bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Forms of Human Protein C: Comparison and Distribution in Human Adult Plasma
Authors: Greffe Brian S , Manco-Johnson Marilyn J , Marlar Richard A 
Published: June 2018

SummaryProtein C (PC) is a vitamin K-dependent protein which functions as both an anticoagulant and profibrinolytic. It is synthesized as a single chain protein (SC-PC) and post-transla-tionally modified into a two chain form (2C-PC). Two chain PC consists of a light chain (LC) and a heavy chain (HC). The present study was undertaken to determine the composition of the molecular forms of PC in plasma. PC was immunoprecipitated, subjected to SDS-PAGE and Western blotting. The blots were scanned by densitometry to determine the distribution of the various forms. The percentage of SC-PC and 2C-PC was found to be 10% and 90% respectively. This is in agreement with previous work. SC-PC and the heavy chain of 2C-PC consisted of three molecular forms (“alpha”, “beta”, and “gamma”). The “alpha” form of HC is the standard 2C form with a MW of 40 Kd. The “beta” form of HC has also been described and has MW which is 4 Kd less than the “alpha” form. The “gamma” species of the SC and 2C-PC has not been previously described. However, its 3 Kd difference from the “beta” form could be due to modification of the “beta” species or to a separate modification of the alpha-HC. The LC of PC was shown to exist in two forms (termed form 1 and form 2). The difference between these two forms is unknown. The molecular forms of PC are most likely due to a post-translational modification (either loss of a carbohydrate or a peptide) rather than from plasma derived degradation.
The Relationship between Anti-Factor Xa Level and Clinical Outcome in Patients Receiving Enoxaparine Low Molecular Weight Heparin to Prevent Deep Vein Thrombosis after Hip Replacement
Authors: Levine M N , Planes A , Hirsh J , Goodyear M , Vochelle N , Gent M 
Published: June 2018

SummaryStudies in experimental animals have demonstrated that there is a relationship between levels of low molecular weight (LMW) heparin and both bleeding and inhibition of thrombosis. The relationship between these outcomes and ex vivo anti-factor Xa levels has been examined in 163 patients undergoing total hip replacement who were given prophylaxis once daily with a LMW heparin (enoxaparine). Fifty patients received 60 mg of enoxaparine and 113 received 40 mg, both regimens being administered subcutaneously once daily. Blood samples for anti-factor Xa levels were collected 12 hours after the injection on the day of surgery and on days 1, 3 and 6, postoperatively. The incidence of wound hematoma was 5.3% when the maximum anti-factor Xa level was ≤0.2 units per ml, but increased to 24.5% when the anti-factor Xa level exceeded 0.2 units per ml, P = 0.0008. The incidence of postoperative thrombosis was low (6.3%) if the minimum anti-factor Xa level exceeded 0.1 units per ml, but increased to 14.6% when ≤0.1 units per ml, and to 18.8% if the anti-factor Xa level was ≤0.05 units per ml. Regression analysis revealed that there was a statistically significant relationship between anti-factor Xa level and wound hematoma, P = 0.002 and anti-factor Xa level and thrombosis, P = 0.03. These findings suggest that when enoxaparine is administered as a once daily subcutaneous injection, the 12 hour anti-factor Xa level should not exceed 0.2 units per ml to minimize bleeding and levels >0.05 units per ml should be obtained to optimize efficacy.
The Effect of Calcium Chloride on Anti-Xa Activity of Heparin and Its Molecular Weight Fractions
Authors: Barrowcliffe T W , Shirley Yvonne Le 
Published: June 2018

