bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant albumins containing additional peptide sequences smaller than barbourin retain the ability of barbourin-albumin to inhibit platelet aggregation
Authors: Wilson Brianna , Eltringham-Smith Louise , Gataiance Sharon , Bhakta Varsha , Sheffield William 
Published: April 2005

SummaryThe previously described fusion protein BLAH6 (Marques JA et al., Thromb Haemost 2001; 86: 902–8) is a recombinant protein that combines the small disintegrin barbourin with hexahisti-dine-tagged rabbit serum albumin (RSA) produced in Pichia pastoris yeast. We sought to determine: (1) if BLAH6 was immunogenic; and (2) if its barbourin domain could be productively replaced with smaller peptides. Purified BLAH6 was injected into rabbits, and anti-barbourin antibodies were universally detected in plasma 28 days later; BLAH6 was, however, equally effective in reducing platelet aggregation in both naïve and pre-treated rabbits. Thrombocytopenia was not observed, and complexing BLAH6 to αIIbβ3 had no effect on antibody detection. The bar-bourin moiety of BLAH6 was replaced with each of four sequences: Pep I (VCKGDWPC); Pep II (VCRGDWPC); Pep III (barbourin 41–54); and Pep IV (LPSPGDWR). The corresponding fusion proteins were tested for their ability to inhibit ADP-induced platelet aggregation. Pep III-LAH6 inhibited neither rabbit nor human platelets. Pep I-LAH6 and Pep IV-LAH6 inhibited rabbit platelet aggregation as effectively as BLAH6, but Pep IV-LAH6 did not inhibit human platelet aggregation. Pep I-LAH6 and Pep II LAH6 inhibited human platelet aggregation with IC50s 10– and 20-fold higher than BLAH6. Cross-immunoprecipitation assays with human platelet lysates confirmed that all proteins and peptides interacted with the platelet integrin αIIbβ3, but with greatly varying affinities. Our results suggest that the antiplatelet activity of BLAH6 can be retained in albumin fusion proteins in which smaller peptides replace the barbourin domain; these proteins may be less immunogenic than BLAH6.
Does human semen contain a functional haemostatic system?
Authors: Greenfield Robert , Birch Brian , Cooper Alan , Lwaleed Bashir 
Published: April 2005

SummaryThere is already evidence that a few components of the haemostatic system exist in semen. If these comprise a functional system, they may have a role in seminal clotting and liquefaction processes and ultimately may influence fertility. What might be expected in semen as collected from fertility clinics i.e., after having both coagulated and subsequently liquefied is uncertain. It does however still contain significant amounts of Tissue Factor (TF) although its effect on semen quality remains poorly understood. The present study analyses semen for Tissue Factor Pathway Inhibitor (TFPI). Measurements were made in seminal plasma, swim-up sperm and prostasomes and its relationship with conventional fertility parameters assessed. TFPI antigen levels in seminal plasma were measured in a total of 176 subjects using an Enzyme-linked immunosorbent assay (ELISA). These include sub-fertile (n=37), normally fertile (n=40), fertile sperm donor (n=34), vasectomized subjects (n=65) and in a further group defined by normality in several parameters derived from the World Health Organization (WHO) fertility criteria and termed “pooled normal semen parameters” (PNSP). For characterization studies, both TFPI activity and antigen were measured on whole semen, swim-up sperm and prostasome-rich fraction (n=5). TFPI levels were significantly higher in normal men as compared to sub-fertile (P<0.01) or vasectomized subjects (P<0.001). TFPI levels were even higher in the donor quality semen and the PNSP group. TFPI levels also correlated with semen liquefaction time, normal semen viscosity, sperm progression, percentage of motile sperm and sperm counts (density). In conclusion, the present finding substantiates the concept of an active clotting system in human semen. TFPI could regulate the activity of abundant TF, as it does elsewhere. Given a functional set of coagulation factors in semen, the TF/TFPI balance might impinge on its liquefaction and hence on global fertility.
Thiazolidinediones inhibit apoptosis and heat shock protein 60 expression in human vascular endothelial cells
Authors: Artwohl Michaela , Hölzenbein Thomas , Fürnsinn Clemens , Freudenthaler Angelika , Huttary Nicole , Waldhäusl Werner , Baumgartner-Parzer Sabina 
Published: April 2005

