bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-specific association of epidermal growth factor gene polymorphisms with acute respiratory distress syndrome
Authors: Sheu C. C. , Zhai R. , Su L. , Tejera P. , Gong M. N. , Thompson B. T. , Chen F. , Christiani D. C.
Published: November 2008

Epidermal growth factor (EGF) is involved in alveolar epithelial repair, lung fluid clearance and inflammation, and is regulated by sex hormones. An unmatched, nested case–control study was conducted to evaluate the associations ofEGFvariants with acute respiratory distress syndrome (ARDS) and the role of sex on the associations betweenEGFvariants and ARDS.

Patients with ARDS risk factors upon intensive care unit admission were enrolled. Cases were 416 Caucasians who developed ARDS and controls were 1,052 Caucasians who did not develop ARDS. Cases were followed for clinical outcomes and 60-day mortality. One functional single nucleotide polymorphism (SNP), rs4444903, and six haplotype-tagging SNPs spanning the entireEGFgene were genotyped.

No individual SNP or haplotype was associated with ARDS risk or outcomes in all subjects. Sex-stratified analyses showed opposite effects ofEGFvariants on ARDS in malesversusin females. SNPs rs4444903, rs2298991, rs7692976 and rs4698803, and haplotypes GGCGTC and ATCAAG were associated with ARDS risk in males. No associations were observed in females. Interaction analysis showed that rs4444903, rs2298991, rs7692976 and rs6533485 significantly interacted with sex for ARDS risk.

The present study suggests that associations of epidermal growth factor gene variants with acute respiratory distress syndrome risk are modified by sex. The current findings should be replicated in other populations.
Fluctuation analysis of lung function as a predictor of long-term response to β2-agonists
Authors: Thamrin C. , Stern G. , Strippoli M-P. F. , Kuehni C. E. , Suki B. , Taylor D. R. , Frey U.
Published: November 2008

The response to β2-agonists differs between asthmatics and has been linked to subsequent adverse events, even death. Possible determinants include β2-adrenoceptor genotype at position 16, lung function and airway hyperresponsiveness. Fluctuation analysis provides a simple parameter α measuring the complex correlation properties of day-to-day peak expiratory flow. The present study investigated whether α predicts clinical response to β2-agonist treatment, taking into account other conventional predictors.

Analysis was performed on previously published twice-daily peak expiratory flow measurements in 66 asthmatic adults over three 6-month randomised order treatment periods: placebo, salbutamol and salmeterol. Multiple linear regression was used to determine the association between α during the placebo period and response to treatment (change in the number of days with symptoms), taking into account other predictors namely β2-adrenoceptor genotype, lung function and its variability, and airway hyperresponsiveness.

The current authors found that α measured during the placebo period considerably improved the prediction of response to salmeterol treatment, taking into account genotype, lung function or its variability, or airway hyperresponsiveness.

The present study provides further evidence that response to β2-agonists is related to the time correlation properties of lung function in asthma. The current authors conclude that fluctuation analysis of lung function offers a novel predictor to identify patients who may respond well or poorly to treatment.
Inhibition of phosphodiesterase 4 enhances lung alveolarisation in neonatal mice exposed to hyperoxia
Authors: Woyda K. , Koebrich S. , Reiss I. , Rudloff S. , Pullamsetti S. S. , Rühlmann A. , Weissmann N. , Ghofrani H. A. , Günther A. , Seeger W. , Grimminger F. , Morty R. E. , Schermuly R. T.
Published: November 2008

Bronchopulmonary dysplasia (BPD) is characterised by impaired alveolarisation, inflammation and aberrant vascular development. Phosphodiesterase (PDE) inhibitors can influence cell proliferation, antagonise inflammation and restore vascular development and homeostasis, suggesting a therapeutic potential in BPD.

The aim of the present study was to investigate PDE expression in the lung of hyperoxia-exposed mice, and to assess the viability of PDE4 as a therapeutic target in BPD.

Newborn C57BL/6N mice were exposed to normoxia or 85% oxygen for 28 days. Animal growth and dynamic respiratory compliance were reduced in animals exposed to hyperoxia, paralleled by decreased septation, airspace enlargement and increased septal wall thickness. Changes were evident after 14 days and were more pronounced after 28 days of hyperoxic exposure. At the mRNA level, PDE1A and PDE4A were upregulated while PDE5A was downregulated under hyperoxia. Immunoblotting confirmed these trends in PDE4A and PDE5A at the protein expression level. Treatment with cilomilast (PDE4 inhibitor, 5 mg·kg−1·day−1) between days 14 and 28 significantly decreased the mean intra-alveolar distance, septal wall thickness and total airspace area and improved dynamic lung compliance.

Pharmacological inhibition of phosphodiesterase improved lung alveolarisation in hyperoxia-induced bronchopulmonary dysplasia, and thus may offer a new therapeutic modality in the clinical management of bronchopulmonary dysplasia.
Potent bronchodilation and reduced stiffness by relaxant stimuli under dynamic conditions
Authors: Ansell T. K. , McFawn P. K. , Noble P. B. , West A. R. , Fernandes L. , Mitchell H. W.
Published: November 2008

Airway relaxation in response to isoprenaline, sodium nitroprusside (SNP) and electrical field stimulation (EFS) was compared under static and dynamic conditions. The capacity of relaxants to reduce airway stiffness and, thus, potentially contribute to bronchodilation was also investigated.

