Measuring protein structural changes on a proteome-wide scale using limited proteolysis-coupled mass spectrometry.

Protein structural changes induced by external perturbations or internal cues can profoundly influence protein activity and thus modulate cellular physiology. A number of biophysical approaches are available to probe protein structural changes, but these are not applicable to a whole proteome in a biological extract. Limited proteolysis-coupled mass spectrometry (LiP-MS) is a recently developed proteomics approach that enables the identification of protein structural changes directly in their complex biological context on a proteome-wide scale.

Cell-wide analysis of protein thermal unfolding reveals determinants of thermostability.

Temperature-induced cell death is thought to be due to protein denaturation, but the determinants of thermal sensitivity of proteomes remain largely uncharacterized. We developed a structural proteomic strategy to measure protein thermostability on a proteome-wide scale and with domain-level resolution. We applied it to , , , and human cells, yielding thermostability data for more than 8000 proteins.

The effect of learning curve on the surgical outcome of viscocanalostomy.

Purpose: To evaluate the influence of learning curve on the surgical outcome of viscocanalostomy.

Methods: Retrospective, interventional study. Chart review of the first consecutive open-angle glaucoma cases that received viscocanalostomy in 1 institution between July 1996 and June 2000.

Secondhand smoke and health-related quality of life in never smokers: results from the SAPALDIA cohort study 2.

Background: Although secondhand smoke (SHS) has been linked with various respiratory conditions and symptoms, its association with health-related quality of life (HRQOL) is unknown.

Methods: A cross-sectional study was performed of 2500 never smokers in Switzerland who participated in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults and completed a 36-Item Short Form Health Survey (SF-36) in 2002. Using linear regression models adjusting for confounders, we measured the association between HRQOL and moderate or high SHS exposure (< or =3 h/d or >3 h/d) compared with no SHS exposure.

Reduced exposure to PM10 and attenuated age-related decline in lung function.

Background: Air pollution has been associated with impaired health, including reduced lung function in adults. Moving to cleaner areas has been shown to attenuate adverse effects of air pollution on lung function in children but not in adults.

Methods: We conducted a prospective study of 9651 adults (18 to 60 years of age) randomly selected from population registries in 1990 and assessed in 1991, with 8047 participants reassessed in 2002.

Effects of passive smoking on heart rate variability, heart rate and blood pressure: an observational study.

Background: Exposure to environmental tobacco smoke (ETS) has been shown to increase the risk for cardiovascular diseases and death, and autonomic dysfunction (specifically, reduced heart rate variability (HRV)) is a predictor of increased cardiac risk. This study tests the hypothesis that ETS exposure reduces HRV in the general population and discusses possible pathways.

Methods: This cross-sectional study was conducted between 2001 and 2003 and is part of the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung Diseases in Adults) study.

[Pneumology. Anti-IgE antibodies in the treatment of asthma].

Omalizumab is a humanized monoclonal antibody that is directed against IgE. It has been shown to improve the control of severe allergic asthma in adults and adolescents. Candidates to the treatment are asthmatic patients with positive prick tests and/or in vitro markers of allergy, altered pulmonary function tests, and persistent daytime or nocturnal symptoms despite appropriate treatment with inhaled corticosteroids and long-acting beta-2-agonists.

[Chronic cough: practical aspects].

A cough is defined as chronic, if it exceeds 8 weeks in length. Post-nasal drip (PND), bronchial asthma and gastro-esophageal reflux (GERD) must be systematically investigated, as these account for 90 percent of chronic cough cases. In addition to medical history and examination which should exclude either a postinfectious cough or coughing related to ACE inhibitor medication, a new evaluation model suggests chest X ray and spirometry as the initial step.

Living near main streets and respiratory symptoms in adults: the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults.

The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA), conducted in 1991 (SAPALDIA 1) in eight areas among 9,651 randomly selected adults aged 18-60 years, reported associations among the prevalence of respiratory symptoms, nitrogen dioxide, and particles with an aerodynamic diameter of less than 10 microg/m3. Later, 8,047 subjects reenrolled in 2002 (SAPALDIA 2). The effects of individually assigned traffic exposures on reported respiratory symptoms were estimated, while controlling for socioeconomic and exposure- and health-related factors.

Respiratory effects of environmental tobacco exposure are enhanced by bronchial hyperreactivity.

Rationale: Exposure to environmental tobacco smoke (ETS) is associated with increased reports of respiratory symptoms and reduced lung function, but the long-term effects of ETS are unclear, notably in healthy individuals with bronchial hyperresponsiveness (BHR).

Objective: To assess the longitudinal effects of ETS exposure on the development of respiratory symptoms and spirometry in subjects with BHR.

Methods: The study population included 1,661 never-smokers from the SAPALDIA (Swiss Study on Air Pollution and Lung Diseases in Adults) cohort, assessed in 1991 (baseline) and 11 yr later, who were symptom-free at baseline.

The absence of dyspnoea, cough and wheezing: a reason for undiagnosed airflow obstruction?

