30 results on '"Mary J. Daniels"'
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2. Soy biodiesel emissions have reduced inflammatory effects compared to diesel emissions in healthy and allergic mice
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Jaime M. Cyphert, Elizabeth Boykin, M. Ian Gilmour, Judy H. Richards, Lisa B. Copeland, Charly King, Todd Q. Krantz, Charles E. Wood, Debora L. Andrews, Mary J. Daniels, Stephen H. Gavett, Richard H. Jaskot, and Marc A. Williams
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Allergy ,medicine.medical_specialty ,Diesel exhaust ,Neutrophils ,Health, Toxicology and Mutagenesis ,Toxicology ,complex mixtures ,Allergic inflammation ,Mice ,Internal medicine ,Hypersensitivity ,medicine ,Animals ,Vehicle Emissions ,Inhalation exposure ,House dust mite ,Air Pollutants ,Inhalation Exposure ,Mice, Inbred BALB C ,medicine.diagnostic_test ,biology ,business.industry ,Chemistry ,medicine.disease ,biology.organism_classification ,Biotechnology ,Endocrinology ,Bronchoalveolar lavage ,Biofuels ,Toxicity ,Female ,Particulate Matter ,Methacholine ,Soybeans ,Inflammation Mediators ,business ,medicine.drug - Abstract
Toxicity of exhaust from combustion of petroleum diesel (B0), soy-based biodiesel (B100), or a 20% biodiesel/80% petrodiesel mix (B20) was compared in healthy and house dust mite (HDM)-allergic mice. Fuel emissions were diluted to target fine particulate matter (PM2.5) concentrations of 50, 150, or 500 μg/m3. Studies in healthy mice showed greater levels of neutrophils and MIP-2 in bronchoalveolar lavage (BAL) fluid 2 h after a single 4-h exposure to B0 compared with mice exposed to B20 or B100. No consistent differences in BAL cells and biochemistry, or hematological parameters, were observed after 5 d or 4 weeks of exposure to any of the emissions. Air-exposed HDM-allergic mice had significantly increased responsiveness to methacholine aerosol challenge compared with non-allergic mice. Exposure to any of the emissions for 4 weeks did not further increase responsiveness in either non-allergic or HDM-allergic mice, and few parameters of allergic inflammation in BAL fluid were altered. Lung and nasal pathology were not significantly different among B0-, B20-, or B100-exposed groups. In HDM-allergic mice, exposure to B0, but not B20 or B100, significantly increased resting peribronchiolar lymph node cell proliferation and production of TH2 cytokines (IL-4, IL-5, and IL-13) and IL-17 in comparison with air-exposed allergic mice. These results suggest that diesel exhaust at a relatively high concentration (500 μg/m3) can induce inflammation acutely in healthy mice and exacerbate some components of allergic responses, while comparable concentrations of B20 or B100 soy biodiesel fuels did not elicit responses different from those caused by air exposure alone.
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- 2015
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3. Phenotypic comparison of allergic airway responses to house dust mite in three rat strains
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Darrell W. Winsett, Mary J. Daniels, Judy H. Richards, Kenneth B. Adler, M. Ian Gilmour, Pramila Singh, Donald L. Doerfler, and Gary E. Hatch
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Pulmonary and Respiratory Medicine ,Allergy ,Physiology ,Lung injury ,medicine.disease_cause ,Rats, Sprague-Dawley ,Atopy ,Interferon-gamma ,Allergen ,Species Specificity ,Rats, Inbred BN ,Physiology (medical) ,Immunopathology ,Hypersensitivity ,Animals ,Medicine ,Lymphocytes ,Lung ,Pulmonary Eosinophilia ,House dust mite ,Interleukin-13 ,biology ,business.industry ,Pyroglyphidae ,Genetic Variation ,Cell Biology ,Immunoglobulin E ,Eosinophil ,biology.organism_classification ,medicine.disease ,Asthma ,Rats ,respiratory tract diseases ,Phenotype ,medicine.anatomical_structure ,Rats, Inbred Lew ,Immunoglobulin G ,Immunology ,Female ,Lymph Nodes ,business ,Bronchoalveolar Lavage Fluid ,Cell Division - Abstract
Brown Norway (BN) rats develop a robust response to antigens in the lung, characterized by a large increase in allergen-specific immune function and pulmonary eosinophilia. The objective of this study was to investigate alternative models by determining whether other rat strains could be sensitized to house dust mite (HDM) antigen and whether the allergic disease process could be worsened with repeated allergen exposure. In general, BN rats sensitized by either subcutaneous or intratracheal routes exhibited increased pulmonary allergy compared with Sprague-Dawley (SD) and Lewis (L) rats. Multiple intratracheal allergen exposures incrementally increased HDM-specific immune function in BN rats but progressively decreased eosinophil recruitment and markers of lung injury. SD rats had more moderate responses, whereas L rats were relatively unresponsive. Because BN rats developed stronger clinical hallmarks of allergic asthma under various immunization regimes compared with SD and L rats, we conclude that the BN is the most appropriate strain for studying allergic asthma-like responses in rats. Phenotypic differences in response to HDM were associated with differences in the Th1/Th2 cytokine balance and antioxidant capacity.
