bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr virus–specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy
Authors: Rossig Claudia , Bollard Catherine M. , Nuchtern Jed G. , Rooney Cliona M. , Brenner Malcolm K. 
Published: October 2002

AbstractPrimary T cells expressing chimeric receptors specific for tumor or viral antigens have considerable therapeutic potential. Unfortunately, their clinical value is limited by their rapid loss of function and failure to expand in vivo, presumably due to the lack of costimulator molecules on tumor cells and the inherent limitations of signaling exclusively through the chimeric receptor. Epstein-Barr virus (EBV) infection of B lymphocytes is near universal in humans and stimulates high levels of EBV-specific helper and cytotoxic T cells, which persist indefinitely. Our clinical studies have shown that EBV-specific T cells generated in vitro will expand, persist, and function for more than 6 years in vivo. We now report that EBV-specific (but not primary) T cells transduced with tumor-specific chimeric receptor genes can be expanded and maintained long-term in the presence of EBV-infected B cells. They recognize EBV-infected targets through their conventional T-cell receptor and tumor targets through their chimeric receptors. They efficiently lyse both. EBV-specific T cells expressing chimeric antitumor receptors may represent a new source of effector cells that would persist and function long-term after their transfer to cancer patients.
Excess incidence of asthma among Finnish cleaners employed in different industries
Authors: Karjalainen A. , Martikainen R. , Karjalainen J. , Klaukka T. , Kurppa K. 
Published: October 2002

The incidence and risk of asthma among female cleaners employed in different industries was explored. An increased risk of asthma has been associated with the cleaning profession, in some but not all studies.All Finnish females employed as cleaners and all those employed in administrative work were followed for asthma incidence through a record linkage in 1986–1998. An individual was defined as an “incident case of asthma” if they received rights for special reimbursement of asthma medication from the national health insurance or were recognized as having occupational asthma. Age-adjusted relative risks (RR) were estimated for cleaners in comparison with those employed in administrative work.There were 2,414 and 5,235 cases of asthma among the cleaners and administrative workers, respectively. The RR was 1.50 (95% confidence interval (CI) 1.43–1.57) in cleaners. The risk was increased in cleaners working in nearly all major sectors of economic activity, but cleaners employed by companies concerned with the manufacture of basic metals (RR 2.47; 95% CI 1.68–3.64) and food products (RR 2.19; 95% CI 1.69–2.85) had the highest risk. Only 25 of the “cases of asthma” among cleaners had been recognized as being occupational asthma.It could be concluded that cleaners have an increased risk of persistent adult-onset asthma. Factors inherent to the environment where cleaning is performed or differences in the cleaning agents used may explain the observed differences between industries.
Physical exercise, sports, and lung function in smokingversusnonsmoking adolescents
Authors: Holmen T.L. , Barrett-Connor E. , Clausen J. , Holmen J. , Bjermer L. 
Published: October 2002

Associations between adolescent smoking habits and exercise, particularly participation in sports and lung function were studied.All students aged 13–19 yrs in Nord-Trøndelag County, Norway, 1995–1997, were invited to join a cross-sectional study. Information on smoking habits and exercise was obtained by self-administered questionnaire. Spirometry was performed in accordance with American Thoracic Society standards.Of the 6,811 students (aged 13–18 yrs, without asthma), 2,993 (44%) reported never-smoking, and 1,342 (20%) reported current smoking (10% daily). Frequency of physical exercise was inversely associated with smoking, but participants in individual sports with lesser endurance, especially body-building and fighting sports, were more likely to be daily smokers than nonparticipants. Both daily (53%) and occasional smokers (43%) were more likely to have quit sports than never-smokers (26%). Never-smokers showed a positive dose-response between physical exercise and lung function (forced vital capacity and forced expiratory volume in one second, adjusted for age and height). No similar significant association was observed in daily smokers.These data suggest that smoking habits in different sports should be considered when promoting physical activity as smoking prevention, and sports organizations should include smoking prevention programmes. Adolescents with better lung function may self-select into sports; this possibility needs to be studied in a longitudinal design.
Dissociation between airway responsiveness to methacholine and responsiveness to antigen
Authors: Kamachi A. , Nasuhara Y. , Nishimura M. , Takahashi T. , Homma Y. , Ohtsuka Y. , Munakata M. 
Published: October 2002