Relaxation responses were recorded in fluid filled bronchial segments from pigs under static conditions and during volume oscillations simulating tidal and twice tidal manoeuvres. Bronchodilation was assessed from the reduction in carbachol-induced lumen pressure, at isovolume points in pressure cycles produced by volume oscillation, and stiffness was assessed from cycle amplitudes.

Under static conditions, all three inhibitory stimuli produced partial relaxation of the carbachol-induced contraction. Volume oscillation alone also reduced the contraction in an amplitude-dependent manner. However, maximum relaxation was observed when isoprenaline or SNP were combined with volume oscillation, virtually abolishing contraction at the highest drug concentrations. The proportional effects of isoprenaline and EFS were not different under static or oscillating conditions, whereas relaxation to SNP was slightly greater in oscillating airways. All three inhibitory stimuli also strongly reduced carbachol-induced airway stiffening.

The current authors conclude that bronchoconstriction is strongly suppressed by combining the inhibitory stimulation of airway smooth muscle with cyclical mechanical strains. The capacity of airway smooth muscle relaxants to also reduce stiffness may further contribute to bronchodilation.
Occupational exposures and COPD: an ecological analysis of international data
Authors: Blanc P. D. , Menezes A. M. B. , Plana E. , Mannino D. M. , Hallal P. C. , Toren K. , Eisner M. D. , Zock J-P.
Published: November 2008

The occupational contribution to chronic obstructive pulmonary disease (COPD) has yet to be put in a global perspective. In the present study, an ecological approach to this question was used, analysing group-level data from 90 sex-specific strata from 45 sites of the Burden of Obstructive Lung Disease study, the Latin American Project for the Investigation of Obstructive Lung Disease and the European Community Respiratory Health Survey follow-up. These data were used to study the association between occupational exposures and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II or above.

Regression analysis of the sex-specific group-level prevalence rates of COPD at each site against the prevalence of occupational exposure and ever-smoking was performed, taking into account mean smoking pack-yrs and mean age by site, sex, study cohort and sample size.

For the entire data set, the prevalence of exposures predicted COPD prevalence (0.8% increase in COPD prevalence per 10% increase in exposure prevalence). By comparison, for every 10% increase in the proportion of the ever-smoking population, the prevalence of COPD GOLD stage II or above increased by 1.3%. Given the observed median population COPD prevalence of 3.4%, the model predicted that a 20% relative reduction in the disease burden (i.e.to a COPD prevalence of 2.7%) could be achieved by a 5.4% reduction in overall smoking rates or an 8.8% reduction in the prevalence of occupational exposures. When the data set was analysed by sex-specific site data, among males, the occupational effect was a 0.8% COPD prevalence increase per 10% change in exposure prevalence; among females, a 1.0% increase in COPD per 10% change in exposure prevalence was observed.

Within the limitations of an ecological analysis, these findings support a worldwide association between dusty trades and chronic obstructive pulmonary disease for both females and males, placing this within the context of the dominant role of cigarette smoking in chronic obstructive pulmonary disease causation.
Extracorporeal pumpless interventional lung assist in clinical practice: determinants of efficacy
Authors: Müller T. , Lubnow M. , Philipp A. , Bein T. , Jeron A. , Luchner A. , Rupprecht L. , Reng M. , Langgartner J. , Wrede C. E. , Zimmermann M. , Birnbaum D. , Schmid C. , Riegger G. A. J. , Pfeifer M.
Published: November 2008

Respiratory acidosis can become a serious problem during protective ventilation of severe lung failure. A pumpless arteriovenous interventional lung assist (iLA) for extracorporeal carbon dioxide removal has been used increasingly to control critical respiratory situations. The present study sought to evaluate the factors determining the efficacy of iLA and calculate its contribution to gas exchange.

In a cohort of 96 patients with severe acute respiratory distress syndrome, haemodynamic parameters, oxygen consumption and carbon dioxide production as well as gas transfer through the iLA were analysed.

The measurements demonstrated a significant dependency of blood flowviathe iLA device on cannula size (mean±sd1.59±0.52 L·min−1for 15 French (Fr), 1.94±0.35 L·min−1for 17 Fr, and 2.22 ±0.45 L·min−1for 19 Fr) and on mean arterial pressure. Oxygen transfer capacity averaged 41.7±20.8 mL·min−1, carbon dioxide removal was 148.0±63.4 mL·min−1. Within two hours of iLA treatment, arterial oxygen partial pressure/inspired oxygen fraction ratio increased significantly and a fast improvement in arterial carbon dioxide partial pressure and pH was observed.

Interventional lung assist eliminates ∼50% of calculated total carbon dioxide production with rapid normalisation of respiratory acidosis. Despite limited contribution to oxygen transfer it may allow a more protective ventilation in severe respiratory failure.
Improved identification of conserved cassette exons using Bayesian networks
Authors: Sinha Rileen , Hiller Michael , Pudimat Rainer , Gausmann Ulrike , Platzer Matthias , Backofen Rolf
Published: November 2008

Background

Alternative splicing is a major contributor to the diversity of eukaryotic transcriptomes and proteomes. Currently, large scale detection of alternative splicing using expressed sequence tags (ESTs) or microarrays does not capture all alternative splicing events. Moreover, for many species genomic data is being produced at a far greater rate than corresponding transcript data, hence in silico methods of predicting alternative splicing have to be improved.

