Faculty Bibliography

The purpose of this exploratory study within the integrated subchronic inhalation exposure study (Lippmann et al., 2005) was to identify genes in heart and lung tissue that changed in expression level as a result of subchronic exposure to concentrated ambient particles (CAPs). Identification of CAPs exposure-related changes in gene expression could serve in the formulation of mechanistic hypotheses and/or to suggest possible biomarkers of exposure. In this exploratory study undertaken here, tissues from multiple replicates of ApoE/low-density-lipoprotein double knockout (DK) mice were examined for relative exposure-related changes in gene expression. Due to limited resources, the number of replicates was three for each tissue (lung and heart) of each exposure condition (CAPs or air control). A rigorous comparison of exposure versus control data using the 'significance analysis of microarrays' (SAM) method indicated that only one gene was differentially expressed at a significant level. However, when using a less restrictive, nonstatistical analytical treatment of the data, several genes that might be involved in PM-related heart or lung pathology, and/or the circadian rhythm of physiological processes, were identified. A more comprehensive study is required to mre definitively assess differences in gene expression in heart and lung resulting from exposure to CAPs

The NYU PM Center subchronic animal inhalation study addressed the issues of composition and sources of ambient fine particulate matter (PM2.5), as well as the relationship of these PM2.5 characteristics to the cellular response of human bronchial epithelial cells. In this simultaneous study, we used an in vitro exposure technique to compare the daily variations of the responses of cells to fine concentrated ambient particles (CAPs) collected from a rural area upwind of New York City for the period of 9 a.m. to 3 p.m. on weekdays only, March-September, 2003. Chemical composition data for CAPs were modeled using factor analysis with varimax orthogonal rotation to determine four particle source categories contributing significant amount of mass to CAPs at Sterling Forest (Tuxedo, NY). These source categories are: (1) regional secondary sulfate characterized by high S, Si, and organic carbon (OC); (2) resuspended soil characterized by high concentrations of Ca, Fe, Al, and Si; (3) oil-fired power plants emissions of the eastern United States identified by presence of V, Ni, and Se; and (4) unknown other sources. To estimate the mass contributions of each individual source category, the CAPs mass concentration was regressed against the factor scores. Regional sulfate was the largest contributor to mass (65%), followed by soil (20%), residual oil combustion (2%), and the other sources contributing 13%. Based on an evaluation of the cellular responses to CAPs and a detailed chemical characterization of the ambient PM2.5, we investigated the sources and individual components of ambient PM2.5 that are responsible for the induced cellular response. Nuclear Factor kappa B (NF-kappa B) was selected as a monitor of cellular stress response that followed after the exposure to CAPs. The results of the NF-kappa B assay were found to be most highly correlated with Ni and V among the individual components, and with the residual oil combustion source category

In order to examine the biologic plausibility of adverse chronic cardiopulmonary effects in humans associated with ambient particulate matter (PM) exposure, we exposed groups of normal mice (C57) and knockout mice that develop atherosclerotic plaque (ApoE-/- and ApoE-/- LDLr-/-) for 6 h/day, 5 days/wk for 5 or 6 mo during the spring/summer of 2003 to either filtered air or 10-fold concentrated ambient particles (CAPs) in Tuxedo, NY (average PM2.5 concentration during exposure = 110 microg/m3). Some of the mice had implanted electrocardiographic monitors. We demonstrated that: (1) this complex interdisciplinary study was technically feasible in terms of daily exposure, collection of air quality monitoring data, the collection, analysis, and interpretation of continuous data on cardiac function, and the collection and analyses of tissues of the animals sacrificed at the end of the study; (2) the daily variations in CAPs were significantly associated, in ApoE-/- mice, with daily variations in cardiac functions; (3) there were significant differences between CAPs and sham-exposed ApoE-/- mice in terms of cardiac function after the end of exposure period, as well as small differences in atherosclerotic plaque density, coronary artery disease, and cell density in the substantia nigra in the brain in the ApoE-/- mice; (4) there are suggestive indications of gene expression changes for genes associated with the control of circadian rhythm in the ApoE-/- LDLr-/- double knockout (DK) mice. These various CAPs-related effects on cardiac function and the development of histological evidence of increased risk of clinically significant disease at the end of exposures in animal models of atherosclerosis provide biological plausibility for the premature mortality associated with PM2.5 exposure in human subjects and provide suggestive evidence for neurogenic disease as well