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- 2003
4. Air pollutant-enhanced respiratory disease in experimental animals
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R C McCrillis, Darrell W. Winsett, M K Selgrade, M.I. Gilmour, and Mary J. Daniels
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Pollutant ,Air Pollutants ,Respiratory tract infections ,Health, Toxicology and Mutagenesis ,Respiratory disease ,Public Health, Environmental and Occupational Health ,Air pollution ,Streptococcus ,Respiratory infection ,Disease ,Biology ,medicine.disease ,medicine.disease_cause ,Rats ,Disease Models, Animal ,Mice ,Air pollutants ,Macrophages, Alveolar ,Toxicity ,Immunology ,Respiratory Hypersensitivity ,medicine ,Animals ,Respiratory Tract Infections ,Research Article - Abstract
Studies in animals have shown that a wide range of airborne particulates including cigarette smoke, acid aerosols, metals, organic compounds, and combustion products can interfere with the normal defense processes of the lung to enhance susceptibility to respiratory infection or exacerbate allergic diseases. Such detrimental effects are less easy to quantify in humans because of the difficulties in obtaining comprehensive exposure history and health status in large populations and because of the inherent dangers of inducing disease in clinical studies. In this article we describe examples of how air pollutants affect lung disease in experimental animal systems. This information can be used to predict the health risk of simple and complex exposures and to lend insight into the mechanisms of air pollution toxicity.
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- 2001
5. Immunotoxicological Analysis of The Immune Adjuvant Effects Of Source-Specific Diesel And Environmental Ambient Particulate Matter In a Murine Sensitization And Challenge Model
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Judy H. Richards, Lisa B. Copeland, Mathew I. Gilmour, Marc A. Williams, Mary J. Daniels, Elizabeth Boykin, and James R. Lehmann
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Diesel fuel ,medicine.anatomical_structure ,Chemistry ,Immunology ,medicine ,Immunopotentiator ,Particulates ,Sensitization - Published
- 2012
6. Differential And Dose-Dependent Inflammatory Responses In A Mouse Model Of Respirable Instillation Of Ambient Airborne, Environmental Diesel And Emission-Source Diesel Pollutant Particles In Vivo
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M. Ian Gilmour, Marc A. Williams, Elizabeth Boykin, Mary J. Daniels, and Lisa B. Copeland
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Pollutant ,Diesel fuel ,Chemistry ,In vivo ,Environmental chemistry ,Dose dependence - Published
- 2011
7. Evaluation of Immunotoxicity of an Urban Profile of Nitrogen Dioxide: Acute, Subchronic, and Chronic Studies
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Elaine C. Crose, MaryJane K. Selgrade, and Mary J. Daniels
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Pollutant ,Health, Toxicology and Mutagenesis ,Physiology ,Spleen ,Mononuclear phagocyte system ,Biology ,Toxicology ,Natural killer cell ,chemistry.chemical_compound ,medicine.anatomical_structure ,Immune system ,chemistry ,Immunopathology ,Toxicity ,Immunology ,medicine ,Nitrogen dioxide - Abstract
Although a number of studies have demonstrated suppression of extrapulmonary immune responses following exposure to NO2, a ubiquitous ambient and indoor air pollutant, most of these studies have utilized extremely high concentrations of NO2 relative to the environment. Our intent was to assess effects of NO2 on extra-pulmonary immune responses using an environmentally relevant exposure regimen. Rats were exposed for 7, 3, 13, 52, or 78 wk to air or a pattern of NO2 designed to mimic episodic pollution in urban areas at concentrations 2–5 times those commonly seen in such areas. Daily exposures consisted of 0.5 ppm for 16 h, a 6-h exposure spike during which the concentration rose to 1.5 ppm, remained there for 2 h, and then returned to 0.5 ppm, and a 2-h down time. Rats were exposed to this profile 5 days/wk; weekend exposures did not include the spike. Blood was drawn and spleens were removed at the end of each exposure period. Spleen cells were assessed for natural killer (NK) cell activity and ...