Results

Here, we show that the use of Bayesian networks (BNs) allows accurate prediction of evolutionary conserved exon skipping events. At a stringent false positive rate of 0.5%, our BN achieves an improved true positive rate of 61%, compared to a previously reported 50% on the same dataset using support vector machines (SVMs). Incorporating several novel discriminative features such as intronic splicing regulatory elements leads to the improvement. Features related to mRNA secondary structure increase the prediction performance, corroborating previous findings that secondary structures are important for exon recognition. Random labelling tests rule out overfitting. Cross-validation on another dataset confirms the increased performance. When using the same dataset and the same set of features, the BN matches the performance of an SVM in earlier literature. Remarkably, we could show that about half of the exons which are labelled constitutive but receive a high probability of being alternative by the BN, are in fact alternative exons according to the latest EST data. Finally, we predict exon skipping without using conservation-based features, and achieve a true positive rate of 29% at a false positive rate of 0.5%.

Conclusion

BNs can be used to achieve accurate identification of alternative exons and provide clues about possible dependencies between relevant features. The near-identical performance of the BN and SVM when using the same features shows that good classification depends more on features than on the choice of classifier. Conservation based features continue to be the most informative, and hence distinguishing alternative exons from constitutive ones without using conservation based features remains a challenging problem.
CellProfiler Analyst: data exploration and analysis software for complex image-based screens
Authors: Jones Thouis R , Kang In Han , Wheeler Douglas B , Lindquist Robert A , Papallo Adam , Sabatini David M , Golland Polina , Carpenter Anne E
Published: November 2008

Background

Image-based screens can produce hundreds of measured features for each of hundreds of millions of individual cells in a single experiment.

Results

Here, we describe CellProfiler Analyst, open-source software for the interactive exploration and analysis of multidimensional data, particularly data from high-throughput, image-based experiments.

Conclusion

The system enables interactive data exploration for image-based screens and automated scoring of complex phenotypes that require combinations of multiple measured features per cell.
Genome-scale study of the importance of binding site context for transcription factor binding and gene regulation
Authors: Westholm Jakub Orzechowski , Xu Feifei , Ronne Hans , Komorowski Jan
Published: November 2008

Background

The rate of mRNA transcription is controlled by transcription factors that bind to specific DNA motifs in promoter regions upstream of protein coding genes. Recent results indicate that not only the presence of a motif but also motif context (for example the orientation of a motif or its location relative to the coding sequence) is important for gene regulation.

Results

In this study we present ContextFinder, a tool that is specifically aimed at identifying cases where motif context is likely to affect gene regulation. We used ContextFinder to examine the role of motif context inS. cerevisiaeboth for DNA binding by transcription factors and for effects on gene expression. For DNA binding we found significant patterns of motif location bias, whereas motif orientations did not seem to matter. Motif context appears to affect gene expression even more than it affects DNA binding, as biases in both motif location and orientation were more frequent in promoters of co-expressed genes. We validated our results against data on nucleosome positioning, and found a negative correlation between preferred motif locations and nucleosome occupancy.

Conclusion

We conclude that the requirement for stable binding of transcription factors to DNA and their subsequent function in gene regulation can impose constraints on motif context.
Insights into the evolutionary origins of clostridial neurotoxins from analysis of the Clostridium botulinum strain A neurotoxin gene cluster
Authors: Doxey Andrew C , Lynch Michael DJ , Müller Kirsten M , Meiering Elizabeth M , McConkey Brendan J
Published: November 2008

Background

Clostridial neurotoxins (CNTs) are the most deadly toxins known and causal agents of botulism and tetanus neuroparalytic diseases. Despite considerable progress in understanding CNT structure and function, the evolutionary origins of CNTs remain a mystery as they are unique toClostridiumand possess a sequence and structural architecture distinct from other protein families. Uncovering the origins of CNTs would be a significant contribution to our understanding of how pathogens evolve and generate novel toxin families.

Results

TheC. botulinumstrain A genome was examined for potential homologues of CNTs. A key link was identified between the neurotoxin and the flagellin gene (CBO0798) located immediately upstream of the BoNT/A neurotoxin gene cluster. This flagellin sequence displayed the strongest sequence similarity to the neurotoxin and NTNH homologue out of all proteins encoded withinC. botulinumstrain A. The CBO0798 gene contains a unique hypervariable region, which in closely related flagellins encodes a collagenase-like domain. Remarkably, these collagenase-containing flagellins were found to possess the characteristic HEXXH zinc-protease motif responsible for the neurotoxin's endopeptidase activity. Additional links to collagenase-related sequences and functions were detected by further analysis of CNTs and surrounding genes, including sequence similarities to collagen-adhesion domains and collagenases. Furthermore, the neurotoxin's HCRn domain was found to exhibit both structural and sequence similarity to eukaryotic collagen jelly-roll domains.

