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Biomedical subjects

J M Samet

Publications and source records attributed to J M Samet.

At least 55 records · Page 3Linked to original sources
PubMed2000

Exposure measurement error in time-series studies of air pollution: concepts and consequences.

Misclassification of exposure is a well-recognized inherent limitation of epidemiologic studies of disease and the environment. For many agents of interest, exposures take place over time and in multiple locations; accurately estimating the relevant exposures for an individual participant in epidemiologic studies is often daunting, particularly within the limits set by feasibility, participant burden, and cost. Researchers have taken steps to deal with the consequences of measurement error by limiting the degree of error through a study's design, estimating the degree of error using a nested validation study, and by adjusting for measurement error in statistical analyses. In this paper, we address measurement error in observational studies of air pollution and health. Because measurement error may have substantial implications for interpreting epidemiologic studies on air pollution, particularly the time-series analyses, we developed a systematic conceptual formulation of the problem of measurement error in epidemiologic studies of air pollution and then considered the consequences within this formulation. When possible, we used available relevant data to make simple estimates of measurement error effects. This paper provides an overview of measurement errors in linear regression, distinguishing two extremes of a continuum-Berkson from classical type errors, and the univariate from the multivariate predictor case. We then propose one conceptual framework for the evaluation of measurement errors in the log-linear regression used for time-series studies of particulate air pollution and mortality and identify three main components of error. We present new simple analyses of data on exposures of particulate matter < 10 microm in aerodynamic diameter from the Particle Total Exposure Assessment Methodology Study. Finally, we summarize open questions regarding measurement error and suggest the kind of additional data necessary to address them.

Air Pollution↗
PubMed2000

Radon and lung cancer risk: taking stock at the millenium.

Radon is a well-established human carcinogen for which extensive data are available, extending into the range of exposures experienced by the general population. Mounting epidemiologic evidence on radon and lung cancer risk, now available from more than 20 different studies of underground miners and complementary laboratory findings, indicates that risks are linear in exposure without threshold. Radon is also a ubiquitous indoor air pollutant in homes, and risk projections imply that radon is the second leading cause of lung cancer after smoking. Recommended control strategies in the United States and other countries, which include testing of most homes and mitigation of those exceeding guideline levels, have been controversial. Further research is needed, drawing on molecular and cellular approaches and continuing the follow-up of the underground miner cohorts, and scientists should work toward constructing mechanistically based models that combine epidemiologic and experimental data to yield risk estimates with enhanced certainty.

Air Pollutants, Radioactive↗
PubMed2000

The National Morbidity, Mortality, and Air Pollution Study. Part I: Methods and methodologic issues.

The Health Effects Institute, established in 1980, is an independent and unbiased source of information on the health effects of motor vehicle emissions. HEI supports research on all major pollutants, including regulated pollutants (such as carbon monoxide, ozone, nitrogen dioxide, and particulate matter) and unregulated pollutants (such as diesel engine exhaust, methanol, and aldehydes). To date, HEI has supported more than 200 projects at institutions in North America and Europe and has published over 100 research reports. Typically, HEI receives half its funds from the US Environmental Protection Agency and half from 28 manufacturers and marketers of motor vehicles and engines in the US. Occasionally, funds from other public and private organizations either support special projects or provide resources for a portion of an HEI study. Regardless of funding sources, HEI exercises complete autonomy in setting its research priorities and in reaching its conclusions. An independent Board of Directors governs HEI. The Institute's Research and Review Committees serve complementary scientific purposes and draw distinguished scientists as members. The results of HEI-funded studies are made available as Research Reports, which contain both the Investigators' Report and the Review Committee's evaluation of the work's scientific quality and regulatory relevance.

Air Pollutants↗
PubMed2000

The National Morbidity, Mortality, and Air Pollution Study. Part II: Morbidity and mortality from air pollution in the United States.

BACKGROUND: Epidemiologic time-series studies conducted in a number of cities have identified, in general, an association between daily changes in concentration of ambient particulate matter (PM) and daily number of deaths (mortality). Increased hospitalization (a measure of morbidity) among the elderly for specific causes has also been associated with PM. These studies have raised concerns about public health effects of particulate air pollution and have contributed to regulatory decisions in the United States. However, scientists have pointed out uncertainties that raise questions about the interpretation of these studies. One limitation to previous time-series studies of PM and adverse health effects is that the evidence for an association is derived from studies conducted in single locations using diverse analytic methods. Statistical procedures have been used to combine the results of these single location studies in order to produce a summary estimate of the health effects of PM. Difficulties with this approach include the process by which cities were selected to be studied, the different analytic methods applied to each single study, and the variety of methods used to measure or account for variables included in the analysis. These individual studies were also not able to account for the effects of gaseous air pollutants in a systematic manner.

