bluuebunny/crossref_metadata_2025_split huggingface dataset:
GSTM1andGSTP1and respiratory health in asthmatic children exposed to ozone
Authors: Romieu I. , Ramirez-Aguilar M. , Sienra-Monge J. J. , Moreno-Macías H. , del Rio-Navarro B. E. , David G. , Marzec J. , Hernández-Avila M. , London S. 
Published: July 2006

Acute exposure to ozone has been related to a wide spectrum of health effects in susceptible individuals. Genetic factors may influence interindividual variation in ozone response. The current authors investigated the relationships between common polymorphisms in two genes involved in response to oxidative stress,i.e.glutathioneS-transferases M1 (GSTM1) and P1 (GSTP1), and both respiratory symptoms and lung function in response to ozone among childhood asthmatics.A total of 151 asthmatic children, who were participants in a randomised controlled trial of antioxidant vitamin supplementation in Mexico City, were studied. Children were genotyped using PCR methods and followed from October 1998–April 2000.Increases in reported breathing difficulty were associated with ozone exposure in children withGSTM1null (8%, 95% confidence interval (CI) 1–15%, per 20-ppb increase in 1-h maximum daily average over 7 days) orGSTP1Valine/Valine (Val/Val) genotypes (14%, 95% CI 5–25%). In children with bothGSTM1null andGSTP1Val/Val genotypes, the increase in breathing difficulty associated with a 20-ppb increase in ozone exposure was even greater (21%, 95% CI 5–39%).GSTP1genotypes were not significantly associated with ozone-related lung function changes.In conclusion, asthmatic children with glutathioneS-transferase M1 null and glutathioneS-transferase P1 Valine/Valine genotypes appear more susceptible to developing respiratory symptoms related to ozone exposure.
An oral selective M3 cholinergic receptor antagonist in COPD
Authors: Lu S. , Parekh D. D. , Kuznetsova O. , Green S. A. , Tozzi C. A. , Reiss T. F. 
Published: July 2006

Cholinergic antagonists have been used since the early 1900s as bronchodilators for chronic obstructive pulmonary disease (COPD). The present study investigated whether an oral muscarinic M3-selective anticholinergic agent (OrM3) would provide an improved therapeutic advantage compared with an inhaled anticholinergic agent in patients with COPD.A 6-week, multicentre, randomised, placebo- and active-controlled, parallel-group study was performed at 56 sites in the USA. In total, 412 male and female patients (aged 35–86 yrs) with a clinical history consistent with COPD were randomised to receive OrM3 0.5, 2, 3 or 4 mg orally once daily, ipratropium bromide 36 μg by inhalation four times daily or placebo.OrM3 demonstrated a significant dose-related improvement in serial forced expiratory volume in one second and a trend for dose-related improvement in patient-reported symptoms compared with placebo. However, at a dose that provided efficacy less than that of ipratropium, the incidence of dose-related, mechanism-based side-effects for OrM3 exceeded those observed for ipratropium.In patients with chronic obstructive pulmonary disease, the oral M3-selective agent did not offer a therapeutic advantage over inhaled ipratropium. These results do not support the hypothesis that high selectivity for muscarinic M3 receptors over airway neuronal M2 receptors will represent a more effective therapy than current inhaled anticholinergics in obstructive airway disease.
The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer
Authors: Lam B. , Wong M. P. , Fung S. L. , Lam D. C. L. , Wong P. C. , Mok T. Y. W. , Lam F. M. , Ip M. S. M. , Ooi C. G. C. , Lam W. K. 
Published: July 2006