Repeated aerosolized antigen challenges to brown Norway (BN) rats generate nonspecific airway hyperresponsiveness (AHR). On the other hand, some studies have demonstrated that repeated antigen challenge could attenuate antigen-specific AHR in BN rats. The authors questioned whether such dissociation in airway responses actually occurs when assessed in a single study in the same animals.The authors simultaneously measured AHR to methacholine and antigen-specific AHR in rats that were repeatedly exposed to aerosolized ovalbumin (OA) for 1 or 3 months after sensitization. Four days after the last challenge, airway responses to methacholine and OA, morphometry of the airways, the cell profile in bronchoalveolar lavage fluid, and cytokine messenger ribonucleic acid (mRNA) expression in the lungs were evaluated.The two types of AHR were modulated in opposite directions by repeated antigen challenges. The AHR to methacholine was significantly increased in the rats receiving antigen challenges compared with the control rats receiving saline challenges after sensitization; whereas, the antigen-specific AHR was significantly decreased. The number of alveolar macrophages in lavaged fluid and the expression of transforming growth factor-β1mRNA in lung tissue was significantly different between the antigen-challenged rats and the control rats.In conclusion, dissociation between nonspecific airway hyperresponsiveness and antigen-specific airway hyperresponsiveness in brown Norway rats after repeated antigen challenges was demonstrated. Sustained airway inflammation with macrophages and/or upregulation of transforming growth factor-β1messenger ribonucleic acid in the lung tissue may be responsible for this dissociation.
Ehlers-Danlos syndrome type IV with few extrathoracic findings: a newly recognized point mutation in the COL3A1 gene
Authors: Watanabe A. , Kawabata Y. , Okada O. , Tanabe N. , Kimura H. , Hatamochi A. , Shinkai H. , Sakai N. , Shimada T. , Hiroshima K. , Kuriyama T. 
Published: October 2002

Ehlers-Danlos syndrome type IV (EDS IV) is caused by mutation within the COL3A1 gene, resulting in the disorder of type III procollagen. The diagnosis is confirmed by demonstrating the synthesis of abnormal type III procollagen molecules from cultured dermal fibroblasts or by identifying the mutation in the COL3A1 gene.The authors report a case of EDS IV caused by a novel point mutation in the COL3A1 gene in a 16-yr-old female. Recurrent haemoptysis and cavitary formation of the lung were evidence of pulmonary involvement. However, extrathoracic manifestations of EDS IV were mostly absent.To the best of the authors' knowledge, all previously reported Ehlers-Danlos syndrome IV patients with respiratory disease had the characteristic findings or histories of Ehlers-Danlos syndrome IV. In the present case, connective tissue friability was suspected due to tissue laceration observed in the biopsied lung specimen, and the diagnosis was made beginning from this pivotal finding.
The combination of single-dose montelukast and loratadine on exercise-induced bronchospasm in children
Authors: Peroni D.G. , Piacentini G.L. , Pietrobelli A. , Loiacono A. , De Gasperi W. , Sabbion A. , Micciolo R. , Boner A.L. 
Published: October 2002

The aim of the study was to evaluate the protective effect of single-dose, combination treatment comprising montelukast (5 mg) and loratadine (10 mg), on exercise-induced bronchoconstriction in asthmatic children. The combination was compared to placebo, loratadine and montelukast alone.Nineteen children were enrolled in a double-blind randomised, single-dose, crossover study. For each treatment patients undertook two treadmill exercise tests, 2 and 12 h respectively after single-dose administration.No significant differences were seen in the maximum fall in forced expiratory volume in one second (FEV1) 2 h after treatment and placebo. Whereas significant differences in maximum fall in FEV1were observed between treatment groups 12 h after administration. Loratadine alone did not show any significant protection or any additional effect in comparison with montelukast alone. Single doses of montelukast and montelukast plus loratadine were significantly more effective than loratadine at 12 h.The present study, performed using single-dose treatments, demonstrated that maximal protective effect by montelukast was obtained 12 h after dosing and that montelukast plus loratadine did not result in significant additive bronchoprotective effects on exercise-induced bronchoconstriction.
Bronchial challenge with flour: early response is dependent on the dose of activated allergen inhaled
Authors: Choudat D. , Fabriès J.F. , Martin J.C. , Villette C. 
Published: October 2002

