bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative splicing regulates activation-induced cytidine deaminase (AID): implications for suppression of AID mutagenic activity in normal and malignant B cells
Authors: Wu Xiaosheng , Darce Jaime R. , Chang Sook Kyung , Nowakowski Grzegorz S. , Jelinek Diane F. 
Published: August 2008

Abstract
The mutagenic enzyme activation-induced cytidine deaminase (AID) is required for immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM) in germinal center (GC) B cells. Deregulated expression of AID is associated with various B-cell malignancies and, currently, it remains unclear how AID activity is extinguished to avoid illegitimate mutations. AID has also been shown to be alternatively spliced in malignant B cells, and there is limited evidence that this also occurs in normal blood B cells. The functional significance of these splice variants remains unknown. Here we show that normal GC human B cells and blood memory B cells similarly express AID splice variants and show for the first time that AID splicing variants are singly expressed in individual normal B cells as well as malignant B cells from chronic lymphocytic leukemia patients. We further demonstrate that the alternative AID splice variants display different activities ranging from inactivation of CSR to inactivation or heightened SHM activity. Our data therefore suggest that CSR and SHM are differentially switched off by varying the expression of splicing products of AID at the individual cell level. Most importantly, our findings suggest a novel tumor suppression mechanism by which unnecessary AID mutagenic activities are promptly contained for GC B cells.
Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials
Authors: Branford Susan , Fletcher Linda , Cross Nicholas C. P. , Müller Martin C. , Hochhaus Andreas , Kim Dong-Wook , Radich Jerald P. , Saglio Giuseppe , Pane Fabrizio , Kamel-Reid Suzanne , Wang Y. Lynn , Press Richard D. , Lynch Kevin , Rudzki Zbigniew , Goldman John M. , Hughes Timothy 
Published: August 2008

AbstractAn international basis for comparison of BCR-ABL mRNA levels is required for the common interpretation of data derived from individual laboratories. This will aid clinical decisions for individual patients with chronic myeloid leukemia (CML) and assist interpretation of results from clinical studies. We aligned BCR-ABL values generated by 38 laboratories to an international scale (IS) where a major molecular response (MMR) is 0.1% or less. Alignment was achieved by application of laboratory-specific conversion factors calculated by comparisons performed with patient samples against a reference method. A validation procedure was completed for 19 methods. We determined performance characteristics (bias and precision) for consistent interpretation of MMR after IS conversion. When methods achieved an average BCR-ABL difference of plus or minus 1.2-fold from the reference method and 95% limits of agreement within plus or minus 5-fold, the MMR concordance was 91%. These criteria were met by 58% of methods. When not met, the MMR concordance was 74% or less. However, irrespective of precision, when the bias was plus or minus 1.2-fold as achieved by 89% of methods, there was good agreement between the overall MMR rates. This indicates that the IS can deliver accurate comparison of molecular response rates between clinical trials when measured by different laboratories.
Sleep-disordered breathing in unilateral diaphragm paralysis or severe weakness
Authors: Steier J. , Jolley C. J. , Seymour J. , Kaul S. , Luo Y. M. , Rafferty G. F. , Hart N. , Polkey M. I. , Moxham J. 
Published: August 2008

Few data exist concerning sleep in patients with hemidiaphragm paralysis or weakness. Traditionally, such patients are considered to sustain normal ventilation in sleep.In the present study, diaphragm strength was measured in order to identify patients with unilateral paralysis or severe weakness. Patients underwent polysomnography with additional recordings of the transoesophageal electromyogram (EMG) of the diaphragm and surface EMG of extra-diaphragmatic respiratory muscles. These data were compared with 11 normal, healthy subjects matched for sex, age and body mass index (BMI).In total, 11 patients (six males, mean±sdage 56.5±10.0 yrs, BMI 28.7±2.8 kg·m−2) with hemidiaphragm paralysis or severe weakness (unilateral twitch transdiaphragmatic pressure 3.3±1.7 cmH2O (0.33±0.17 kPa) were studied. They had a mean±sdrespiratory disturbance index of 8.1±10.1 events·h−1during non-rapid eye movement (NREM) sleep and 26.0±17.8 events·h−1during rapid eye movement (REM) sleep (control groups 0.4±0.4 and 0.7±0.9 events·h−1, respectively). The diaphragm EMG, as a percentage of maximum, was double that of the control group in NREM sleep (15.3±5.3versus8.9±4.9% max, respectively) and increased in REM sleep (20.0±6.9% max), while normal subjects sustained the same level of activation (6.2±3.1% max).Patients with unilateral diaphragm dysfunction are at risk of developing sleep-disordered breathing during rapid eye movement sleep. The diaphragm electromyogram, reflecting neural respiratory drive, is doubled in patients compared with normal subjects, and increases further in rapid eye movement sleep.
Fluticasone propionate reduces bacterial airway epithelial invasion
Authors: Barbier M. , Agustí A. , Albertí S. 
Published: August 2008

