuing during icehouse conditions.
C-4 sterol demethylation enzymes distinguish bacterial and eukaryotic sterol synthesis
Authors: Lee Alysha K. , Banta Amy B. , Wei Jeremy H. , Kiemle David J. , Feng Ju , Giner José-Luis , Welander Paula V. 
Published: May 2018

Significance
Sterols are essential eukaryotic lipids that can be preserved as steroids in sedimentary rocks for billions of years. Because eukaryotes are the predominant modern day producers of these lipids, fossilized sterols are used as geological biomarkers for the presence of specific eukaryotes in ancient environments. Sterol lipids are also produced by a few bacteria, but the biosynthesis and function of sterols in bacteria are not as well-understood. In this study, we used a combination of bioinformatics and lipid analyses to identify bacterial sterol synthesis proteins. Our results indicate that bacteria have evolved distinct aspects of the sterol synthesis pathway independent of eukaryotes and show that exploring sterol physiology in bacteria can provide insight into this geologically relevant pathway.