Specific bronchial challenges provide information about the relationship between inhaled dose of allergen and change in lung function, but the intermediate pathways remain largely obscure. The aim of this study was to investigate the relationships between the early asthmatic response and 1) the inhaled dose of wheat flour, 2) the concentration of wheat flour, 3) the duration of the exposure, and 4) the deactivation of inhaled allergens and mediators.Thirty-one patients with occupational asthma to wheat flour were studied. Particle aerosols were generated by a computer-controlled aerosoliser and the results were expressed as the provocative dose causing a 20% fall in forced expiratory volume in one second (FEV1) (PD20). The cumulative dose (from the beginning of the challenge), the last inhaled dose, and an estimated dose (taking into account exponential deactivation), were calculated.Twenty patients had high reactivity to flour (reaching a PD20value). Eleven patients had intermediate reactivity (no measurable PD20but significantly greater fall in FEV1compared with lactose challenge). A better correlation between change in FEV1and dose was obtained for the estimated dose than for the cumulative or last inhaled dose.The bronchial response to wheat flour can be measured by the individual specific hyperreactivity and is expressed by provocative dose of flour. However, deactivation of the allergen and mediators has to be taken into account. This problem can be addressed by using a mathematical model.
Domestic exposure to formaldehyde significantly increases the risk of asthma in young children
Authors: Rumchev K.B. , Spickett J.T. , Bulsara M.K. , Phillips M.R. , Stick S.M. 
Published: October 2002

Concern has arisen in recent years about indoor air pollution as a risk factor for asthma.Formaldehyde exposure was examined in relation to asthma among young children (between 6 months and 3 yrs old) in a population-based control study carried out in Perth, Western Australia, between 1997–1999. An association between exposure to formaldehyde and asthma in young children has been suggested. Cases (n=88), whose parents were recruited at Princess Margaret Hospital Accident and Emergency Dept (Perth, Western Australia), were children discharged with asthma as the primary diagnosis. Controls (n=104), who were children in the same age group without asthma diagnosed by a doctor, were identified from birth records through the Health Dept of Western Australia (Perth, Western Australia). Health outcomes for the children were studied using a respiratory questionnaire and skin-prick tests. Formaldehyde, average temperature and relative humidity were measured on two occasions, winter (July–September 1998) and summer (December 1998–March 1999) in the child's bedroom and in the living room.The study found seasonal differences in formaldehyde levels in the children's bedrooms and living rooms with significantly greater formaldehyde exposure during the summer period for case and control subjects. The generalised estimating equation model showed that children exposed to formaldehyde levels of ≥60 µg·m−3are at increased risk of having asthma.The results suggest that domestic exposure to formaldehyde increases the risk of childhood asthma.
Resistance to Fas-mediated apoptosis in human lung fibroblast
Authors: Tanaka T. , Yoshimi M. , Maeyama T. , Hagimoto N. , Kuwano K. , Hara N. 
Published: October 2002

The current authors have demonstrated previously that epithelial cell apoptosis, induced by the Fas-Fas ligand pathway, might be involved in fibrosing lung diseases. Whereas lung epithelial cells are sensitive to the Fas-mediated apoptosis, lung fibroblasts may be resistant to Fas-mediated apoptosis and replace damaged epithelial cells.The WI-38 lung fibroblast cell line and primary lung fibroblasts were used to examine the resistant to Fas-mediated apoptosis and the association of anti-apoptotic proteins with this resistance.The administration of agonistic anti-Fas antibody (CH-11) or cycloheximide alone did not induce apoptosis, whereas the co-administration of CH-11 with cycloheximide induced apoptosis in WI-38 cells, in which caspase‐8 and ‐3, but not ‐9, were activated, and X chromosome-linked inhibitor of apoptosis (ILP) and FLICE-like inhibitor protein (FLIPL), but not bcl‐xLand bcl‐2, were remarkably down regulated. Primary lung fibroblasts were also resistant to Fas-mediated apoptosis, and ILP and FLIP appeared to be involved in this resistance. Furthermore, the results of immunohistochemistry demonstrated that fibroblasts expressed ILP and FLIPLproteins in lung tissues from patients with idiopathic pulmonary fibrosis.These results suggest that anti-apoptotic proteins such as X chromosome-linked inhibitor of apoptosis and FLICE-like inhibitor protein may play an important role in preventing Fas-mediated apoptosis in lung fibroblasts, and participate in the development of pulmonary fibrosis.
Hospital-acquired pneumonia: microbiological data and potential adequacy of antimicrobial regimens
Authors: Leroy O. , Giradie P. , Yazdanpanah Y. , Georges H. , Alfandari S. , Sanders V. , Devos P. , Beaucaire G. 
Published: October 2002

