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Oxidant Effects on Rat and Human Lung Proteinase Inhibitors

David A Johnson
R Steve Winters
Kwan R Lee
Craig E Smith
December 1990
Research Report 37

This report describes a study by Dr. Johnson and colleagues to test the hypothesis that inhaled oxidants can cause lung damage by inactivating the proteinase inhibitors that normally protect the lung from proteolysis. In the first set of experiments, the functional activity of rat alpha-1-proteinase inhibitor (á1-PI) was measured in rat lung lavage fluid from rats exposed acutely or chronically to varying concentrations of NO2, diesel exhaust, O3, and O3 in conjunction with CO2.

Markers of Exposure to Diesel Exhaust in Railroad Workers

Marc B Schenker
Steven J Samuels
Norman Y Kado
S Katharine Hammond
Thomas J Smith
Susan R Woskie
October 1990
Research Report 33

This report describes a study by Dr. Schenker and colleagues to investigate the usefulness of urinary mutagenicity as a biological marker of occupational diesel exhaust exposure. Personal exposure to diesel exhaust over 2 consecutive work shifts was monitored via personal air samplers in 87 railroad workers, with adjustment for first-hand and environmental tobacco smoke exposure. Urine samples collected at the end of shifts were evaluated for mutagenicity and analyzed for any correlation with diesel exhaust exposure.

Acute Effects of Carbon Monoxide on Cardiac Electrical Stability

Richard L Verrier
Alex K Mills
William A Skornik
October 1990
Research Report 35

This report describes a study by Dr. Verrier and colleagues to explore the effects of acute carbon monoxide (CO) exposure on cardiac electrical stability through a number of biological models. Experiments involved cardiac electrical testing of conscious and anesthetized dogs with normal and ischemic hearts who were exposed to CO for 2 or 24 hours. The experimental plan explored both the direct effects of CO exposure on the myocardium and possible indirect effects through alterations in the ability of platelets to aggregate or changes in nervous system activity.

Metabolic Activation of Nitropyrenes and Diesel Particulate Extracts

Alan M Jeffrey
Regina M Santella
Diana Wong
Ling-Ling Hsieh
Volker Heisig
George Doskocil
Soraya Ghayourmanesh
July 1990
Research Report 34

This report describes a study by Dr. Jeffrey and colleagues to investigate the potential genotoxicity of components of diesel engine emissions using a variety of biological systems. In the first set of in vitro experiments, radiolabeled nitropyrenes were administered to DNA isolated from human bronchial tissue, mouse embryo fibroblasts, and rabbit tracheal tissue, and elution times were compared by high-pressure liquid chromatography. Antisera antibodies were also prepared against DNA modified by 1-nitrosopyrene to test for the presence of DNA adducts.

Respiratory Carcinogenesis of Nitroaromatics

Richard C Moon
Kandala VN Rao
Carol J Detrisac
April 1990
Research Report 32

This report describes a study by Dr. Moon and colleagues to investigate the carcinogenic potential of 1-nitropyrene, a mutagenic constituent of diesel exhaust particles, using a hamster respiratory-carcinogenesis model. Male hamsters were exposed to 1 or 2 mg of 1-nitropyrene via intratracheal administration either once or twice a week for 92 weeks. In order to study activity as a cocarcinogen, 1 or 2 mg of 1-nitropyrene was administered in combination with 0.25 mg of the known environmental carcinogen benzo[α]pyrene once per week for 92 weeks.

Acute Effects of Carbon Monoxide Exposure on Individuals with Coronary Artery Disease

Elizabeth N Allred
Eugene R Bleecker
Bernard R Chaitman
Thomas E Dahms
Sidney O Gottlieb
Jack D Hackney
Denise Hayes
Marcello Pagano
Ronald H Selvester
Sandra M Walden
Jane Warren
November 1989
Research Report 25

This report from the HEI Multicenter CO Study examined the effect of carbon monoxide (CO) exposure of male human participants with coronary artery disease, with a particular focus on myocardial ischemia onset during exercise. The participants were exposed to air or to CO concentrations sufficient to elevate blood carboxyhemoglobin (COHb) levels to 2% or 4% during exercise. The primary health endpoints examined were the time to onset of exercise-induced angina, and the time to a predefined ST-segment change.

