bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Spleen Insoluble Fibrinolytic Proteinase Acting at Neutral pH: Its Partial Purification and Characterization
Authors: Okamoto Utako , Nagamatsu Yoko , Amemiya Takehiko 
Published: July 2018

SummaryAn insoluble fibrinolytic enzyme with a molecular weight of approximately 30000, was purified from the human spleen. A single protein band possessing fibrinolytic activity was obtained on polyacrylamide gel disk electrophoresis at pH 4.5.The enzyme, tentatively termed spleen fibrinolytic proteinase (SFP), degraded fibrinogen at neutral pH following Michaelis-Menten kinetics. This fibrinogenolytic activity was not inhibited by t-AMCHA, a specific plasmin inhibitor. SFP barely degraded certain synthetic ester or polypeptide substrates for trypsin, chymotrypsin, plasmin, Xa, elastase and collagenase. These results indicate a different nature for SFP compared to other enzymes examined. SFP was found to digest no elastin and its fibrinogenolytic activity was strongly inhibited by STI, indicating that it was not an elastase. SFP required neither Zn++ nor Ca+ + for its fibrinogenolytic activity, indicating that it differed from metal-dependent proteinases such as collagenase. SFP was inhibited by DFP but not by TLCK, suggesting that it contains an active serine residue, but no trypsin type histidine at its active center. These results appear to show that SFP is a unique proteinase in the spleen, which is capable of degrading fibrin and fibrinogen at neutral pH.
A Method to Determine the Optimal Intensity of Oral Anticoagulant Therapy
Authors: Rosendaal F R , Cannegieter S C , van der Meer F J M , Briët E 
Published: July 2018

SummaryOral anticoagulant therapy has been shown to be effective for several indications. The optimal intensity of anticoagulation for each indication, however, is largely unknown. To determine this optimal intensity, randomised clinical trials are conducted in which two target levels of anticoagulation are compared. This approach is inefficient, since the choice of the target levels will be arbitrary. Moreover, the achieved intensity is not taken into account.We propose a method to determine the optimal achieved intensity of anticoagulation. This method can be applied within a clinical trial as an “efficacy-analysis”, but also on data gathered in day-to-day patient care.In this method, INR-specific incidence rates of events, either thromboembolic or hemorrhagic, are calculated. The numerator of the incidence rate is based on data on the INR at the time of the event. The denominator consists of the person-time at each INR value, summed over all patients, and is calculated from all INR measurements of all patients during the follow-up interval. This INR-specific person-time is calculated with the assumption of a linear increase or decrease between two consecutive INR determinations. Since the incidence rates may be substratified on covariates, efficient assessment of the effects of other factors (e.g. age, sex, comedication) by multivariate regression analysis becomes possible.This method allows the determination of the optimal pharmacological effects of anticoagulation, which can form a rational starting point for choosing the target levels in subsequent clinical trials.
Herpes Simplex Virus Decreases Endothelial Cell Plasminogen Activator Inhibitor
Authors: Bok Robert A , Jacob Harry S , Balla Jozsef , Juckett Margaret , Stelle Theresa , Shatos Marie A , Vercellotti Gregory M 
Published: July 2018

SummaryHerpes simplex virus (HSV) infection is histopathologically associated with vascular injury, fibrinoid necrosis and inflammatory cell infiltrates. We have previously shown in vitro that HSV infection of human umbilical vein endothelial cells (HUVEC) promotes a procoagulant phenotype manifest by the induction of tissue factor, the loss of thrombomodulin, and an increase in platelet adhesion. In these studies we examined the effects of HSV infection on HUVEC plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA). HSV infection caused the loss of PAI-1 in the extracellular matrix (ECM) and that released into the supernatant of HUVEC. Both activity and antigen levels of the Serpin inhibitor are diminished as a result of HSV infection. The loss of inhibitor is not secondary to diminished vitronectin (Vn), the primary binding protein of PAI-1 in the ECM, but appears to be secondary to decreased synthesis at the RNA level. Tissue plasminogen activator (t-PA). synthesis is also decreased in endothelial HSV infection. PAI-1 loss may further promote a procoagulant phenotype in HSV infection in vivo.
The Role of Cyclic Nucleotides in the Release of Tissue-Type Plasminogen Activator and von Willebrand Factor
Authors: Tranquille N , Emeis J J 
Published: July 2018