SummaryThis study evaluated direct effects of peroxisome proliferator-activated receptor γ (PPARγ) agonists, including thiazolidinediones (TZDs), on vascular cell apoptosis and related protein expression to test the hypothesis that these effects are dependent on i) the respective agent’s structure and ii) endothelial cells’ vascular origin. Exposure (48 h) of human umbilical vein endothelial cells (HUVECs, n=6) to up to 10μM troglitazone (TRO), rosiglitazone, pioglitazone, and to up to 50μM RWJ241947=MCC-555 (RWJ) inhibited (p<0.05) apoptosis by 8–25%, whereas 15-deoxy-Δ12–14-prostaglandin J2 (PGJ2) triggered (50μM:+400%, p<0.05) endothelial cell death versus control (=100%). Moreover, RWJ (50μM) completely abrogated TNF-α (2000U/ml) and stearic acid (200μM) induced apoptosis in HUVECs. Similar results were obtained in human adult (saphenous) vein- and aortic endothelial cells, the latter showing no anti-apoptotic response to TRO. In HUVECs, TZDs’ anti-apoptotic effects inversely correlated (r=-0.95, p<0.01) with increased (p<0.05) expression of the apoptosis-inhibitor bcl-2, whereas PGJ2-induced apoptosis was associated with upregulation of c-myc (+447%) and E2F-1 (+339%). Additionally, TZDs (by 25–39%) and PGJ2 (-70%) reduced (p<0.05) expression of heat shock protein 60 (hsp60) showing no correlation with apoptosis (r=0.14, n.s.). Modulation of apoptosis by PPARγ agonists differs in endothelial cells dependent on their vascular origin and the agonists’ structure. Thiazolidinediones’ ability to reduce both, endothelial apoptosis and hsp60 expression could well add to beneficial vascular effects attributed to these oral antidiabetic drugs.
Impact of adjunctive tirofiban administration on myocardial perfusion and mortality in patients undergoing primary angioplasty for ST-segment elevation myocardial infarction
Authors: De Luca Giuseppe , Smit Jaap , Ernst Nicolette , Suryapranata Harry , Ottervanger Jan , Hoorntje Jan , Dambrink Jan-Henk , Gosslink Marcel , de Boer Menko-Jan , van’t Hof Arnoud 
Published: April 2005

SummarySeveral studies have shown that suboptimal myocardial perfusion may be observed despite optimal epicardial recanalisation in patients undergoing primary angioplasty for ST-segment elevation myocardial infarction (STEMI), resulting in unfavourable outcome. The aim of the current study was to evaluate the benefits in myocardial perfusion and mortality from adjunctive tirofiban administration in patients undergoing primary angioplasty for (STEMI). A total of 1,969 patients with STEMI treated by primary angioplasty represent the population of the current study. All clinical, angiographic and follow-up data were prospectively collected. Tirofiban was administrated in 481 patients (24.4%) (all before angioplasty). Tirofiban was associated with less distal embolisation (11.7% vs 16.1%, p = 0.048), better postprocedural MBG 3 (50.9% vs 39.7%, adjusted p < 0.0001) and a significant reduction in 1-year mortality (3% vs 6.4%, adjusted p = 0.045). The benefits in mortality were confirmed in all subgroups identified according to the quartiles of the propensity score. This study shows that, when compared to control group, adjunctive tirofiban before primary angioplasty for STEMI is associated with better myocardial perfusion and a reduction in 1-year mortality.
Contrast medium attenuates platelet activation and platelet-leukocyte cross–talk
Authors: Ji Qiushang , Ghaly Melania , Hjemdahl Paul , Tornvall Per , Li Nailin 
Published: April 2005

SummaryThe influence of ionic and non-ionic contrast media (CM) on platelet and leukocyte activation and platelet-leukocyte crosstalk was investigated in hirudinized whole blood. The blood was incubated with and without the ionic CM ioxaglate and the nonionic CM iodixanol at 37ºC for 5 min, without or with stirring. Platelet and leukocyte activation and platelet-leukocyte aggregation were measured using whole blood flow cytometry. When blood samples were pre-incubated in the presence of 2%, 5%, and 10% of CM without stirring, both ioxaglate and iodixanol had little effect on unstimulated samples, but dose-independently decreased 1 μM ADP-induced platelet P-selectin expression and fibrinogen binding, and thus platelet-leukocyte aggregate formation. Ioxaglate had little effect on leukocyte CD11b expression, whilst iodixanol slightly enhanced resting and N-formyl-methionyl-leucyl-phenylalanine (fMLP; 0.1 μM)-stimulated leukocyte CD11b expression. Blood samples were also incubated with stirring to investigate the impact of CM (5% of ioxaglate or iodixanol) on platelet-leukocyte cross-talk. Collagen induced marked platelet activation and platelet-leukocyte aggregation, and subsequently elevated leukocyte CD11b expression. The latter was attenuated by ioxaglate and iodixanol, and was accompanied by reduced platelet-leukocyte aggregation. In conclusion, the CM ioxaglate and iodixanol attenuate platelet activation and platelet-leukocyte cross-talk. Inhibitory effects of the contrast agents on this cross-talk are apparently exerted by reducing heterotypic conjugation, and may be beneficial in connection with PCI.
Elevated factor VIII is a risk factor for idiopathic venous thromboembolism in Canada – is it necessary to define a new upper reference range for factor VIII?
Authors: Langlois Nicole , Webster Marc , Jaffey James , Anderson Josdalyne , Wells Philip 
Published: April 2005