DNA Binding by 1-Nitropyrene and Dinitropyrenes in Vitro and in Vivo: Effects of Nitroreductase Induction

Frederick A Beland
November 1989
Research Report 31

This report describes a study by Dr. Beland to investigate the extents to which 1-nitropyrene and 1,6-dinitropyrene, two PAHs found in diesel exhaust, bind DNA in order to better understand the higher relative mutagenicity of 1,6-Dinitropyrene. DNA binding was determined in rats by assay of tissue isolated from a variety of organs. A subset of rats was pretreated with 1-nitropyrene to determine any effect on induction of nitroreductases and subsequent DNA binding by both nitropyrenes.

Influence of Experimental Pulmonary Emphysema on Toxicological Effects from Inhaled Nitrogen Dioxide and Diesel Exhaust

Joe L Mauderly
David E Bice
Yung S Cheng
Nancy A Gillett
Rogene F Henderson
John A Pickrell
Ronald K Wolff
October 1989
Research Report 30

This report describes a study by Dr. Mauderly and colleagues to examine the influence of preexisting pulmonary emphysema on adverse health effects induced by chronic exposure of rats to diesel engine exhaust (DEE) or NO2. Rats were exposed 7 hours/day, 5 days/week for 24 months to 9.5 ppm NO2 or 3.5 mg soot/m3 DEE. Prior to exposure, a subset of rats was instilled with the proteolytic enzyme elastase to induce pulmonary emphysema.

Early Markers of Lung Injury

John N Evans
David R Hemenway
Jason Kelley
September 1989
Research Report 29

This report describes a study by Dr. Evans and colleagues to develop an early marker of lung injury that changes in response to exposure to NO2, which is an important component of mobile source emissions. Rats were exposed to NO2 in concentrations ranging from 0.5 to 30 ppm for 6 hours per day for periods ranging from 2 days to 4 weeks. Urine and bronchoalveloar lavage samples were collected and analyzed for the presence of the lung injury markers hydroxylysin, angiotensin-converting enzyme, and desmosine.

Nitrogen Dioxide and Respiratory Infection: Pilot Investigations

Jonathan M Samet
John Spengler
September 1989
Research Report 28

This report describes two pilot investigations for a longitudinal study of infants designed to determine if NO2 exposure from cooking stoves increases the incidence or severity of respiratory infections during the first 18 months of life. In the first study, Drs. Samet and Spengler selected 147 households with electric or gas stoves and infants for home indoor monitoring of NO2 concentrations; the infants\' mothers completed a daily calendar-diary on respiratory symptoms and provided illness information every 2 weeks.

Cardiovascular Effects of Chronic Carbon Monoxide and High-Altitude Exposure

James J McGrath
July 1989
Research Report 27

This report describes a study by Dr. McGrath to investigate the effect of chronic exposure of rats to CO at high altitude. Male rats were exposed for 6 weeks to CO ranging from 0 to 500 ppm at simulated altitudes ranging from 3,300 to 18,000 feet. The following weekly measurements were taken throughout the exposure period: weight, hematocrit, hemoglobin, and carboxyhemoglobin concentrations. Arterial pH, partial pressure of CO in the blood (PCO2) and PO2 were measured, as were blood pressure and ECG.

Investigation of a Potential Cotumorigenic Effect of the Dioxides of Nitrogen and Sulfur, and of Diesel-Engine Exhaust, on the Respiratory Tract of Syrian Golden Hamsters

Uwe Heinrich
Ulrich Mohr
Rainer Fuhst
Carsten Brockmeyer
May 1989
Research Report 26

This report describes a study by Dr. Heinrich and colleagues to investigate the effects of exposure to NO2 and SO2 or diesel engine exhaust on tumor formation in hamsters. Hamsters were exposed for 6, 10.5, 15, or 18 months to whole diesel exhaust, diesel exhaust without particles, or a mixture of NO2 and SO2. Additional groups of animals exposed to each test atmosphere were also injected with 3 or 6 mg of diethylnitrosamine/kg body weight to evaluate any enhancing effect of diethylnitrosamine on exposure-related changes.

