bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality of workers at a nickel carbonyl refinery, 1958–2000
Authors: Sorahan T , Williams S P 
Published: January 2005

Background:Excess risks of respiratory cancer have been shown in some groups of nickel exposed workers. It is clear, however, that not all forms of nickel exposure are implicated in these excess risks.Aim:To determine whether occupational exposures received in a modern nickel carbonyl refinery lead to increased risks of cancer, in particular nasal cancer and lung cancer.Methods:The mortality experienced by a cohort of 812 workers employed at a nickel refinery was investigated. Study subjects were all male workforce employees first employed in the period 1953–92 who had at least five years’ employment with the company. Observed numbers of cause specific deaths were compared with expectations based on national mortality rates; SMRs were also calculated by period from commencing employment, year of commencing employment, and type of work.Results:Overall, standardised mortality ratios (SMRs) were close to 100 for all causes (Obs 191, SMR 96, 95% CI 83 to 111), all neoplasms (Obs 63, SMR 104, 95% CI 80 to 133), non-malignant diseases of the respiratory system (Obs 18, SMR 97, 95% CI 57 to 153), and diseases of the circulatory system (Obs 85, SMR 94, 95% CI 75 to 116). There were no significantly increased SMRs for any site of cancer. There was a non-significant excess for lung cancer (Obs 28, Exp 20.17, SMR 139, 95% CI 92 to 201), and in subgroup analyses a significantly increased SMR of 231 (Obs 9) was found for those 142 workers with at least five years’ employment in the feed handling and nickel extraction departments. In the total cohort there was a single death from nasal cancer (Exp 0.10).Conclusions:The non-significant excess of lung cancer deaths may well be a chance finding, but in light of previous studies some role for nickel exposures cannot be excluded.
Patient satisfaction with occupational health physicians, development of a questionnaire
Authors: Verbeek J H , de Boer A G , van der Weide W E , Piirainen H , Anema J R , van Amstel R J , Hartog F 
Published: January 2005

Aims:To develop a questionnaire that measures specific aspects of patient satisfaction with occupational health physicians.Methods:General patient satisfaction questionnaires, a literature survey, and interviews with patients were used. An initial questionnaire was distributed among sick listed patients (n = 432) of occupational physicians (n = 90) from different occupational health services. To reduce items and to develop scales exploratory factor analysis and reliability analysis was used. A linear regression model was used to predict satisfaction ratings from the scales of the questionnaire.Results:Questions about independence of the occupational physician were difficult to ask unambiguously. The factor analysis revealed five relevant factors which were named “being taken seriously as a patient”, “attitude towards occupational health services”, “trust and confidentiality”, “expectations”, and “comfort and access”. All scales could be reduced to a maximum of five items without reducing the scale reliability too much. In the regression analysis, 71% of the variance of satisfaction ratings was explained by the first four scales and most by the first scale. “Comfort and access” did not contribute significantly to the model.Conclusions:A short questionnaire was developed to measure different aspects of patient satisfaction specific for occupational health. Whether the questionnaire can effectively lead to quality improvement in occupational health services should be investigated.
Epimorphin expression in interstitial pneumonia
Authors: Terasaki Yasuhiro , Fukuda Yuh , Suga Moritaka , Ikeguchi Naoki , Takeya Motohiro 
Published: January 2005