The aim of this study was to evaluate the role of autofluorescence bronchoscopy (AFB) in the routine work-up of lung cancer.Consecutive patients with atypical or suspicious cells in sputum or bronchial aspirate, no localising abnormality on chest radiography and nondiagnostic white-light bronchoscopic (WLB) results were recruited. WLB and AFB were performed sequentially during the same session. All abnormal areas detected by WLB, AFB or both were sampled and the biopsy specimens sent for histological examination.Sixty-two patients were recruited within the 32-month study period. Seventeen had no endobronchial lesion detected. Among the 45 patients with endobronchial lesions, 37 had lesions with a histopathological grade of mild dysplasia or less; of the eight patients who had a lesion with a histological grade of moderate dysplasia or worse, five were found to have lung cancer, two invasive lung cancer and three an intra-epithelial neoplasm (severe dysplasia). Lesions showing moderate dysplasia or worse were more commonly found in patients with suspicious cells than in those with atypical cells on sputum examination. AFB was more sensitive than WLB (91versus58%) at detecting these lesions, but less specific (26versus50%).A combination of white-light and autofluorescence bronchoscopy can increase the diagnostic yield of this invasive procedure in patients exhibiting abnormal sputum cytology.
TENOR risk score predicts healthcare in adults with severe or difficult-to-treat asthma
Authors: Miller M. K. , Lee J. H. , Blanc P. D. , Pasta D. J. , Gujrathi S. , Barron H. , Wenzel S. E. , Weiss S. T. 
Published: July 2006

The aim of the present study was to predict which patients with severe or difficult-to-treat asthma are at highest risk for healthcare utilisation can be predicted so as to optimise clinical management.Data were derived from 2,821 adults with asthma enrolled in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. Multiple potential predictors were assessed at baseline using a systematic algorithm employing stepwise logistic regression. Outcomes were asthma-related hospitalisations or emergency department (ED) visits within 6 months following baseline.Overall, 239 subjects (8.5%) reported hospitalisation or ED visits at follow-up. Predictors retained after multivariate analysis were as follows: younger age; female sex; non-white race; body mass index ≥35 kg·m-2; post-bronchodilator per cent predicted forced vital capacity <70%; history of pneumonia; diabetes; cataracts; intubation for asthma; and three or more steroid bursts in the prior 3 months. A final risk score derived from the logistic regression model ranged from 0–18 and was highly predictive (c-index: 0.78) of hospitalisation or ED visits. This tool was re-tested in a prospective validation using outcomes at 12- to 18-months follow-up among the same cohort (c-index: 0.77).The risk score derived is a clinically useful tool for assessing the likelihood of asthma-related hospitalisation or emergency department visits in adults with severe and difficult-to-treat asthma.
Incidence of asthma and net change in symptoms in relation to changes in obesity
Authors: Chinn S. , Downs S. H. , Anto J. M. , Gerbase M. W. , Leynaert B. , de Marco R. , Janson C. , Jarvis D. , Künzli N. , Sunyer J. , Svanes C. , Zemp E. , Ackermann-Liebrich U. , Burney P. 
Published: July 2006

The incidence of asthma has been reported to be associated with obesity. An alternative analysis, of net change in prevalence, does not require exclusion of those with asthma at baseline.Follow-up data were obtained from 9,552 participants in the European Community Respiratory Health Survey and the Swiss cohort Study on Air Pollution and Lung Disease in Adults. Incidence of asthma was analysed by proportional hazards regression, and net changes in symptoms and asthma status by generalised estimating equations, by obesity group.Incidence and net change in ever having had asthma were greater in females than in males, and in participants who remained obese compared with those who were never obese (hazard ratio 2.00, 95% confidence interval 1.25–3.20; excess net change 2.8%, 0.4–5.3% per 10 yrs). The effect of being obese on net change in diagnosed asthma was greater in females than in males, but for net change in wheeze without a cold it was greater in males.The present results are consistent with asthma being more frequently diagnosed in females, especially obese females. These findings may help to explain the reports of a stronger association between asthma and obesity in females than in males.
Participation of the PI-3K/Akt-NF-κB signaling pathways in hypoxia-induced mitogenic factor-stimulated Flk-1 expression in endothelial cells
Authors: Tong Qiangsong , Zheng Liduan , Lin Li , Li Bo , Wang Danming , Huang Chuanshu , Matuschak George M , Li Dechun 
Published: July 2006