Conclusion

Multiple lines of evidence suggest that the neurotoxin and adjacent genes evolved from an ancestral collagenase-like gene cluster, linking CNTs to another major family of clostridial proteolytic toxins. Duplication, reshuffling and assembly of neighboring genes within the BoNT/A neurotoxin gene cluster may have lead to the neurotoxin's unique architecture. This work provides new insights into the evolution ofC. botulinumneurotoxins and the evolutionary mechanisms underlying the origins of virulent genes.
Towards systems genetic analyses in barley: Integration of phenotypic, expression and genotype data into GeneNetwork
Authors: Druka Arnis , Druka Ilze , Centeno Arthur G , Li Hongqiang , Sun Zhaohui , Thomas William TB , Bonar Nicola , Steffenson Brian J , Ullrich Steven E , Kleinhofs Andris , Wise Roger P , Close Timothy J , Potokina Elena , Luo Zewei , Wagner Carola , Schweizer Günther F , Marshall David F , Kearsey Michael J , Williams Robert W , Waugh Robbie
Published: November 2008

Background

A typical genetical genomics experiment results in four separate data sets; genotype, gene expression, higher-order phenotypic data and metadata that describe the protocols, processing and the array platform. Used in concert, these data sets provide the opportunity to perform genetic analysis at a systems level. Their predictive power is largely determined by the gene expression dataset where tens of millions of data points can be generated using currently available mRNA profiling technologies. Such large, multidimensional data sets often have value beyond that extracted during their initial analysis and interpretation, particularly if conducted on widely distributed reference genetic materials. Besides quality and scale, access to the data is of primary importance as accessibility potentially allows the extraction of considerable added value from the same primary dataset by the wider research community. Although the number of genetical genomics experiments in different plant species is rapidly increasing, none to date has been presented in a form that allows quick and efficient on-line testing for possible associations between genes, loci and traits of interest by an entire research community.

Description

Using a reference population of 150 recombinant doubled haploid barley lines we generated novel phenotypic, mRNA abundance and SNP-based genotyping data sets, added them to a considerable volume of legacy trait data and entered them into the GeneNetwork http://www.genenetwork.org. GeneNetwork is a unified on-line analytical environment that enables the user to test genetic hypotheses about how component traits, such as mRNA abundance, may interact to condition more complex biological phenotypes (higher-order traits). Here we describe these barley data sets and demonstrate some of the functionalities GeneNetwork provides as an easily accessible and integrated analytical environment for exploring them.

Conclusion

By integrating barley genotypic, phenotypic and mRNA abundance data sets directly within GeneNetwork's analytical environment we provide simple web access to the data for the research community. In this environment, a combination of correlation analysis and linkage mapping provides the potential to identify and substantiate gene targets for saturation mapping and positional cloning. By integrating datasets from an unsequenced crop plant (barley) in a database that has been designed for an animal model species (mouse) with a well established genome sequence, we prove the importance of the concept and practice of modular development and interoperability of software engineering for biological data sets.
Application of dissociation curve analysis to radiation hybrid panel marker scoring: generation of a map of river buffalo (B. bubalis) chromosome 20
Authors: Kochan Kelli J , Amaral M Elisabete J , Agarwala Richa , Schäffer Alejandro A , Riggs Penny K
Published: November 2008

Background

Fluorescence of dyes bound to double-stranded PCR products has been utilized extensively in various real-time quantitative PCR applications, including post-amplification dissociation curve analysis, or differentiation of amplicon length or sequence composition. Despite the current era of whole-genome sequencing, mapping tools such as radiation hybrid DNA panels remain useful aids for sequence assembly, focused resequencing efforts, and for building physical maps of species that have not yet been sequenced. For placement of specific, individual genes or markers on a map, low-throughput methods remain commonplace. Typically, PCR amplification of DNA from each panel cell line is followed by gel electrophoresis and scoring of each clone for the presence or absence of PCR product. To improve sensitivity and efficiency of radiation hybrid panel analysis in comparison to gel-based methods, we adapted fluorescence-based real-time PCR and dissociation curve analysis for use as a novel scoring method.

Results

As proof of principle for this dissociation curve method, we generated new maps of river buffalo (Bubalus bubalis) chromosome 20 by both dissociation curve analysis and conventional marker scoring. We also obtained sequence data to augment dissociation curve results. Few genes have been previously mapped to buffalo chromosome 20, and sequence detail is limited, so 65 markers were screened from the orthologous chromosome of domestic cattle. Thirty bovine markers (46%) were suitable as cross-species markers for dissociation curve analysis in the buffalo radiation hybrid panel under a standard protocol, compared to 25 markers suitable for conventional typing. Computational analysis placed 27 markers on a chromosome map generated by the new method, while the gel-based approach produced only 20 mapped markers. Among 19 markers common to both maps, the marker order on the map was maintained perfectly.

