Publications

Efficient gas exchange in the lungs depends on regulation of the amount of fluid in the thin (average 0.2 mum) liquid layer lining the alveolar epithelium. Fluid fluxes are regulated by ion transport across the alveolar epithelium, which is composed of alveolar type I (TI) and type II (TII) cells. The accepted paradigm has been that TII cells, which cover <5% of the internal surface area of the lung, transport Na(+) and Cl(-) and that TI cells, which cover >95% of the surface area, provide a route for water absorption. Here we present data that TI cells contain functional epithelial Na(+) channels (ENaC), pimozide-sensitive cation channels, K(+) channels, and the cystic fibrosis transmembrane regulator. TII cells contain ENaC and cystic fibrosis transmembrane regulator, but few pimozide-sensitive cation channels. These findings lead to a revised paradigm of ion and water transport in the lung in which (i) Na(+) and Cl(-) transport occurs across the entire alveolar epithelium (TI and TII cells) rather than only across TII cells; and (ii) by virtue of their very large surface area, TI cells are responsible for the bulk of transepithelial Na(+) transport in the lung.

The Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM), initiated in 2000, investigates the prevalence and correlates of changes in fat distribution, insulin resistance, and dyslipidemia among human immunodeficiency virus (HIV)-infected men and women compared with a population-based group of control men and women. Between June 2000 and September 2002, 1,480 participants (1,183 HIV-infected persons and 297 controls) were enrolled in FRAM. Measurements taken included whole-body magnetic resonance imaging for quantification of regional fat, anthropometric measurements, central laboratory analysis of metabolites, and assessment of symptoms, sociodemographic factors, and lifestyle. Similar measurements were repeated among FRAM participants 4 years later (FRAM 2) for investigation of the progression of fat distribution changes, insulin resistance, and hyperlipidemia. In FRAM 2, which is ongoing, investigators are also determining the associations of subclinical cardiovascular disease, as measured by carotid intimal-medial wall thickness, with HIV infection, fat distribution changes, insulin resistance, and other proatherogenic changes in serum lipid levels. The demographic characteristics of HIV-infected FRAM men and women were comparable to those reported from a national random sampling of HIV-infected men and women receiving medical care in the United States. The representativeness of the FRAM sample increases its value as a resource for studies on fat distribution, metabolic changes, and atherosclerosis in HIV infection.

Ozone (O(3)) is an important component of air pollution and a potent oxidant of biomolecules. To address the hypothesis that elevated ambient O(3) can induce cytogenetic damage in healthy people, we collected buccal cells from two groups of students (N = 126) from University of California, Berkeley, in the spring and again in the fall. One group spent their summer in the Los Angeles (LA) area where summer O(3) concentrations are significantly higher than in the San Francisco Bay (SF) area, and another remained in SF. During the school year, all students were exposed to low O(3) levels in SF. The micronucleus assay in a total of 611,000 buccal cells demonstrated that, in the fall, micronuclei (MN) in normal cells for the LA group had increased 39% relative to levels in the spring (1.52 and 0.87 MN/1,000 cells, respectively, P = 0.001). Students who spent the summer in SF had a 12.7% increase (P = 0.48). A similar effect of season was seen in degenerated buccal cells for the LA group (3.23 versus 1.88 MN/1,000 cells, P = 0.003). LA but not SF subjects also had more degenerated cells in the fall sample (P = 0.003). These findings were paralleled by an increase in MN and nucleoplasmic bridges in lymphocytes and MN in buccal cells in a sub-group of 15 students who underwent a 4-h controlled exposure to 200 p.p.b. O(3). This cytogenetic evidence, along with recent studies linking O(3) exposure to elevated lung cancer risk and mortality, suggest potential public health implications from exposures to high oxidant environments.