Altered Susceptibility to Viral Respiratory Infection During Short-Term Exposure to Nitrogen Dioxide

Richard M Rose
Paula Pinkston
William A Skornik
March 1989
Research Report 24

This report examined the effect of nitrogen dioxide exposure on the sensitivity of the lower respiratory tract to viral infection and reinfection. Dr. Rose and colleagues exposed mice to concentrations of nitrogen dioxide ranging from 1-10 ppm or to air prior to and after inoculation with varying doses of murine cytomegalovirus. A subset of mice was reinfected 30 days later. Infection status, macrophage phagocytic uptake, lymphocyte function, and virus-specific antibody levels were measured, and the results were compared by exposure condition.

Detection of Paracrine Factors in Oxidant Lung Injury

Keith A Tanswell
February 1989
Research Report 22

This report addressed the hypothesis that hypertrophy of the lung after oxidant injury with ozone or oxygen is due to local generation of lung-specific growth factors. Dr. Tanswell exposed rats to either 85% oxygen, 1 ppm ozone, or air for up to two weeks while samples of plasma, lung washings, and lung tissue were periodically collected. These samples were tested for their effect on the DNA synthesis of purified populations of three major lung cell types (pneumocyte, fibroblast, and endothelial cell) in culture.

Responses of Susceptible Subpopulations to Nitrogen Dioxide

Paul E Morrow
Mark J Utell
February 1989
Research Report 23

This report investigated changes in pulmonary function, as well as the occurrence of symptoms, in potentially susceptible human subpopulations exposed to nitrogen dioxide. Drs. Morrow and Utell exposed healthy individuals and individuals with asthma, chronic obstructive pulmonary disease, and acute respiratory infection to air or 0.3 ppm nitrogen dioxide. The exposure period (four hours per day for five consecutive days) included defined periods of moderate exercise and pulmonary function measurements including spirometry, airway conductance, airway reactivity, and symptoms.

Maximal Aerobic Capacity at Several Ambient Concentrations of Carbon Monoxide at Several Altitudes

Steven M Horvath
James W Agnew
Jeames A Wagner
John F Bedi
December 1988
Research Report 21

This report examined the interactive effects induced by exposure to altitude and carbon monoxide. Dr. Horvath and colleagues exposed 23 healthy young human volunteers living at sea level to concentrations of 0, 50, 100, or 150 ppm carbon monoxide in a hyperbaric chamber simulating altitudes of 55, 1,524, 2,134, or 3, 048 meters above sea level. Maximal aerobic capacity tests were performed under each exposure condition while respiratory and cardiac variables and blood levels of carboxyhemoglobin, hemoglobin, and lactate were monitored.

Modulation of Pulmonary Defense Mechanisms Against Viral and Bacterial Infections by Acute Exposures to Nitrogen Dioxide

George J Jakab
November 1988
Research Report 20

This report investigated the influence of acute exposure to nitrogen dioxide on susceptibility to and severity of viral and bacterial infection in mice. Dr. Jakab exposed normal and immunosuppressed mice to concentrations of nitrogen dioxide ranging from 1 to 30 ppm before or after bacterial or viral challenge and measured host resistance to infection by physiologic parameters.

Potential Health Effects of Manganese in Emissions from Trap-Equipped Diesel Vehicles

Health Effects Institute
September 1988
Special Report

The use of ceramic particulate traps, in conjunction with manganese fuel additives, has been viewed as a way to reduce emissions of particulate matter from diesel-fueled vehicles. This Special Report focuses on the potential health effects from increased public exposure to manganese emissions from such use.