Conclusion

Dissociation curve analysis is reliable and efficient for radiation hybrid panel scoring, and is more sensitive and robust than conventional gel-based typing methods. Several markers could be scored only by the new method, and ambiguous scores were reduced. PCR-based dissociation curve analysis decreases both time and resources needed for construction of radiation hybrid panel marker maps and represents a significant improvement over gel-based methods in any species.
Transcriptional response of rat frontal cortex following acute In Vivo exposure to the pyrethroid insecticides permethrin and deltamethrin
Authors: Harrill Joshua A , Li Zhen , Wright Fred A , Radio Nicholas M , Mundy William R , Tornero-Velez Rogelio , Crofton Kevin M
Published: November 2008

Background

Pyrethroids are neurotoxic pesticides that interact with membrane bound ion channels in neurons and disrupt nerve function. The purpose of this study was to characterize and explore changes in gene expression that occur in the rat frontal cortex, an area of CNS affected by pyrethroids, following an acute low-dose exposure.

Results

Rats were acutely exposed to either deltamethrin (0.3 – 3 mg/kg) or permethrin (1 – 100 mg/kg) followed by collection of cortical tissue at 6 hours. The doses used range from those that cause minimal signs of intoxication at the behavioral level to doses well below apparent no effect levels in the whole animal. A statistical framework based on parallel linear (SAM) and isotonic regression (PIR) methods identified 95 and 53 probe sets as dose-responsive. The PIR analysis was most sensitive for detecting transcripts with changes in expression at the NOAEL dose. A sub-set of genes (Camk1g,Ddc,Gpd3,c-fosandEgr1) was then confirmed by qRT-PCR and examined in a time course study. Changes in mRNA levels were typically less than 3-fold in magnitude across all components of the study. The responses observed are consistent with pyrethroids producing increased neuronal excitation in the cortex following a low-dosein vivoexposure. In addition, Significance Analysis of Function and Expression (SAFE) identified significantly enriched gene categories common for both pyrethroids, including some relating to branching morphogenesis. Exposure of primary cortical cell cultures to both compounds resulted in an increase (~25%) in the number of neurite branch points, supporting the results of the SAFE analysis.

Conclusion

In the present study, pyrethroids induced changes in gene expression in the frontal cortex near the threshold for decreases in ambulatory motor activityin vivo. The penalized regression methods performed similarly in detecting dose-dependent changes in gene transcription. Finally, SAFE analysis of gene expression data identified branching morphogenesis as a biological process sensitive to pyrethroids and subsequentin vitroexperiments confirmed this predicted effect. The novel findings regarding pyrethroid effects on branching morphogenesis indicate these compounds may act as developmental neurotoxicants that affect normal neuronal morphology.
Study of membrane potential in T lymphocytes subpopulations using flow cytometry
Authors: Mello de Queiroz Fernanda , Ponte Cristiano G , Bonomo Adriana , Vianna-Jorge Rosane , Suarez-Kurtz Guilherme
Published: November 2008

Background

Ion channels are involved in the control of membrane potential (ψ) in a variety of cells. The maintenance of ψ in human T lymphocytes is essential for T-cell activation and was suggested to depend mostly on the voltage-gated Kv1.3 channel. Blockage of Kv1.3 inhibits cytokine production and lymphocyte proliferationin vitroand suppresses immune responsein vivo. T lymphocytes are a heterogeneous cell population and the expression of Kv1.3 varies among cell subsets. Oxonol diBA-C4-(3) was used to determine ψ by flow cytometry. The presence of distinct T cell subsets was evaluated by immunophenotyping techniques and the contribution of Kv1.3 channels for the maintenance of ψ was investigated using selective blockers.

Results

The distribution of ψ in T lymphocytes varied among blood donors and did not always follow a unimodal pattern. T lymphocytes were divided into CD3+/CD45RO-and CD3+/CD45RO+subsets, whose peak channel values of ψ were -58 ± 3.6 mV and -37 ± 4.1 mV, respectively. MgTX (specific inhibitor of Kv1.3 channels) had no significant effect in the ψ of CD3+/CD45RO-subsets but depolarized CD3+/CD45RO+cells to -27 ± 5.1 mV.

Conclusion

Combination of optical methods for determination of ψ by flow cytometry with immuophenotyping techniques opens new possibilities for the study of ion channels in the biology of heterogeneous cell populations such as T lymphocyte subsets.
Acquisition of methicillin-resistant Staphylococcus aureus after living donor liver transplantation: a retrospective cohort study
Authors: Hashimoto Masao , Sugawara Yasuhiko , Tamura Sumihito , Kaneko Junichi , Matsui Yuichi , Togashi Junichi , Moriya Kyoji , Koike Kazuhiko , Makuuchi Masatoshi
Published: November 2008

Background

The incidence and risk factors of methicillin-resistantStaphylococcus aureus(MRSA) acquisition after living donor liver transplantation (LDLT) are unclear. The aim of the present study was to assess the incidence and to analyze the risk factors for the acquisition of MRSA after LDLT in adults by multivariate analysis.

Methods

We retrospectively reviewed the data from 158 adult patients that underwent LDLT at the Tokyo University Hospital. The microbiologic and medical records of the patients from admission to 3 months after LDLT were reviewed. Uni- and multivariate analyses were performed to identify the risk factors for postoperative acquisition of MRSA.

Results

Postoperative MRSA acquisition was detected in 35 of 158 patients by median postoperative day 18. Age (>= 60 y) and perioperative dialysis and/or apheresis predicted postoperative MRSA acquisition by multivariate analysis. In contrast, postoperative use of fluoroquinolone was negatively associated with acquisition of MRSA.

