bluuebunny/crossref_metadata_2025 huggingface dataset:
Interference of CREB‐dependent transcriptional activation by expanded polyglutamine stretches – augmentation of transcriptional activation as a potential therapeutic strategy for polyglutamine diseases
Authors: Shimohata M. , Shimohata T. , Igarashi S. , Naruse S. , Tsuji S.
Published: April 2005

On the basis of the hypothesis that the interaction of mutant proteins with expanded polyglutamine stretches with transcriptional co‐activator, TAFII130, leads to transcriptional dysregulation, the transcriptional activation of c‐Fos and its suppression by expanded polyglutamine stretches was investigated. The phosphorylation of cAMP‐responsive element binding protein (CREB) and induction of c‐Fos in response to cAMP were strongly suppressed in Neuro2a cells expressing expanded polyglutamine. The suppression of CREB‐dependent transcriptional activation was reversibly rescued by increasing the concentration of cAMP. Expanded polyglutamine‐induced cytotoxicity was also substantially suppressed by augmenting CREB‐dependent transcriptional activation with a high concentration of cAMP. FR901228, a histone deacetylase inhibitor, was also demonstrated as rescuing the expanded polyglutamine‐induced suppression of CREB phosphorylation and c‐Fos expression. Furthermore, nuclear fragmentation was significantly suppressed by FR901228. The co‐expression of dominant‐negative CREB vectors considerably abrogated the suppressive effect of cAMP and FR901228 on the expanded polyglutamine‐induced nuclear fragmentation, suggesting that these compounds suppress polyglutamine‐induced cytotoxicity, largely, via the enhancement of CREB‐dependent transcriptional activation. These findings suggest that the interference of CREB‐dependent transcriptional activation by expanded polyglutamine stretches is involved in the pathogenetic mechanisms underlying neurodegeneration, and that the augmentation of CREB‐dependent transcriptional activation is a potential strategy in treating polyglutamine diseases.
Association of the −159 CD14 gene polymorphism and lack of association of the −308 TNFA and Q551R IL‐4RA polymorphisms with severe chronic periodontitis in Swedish Caucasians
Authors: Donati Mauro , Berglundh Tord , Hytönen Ann‐Marie , Hahn‐Zoric Mirjana , Hanson Lars‐Å. , Padyukov Leonid
Published: April 2005

Background: Severe forms of periodontitis are suggested to have a genetic basis.

Objective: The aim of the present investigation was to study the association of gene polymorphisms related to some immune regulation components (G‐308A TNFA, Q551R IL‐4RA and C‐159T CD14) with severe chronic periodontitis.

Materials and Methods: Sixty patients (aged 36–74 years; mean 54.5±8.5) with severe and generalized chronic periodontitis were included. The patients exhibited bone loss >50% at all teeth. Thirty‐nine periodontally healthy subjects between 35 and 78 years of age (mean 51.0±10.9) were recruited as controls. DNA was isolated from peripheral blood cells and genotyping was performed by combination of PCR and restriction endonuclease mapping.

Results: While gene polymorphisms for TNFA and IL‐4RA did not show any association with severe chronic periodontitis, the analysis of the −159 CD14 gene polymorphism revealed significant differences between test and control groups. The proportion of subjects that exhibited the TT genotype was significantly smaller in the group with severe periodontitis than in periodontal healthy group (p=0.028; Fisher's exact test). The C allele carriage was 90% in the periodontitis group and significantly higher than in the healthy control group (72%).

Conclusion: It is suggested that the −159 CD14 gene polymorphism is associated with chronic periodontitis in Caucasian subjects of a north European origin.
Clinical risk factors associated with incidence and progression of periodontal conditions in pregnant women
Authors: Moss Kevin L. , Beck James D. , Offenbacher Steven
Published: April 2005

Objectives: Few large studies have investigated the progression of periodontal conditions during pregnancy in a comprehensive manner. This study aimed to identify clinical factors that were predictive of incidence/progression of periodontal measures in pregnant women adjusting for relevant predictors.

Material and Methods: Periodontal examinations were conducted on 891 pregnant women prior to 26 weeks gestational age and within 48 h after delivery. Gingivitis/periodontitis incidence/progression (GPIP) was defined as four plus sites with 2+ mm increase in probing depth (PD) that resulted in PD of at least 4 mm at delivery. Multivariable models including relevant clinical variables and significant covariates were developed.