This study reports that subchronic exposure of Tuxedo, NY concentrated ambient particulates (CAPs) produces neuropathological damage in the brains of Apo E-deficient mice (Apo E-/-). These genetically modified mice are characterized by elevated levels of oxidative stress (OS) in the brain. Microscopic examination of coronal sections of the brain, immunocytochemically stained for dopamineric neurons, indicated that neurons from the substantia nigral nucleus compacta were significantly reduced by 29% in CAPs-exposed Apo E-/- mice relative to air-exposed Apo E-/- controls. In addition, statistically significant increases (p < .05) in immunocytochemically stained astrocytes were noted. The dopaminergic neurons of the nucleus compact are specifically targeted in Parkinson's disease. The present study expands the systems affected by particulate matter to include the brain, and supports an environmental role for the development of neurodegeneration in OS-susceptible individuals

Normal mice (C57) and mice prone to develop atherosclerosis (ApoE-/-) were implanted with electrocardiograph (EKG), core body temperature, and motion transmitters were exposed daily for 6 h to Tuxedo, NY, concentrated ambient particles (CAPs) for 5 day/wk during the spring and summer of 2003. The series of 5-min EKG monitoring and body-temperature measurements were obtained for each animal in the CAPs and filtered air sham exposure groups. Our hypothesis was that chronic exposure could cause cumulative health effects. We used our recently developed nonparametric method to estimate the daily time periods that mean heart rates (HR), body temperature, and physical activity differed significantly between the CAPs and sham exposed group. CAPs exposure most affected heart rate between 1:30 a.m. and 4:30 a.m. With the response variables being the average heart rate, body temperature, and physical activity, we adopted a two-stage modeling approach to obtain the estimates of chronic and acute effects on the changes of these three response variables. In the first stage, a time-varying model estimated daily crude effects. In the second stage, the true means of the estimated crude effects were modeled with a polynominal function of time for chronic effects, a linear term of daily CAPs exposure concentrations for acute effects, and a random component for unknown noise. A Bayesian framework combined these two stages. There were significant decreasing patterns of HR, body temperature, and physical activity for the ApoE-/- mice over the 5 mo of CAPs exposure, with smaller and nonsignificant changes for the C57 mice. The chronic effect changes of the three response variables for ApoE-/- mice were maximal in the last few weeks. There was also a significant relationship between CAPs exposure concentration and short-term changes of heart rate in ApoE-/- mice during exposure. Response variables were also defined for examining fluctuations of 5-min heart rates within long (i.e., 3-6 h) and short time periods (i.e., approximately 15 min). The results for the ApoE-/- mice showed that heart-rate fluctuation within the longer periods increased to 1.35-fold by the end of exposure experiment, while the heart-rate fluctuation within 15 min decreased to 0.7-fold

