bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers of early respiratory effects in smoking adolescents
Authors: Van Miert E. , Sardella A. , Bernard A. 
Published: May 2011

Noninvasive biomarkers can be used to evaluate airways damage caused by tobacco smoke, but studies so far have only involved adult smokers. In this study, we evaluated whether such biomarkers can detect early respiratory effects in adolescents passively or actively exposed to tobacco smoke.In a cross-sectional study of 845 adolescents (mean age 16 yrs), we measured exhaled nitric oxide (NO) and various epithelial markers in nasal lavage fluid (NALF) and serum, including Clara cell protein (CC16) and surfactant protein (SP)-D. Information about smoking habits and potential confounders was collected by questionnaire. Four groups of equal size (n=36), of nonsmokers, passive smokers, light smokers (<5 cigarettes·day−1, median 0.08 pack-yrs) and heavy smokers (≥5 cigarettes·day−1, median 0.35 pack-yrs), were matched using an automated procedure.The levels of exhaled NO and of CC16 in NALF were significantly decreased in the group of heavy smokers. A trend towards lower levels of CC16 in NALF was observed in passive smokers. There were no significant changes in serum CC16 and SP-D, which suggests that the deep lung epithelium had not yet been affected by smoking.In conclusion, tobacco smoke can cause early changes in the airways of adolescents with a cumulative smoking history of <1 pack-yr.
Small airways function declines after allogeneic haematopoietic stem cell transplantation
Authors: Lahzami S. , Schoeffel R.E. , Pechey V. , Reid C. , Greenwood M. , Salome C.M. , Berend N. , King G.G. 
Published: May 2011

Bronchiolitis obliterans (BO) following allogeneic haematopoietic stem cell transplantation (HSCT) affects peripheral airways. Detection of BO is presently delayed by the low sensitivity of spirometry.We examined the relationship between peripheral airway function and time since HSCT, and compared it with spirometry and clinical indices in 33 clinically stable allogeneic HSCT recipients. The following measurements were performed: lung function, exhaled nitric oxide, forced oscillatory respiratory system resistance and reactance, acinar (Sacin) and conductive airways ventilation heterogeneity and lung clearance index (LCI) measured by multiple breath nitrogen washout. 22 patients underwent repeat visits from which short-term changes were examined.Median time post HSCT was 12 months. Eight patients were clinically diagnosed as having BO. In multivariate analysis, time since HSCT was predicted by Sacinand forced expiratory volume in 1 s % predicted. 20 patients had abnormal Sacinwith normal spirometry, whereas none had airflow obstruction with normal Sacin. Sacinand LCI were the only measures to change significantly between two visits, with both worsening. Change in Sacinwas the only parameter to correlate with change in chronic graft-versus-host disease grade.In conclusion, peripheral airways ventilation heterogeneity worsens with time after HSCT. Sacinmay be more sensitive than spirometry in detecting BO at an early stage, which needs confirmation in a prospective study.
HLA-DRB1* alleles and symptoms associated with Heerfordt's syndrome in sarcoidosis
Authors: Darlington P. , Tallstedt L. , Padyukov L. , Kockum I. , Cederlund K. , Eklund A. , Grunewald J. 
Published: May 2011

Heerfordt's syndrome (HS) consists in its complete form of uveitis, parotid or salivary gland enlargement and cranial nerve palsy. The objective of the present study was to analyse if there are also links between HLA-DRB1* alleles and HS, as it is a specific phenotype of sarcoidosis.1,000 patients with sarcoidosis, out of whom 83 had symptoms associated with HS, were included in the study together with a group of 2,000 healthy individuals from the same population, matched for sex and age. HLA-DRB1* allelic groups were determined for all individuals, and comparisons were made between different disease subgroups and between patients and healthy controls.We found that the HLA-DRB1*04 allele was overrepresented in patients with symptoms associated with HS. 83 (8.3%) of all patients had one or more of the symptoms and 46 (55%) of them were HLA-DRB1*04 positive. 44 (55%) of the patients with ocular sarcoidosis,i.e.the most common symptom associated with HS, were HLA-DRB1*04 positive, compared with 35.9% of healthy controls (p=0.0008), and only 26.6% of the whole group of sarcoidosis patients (p<0.0001).HLA-DRB1*04 seems to protect against overall sarcoidosis but appears to be a significant risk factor for ocular sarcoidosis as well as for other manifestations associated with HS.
Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study
Authors: Hollams E.M. , Hart P.H. , Holt B.J. , Serralha M. , Parsons F. , de Klerk N.H. , Zhang G. , Sly P.D. , Holt P.G. 
Published: May 2011