SummaryThe modulation of the induced acute release of tissue-type plasminogen activator (t-PA) and of von Willebrand factor (vWF) by compounds affecting cyclic nucleotide levels was studied, using an isolated rat hindleg perfusion system. Platelet-activating factor (PAF; 5 nM) or bradykinin (0.8 (μM) were used to induce release of t-PA and vWF.The guanylate cyclase activators sodium nitroprusside and atrial natriuretic factor reduced the induced release of t-PA and vWF. Release was not affected by inhibiting nitric oxide production with NG-nitro-L-arginine. The effects of nitroprusside and atrial natriuretic factor could not be reproduced by infusion of 8-bromo-cGMP.The adenylate cyclase activator forskolin had no effect on bradykinin-induced release of t-PA and vWF, reduced PAF-induced t-PA release, but potentiated PAF-induced vWF release. These modulatory effects were only partially mimicked by infusion of 8-bromo-cAMP.None of the compounds tested was able to induce the release of t-PA or of vWF in the absence of stimulation by bradykinin or platelet-activating factor. Cyclic nucleotides can thus modulate, but not induce, the acute release of t-PA and vWF from perfused rat hindlegs.
The Course of Preexistent Immune Abnormalities in HIV Negative Haemophiliacs Treated for Two Years with a Monoclonal Purified Factor VIII Concentrate
Authors: Smid W M , van der Meer J , Smit J W , Halie M R 
Published: July 2018

SummaryThe administration of factor VIII concentrates has been associated with immune abnormalities in patients with severe haemophilia A, even in the absence of HIV infection.The effects of a monoclonal purified factor VIII concentrate, Hemofil M (Baxter), on preexistent immune abnormalities were assessed over a 2 year period in 22 HIV negative haemophiliacs. They were treated previously with other concentrates, and received Hemofil T from 1983 to 1988. No HIV infection was demonstrated. No serologic evidence for other viral (re)-infections was seen. A decrease of HLA-DR expression on non-B lymphocytes in the first year (P = 0.026), and a decrease of T4-T8 ratio over the 2 years were found (P = 0.0016). Skin tests were non-contributive. The decrease in HLA-DR expression is suggestive for an improved immune function, possibly due to a reduced content of protein or virus in this concentrate.
Problems of Oral Anticoagulation in an Adult with Homozygous Protein C Deficiency and Late Onset of Thrombosis
Authors: Pescatore P , Horellou H M , Conard J , Piffoux M , Van Dreden P , Ruskone-Fourmestraux A , Samama M 
Published: July 2018

SummaryWe describe a 57-year-old woman with homozygous protein C deficiency and mild thrombotic manifestations consisting of three spontaneous distal deep vein thromboses occurring after the age of 45. Previous surgery and pregnancies had been uneventful. Low but detectable protein C antigen and activity levels (both 20%) were discovered on the occasion of skin necrosis induced by oral anticoagulation. This therapy was interrupted because of skin necrosis and several episodes of disseminated intravascular coagulation (DIC) at the initiation of treatment despite a cautious protocol. No recurrent thromboembolic event has occurred in our patient using prophylactic doses of low molecular weight heparin for 24 months. New therapeutic approaches might be the administration of low molecular weight heparin or oral anticoagulation associated with protein C replacement in the induction period. This case reflects the variability of expression of protein C deficiency as well as the potential hazards of antivitamin K anticoagulation in this disorder.
Changes in β2-Glycoprotein I Antigenicity Induced by Phospholipid Binding
Authors: Wagenknecht Dawn R , McIntyre John A 
Published: July 2018

Summaryβ2-glycoprotein I (β2GPI) or apolipoprotein H has been described as a necessary cofactor for antiphospholipid antibody (aPA) binding in ELISA. Some investigators disagree with the β2-GPI requirement whereas data from other laboratories indicate that β2GPI, not phospholipid (PL), is the antigen for aPA. To investigate the cofactor we have produced three IgG1 monoclonal antibodies (mAb) to human β2GPI; 3G9, 1B4 and 3D11. Western blot analyses showed the mAb to bind human β2GPI (40 kDa), but no reactivity was observed with adult or fetal bovine sera. In contrast, rabbit anti-β2GPI reacted with both human and bovine sera. None of the mAb reacted with phosphatidylserine (PS) or cardiolipin (CL) by ELISA. There were no significant differences in ELISA binding to purified β2GPI when the mAb were adjusted to the same concentration. mAb 3G9 and 1B4 gave stronger signals in ELISA after β2GPI bound to PS; the increase for 3G9 was significantly greater than for 1B4 (p <0.002). mAb 3D 11 was unique inasmuch as it failed to recognize β2PGI bound to PS. In comparison, the rabbit anti-β2GPI was unaffected by PS-β2GPI binding. These observations indicate that the mAb recognize three distinct epitopes on β2GPI. The data suggest that β2GPI undergoes conformational changes subsequent to binding PL. Our findings are consistent with the hypothesis that aPA recognize a β2GPI neotope formed subsequent to binding PL.
Use of Chromogenic Substrate S-2251 for Determination of Plasminogen Activator in Rat Ovaries
Authors: Shimada H , Mori T , Takada A , Takada Y , Noda Y , Takai I , Kohda H , Nishimura T 
Published: July 2018