SummaryPrevious studies suggest elevated factor VIII is a common, independent risk factor for venous thromboembolism (VTE); however, these studies included secondary and idiopathic VTE. We sought to explore the association between elevated factor VIII and VTE in Canadian patients with idiopathic thrombosis, and confirm the current upper factor VIII reference range was appropriate. We enrolled 300 consecutive patients with idiopathic VTE who were matched to friend controls by age, sex and ethnicity. Factor VIII levels were measured and compared between cases and controls. The optimal cut-off value to designate factor VIII levels as elevated was determined using a variety of methods. The optimal upper cut-off value for factor VIII levels was 270 IU/dl. In the logistic regression analysis, cases were more likely to have elevated factor VIII levels (OR:8.76), as were females (OR:1.93) and older subjects (OR:1.05). Factor VIII cutoffs for a 95% specificity by age were 238 IU/dl for subjects <40 years, 248 IU/dl age 40–55 years, 261 IU/dl age 56–70 years, and 313 IU/dl age >70. Our findings confirm that elevated factor VIII is associated with an increased risk of idiopathic VTE. In our patients and matched controls, the current upper limit of normal (150 IU/dl) for factor VIII is not of clinical use. We propose that the upper limit be increased to 270 IU/dl or individual labs should establish their upper limit if they wish their assays to be discriminatory in patients with VTE. Age specific cut-offs may be clinically relevant.
Reasons for a Scientific Portrayal of Nature in Medieval Commentaries on the Qur'ān
Authors: Morrison Robert 
Published: April 2005

AbstractMy earlier research has shown that Nizām al-Dīn al-Nīsābūris (d. c. 1329 C.E.) portrayal of nature in his tafsīr was faithful to science and falsafa. In this paper, through more comparisons with Fahr al-Dīn al-Rāzī's(d. 1209 C.E.) tafsīr, we will find that additional scientific information enhances the reader's understanding of certain āyāt. I will investigate two specific cases in which Nīsābūrī proposed a physical explanation for how the motionsof the heavens could be an intermediary for God's control over terrestrial events. Finally, I will investigate the place of Nīsābūrī's portrayals of nature in his religious thought.
High Quality Oxygen Measurements from Profiling Floats: A Promising New Technique
Authors: Körtzinger Arne , Schimanski Jens , Send Uwe 
Published: April 2005

Abstract
Two state-of-the-art profiling floats were equipped with novel optode-based oceanographic oxygen sensors. Both floats were simultaneously deployed in the central Labrador Sea gyre on 7 September 2003. They drift at a depth of 800 db and perform weekly profiles of temperature, salinity, and oxygen in the upper 2000 m of the water column. The initial results from the first 6 months of operation are presented. Data are compared with a small hydrographic oxygen survey of the deployment site. They are further examined for measurement quality, including precision, accuracy, and drift aspects. The first 28 profiles obtained are of high quality and show no detectable sensor drift. A method of long-term drift control is described and a few suggestions for the operation protocol are provided.
Topical Glyceryl Trinitrate Application in the Treatment of Chronic Supraspinatus Tendinopathy
Authors: Paoloni Justin A. , Appleyard Richard C. , Nelson Janis , Murrell George A.C. 
Published: April 2005