Adequate antimicrobial therapy is a main approach employed to decrease the mortality associated with hospital-acquired pneumonia (HAP). All methods that optimise empirical treatment without increasing antibiotic selective pressure are relevant. Categorisation of patients according to HAP time of onset, severity and risk factors (American Thoracic Society (ATS) classification) or duration of mechanical ventilation and prior antibiotics (Trouillet's classification) are two such methods. The aim of this study was to catagorise patients with HAP according to these classifications and to determine the frequency of resistant pathogens and the most adequate antimicrobial regimens in each group.A total 124 patients with bacteriologically proven HAP were studied. The ATS classification categorised patients by increasing frequency of resistant pathogens from 0–30.3%. The ATS empirical antibiotic recommendations appeared valid but proposed combinations including vancomycin for 72.5% of patients. Trouillet's classification categorised patients into four groups with a frequency of resistant pathogens from 4.9–35.6%. Vanomycin was proposed for 48.5% of patients.The American Thoracic Society classification appears to be more specific than Trouillet's for predicting the absence of resistant causative pathogens in hospital-acquired pneumonia but could lead to a greater use of vanomycin. Stratification combining the two classifications is an interesting alternative.
Effect of surfactant on pharyngeal mechanics in sleeping humans: implications for sleep apnoea
Authors: Morrell M.J. , Arabi Y. , Zahn B.R. , Meyer K.C. , Skatrud J.B. , Safwan Badr M. 
Published: October 2002

Instillation of surfactant into the pharyngeal lumen reduces the pressure required to reopen an occluded airway, and decreases the apnoea/hypopnoea index (AHI). The authors hypothesised that surfactant also reduces the sleep-related increase in pharyngeal resistance. To test this hypothesis two single blind, crossover, placebo-controlled studies were performed.In protocol A seven male, asymptomatic snoring subjects were studied during sleep. Inspiratory pharyngeal resistance was calculated from plots of airflowversussupraglottic pressure (seven breaths) before and after surfactant or saline instillation. In protocol B, in a different group of seven male subjects with sleep apnoea (AHI 15.2 (12) events·h−1) the effect of surfactant or saline on sleep disordered breathing was measured, for 1 h immediately before and after surfactant or saline instillation.Surfactant decreased pharyngeal resistance calculated at peak pressure (group mean (sd): preversuspost 83.7 (76.4)versus49.4 (71.1) cmH2O·L−1·s−1) and significantly reduced the respiratory disturbance index (RDI preversuspost 79.7 (58.7)versus59.6 (56.9) events·h−1). Saline did not decrease resistance (preversuspost 58.6 (31.1)versus72.5 (73.4) cmH2O·L−1·s−1) or RDI (preversuspost 75.3 (42.4)versus79.9 (46.1) events·h−1).Surfactant reduced the collapsibility of the pharynx and led to a modest reduction in respiratory disturbance index. The authors speculate that surfactant may delay occlusion by reducing the liquid “bridging” within the folded pharyngeal lining.
Obliterative bronchiolitis: varying presentations and clinicopathological correlation
Authors: Markopoulou K.D. , Cool C.D. , Elliot T.L. , Lynch D.A. , Newell J.D. , Hale V.A. , Brown K.K. , Schwarz M.I. , Tuder R.M. 
Published: October 2002