Results: While several clinical measures were significantly associated with the outcome, having 10% of sites with bleeding on probing (BOP) and four plus sites with PD 4 mm (PD4) were the best two predictors of GPIP (odds ratio (OR)=2.8, 95% confidence interval (CI)=1.8–4.2; OR=2.0, 95% CI=1.4–2.9, respectively), adjusting for maternal race, age, enrollment weight, smoking during pregnancy, marital status, food stamp eligibility, and private health insurance. Multivariable models assessed the impact of BOP on the PD4–GPIP relationship. PD4 was significant in the presence of BOP (low BOP OR=1.3, 95% CI=0.5–3.3; high BOP OR=3.0, 95% CI=2.2–4.3).

Conclusions: Enrollment BOP and PD4 were significant predictors of PD in pregnant women, however; PD4 is only a predictor with BOP.
Implant therapy in partially edentulous, periodontally compromised patients: a review
Authors: Van der Weijden G. A. , Van Bemmel K. M. , Renvert S.
Published: April 2005

Aim: The purpose of the present study was to perform a review using a systematic approach to evaluate the long‐term (5 years) success of implants placed in partially edentulous patients with a history of periodontitis as evidenced by loss of supporting bone and implant loss.

Material & Methods: An electronic search of the National Library of Medicine, Washington DC (Medline‐PubMed) was performed using specific search terms to identify studies assessing, in periodontitis patients, the success of implants with regard to bone level outcomes. Search was performed on abstracts registered up to October 2003.

Results: The searches identified 877 abstracts. Titles and abstracts were independently screened by two reviewers (G.A.W. & K.M.B.) to identify publications that met the inclusion criteria. Review of these abstracts resulted in 13 publications for detailed review. These papers were reviewed by the three authors. Finally four papers which met the criteria of eligibility were independently selected by the three reviewers.

Conclusion: Based on the limited data, it seems justified to conclude that the outcome of implant therapy in periodontitis patients may be different compared to individuals without such a history as evidenced by loss of supporting bone and implant loss.
Estimating hc/k from sunlight
Authors: Pesic Peter
Published: April 2005

The blackbody approximation is used for the visible solar spectrum to find an order of magnitude estimate for hc/k.
Analysis of the linearity of half periods of the Lorentz pendulum
Authors: Wickramasinghe T. , Ochoa R.
Published: April 2005

We analyze the motion of the Lorentz pendulum, a simple pendulum whose length is changed at a constant rate k. We show both analytically and numerically that the half period Tn, the time between half oscillations as measured from midpoint to midpoint, increases linearly with the oscillation number n such that Tn+1−Tn≈kπ2/2g, where g is the acceleration due to gravity. A video camera is used to record the motion of the oscillating bob of the pendulum and verify the linearity of Tn with oscillation number. The theory and the experiment are suitable for an advanced undergraduate laboratory.
Measurement of the giant nonlinear response of dye-doped liquid crystals
Authors: McConville Sandra , Laurent David , Guarino Alessio , Residori Stefania
Published: April 2005

We present an experimental method for measuring the nonlinear optical response of a dye-doped liquid crystal cell. We show that a very large response is obtained for a very low input light intensity. The nonlinear optical response as a function of the dye concentration in the liquid crystal host is characterized by the optical nonlinear coefficient n2. The experiment provides advanced undergraduate students experience in soft matter and nonlinear optics.
Conventions and inertial reference frames
Authors: Martı́nez Alberto A.
Published: April 2005

This article discusses the role of conventions in defining the concept of inertial reference frame, and it specifies key historical evidence, up to now widely ignored, connecting Poincaré, Einstein, and Reichenbach’s analyses of simultaneity.
Measuring and calculating bar flexural vibration frequencies
Authors: Moloney Michael J.
Published: April 2005

When a solid cylindrical bar free at both ends is suspended by loops of thread, damping is greatly reduced, and many precise longitudinal and lateral (flexural) frequencies can then be readily observed. The standard equation for flexural vibration frequencies is inaccurate for the higher modes, so the corrections proposed by Rayleigh and Timoshenko must be considered. By incorporating these corrections, the author has developed an approximation that agrees well with experiment and gives an idea of Poisson’s ratio for the bar.
SPACETIME SYMMETRY RESTORATION IN COSMOLOGICAL MODELS WITH KALB–RAMOND AND SCALAR FIELDS
Authors: DI GREZIA E. , MANGANO G. , MIELE G.
Published: April 2005

We study symmetry of spacetime in the presence of a minimally coupled scalar field interacting with a Kalb–Ramond tensor fields in a homogeneous but initially anisotropic universe. The analysis is performed for the two relevant cases of a pure cosmological constant and a minimal quadratic, renormalizable, interaction term. In both cases, due to expansion, a complete spatial symmetry restoration is dynamically obtained.
CONFORMAL SIGMA MODELS WITH ANOMALOUS DIMENSIONS AND RICCI SOLITONS
Authors: NITTA MUNETO
Published: April 2005