Fluticasone propionate reduces the frequency and severity of the episodes of exacerbation of chronic obstructive pulmonary disease (COPD).Streptococcus pneumoniaeandHaemophilus influenzaeare frequently isolated in these episodes. Both express phosphorylcholine, an epitope that mediates their interaction with airway epithelial cellsviathe platelet-activating factor receptor (PAFR).The present work studies the effects of fluticasone propionate on the expression of PAFR on human airway epithelial cells, the invasion of these cells byS. pneumoniaeandH. influenzae, and the course of pneumococcal infectionin vivo. The following were used in the experiments:S. pneumoniaeandH. influenzaeisolated from patients with COPD, cell cultures of type II pneumocytes and bronchoepithelial cells, and a mouse model of lung infection.Fluticasone propionate was found to reduce PAFR expression on the surface of the two cells types studied. AllS. pneumoniaeandH. influenzaeisolates expressed phosphorylcholine. Treatment of both cells lines with fluticasone propionate reduced invasion of both microorganisms and reduced the bacterial load of mice infected withS. pneumoniae.Fluticasone propionate reduces the invasion of airway epithelial cells byStreptococcus pneumoniaeandHaemophilus influenzaethrough its effect on platelet-activating factor receptor. These results may help explain the beneficial effects of fluticasone propionate on chronic obstructive pulmonary disease exacerbations.
Antenatal infection in the rabbit impairs post-natal growth and lung alveolarisation
Authors: Gras-Le Guen C. , Denis C. , Franco-Montoya M-L. , Jarry A. , Delacourt C. , Potel G. , Bourbon J. , Roze J-C. , Jarreau P-H. 
Published: August 2008

Clinical and experimental studies indicate an association between chorioamnionitis and bronchopulmonary dysplasia in preterm infants. The present authors hypothesised that, in the rabbit, antenatal infection may impair lung development after birth, despite effective maternal antibiotic therapy.Pregnant rabbits received an intra-uterine inoculation of 103Escherichia colicolony forming units or vehicle at the end of gestation (day 29). Intravenous ceftriaxone therapy was initiated 8 h after inoculation for a period of 8 days. Pups born between 60 and 84 h after inoculation were kept with their mother until sacrifice on days 0, 1, 5, 8 and 15.Blood cultures from antenatally infected animals were sterile at birth. Postnatal growth was significantly impaired by day 8. Lung morphometry showed a significant decrease of alveolar surface density and interstitial density, with a significant increase of alveolar airspace volume, indicating impaired alveolarisation for the first 2 weeks of postnatal life. Inflammatory and apoptotic processes were not detected in the lung at birth or subsequently.Intra-uterine infection in rabbits is, therefore, responsible for concomitant postnatal growth retardation and abnormal pulmonary development despite early and effective antenatal antibiotic therapy. This may constitute an alternative model to study the consequences of antenatal infection on postnatal growth and lung development.
Comparison of tuberculosis surveillance systems in low-incidence industrialised countries
Authors: Mor Z. , Migliori G. B. , Althomsons S. P. , Loddenkemper R. , Trnka L. , Iademarco M. F. 
Published: August 2008