Vitamin D has been linked in some studies with atopy- and asthma-associated phenotypes in children with established disease, but its role in disease inception at the community level is less clear. The aim of the present study was to investigate associations between vitamin D status and biological signatures indicative of allergy and asthma development in children aged 6 and 14 years in Perth, WA, Australia (latitude 32° S).Serum vitamin D was assayed in 989 6-yr-olds and 1,380 14-yr-olds from an unselected community birth cohort; 689 subjects were assessed at both ages. Vitamin D levels were assessed as a risk modifier for respiratory and allergic outcomes at both ages, using previously ascertained phenotypic data. The predictive value of vitamin D levels at age 6 yrs for development of clinical phenotypes at age 14 yrs was also examined.Serum vitamin D levels in children of both ages were negatively associated with concurrent allergic phenotypes; sex stratification revealed that this association was restricted mainly to males. Furthermore, vitamin D levels at age 6 yrs were significant predictors of subsequent atopy/asthma-associated phenotypes at age 14 yrs.In an unselected community setting, children (particularly males) with inadequate vitamin D are at increased risk of developing atopy, and subsequently bronchial hyperresponsiveness (BHR) and asthma. In a large unselected cohort, males with inadequate vitamin D at 6 and 14 yrs of age had increased atopy and BHR. Low vitamin D at age 6 yrs was a predictor of atopy and asthma at 14 yrs of age.
Association of the transfer coefficient of the lung for carbon monoxide with emphysema progression in male smokers
Authors: Mohamed Hoesein F.A.A. , Zanen P. , van Ginneken B. , van Klaveren R.J. , Lammers J-W.J. 
Published: May 2011

A decreased transfer coefficient of the lung for carbon monoxide (KCO) is associated with emphysema. We evaluated whether in heavy smokers, baselineKCOwas associated with the progression of computed tomography (CT)-detected emphysema, and the progression of airflow limitation.Heavy smokers, mean±sd41.3±18.7 pack-yrs, participating in a lung cancer screening trial underwent diffusion testing and CT scanning of the lungs. CT scanning was repeated after median (25th–75th percentile) 2.8 (2.7–3.0) yrs and emphysema was assessed by lung densitometry using the 15th percentile. The association betweenKCOat baseline with progression of emphysema and lung function decline was assessed by multiple linear regression, correcting for baseline CT-quantified emphysema severity and forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), age, height, body mass index, pack-yrs and smoking status (current or former smoker).522 participants aged 60.1±5.4 yrs were included. Mean±sd15th percentile was -938±19, absolute FEV1/FVC was 71.6±9% andKCOwas 1.23±0.25, which is 81.8±16.5% of predicted. By interpolation, a onesd(0.25) lowerKCOvalue at baseline predicted a 1.6 HU lower 15th percentile and a 0.78% lower FEV1/FVC after follow-up (p<0.001).A lower baselineKCOvalue is independently associated with a more rapid progression of emphysema and airflow limitation in heavy smokers.
Patterns of airway disease and the clinical diagnosis of asthma in the Busselton population
Authors: Musk A.W. , Knuiman M. , Hunter M. , Hui J. , Palmer L.J. , Beilby J. , Divitini M. , Mulrennan S. , James A. 
Published: May 2011