We present new non-Ricci-flat Kähler metrics with U(N) and O(N) isometries as target manifolds of superconformally invariant sigma models with an anomalous dimension. They are so-called Ricci solitons, special solutions to a Ricci-flow equation. These metrics explicitly contain the anomalous dimension and reduce to Ricci-flat Kähler metrics on the canonical line bundles over certain coset spaces in the limit of vanishing anomalous dimension.
SIMILARITY OF XML-SCHEMA ELEMENTS SUPPORTED BY DOMAIN ONTOLOGIES
Authors: FORMICA ANNA
Published: April 2005

XML-Schemas and domain ontologies are two key features of the Semantic Web. The possibility of assessing similarity between concepts is becoming a fundamental support in e-commerce and business transactions. In this paper a method for evaluating similarity of XML-Schema elements is proposed, by making use of domain ontologies. The method is inspired by a previous proposal concerning concept similarity within an enterprise ontology management system developed at IASI.
ANALYZING DYNAMIC BEHAVIOR OF LARGE-SCALE SYSTEMS THROUGH MODEL TRANSFORMATION
Authors: SHIN MICHAEL E. , LEVIS ALEXANDER H. , WAGENHALS LEE W. , KIM DAE-SIK
Published: April 2005

This paper describes model transformation for analyzing dynamic behavior of large-scale systems. The Unified Modeling Language (UML) based system model is transformed into the Colored Petri Nets (CPN) model, which is used for analyzing the scenarios of the use cases of a system and checking freedom of system deadlock at an early stage of software development.

The CPN model that is executable is hierarchically structured on the basis of the functional decomposition of a large-scale system. The UML-based system model consisting of the use case model, class model and collaboration model is not executable so that the dynamic behavior of the system cannot be analyzed until implementation of the system. However, the UML-based system model has no hierarchical structure to be transformed into the hierarchical CPN model as well. The discrepancies of dynamic and structural views in the two models are resolved by transformation of the UML model into the layered, executable CPN model with three layers — the use case layer, object layer and operation layer. The model transformation is carried out using relationships among the use case model, class model, and collaboration model of the UML.

With the executable CPN model transformed, the dynamic properties of the system are analyzed using the simulation technique, occurrence graph, and state space report provided by the Design/CPN tool. The approach in this paper is validated through two case studies — the gas station system and the distributed factory automation system.
OPTIMAL CONTROL OF A HYSTERESIS SYSTEM BY MEANS OF CO-OPERATIVE CO-EVOLUTION
Authors: BOONLONG KITTIPONG , CHAIYARATANA NACHOL , KUNTANAPREEDA SUWAT
Published: April 2005

This paper presents the use of a co-operative co-evolutionary genetic algorithm (CCGA) for solving optimal control problems in a hysteresis system. The hysteresis system is a hybrid control system which can be described by a continuous multivalued state-space representation that can switch between two possible discrete modes. The problems investigated cover the optimal control of the hysteresis system with fixed and free final state/time requirements. With the use of the Pontryagin maximum principle, the optimal control problems can be formulated as optimisation problems. In this case, the decision variables consist of the value of control signal when a switch between discrete modes occurs while the objective value is calculated from an energy cost function. The simulation results indicate that the use of the CCGA is proven to be highly efficient in terms of the minimal energy cost obtained in comparison to the results given by the searches using a standard genetic algorithm and a dynamic programming technique. This helps to confirm that the CCGA can handle complex optimal control problems by exploiting a co-evolutionary effect in an efficient manner.
FINDING CONSERVED WELL-ORDERED RNA STRUCTURES IN GENOMIC SEQUENCES
Authors: LE SHU-YUN , MAIZEL JACOB V. , ZHANG KAIZHONG
Published: April 2005

Recent advances in RNA studies show that the well-ordered, structured RNAs perform a broad functions in various biological mechanisms. Included among these functions are regulations of gene expression at multiple levels by diversified ribozymes and various RNA regulatory elements. The discovered microRNAs (miRNAs) with a distinct stem-loops are a new class of RNA regulatory elements. The prediction of those well-ordered folding sequences (WFS) associated with the RNA regulatory elements in genomic sequences is very helpful for our understandings of RNA-based gene regulations. We present here a new computational method in searching for the conserved WFS in genomes. In the method, the WFS is assessed by a quantitative measure E diff that is defined as the difference of free energies between the computed optimal structure (OS) and its corresponding optimal restrained structure where all the previous base pairings in the OS are forbidden. From those WFS with high E diff scores, the conserved WFS is determined by computing the maximal similarity score (MSS) between the two compared structures. In practice, we first search for those distinct WFS with high statistical significance in genomic sequences and then seek for those conserved WFS with high MSS. The potential and implications of our discoveries in the genome of Caenorhabditis elegans are discussed.
Differential effects of salt on renal hemodynamics and potential pressure transmission in stroke-prone and stroke-resistant spontaneously hypertensive rats
Authors: Abu-Amarah Isam , Bidani Anil K. , Hacioglu Rifat , Williamson Geoffrey A. , Griffin Karen A.
Published: April 2005