Adolescent↗
PubMed1999

Arsenite exposure of cultured airway epithelial cells activates kappaB-dependent interleukin-8 gene expression in the absence of nuclear factor-kappaB nuclear translocation.

Airway epithelial cells respond to certain environmental stresses by mounting a proinflammatory response, which is characterized by enhanced synthesis and release of the neutrophil chemotactic and activating factor interleukin-8 (IL-8). IL-8 expression is regulated at the transcriptional level in part by the transcription factor nuclear factor (NF)-kappaB. We compared intracellular signaling mediating IL-8 gene expression in bronchial epithelial cells cultured in vitro and exposed to two inducers of cellular stress, sodium arsenite (As(III)), and vanadyl sulfate (V(IV)). Unstimulated bronchial epithelial cells expressed IL-8, and exposure to both metal compounds significantly enhanced IL-8 expression. Overexpression of a dominant negative inhibitor of NF-kappaB depressed both basal and metal-induced IL-8 expression. Low levels of nuclear NF-kappaB were constitutively present in unstimulated cultures. These levels were augmented by exposure to V(IV), but not As(III). Accordingly, V(IV) induced IkappaBalpha breakdown and NF-kappaB nuclear translocation, whereas As(III) did not. However, both As(III) and V(IV) enhanced kappaB-dependent transcription. In addition, As(III) activation of an IL-8 promoter-reporter construct was partially kappaB-dependent. These data suggested that As(III) enhanced IL-8 gene transcription independently of IkappaB breakdown and nuclear translocation of NF-kappaB in part by enhancing transcription mediated by low levels of constitutive nuclear NF-kappaB.

Arsenites↗
PubMed1999

Smoking in China: findings of the 1996 National Prevalence Survey.

CONTEXT: As the world's largest producer and consumer of tobacco products, China bears a large proportion of the global burden of smoking-related disease and may be experiencing a tobacco epidemic. OBJECTIVE: To develop an evidence-based approach supporting tobacco control initiatives in China. DESIGN AND SETTING: A population-based survey consisting of a 52-item questionnaire that included information on demographics, smoking history, smoking-related knowledge and attitudes, cessation, passive smoke exposure, and health status was administered in 145 disease surveillance points in the 30 provinces of China from March through July 1996. PARTICIPANTS: A nationally representative random sample of 128766 persons aged 15 to 69 years were asked to participate; 120298 (93.8%) provided data and were included in the final analysis. About two thirds of those sampled were from rural areas and one third were from urban areas. MAIN OUTCOME MEASURES: Current smoking patterns and attitudes; changes in smoking patterns and attitudes compared with results of a previous national survey conducted in 1984. RESULTS: A total of 41187 respondents smoked at least 1 cigarette per day, accounting for 34.1% of the total number of respondents, an increase of 3.4 percentage points since 1984. Current smoking continues to be prevalent among more men (63%) than women (3.8%). Age at smoking initiation declined by about 3 years for both men and women (from 28 to 25 years). Only a minority of smokers recognized that lung cancer (36%) and heart disease (4%) can be caused by smoking. Of the nonsmokers, 53.5% were exposed to environmental tobacco smoke at least 15 minutes per day on more than 1 day per week. Respondents were generally supportive of tobacco control measures. CONCLUSION: The high rates of smoking in men found in this study signal an urgent need for smoking prevention and cessation efforts; tobacco control initiatives are needed to maintain or decrease the currently low smoking prevalence in women.

Adolescent↗
PubMed1999

Dear author--advice from a retiring editor.

This commentary, detailing the handling of a manuscript by the editor and guiding authors on preparing manuscripts and responding to reviews, provides parting advice to authors from a retiring editor. A close reading of this commentary will give some insight into the editorial process at the American Journal of Epidemiology through the observations of one of its editors.

Periodicals as Topic↗
PubMed1999

Respiratory epithelial cells demonstrate lactoferrin receptors that increase after metal exposure.