AbstractBackgroundHypoxia-induced mitogenic factor (HIMF), a lung-specific growth factor, promotes vascular tubule formation in a matrigel plug model. We initially found that HIMF enhances vascular endothelial growth factor (VEGF) expression in lung epithelial cells. In present work, we tested whether HIMF modulates expression of fetal liver kinase-1 (Flk-1) in endothelial cells, and dissected the possible signaling pathways that link HIMF to Flk-1 upregulation.MethodsRecombinant HIMF protein was intratracheally instilled into adult mouse lungs, Flk-1 expression was examined by immunohistochemistry and Western blot. The promoter-luciferase reporter assay and real-time RT-PCR were performed to examine the effects of HIMF on Flk-1 expression in mouse endothelial cell line SVEC 4–10. The activation of NF-kappa B (NF-κB) and phosphorylation of Akt, IKK, and IκBα were examined by luciferase assay and Western blot, respectively.ResultsIntratracheal instillation of HIMF protein resulted in a significant increase of Flk-1 production in lung tissues. Stimulation of SVEC 4–10 cells by HIMF resulted in increased phosphorylation of IKK and IκBα, leading to activation of NF-κB. Blocking NF-κB signaling pathway by dominant-negative mutants of IKK and IκBα suppressed HIMF-induced Flk-1 upregulation. Mutation or deletion of NF-κB binding site within Flk-1 promoter also abolished HIMF-induced Flk-1 expression in SVEC 4–10 cells. Furthermore, HIMF strongly induced phosphorylation of Akt. A dominant-negative mutant of PI-3K, Δp85, as well as PI-3K inhibitor LY294002, blocked HIMF-induced NF-κB activation and attenuated Flk-1 production.ConclusionThese results suggest that HIMF upregulates Flk-1 expression in endothelial cells in a PI-3K/Akt-NF-κB signaling pathway-dependent manner, and may play critical roles in pulmonary angiogenesis.
PIPE: a protein-protein interaction prediction engine based on the re-occurring short polypeptide sequences between known interacting protein pairs
Authors: Pitre Sylvain , Dehne Frank , Chan Albert , Cheetham Jim , Duong Alex , Emili Andrew , Gebbia Marinella , Greenblatt Jack , Jessulat Mathew , Krogan Nevan , Luo Xuemei , Golshani Ashkan 
Published: July 2006

Abstract

Background
Identification of protein interaction networks has received considerable attention in the post-genomic era. The currently available biochemical approaches used to detect protein-protein interactions are all time and labour intensive. Consequently there is a growing need for the development of computational tools that are capable of effectively identifying such interactions.

Results
Here we explain the development and implementation of a novel Protein-Protein Interaction Prediction Engine termed PIPE. This tool is capable of predicting protein-protein interactions for any target pair of the yeast Saccharomyces cerevisiae proteins from their primary structure and without the need for any additional information or predictions about the proteins. PIPE showed a sensitivity of 61% for detecting any yeast protein interaction with 89% specificity and an overall accuracy of 75%. This rate of success is comparable to those associated with the most commonly used biochemical techniques. Using PIPE, we identified a novel interaction between YGL227W (vid30) and YMR135C (gid8) yeast proteins. This lead us to the identification of a novel yeast complex that here we term vid30 complex (vid30c). The observed interaction was confirmed by tandem affinity purification (TAP tag), verifying the ability of PIPE to predict novel protein-protein interactions. We then used PIPE analysis to investigate the internal architecture of vid30c. It appeared from PIPE analysis that vid30c may consist of a core and a secondary component. Generation of yeast gene deletion strains combined with TAP tagging analysis indicated that the deletion of a member of the core component interfered with the formation of vid30c, however, deletion of a member of the secondary component had little effect (if any) on the formation of vid30c. Also, PIPE can be used to analyse yeast proteins for which TAP tagging fails, thereby allowing us to predict protein interactions that are not included in genome-wide yeast TAP tagging projects.

Conclusion
PIPE analysis can predict yeast protein-protein interactions. Also, PIPE analysis can be used to study the internal architecture of yeast protein complexes. The data also suggests that a finite set of short polypeptide signals seem to be responsible for the majority of the yeast protein-protein interactions.
Increased large conductance calcium-activated potassium (BK) channel expression accompanied by STREX variant downregulation in the developing mouse CNS
Authors: MacDonald Stephen H-F , Ruth Peter , Knaus Hans-Guenther , Shipston Michael J 
Published: July 2006

Abstract

Background
Large conductance calcium- and voltage activated potassium (BK) channels are important determinants of neuronal excitability through effects on action potential duration, frequency and synaptic efficacy. The pore- forming subunits are encoded by a single gene, KCNMA1, which undergoes extensive alternative pre mRNA splicing. Different splice variants can confer distinct properties on BK channels. For example, insertion of the 58 amino acid stress-regulated exon (STREX) insert, that is conserved throughout vertebrate evolution, encodes channels with distinct calcium sensitivity and regulation by diverse signalling pathways compared to the insertless (ZERO) variant. Thus, expression of distinct splice variants may allow cells to differentially shape their electrical properties during development. However, whether differential splicing of BK channel variants occurs during development of the mammalian CNS has not been examined.