Salt-supplemented stroke-prone spontaneously hypertensive rats (SHRsp) develop more severe hypertension-induced renal damage (HIRD) compared with their progenitor SHR. The present studies were performed to examine whether in addition to increasing the severity of hypertension salt also enhanced the transmission of such hypertension to the renal vascular bed in the SHRsp. “Step” and “dynamic” renal blood flow (RBF) autoregulation (AR) were examined in ∼12-wk-old SHR and SHRsp after 3–5 days of an 8% NaCl diet. During step AR under anesthesia ( n = 8–11), RBF was significantly higher in the SHRsp at all perfusion pressures ( P < 0.01), but AR capacity was not different. Similarly, in separate conscious chronically instrumented rats ( n = 8 each), both blood pressure (BP) and RBF were modestly but significantly higher at baseline before salt in the SHRsp ( P < 0.05). However, transfer function analysis did not show significant differences in the admittance gain parameters. However, after 3–5 days of salt, although average BP was not significantly altered in either strain, RBF increased further in the SHRsp and there was a significantly greater transfer of BP into RBF power in the SHRsp. This was reflected in the significantly higher admittance gain parameters at most frequencies including the heartbeat frequency ( P < 0.05 maximum). These differential hemodynamic effects of salt have the potential to enhance BP transmission to the renal vascular bed and also contribute to the more severe HIRD observed in the salt-supplemented SHRsp.
High ambient glucose is effect neutral on cell death and proliferation in human proximal tubular epithelial cells
Authors: Morais Christudas , Westhuyzen Justin , Pat Betty , Gobe Glenda , Healy Helen
Published: April 2005

In vitro models of diabetic nephropathy that assess the role of hyperglycemia on proximal tubular cell turnover commonly compare cells in a high-glucose medium (25 or 30 mM) with a low-glucose medium (5 to 6.1 mM). Any cellular growth changes observed are usually attributed to the effect of high glucose. We hypothesize that in such experiments, glucose concentrations in the low-glucose medium may decline during the course of the experiments to levels that inhibit cell growth leading to the comparative conclusion that high glucose induces hyperplasia and/or hypertrophy. In this study, primary cultures of human proximal tubular epithelial cells (PTEC) and immortalized HK-2 cells were exposed to low (5 mM) or high (17, 30, or 47 mM) glucose for up to 6 days (PTEC) and 48 h (HK-2). When culture media were not replenished, low glucose induced a significant increase in necrosis and release of lactate dehydrogenase and a decrease in proliferation, metabolic activity, and protein content without any changes in apoptosis. High-glucose media failed to induce any of these changes. Glucose was undetectable in the low-glucose culture medium after 72 h. No significant differences were observed between any of the treatment groups when culture media were replenished daily. We conclude that regular replenishment of culture media is necessary to prevent the emergence of artifactual and misleading differences between high- and low-glucose groups. The current knowledge of the pathophysiology of high glucose based on cell culture systems may need to be reevaluated.
Effect of vaginal distension on blood flow and hypoxia of urogenital organs of the female rat
Authors: Damaser M. S. , Whitbeck C. , Chichester P. , Levin R. M.
Published: April 2005

Vaginal delivery of children causes traumatic injury to tissues of the pelvic floor and is correlated with stress urinary incontinence; however, the exact mechanism of organ and tissue injury leading to incontinence development is unknown. The purpose of this project was to test the hypothesis that vaginal distension results in decreased blood flow to, and hypoxia of, the urogenital organs responsible for continence, which would suggest an ischemic and/or reperfusion mechanism of injury. Thirteen female rats underwent vaginal distension for 1 h. Thirteen age-matched rats were sham-distended controls. Blood flow to the bladder, urethra, and vagina were determined using a microsphere technique. Hypoxia of these organs was determined by immunohistochemistry. Blood flow to all three organs was significantly decreased just before release of vaginal distension. Bladder blood flow decreased further immediately after release of vaginal distension and continued to be significantly decreased 15 min after the release. Blood flow to both the urethra and vagina tripled immediately after release, inducing a rapid return to normal values. Vaginal distension resulted in extensive smooth muscle hypoxia of the bladder, as well as extensive hypoxia of the vaginal epithelium and urethral hypoxia. Bladders from sham-distended rats demonstrated urothelial hypoxia as well as focal hypoxic areas of the detrusor muscle. We have clearly demonstrated that vaginal distension results in decreased blood flow to, and hypoxia of, the bladder, urethra, and vagina, supportive of hypoxic injury as a possible mechanism of injury leading to stress urinary incontinence.
Prevalence of venous thromboembolism at a teaching hospital in Okinawa, Japan
Authors: Kishimoto Mitsumasa , Tokuda Yasuharu , Narita Masashi , Kitazono Hidetaka , Ito Hiroki , Seto Todd , Sumida Kenneth , Gelber Rebecca , Lim Hwee
Published: April 2005

