bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphoinositide 3-kinase δ inhibitor suppresses interleukin-17 expression in a murine asthma model
Authors: Park S.J. , Lee K.S. , Kim S.R. , Min K.H. , Moon H. , Lee M.H. , Chung C.R. , Han H.J. , Puri K.D. , Lee Y.C. 
Published: March 2010

Phosphoinositide 3-kinases (PI3Ks) contribute to the pathogenesis of asthma by regulating the activation of inflammatory mediators, inflammatory cell recruitment and immune cell function. Recent findings have indicated that PI3Ks also regulate the expression of interleukin (IL)-17, which has been recognised as an important cytokine involved in airway inflammation.In the present study, we investigated a role of PI3Kδ in the regulation of IL-17 expression in allergic airway disease using a murine model of asthma.After ovalbumin inhalation, administration of a selective p110δ inhibitor, IC87114, significantly attenuated airway infiltration of total cells, lymphocytes, neutrophils and eosinophils, as well as airway hyperresponsiveness, and attenuated the increase in IL-17 protein and mRNA expression. Moreover, IC87114 reduced levels of IL-4, -5 and -13, expression of keratinocyte chemoattractant protein and mRNA, and nuclear factor (NF)-κB activity. In addition, a NF-κB inhibitor, BAY 11-7085 substantially reduced the increase in IL-17 protein levels. Our results also showed that inhibition of IL-17 activity with an anti-IL-17 antibody remarkably reduced airway inflammation and hyperresponsiveness.These findings suggest that inhibition of the p110δ signalling pathway suppresses IL-17 expression through regulation of NF-κB activity and, thus, has therapeutic potential in asthma.
Fasudil reduces monocrotaline-induced pulmonary arterial hypertension: comparison with bosentan and sildenafil
Authors: Mouchaers K.T.B. , Schalij I. , de Boer M.A. , Postmus P.E. , van Hinsbergh V.W.M. , van Nieuw Amerongen G.P. , Vonk Noordegraaf A. , van der Laarse W.J. 
Published: March 2010

Pulmonary arterial hypertension (PAH) still cannot be cured, warranting the search for novel treatments.Fasudil (a Rho kinase inhibitor) was compared with bosentan (an endothelin receptor blocker) and sildenafil (a phosphodiesterase 5 inhibitor), with emphasis on right ventricular (RV) function, in a reversal rat model of monocrotaline (MCT)-induced PAH. In addition, the effects of combining bosentan or sildenafil with fasudil were studied.MCT (40 mg·kg body weight−1) induced clear PAH in male Wistar rats (n = 9). After 28 days, echocardiography, RV catheterisation and histochemistry showed that cardiac frequency, stroke volume and RV contractility had deteriorated, accompanied by RV dilatation and hypertrophy, and marked pulmonary arterial wall thickening. Mean pulmonary arterial pressure and pulmonary vascular resistance increased significantly compared to healthy rats (n = 9). After 14 days, MCT-treated rats received a 14-day oral treatment with bosentan, sildenafil, fasudil or a combination of fasudil with either bosentan or sildenafil (all n = 9). All treatments preserved cardiac frequency, stroke volume and RV contractility, and reduced pulmonary vascular resistance and RV dilatation. Fasudil lowered RV systolic pressure and mean pulmonary arterial pressure significantly, by reducing pulmonary arterial remodelling, which reduced RV hypertrophy. Combining bosentan or sildenafil with fasudil had no synergistic effect.Fasudil significantly improved PAH, to a greater degree than did bosentan and sildenafil.
Systemic sclerosis and bilateral lung transplantation: a single centre experience
Authors: Saggar R. , Khanna D. , Furst D.E. , Belperio J.A. , Park G.S. , Weigt S.S. , Kubak B. , Ardehali A. , Derhovanessian A. , Clements P.J. , Shapiro S. , Hunter C. , Gregson A. , Fishbein M.C. , Lynch III J.P. , Ross D.J. , Saggar R. 
Published: March 2010