Results
Using quantitative real-time polymerase chain reaction (RT-PCR) Taqman™ assays, we demonstrate that total BK channel transcripts are up regulated throughout the murine CNS during embryonic and postnatal development with regional variation in transcript levels. This upregulation is associated with a decrease in STREX variant mRNA expression and an upregulation in ZERO variant expression.

Conclusion
As BK channel splice variants encode channels with distinct functional properties the switch in splicing from the STREX phenotype to ZERO phenotype during embryonic and postnatal CNS development may provide a mechanism to allow BK channels to control distinct functions at different times of mammalian brain development.
Why are physicians not persuaded by scientific evidence? A grounded theory interview study
Authors: Sekimoto Miho , Imanaka Yuichi , Kitano Nobuko , Ishizaki Tatsuro , Takahashi Osamu 
Published: July 2006

Abstract

Background
The government-led "evidence-based guidelines for cataract treatment" labelled pirenoxine and glutathione eye drops, which have been regarded as the standard care for cataracts in Japan, as lacking evidence of effectiveness, causing great upset among ophthalmologists and professional ophthalmology societies. This study investigated the reasons why such "scientific evidence of treatment effectiveness" is not easily accepted by physicians, and thus, why they do not change their clinical practices to reflect such evidence.

Methods
We conducted a qualitative study based on grounded theory to explore physicians' awareness of "scientific evidence" and evidence-supported treatment in relation to pirenoxine and glutathione eye drops, and to identify current barriers to the implementation of evidence-based policies in clinical practice. Interviews were conducted with 35 ophthalmologists and 3 general practitioners on their prescribing behaviours, perceptions of eye drop effectiveness, attitudes toward the eye drop guideline recommendations, and their perceptions of "scientific evidence."

Results
Although few physicians believed that eye drops are remarkably effective, the majority of participants reported that they prescribed eye drops to patients who asked for them, and that such patients accounted for a considerable proportion of those with cataracts. Physicians seldom attempted to explain to patients the limitations of effectiveness or to encourage them to stop taking the eye drops. Physicians also acknowledged the benefits of prescribing such drugs, which ultimately outweighed any uncertainty of their effectiveness. These benefits included economic incentives and a desire to be appreciated by patients. Changes in clinical practice were considered to bring little benefit to physicians or patients. Government approval, rarity of side effects, and low cost of the drops also encouraged prescription.

Conclusion
Physicians occasionally provide treatment without expecting remarkable therapeutic effectiveness, as exemplified by the use of eye drops. This finding highlights that scientific evidence alone cannot easily change physicians' clinical practices, unless evidence-based practices are accepted by the general public and supported by health policy.
Assessment of skeletal muscle fatigue of road maintenance workers based on heart rate monitoring and myotonometry
Authors: Roja Zenija , Kalkis Valdis , Vain Arved , Kalkis Henrijs , Eglite Maija 
Published: July 2006

AbstractObjectiveThis research work is dedicated to occupational health problems caused by ergonomic risks. The research object was road building industry, where workers have to work very intensively, have long work hours, are working in forced/constrained work postures and overstrain during the work specific parts of their bodies. The aim of this study was to evaluate the work heaviness degree and to estimate the muscle fatigue of workers after one week work cycle. The study group consisted of 10 road construction and maintenance workers and 10 pavers aged between 20 and 60 years.MethodsPhysical load were analyzed by measuring heart rate (HR), work postures (OWAS) and perceived exertion (RPE). Assessments of the muscles strain and functional state (tone) were carried out using myotonometric (MYO) measurements. The reliability of the statistical processing of heart rate monitoring and myotonometry data was determined using correlating analysis.ResultsThis study showed that that road construction and repairing works should be considered as a hard work according to average metabolic energy consumption 8.1 ± 1.5 kcal/min; paving, in its turn, was a moderately hard work according to 7.2 ± 1.1 kcal/min. Several muscle tone levels were identified allowing subdivision of workers into three conditional categories basing on muscle tone and fatigue: I – absolute muscle relaxation and ability to relax; II – a state of equilibrium, when muscles are able to adapt to the work load and are partly able to relax; and III – muscle fatigue and increased tone. It was also found out that the increase of muscle tone and fatigue mainly depend on workers physical preparedness and length of service, and less – on their age.ConclusionWe have concluded that a complex ergonomic analysis consisting of heart rate monitoring, assessment of compulsive working postures and myotonometry is appropriate to assess the work heaviness degree and can provide prognosis of occupational pathology or work-related musculoskeletal disorders for the workers under different workload conditions. These results can also be used when deciding on necessary rest time and its periodicity.
Fine scale structural variants distinguish the genomes of Drosophila melanogaster and D. pseudoobscura
Authors: Macdonald Stuart J , Long Anthony D 
Published: July 2006