Background Topical glyceryl trinitrate therapy has previously demonstrated short-term pain reduction in patients with supraspinatus tendinopathy. Hypothesis Topical glyceryl trinitrate improves outcome measures in patients with supraspinatus tendinopathy. Study Design Randomized controlled clinical trial; Level of evidence, 1. Methods Fifty-three patients (57 shoulders) were recruited, and the authors completed a prospective, randomized, double-blinded, placebo-controlled clinical trial of continuous topical glyceryl trinitrate treatment (1.25 mg/24-h glyceryl trinitrate). Results The glyceryl trinitrate group had significantly reduced shoulder pain with activity, at night, and at rest at week 24 (P =. 03); reduced internal rotation impingement at week 24 (P =. 02); increased range of motion in abduction and internal rotation at week 24 (P =. 04); and increased force at weeks 12 and 24 with supraspinatus muscle testing (P =. 001), external rotation (P =. 04), internal rotation (P =. 01), adduction (P =. 04), and subscapularis pushoff (P =. 01). Forty-six percent of patients on glyceryl trinitrate patches were asymptomatic with activities of daily living at 6 months compared with 24% of patients with tendon rehabilitation alone (P =. 007, χ2 analysis). Mean effect size for all outcome measures was 0.26. Discussion Topical glyceryl trinitrate treatment significantly improved pain scores, range of motion, internal rotation impingement, muscular force, and patient outcomes in patients with supraspinatus tendinopathy. Topical glyceryl trinitrate should be included as part of nonsurgical management of chronic tendinopathies.
Junctional adhesion molecule-A deficiency increases hepatic ischemia-reperfusion injury despite reduction of neutrophil transendothelial migration
Authors: Khandoga Andrej , Kessler Julia S. , Meissner Herbert , Hanschen Marc , Corada Monica , Motoike Toshiyuki , Enders Georg , Dejana Elisabetta , Krombach Fritz 
Published: April 2005

AbstractThe endothelial receptors that control leukocyte transmigration in the postischemic liver are not identified. We investigated the role of junctional adhesion molecule-A (JAM-A), a receptor expressed in endothelial tight junctions, leukocytes, and platelets, for leukocyte transmigration during hepatic ischemia-reperfusion (I/R) in vivo. We show that JAM-A is up-regulated in hepatic venular endothelium during reperfusion. I/R-induced neutrophil transmigration was attenuated in both JAM-A-/- and endothelial JAM-A-/- mice as well as in mice treated with an anti-JAM-A antibody, whereas transmigration of T cells was JAM-A independent. Postischemic leukocyte rolling remained unaffected in JAM-A-/- and endothelial JAM-A-/- mice, whereas intravascular leukocyte adherence was increased. The extent of interactions of JAM-A-/- platelets with the postischemic endothelium was comparable with that of JAM-A+/+ platelets. The I/R-induced increase in the activity of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and sinusoidal perfusion failure was not reduced in JAM-A-/- mice, while the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive hepatocytes was significantly higher. Thus, we show for the first time that JAM-A is up-regulated in hepatic venules and serves as an endothelial receptor of neutrophil transmigration, but it does not mediate leukocyte rolling, adhesion, or platelet-endothelial cell interactions. JAM-A deficiency does not reduce I/R-induced microvascular and hepatocellular necrotic injury, but increases hepatocyte apoptosis, despite attenuation of neutrophil infiltration. (Blood. 2005;106:725-733)
Identification and characterization of epitopes of the receptor for hyaluronic acid–mediated motility (RHAMM/CD168) recognized by CD8+ T cells of HLA-A2–positive patients with acute myeloid leukemia
Authors: Greiner Jochen , Li Li , Ringhoffer Mark , Barth Thomas F. E. , Giannopoulos Krzysztof , Guillaume Phillipe , Ritter Gerd , Wiesneth Markus , Döhner Hartmut , Schmitt Michael 
Published: April 2005

AbstractThe receptor for hyaluronic acid–mediated motility (RHAMM/CD168) has been described as a leukemia-associated antigen. To define T-cell epitopes of RHAMM/CD168 toward specific immunotherapies for acute myeloid leukemia (AML), 10 potential HLA-A2–binding RHAMM/CD168 peptides (R1 to R10) were synthesized based on computer algorithms and screened by enzyme-linked immunospot (ELISPOT) analysis using CD8+ T cells isolated from peripheral blood (PB) of patients with AML and healthy donors. We found that CD8+ cells from 7 of 13 (54%) patients with AML presensitized with peptides R3 (ILSLELMKL) or R5 (SLEENIVIL) specifically recognized T2 cells pulsed with R3 (39%) or R5 (15%) peptide. In contrast, only 4 of 21 (19%) healthy volunteers had CD8+ cells reactive with R3- or R5-pulsed T2 cells after presensitization. The presence of R3 peptide–specific effector T cells in the peripheral blood of patients with AML could be confirmed by staining as HLA-A2/R3 peptide tetramer+ CCR7-CD45RA+ cells. In chromium-51 release assays, peptide-primed CD8+ T cells from patients with AML were able to lyse RHAMM/CD168 peptide–pulsed T2 cells, AML blasts, and dendritic cells generated thereof (AML DCs). Transfection of COS7 cells with RHAMM/CD168 cDNA revealed that peptides R3 and R5 are naturally processed epitopes of RHAMM/CD168 that are presented in an HLA-A2–restricted manner. In summary, RHAMM/CD168 is a promising target for immunotherapies in patients with AML, and we have therefore initiated a clinical vaccination trial with R3 peptide. Because RHAMM/CD168 is also expressed in various other hematologic malignancies and solid tumors, vaccines targeting this antigen may have even wider application.
PREP-Mt: predictive RNA editor for plant mitochondrial genes
Authors: Mower Jeffrey P 
Published: April 2005