AbstractEpimorphin modulates epithelial morphogenesis in embryonic mouse organs. We previously suggested that epimorphin contributes to repair of bleomycin-induced pulmonary fibrosis in mice via epithelium-mesenchyme interactions. To clarify the role of epimorphin in human lungs, we evaluated epimorphin expression and localization in normal lungs, lungs with nonspecific interstitial pneumonia (NSIP), and lungs with usual interstitial pneumonia (UIP); we also studied the effect of recombinant epimorphin on cultured human alveolar epithelial cells in vitro. Northern and Western blotting analyses revealed that epimorphin expression in NSIP samples were significantly higher than those in control lungs and lungs with UIP. Immunohistochemistry showed strong epimorphin expression in mesenchymal cells of early fibrotic lesions and localization of epimorphin protein on mesenchymal cells and extracellular matrix of early fibrotic lesions in the nonspecific interstitial pneumonia group. Double-labeled fluorescent images revealed expression of matrix metalloproteinase 2 in re-epithelialized cells overlying epimorphin-positive early fibrotic lesions. Immunohistochemistry and metalloproteinase activity assay demonstrated augmented expression of metalloproteinase induced by recombinant epimorphin in human alveolar epithelial cells. These findings suggest that epimorphin contributes to repair of pulmonary fibrosis in nonspecific interstitial pneumonia, perhaps partly by inducing expression of matrix metalloproteinase 2, which is an important proteolytic factor in lung remodeling.
Predominant constitutive CFTR conductance in small airways
Authors: Wang Xiaofei , Lytle Christian , Quinton Paul M 
Published: January 2005

Abstract
Background
The pathological hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter.

Methods
We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole.

Results
In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath) of the bronchiole was small (mean ± sem: -3 ± 1 mV; n = 25), but when gluconate replaced luminal Cl-, the bionic Cl- diffusion potentials (-58 ± 3 mV; n = 25) were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl- permeability was at least 5 times greater than Na+ permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 μM)+IBMX (100 μM), ATP (100 μM), or adenosine (100 μM), but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM), GlyH-101* (5–50 μM), and CFTRInh-172* (5 μM). RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways.

Conclusion
These results indicate that the small airway of the pig is characterized by a constitutively active Cl- conductance that is most likely due to CFTR.
GATA: a graphic alignment tool for comparative sequence analysis
Authors: Nix David A , Eisen Michael B 
Published: January 2005

Abstract
Background
Several problems exist with current methods used to align DNA sequences for comparative sequence analysis. Most dynamic programming algorithms assume that conserved sequence elements are collinear. This assumption appears valid when comparing orthologous protein coding sequences. Functional constraints on proteins provide strong selective pressure against sequence inversions, and minimize sequence duplications and feature shuffling. For non-coding sequences this collinearity assumption is often invalid. For example, enhancers contain clusters of transcription factor binding sites that change in number, orientation, and spacing during evolution yet the enhancer retains its activity. Dot plot analysis is often used to estimate non-coding sequence relatedness. Yet dot plots do not actually align sequences and thus cannot account well for base insertions or deletions. Moreover, they lack an adequate statistical framework for comparing sequence relatedness and are limited to pairwise comparisons. Lastly, dot plots and dynamic programming text outputs fail to provide an intuitive means for visualizing DNA alignments.

Results
To address some of these issues, we created a stand alone, platform independent, graphic alignment tool for comparative sequence analysis (GATA http://gata.sourceforge.net/). GATA uses the NCBI-BLASTN program and extensive post-processing to identify all small sub-alignments above a low cut-off score. These are graphed as two shaded boxes, one for each sequence, connected by a line using the coordinate system of their parent sequence. Shading and colour are used to indicate score and orientation. A variety of options exist for querying, modifying and retrieving conserved sequence elements. Extensive gene annotation can be added to both sequences using a standardized General Feature Format (GFF) file.

Conclusions
GATA uses the NCBI-BLASTN program in conjunction with post-processing to exhaustively align two DNA sequences. It provides researchers with a fine-grained alignment and visualization tool aptly suited for non-coding, 0–200 kb, pairwise, sequence analysis. It functions independent of sequence feature ordering or orientation, and readily visualizes both large and small sequence inversions, duplications, and segment shuffling. Since the alignment is visual and does not contain gaps, gene annotation can be added to both sequences to create a thoroughly descriptive picture of DNA conservation that is well suited for comparative sequence analysis.
Variants in the vitamin D receptor gene and asthma
Authors: Wjst Matthias 
Published: January 2005

Abstract
Background
Early lifetime exposure to dietary or supplementary vitamin D has been predicted to be a risk factor for later allergy. Twin studies suggest that response to vitamin D exposure might be influenced by genetic factors. As these effects are primarily mediated through the vitamin D receptor (VDR), single base variants in this gene may be risk factors for asthma or allergy.

