bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensinogen gene G-6A polymorphism influences idiopathic pulmonary fibrosis disease progression
Authors: Molina-Molina M. , Xaubet A. , Li X. , Abdul-Hafez A. , Friderici K. , Jernigan K. , Fu W. , Ding Q. , Pereda J. , Serrano-Mollar A. , Casanova A. , Rodríguez-Becerra E. , Morell F. , Ancochea J. , Picado C. , Uhal B. D. 
Published: May 2008

Angiotensin II is a growth factor that plays a key role in the physiopathology of idiopathic pulmonary fibrosis (IPF). A nucleotide substitution of an adenine instead of a guanine (G-6A) in the proximal promoter region of angiotensinogen (AGT), the precursor of angiotensin II, has been associated with an increased gene transcription rate.In order to investigate whether the G-6A polymorphism of the AGT gene is associated with IPF development, severity and progression, the present study utilised a case–control study design and genotyped G-6A in 219 patients with IPF and 224 control subjects.The distribution of G-6A genotypes and alleles did not significantly differ between cases and controls. The G-6A polymorphism of the AGT gene was not associated with disease severity at diagnosis. The presence of the A allele was strongly associated with increased alveolar arterial oxygen tension difference during follow-up, after controlling for the confounding factors. Higher alveolar arterial oxygen tension changes over time were observed in patients with the AA genotype (0.37±0.7 mmHg (0.049±0.093 kPa) per month) compared to GA genotype (0.12±1 mmHg (0.016±0.133 kPa) per month) and GG genotype (0.2±0.6 mmHg (0.027±0.080 kPa) per month).G-6A polymorphism of the angiotensinogen gene is associated with idiopathic pulmonary fibrosis progression but not with disease predisposition. This polymorphism could have a predictive significance in idiopathic pulmonary fibrosis patients.
Adrenal suppression in bronchiectasis and the impact of inhaled corticosteroids
Authors: Holme J. , Tomlinson J. W. , Stockley R. A. , Stewart P. M. , Barlow N. , Sullivan A. L. 
Published: May 2008

The present study identified three patients with bronchiectasis receiving inhaled corticosteroids (ICSs) who had symptomatic adrenal suppression secondary to ICS. The prevalence of adrenal suppression is unknown in bronchiectasis. The frequency of adrenal suppression and the impact of ICS use in bronchiectasis patients were examined.In total, 50 outpatients (33 receiving ICSs) underwent a short Synacthen test and completed a St George’s Respiratory Questionnaire (SGRQ). Symptoms of adrenal suppression, steroid use and lung function were compared between subjects who were suppressed and those who were not.Adrenal suppression was evident in 23.5% of subjects who did not receive ICSs and 48.5% of those who did. Basal cortisol and the increments by which cortisol increased 30 min after Synacthen were lower in suppressed than in nonsuppressed subjects. The incremental cortisol rise was negatively correlated with SGRQ impacts and total score, suggesting a worse quality of life in those who had an impaired adrenal response. The greatest frequency of generalised symptoms was seen in the suppressed group.A significant proportion of subjects with bronchiectasis have evidence of adrenal suppression, and this is increased when inhaled corticosteroids are also used. Impairment of the cortisol response to stimulation is associated with poorer health status.
Workplace-specific challenges as a contribution to the diagnosis of occupational asthma
Authors: Rioux J-P. , Malo J-L. , L’Archevêque J. , Rabhi K. , Labrecque M. 
Published: May 2008

The diagnosis of occupational asthma can be made by exposing workers to the relevant agent either in a hospital laboratory through specific inhalation challenges (SICs) or in the workplace. As suggested by several authors, workers with negative laboratory SIC can be monitored at the workplace under supervision. The present study aims to assess the frequency of, and identify factors associated with, a positive workplace reaction in workers with negative SIC in the laboratory.The results of workplace challenges were examined in 99 workers who underwent negative SIC between 1994 and 2004. A positive reaction either in the SIC or in the workplace was defined as a sustained fall in forced expiratory volume in one second of ≥20%.In total, 22 (22.2%) workers showed positive responses at the workplace. These subjects more often had increased baseline methacholine responsiveness (90.5versus67.6%). They also underwent more days of SIC testing (4.9versus3.3 days) and were exposed more often to two or more agents (56versus28.4%) and for a longer period of time (363.3 versus220.4 min) in the laboratory.The present study illustrates the usefulness of workplace monitoring of airway function in the investigation of occupational asthma and identifies factors that are more often associated with a positive reaction.
Antimicrobial peptides in lung transplant recipients with bronchiolitis obliterans syndrome
Authors: Anderson R. L. , Hiemstra P. S. , Ward C. , Forrest I. A. , Murphy D. , Proud D. , Lordan J. , Corris P. A. , Fisher A. J. 
Published: May 2008