The comparative analysis of National Tuberculosis Control Programmes (NTPs) in industrialised, low-tuberculosis-incidence countries is limited. Analysis of applied methods, function and accumulated experience contributes to improving global tuberculosis control.A questionnaire addressing NTP surveillance infrastructure and characteristics was completed in 19 industrialised countries, with populations of >3 million and annual notified tuberculosis incidence rates of <16 cases per 100,000 population (2003 data).All European countries surveyed adopted World Health Organization Collaborating Centre for the Surveillance of Tuberculosis in Europe (EuroTB) definitions. Surveillance information, which usually includes names, was transferred electronically to the national level in 17 out of the 19 countries. Surveillance systems capture process and social determinants. Case notification to the central level occurred within a median period of 7 days, independent of mandatory notification requirements. The mean completeness of tuberculosis case-reporting was estimated to be 93.5% (range 65–100%). Integration between HIV and tuberculosis registries was performed in two countries, and, in seven others, both databases were cross-matched periodically.National Tuberculosis Control Programme function in industrialised low-incidence countries utilises well-established infrastructure and relies upon centralised operations. Approaches are consistent with current World Health Organization surveillance recommendations. The present study lays collaborative groundwork for additional multinational analyses for the enhancement of global tuberculosis surveillance, which may assist policy-makers in countries moving from medium to low rates of incidence.
Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis
Authors: Ruhwald M. , Bodmer T. , Maier C. , Jepsen M. , Haaland M. B. , Eugen-Olsen J. , Ravn P. 
Published: August 2008

The aim of the present study was to evaluate the potential of diagnostic tests based on interferon-γ inducible protein (IP)-10 and monocyte chemotactic protein (MCP)-2, and compare the performance with the QuantiFERON TB® Gold In-Tube (QFT-IT; Cellestis, Carnagie, Australia) test.IP-10 and MCP-2 were determined in supernatants from whole blood stimulated withMycobacterium tuberculosis-specific antigens. Samples were obtained from 80 patients with culture- and/or PCR-proven tuberculosis (TB), and 124 unexposed healthy controls: 86 high school students and 38 high school staff. IP-10 and MCP-2 test cut-offs were established based on receiver operating characteristic curve analysis.TB patients produced significantly higher levels (median) of IP-10 (2158 pg·mL−1) and MCP-2 (379 pg·mL−1) compared with interferon (IFN)-γ (215 pg·mL−1). The QFT-IT, IP-10 and MCP-2 tests detected 81, 83 and 71% of the TB patients; 0, 3 and 0% of the high school students and 0, 16 and 3% of the staff, respectively. Agreement between tests was high (>89%). By combining IP-10 and IFN-γ tests, the detection rate increased among TB patients to 90% without a significant increase in positive responders among the students.In conclusion, interferon-γ inducible protein-10 and monocyte chemotactic protein-2 responses toMycobacterium tuberculosis-specific antigens could be used to diagnose infection. Combining interferon-γ inducible protein-10 and interferon-γ may be a simple approach to increase the detection rate of theMycobacterium tuberculosis-specificin vitrotests.
Computed tomography assessment of lung volume changes after bronchial valve treatment
Authors: Coxson H. O. , Nasute Fauerbach P. V. , Storness-Bliss C. , Müller N. L. , Cogswell S. , Dillard D. H. , Finger C. L. , Springmeyer S. C. 
Published: August 2008

The aim of the present study was to correlate clinical outcome measures following treatment with bronchial valves with regional lung volume. Computed tomography (CT) scan data from 57 subjects with severe emphysema were obtained from nine North American clinical trial sites. IBV® Valves (Spiration, Inc., Redmond, WA, USA) were placed to occlude segmental and subsegmental bronchi in right and left upper lobes using a flexible bronchoscope. Subjects completed a St George's Respiratory Questionnaire (SGRQ), pulmonary function test (PFT) and exercise capacity test. CT scans were analysed at baseline and at 1, 3 or 6 months after treatment to measure total and lobar lung density, volume and mass.Total lung volumes measured using CT were strongly correlated with PFT and did not change with treatment. However, the treated upper lobes significantly decreased in volume in 88% of the observations, by mean±sd335±444 mL, or a decrease of 10.2% in the 6 month data. The untreated lobes had an 11.6% increase in volume. Changes in regional lung volume were associated with clinically meaningful improvements in SGRQ (-8.95±16.22), but not clinically meaningful PFT changes.The significant health status improvements reported by subjects following bilateral bronchial valve treatment are associated with regional lung volume changes and interlobar shift measured using computed tomography.
ExoU-induced procoagulant activity inPseudomonas aeruginosa-infected airway cells
Authors: Plotkowski M. C. , Feliciano L. F. P. , Machado G. B. S. , Cunha L. G. , Freitas C. , Saliba A. M. , de Assis M. C. 
Published: August 2008