Lung involvement is the leading cause of death in systemic sclerosis (SSc), but lung transplantation (LT) for systemic disease remains controversial. Our objective was to comprehensively evaluate post-LT outcomes for SSc compared to idiopathic pulmonary fibrosis (IPF).We retrospectively evaluated bilateral LT recipients (LTRs) with SSc or IPF at our centre between January 1, 2003 and December 31, 2007. The primary end-point was all-cause mortality at 1 yr post-LT. Secondary end-points included assessments of acute rejection (AR), pulmonary function, infection and chronic rejection.14 patients with SSc and 38 patients with IPF underwent LT. Apart from a younger SSc cohort (53.2versus58.8 yrs; p = 0.02), the two groups were well matched. 1-yr all-cause mortality was no different between SSc (6.6%) and IPF (13.1%) groups, after adjusting for age (p = 0.62). Rates of (AR) ≥2 were significantly increased for the SSc compared with the IPF group (hazard ratio (HR) 2.91; p = 0.007). Other end-points, including chronic rejection, infection and pulmonary function, showed no differences.SSc LTRs experience similar survival 1 yr post-LT when compared to IPF. AR rates may be significantly higher in the SSc group. Longer follow-up is necessary to determine the effects of gastrointestinal dysfunction and AR on late allograft function in SSc LTR.
Plasmacytoid dendritic cells in pulmonary lymphoid follicles of patients with COPD
Authors: Van Pottelberge G.R. , Bracke K.R. , Van den Broeck S. , Reinartz S.M. , van Drunen C.M. , Wouters E.F. , Verleden G.M. , Vermassen F.E. , Joos G.F. , Brusselle G.G. 
Published: March 2010

Plasmacytoid dendritic cells (pDCs) are professional antigen-presenting cells with antiviral and tolerogenic capabilities. Viral infections and autoimmunity are proposed to be important mechanisms in the pathogenesis of chronic obstructive pulmonary disease (COPD).The study aimed to quantify blood dendritic cell antigen 2-positive pDCs in lungs of subjects with or without COPD by immunohistochemistry and flow cytometry, combined with the investigation of the influence of cigarette smoke extract (CSE) on the function of pDCsin vitro.pDCs were mainly located in lymphoid follicles, a finding compatible with their expression of lymphoid homing chemokine receptors CXCR3 and CXCR4. pDC accumulated in the lymphoid follicles and in lung digests of patients with mild to moderate COPD, compared with smokers without airflow limitation and patients with COPD Global Initiative for Chronic Obstructive Lung disease (GOLD) stage III–IV. Exposing maturing pDC of healthy subjects to CSEin vitrorevealed an attenuation of the expression of co-stimulatory molecules and impaired interferon-α production. Maturing pDC from patients with COPD produced higher levels of tumour necrosis factor (TNF)-α and interleukin (IL)-8 compared to pDC from healthy subjects.CSE significantly impairs the antiviral function of pDCs. In COPD, a GOLD stage dependent accumulation of pDC in lymphoid follicles is present, combined with an enhanced production of TNF-α and IL-8 by maturing pDCs.
Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults
Authors: Sistonen S. , Malmberg P. , Malmström K. , Haahtela T. , Sarna S. , Rintala R.J. , Pakarinen M.P. 
Published: March 2010

Although after oesophageal atresia (OA) repair in infancy, respiratory problems are common, their natural history remains unclear. We assessed morbidity, pulmonary function (PF), and bronchial hyperresponsiveness (BHR) in adults with repaired OA respiratory.588 patients who underwent surgery for OA during 1947–1985 were identified and those 262 who were alive and had their native oesophagus were included. Respiratory symptoms and respiratory symptom-related quality of life (RSRQoL) were assessed by questionnaire and interview, and the patients underwent spirometry, a histamine challenge test, and an exhaled nitric oxide test. For the questionnaires, we added 287 carefully matched general population-derived controls.Among the 101 (58 male) patients, median age 36 yrs (range 22–56 yrs), respiratory morbidity was significantly increased compared to controls. Patients had more respiratory symptoms and infections, as well as asthma and allergies, and more often impaired RSRQoL (p<0.001 for all). PF tests revealed restrictive ventilatory defect in 21 (21%) patients, obstructive ventilatroy defect in 21 (21%) patients, and both in 36 (36%) patients. A total of 41 (41%) had BHR, and in 15 (15%), it was consistent with asthma. The most significant risk factors for restrictive ventilatory defect were thoracotomy-induced rib fusions (OR 3.4, 95% CI 1.3–8.7; p = 0.01) and oesophageal epithelial metaplasia (OR 3.0, 95% CI 1.0–8.9; p = 0.05).After repair of OA, respiratory-related morbidity, restrictive ventilatory defect and BHR extended into adulthood. Nearly half the patients had BHR and over half had a restrictive ventilatory defect. Thoracotomy-induced rib fusions and gastro-oesophageal reflux-associated oesophageal epithelial metaplasia were the strongest risk factors for restrictive ventilatory defect.
An experimental model of pneumonia induced by methicillin-resistantStaphylococcus aureusin ventilated piglets
Authors: Martínez-Olondris P. , Sibila O. , Agustí C. , Rigol M. , Soy D. , Esquinas C. , Piñer R. , Luque N. , Guerrero L. , Quera M.Á. , Marco F. , de la Bellacasa J.P. , Ramirez J. , Torres A. 
Published: March 2010