Results
951 individuals from 224 pedigrees with at least 2 asthmatic children were analyzed for 13 SNPs in the VDR. There was no preferential transmission to children with asthma. In their unaffected sibs, however, one allele in the 5' region was 0.5-fold undertransmitted (p = 0.049), while two other alleles in the 3' terminal region were 2-fold over-transmitted (p = 0.013 and 0.018). An association was also seen with bronchial hyperreactivity against methacholine and with specific immunoglobulin E serum levels.

Conclusion
The transmission disequilibrium in unaffected sibs of otherwise multiple-affected families seem to be a powerful statistical test. A preferential transmission of vitamin D receptor variants to children with asthma could not be confirmed but raises the possibility of a protective effect for unaffected children.
Microarray analysis of gene expression profiles of cardiac myocytes and fibroblasts after mechanical stress, ionising or ultraviolet radiation
Authors: Boerma Marjan , van der Wees Caroline GC , Vrieling Harry , Svensson J Peter , Wondergem Jan , van der Laarse Arnoud , Mullenders Leon HF , van Zeeland Albert A 
Published: January 2005

Abstract
Background
During excessive pressure or volume overload, cardiac cells are subjected to increased mechanical stress (MS). We set out to investigate how the stress response of cardiac cells to MS can be compared to genotoxic stresses induced by DNA damaging agents. We chose for this purpose to use ionising radiation (IR), which during mediastinal radiotherapy can result in cardiac tissue remodelling and diminished heart function, and ultraviolet radiation (UV) that in contrast to IR induces high concentrations of DNA replication- and transcription-blocking lesions.

Results
Cultures enriched for neonatal rat cardiac myocytes (CM) or fibroblasts were subjected to any one of the three stressors. Affymetrix microarrays, analysed with Linear Modelling on Probe Level, were used to determine gene expression patterns at 24 hours after (the start of) treatment. The numbers of differentially expressed genes after UV were considerably higher than after IR or MS. Remarkably, after all three stressors the predominant gene expression response in CM-enriched fractions was up-regulation, while in fibroblasts genes were more frequently down-regulated. To investigate the activation or repression of specific cellular pathways, genes present on the array were assigned to 25 groups, based on their biological function. As an example, in the group of cholesterol biosynthesis a significant proportion of genes was up-regulated in CM-enriched fractions after MS, but down-regulated after IR or UV.

Conclusion
Gene expression responses after the types of cellular stress investigated (MS, IR or UV) have a high stressor and cell type specificity.
Doxycycline-regulated gene expression in the opportunistic fungal pathogen Aspergillus fumigatus
Authors: Vogt Keith , Bhabhra Ruchi , Rhodes Judith C , Askew David S 
Published: January 2005

Abstract
Background
Although Aspergillus fumigatus is an important human fungal pathogen there are few expression systems available to study the contribution of specific genes to the growth and virulence of this opportunistic mould. Regulatable promoter systems based upon prokaryotic regulatory elements in the E. coli tetracycline-resistance operon have been successfully used to manipulate gene expression in several organisms, including mice, flies, plants, and yeast. However, the system has not yet been adapted for Aspergillus spp.