Human airway epithelial cells can increase expression of both lactoferrin and ferritin after exposure to catalytically active metal. These proteins transport and store metal, with coordination sites fully complexed, and therefore can diminish the oxidative stress. The intracellular transport of lactoferrin results in a transfer of complexed metal to ferritin, where it is stored in a less reactive form. This effort to control the injurious properties of metals would be facilitated by lactoferrin receptors (LfRs) on airway epithelial cells. We tested the hypotheses that 1) LfRs exist on respiratory epithelial cells and 2) exposure to both an air pollution particle, which has abundant concentrations of metals, and individual metal salts increase the expression of LfRs. Before exposure to either the particle or metals, incubation of BEAS-2B cells with varying concentrations of 125I-labeled lactoferrin demonstrated lactoferrin binding that was saturable. Measurement of 125I-lactoferrin binding after the inclusion of 100 micrograms/ml of oil fly ash in the incubation medium demonstrated increased binding within 5 min of exposure, which reached a maximal value at 45 min. Inclusion of 1.0 mM deferoxamine in the incubation of BEAS-2B cells with 100 micrograms/ml of oil fly ash decreased lactoferrin binding. Comparable to the particle, exposure of BEAS-2B cells to either 1.0 mM vanadyl sulfate or 1.0 mM iron (III) sulfate, but not to nickel sulfate, for 45 min elevated LfR activity. We conclude that LfRs on respiratory epithelial cells increased after exposure to metal. LfRs could participate in decreasing the oxidative stress presented to the lower respiratory tract by complexing catalytically active metals.

Air Pollution↗
PubMed1999

Activation of the EGF receptor signaling pathway in human airway epithelial cells exposed to metals.

We have previously shown that exposure to combustion-derived metals rapidly (within 20 min) activated mitogen-activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK), in the human bronchial epithelial cell line BEAS. To study the mechanisms responsible for metal-induced activation of ERK, we examined the effect of noncytotoxic exposures to As, Cu, V, or Zn on the kinases upstream of ERK in the epidermal growth factor (EGF) receptor signaling pathway. Western blotting using phospho-specific ERK1/2 antibody demonstrated the selective MEK1/2 inhibitor PD-98059 blocked metal-induced phosphorylation of ERK1/2. Meanwhile, Western blotting using a phospho-specific MEK1/2 antibody showed that these metals induce a rapid phosphorylation of MEK1/2. Kinase activity assays confirmed the activation of MEK1/2 by metal treatment. Immunoprecipitation studies demonstrated that As, Cu, V, or Zn induces EGF receptor phosphorylation. Furthermore, the EGF receptor-specific tyrosine kinase inhibitor (PD-153035) significantly blocked the phosphorylation of MEK1/2 initiated by metals. Interestingly, we observed low levels of Raf-1 activity that were not increased by metal exposure in these cells through kinase activity assay. Finally, transfection assays showed that MEK1/2 inhibition could inhibit trans-activation of Elk1, a transcription factor in the ERK pathway, in BEAS cells exposed to metals. Together, these data demonstrate that As, Cu, V, and Zn can activate the EGF receptor signaling pathway in BEAS cells and suggest that this mechanism may be involved in pulmonary responses to metal inhalation.

Air Pollutants↗
PubMed1999

Effects of aqueous extracts of PM(10) filters from the Utah valley on human airway epithelial cells.

We hypothesized that the reduction in hospital respiratory admissions in the Utah Valley during closure of a local steel mill in 1986-1987 was attributable in part to decreased toxicity of ambient air particles. Sampling filters for particulate matter < 10 micrometer (PM(10)) were obtained from a Utah Valley monitoring station for the year before (year 1), during (year 2), and after (year 3) the steel mill closure. Aqueous extracts of the filters were analyzed for metal content and oxidant production and added to cultures of human respiratory epithelial (BEAS-2B) cells for 2 or 24 h. Year 2 dust contained the lowest concentrations of soluble iron, copper, and zinc and showed the least oxidant generation. Only dust from year 3 caused cytotoxicity (by microscopy and lactate dehydrogenase release) at 500 microgram/ml. Year 1 and year 3, but not year 2, dust induced expression of interleukin-6 and -8 in a dose-response fashion. The effects of ambient air particles on human respiratory epithelial cells vary significantly with time and metal concentrations.

Air Pollutants, Occupational↗
PubMed1999

Tyrosine phosphatases as targets in metal-induced signaling in human airway epithelial cells.