The objectives of the study were to validate a model of methicillin-resistantStaphylococcus aureus(MRSA) pneumonia in ventilated piglets and to study the time-course of biological markers and histopathological changes.12 piglets were intubated and inoculated with 15 mL of a suspension of 106colony forming units of MRSA in every lobe through the bronchoscope channel. The piglets were ventilated for 12 h (n = 6) and 24 h (n = 6). Clinical parameters were assessed every 6 h and pro-inflammatory cytokines were measured in serum and in bronchoalveolar lavage (BAL) at baseline and sacrifice. Histopathology of each lobe and cultures from blood, lungs and BAL were performed.Animals developed histopathological evidence of pneumonia at necropsy. At 12 h, pneumonia was present in all animals and was severe pneumonia at 24 h. Microbiological studies confirmed the presence of MRSA. A significant increase in interleukin (IL)-6, IL-8 and tumour necrosis factor-α values was seen in BAL at 24 h and IL-6 at 12 h. In serum, only IL-6 levels had increased significantly at 24 h.In ventilated piglets, bronchoscopic inoculation of MRSA induces pneumonia at 12 h and severe pneumonia at 24 h. This severity was associated with a corresponding increase in systemic and local inflammatory response.
CDK-Taverna: an open workflow environment for cheminformatics
Authors: Kuhn Thomas , Willighagen Egon L , Zielesny Achim , Steinbeck Christoph 
Published: March 2010

AbstractBackgroundSmall molecules are of increasing interest for bioinformatics in areas such as metabolomics and drug discovery. The recent release of large open access chemistry databases generates a demand for flexible tools to process them and discover new knowledge. To freely support open science based on these data resources, it is desirable for the processing tools to be open source and available for everyone.ResultsHere we describe a novel combination of the workflow engine Taverna and the cheminformatics library Chemistry Development Kit (CDK) resulting in a open source workflow solution for cheminformatics. We have implemented more than 160 different workers to handle specific cheminformatics tasks. We describe the applications of CDK-Taverna in various usage scenarios.ConclusionsThe combination of the workflow engine Taverna and the Chemistry Development Kit provides the first open source cheminformatics workflow solution for the biosciences. With the Taverna-community working towards a more powerful workflow engine and a more user-friendly user interface, CDK-Taverna has the potential to become a free alternative to existing proprietary workflow tools.
Comprehensive analysis of MHC class I genes from the U-, S-, and Z-lineages in Atlantic salmon
Authors: Lukacs Morten F , Harstad Håvard , Bakke Hege G , Beetz-Sargent Marianne , McKinnel Linda , Lubieniecki Krzysztof P , Koop Ben F , Grimholt Unni 
Published: March 2010

AbstractBackgroundWe have previously sequenced more than 500 kb of the duplicated MHC class I regions in Atlantic salmon. In the IA region we identified the loci for the MHC class I geneSasa-UBAin addition to a soluble MHC class I molecule,Sasa-ULA. A pseudolocus forSasa-UCAwas identified in the nonclassical IB region. Both regions contained genes for antigen presentation, as wells as orthologues to other genes residing in the human MHC region.ResultsThe genomic localisation of two MHC class I lineages (Z and S) has been resolved. 7 BACs were sequenced using a combination of standard Sanger and 454 sequencing. The new sequence data extended the IA region with 150 kb identifying the location of one Z-lineage locus,ZAA. The IB region was extended with 350 kb including three new Z-lineage loci,ZBA,ZCAandZDAin addition to aUGAlocus. An allelic version of the IB region contained a functionalUDAlocus in addition to theUCApseudolocus. Additionally a BAC harbouring two MHC class I genes (UHA) was placed on linkage group 14, while a BAC containing the S-lineage locusSAA(previously known asUAA) was placed on LG10. Gene expression studies showed limited expression range for all class I genes with exception ofUBAbeing dominantly expressed in gut, spleen and gills, andZAAwith high expression in blood.ConclusionHere we describe the genomic organization of MHC class I loci from the U-, Z-, and S-lineages in Atlantic salmon. Nine of the described class I genes are located in the extension of the duplicated IA and IB regions, while three class I genes are found on two separate linkage groups. The gene organization of the two regions indicates that the IB region is evolving at a different pace than the IA region. Expression profiling, polymorphic content, peptide binding properties and phylogenetic relationship show that Atlantic salmon has only one MHC class Ia gene (UBA), in addition to a multitude of nonclassical MHC class I genes from the U-, S- and Z-lineages.
Mercury-induced hepatotoxicity in zebrafish: in vivo mechanistic insights from transcriptome analysis, phenotype anchoring and targeted gene expression validation
Authors: Ung Choong Yong , Lam Siew Hong , Hlaing Mya Myintzu , Winata Cecilia Lanny , Korzh Svetlana , Mathavan Sinnakaruppan , Gong Zhiyuan 
Published: March 2010