SummaryThe anti-Xa activities of unfractionated heparin (UFH) and nine low molecular weight heparins (LMWH) have been measured in the presence and absence of 3 mM CaCl2, using bovine Factor Xa, purified human AT III and an amidolytic assay. The addition of CaCl2 increased the activity of UFH by 93%, but the effect on LMWH was less, ranging from −20% to +55%. Studies of gel filtration fractions of UFH showed marked Mr dependence of the CaCl2 effect in the range 4,000-12,000. The differences among the various LMW heparins with respect to the effect of CaCl2 were closely correlated with the amount of polysaccharide above an Mr of 6,500. Kinetic studies confirmed the potentiation of the activity of UFH with bovine Xa and showed an even more marked effect using human Xa.
Differential Ability of Agonists to Express Distinct Pools of Fibrinogen (Gpllb/llla) Receptors which Can Mediate the Aggregation of Human Platelets
Authors: Watts Ian S , Keery Rebecca J , Lumley Philip 
Published: June 2018

SummaryWe have investigated the effect of two procedures that modify human platelet surface membrane glycoprotein (Gp) IIb and IIIa complexes upon whole blood platelet aggregation to a range of agonists. (A) Irreversible disruption of complexes by temporary (30 min) Ca2+-deprivation with EGTA at 37° C. (B) Binding of a monoclonal antibody M148 to the complex. EGTA exposure abolished aggregation to ADP, adrenaline and PAF. In contrast, full aggregation curves to collagen and U-46619 could still be established. EGTA exposure reduced M148 binding to platelets by 80%. Excess M148 abolished aggregation to ADP, PAF, collagen and U-46619. However, upon removal of unbound antibody from platelets full aggregation curves to collagen and U-46619 but not to ADP and PAF could be re-established. Thus human platelet aggregation to ADP, PAF and adrenaline appears absolutely dependent upon surface membrane GpIIb/IIIa complexes. In contrast, collagen and U-46619 cause expression of an additional distinct pool of Gp complexes inaccessible to EGTA and M148 in unstimulated platelets which is intimately involved in aggregation to these agonists.
A Variant of Glanzmann's Thrombasthenia Characterized by Abnormal Glycoprotein IIb/IIIa Complex Formation
Authors: Fournier Dominique J , Kabral Arnold , Castaldi Peter A , Berndt Michael C 
Published: June 2018

SummaryGlanzmann's thrombasthenia is a congenital bleeding abnormality characterized by absent platelet aggregation due to the failure of fibrinogen to bind to activated thrombasthenic platelets. In the majority of cases, this defect is caused by the absence or marked reduction of a specific fibrinogen-binding aggregation receptor, the GP IIb/IIIa complex. E.T., an 18-year-old female with a life-long history of bleeding and easy bruising, had the normal clinical features of Glanzmann's thrombasthenia. Surprisingly, sodium dodecyl sulphate-polyacrylamide gel electrophoresis of her platelets showed no apparent abnormality of the GP IIb/IIIa complex. Control platelets washed in the presence of 2 mM EDTA and control and patient platelets washed in the presence of 2 mM calcium ions showed normal reactivity with anti-GP IIb, anti-GP Ilia, and anti-GP IIb/IIIa complex specific monoclonal antibodies as evaluated by flow cytometry. In contrast, patient's platelets washed in the presence of 2 mM EDTA reacted with anti-GP IIb, anti-GP Ilia, but not with the complex-specific monoclonal antibodies. The increased susceptibility of the patient's GP IIb/IIIa complex to EDTA dissociation was confirmed by crossed immunoelectrophoresis (CIE). CIE analysis further indicated that the patient's GP IIb/IIIa complex did not bind fibrinogen. The combined results suggest that this patient has Glanzmann's thrombasthenia due to an abnormal association of the GP IIb/IIIa complex which results in the failure of the complex to bind fibrinogen.
Mechanism of Potentiation by Manganese Ion of Aggregation of Porcine Pancreatic Elastase-Treated Human Platelets
Authors: Azuma Hiroyuki , Shigekiyo Toshio , Miura Shinji , Uno Yuka , Saito Shiro 
Published: June 2018