Factors Affecting Possible Carcinogenicity of Inhaled Nitropyrene Aerosols

Ronald K Wolff
Edward Barr
James A Bond
Arthur F Eidson
William C Griffith
Fletcher F Hahn
Jack R Harkema
Rogene F Henderson
Charles E Mitchell
Simon J Rothenberg
George M Shopp
James D Sun
August 1988
Research Report 19

This report assessed in rats the carcinogenicity of inhaled 1-nitropyrene, a compound frequently adsorbed to diesel particulate matter, and whether this effect is modified when 1-nitropyrene is associated with particles or irritant gases. Dr. Wolff and colleagues exposed rats to atmospheres containing 14C radiolabeled 1-nitropyrene alone or in combination with gallium oxide, sulfur dioxide, or both. After exposure, tissue samples were analyzed for radiolabel content to determine the tissue distribution of 1-nitropyrene and its metabolites.

Respiratory Infections in Coal Miners Exposed to Nitrogen Oxides

Michael Jacobsen
Tom A Smith
J Fintan Hurley
Alastair Robertson
Ralph Roscrow
July 1988
Research Report 18

This report investigated the association of occupational exposure to nitrogen oxides with respiratory infections in British coal miners. Dr. Jacobsen and colleagues leveraged data from the Pneumoconiosis Field Research Study, a long-term epidemiological study of British coal miners with information for the years 1953-1978.

Studies on the Metabolism and Biological Effects of Nitropyrene and Related Nitro-polycyclic Aromatic Compounds in Diploid Human Fibroblasts

Veronica M Maher
Joe Dale Patton
J Justin McCormick
March 1988
Research Report 17

This report describes a study by Dr. Maher and colleagues to investigate the biological effects of nitropyrene compounds, found in diesel emission particulate, on diploid human fibroblasts in culture in order to better evaluate potential health effects. Diploid human fibroblasts from normal individuals and individuals with a genetic predisposition to cancer were studied and compared through a series of experiments.

Metabolism and Biological Effects of Nitropyrene and Related Compounds

Charles M King
February 1988
Research Report 16

This report describes a study by Dr. King to investigate in rats the carcinogenetic properties of nitropyrene and related compounds and how these compounds are metabolically activated in target tissues. Nitropyrenes and related nitroaromatics are of interest because of their ubiquity in diesel emissions and reported carcinogenicity.

Susceptibility to Virus Infection with Exposure to Nitrogen Dioxide

Thomas J Kulle
Mary Lou Clements
January 1987
Research Report 15

This report addressed the hypothesis that exposure to oxidant air pollutants enhances susceptibility to viral infection. Drs. Kulle and Clements exposed healthy human volunteers who were seronegative to cold-adapted influenza A virus to clean air or nitrogen dioxide concentrations of 1, 2, or 3 ppm for two hours a day for three consecutive days. Live influenza A virus was administered intranasally to all participants after the second day of exposure.

The Effects of Ozone and Nitrogen Dioxide on Lung Function in Healthy and Asthmatic Adolescents

Jane Koenig
William E Pierson
Susan Gayle Marshall
David S Covert
Michael S Morgan
Gerald van Belle
January 1987
Research Report 14

This report investigated whether asthmatic and healthy adolescents differ in their sensitivity to near-ambient concentrations of ozone and nitrogen dioxide. Dr. Koenig and colleagues exposed healthy and asthmatic participants to concentrations of 0.12 and 0.18 ppm ozone or 0.12 and 0.18 ppm nitrogen dioxide during rest or rest followed by moderate exercise.

Effects of Nitrogen Dioxide on Alveolar Epithelial Barrier Properties

Edward D Crandall
Jeffrey M Cheek
Marian E Shaw
Edward M Postlethwait
October 1987
Research Report 13

This report describes a study by Dr. Crandall and colleagues to investigate the ability of nitrogen dioxide (NO2) to adversely alter the barrier and transport properties of mammalian alveolar epithelium and cause pulmonary edema. Rat type II alveolar cell monolayers cultured on non-porous and porous surfaces were used as models of isolated alveolar epithelium for in vitro exposure to NO2.

Neurotoxicity of Prenatal Carbon Monoxide Exposure

Laurence D Fechter
September 1987
Research Report 12

This report describes a study by Dr. Fechter to investigate the effect of prenatal and neonatal exposure to low levels of carbon monoxide (CO) on the developing rat brain. Groups of rats were exposed prenatally, or prenatally plus 10 days neonatally to take into account the fact that the developing rat brain is considerably less mature at birth than the primate brain. Consequently, rats were exposed to CO concentrations ranging from 75-300 ppm through the period of neuronal proliferation and into the period of synapse formation.