AbstractBackgroundMercury is a prominent environmental contaminant that causes detrimental effects to human health. Although the liver has been known to be a main target organ, there is limited information onin vivomolecular mechanism of mercury-induced toxicity in the liver. By using transcriptome analysis, phenotypic anchoring and validation of targeted gene expression in zebrafish, mercury-induced hepatotoxicity was investigated and a number of perturbed cellular processes were identified and compared with those captured in thein vitrohuman cell line studies.ResultsHepato-transcriptome analysis of mercury-exposed zebrafish revealed that the earliest deregulated genes were associated with electron transport chain, mitochondrial fatty acid beta-oxidation, nuclear receptor signaling and apoptotic pathway, followed by complement system and proteasome pathway, and thereafter DNA damage, hypoxia, Wnt signaling, fatty acid synthesis, gluconeogenesis, cell cycle and motility. Comparative meta-analysis of microarray data between zebrafish liver and human HepG2 cells exposed to mercury identified some common toxicological effects of mercury-induced hepatotoxicity in both models. Histological analyses of liver from mercury-exposed fish revealed morphological changes of liver parenchyma, decreased nucleated cell count, increased lipid vesicles, glycogen and apoptotic bodies, thus providing phenotypic evidence for anchoring of the transcriptome analysis. Validation of targeted gene expression confirmed deregulated gene-pathways from enrichment analysis. Some of these genes responding to low concentrations of mercury may serve as toxicogenomic-based markers for detection and health risk assessment of environmental mercury contaminations.ConclusionMercury-induced hepatotoxicity was triggered by oxidative stresses, intrinsic apoptotic pathway, deregulation of nuclear receptor and kinase activities including Gsk3 that deregulates Wnt signaling pathway, gluconeogenesis, and adipogenesis, leading to mitochondrial dysfunction, endocrine disruption and metabolic disorders. This study provides important mechanistic insights into mercury-induced liver toxicity in a whole-animal physiology context, which will help in understanding the syndromes caused by mercury poisoning. The molecular conservation of mercury-induced hepatotoxicity between zebrafish and human cell line reveals the feasibility of using zebrafish to model molecular toxicity in human for toxicant risk assessments.
An insight into the sialome of Glossina morsitans morsitans
Authors: Alves-Silva Juliana , Ribeiro José MC , Abbeele Jan Van Den , Attardo Geoffrey , Hao Zhengrong , Haines Lee R , Soares Marcelo B , Berriman Matthew , Aksoy Serap , Lehane Michael J 
Published: March 2010

Abstract

Background
Blood feeding evolved independently in worms, arthropods and mammals. Among the adaptations to this peculiar diet, these animals developed an armament of salivary molecules that disarm their host's anti-bleeding defenses (hemostasis), inflammatory and immune reactions. Recent sialotranscriptome analyses (from the Greek sialo = saliva) of blood feeding insects and ticks have revealed that the saliva contains hundreds of polypeptides, many unique to their genus or family. Adult tsetse flies feed exclusively on vertebrate blood and are important vectors of human and animal diseases. Thus far, only limited information exists regarding the Glossina sialome, or any other fly belonging to the Hippoboscidae.