Mechanisms other than classical alloimmunity are implicated in the pathogenesis of bronchiolitis obliterans syndrome (BOS). It was hypothesised that antimicrobial peptides (AMPs), elements of the innate immune response, have a role in BOS pathogenesis.Pulmonary expression of the neutrophil-derived AMPs human cathelicidin (hCAP)-18/LL-37 and α-defensins (human neutrophil peptides (HNP) 1–3), and the epithelial cell-derived AMPs human β-defensin (hBD)-2, elafin and secretory leukoprotease inhibitor (SLPI) were measured in stable lung transplant recipients and those with BOS. The relationship between airway pathogens and AMP levels was examined.Bronchoalveolar lavage (BAL) was performed on 44 lung transplant recipients (30 stable, 14 with BOS). BAL was cultured for pathogens and ELISA for AMPs was performed. The presence of airway pathogens was associated with significantly increased levels of neutrophil-derived and epithelial-derived AMPs. When patients without pathogens in BAL fluid were analysed, eight recipients with BOS had elevated hCAP-18/LL-37 and HNP 1–3 compared with 25 stable recipients. hBD-2 and elafin levels were comparable in BOS and stable recipients, but SLPI levels were reduced in BOS.Bronchiolitis obliterans syndrome is associated with elevated airway human cathelicidin 18/LL-37 and human neutrophil peptides 1–3 from activated neutrophils, even in the absence of pathogens. Together with reduced airway secretory leukoprotease inhibitor this may favour nonalloimmune airway injury with reduced antiprotease defence and increased neutrophil degranulation.
Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice
Authors: Southam D. S. , Ellis R. , Wattie J. , Young S. , Inman M. D. 
Published: May 2008

Despite the effectiveness of corticosteroids at resolving airway inflammation, they are only moderately effective at attenuating airway hyperresponsiveness (AHR). The extent to which corticosteroids are able to reverse or inhibit the development of sustained AHR is not known. The present study aimed to determine whether budesonide can resolve and or prevent the development of sustained AHR in mice.Mice were chronically exposed to allergen and treated with budesonide either: 1) briefly during the final weeks of exposure to allergen; 2) prolonged concurrently throughout exposure to allergen; or 3) delayed following final exposure to allergen. AHR was assessed 24 h (brief treatment) or 4 weeks (prolonged concurrent and delayed treatments) following final exposure to allergen.Brief budesonide intervention significantly attenuated the inflammation-associated AHR assessed immediately following final exposure to allergen. Similarly, prolonged concurrent budesonide treatment prevented the development of sustained AHR. Delayed budesonide intervention, however, did not resolve sustained AHR.In conclusion, the early introduction and, importantly, the persistence of corticosteroid treatment prevented the development of sustained airway hyperresponsiveness; however, the inability of corticosteroids to reverse established airway dysfunction indicates a limitation in their use for the complete, long-term management of airway hyperresponsiveness.
Early mortality in patients with community-acquired pneumonia: causes and risk factors
Authors: Garcia-Vidal C. , Fernández-Sabé N. , Carratalà J. , Díaz V. , Verdaguer R. , Dorca J. , Manresa F. , Gudiol F. 
Published: May 2008