Conclusion

MRSA arose early after LDLT in adults with a high incidence (35 of 158 patients). Surveillance culture should be checked periodically after LDLT to identify and prevent the transmission of MRSA.
XM02 is superior to placebo and equivalent to Neupogen™ in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy
Authors: del Giglio A , Eniu A , Ganea-Motan D , Topuzov E , Lubenau H
Published: November 2008

Background

Recombinant granulocyte colony-stimulating factors (G-CSFs) such as Filgrastim are used to treat chemotherapy-induced neutropenia. We investigated a new G-CSF, XM02, and compared it to Neupogen™ after myelotoxic chemotherapy in breast cancer (BC) patients.

Methods

A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were randomised to treatment with daily injections (subcutaneous 5 μg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of XM02 (n = 140), Neupogen™ (n = 136) or placebo (n = 72). The primary endpoint was the duration of severe neutropenia (DSN) in cycle 1.

Results

The mean DSN in cycle 1 was 1.1, 1.1, and 3.9 days in the XM02, Neupogen™, and placebo group, respectively. Superiority of XM02 over placebo and equivalence of XM02 with Neupogen™ could be demonstrated. Toxicities were similar between XM02 and Neupogen™.

Conclusion

XM02 was superior to placebo and equivalent to Neupogen™ in reducing DSN after myelotoxic chemotherapy.

Trial Registration

Current Controlled Trials ISRCTN02270769
A novel expression platform for the production of diabetes-associated autoantigen human glutamic acid decarboxylase (hGAD65)
Authors: Wang Xiaofeng , Brandsma Martin , Tremblay Reynald , Maxwell Denis , Jevnikar Anthony M , Huner Norm , Ma Shengwu
Published: November 2008

Background

Human glutamic acid decarboxylase 65 (hGAD65) is a key autoantigen in type 1 diabetes, having much potential as an important marker for the prediction and diagnosis of type 1 diabetes, and for the development of novel antigen-specific therapies for the treatment of type 1 diabetes. However, recombinant production of hGAD65 using conventional bacterial or mammalian cell culture-based expression systems or nuclear transformed plants is limited by low yield and low efficiency. Chloroplast transformation of the unicellular eukaryotic alga Chlamydomonas reinhardtii may offer a potential solution.

Results

A DNA cassette encoding full-length hGAD65, under the control of the C. reinhardtii chloroplast rbcL promoter and 5'- and 3'-UTRs, was constructed and introduced into the chloroplast genome of C. reinhardtii by particle bombardment. Integration of hGAD65 DNA into the algal chloroplast genome was confirmed by PCR. Transcriptional expression of hGAD65 was demonstrated by RT-PCR. Immunoblotting verified the expression and accumulation of the recombinant protein. The antigenicity of algal-derived hGAD65 was demonstrated with its immunoreactivity to diabetic sera by ELISA and by its ability to induce proliferation of spleen cells from NOD mice. Recombinant hGAD65 accumulated in transgenic algae, accounts for approximately 0.25–0.3% of its total soluble protein.

Conclusion

Our results demonstrate the potential value of C. reinhardtii chloroplasts as a novel platform for rapid mass production of immunologically active hGAD65. This demonstration opens the future possibility for using algal chloroplasts as novel bioreactors for the production of many other biologically active mammalian therapeutic proteins.
Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells
Authors: Urueña Claudia , Cifuentes Claudia , Castañeda Diana , Arango Amparo , Kaur Punit , Asea Alexzander , Fiorentino Susana
Published: November 2008

Background

There is ethnopharmacological evidence thatPetiveria alliaceacan have antitumor activity; however, the mechanism of its cytotoxic activity is not well understood. We assessed multiplein vitrobiological activities of an ethyl acetate soluble plant fraction over several tumor cell lines.

Methods

Tumor cell lines were evaluated using the following tests: trypan blue exclusion test, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], flow cytometry, cytoskeleton organization analysis, cell cycle, mitochondria membrane depolarization, clonogenicity test, DNA fragmentation test and differential protein expression by HPLC-Chip/MS analysis. F4 fraction characterization was made by HPLC-MS.

Results

Petiveria alliaceafraction characterized by de-replication was found to alter actin cytoskeleton organization, induce G2 cell cycle arrest and cause apoptotic cell death in a mitochondria independent way. In addition, we found down regulation of cytoskeleton, chaperone, signal transduction proteins, and proteins involved in metabolic pathways. Finally up regulation of proteins involved in translation and intracellular degradation was also observed.

Conclusion

The results of this study indicate thatPetiveria alliaceaexerts multiple biological activitiesin vitroconsistent with cytotoxicity. Further studies in animal models are needed butPetiveria alliaceaappears to be a good candidate to be used as an antitumor agent.
Child health insurance coverage: a survey among temporary and permanent residents in Shanghai
Authors: Lu Mingshan , Zhang Jing , Ma Jin , Li Bing , Quan Hude
Published: November 2008

Background

Under the current healthcare system in China, there is no government-sponsored health insurance program for children. Children from families who move from rural and interior regions to large urban centres without a valid residency permit might be at higher risk of being uninsured due to their low socioeconomic status. We conducted a survey in Shanghai to describe children's health insurance coverage according to their migration status.