The aim of this study was to examine how objective measures related to lung function cluster in the general population and how the patterns relate to asthma and bronchitis as diagnosed by a doctor (DDA and DDB, respectively).A cross-sectional survey of an age-stratified random general population sample of 1,969 adults from the electoral register of Busselton (Australia) was performed in 2005–2007. Respiratory symptoms, DDA ever, DDB ever, recent wheezing and smoking history, together with anthropometric measurements, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), methacholine challenge or bronchodilator response, exhaled nitric oxide (eNO), skin-prick tests to common allergens, and blood eosinophil and neutrophil counts were studied. Cluster analysis (variables sex, age, atopy, FEV1% predicted, FEV1/FVC, airway hyperresponsiveness, eNO, log eosinphil count, log neutrophil count and body mass index) was used to identify phenotypic patterns.Seven clusters (subjects with DDA and DDB, respectively) were identified: normal males (n=467; 7 and 13%), normal females (n=477; 12 and 18%), obese females (n=250; 16 and 28%), atopic younger adults (n=330; 21 and 17%), atopic adults with high eNO (n=130; 30 and 25%), atopic males with reduced FEV1(n=103; 33 and 32%) and atopic adults with bronchial hyperreactivity (n=212; 40 and 26%).The clinical diagnosis of asthma (ever) and bronchitis (ever) is not specific for any of the clustering patterns of airway abnormality.
Efficacy of pleurodesis for malignant pleural effusions in breast cancer patients
Authors: Hirata T. , Yonemori K. , Hirakawa A. , Shimizu C. , Tamura K. , Ando M. , Katsumata N. , Tanimoto M. , Fujiwara Y. 
Published: May 2011

This study retrospectively compared long-term outcomes between two groups of breast cancer patients with malignant pleural effusion (MPE): those receiving only systemic therapy (ST) and those receiving ST following initial pleurodesis (P-ST).We identified 180 breast cancer patients from the National Cancer Center Hospital (Tokyo, Japan) database who had received ST and P-ST as an initial treatment for MPE between 1997 and 2008 for study inclusion. Pleural progression-free survival (PPFS) was defined as the time from ST in the ST group and from pleurodesis in the P-ST group to the first observation of pleural progression or death from any cause.Of the 180 patients, 78 received ST and 102 received P-ST after MPE diagnosis. Median duration of follow-up was 12.7 months (range 0.9–80.1 months). Median PPFS for the ST group and the P-ST group was 4.1 and 8.5 months, respectively. The difference in PPFS between the two groups was statistically significant (p<0.001) and the hazard ratio after adjusting for prognostic factors in the P-ST group relative to the ST group was 0.24.Our results suggest that the efficacy of P-ST may be superior to that of ST alone with respect to local control of pleural effusions in breast cancer patients.
Properties of the COPD assessment test in a cross-sectional European study
Authors: Jones P.W. , Brusselle G. , Dal Negro R.W. , Ferrer M. , Kardos P. , Levy M.L. , Perez T. , Soler Cataluña J.J. , van der Molen T. , Adamek L. , Banik N. 
Published: May 2011

A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice.The performance of the eight-item COPD assessment test (CAT) was analysed in 1,817 patients from primary care in seven European countries. The CAT has a scoring range of 0–40 (high score representing poor health status).Mean CAT scores indicated significant health status impairment that was related to severity of airway obstruction, but within each Global Initiative for Obstructive Lung Disease stage (I to IV) there was a wide range of scores (I: 16.2±8.8; II: 16.3±7.9; III: 19.3±8.2; and IV: 22.3±8.7; IversusII, p = 0.88; IIversusIII, p<0.0001; IIIversusIV, p = 0.0001). CAT scores showed relatively little variability across countries (within ±12% of the mean across all countries). Scores were significantly better in patients who were stable (17.2±8.3)versusthose suffering an exacerbation (21.3±8.4) (p<0.0001); and in patients with no (17.3±8.1) or one or two (16.6±8.2)versusthree or more (19.7±8.5) comorbidities (p<0.0001 for both). The CAT distinguished between classes of other impairment measures and was strongly correlated with the St George’s Respiratory Questionnaire (r = 0.8, p<0.0001).The CAT is a simple and easy-to-use questionnaire that distinguishes between patients of different degrees of COPD severity and appears to behave the same way across countries.
Development of a decision tree to assess the severity and prognosis of stable COPD
Authors: Esteban C. , Arostegui I. , Moraza J. , Aburto M. , Quintana J.M. , Pérez-Izquierdo J. , Aizpiri S. , Capelastegui A. 
Published: May 2011