Abstract
Background
A primary objective of comparative genomics is to identify genomic elements of functional significance that contribute to phenotypic diversity. Complex changes in genome structure (insertions, duplications, rearrangements, translocations) may be widespread, and have important effects on organismal diversity. Any survey of genomic variation is incomplete without an assessment of structural changes.

Results
We re-examine the genome sequences of the diverged species Drosophila melanogaster and D. pseudoobscura to identify fine-scale structural features that distinguish the genomes. We detect 95 large insertion/deletion events that occur within the introns of orthologous gene pairs, the majority of which represent insertion of transposable elements. We also identify 143 microinversions below 5 kb in size. These microinversions reside within introns or just upstream or downstream of genes, and invert conserved DNA sequence. The sequence conservation within microinversions suggests they may be enriched for functional genetic elements, and their position with respect to known genes implicates them in the regulation of gene expression. Although we found a distinct pattern of GC content across microinversions, this was indistinguishable from the pattern observed across blocks of conserved non-coding sequence.

Conclusion
Drosophila has long been known as a genus harboring a variety of large inversions that disrupt chromosome colinearity. Here we demonstrate that microinversions, many of which are below 1 kb in length, located in/near genes may also be an important source of genetic variation in Drosophila. Further examination of other Drosophila genome sequences will likely identify an array of novel microinversion events.
ppGalNAc-T13: A New Molecular Marker of Bone Marrow Involvement in Neuroblastoma
Authors: Berois Nora , Blanc Etienne , Ripoche Hugues , Mergui Xénia , Trajtenberg Felipe , Cantais Sabrina , Barrois Michel , Dessen Philippe , Kågedal Bertil , Bénard Jean , Osinaga Eduardo , Raguénez Gilda 
Published: July 2006

Abstract
Background: To identify new molecular markers of bone marrow dissemination in human neuroblastoma (NB), we studied the transcriptome profiles of malignant neuroblasts established from the human MYCN-amplified IGR-N-91 model.
Methods: This experimental model includes human neuroblastoma cells derived from a subcutaneous stage 4 disease, myocardium (Myoc) and bone marrow (BM) metastatic cells.
Results: Gene expression profiles obtained with Agilent oligo microarrays revealed a set of 107 differentially expressed genes in the metastatic neuroblasts. This set included up-regulated genes involved in chemoresistance, cell motility, neuronal structure/signaling, and the recently characterized GALNT13 gene encoding a glycosyltransferase that initiates mucin-type O-glycosylation. Because the glycosylation process is involved in the progression of primary tumor to metastatic disease, we investigated whether the most strongly up-regulated gene, GALNT13, might be a marker of bone marrow involvement in stage 4 NB patients. Importantly, in the BM of healthy adults no GALNT13 transcript was detected with analysis by quantitative (n = 3) and nested reverse transcription-PCR (n = 4) assays. In contrast, GALNT13 transcripts were detected in 23/23 cytologically involved BM samples obtained at diagnosis of stage 4 NB patients and in 5/27 cytologically noninvolved BM samples obtained from patients with stage 1–4 and 4S and treated stage 4 NB. The quantitative measurements of tyrosine hydroxylase (TH), ganglioside D2 synthase, dopa decarboxylase, and GALNT13 transcript values were compared in the same NB patients, and the results showed that GALNT13 expression was most highly correlated to poor clinical outcome at diagnosis.
Conclusion: We propose ppGalNAc-T13 as a new informative marker for the molecular diagnosis of BM involvement and the follow-up of minimal residual disease in NB patients.