Method

Between 2005 and 2006, we conducted an in-person health survey of the adult care-givers of children aged 7 and under, residing in five districts of Shanghai. We compared uninsurance rates between temporary and permanent child residents, and investigated factors associated with child health uninsurance.

Results

Even though cooperative insurance eligibility has been extended to temporary residents of Shanghai, the uninsurance rate was significantly higher among temporary (65.6%) than permanent child residents (21.1%, adjusted odds ratio (OR): 5.85, 95% confidence interval (95% CI): 4.62–7.41). For both groups, family income was associated with having child health insurance; children in lower income families were more likely to be uninsured (OR: 1.96, 95% CI: 1.40–2.96).

Conclusion

Children must rely on their parents to make the insurance purchase decision, which is constrained by their income and the perceived benefits of the insurance program. Children from migrant families are at even higher risk for uninsurance due to their lower socioeconomic status. Government initiatives specifically targeting temporary residents and providing health insurance benefits for their children are urgently needed.
Apolipoprotein gene polymorphisms and plasma levels in healthy Tunisians and patients with coronary artery disease
Authors: Bahri Raoudha , Esteban Esther , Moral Pedro , Hassine Mohsen , Hamda Khaldoun Ben , Chaabani Hassen
Published: November 2008

Aim

To analyze apolipoprotein gene polymorphisms in the Tunisian population and to check the relation of these polymorphisms and homocysteine, lipid and apolipoprotein levels to the coronary artery disease (CAD).

Methods

In healthy blood donors and in patients with CAD complicated by myocardial infarction (MI) four apolipoprotein gene polymorphisms [APO (a) PNR, APO E, APO CI and APO CII] were determined and plasma levels of total homocysteine, total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HLD-C) and apolipoproteins (apo A-I, Apo B, Apo E) were measured.

Results

Analysis of the four apolipoprotein gene polymorphisms shows a relative genetic homogeneity between Tunisian population and those on the other side of Mediterranean basin. Compared to controls, CAD patients have significantly higher main concentrations of TC, TG, LDL-C, apo B and homocysteine, and significantly lower ones of HDL-C, apo A-I and apo E. The four apolipoprotein gene polymorphisms have not showed any significant differences between patients and controls. However, the APO E4 allele appears to be associated to the severity of CAD and to high levels of atherogenic parameters and low level of apo E, which has very likely an anti-atherogenic role.

Conclusion

Although APO (a) PNR, APO CI and APO CII genes are analyzed in only few populations, they show a frequency distribution, which is not at variance with that of APO E gene and other widely studied genetic markers. In the Tunisian population the APO E 4 appears to be only indirectly involved in the severity of CAD. In the routine practice, in addition of classic parameters, it will be useful to measure the concentration of apo E and that of Homocysteine and if possible to determine the APO E gene polymorphism.
Variation in genes encoding eosinophil granule proteins in atopic dermatitis patients from Germany
Authors: Parwez Qumar , Stemmler Susanne , Epplen Jörg T , Hoffjan Sabine
Published: November 2008

Background

Atopic dermatitis (AD) is believed to result from complex interactions between genetic and environmental factors. A main feature of AD as well as other allergic disorders is serum and tissue eosinophilia. Human eosinophils contain high amounts of cationic granule proteins, including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), eosinophil peroxidase (EPO) and major basic protein (MBP). Recently, variation in genes encoding eosinophil granule proteins has been suggested to play a role in the pathogenesis of allergic disorders. We therefore genotyped selected single nucleotide polymorphisms within theECP, EDN, EPOandMBPgenes in a cohort of 361 German AD patients and 325 healthy controls.

Results

Genotype and allele frequencies did not differ between patients and controls for all polymorphisms investigated in this study. Haplotype analysis did not reveal any additional information.

Conclusion

We did not find evidence to support an influence of variation in genes encoding eosinophil granule proteins for AD pathogenesis in this German cohort.
Hispanic Latin America, Spain and the Spanish-speaking Caribbean: A rich source of reference material for public health, epidemiology and tropical medicine
Authors: Williams John R , Bórquez Annick , Basáñez María-Gloria
Published: November 2008

There is a multiplicity of journals originating in Spain and the Spanish-speaking countries of Latin America and the Caribbean (SSLAC) in the health sciences of relevance to the fields of epidemiology and public health. While the subject matter of epidemiology in Spain shares many features with its neighbours in Western Europe, many aspects of epidemiology in Latin America are particular to that region. There are also distinctive theoretical and philosophical approaches to the study of epidemiology and public health arising from traditions such as the Latin American social medicine movement, of which there may be limited awareness. A number of online bibliographic databases are available which focus primarily on health sciences literature arising in Spain and Latin America, the most prominent being Literatura Latinoamericana en Ciencias de la Salud (LILACS) and LATINDEX. Some such as LILACS also extensively index grey literature. As well as in Spanish, interfaces are provided in English and Portuguese. Abstracts of articles may also be provided in English with an increasing number of journals beginning to publish entire articles written in English. Free full text articles are becoming accessible, one of the most comprehensive sources being the Scientific Electronic Library Online (SciELO). There is thus an extensive range of literature originating in Spain and SSLAC freely identifiable and often accessible online, and with the potential to provide useful inputs to the study of epidemiology and public health provided that any reluctance to explore these resources can be overcome. In this article we provide an introduction to such resources.
Sumatriptan Inhibits Synaptic Transmission in the Rat Midbrain Periaqueductal Grey
Authors: Jeong Hyo-Jin , Chenu David , Johnson Emma E , Connor Mark , Vaughan Christopher W
Published: November 2008

Background:

There is evidence to suggest that the midbrain periaqueductal grey (PAG) has a role in migraine and the actions of the anti-migraine drug sumatriptan. In the present study we examined the serotonergic modulation of GABAergic and glutamatergic synaptic transmission in rat midbrain PAG slices in vitro.