Limited data suggest that Asian Americans may have a lower risk of venous thromboembolism (VTE) than Caucasians. However, the actual prevalence of VTE among Asians remains controversial, and has not been described in Japan. We studied all 131,060 patients hospitalized at a single medical centre in Japan (January 1987 – December 1999). Patients with VTE were identified through discharge diagnoses. Hospital records were reviewed for information on patient demographics, risk factors, and diagnostic modalities. VTE occurred in 0.11% of admissions (n=141, 95%CI 0.09–0.13%). Mean age (±SD) was 64±17 years, 70% were women, 91% had deep vein thrombosis, and 29% pulmonary embolism. Among hospitalized patients 50–69 years old, VTE was significantly more common among women than men (0.31% vs. 0.08%; OR 3.88; 95%CI 1.45–6.31). We found a low prevalence of VTE in Japan compared to that reported in the US. Future studies are needed to clarify the reasons for our findings.
Lipoprotein (a) and other prothrombotic risk factors in Caucasian women with unexplained recurrent miscarriage
Authors: Krause Manuela , Sonntag Barbara , Klamroth Robert , Heinecke Achim , Scholz Carola , Langer Claus , Scharrer Inge , Greb Robert , von Eckardstein Arnold , Nowak-Göttl Ulrike
Published: April 2005

From 1998 to 2003, 133 Caucasian women aged 17–40 years (median 29 years) suffering from unexplained recurrent miscarriage (uRM) were consecutively enrolled. In patients and 133 age-matched healthy controls prothrombotic risk factors (factor V (FV) G1691A, factor II (FII) G20210A, MTHFR T677T, 4G/5G plasminogen activator inhibitor (PAI)-1, lipoprotein (Lp) (a), protein C (PC), protein S (PS), antithrombin (AT), antiphospholipid/anticardiolipin (APA/ACA) antibodies) as well as associated environmental conditions (smoking and obesity) were investigated. 70 (52.6%) of the patients had at least one prothrombotic risk factor compared with 26 control women (19.5%; p<0.0001). Body mass index (BMI; p=0.78) and smoking habits (p=0.44) did not differ significantly between the groups investigated. Upon univariate analysis the heterozygous FV mutation, Lp(a) > 30 mg/dL, increased APA/ACA and BMI > 25 kg/m2 in combination with a prothrombotic risk factor were found to be significantly associated with uRM. In multivariate analysis, increased Lp(a) (odds ratio (OR): 4.7/95% confidence interval (CI): 2.0–10.7), the FV mutation (OR:3.8/CI:1.4–10.7), and increased APA/ACA (OR: 4.5/CI: 1.1–17.7) had independent associations with uRM.
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

The 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

There 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

This 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

Several 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

The 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

Previous 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

My 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

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.
Relationship between plasma arc cutting acoustic and cut quality
Authors: Xue W. , Kusumoto K. , Nezu K.
Published: April 2005

The tremendous acoustic signal exiting during the plasma arc cutting process includes a lot of information about this process and has a close relation with cut quality. To investigate the relationship between the plasma arc cutting acoustic and cut quality, a number of experiments have been carried out. In the present study, cut quality by plasma arc is described by top and bottom kerf widths, bevel angle, and attached dross state, and the relationship between the evaluation items for cut quality and the SPL (sound pressure level) of the cutting acoustic is investigated in detail. It is shown that the SPL reaches a maximum as the bottom kerf width equals the diameter of the plasma arc potential core. The attached dross and kerf widths in a state of free dross obviously affect the low and high frequency components of the plasma arc cutting acoustic, respectively. These results also suggest the possibility of designing an acoustic-based monitoring system for the plasma arc cutting process.
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

The 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

The 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

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

Background

There 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.

Methods

Our 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.

Discussion

We 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

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.