The first 48 h of evolution of patients with community-acquired pneumonia (CAP) are critical. The aim of the present study was to determine the frequency, causes and factors associated with early mortality in CAP.Nonimmunocompromised adults hospitalised with CAP were prospectively observed from 1995 to 2005. Early deaths, defined as death due to any cause ≤48 h after admission, were compared with all patients who survived >48 h. Furthermore, early deaths were compared with late deaths (patients who died >48 h) and with survivors.Of 2,457 patients, 57 (2.3%) died ≤48 h after admission. Overall mortality was 7.7%. The main causes of early mortality were respiratory failure and septic shock/multiorgan failure. Independent factors associated with early deaths were increased age, altered mental status at presentation, multilobar pneumonia, shock at admission, pneumococcal bacteraemia and discordant empiric antibiotic therapy.Currently, early mortality is relatively low and is caused by pneumonia-related factors. It occurs mainly among the elderly and in patients presenting with altered mental status, multilobar pneumonia and septic shock. Pneumococcal bacteraemia and discordant antibiotic therapy, mainly due to lack of coverage againstPseudomonas aeruginosaare also significant risk factors.
Predictors of outcomes in COPD exacerbation cases presenting to the emergency department
Authors: Roche N. , Zureik M. , Soussan D. , Neukirch F. , Perrotin D. ,   the Urgence BPCO (COPD Emergency) Scientific Committee and investigators
Published: May 2008

The aim of the present prospective multicentric study was to develop a simple rule for the prediction of poor outcome in patients presenting to emergency departments with initially non-life threatening-chronic obstructive pulmonary disease (COPD) exacerbations in a real-life setting.All patients with an acute exacerbation of COPD visiting the emergency departments of 103 hospitals during a 3-month period were included, except those who immediately required intensive care unit admission and/or ventilatory support. The data collected included patient characteristics, in-hospital outcomes (mortality and length of stay) and mode of discharge (unsupported or need for post-hospital assistance).The in-hospital mortality rate was 7.4% (59 out of 794). Independent prognostic factors were age, number of clinical signs of severity (among cyanosis, impaired neurological status, lower limb oedema, asterixis and use of accessory inspiratory or expiratory muscles) and dyspnoea grade in the stable state. The need for post-hospital support was also predicted by female sex. In order to construct and validate a prediction score for mortality based on these items, patients were randomly allocated to a derivation and a validation cohort. The prediction score showed good discrimination, with a c-statistic of 0.79 in the derivation cohort and 0.83 in the validation cohort.Thus simple purely clinical factors can reliably predict the risk of death and requirement for post-hospital support in an initially non-life threatening-acute exacerbation of chronic obstructive pulmonary disease. Their use needs to be prospectively validated.
The lectin-like domain of thrombomodulin protects against ischaemia–reperfusion lung injury
Authors: Geudens N. , Van de Wouwer M. , Vanaudenaerde B. M. , Vos R. , Van De Wauwer C. , Verleden G. M. , Verbeken E. , Lerut T. , Van Raemdonck D. E. M. , Conway E. M. 
Published: May 2008

Ischaemia–reperfusion injury of the lung is a major cause of morbidity and mortality, particularly following lung transplantation, the mainstay treatment for patients with end-stage pulmonary disease. Effective measures to prevent this complication are lacking. Thrombomodulin (TM) is an endothelial cell receptor and cofactor for thrombin-mediated generation of the anticoagulant and anti-inflammatory activated protein C (APC). The N-terminal lectin-like domain (LLD) of TM has no direct effects on coagulation, but has distinct anti-inflammatory properties, interfering with leukocyte adhesion, complement activation and cytokine generation, all of which are hallmarks of ischaemia–reperfusion injury. Using a murine model of lung ischaemia–reperfusion injury (90 min ischaemia, 4 h reperfusion), the present study shows that mice lacking the LLD of TM respond with increased extravasation of neutrophils and macrophages into the lung parenchyma and bronchoalveolar fluid (BALF), with augmented BALF levels of cytokines interleukin (IL)-1β and granulocyte-monocytic colony-stimulating factor (GM-CSF). Pre-treatment of wild-type mice with recombinant LLD, as compared with controls, significantly suppresses protein leakage and accumulation of leukocytes in the BALF.These novel findings support further evaluation of recombinant lectin-like domain of thrombomodulin to protect the lung against tissue-damaging pro-inflammatory responses following ischaemia-reperfusion.
Microsatellite DNA instability and COPD exacerbations
Authors: Makris D. , Tzanakis N. , Damianaki A. , Ntaoukakis E. , Neofytou E. , Zervou M. , Siafakas N. M. , Tzortzaki E. G. 
Published: May 2008