The objective of this study is to characterize the ambient air quality of the South Bronx, New York City (NYC), having high concentrations of diesel trucks and waste transfer facilities. We employed a mobile laboratory for continuous measurements of concentrations of fine particulate matter (PM2.5), black carbon (BC), and gaseous pollutants at 6 locations for three-four weeks each during the period of April 2001-February 2003. Integrated 24-hr PM2.5 samples were also collected for elemental and PAHs analyses. South Bronx PM2.5 and BC levels were compared to those at Bronx PS 154 (NYSDEC site) and at Hunter College in the Lower Manhattan. Although the median daily PM2.5 concentrations agreed within 20%, the median hourly BC concentrations were higher at all South Bronx sites ranging from 2.2 to 3.8 mug m(-3), compared to 1.0-2.6 mug m(-3) at Hunter College. Continuous Aethelometer measurements at additional 27 sampling sites in the South Bronx were conducted along major highways. BC concentrations Varied within each site, depending on time-of-day, with a large spatial variability from site-to-site. Daily median BC concentrations varied from 1.7 to 12 mug m(-3) on the weekdays, and were lower (0.50-2.9 mug m(-3)) on the weekends; Elemental concentrations were higher at all South Bronx sites than those at Hunter College for all measured elements but Ni and V, and at the Hunts Point, an industrial location, were approximately 2.5-fold higher. The average sum of 35 PAHs was 225 ng m(-3), which is 4.5 times larger than representative regional concentrations in Jersey City, NJ. Among the individual PAHs, 3,6-dimethylphenanthrene had the highest concentrations, and the overall PAH fingerprint differed from signal for Jersey City. Our data indicates that highways encircling the South Bronx are having a measurable adverse influence on residents' exposure to pollutants compared to other NYC areas. (C) 2004 Elsevier Ltd. All rights reserved

The South Bronx is a low-income, minority community in New York City. It has one of the highest asthma rates in the country, which community residents feel is related to poor air quality. Community residents also feel that the air quality data provided by the New York State Department of Environmental Conservation (DEC) through its network of monitoring stations do not reflect the poor quality of the air they breathe. This is due to the fact that these monitoring stations are located 15 m above ground. In the year 2001 this project collected air quality data at three locations in the study area. They were collected close to ground-level at a height of 4 m by a mobile laboratory placed in a van as part of the South Bronx Environmental Health and Policy Study. This paper compares data collected by the project with data from DEC's monitoring stations in Bronx County during the same periods. The goal of the comparison is to gain a better understanding of differences in measured air quality concentrations at these different heights. Although there is good agreement in the data among DEC stations there are some important differences between ground-level measurements and DEC data. For PM2.5 the measured concentrations by the van were similar to those recorded by DEC stations. In the case of ozone, the concentrations recorded at ground level were similar or lower than those recorded by DEC stations. For NO2, however, the concentrations recorded at ground level were over twice as high as those recorded by DEC. In the case of SO2, ground level measurements were substantially higher in August but very similar in the other two periods. CO concentrations measured at ground-level tend to be 60-90% higher than those recorded by DEC monitoring stations. Despite these differences, van measurements Of SO2, and CO concentrations were well below EPA standards. (C) 2004 Elsevier Ltd. All rights reserved

Epidemiology studies suggest that exposure to air pollution increases the frequency of cardiac arrhythmias. A limitation of these studies is that it is difficult to link an increased risk of arrhythmias to a specific air pollutant. Animal exposure studies offer the opportunity to examine the effects of concentrated ambient fine particulate matter (PM), ultrafine PM, and copollutant gases separately. Male Fischer 344 rats, aged 18 mo, with implanted electrocardiograph (ECG) transmitters were used to determine the effects of PM on the frequency of arrhythmias. We found that old F344 rats had many spontaneous arrhythmias. An arrhythmia classification system was developed to quantify arrhythmia frequency. Arrhythmias were broadly grouped into two categories: premature beats and delayed beats. The rats were exposed to concentrated ambient PM (CAPS) or air for 4 h. The rats were exposed twice with a crossover design so each rat could serve as its own control. The CAPS concentrations were 160 microg/m(3) and 200 microg/m(3) for the first and second exposures, respectively. There was a significant increase in the frequency of irregular and delayed beats after exposure to CAPS. The same rats were subsequently exposed to laboratory-generated ultrafine carbon particles, to SO(2), or to air with a repeated crossover design. In these experiments there was no significant change in the frequency of any category of spontaneous arrhythmia following exposure to ultrafine carbon or SO(2). Thus, this study adds supporting evidence that acute exposure to elevated levels of ambient PM increases the frequency of cardiac arrhythmias