Objectives: The diagnosis of obstructive lung disease (OLD) may be overlooked because of the poor correlation between the intensity of symptoms and the severity of airway obstruction (AO). Undiagnosed airflow obstruction (UDAO) is associated with health impairment and mortality. Questions remain such as the reasons for its occurrence and the underlying diseases.

Heart rate variability in an ageing population and its association with lifestyle and cardiovascular risk factors: results of the SAPALDIA study.

Aims: (i) To report associations between cardiovascular risk factors and heart rate variability (HRV) in a general population and (ii) to provide normal values for various HRV measurements in a healthy European general population sample aged >or=50.

Methods And Results: Twenty-four-hour electrocardiograms were recorded in 1742 randomly selected SAPALDIA (Swiss cohort study on Air Pollution and Lung Diseases in Adults) participants aged >or=50. In multivariate regression analyses, women (n=895) had a 6.

Bronchial hyperresponsiveness and the development of asthma and COPD in asymptomatic individuals: SAPALDIA cohort study.

Background: Bronchial hyperresponsiveness (BHR) is a common feature of asthma. However, BHR is also present in asymptomatic individuals and its clinical and prognostic significance is unclear. We hypothesised that BHR might play a role in the development of chronic obstructive pulmonary disease (COPD) as well as asthma.

[Pneumonology. Ultrasound-guided transbronchial needle aspiration].

After discovering a lung cancer without extrathoracic metastases, the preoperative mediastinal check-up is of great importance to determine the patients operability. The 78% specificity of activity measuring FDG in a PET examination is clearly insufficient to avoid a biopsy of the incriminated lymph nodes. The investigation of a suspected malignant adenopathy justifies a complete examination by mediastinoscopy or-tomy, which are considered gold standards.

Passive smoking exposure among adults and the dynamics of respiratory symptoms in a prospective multicenter cohort study.

Objectives: The aim of this study was to measure the effects of past exposure to environmental tobacco smoke on the day-to-day dynamics of four respiratory-symptom classes in a diary study including adult never-smokers.

Methods: As part of SAPALDIA (Swiss study on air pollution and lung diseases in adults), a prospective multicenter cohort study, 1421 life-time adult nonsmokers were followed for 2 years with the use of daily questionnaires filled out during one to six periods of 4 weeks spread over 2 years (1992-1993). The hazard ratios (HR) of getting or losing respiratory symptoms from one day to another were determined in association with past exposure to environmental tobacco smoke.

Prevalence of renal impairment and its association with cardiovascular risk factors in a general population: results of the Swiss SAPALDIA study.

Background: Impaired renal function is evolving as an independent marker of the risk of cardiovascular morbidity and mortality. Little is known about the prevalence of impaired renal function and its relationship to cardiovascular risk factors in the Swiss general population.

Methods: SAPALDIA comprises a random sample of the Swiss population established in 1991, originally to investigate the health effects of long-term exposure to air pollution.

[Do inhaled corticosteroids reduce mortality in chronic obstructive pulmonary disease?].

In Switzerland, high dose of inhaled corticosteroids are frequently prescribed to COPD patients. Observational studies have suggested a reduction in mortality, although several randomised controlled trials did not show such a beneficial effect. Two important exposure biases are highlighted by a careful review of the methodological aspects of these observational studies: the immortal time bias and the failure to perform a time dependent analysis lead to underestimate the risk of death among exposed patients therefore incorrectly suggesting a survival benefit of regular inhaled steroid use.

Reference values for methacholine reactivity (SAPALDIA study).

Background: The distribution of airway responsiveness in a general population of non-smokers without respiratory symptoms has not been established, limiting its use in clinical and epidemiological practice. We derived reference equations depending on individual characteristics (i.e.

Longitudinal validity of spirometers--a challenge in longitudinal studies.

Question Under Study: Pulmonary function testing (PFT) in longitudinal studies involves the repeated use of spirometers over long time periods. We assess the comparability of PFT results taken under biologic field conditions using thirteen certified devices of various technology and age. Comparability of measurements across devices and over time is relevant both in clinical and epidemiological research.

Follow-up of the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA 2) 1991-2003: methods and characterization of participants.

Objectives: The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) was designed to investigate the health effects from long-term exposure to air pollution.

Methods: The health assessment at recruitment (1991) and at the first reassessment (2001-3) consisted of an interview about respiratory health, occupational and other exposures, spirometry, a methacholine bronchial challenge test, end-expiratory carbon monoxide (CO) measurement and measurement for atopy. A bio bank for DNA and blood markers was established.

Expression of alphasmooth muscle actin in lens epithelia from human donors and cataract patients.

In order to re-evaluate functional implications of alphasmooth muscle actin (alphaSMA) expression in lens epithelial cells (LECs), we assessed its presence in donor lenses without visible opacities (DON), lenses with mature cataract (CAT), and cataractous lenses with posterior subcapsular opacities (PSO) or anterior subcapsular fibrosis (ASF). The levels of alphaSMA and transforming growth factor-beta2 (TGFbeta2) mRNAs were measured by classical and real-time PCR. Expression and structural organisation of alphaSMA protein and beta-catenin were monitored by Western blotting and confocal microscopy.