SummaryA simple, specific and reproducible method for determination of plasminogen activator activity in rat ovaries has been developed by using the chromogenic substrate S-2251. The two steps of enzymatic reactions, i. e. activation of plasminogen and subsequent hydrolysis of the substrate was performed in one step incubation. A linear relationship was observed between the amount of chromogen produced and activator activity in the range of the optical density from 0.05 to 1.20 for 30 min’s incubation. Endogenous activity of non-specific proteases, plasmin or plasmin inhibitors which might be contained in rat ovaries turned out not to interfere with the specificity of a standardized assay procedure. Reproducibility was firmly established with coefficient of variation not exceeding 10%. Using this method, a marked increase followed by a drastic decrease in the activator activity was shown with rat ovaries around the time of ovulation after the injection of human chorionic gonadotropin.
Circulating Immune Complexes Pre and Post Clotting Factor Infusion in Hemophilia
Authors: Gomperts Edward D , Jordan Stanley , Berg Debbie , Sakai Rebecca , Boylen Lois 
Published: July 2018

SummaryCirculating immune complexes (CICs) were studied by the Raji cell radioimmune-assay (Raji-RIA) and Clq-solid phase assay (Clq-SPA) in sera samples obtained pre and post replacement infusion from 21 young hemophiliac patients (Mean age 9.5 years). Seven patients had repeat studies. Sixteen patients were selected randomly; the other five were selected as having potential infusion related disease processes. All patients had received multiple infusions prior to entering the study. Five patients were infused with FIX concentrates (2 Hemophilia B, one FVII deficiency, 2 with inhibitors to FVIII). Of the hemophilia A patients (13 severe; 3 mild/moderate), six were infused with ABO-Rh type specific cryoprecipitate and 10 were infused with factor concentrate. Preinfusion sera samples evaluated by the Raji-RIA showed 14 of 28 (50%) sera positive. Eleven of 28 (39.3 %) were positive post infusion in the Raji-RIA. Pre and post infusion studies of the same sera samples using the Clq-SPA showed 5 of 28 (17.9%) positive pre-infusion and 4 of 28(14.3%) positive post infusion. No statistically significant relationship between pre and post infusion studies could be demonstrated.There was no obvious correlation between CIC levels and patient age, race, Epe of infusate, ABO-Rh blood type, hepatosplenomegaly, the presence or absence of HBsAG, antibody, or chronic joint changes. CICs were detected in the three patients with SGOT/SGPT levels greater than 5 times normal, in both patients with chronic renal disease (chronic glomerulonephritis), and two children who had previously demonstrated a Coombs’-positive hemolytic anemia after factor concentrate infusion. Six of eight patients with extremely high levels of CICs had associated clinical or laboratory abnormalities.This data indicated that CICs (as detected by the Raji-RIA) are present in increased frequency in hemophiliac patients. Although individual patients developed CICs post infusion, there is no clinical or statistical data supporting a common infusate immunogen. CICs were present in patients with serum hepatitis and other immune related disorders, probably secondary to factor infusion. The immunopathogenicity and origin of CICs in hemophiliacs is uncertain.
Glanzmann’s Thrombasthenia
Authors: Khanduri U , Pulimood R , Sudarasanam A , Carman R H , Jadhav M , Pereira S 
Published: July 2018