Results
Here we describe the construction of plasmid vectors that can be used to regulate gene expression in A. fumigatus using a simple co-transfection approach. Vectors were generated in which the tetracycline transactivator (tTA) or the reverse tetracycline transactivator (rtTA2s-M2) are controlled by the A. nidulans gpdA promoter. Dominant selectable cassettes were introduced into each plasmid, allowing for selection following gene transfer into A. fumigatus by incorporating phleomycin or hygromycin into the medium. To model an essential gene under tetracycline regulation, the E. coli hygromycin resistance gene, hph, was placed under the control of seven copies of the TetR binding site (tetO7) in a plasmid vector and co-transfected into A. fumigatus protoplasts together with one of the two transactivator plasmids. Since the hph gene is essential to A. fumigatus in the presence of hygromycin, resistance to hygromycin was used as a marker of hph reporter gene expression. Transformants were identified in which the expression of tTA conferred hygromycin resistance by activating expression of the tetO7-hph reporter gene, and the addition of doxycycline to the medium suppressed hygromycin resistance in a dose-dependent manner. Similarly, transformants were identified in which expression of rtTA2s-M2 conferred hygromycin resistance only in the presence of doxycycline. The levels of doxycycline required to regulate expression of the tetO7-hph reporter gene were within non-toxic ranges for this organism, and low-iron medium was shown to reduce the amount of doxycycline required to accomplish regulation.

Conclusions
The vectors described in this report provide a new set of options to experimentally manipulate the level of specific gene products in A. fumigatus
General practitioners' reasoning when considering the diagnosis heart failure: a think-aloud study
Authors: Skånér Ylva , Backlund Lars , Montgomery Henry , Bring Johan , Strender Lars-Erik 
Published: January 2005

Abstract
Background
Diagnosing chronic heart failure is difficult, especially in mild cases or early in the course of the disease, and guidelines are not easily implemented in everyday practice. The aim of this study was to investigate general practitioners' diagnostic reasoning about patients with suspected chronic heart failure in comparison with recommendations in European guidelines.

Methods
Think-aloud technique was used. Fifteen general practitioners reasoned about six case vignettes, representing authentic patients with suspected chronic heart failure. Information about each case was added successively in five steps. The general practitioners said their thoughts aloud while reasoning about the probability of the patient having chronic heart failure, and tried to decide about the diagnosis. Arguments for and against chronic heart failure were analysed and compared to recommendations in guidelines.

Results
Information about ejection fraction was the most frequent diagnostic argument, followed by information about cardiac enlargement or pulmonary congestion on chest X-ray. However, in a third of the judgement situations, no information about echocardiography was utilized in the general practitioners' diagnostic reasoning. Only three of the 15 doctors used information about a normal electrocardiography as an argument against chronic heart failure. Information about other cardio-vascular diseases was frequently used as a diagnostic argument.

Conclusions
The clinical information was not utilized to the extent recommended in guidelines. Some implications of our study are that 1) general practitioners need more information about how to utilize echocardiography when diagnosing chronic heart failure, 2) guidelines ought to give more importance to information about other cardio-vascular diseases in the diagnostic reasoning, and 3) guidelines ought to treat the topic of diastolic heart failure in a clearer way.
Lymphocyte subsets in hemophilic patients with hepatitis C virus infection with or without human immunodeficiency virus co-infection: a nested cross-sectional study
Authors: Zhang Mingdong , O'Brien Thomas R , Kopp William C , Goedert James J ,   for the Multicenter Hemophilia Cohort Study
Published: January 2005

Abstract
Background
With chronic infection, hepatitis C virus (HCV) RNA can be detected in B cells and associated with B-cell disorders, but these are not well defined.

Methods
The relationship between HCV infection and lymphocyte subpopulations was evaluated rigorously in 120 asymptomatic hemophilic patients, randomly selected from a prospective cohort study. CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells were quantified by flow cytometry using cryopreserved peripheral blood mononuclear cells of 24 hemophilic patients in each of five age-matched groups [uninfected; chronic HCV with or without human immunodeficiency virus (HIV); and cleared HCV with or without HIV].

Results
As expected, patients with HIV had significantly reduced CD4+ and increased CD8+ T cells. Irrespective of HIV, patients with chronic HCV infection had approximately 25% fewer CD19+ B cells than those without chronic HCV infection.