The present study addressed the question whether ExoU, aPseudomonas aeruginosatoxin with phospholipase A2 (PLA2) activity, may induce airway epithelial cells to overexpress tissue factor (TF) and exhibit a procoagulant phenotype.Cells from the human bronchial epithelial BEAS-2B line were infected with an ExoU-producingP. aeruginosastrain, pre-treated or not with the cytosolic PLA2 inhibitor methylarachidonyl fluorophosphate (MAFP), or with two ExoU-deficient mutants. Control noninfected and infected cells were assessed for the expression of: 1) TF mRNA by RT-PCR; 2) cell-associated TF by enzyme immunoassay and flow cytometry; 3) procoagulant activity by a colorimetric assay; and 4) microparticle-associated TF by flow cytometry. An enzyme immunoassay was also used to assess cell-associated TF in lung extracts from mice infected intratracheally with ExoU-producing and -deficient bacteria.Cells infected with the wild-type bacteria had higher levels of TF mRNA, cell-associated TF expression, procoagulant activity and released microparticle-associated TF than cells infected with the mutants. Bacterial treatment with MAFP significantly reduced the expression of TF by infected cells. Lung samples from mice infected with the wild-type bacteria exhibited higher levels of cell-associated TF and procoagulant activity.The present results demonstrate that ExoU may contribute to the pathogenesis of lung injury by inducing a tissue factor-dependent procoagulant activity in airway epithelial cells.
The response to combination therapy treatment regimens in severe/difficult-to-treat asthma
Authors: Campbell J. D. , Borish L. , Haselkorn T. , Rasouliyan L. , Lee J. H. , Wenzel S. E. , Sullivan S. D. 
Published: August 2008

The aim of the present study was to assess the response of high-dose salmeterol/fluticasone combination (SFC) and low-dose SFC compared with regimens without inhaled corticosteroid (ICS) plus long-acting β-agonist (LABA) in a large cohort with severe or difficult-to-treat asthma.Subjects were administered low-dose SFC (100/50 or 250/50 μg) or high-dose SFC (500/50 μg), and a control group received medications that could include ICS or LABA but not both. The present authors calculated unadjusted and propensity score-adjusted differences in outcomes consistent with components of asthma control, comparing high-dose and low-dose SFC cohorts with controls.The low-dose SFC cohort had higher asthma-related quality of life and fewer asthma control problems compared with controls. The high-dose SFC cohort had higher forced expiratory volume in one second but higher odds of having severe asthma compared with controls.The present results support the evidence that some asthmatics achieve better outcomes while receiving a low-dose salmeterol/fluticasone combination, but also suggest that those on a high-dose salmeterol/fluticasone combination fail to achieve significant improvement in many control-related health outcomes as compared with similar patients not receiving salmeterol/fluticasone combination. These findings suggest a limited value of high-dose salmeterol/fluticasone combination compared with the alternatives. While additional studies are needed, the present findings call for alternative therapeutic approaches in severe/difficult-to-treat asthma for those unable to attain asthma control with or without salmeterol/fluticasone combination.
Decreased FOXP3 expression in small airways of smokers with COPD
Authors: Isajevs S. , Taivans I. , Strazda G. , Kopeika U. , Bukovskis M. , Gordjusina V. , Kratovska A. 
Published: August 2008