SummaryIn the 14 year period from June, 1966 to June, 1980, 42 cases of Glanzmann’s thrombasthenia have been diagnosed, all fulfilling the criteria of prolonged bleeding time, with normal venous platelet count, defective clot retraction and decreased platelet aggregation, associated with a lifelong bleeding tendency. Few cases have been reported from India though it is the fourth most common congenital bleeding disorder among the patients seen at the Christian Medical College Hospital, Vellore. The large number of such cases found in South India as compared with reports from other parts of the world may be due to the high degree of consanguinity which is part of the accepted culture in this area. Reliable diagnosis of this condition is possible with fairly simple laboratory procedures.
Impact of Patient-Prosthesis Mismatch following Aortic Valve Replacement on Long-Term Survival and Quality of Life
Authors: Hoffmann Grischa , Abraham-Westphal Selam , Attmann Tim , Frank Derk , Lutter Georg , Cremer Jochen , Petzina Rainer 
Published: July 2018

Abstract
Background The impact of patient-prosthesis mismatch (PPM) after aortic valve replacement (AVR) on long-term survival and quality of life (QoL) remains controversial. The objective of this study was to evaluate the impact of PPM on long-term survival and QoL in a large cohort of patients treated with isolated stented biological AVR in a single-center experience.
Methods We analyzed data of 632 consecutive patients following isolated stented biological AVR between 2007 and 2012 at our institution. We evaluated the QoL (393 evaluable patients) using the Short Form 12-item Health Survey (SF-12) questionnaire via telephone call and the impact of PPM on long-term survival (533 evaluable patients) by Kaplan–Meier's estimate.
Results Severe PPM (<0.65 cm2/m2) had a negative impact on physical component summary (PCS) score (SF-12) compared with patients with moderate or no PPM (p = 0.014), while the mental component summary (MCS) score (SF-12) was not affected by the degree of PPM (p = 0.133). Long-term survival was not different among the three different PPM groups investigated (p = 0.75).
Conclusion Severity of PPM demonstrated no influence on long-term survival and MCS score (SF-12), but it was associated with a lower PCS score (SF-12) in patients with severe PPM.
Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide
Authors: Liu Bee Hui , Jobichen Chacko , Chia C. S. Brian , Chan Tim Hon Man , Tang Jing Ping , Chung Theodora X. Y. , Li Jia , Poulsen Anders , Hung Alvin W. , Koh-Stenta Xiaoying , Tan Yaw Sing , Verma Chandra S. , Tan Hong Kee , Wu Chan-Shuo , Li Feng , Hill Jeffrey , Joy Joma , Yang Henry , Chai Li , Sivaraman J. , Tenen Daniel G. 
Published: July 2018

Significance
Hepatocellular carcinoma (HCC) is leading cause of death due to late discovery and lack of effective treatment. The finding of the Sal-like 4 (SALL4)–NuRD interaction in HCC opens a new therapeutic direction targeting an epigenetic regulator. Here, we identified the SALL4–NuRD binding site through structural resolution of the crystal complex, providing valuable insight for the development of antagonists against this interaction. Our subsequent design of a therapeutic peptide has demonstrated the possibility to develop a first-in-class drug targeting the SALL4–NuRD interaction in HCC. Furthermore, we discovered that the therapeutic peptide exhibits robust antitumor properties and works by inhibiting the repressive function of SALL4. Our work could also be beneficial to a broad range of solid cancers and leukemic malignancies with elevated SALL4.
Personal values and the acceptance of immigrants: why national identification matters / Los valores personales y la aceptación de inmigrantes: ¿Por qué es importante la identificación nacional?
Authors: Miglietta Anna , Tartaglia Stefano , Loera Barbara 
Published: July 2018

: The study focused on the relations between Italian nationals’ personal values and their expectations towards the way ethnic minorities should acculturate. The main aim was to understand whether nationals’ personal values predict their acculturation preferences towards immigrants, both directly and through national identity. Four hundred and forty-six Italian high school students ( M age = 19.1; SD = 0.57; females = 54.4%) completed a self-administered questionnaire assessing personal values, nationalism, patriotism, acculturation preferences and demographics. An SEM model with bootstrapping estimations was tested. As expected, the results highlighted that personal values predict acculturation preferences towards immigrants in two ways — directly and also through an indirect effect on nationalism — supporting the claim that ingroup and outgroup definitions are closely intertwined. The results also highlighted the need to differentiate between nationalism and patriotism, with the latter having no influence on Italian nationals’ readiness to accept immigrants. Overall, the research demonstrates the relevance of personal values in studying intergroup relations and draws attention to the potential value of communication policies centred on self-transcendence values to improve interethnic relations.
Perseverance and passion for achieving long-term goals: transcultural adaptation and validation of the Grit-S scale / Perseverancia y pasión por la consecución de objetivos a largo plazo: adaptación transcultural y validación de la escala Grit-S
Authors: Fernández-Martín Francisco D. , Arco-Tirado Jose L. , Soriano-Ruíz María 
Published: July 2018