Effects of Ozone and Nitrogen Dioxide on Human Lung Proteinase Inhibitors

David A Johnson
August 1987
Research Report 11

Addressing the need for better assessment of human exposure to mobile source emissions, this report investigates proteinase inhibitor activity as a potential biomarker of oxidant exposure. In this study by Dr. Johnson, human participants were exposed to 0.5 ppm ozone for four hours on consecutive days and to concentrations ranging from 0.6-2 ppm nitrogen dioxide for three hours. Blood samples were obtained and the functional activity of the proteinase inhibitors, alpha-1-proteinase, and bronchial leukocyte proteinase was assessed.

Predictive Models for Disposition of Inhaled Diesel Exhaust Particles in Humans and Laboratory Species

July 1987
Research Report 10

Dr. Yu's project addressed several important issues regarding improved quantification of dose from known concentrations of atmospheric particulate matter. By focusing first on a specific category of automotive-derived particles, diesel exhaust particulate, Dr. Yu was able to characterize those aerosol properties (such as the mass medican aerodynamic diameter and size distribution) that influence regional deposition. After formulating a mathematical deposition model, Dr.

Biochemical and Metabolic Response to Nitrogen Dioxide-Induced Endothelial Injury

Jawaharlah M Patel
Edward R Block
June 1987
Research Report 9

Nitrogen dioxide is a ubiquitous air pollutant resulting from the combustion of fossil fuels. Since NO2 is a reactive free radical, one postulated mechanism on NO2 pulmonary injury involves peroxidation of membrane lipids. Dr. Patel and colleagues at the University of Florida evaluated the dose- and time-dependent effects of NO2 exposure by measuring metabolic function, biochemical and biophysical parameters. The porcine pulmonary artery and aortic endothelial cells in monoculture cells were exposed to 3 or 5ppm of NO2 or air for 3-24 hours.

Automotive Methanol Vapors and Human Health: An Evaluation of Existing Scientific Information and Issues for Future Research

Health Effects Institute
May 1987
Special Report

Report of the Institute's Health Research Committee. This report summarizes what emissions-related health problems, if any, would emerge if methanol were to become more widely used as an automotive fuel. Methanol-fueled vehicles emit both formaldehyde and methanol vapors. in 1985, HEI started a research program to investigate the potential health effects of aldehydes, including formaldehyde. Before proceeding with research on methanol vapors, the HEI Health Research Committee decided to undertake additional analysis.

Effects of Inhaled Nitrogen Dioxide and Diesel Exhaust on Developing Lung

Joe L Mauderly
David E Bice
Robert L Carpenter
Nancy A Gillett
Rogene F Henderson
John A Pickrell
Ronald K Wolff
May 1987
Research Report 8

Previous research has reported that the lung development of animals exposed to oxidant gases early in life might be impaired, or that developing lungs might be more susceptible than adult lungs to inhaled toxicants. Dr. Mauderly and colleagues at the Lovelace Biomedical and Environmental Research Institute examined the age-related differences in the physiological responses of rats to inhaled automotive emissions. The younger group was exposed during gestation and through the age of six months, while the older group was exposed between the age of six and twelve months.

DNA Adducts of Nitropyrene Detected by Specific Antibodies

John D Groopman
April 1987
Research Report 7

Research Report 7 describes a study that attempted to produce monoclonal antibodies to DNA adducts of nitropyrene that could be used to study the mechanism of nitropyrene-induced carcinogenesis or develop analytical techniques for monitoring exposed populations. Dr. Groopman immunized mice against nitropolycyclic aromatic hydrocarbons conjugated with a carrier protein to study the progression of immune response. Dr. Groopman injected four antigens into groups of BALB/c, AJ, and NZB mice. Two of the antigens failed to produce any immune response.