- Published
- 1991
8. Acute, Subchronic, and Chronic Exposure to a Simulated Urban Profile of Ozone: Effects on Extrapulmonary Natural Killer Cell Activity and Lymphocyte Mitogenic Responses
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Elaine C. Grose, M K Selgrade, and Mary J. Daniels
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biology ,Health, Toxicology and Mutagenesis ,Lymphocyte ,Physiology ,Spleen ,Histology ,Toxicology ,Natural killer cell ,medicine.anatomical_structure ,Lymphatic system ,Concanavalin A ,Toxicity ,Immunology ,medicine ,biology.protein ,Bone marrow - Abstract
Rats were exposed for 7, 3, 73, 52, or 78 wk to air or a simulated urban profile of O3 designed to mimic diurnal exposure patterns frequently seen in worst-case summer environments. Daily exposures consisted of a background level of 0.06 ppm for a period of 73 h, a broad exposure spike rising from 0.06 to 0.25 ppm and returning to 0.06 ppm over 9 h, and a 2 h downtime. Integration of the spike portion of the exposure pattern was equivalent to a 9-h square-wave exposure pattern of 0.79 ppm. Rats were exposed to this profile 5 days/wk; weekend exposures were to background levels only Spleens were removed and blood was drawn at the end of the exposure periods. Spleen cells were assessed for natural killer cell (NKC) activity and responses to T-cell mitogens, phytohemagglutinin and concanavalin A, and the B-cell mitogen, Salmonella typhimurium glycoprotein. Peripheral blood leukocytes (PSU were also assessed for responses to T-cell mitogens. Sections from spleen, femur (including bone marrow), thymus,...
- Published
- 1990
9. Modulation of pulmonary inflammatory responses and antimicrobial defenses in mice exposed to diesel exhaust
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Q. T. Krantz, M. Ian Gilmour, Mary J. Daniels, Kymberly M. Gowdy, Ilona Jaspers, and William P. Linak
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Time Factors ,Neutrophils ,Inflammation ,Lung injury ,Toxicology ,Mice ,Immune system ,Occupational Exposure ,medicine ,Animals ,Uteroglobin ,Respiratory system ,Lung ,Respiratory Tract Infections ,Vehicle Emissions ,Pharmacology ,Air Pollutants ,Mice, Inbred BALB C ,Pulmonary Surfactant-Associated Protein A ,Chemistry ,Surfactant protein D ,Pneumonia ,Intercellular Adhesion Molecule-1 ,Pulmonary Surfactant-Associated Protein D ,Surfactant protein A ,Up-Regulation ,Immunology ,Toxicity ,Cytokines ,Tumor necrosis factor alpha ,Female ,medicine.symptom - Abstract
Diesel exhaust (DE) is a major component of urban air pollution and has been shown to increase the severity of infectious and allergic lung disease. The purpose of this study was to evaluate the effects of DE exposure on pulmonary inflammation, mediator production and antimicrobial defenses in an exposure model that had previously been shown to increase susceptibility to influenza. BALB/c mice were exposed to filtered air, or to DE diluted to yield 0.5 or 2 mg/m(3) of diesel exhaust particles (DEP) for 4 h per day for 1 or 5 days. Immediately and 18 h after one or five diesel exposures mice were euthanized to assess both immediate and delayed effects. DE exposure for 5 days at either concentration caused higher neutrophil numbers and lesion scoring compared to air controls. Intracellular adhesion molecule-1 (ICAM-1), which recruits inflammatory cells and is an entry site for rhinoviruses was increased immediately after 1 or 5 days of DE exposure. Several inflammatory and immune cytokines (TNF-alpha, MIP-2, IL-6, IFN-gamma, and IL-13) were also upregulated at various time points and concentrations. In contrast, clara cell secretory protein (CCSP), surfactant protein A (SP-A), and surfactant protein D (SP-D) which are important host defense molecules, were significantly decreased at both the message and protein level with DE exposure. We conclude that exposure to moderate and high occupational levels of DE caused an increase in lung injury and inflammation, and a decrease in host defense molecules, which could result in increased susceptibility to respiratory pathogens.