SummaryThe effect of manganese ion (Mn2+) on the aggregation of porcine pancreatic elastase-treated platelets (ETP) induced by fibrinogen (Fbg) was studied. Mn2+ enhanced the aggregation of ETP on addition of Fbg specifically and dose-dependently. This effect of Mn2+ was not associated with the formation of thromboxane A2, and was not affected by pretreatment of ETP with acetylsalicylic acid in the presence of Mn2+. Moreover, it was not dependent on extracellular adenosine diphosphate, as shown by removal of extracellular adenosine diphosphate by pretreatment of ETP with creatine phosphate/creatine phosphokinase. Studies on the binding of 125I-Fbg to ETP showed that Mn2+ increased the Kd value of binding but did not affect the number of Fbg binding sites. These results indicate that Mn2+ specifically and dose-dependently potentiated Fbg-induced aggregation of ETP and that this effect of Mn2+ may be due to an increase in the affinity of binding of Fbg to the glycoprotein IIb-IIIa complex on the membranes of ETP.
Thrombin Stimulated Platelet Accumulation on Protein Coated Glass Capillaries: Role of Adhesive Platelet α-Granule Proteins
Authors: Mulvihill Juliette N , Davies J Andrew , Toti Florence , Freyssinet Jean-Marie , Cazenave Jean-Pierre 
Published: June 2018

SummaryThe generation of trace amounts of thrombin at artificial surfaces in contact with blood is likely to be a contributing factor in thrombosis on biomaterials. Using an in vitro capillary perfusion system, platelet accumulation on glass surfaces, uncoated or precoated with purified bovine collagen or human plasma proteins, was determined in the presence or absence of preadsorbed purified human thrombin. Static adsorption for 15 min at 22° C from solutions of thrombin 100 NIH units (33 μg)/ml gave surface concentrations in the range 0.019-0.101 μg/cm2. Protein coated capillaries, thrombin treated or untreated, were perfused for 2 min at 37° C with suspensions of washed 111In-labeled human platelets in Tyrode's-albumin buffer containing 40% washed red blood cells, under conditions of controlled, non pulsatile laminar flow (50 s−1 or 2,000 s−1). Platelet accumulation was increased in the presence of surface adsorbed thrombin on uncoated and albumin or fibrinogen coated glass but little affected on fibronectin or collagen coated glass. On von Willebrand factor (vWF) coated glass, thrombin enhancement was observed only at high shear forces. In experiments using antibodies against human platelet α-granule proteins, thrombin stimulated platelet deposition in uncoated glass capillaries was inhibited at 2,000 s−1 by anti-vWF and to a lesser extent by anti-fibrinogen but not by antithrombospondin antibodies.
Inhibition of Platelet Thromboxane Formation and Phosphoinositides Breakdown by Osthole from Angelica pubescens
Authors: Ko Feng-Nien , Wu Tian-Shung , Liou Meei-Jen , Huang Tur-Fu , Teng Che-Ming 
Published: June 2018

SummaryOsthole, isolated from Chinese herb Angelica pubescens, inhibited platelet aggregation and ATP release induced by ADP, arachidonic acid, PAF, collagen, ionophore A23187 and thrombin in washed rabbit platelets. It showed a weak activity in platelet-rich plasma. Osthole inhibited the thromboxane B2 formation caused by arachidonic acid, collagen, ionophore A23187 and thrombin in washed platelets, and also the thromboxane B2 formation caused by the incubation of lysed platelet homogenate with arachidonic acid. The generation of inositol phosphates in washed platelets caused by collagen, PAF and thrombin was suppressed by osthole. These data indicate that the inhibitory effect of osthole on platelet aggregation and release reaction was due to the inhibition of thromboxane formation and phosphoinositides breakdown.
Ouabain Enhances Basal and Stimulus-Induced Cytoplasmic Calcium Concentrations in Platelets
Authors: Lees A D , Wilson J , Orchard C H , Orchard M A 
Published: June 2018