Results:

Serotonin (5-hydroxytriptamine, 5-HT, IC50= 142 nM) and the selective serotonin reuptake inhibitor fluoxetine (30 μM) produced a reduction in the amplitude of GABAA-mediated evoked inhibitory postsynaptic currents (IPSCs) in all PAG neurons which was associated with an increase in the paired-pulse ratio of evoked IPSCs. Real time PCR revealed that 5-HT1A, 5-HT1B, 5-HT1D and 5-HT1F receptor mRNA was present in the PAG. The 5-HT1A, 5-HT1B and 5-HT1D receptor agonists 8-OH-DPAT (3 μM), CP93129 (3 μM) and L694247 (3 μM), but not the 5-HT1F receptor agonist LY344864 (1 – 3 μM) inhibited evoked IPSCs. The 5-HT (1 μM) induced inhibition of evoked IPSCs was abolished by the 5-HT1B antagonist NAS181 (10 μM), but not by the 5-HT1A and 5-HT1D antagonists WAY100135 (3 μM) and BRL15572 (10 μM). Sumatriptan also inhibited evoked IPSCs with an IC50of 261 nM, and reduced the rate, but not the amplitude of spontaneous miniature IPSCs. The sumatriptan (1 μM) induced inhibition of evoked IPSCs was abolished by NAS181 (10 μM) and BRL15572 (10 μM), together, but not separately. 5-HT (10 μM) and sumatriptan (3 μM) also reduced the amplitude of non-NMDA mediated evoked excitatory postsynaptic currents (EPSCs) in all PAG neurons tested.

Conclusion:

These results indicate that sumatriptan inhibits GABAergic and glutamatergic synaptic transmission within the PAG via a 5-HT1B/D receptor mediated reduction in the probability of neurotransmitter release from nerve terminals. These actions overlap those of other analgesics, such as opioids, and provide a mechanism by which centrally acting 5-HT1B and 5-HT1D ligands might lead to novel anti-migraine pharmacotherapies.
FMRI Connectivity Analysis of Acupuncture Effects on an Amygdala-Associated Brain Network
Authors: Qin Wei , Tian Jie , Bai Lijun , Pan Xiaohong , Yang Lin , Chen Peng , Dai Jianping , Ai Lin , Zhao Baixiao , Gong Qiyong , Wang Wei , von Deneen Karen M , Liu Yijun
Published: November 2008

Background:

Recently, increasing evidence has indicated that the primary acupuncture effects are mediated by the central nervous system. However, specific brain networks underpinning these effects remain unclear.

Results:

In the present study using fMRI, we employed a within-condition interregional covariance analysis method to investigate functional connectivity of brain networks involved in acupuncture. The fMRI experiment was performed before, during and after acupuncture manipulations on healthy volunteers at an acupuncture point, which was previously implicated in a neural pathway for pain modulation. We first identified significant fMRI signal changes during acupuncture stimulation in the left amygdala, which was subsequently selected as a functional reference for connectivity analyses. Our results have demonstrated that there is a brain network associated with the amygdala during a resting condition. This network encompasses the brain structures that are implicated in both pain sensation and pain modulation. We also found that such a pain-related network could be modulated by both verum acupuncture and sham acupuncture. Furthermore, compared with a sham acupuncture, the verum acupuncture induced a higher level of correlations among the amygdala-associated network.

Conclusion:

Our findings indicate that acupuncture may change this amygdala-specific brain network into a functional state that underlies pain perception and pain modulation.
Congenital scoliosis in monozygotic twins: case report and review of possible factors contributing to its development
Authors: Kaspiris Angelos , Grivas Theodoros B , Weiss Hans-Rudolf
Published: November 2008

Background

The exact etiology of congenital scoliosis remains unknown as yet. It seems that its development may be influenced by both genetic predisposition and environmental factors, at varying degrees. International bibliography features few cases of monozygotic twins with congenital scoliosis. The aim of this study is to report a case in monozygotic twins and review the literature relating to the description of similar cases as well as the pathophysiological mechanism involved in its development.

Methods

Clinical examination and simple X-rays revealed scoliosis of differing degrees and types in male monozygotic twins with moderate mental retardation and dyslalia.

Results

Congenital scoliosis identified in both twins. In the first, this was manifested as left thoracic scoliosis, with Cobb angle of 34 degrees while in the second as left thoracolumbar scoliosis with Cobb angle of 10 degrees. Both were found to suffer from incarcerated hemivertebrae.

Conclusion

According to both its clinical identification and severity and to its course, not only the genetic but the environmental factors seem to play a leading role in the appearance of the condition.