Increased frequency of microsatellite DNA instability (MSI) has been detected in the sputum of chronic obstructive pulmonary disease (COPD) patients. The aim of the present study was to investigate the relationship between MSI in sputum cells and exacerbation frequency, which is an important parameter in the clinical course of the disease.Induced sputum samples and peripheral blood obtained from 36 patients with COPD at stable state were analysed. The control group consisted of 30 nonsmoking healthy subjects. DNA was extracted and analysed for MSI using the following microsatellite markers: RH70958, D5S207, D6S2223, D6S344, D6S263, G29802, D13S71, D14S588, D14S292 and D17S250. Following MSI analysis, exacerbations were recorded for 3 yrs in total.No MSI was detected in healthy nonsmokers. A total of 18 (50%) out of 36 patients exhibited MSI in their sputum cells. Patients who exhibited MSI showed significantly increased frequency of exacerbations compared with patients that did not. In addition, a significantly increased frequency of purulent and of severe type exacerbations was found in patients exhibiting MSI. Patients positive for marker G29802, D13S71 or D14S588 presented increased exacerbation frequency.The significant association between microsatellite DNA instability and chronic obstructive pulmonary disease exacerbations indicates that somatic mutations could be involved in the pathogenesis and natural history of the disease.
BatchPrimer3: A high throughput web application for PCR and sequencing primer design
Authors: You Frank M , Huo Naxin , Gu Yong Qiang , Luo Ming-cheng , Ma Yaqin , Hane Dave , Lazo Gerard R , Dvorak Jan , Anderson Olin D 
Published: May 2008

AbstractBackgroundMicrosatellite (simple sequence repeat – SSR) and single nucleotide polymorphism (SNP) markers are two types of important genetic markers useful in genetic mapping and genotyping. Often, large-scale genomic research projects require high-throughput computer-assisted primer design. Numerous such web-based or standard-alone programs for PCR primer design are available but vary in quality and functionality. In particular, most programs lack batch primer design capability. Such a high-throughput software tool for designing SSR flanking primers and SNP genotyping primers is increasingly demanded.ResultsA new web primer design program, BatchPrimer3, is developed based on Primer3. BatchPrimer3 adopted the Primer3 core program as a major primer design engine to choose the best primer pairs. A new score-based primer picking module is incorporated into BatchPrimer3 and used to pick position-restricted primers. BatchPrimer3 v1.0 implements several types of primer designs including generic primers, SSR primers together with SSR detection, and SNP genotyping primers (including single-base extension primers, allele-specific primers, and tetra-primers for tetra-primer ARMS PCR), as well as DNA sequencing primers. DNA sequences in FASTA format can be batch read into the program. The basic information of input sequences, as a reference of parameter setting of primer design, can be obtained by pre-analysis of sequences. The input sequences can be pre-processed and masked to exclude and/or include specific regions, or set targets for different primer design purposes as in Primer3Web and primer3Plus. A tab-delimited or Excel-formatted primer output also greatly facilitates the subsequent primer-ordering process. Thousands of primers, including wheat conserved intron-flanking primers, wheat genome-specific SNP genotyping primers, andBrachypodiumSSR flanking primers in several genome projects have been designed using the program and validated in several laboratories.ConclusionBatchPrimer3 is a comprehensive web primer design program to develop different types of primers in a high-throughput manner. Additional methods of primer design can be easily integrated into future versions of BatchPrimer3. The program with source code and thousands of PCR and sequencing primers designed for wheat andBrachypodiumare accessible athttp://wheat.pw.usda.gov/demos/BatchPrimer3/.
An intracellular motif of GLUT4 regulates fusion of GLUT4-containing vesicles
Authors: Heyward Catherine A , Pettitt Trevor R , Leney Sophie E , Welsh Gavin I , Tavaré Jeremy M , Wakelam Michael JO 
Published: May 2008

Abstract

Background
Insulin stimulates glucose uptake by adipocytes through increasing translocation of the glucose transporter GLUT4 from an intracellular compartment to the plasma membrane. Fusion of GLUT4-containing vesicles at the cell surface is thought to involve phospholipase D activity, generating the signalling lipid phosphatidic acid, although the mechanism of action is not yet clear.