SummaryIncubation of platelet-rich plasma (PRP) with ouabain, an inhibitor of sodium/potassium ATPase (Na+/K+ ATPase), induced a significant rise in basal platelet intracellular calcium concentration ([Ca2+]i) when measured using fura 2. Ouabain induced an enhanced aggregation response to low doses of collagen in both PRP and washed platelets loaded with aequorin. In aequorin loaded platelets this enhanced aggregation response was associated with an enhanced rise in [Ca2+]j such that the relationship between [Ca2+]i and aggregation was unchanged. As inhibition of plasma membrane Na+/K+ ATPase would lead to a raised intracellular sodium ion concentration ([Na+]i) the results suggest that in the platelet, [Na+]i can modulate [Ca2+]i and hence influence the response of platelets to stimuli such as collagen.
Rat Platelets Adhere to Human Thrombin-Treated Rat Lungs under Flow Conditions
Authors: Venturini Catherine M , Fenton John W , Minnear Fred L , Kaplan John E 
Published: June 2018

SummaryPlatelet attachment to thrombin-treated endothelium was examined under flow conditions in the vascular bed of isolated perfused rat lungs. The infused thrombin bound to the pulmonary endothelium in a specific, competitive manner as shown by displacement of 125I-α-thrombin with an excess of cold diiso-propylfluoro-phosphate-α-thrombin. α-Thrombin significantly increased the attachment of isolated 51Cr-labelled rat platelets to the perfused lungs. Scanning and high voltage electron microscopy showed single platelets in various stages of activation attached to pulmonary endothelium. The receptor binding site and catalytic activity of thrombin were essential to the enhancement of platelet attachment. Aspirin given to rats before the lung isolation had no effect on thrombin-induced platelet attachment. Thus, endothelial bound thrombin initiates platelet activation and enhances subsequent platelet attachment.
Prostanoid Release from Ex Vivo Perfused Canine Arteries and Veins: Effects of Prolonged Perfusion, Intermittent Perfusion, as well as Exposure to Exogenous Arachidonic Acid, Thrombin and Bradykinin
Authors: Brunkwall Jan S , Stanley James C , Kresowik Timothy F , Graham Linda M , Burkel William E , Bergqvist David 
Published: June 2018

SummaryRegulation of prostanoid release from ex vivo perfused vessel segments is not fully understood. A series of perfusion experiments were performed with canine arteries and veins to define certain regulatory phenomena. Arteries were perfused with pulsatile flow of 90 ml/min at a pressure of 100 mmHg, and veins with nonpulsatile flow of 90 ml/min at a pressure of 7 mmHg. Segments were perfused with Hanks' balanced salt solution for five 15-min periods with the perfusate exchanged after each study period. With onset of perfusion, there was an initial burst of prostacyclin release to 127 ± 40 pg/mm2, declining to 32 ± 10 pg/mm2 after 60 minutes (p <0.005). If perfusion continued for 5.5 hours, there was a stable release period between 1 and 3 hours, followed by a very slow decline. At that time addition of arachidonic acid (AA) increased prostacyclin release six-fold (p <0.01). Vessels perfused for 1 hour and then rested for another hour, responded to reperfusion at the second onset of flow with a two-fold increase in prostacyclin release (p <0.01). Vessels perfused with thrombin, bradykinin or A A (either added to each perfusate or only to the last perfusate) exhibited greater prostacyclin release than did control segments. Release of thromboxane steadily declined with time in all parts of the study, and only increased with the addition of A A to the perfusate. These data indicate that vessel segments subjected to ex vivo perfusion do not maximally utilize enzyme systems responsible for prostanoid production, and after 1 hour perfusion have not depleted their phospholipids, and maintain functioning levels of phospholipase and cyclooxygenase activity. This perfusion model allows for the study of prostacyclin and thromboxane release from arteries and veins and their response to various drugs and other stimuli.
Quality of Life in Children with Epilepsy in Private and Public Tertiary Care Centers in India
Authors: Karnavat Purva , Hegde Anaita , Kulkarni Shilpa 
Published: June 2018