In obliterative bronchiolitis, inflammation and fibrosis lead to narrowing or occlusion of bronchiolar lumina.To determine how bronchiolar structural alterations relate to lung physiology, 19 patients with a pathological diagnosis of obliterative bronchiolitis were studied. The bronchiolar inflammatory and fibrotic features were correlated to the clinical presentation, and lung function tests.Eleven patients demonstrated airflow limitation, one had a restrictive pattern and one had a mixed pattern, two had isolated gas trapping, but four had normal spirometry. Mild-to-moderate bronchiolar inflammation was invariably present. It involved 60% of bronchioles subepithelially and 54% in the adventitia. Subepithelial fibrosis was observed in 15 patients and adventitial in 12. Adventitial bronchiolar inflammation correlated with forced expiratory volume in one second and forced vital capacity and inversely correlated with residual volume. Subepithelial fibrosis inversely correlated with subepithelial and adventitial inflammation. High-resolution computed tomography in 10 patients revealed inspiratory (five out of 10) and expiratory air trapping (five out of five), ground glass opacities (seven out of 10), bronchial wall thickening (five out of 10), bronchiectasis (two out of 10) and centrilobular nodules (two out of 10).The present study suggests that inflammation and fibrosis occurs in bronchioles at different time points in the disease process, or that there is no transition between these types of pathology in the same patient. No correlation was observed between the degree of bronchiolar fibrosis and the degree of airflow limitation.
The Liverpool Lung Project: a molecular epidemiological study of early lung cancer detection
Authors: Field J.K. , Youngson J.H. 
Published: October 2002

Lung cancer is the major cause of death from neoplastic disease in the world, and even with politically-motivated smoking cessation campaigns throughout Europe, the disease remains the major cause of death. The development of molecular epidemiological population-based research into early lung cancer detection, such as the Liverpool Lung Project (LLP), may provide a way forward. This is the first major molecular epidemiological study of detection of early lung cancer.The use of molecular epidemiological risk assessments prior to clinical diagnosis and markers of preclinical carcinogenesis in patients with a high risk of developing lung cancer will reduce the incidence of clinically-detectable lung cancer, given the appropriate intervention strategies.The aims are as follows: 1) to prepare a molecular genetic and epidemiological risk assessment model based on environmental exposures and genetic predisposition; 2) to develop an archive of specimens relating to at-risk individuals and those with lung cancer; 3) to redefine lung cancer based on molecular pathology using the fields of expression profiling, genetic instability and molecular cytogenetics; 4) to identify and assess novel markers of precarcinogenesis in high-risk populations; and 5) to facilitate the development of new treatment strategies (e.g.chemoprevention programmes and targeted drug therapies).The LLP has two components: 1) a case-controlled study of newly-diagnosed cases of lung cancer that will provide a baseline, risk assessment; and 2) a prospective cohort study to be carried out over a 10-yr period that will identify markers of preclinical carcinogenesis. In-depth interviews are carried out using structured and semi-structured questionnaires. Sputum, blood and tumour specimens are collected and will be assessed for specific molecular markers (e.g.genetic instability, mutation and expression profiling, and methylation status).Conclusions from The Liverpool Lung Project will be based around molecular-epidemiological and genotyping risk assessment models, as well as redefining the disease, and ultimately contributing to the development of new early lung cancer detection and treatment strategies.
Side-effects of antituberculosis drug treatment in patients with chronic renal failure
Authors: Quantrill S.J. , Woodhead M.A. , Bell C.E. , Hardy C.C. , Hutchison A.J. , Gokal R. 
Published: October 2002

Patients with chronic renal failure (CRF) have a high incidence of tuberculosis (TB). Those from the Indian subcontinent are at particular risk. The frequency of side-effects associated with antituberculous treatment in a group of patients with CRF was studied.All cases of TB in patients with CRF occurring over a 13‐yr period at the Manchester Royal Infirmary, from 1986–1999, were identified by diagnostic coding, microbiology records and a TB database. The case notes were then reviewed.Twenty-four cases were identified, eight predialysis and 16 requiring regular dialysis. TB occurring in the dialysis group was extrapulmonary in every case. Nineteen of 24 (79%) patients were of Indian subcontinent origin and 14 of 16 (87%) dialysis patients were non-Caucasian. Adverse effects of treatment occurred in two of eight (25%) in the predialysis group and nine of 16 (56%) of the dialysis group. These were most commonly neuropsychiatric (6), hepatic (4) and gastrointestinal (4). Neuropsychiatric symptoms occurred exclusively in dialysis patients.In conclusion, a high incidence of side-effects from antituberculous medication, especially neuropsychiatric, hepatic and gastrointestinal, was identified in patients with chronic renal failure. Careful monitoring for side-effects is essential in this group, and consideration should be given to administering antituberculous chemoprophylaxis to all high-risk groups.