The aim of this study was to develop and validate a new method: a classification and regression tree (CART) based on easily accessible measures to predict mortality in patients with stable chronic obstructive pulmonary disease (COPD).This was a prospective study of two independent prospective cohorts: a derivation cohort with 611 recruited patients and a validation cohort with 348 patients, all followed for 5 yrs. CART analysis was used to predict 5-yr mortality risk using the following covariates from the derivation cohort: age, % predicted forced expiratory volume in 1 s (FEV1), dyspnoea, physical activity, general health and number of hospital admissions for COPD exacerbations in the previous 2 yrs.Age (≥75 or <75 yrs) provided the first branch of the COPD-CART. The highest mortality risk (0.74) was seen in patients >75 yrs of age with higher levels of dyspnoea and FEV1<50% pred. Patients with the lowest risk of 5-yr mortality (0.04) were <55 yrs of age with FEV1>35% pred and one or no recent hospitalisations for COPD exacerbations.A simple decision tree that uses variables commonly gathered by physicians can provide a quick assessment of the severity of the disease, as measured by the risk of 5-yr mortality.
Effectiveness and safety of leflunomide for pulmonary and extrapulmonary sarcoidosis
Authors: Sahoo D.H. , Bandyopadhyay D. , Xu M. , Pearson K. , Parambil J.G. , Lazar C.A. , Chapman J.T. , Culver D.A. 
Published: May 2011

Leflunomide has been reported as an alternative therapy in sarcoidosis. However, the published data are limited.We performed a retrospective chart review of the tolerance and effects of leflunomide therapy in patients with sarcoidosis.76 patients were included. The most common reasons for initiation were progression of disease or failure of other immunomodulator therapy. Side-effects attributable to leflunomide were noted in 34% of subjects, prompting discontinuation in 17%. The lungs were a target of therapy in 33 (44%) and extrapulmonary organs were a target in 45 (59%). The mean±sdchange in forced vital capacity in the 6 months prior to leflunomide was −0.1±0.3 L, and it was +0.09±0.3 L in the following 6 months (p=0.01). For extrapulmonary target organ response, 51% had a good response and 32% a partial response. The median corticosteroid dose at initiation was 10 mg (interquartile range 5–20) mg at baseline, and 0 (0–10) mg at the 6-month follow-up (p<0.001).Leflunomide is a viable alternative agent for pulmonary and extrapulmonary sarcoidosis. Leflunomide appears to facilitate reduction of steroid dose and can be considered as monotherapy or as add-on therapy in cases of progressive disease.
Escherichia coli genome-wide promoter analysis: Identification of additional AtoC binding target elements
Authors: Pilalis Eleftherios , Chatziioannou Aristotelis A , Grigoroudis Asterios I , Panagiotidis Christos A , Kolisis Fragiskos N , Kyriakidis Dimitrios A 
Published: May 2011

Abstract

Background
Studies on bacterial signal transduction systems have revealed complex networks of functional interactions, where the response regulators play a pivotal role. The AtoSC system of E. coli activates the expression of atoDAEB operon genes, and the subsequent catabolism of short-chain fatty acids, upon acetoacetate induction. Transcriptome and phenotypic analyses suggested that atoSC is also involved in several other cellular activities, although we have recently reported a palindromic repeat within the atoDAEB promoter as the single, cis-regulatory binding site of the AtoC response regulator. In this work, we used a computational approach to explore the presence of yet unidentified AtoC binding sites within other parts of the E. coli genome.