Abstract
Background
In plants, RNA editing is a process that converts specific cytidines to uridines and uridines to cytidines in transcripts from virtually all mitochondrial protein-coding genes. There are thousands of plant mitochondrial genes in the sequence databases, but sites of RNA editing have not been determined for most. Accurate methods of RNA editing site prediction will be important in filling in this information gap and could reduce or even eliminate the need for experimental determination of editing sites for many sequences. Because RNA editing tends to increase protein conservation across species by "correcting" codons that specify unconserved amino acids, this principle can be used to predict editing sites by identifying positions where an RNA editing event would increase the conservation of a protein to homologues from other plants. PREP-Mt takes this approach to predict editing sites for any protein-coding gene in plant mitochondria.

Results
To test the general applicability of the PREP-Mt methodology, RNA editing sites were predicted for 370 full-length or nearly full-length DNA sequences and then compared to the known sites of RNA editing for these sequences. Of 60,263 cytidines in this test set, PREP-Mt correctly classified 58,994 as either an edited or unedited site (accuracy = 97.9%). PREP-Mt properly identified 3,038 of the 3,698 known sites of RNA editing (sensitivity = 82.2%) and 55,956 of the 56,565 known unedited sites (specificity = 98.9%). Accuracy and sensitivity increased to 98.7% and 94.7%, respectively, after excluding the 489 silent editing sites (which have no effect on protein sequence or function) from the test set.

Conclusion
These results indicate that PREP-Mt is effective at identifying C to U RNA editing sites in plant mitochondrial protein-coding genes. Thus, PREP-Mt should be useful in predicting protein sequences for use in molecular, biochemical, and phylogenetic analyses. In addition, PREP-Mt could be used to determine functionality of a mitochondrial gene or to identify particular sequences with unusual editing properties. The PREP-Mt methodology should be applicable to any system where RNA editing increases protein conservation across species.
Inhaled corticosteroids for abnormal pulmonary function in children with a history of Chronic Lung Disease of Infancy: study protocol [ISRCTN55153521]
Authors: Alotaibi Saad , Johnson David , Montegomery Mark , Sauve Reginald , Spier Sheldon 
Published: April 2005

AbstractBackgroundThere is considerable evidence from the literature that children with chronic lung disease of infancy (CLD) have abnormal pulmonary function in childhood and this could have an impact on their life quality and overall health. There are similarities between CLD and asthma, and corticosteroids are the mainstay treatment for asthma. Many physicians use inhaled corticosteroids in children with CLD with no evidence. Therefore we wish to conduct a randomized double-blinded placebo controlled trial to test for the role of inhaled corticosteroids in children aged from3 to 9 years with a history of CLD. Our primary hypothesis will be that inhaled corticosteroids are beneficial in children with CLD.MethodsOur primary hypothesis is that using inhaled steroids; Beclomethasone Dipropionate (QVAR) 100 mcg 2 puffs 2 times a day for 6 weeks will improve the respiratory system resistance and the quality of life in children with CLD.DiscussionWe propose that Beclomethasone Dipropionate (QVAR) will affect the pulmonary function after 6 weeks of treatment. In summary we think that our study will highlight knowledge on whether the use of inhaled steroids is clinically effective for CLD.
The role of Mediterranean diet in the epidemiology of metabolic syndrome; converting epidemiology to clinical practice
Authors: Panagiotakos Demosthenes B , Polychronopoulos Evangelos 
Published: April 2005

Abstract
Metabolic syndrome is a collection of associated conditions such as dyslipidemia, high blood pressure, impaired glucose tolerance and tendency to develop fat around the abdomen. It is now well known that individuals with the metabolic syndrome are at high risk for atherosclerosis and, especially, coronary heart disease. However, it has been suggested that people with the metabolic syndrome may benefit from aggressive lifestyle modification, through diet and exercise. In this review we summarize scientific evidence regarding the effect of Mediterranean diet on the development of metabolic syndrome.