CD4+CD25+ FOXP3-positive T-regulatory cells have an important role in controlling immune and inflammatory reactions. The present authors hypothesise that these cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to characterise the expression of FOXP3 in large and small airways of nonsmokers, smokers with normal lung function and COPD patients.A total of 19 nonsmokers, 20 smokers with normal lung function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral nonsmall cell carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate FOXP3 expression in large and small airways.Smokers with normal lung function and COPD patients had increased numbers of FOXP3-positive cells in large airways compared with nonsmokers. A positive correlation was observed between FOXP3 expression in large airways and smoked pack-yrs. In small airways, COPD patients had decreased numbers of FOXP3-positive cells, compared with asymptomatic smokers and nonsmokers, that negatively correlated with airflow obstruction.To conclude, chronic obstructive pulmonary disease is characterised by upregulation of FOXP3-positive cells in large airways but a downregulation in small airways that correlated with airflow limitation. The results of the present study contribute to a better understanding of the pathogenesis of chronic obstructive pulmonary disease.
Physical training does not increase allergic inflammation in asthmatic children
Authors: Moreira A. , Delgado L. , Haahtela T. , Fonseca J. , Moreira P. , Lopes C. , Mota J. , Santos P. , Rytilä P. , Castel-Branco M. G. 
Published: August 2008

The effects of a 3-month physical training programme on airway inflammation and clinical outcomes were studied in school-aged children with asthma.Subjects with persistent allergic asthma (aged 12.7±3.4 yrs; n = 34) were randomly allocated into training and control groups. Exercise consisted of twice-weekly 50-min sessions for 12 weeks. Inflammation was assessed by levels of exhaled nitric oxide, blood eosinophils, eosinophil cationic protein, C-reactive protein, and total and mite-specific immunoglobulin (Ig)E. Lung volumes and bronchial responsiveness to methacholine were determined. The Paediatric Asthma Quality of Life Questionnaire and Paediatric Asthma Caregiver's Quality of Life Questionnaire were used to evaluate activity restrictions, symptoms and emotional stress. The efficacy of the training was assessed by accelerometry.Following the programme, the exercise group spent twice as much time as the controls undertaking moderate-to-vigorous activities. No differences in changes were seen between groups for asthma outcomes. However, total IgE decreased more in the exercise group, as did mite-specific IgE.Training did not increase inflammation in children with persistent asthma, and may have decreased both total and allergen-specific immunoglobulin E levels. It is concluded that there is no reason to discourage asthmatic children with controlled disease to exercise.
Changes in lung volumes and airway responsiveness following haematopoietic stem cell transplantation
Authors: Barisione G. , Bacigalupo A. , Crimi E. , Van Lint M. T. , Lamparelli T. , Brusasco V. 
Published: August 2008

Changes in lung volume occur following haematopoietic stem cell transplantation (HSCT); airway hyperresponsiveness was occasionally reported, without mechanistic explanation. The present authors studied 17 patients by standard methacholine (MCh) challenge before and then 3 and 12 months after HSCT (n = 16 and n = 13, respectively). Another 6 patients were challenged before and 3 months after HSCT using a modified challenge to investigate the effect of deep inhalations.No patient developed bronchiolitis obliterans or bronchiolitis obliterans organising pneumonia. At 3 months, forced vital capacity (FVC) was significantly reduced by 0.33±0.55 L, forced expiratory volume in one second (FEV1) by 0.31±0.50 L, total lung capacity (TLC) by 0.39±0.37 L and single-breath diffusing capacity of the lung for carbon monoxide (DL,CO) by 15±12%. At 12 months, TLC decreased by 0.43±0.36 L andDL,COby 8±8%. With standard challenge, no significant changes in FEV1response to MCh were observed after HSCT but FVC decreased significantly less after HSCT compared with prior to HSCT, suggesting less air trapping. With modified challenge, deep inhalations reversed the MCh-induced decrease in partial expiratory flow more after HSCT compared with before HSCT and this correlated with TLC decrements.In conclusion, an increase in airway responsiveness is unlikely after haematopoietic stem cell transplantation, at least in patients without pulmonary complications, and mechanisms opposing airway narrowing may blunt the bronchoconstrictor response.