No abstract

BackgroundSystemic lupus erythematosus (SLE) is a chronic disease of unclear etiology, characterized by an overactive immune system and the production of antibodies that may target normal tissues of many organ systems, including the kidneys. It can arise at any age and occurs mainly in women.ObjectiveOur aim was to evaluate the potential influence of particulate matter (PM) air pollution on clinical aspects of SLE.MethodsWe studied a clinic cohort of SLE patients living on the island of Montreal, followed annually with a structured clinical assessment. We assessed the association between ambient levels of fine PM [median aerodynamic diameter ≤ 2.5 μm (PM2.5)] measured at fixed-site monitoring stations and SLE disease activity measured with the SLE Disease Activity Index, version 2000 (SLEDAI-2K), which includes anti–double-stranded DNA (anti-dsDNA) serum-specific autoantibodies and renal tubule cellular casts in urine, which reflects serious renal inflammation. We used mixed effects regression models that we adjusted for daily ambient temperatures and ozone levels.ResultsWe assessed 237 patients (223 women) who together had 1,083 clinic visits from 2000 through 2007 (mean age at time of first visit, 41.2 years). PM2.5 levels were associated with anti-dsDNA and cellular casts. The crude and adjusted odds ratios (reflecting a 10-μg/m3 increase in PM2.5 averaged over the 48 hr prior to clinical assessment) were 1.26 [95% confidence interval (CI), 0.96–1.65] and 1.34 (95% CI, 1.02–1.77) for anti-dsDNA antibodies and 1.43 (95% CI, 1.05–1.95) and 1.28 (0.92–1.80) for cellular casts. The total SLEDAI-2K scores were not associated with PM2.5 levels.ConclusionsWe provide novel data that suggest that short-term variations in air pollution may influence disease activity in established autoimmune rheumatic disease in humans. Our results add weight to concerns that pollution may be an important trigger of inflammation and autoimmunity.

Retroviral integrase (IN) catalyzes the integration of double-stranded viral DNA into the host cell genome. The reaction can be divided in two steps: 3P P-end processing and DNA strand transfer. Here we studied the effect of short oligonucleotides (ODNs) on human immunodeficiency virus type 1 (HIV-1) IN. ODNs were either specific, with sequences representing the extreme termini of the viral long terminal repeats, or nonspecific. All ODNs were found to competitively inhibit the processing reaction with K i values in the nM range for the best inhibitors. Our studies on the interaction of IN with ODNs also showed that: (i) besides the 3P P-terminal GT, the interaction of IN with the remaining nucleotides of the 21-mer specific sequence was also important for an effective interaction of the enzyme with the substrate; (ii) in the presence of specific ODNs the activity of the enzyme was enhanced, a result which suggests an ODNinduced conformational change of HIV-1 IN.z 1999 Federation of European Biochemical Societies.

Xenopus laevis tadpoles were exposed for 48 h during sexual differentiation to atrazine at 21 microg/L under static laboratory conditions at 21+/-0.5 degrees C. After this exposure period, tadpoles were fixed and the kidney-gonad complex was microdissected. Quantitative histological analysis of the gonad revealed a 57% reduction in testicular volume among atrazine-exposed tadpoles. In addition, primary spermatogonial cell nests that represent germ cells for the life of the organism were reduced by 70%. Nursing cells, which provide nutritive support for the developing germ cells, had declined by 74%. Testicular resorption was observed among 70% and aplasia or failure of full development of the testis was recorded in 10% of the atrazine-exposed tadpoles. Because cell nests represent the pool of primordial germ cells for the reproductive life of the organism, the combined reduction in spermatogonial cell nests and nursing cells suggest that a pulse exposure to 21 microg/L of atrazine during sexual differentiation could significantly reduce reproduction during the reproductive life of these animals.