Results
As part of the effort to sequence the genome of Glossina morsitans morsitans, several organ specific, high quality normalized cDNA libraries have been constructed, from which over 20,000 ESTs from an adult salivary gland library were sequenced. These ESTs have been assembled using previously described ESTs from the fat body and midgut libraries of the same fly, thus totaling 62,251 ESTs, which have been assembled into 16,743 clusters (8,506 of which had one or more EST from the salivary gland library). Coding sequences were obtained for 2,509 novel proteins, 1,792 of which had at least one EST expressed in the salivary glands. Despite library normalization, 59 transcripts were overrepresented in the salivary library indicating high levels of expression. This work presents a detailed analysis of the salivary protein families identified. Protein expression was confirmed by 2D gel electrophoresis, enzymatic digestion and mass spectrometry. Concurrently, an initial attempt to determine the immunogenic properties of selected salivary proteins was undertaken.

Conclusions
The sialome of G. m. morsitans contains over 250 proteins that are possibly associated with blood feeding. This set includes alleles of previously described gene products, reveals new evidence that several salivary proteins are multigenic and identifies at least seven new polypeptide families unique to Glossina. Most of these proteins have no known function and thus, provide a discovery platform for the identification of novel pharmacologically active compounds, innovative vector-based vaccine targets, and immunological markers of vector exposure.
Distinct genotypic profiles of the two major clades of Mycobacterium africanum
Authors: Vasconcellos Sidra E Gonçalves , Huard Richard C , Niemann Stefan , Kremer Kristin , Santos Adalberto R , Suffys Philip N , Ho John L 
Published: March 2010

Abstract

Background

Mycobacterium tuberculosis is the principal etiologic agent of human tuberculosis (TB) and a member of the M. tuberculosis complex (MTC). Additional MTC species that cause TB in humans and other mammals include Mycobacterium africanum and Mycobacterium bovis. One result of studies interrogating recently identified MTC phylogenetic markers has been the recognition of at least two distinct lineages of M. africanum, known as West African-1 and West African-2.

Methods
We screened a blinded non-random set of MTC strains isolated from TB patients in Ghana (n = 47) for known chromosomal region-of-difference (RD) loci and single nucleotide polymorphisms (SNPs). A MTC PCR-typing panel, single-target standard PCR, multi-primer PCR, PCR-restriction fragment analysis, and sequence analysis of amplified products were among the methods utilized for the comparative evaluation of targets and identification systems. The MTC distributions of novel SNPs were characterized in the both the Ghana collection and two other diverse collections of MTC strains (n = 175 in total).

Results
The utility of various polymorphisms as species-, lineage-, and sublineage-defining phylogenetic markers for M. africanum was determined. Novel SNPs were also identified and found to be specific to either M. africanum West African-1 (Rv1332
523; n = 32) or M. africanum West African-2 (nat
751; n = 27). In the final analysis, a strain identification approach that combined multi-primer PCR targeting of the RD loci RD9, RD10, and RD702 was the most simple, straight-forward, and definitive means of distinguishing the two clades of M. africanum from one another and from other MTC species.

Conclusion
With this study, we have organized a series of consistent phylogenetically-relevant markers for each of the distinct MTC lineages that share the M. africanum designation. A differential distribution of each M. africanum clade in Western Africa is described.
Cholesterol treatment with statins: Who is left out and who makes it to goal?
Authors: Franks Peter , Tancredi Daniel , Winters Paul , Fiscella Kevin 
Published: March 2010

Abstract

Background
Whether patient socio-demographic characteristics (age, sex, race/ethnicity, income, and education) are independently associated with failure to receive indicated statin therapy and/or to achieve low density lipoprotein cholesterol (LDL-C) therapy goals are not known. We examined socio-demographic factors associated with a) eligibility for statin therapy among those not on statins, and b) achievement of statin therapy goals.

Methods
Adults (21-79 years) participating in the United States (US) National Health and Nutrition Examination Surveys, 1999-2006 were studied. Statin eligibility and achievement of target LDL-C was assessed using the US Third Adult Treatment Panel (ATP III) on Treatment of High Cholesterol guidelines.

Results
Among 6,043 participants not taking statins, 10.4% were eligible. Adjusted predictors of statin eligibility among statin non-users were being older, male, poorer, and less educated. Hispanics were less likely to be eligible but not using statins, an effect that became non-significant with adjustment for language usually spoken at home. Among 537 persons taking statins, 81% were at LDL-C goal. Adjusted predictors of goal failure among statin users were being male and poorer. These risks were not attenuated by adjustment for healthcare access or utilization.

Conclusion
Among person's not taking statins, the socio-economically disadvantaged are more likely to be eligible and among those on statins, the socio-economically disadvantaged are less likely to achieve statin treatment goals. Further study is needed to identify specific amenable patient and/or physician factors that contribute to these disparities.