The objective of this study was to undertake the transcultural adaptation and validation of the Short Grit Scale (Grit-S) to measure university students’ levels of perseverance and passion for achieving long-term goals. To accomplish this, the Grit-S scale was linguistically and culturally adapted from English to Spanish via the Translation, Review, Adjudication, Pre-testing and Documentation method. After that, the adapted scale was administered to a convenience sample of 1,129 university students comprised of 29.6% males and 70.4% females with a mean age of 21, and finally, its psychometric properties were analysed and compared to the original version. The results reveal acceptable values for the internal consistency of the total scale (α = .71) and outstanding fit indexes for the proposed two-factor structural model (i.e., Consistency of Interest and Perseverance of Effort) ( RMSEA = .041, CFI = .96), and the parameters of transcultural adaptation were similar to those in its original version.
Scarification of Exotic and Indigenous Plant Seeds in Nigeria: Effect on Dormancy and Germination
Authors: Emmanuel Amodu , Olayinka Osuolale 
Published: July 2018

ABSTRACTDormancy is exhibited in many seed producing plants. It could be endogenous or exogenous, depending on the plant and the type of seed the plant produce. A survival strategy, plant use to conserve their genetic materials during unfavourable conditions. Scarification treatments has been used in this work to break the dormancy ofAnacardium occidentale, Annona muricata, Jatropha curcas, Tamarindus indicaandArtocarpus heterophyllususing 65% Nitric acid (HNO3), 65% Sulphuric acid (H2SO4), 0.5% Potassium tetraoxosulphate(VI) (K2SO4), 0.5% Urea (CH4N2O), 43% Ethanol (C2H6O) and Distilled water. Nitric acid (65% HNO3) produced the best result forAnacardium occidentalewith high numbers of seedlings and a germination period of 15 days.Jatropha curcasdid not produce a favourable result from the treatments.Tamarindus indica,water treatment produced the best result with six days of germination shorter than the controlled value (16 days). Nitric acid (65% HNO3) and water favorAnnona muricatawith germination period of 19 days as against 24 days for control experiment. Water and Potassium sulphate are the best treatments forArtocarpus heterophyllusas they produce viable seedlings with short germination period of 14 and 15 days which give a good result better than the 18 days of the control experiment.
Feedforward and feedback control share an internal model of the arm’s dynamics
Authors: Maeda Rodrigo S. , Cluff Tyler , Gribble Paul L. , Pruszynski J. Andrew 
Published: July 2018

AbstractHumans have a remarkable capacity to learn novel movement patterns in a wide variety of contexts. Recent work has shown that, when countering external forces, the nervous system adjusts not only voluntary (ie. feedforward) control but also reflex (ie. feedback) responses. Here we show that directly altering the physical properties of the arm (i.e. intersegmental dynamics) causes the nervous system to adjust feedforward control and that this learning also transfers to feedback responses even though they were never directly trained. In our first experiment, we altered intersegmental dynamics by asking participants to generate pure elbow movements with the shoulder joint either free to rotate or locked. Locking the shoulder joint cancels the interaction forces that arise at the shoulder during forearm rotation and thus removes the need to activate shoulder muscles to prevent shoulder joint rotation. We first asked whether the nervous system learns this altered mapping of intersegmental dynamics. In the baseline phase, we found robust activation of shoulder flexor muscles for pure elbow flexion trials prior to movement onset – as required to counter the intersegmental dynamics. After locking the shoulder joint in the adaptation phase, we found a substantial reduction in shoulder muscle activity over many trials. After unlocking the shoulder joint in the post-adaptation phase, we observed after-effects, as participants made systematic hand path errors. In our second experiment, we investigated whether such learning transfers to feedback control. Mechanical perturbations applied to the limb in the baseline phase revealed that feedback responses, like feedforward control, also appropriately countered intersegmental dynamics. In the adaptation phase, we found a substantial reduction in shoulder feedback responses – as appropriate for the altered intersegmental dynamics. We also found that this decay in shoulder feedback responses correlated across subjects with the amount of decay during feedforward control. Our work adds to the growing evidence that feedforward and feedback control share an internal model of the arm’s dynamics.