Telomeres in interstitial lung diseases

Interstitial lung diseases (ILD) encompass a group of conditions involving fibrosis and/or inflammation of the pulmonary parenchyma. Telomeres are repetitive DNA sequences at chromosome ends which protect against genome instability. At each cell division, telomeres shorten, but the telomerase complex partially counteracts progressive loss of telomeres by catalysing the synthesis of telomeric repeats. Once critical telomere shortening is reached, cell cycle arrest or apoptosis are triggered. Telomeres progressively shorten with age. A number of rare genetic mutations have been identified in genes encoding for components of the telomerase complex, including telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC), in familial and, less frequently, in sporadic fibrotic ILDs. Defects in telomerase result in extremely short telomeres. More rapidly progressive disease is observed in fibrotic ILD patients with telomere gene mutations, regardless of underlying diagnosis. Associations with common single nucleotide polymorphisms in telomere related genes have also been demonstrated for various ILDs. Shorter peripheral blood telomere lengths compared to age-matched healthy individuals are found in a proportion of patients with fibrotic ILDs, and in idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (HP) have been linked to worse survival, independently of disease severity. Greater susceptibility to immunosuppressant-induced side effects in patients with short telomeres has been described in patients with IPF and with fibrotic HP. Here, we discuss recent evidence for the involvement of telomere length and genetic variations in the development, progression, and treatment of fibrotic ILDs

Temporal build-up of electromagnetically induced transparency and absorption resonances in degenerate two-level transitions

The temporal evolution of electromagnetically induced transparency (EIT) and absorption (EIA) coherence resonances in pump-probe spectroscopy of degenerate two-level atomic transition is studied for light intensities below saturation. Analytical expression for the transient absorption spectra are given for simple model systems and a model for the calculation of the time dependent response of realistic atomic transitions, where the Zeeman degeneracy is fully accounted for, is presented. EIT and EIA resonances have a similar (opposite sign) time dependent lineshape, however, the EIA evolution is slower and thus narrower lines are observed for long interaction time. Qualitative agreement with the theoretical predictions is obtained for the transient probe absorption on the $^{85}Rb$ $D_{2}$ line in an atomic beam experiment.Comment: 10 pages, 9 figures. Submitted to Phys. Rev.

Fibrotic Hypersensitivity Pneumonitis: Key Issues in Diagnosis and Management

The diagnosis of hypersensitivity pneumonitis (HP) relies on the clinical evaluation of a number of features, including a history of significant exposure to potentially causative antigens, physical examination, chest CT scan appearances, bronchoalveolar lavage lymphocytosis, and, in selected cases, histology. The presence of fibrosis is associated with higher morbidity and mortality. Differentiating fibrotic HP from the idiopathic interstitial pneumonias can be a challenge. Furthermore, even in the context of a clear diagnosis of fibrotic HP, the disease behaviour can parallel that of idiopathic pulmonary fibrosis in a subgroup, with inexorable progression despite treatment. We review the current knowledge on the diagnosis, management, and prognosis of HP with particular focus on the fibrotic phenotype

Enhanced absorption Hanle effect on the Fg=F->Fe=F+1 closed transitions

We analyse the Hanle effect on a closed $F_g\to F_e=F_g+1$ transition. Two configurations are examined, for linear- and circular-polarized laser radiation, with the applied magnetic field collinear to the laser light wavevector. We describe the peculiarities of the Hanle signal for linearly-polarized laser excitation, characterized by narrow bright resonances at low laser intensities. The mechanism behind this effect is identified, and numerical solutions for the optical Bloch equations are presented for different transitions.Comment: to be published in J. Opt. B, special issue on Quantum Coherence and Entanglement (February 2001

Current Switch by Coherent Trapping of Electrons in Quantum Dots

We propose a new transport mechanism through tunnel-coupled quantum dots based on the coherent population trapping effect. Coupling to an excited level by the coherent radiation of two microwaves can lead to an extremely narrow current antiresonance. The effect can be used to determine interdot dephasing rates and is a mechanism for a very sensitive, optically controlled current switch.Comment: to appear in Phys. Rev. Let

Features of Magneto-Optical Resonances in an Elliptically Polarized Traveling Light Wave

The parameters of nonlinear absorption magneto-optical resonances in the Hanle configuration have been studied as functions of the ellipticity of a traveling light wave. It has been found that these parameters (amplitude, width, and amplitude-to-width ratio) depend strongly on the polarization of the light wave. In particular, the resonance amplitude can increase by more than an order of magnitude when the polarization changes from linear to optimal elliptic. It has been shown that this effect is associated with the Doppler frequency shift for atoms in a gas. The theoretical results have been corroborated in experiments in Rb vapor.Comment: 5 page

Prevalence and effects of emphysema in never-smokers with rheumatoid arthritis interstitial lung disease

AIMS: Autoimmune conditions such as rheumatoid arthritis-related interstitial lung disease (RA-ILD) have been linked to the existence of emphysema in never-smokers. We aimed to quantify emphysema prevalence in RA-ILD never-smokers and investigate whether combined pulmonary fibrosis and emphysema (CPFE) results in a worsened prognosis independent of baseline disease extent. METHODS: RA-ILD patients presenting to the Royal Brompton Hospital (n=90) and Asan Medical Center (n=155) had CT's evaluated for a definite usual interstitial pneumonia (UIP) pattern, and visual extents of emphysema and ILD. RESULTS: Emphysema, identified in 31/116 (27%) RA-ILD never-smokers, was associated with obstructive functional indices and conformed to a CPFE phenotype: disproportionate reduction in gas transfer (DLco), relative preservation of lung volumes. Using multivariate logistic regression, adjusted for patient age, gender and ILD extent, emphysema presence independently associated with a CT-UIP pattern in never-smokers (0.009) and smokers (0.02). On multivariate Cox analysis, following adjustment for patient age, gender, DLco, and a CT-UIP pattern, emphysema presence (representing the CPFE phenotype) independently associated with mortality in never-smokers (p=0.04) and smokers (p<0.05). CONCLUSION: 27% of RA-ILD never-smokers demonstrate emphysema on CT. Emphysema presence in never-smokers independently associates with a definite CT-UIP pattern and a worsened outcome following adjustment for baseline disease severity