We previously showed that exposure to metal-laden combustion particles disregulates protein tyrosine phosphate homeostasis in human airway epithelial cells (HAEC). More recently, we reported that exposure to certain metal ions activates mitogen-activated protein kinases in HAEC. To study the mechanism responsible, we examined the effects of arsenic (As), vanadium (V), and zinc (Zn) on tyrosine phosphate catabolism in BEAS S6 cells or cultured human bronchial epithelial cells. Western blots and immunocytochemical analyses showed that exposure to noncytotoxic levels of As, V, or Zn resulted in increased levels of protein phosphotyrosines in HAEC. Tyrosine phosphatase activity, measured against [(32)P]-labeled PolyGlu:Tyr, was markedly inhibited in cells treated with V or Zn but was unaffected by exposure to As. Fast performance liquid chromatography fractionation and subsequent in-gel phosphatase activity assay of HAEC protein extracts revealed the presence of numerous tyrosine phosphatases, of varying molecular weights, that were effectively inhibited by exposure to V or Zn ions. As had no discernible effect on these enzymes. The protein tyrosine phosphatase PTP1B, immunoprecipitated from HAEC, was similarly inhibited by V and Zn but not by As ions. These data show that V and Zn may induce tyrosine phosphate accumulation by inhibiting dephosphorylation and implicate kinase activation as the mechanism in HAEC exposed to As. These findings suggest that metal exposure can activate signaling pathways through multiple mechanisms.

Arsenic↗
PubMed1999

Workshop summary: assessing exposure to environmental tobacco smoke in the workplace.

Environmental tobacco smoke (ETS) is a term now widely used to refer to the mixture of sidestream smoke and exhaled mainstream smoke that pollutes air in locations where tobacco smoking is taking place. A multidisciplinary workshop was convened to address key issues related to ETS exposure in the workplace in order to prepare the groundwork for a risk assessment of the hazard ETS poses to workers. Workshop participants concluded that substantial evidence was now available on worker exposure to ETS using both direct and indirect approaches to exposure assessment and that these data could be used to project distribution of exposures to ETS in the nation's workplaces. This summary of the discussions at the workshop is an overview of the suggested approach to exposure assessment.

Air Pollutants, Occupational↗
PubMed1999

Summary: workshop on health risks attributable to ETS exposure in the workplace.

This 1998 workshop was convened to address the health risks of exposure to environmental tobacco smoke (ETS) in the workplace. It was paired with a 1997 workshop on issues related to ETS exposure in work environments ((italic)1(/italic)). In the 1998 workshop, a multidisciplinary group of participants was charged with reviewing evidence on the quantitative risks to health posed by ETS and to discuss development of risk assessment methodology for the future. The overall charges for the present workshop were to consider various health outcomes and make recommendations regarding those health outcomes to be included in assessment of health risk resulting from ETS in the workplace; to consider available studies addressing these health outcomes and to evaluate the validity of data for estimating risk from occupational ETS exposure; to review and evaluate mathematical models useful for estimating the risk due to ETS exposure; to examine dose-response models and to characterize the models regarding validity and uncertainty in estimating health risk attributable to ETS exposure in the workplace.

Asthma↗
PubMed1999

Occupational exposure to environmental tobacco smoke and health risk assessment.

This article addresses concepts of environmental tobacco smoke (ETS) exposure assessment relevant for health risk assessment based on human studies. We present issues that should be considered when selecting a method for ETS exposure assessment for the purposes of health risk assessment and review data on ETS exposure levels in the workplace and in home environments. Two types of estimates are needed for a quantitative risk assessment of the health effects resulting from occupational ETS exposure: (italic)a(/italic)) an unbiased estimate of the exposure-effect (or dose-response) relation between ETS and the health effect of interest, and (italic)b(/italic)) estimates of the distribution of ETS exposure in different workplaces. By combining the estimated exposure-effect relation with information on exposure distribution for a population of interest, we can calculate the proportions of disease cases attributable to occupational ETS exposure as well as the excess number of cases due to specified exposure conditions. Several dimensions of the exposure profile should be considered when assessing ETS exposure for estimating the exposure-effect relation, including the magnitude of exposure and the biologically relevant time specificity of exposure. The magnitude of exposure is determined by the ETS source strength, environmental factors modifying concentrations, and duration of exposure. Time specificity considerations include the latency period for each health outcome of interest, the time-exposure profile relevant for different disease mechanisms, and the sensitive age period with regard to health effects. The most appropriate indicator of ETS exposure depends on these factors and on the time period that can be assessed with different methods.

Environmental Monitoring↗
PubMed1999

Environmental tobacco smoke exposure and asthma in adults.

Environmental tobacco smoke (ETS) contaminates indoor air in homes and workplaces. Although the adverse effects of active cigarette smoking on the respiratory tract have been extensively characterized, the effects of ETS exposure on adult asthma have not yet been investigated extensively and the available data are limited. This article examines the evidence for ETS exposure as a cause of asthma and asthma exacerbation in adults, and for ETS exposure in the workplace specifically as contributing to these health effects. It addresses methodological barriers that limit the available data and evaluates the adequacy of the data for risk assessment.

Adult↗