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- 2007
10. Comparative toxicity of size-fractionated airborne particulate matter obtained from different cities in the United States
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Rachelle M. Duvall, Terry Gordon, Elizabeth Boykin, Robert B. Devlin, Lisa A. Dailey, Seung-Hyun Cho, Donald L. Doerfler, M. Ian Gilmour, John K. McGee, and Mary J. Daniels
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Health, Toxicology and Mutagenesis ,Air pollution ,Toxicology ,medicine.disease_cause ,Salt lake ,chemistry.chemical_compound ,Mice ,Animal science ,medicine ,Animals ,Sulfate ,Cities ,Particle Size ,Air Pollutants ,Mice, Inbred BALB C ,medicine.diagnostic_test ,Chemistry ,Size fractionated ,Particulates ,United States ,Bronchoalveolar lavage ,Toxicity ,Female ,Particulate Matter ,Particle size ,Bronchoalveolar Lavage Fluid ,Biomarkers ,Environmental Monitoring - Abstract
Hundreds of epidemiological studies have shown that exposure to ambient particulate matter (PM) is associated with dose-dependent increases in morbidity and mortality. While early reports focused on PM less than 10 microm (PM10), numerous studies have since shown that the effects can occur with PM stratified into ultrafine (UF), fine (FI), and coarse (CO) size modes despite the fact that these materials differ significantly in both evolution and chemistry. Furthermore the chemical makeup of these different size fractions can vary tremendously depending on location, meteorology, and source profile. For this reason, high-volume three-stage particle impactors with the capacity to collect UF, FI, and CO particles were deployed to four different locations in the United States (Seattle, WA; Salt Lake City, UT; Sterling Forest and South Bronx, NY), and weekly samples were collected for 1 mo in each place. The particles were extracted, assayed for a standardized battery of chemical components, and instilled into mouse lungs (female BALB/c) at doses of 25 and 100 microg. Eighteen hours later animals were euthanized and parameters of injury and inflammation were monitored in the bronchoalveolar lavage fluid and plasma. Of the four locations, the South Bronx coarse fraction was the most potent sample in both pulmonary and systemic biomarkers, with a strong increase in lung inflammatory cells as well as elevated levels of creatine kinase in the plasma. These effects did not correlate with lipopolysaccharide (LPS) or total zinc or sulfate content, but were associated with total iron. Receptor source modeling on the PM2.5 samples showed that the South Bronx sample was heavily influenced by emissions from coal fired power plants (31%) and mobile sources (22%). Further studies will assess how source profiles correlate with the observed effects for all locations and size fractions.
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- 2007
11. Murine pulmonary inflammatory responses following instillation of size-fractionated ambient particulate matter
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Mary J. Daniels, Paul Evansky, M. Ian Gilmour, Colin A J Dick, Pramila Singh, and Susanne Becker
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Health, Toxicology and Mutagenesis ,Toxicology ,medicine.disease_cause ,chemistry.chemical_compound ,Mice ,Lactate dehydrogenase ,Ultrafine particle ,medicine ,Animals ,Particle Size ,Lung ,Cardiopulmonary disease ,Air Pollutants ,Pneumonia ,Particulates ,Molecular biology ,Oxidative Stress ,chemistry ,Neutrophil Infiltration ,Immunology ,Toxicity ,Particle ,Cytokines ,Female ,Particle size ,Oxidative stress - Abstract
The mechanisms for increased cardiopulmonary disease in individuals exposed to particulate air pollution are associated with fine and ultrafine particles that have a high oxidative potential. Particulate matter (PM) from Research Triangle Park (NC) was collected and separated into 3 different size fractions: coarse (CO;3.5 microm), fine (FI; 1.7-3.5 microm), and fine/ultrafine (FU;1.7 microm) using impaction and electrostatic precipitation. Particle chemistry indicated the presence of sulfates, zinc, iron, and copper in all fractions. CD1 mice were intratracheally instilled with 10, 50, or 100 microg of each fraction. After 18 h, the lungs were lavaged and assayed for signs of inflammation. All particles produced increases in neutrophil number, and this was highest in the high-dose FU group. Biochemical analysis revealed ni change in lactate dehydrogenase (LDH) activity, and increased albumin and tumor necrosis factor (TNF)-alpha levels were only seen with the high-dose FI particles. Interleukin 6 (IL-6) levels were increased over control levels after treatment with 100 microg of all 3 particle sizes. To determine whether oxidative stress may contribute to these effects, antioxidant levels in the ling were boosted by an intraperitoneal (ip) injection with dimethylthiourea (DMTU). This treatment resulted in a twofold increase in the total antioxidant capacity of the lung and decreased the PM-induced cytokine and neutrophil influx up to 50%. The data indicate that on the equal mass basis, ambient particles of these three size ranges produce pulmonary inflammation, and that increasing the antioxidant capacity of the lung reduces particle-induced cytokine and cellular responses.