Abstract
Background Pediatric epilepsy is associated with various comorbidities. It is known that children with epilepsy have a compromised health-related quality of life (QOL) and may be affected across physical, psychological, social, and educational domains.
Aims and Objectives (1) To study QOL in children with epilepsy from private and public outpatient departments, (2) study various risk factors affecting QOL, and (3) compare risk factors between groups.
Methods Sample consisted of 400 and 201 children aged 5 to 18 years from private and public settings with epilepsy taking antiepileptic drugs (AEDs) for at least 6 months. Structured case record form was used to collect data on sociodemographic, clinical, and treatment parameters. QOL was measured by the Pediatric Quality of Life Inventory (PedsQL) questionnaire (in the local language). Adverse effects were monitored by Pediatric Epilepsy Side Effects Questionnaire (PESQ). Univariate regression analysis was performed on the data (p < 0.005).
Results Overall PedsQL score was 67.21 ± 29.391 and 78.66 ± 9.161 in private and public settings, respectively (p = 0.000). QOL was affected significantly by age of the child, educational and economic background of the caregivers, age at the onset of epilepsy, seizure frequency, duration of treatment, number of drugs, presence of comorbidities, intelligence quotient (IQ) levels of children, and PESQ score in both the groups. Total PESQ score was 18.63 ± 17.02 and 7.69 ± 10.646 in private and public settings, respectively (p = 0.000).
Conclusions Children with epilepsy have a compromised QOL. Risk factors relating to QOL are numerous. Educational and economic status of caregivers plays a significant role in awareness of the problem.
Deletion of Extra Domain A of Fibronectin Reduces Acute Myocardial Ischaemia/Reperfusion Injury in Hyperlipidaemic Mice by Limiting Thrombo-Inflammation
Authors: Chorawala Mehul , Prakash Prem , Doddapattar Prakash , Jain Manish , Dhanesha Nirav , Chauhan Anil 
Published: June 2018

Background Fibronectin splicing variant containing extra domain A (Fn-EDA), which is an endogenous ligand for Toll-like receptor 4 (TLR4), is present in negligible amounts in the plasma of healthy humans, but markedly elevated in patients with co-morbid conditions including diabetes and hyperlipidaemia, which are risk factors for myocardial infarction (MI). Very little is known about the role of Fn-EDA in the pathophysiology of acute MI under these co-morbid conditions.
Materials and Methods We determined the role of Fn-EDA in myocardial ischaemia/reperfusion (I/R) injury in the hyperlipidaemic apolipoprotein E-deficient (ApoE−/−) mice. Infarct size, plasma cardiac troponin I (cTnI) levels, intravascular thrombosis (CD41-positive), neutrophil infiltration (Ly6 B.2-positive), neutrophil extracellular traps (citrullinated H3-positive) and myocyte apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling-positive) were assessed in myocardial I/R injury model (1-hour ischaemia/23 hours of reperfusion).
Results Irrespective of gender, Fn-EDA−/−ApoE−/− mice exhibited smaller infarct size and decreased cTnI levels concomitant with reduced post-ischaemic intra-vascular thrombi, neutrophils influx, neutrophil extracellular traps and myocyte apoptosis (p < 0.05 vs. ApoE−/− mice). Genetic deletion of TLR4 attenuated myocardial I/R injury in ApoE−/− mice (p < 0.05 vs. ApoE−/− mice), but did not further reduce in Fn-EDA−/− ApoE−/− mice suggesting that Fn-EDA requires TLR4 to mediate myocardial I/R injury. Bone marrow transplantation experiments revealed that Fn-EDA exacerbates myocardial I/R injury through TLR4 expressed on the haematopoietic cells. Infusion of a specific inhibitor of Fn-EDA, 15 minutes post-reperfusion, into ApoE−/− mice attenuated myocardial I/R injury.
Conclusion Fn-EDA exacerbates TLR4-dependent myocardial I/R injury by promoting post-ischaemic thrombo-inflammatory response. Targeting Fn-EDA may reduce cardiac damage following coronary artery re-canalization after acute MI.
Mitochondrial Neurogastrointestinal Encephalomyopathy Disease in Three Siblings from Pakistan with a Novel Mutation
Authors: Durrani Sana , Chen Bee , Yakob Yusnita , Hian Lua , Afroze Bushra 
Published: June 2018

AbstractMitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare multisystem autosomal recessive disorder. The disease is clinically heterogeneous with gastrointestinal symptoms of intestinal dysmotility and cachexia as well as neurological symptoms of ophthalmoplegia, neuropathy, sensorineural hearing impairment, and diffuse leukoencephalopathy being most prominent. MNGIE is caused by mutations in TYMP, a gene that encodes thymidine phosphorylase (TP)—a cytosolic enzyme. Mutations in TYMP lead to very low TP catalytic activity, resulting in dramatically increased thymidine and deoxyuridine in plasma. We describe the clinical, biochemical, and neuroimaging findings of three boys with MNGIE from a Pakistani family with a novel homozygous mutation, c.798_801dupCGCG p. (Ala268Argfs*?), in exon 7 of TYMP.
Analysis of cysteine protease inhibitor gene (BmCPI) promoter activity in silkworms using bac-to-bac baculovirus systems
Authors: Tian Sha , Zhang Ziyu , Zhang Renze , Liu Qing , Xu Shuping , Gong Jing , Hou Yong 
Published: June 2018

ABSTRACT
A cysteine protease inhibitor of Bombyx mori (BmCPI) plays an important role in pupation, molting, and dissociation of tissues. The present study identified and analyzed the BmCPI promoter region to better understand its functional regulatory mechanisms. Eight promoter fragments of different lengths were analyzed using an improved Bac-to-Bac expression system. Luciferase activities were investigated both in BmE cells and larval organisms after infection with the Bac-to-Bac system, and similar changes in activity were observed in both models. Strong activity was detected in the longest promoter (2005 bp, −1969 to +36), and activity changed significantly with truncation of promoter length. An electrophoretic mobility shift assay showed that the promoter region from −32 to +6 bp played a critical role in activating the downstream gene promoter element, where some potential elements were also predicted by informatics tools. The findings offer a basic reference for the mechanism of transcriptional regulation of BmCPI.
Calciphylaxis in a patient without renal failure
Authors: Hesse Amber , Herber Andrew , Breunig Mike 
Published: June 2018

ABSTRACT
Calciphylaxis is a rare disease that typically presents in patients with end-stage renal disease on dialysis or those who have received a renal transplant. Nonuremic calciphylaxis leads to ischemia and subsequent necrosis of subcutaneous tissue. Diseases associated with nonuremic calciphylaxis include primary hyperparathyroidism, connective tissue disease, malignancy, and alcoholic liver disease. Due to its high mortality, early identification and an aggressive multidisciplinary treatment approach is necessary to improve patient outcomes.
Using drug monitoring programs to optimize pain management for elective surgery patients
Authors: Lowry Robert 
Published: June 2018

ABSTRACT
This article describes an innovative workflow that incorporates the prescription drug monitoring program (PDMP) into a suggested workflow for managing pain in elective surgery patients. Using the PDMP and working with the patient's pain management provider, clinicians can make sure that patients on chronic opioid therapy are identified before admission so that their care can be individualized, a plan developed to manage postoperative pain, and the patient can be transitioned seamlessly back to outpatient pain management.
Understanding posterior reversible encephalopathy syndrome
Authors: Fittro Kenneth , Dizon Roderick 
Published: June 2018

ABSTRACT
Posterior reversible encephalopathy syndrome is a characteristic clinical-radiographic syndrome with diverse and multifactorial causes. Symptoms include headache, altered mental status, seizures, nausea and vomiting, and vision abnormalities. The syndrome is treated by lowering BP, administering anticonvulsant medications, correcting metabolic abnormalities, and removing offending agents. Secondary complications include ischemia, hemorrhage, and cerebral infarction.