Results
Through the implementation of a computational de novo motif detection workflow, a set of candidate motifs was generated, representing putative AtoC binding targets within the E. coli genome. In order to assess the biological relevance of the motifs and to select for experimental validation of those sequences related robustly with distinct cellular functions, we implemented a novel approach that applies Gene Ontology Term Analysis to the motif hits and selected those that were qualified through this procedure. The computational results were validated using Chromatin Immunoprecipitation assays to assess the in vivo binding of AtoC to the predicted sites. This process verified twenty-two additional AtoC binding sites, located not only within intergenic regions, but also within gene-encoding sequences.

Conclusions
This study, by tracing a number of putative AtoC binding sites, has indicated an AtoC-related cross-regulatory function. This highlights the significance of computational genome-wide approaches in elucidating complex patterns of bacterial cell regulation.
Resistance to organic hydroperoxides requires ohr and ohrR genes in Sinorhizobium meliloti
Authors: Fontenelle Catherine , Blanco Carlos , Arrieta Morgane , Dufour Virginie , Trautwetter Annie 
Published: May 2011

Abstract

Background

Sinorhizobium meliloti is a symbiotic nitrogen-fixing bacterium that elicits nodules on roots of host plants Medicago sativa. During nodule formation bacteria have to withstand oxygen radicals produced by the plant. Resistance to H2O2 and superoxides has been extensively studied in S. meliloti. In contrast resistance to organic peroxides has not been investigated while S. meliloti genome encodes putative organic peroxidases. Organic peroxides are produced by plants and are highly toxic. The resistance to these oxygen radicals has been studied in various bacteria but never in plant nodulating bacteria.

Results
In this study we report the characterisation of organic hydroperoxide resistance gene ohr and its regulator ohrR in S. meliloti. The inactivation of ohr affects resistance to cumene and ter-butyl hydroperoxides but not to hydrogen peroxide or menadione in vitro. The expression of ohr and ohrR genes is specifically induced by organic peroxides. OhrR binds to the intergenic region between the divergent genes ohr and ohrR. Two binding sites were characterised. Binding to the operator is prevented by OhrR oxidation that promotes OhrR dimerisation. The inactivation of ohr did not affect symbiosis and nitrogen fixation, suggesting that redundant enzymatic activity exists in this strain. Both ohr and ohrR are expressed in nodules suggesting that they play a role during nitrogen fixation.

Conclusions
This report demonstrates the significant role Ohr and OhrR proteins play in bacterial stress resistance against organic peroxides in S. meliloti. The ohr and ohrR genes are expressed in nodule-inhabiting bacteroids suggesting a role during nodulation.
The temporal and spatial expression pattern of the LGI1 epilepsy predisposition gene during mouse embryonic cranial development
Authors: Silva Jeane , Wang Guanghu , Cowell John K 
Published: May 2011

Abstract

Background
Mutations in the LGI1 gene predispose to a rare, hereditary form of temporal epilepsy. Currently, little is known about the temporal and spatial expression pattern of Lgi1 during normal embryogenesis and so to define this more clearly we used a transgenic mouse line that expresses GFP under the control of Lgi1 cis-regulatory elements.

Results
During embryonic brain growth, high levels of Lgi1 expression were found in the surface ectoderm, the neuroepithelium, mesenchymal connective tissue, hippocampus, and sensory organs, such as eye, tongue, and the olfactory bulb. Lgi1 was also found in the cranial nerve nuclei and ganglia, such as vestibular, trigeminal, and dorsal ganglia. Expression of Lgi1 followed an orchestrated pattern during mouse development becoming more subdued in areas of the neocortex of the mid- and hind-brain in early postnatal animals, although high expression levels were retained in the choroid plexus and hippocampus. In late postnatal stages, Lgi1 expression continued to be detected in many areas in the brain including, hippocampus, paraventricular thalamic nuclei, inferior colliculus, and the cerebral aqueduct. We also showed that Lgi1-expressing cells co-express nestin, DCX, and beta-III tubulin suggesting that Lgi1-expressing cells are migratory neuroblasts.

Conclusion
These observations imply that Lgi1 may have a role in establishing normal brain architecture and neuronal functions during brain development suggesting that it may be involved in neurogenesis and neuronal plasticity, which become more specifically defined in the adult animal.