Results
Here we report the identification of a putative phosphatidic acid-binding motif in a GLUT4 intracellular loop. Mutation of this motif causes a decrease in the insulin-induced exposure of GLUT4 at the cell surface of 3T3-L1 adipocytes via an effect on vesicle fusion.

Conclusion
The potential phosphatidic acid-binding motif identified in this study is unique to GLUT4 among the sugar transporters, therefore this motif may provide a unique mechanism for regulating insulin-induced translocation by phospholipase D signalling.
Identification of SNPs and INDELS in swine transcribed sequences using short oligonucleotide microarrays
Authors: Bischoff Steve R , Tsai Shengdar , Hardison Nicholas E , York Abby M , Freking Brad A , Nonneman Dan , Rohrer Gary , Piedrahita Jorge A 
Published: May 2008

Abstract

Background
Genome-wide detection of single feature polymorphisms (SFP) in swine using transcriptome profiling of day 25 placental RNA by contrasting probe intensities from either Meishan or an occidental composite breed with Affymetrix porcine microarrays is presented. A linear mixed model analysis was used to identify significant breed-by-probe interactions.

Results
Gene specific linear mixed models were fit to each of the log2 transformed probe intensities on these arrays, using fixed effects for breed, probe, breed-by-probe interaction, and a random effect for array. After surveying the day 25 placental transcriptome, 857 probes with a q-value ≤ 0.05 and |fold change| ≥ 2 for the breed-by-probe interaction were identified as candidates containing SFP. To address the quality of the bioinformatics approach, universal pyrosequencing assays were designed from Affymetrix exemplar sequences to independently assess polymorphisms within a subset of probes for validation. Additionally probes were randomly selected for sequencing to determine an unbiased confirmation rate. In most cases, the 25-mer probe sequence printed on the microarray diverged from Meishan, not occidental crosses. This analysis was used to define a set of highly reliable predicted SFPs according to their probability scores.

Conclusion
By applying a SFP detection method to two mammalian breeds for the first time, we detected transition and transversion single nucleotide polymorphisms, as well as insertions/deletions which can be used to rapidly develop markers for genetic mapping and association analysis in species where high density genotyping platforms are otherwise unavailable.
SNPs and INDELS discovered by this approach have been publicly deposited in NCBI's SNP repository dbSNP. This method is an attractive bioinformatics tool for uncovering breed-by-probe interactions, for rapidly identifying expressed SNPs, for investigating potential functional correlations between gene expression and breed polymorphisms, and is robust enough to be used on any Affymetrix gene expression platform.
Genomic Organization of Zebrafish microRNAs
Authors: Thatcher Elizabeth J , Bond Jordan , Paydar Ima , Patton James G 
Published: May 2008

Abstract

Background
microRNAs (miRNAs) are small (~22 nt) non-coding RNAs that regulate cell movement, specification, and development. Expression of miRNAs is highly regulated, both spatially and temporally. Based on direct cloning, sequence conservation, and predicted secondary structures, a large number of miRNAs have been identified in higher eukaryotic genomes but whether these RNAs are simply a subset of a much larger number of noncoding RNA families is unknown. This is especially true in zebrafish where genome sequencing and annotation is not yet complete.

Results
We analyzed the zebrafish genome to identify the number and location of proven and predicted miRNAs resulting in the identification of 35 new miRNAs. We then grouped all 415 zebrafish miRNAs into families based on seed sequence identity as a means to identify possible functional redundancy. Based on genomic location and expression analysis, we also identified those miRNAs that are likely to be encoded as part of polycistronic transcripts. Lastly, as a resource, we compiled existing zebrafish miRNA expression data and, where possible, listed all experimentally proven mRNA targets.

Conclusion
Current analysis indicates the zebrafish genome encodes 415 miRNAs which can be grouped into 44 families. The largest of these families (the miR-430 family) contains 72 members largely clustered in two main locations along chromosome 4. Thus far, most zebrafish miRNAs exhibit tissue specific patterns of expression.