Effect of Nitrogen Dioxide, Ozone, and Peroxyacetyl Nitrate on Metabolic and Pulmonary Function

Deborah M Drechsler-Parks
April 1987
Research Report 6

Dr. Drechsler-Parks and colleagues at the Institute of Environmental Stress sought to examine the effects of nitrogen dioxide, ozone, and peroxyacetyl nitrate on metabolic and pulmonary function. Because it is possible that two or more pollutants could interact in ambient air and cause effects that could not be predicted from the effects observed with the individual pollutants, the investigators examined varying levels of different pollutants in 32 non-smoking men and women (8 men and 8 women 18-26 years of age and 8 men and 8 women 51-76 years of age).

An Investigation into the Effect of a Ceramic Particle Trap on the Chemical Mutagens in Diesel Exhaust

Susan T Bagley
Linda D Dorie
David G Leddy
John H Johnson
January 1987
Research Report 5

Dr. Bagley and colleagues at Michigan Technical University examined the chemical mutagenic effects of a ceramic particle trap on a medium-duty diesel engine. Diesel exhaust particles and vapor phase samples were collected from diluted (15:1) exhaust of a 10.4L displacement Caterpillar 3208 engine. The investigators compared uncontrolled (baseline) emissions with exhaust that had been modified by the use of an uncatalyzed monolithic ceramic trap.

The Metabolic Activation and DNA Adducts of Dinitropyrenes

Frederick A Beland
August 1986
Research Report 4

Nitrated polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants that often contain genotoxic activity. Dinitropyrenes are a class of PAHs that are associated with diesel exhaust. In this study, Dr. Beland and colleagues at the University of Arkansas for Medical Sciences sought to determine what factors contribute to the extreme genotoxicity of dinitropyrenes in bacteria and to establish if the same factors were important for the genotoxicity of dinitropyrenes in mammalian systems.

Transport of Macromolecules and Particles at Target Sites for Deposition of Air Pollutants

TT Crocker
DK Bhalla
February 1986
Research Report 3

The pulmonary epithelium is a cellular, avascular layer of tissue that is the first point of contact between the lung and inhaled pollutants. Previous research has indicated that altered epithelial permeability may be an early marker of subsequent lung damage. Dr. Crocker and colleagues at the University of California, Irvine sought to study the study the sites of epithelial injury in rat airways following inhalation of formaldehyde, ozone, and nitrogen dioxide.

Disposition and Metabolism of Free and Particle-Associated Nitropyrenes After Inhalation

James A Bond
Michele A Medinsky
James D Sun
January 1986
Research Report 2

Nitro-polynuclear aromatic hydrocarbons, including 1-nitropyrene, are constituents of diesel exhaust. Previous fractionation research has suggested that 1-nitropyrene and various dinitropyrenes may account for 20-50% of the total mutagenicity in the diesel particle extract (DPE). Dr. Bond and colleagues at the Inhalation Toxicology Research Institute examined the biological fate of inhaled 14C-1-nitropyrene (NP) in Fischer-344 rats.

Gasoline Vapor Exposure and Human Cancer: Evaluation of Existing Scientific Information and Recommendations for Future Research

Health Effects Institute
September 1985
Special Report

Report of the Institute's Health Review Comittee, September 1985. Supplement, January 1988. This report contains a review of data on the health effects of unburnt gasoline vapors, and evaluates the need for a research program to address major unresolved issues, especially in regard to the carcinogenicity of gasoline vapors. The supplement summarizes additional data published between 1985 and 1988 in response to a proposed regulatory strategy to reduce hydrocarbon emissions from mobile sources.

Estimation of Risk of Glucose 6-Phosphate Dehydrogenase Deficient Red Cells to Ozone and Nitrogen Dioxide

Marie A Amoruso
August 1985
Research Report 1

Acute hemolytic anemia is associated with a deficiency in glucose 6-phosphate dehydrogenase (G6PD), an X-linked inheritable characteristic. Hemolytic anemia is thought to be caused by a depletion of glutathione and other reducing compounds in red blood cells. Dr. Amoruso and colleagues sought to experimentally test the Calabrese hypothesis, which suggests that G6PD-deficient individuals may be at an increased risk of hemolysis during exposure to low levels of oxidants such as ozone.