Conclusions
These data support the hypothesis that asymptomatic patients with chronic HCV infection have an altered B-lymphocyte population.
Irradiation specifically sensitises solid tumour cell lines to TRAIL mediated apoptosis
Authors: Marini Patrizia , Schmid Angelika , Jendrossek Verena , Faltin Heidrun , Daniel Peter T , Budach Wilfried , Belka Claus 
Published: January 2005

Abstract
Background
TRAIL (tumor necrosis factor related apoptosis inducing ligand) is an apoptosis inducing ligand with high specificity for malignant cell systems. Combined treatment modalities using TRAIL and cytotoxic drugs revealed highly additive effects in different tumour cell lines. Little is known about the efficacy and underlying mechanistic effects of a combined therapy using TRAIL and ionising radiation in solid tumour cell systems. Additionally, little is known about the effect of TRAIL combined with radiation on normal tissues.

Methods
Tumour cell systems derived from breast- (MDA MB231), lung- (NCI H460) colorectal- (Colo 205, HCT-15) and head and neck cancer (FaDu, SCC-4) were treated with a combination of TRAIL and irradiation using two different time schedules. Normal tissue cultures from breast, prostate, renal and bronchial epithelia, small muscle cells, endothelial cells, hepatocytes and fibroblasts were tested accordingly. Apoptosis was determined by fluorescence microscopy and western blot determination of PARP processing. Upregulation of death receptors was quantified by flow cytometry.

Results
The combined treatment of TRAIL with irradiation strongly increased apoptosis induction in all treated tumour cell lines compared to treatment with TRAIL or irradiation alone. The synergistic effect was most prominent after sequential application of TRAIL after irradiation. Upregulation of TRAIL receptor DR5 after irradiation was observed in four of six tumour cell lines but did not correlate to tumour cell sensitisation to TRAIL. TRAIL did not show toxicity in normal tissue cell systems. In addition, pre-irradiation did not sensitise all nine tested human normal tissue cell cultures to TRAIL.

Conclusions
Based on the in vitro data, TRAIL represents a very promising candidate for combination with radiotherapy. Sequential application of ionising radiation followed by TRAIL is associated with an synergistic induction of cell death in a large panel of solid tumour cell lines. However, TRAIL receptor upregulation may not be the sole mechanism by which sensitation to TRAIL after irradiation is induced.
Randomized clinical trial of surgery versus conservative therapy for carpal tunnel syndrome [ISRCTN84286481]
Authors: Martin Brook I , Levenson Linda M , Hollingworth William , Kliot Michel , Heagerty Patrick J , Turner Judith A , Jarvik Jeffrey G 
Published: January 2005

Abstract
Background
Conservative treatment remains the standard of care for treating mild to moderate carpal tunnel syndrome despite a small number of well-controlled studies and limited objective evidence to support current treatment options. There is an increasing interest in the usefulness of wrist magnetic resonance imaging could play in predicting who will benefit for various treatments.

Method and design
Two hundred patients with mild to moderate symptoms will be recruited over 3 1/2 years from neurological surgery, primary care, electrodiagnostic clinics. We will exclude patients with clinical or electrodiagnostic evidence of denervation or thenar muscle atrophy.
We will randomly assign patients to either a well-defined conservative care protocol or surgery. The conservative care treatment will include visits with a hand therapist, exercises, a self-care booklet, work modification/ activity restriction, B6 therapy, ultrasound and possible steroid injections. The surgical care would be left up to the surgeon (endoscopic vs. open) with usual and customary follow-up. All patients will receive a wrist MRI at baseline.
Patients will be contacted at 3, 6, 9 and 12 months after randomization to complete the Carpal Tunnel Syndrome Assessment Questionnaire (CTSAQ). In addition, we will compare disability (activity and work days lost) and general well being as measured by the SF-36 version II. We will control for demographics and use psychological measures (SCL-90 somatization and depression scales) as well as EDS and MRI predictors of outcomes.

Discussion
We have designed a randomized controlled trial which will assess the effectiveness of surgery for patients with mild to moderate carpal tunnel syndrome. An important secondary goal is to study the ability of MRI to predict patient outcomes.