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- 2003
12. Kinetic profile of influenza virus infection in three rat strains
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Mary J, Daniels, MaryJane K, Selgrade, Donald, Doerfler, and M Ian, Gilmour
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L-Lactate Dehydrogenase ,Neutrophils ,Proteins ,Cell Count ,Pulmonary Edema ,Rats, Inbred Strains ,Rats ,Rodent Diseases ,Disease Models, Animal ,Orthomyxoviridae Infections ,Species Specificity ,Influenza A virus ,Macrophages, Alveolar ,Animals ,Cytokines ,Female ,Genetic Predisposition to Disease ,Bronchoalveolar Lavage Fluid ,Lung - Abstract
Influenza is a respiratory tract disease of viral origin that can cause major epidemics in humans. The influenza virus infects and damages epithelial cells of the respiratory tract and causes pneumonia. Lung lesions of mice infected with influenza virus resembles those seen in humans with influenza, and can result in severe and even fatal pneumonia. In contrast, experimental infection of rats with the virus induces a milder form of the disease, with no mortality. The purpose of the study reported here was to determine the time course of influenza infection and lung injury in Brown Norway (BN), Fischer-344 (F344), and Sprague-Dawley (SD) rats to ascertain whether genetic background impacts susceptibility to infection and host responses. Rats of each strain were inoculated intranasally with 10,000 plaque-forming units of rat-adapted influenza virus (RAIV), and lungs were assessed at postinoculation hour (PIH) 2, 24, 48, 72, and 144 for viral titer, inflammatory cells, pro-inflammatory cytokines, and biochemical indicators of lung edema (protein) and injury (lactate dehydrogenase [LD] activity). Virus titer peaked at PIH 24, and was 100-fold higher in the F344 and SD, compared with the BN strain. Alveolar macrophages, LD activity, and total protein concentration were higher in the BN rats, whereas neutrophil numbers and interleukin 6 and tumor necrosis factor-alpha activities were greatest in the bronchoalveolar lavage fluid of F344 and SD rats. The results indicate that F344 and SD rats respond in similar manner to viral infection, whereas viral replication was more limited in BN rats and was associated with a different profile of pulmonary cells.
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- 2003
13. Mortality in dioxin-exposed mice infected with influenza: mitochondrial toxicity (reye's-like syndrome) versus enhanced inflammation as the mode of action
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Lisa R. Bishop, Robert W. Luebke, Carey B. Copeland, Mary J. Daniels, and M. Ian Gilmour
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Blood Glucose ,Polychlorinated Dibenzodioxins ,medicine.medical_treatment ,Physiology ,Inflammation ,Biology ,Toxicology ,Virus ,Mice ,Orthomyxoviridae Infections ,medicine ,Animals ,Aspartate Aminotransferases ,Lung ,medicine.diagnostic_test ,Reye Syndrome ,Body Weight ,Antibody titer ,Alanine Transaminase ,Organ Size ,medicine.disease ,Titer ,Mitochondrial toxicity ,Bronchoalveolar lavage ,Cytokine ,Influenza A virus ,Immunology ,Environmental Pollutants ,Female ,medicine.symptom ,Viral load ,Bronchoalveolar Lavage Fluid - Abstract
Increased mortality following influenza A infection was reported in B6C3F1 mice exposed to a low (0.01 micro g/kg) dose of dioxin. However, mortality was not associated with increased viral load and antibody titers to the virus were not decreased at doses of TCDD < or = 10 micro g/kg, suggesting that viral overgrowth, secondary to immunosuppression, was not the proximate cause of death. We tested the hypothesis that mitochondrial toxicity and dysfunction, similar to Reye's syndrome (RS) in humans, is responsible for increased mortality in dioxin-exposed, infected B6C3F1 female mice, based on similarities in the biochemical and immunological events that occur in RS and in TCDD-exposed animals. Endpoints were also included to test the hypothesis that increased pulmonary inflammation following dioxin exposure, in the absence of mitochondrial toxicity, was associated with increased mortality. Dose-related effects of TCDD alone, infection with influenza A alone, and combined TCDD exposure/influenza infection were evaluated. Mice were given a single ip injection of 0, 0.001, 0.01, 0.1, or 1.0 micro g TCDD/kg, 7 days before infection by intranasal instillation of an estimated LD(10-20) of influenza A Hong Kong/8/68 (H3N2) and were terminated 1, 7, and 10 days after infection. Serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected for various measurements, including clinical chemistries, cell counts, cytokine analysis, and viral titers. Exposure to < or = 1.0 micro g TCDD/kg did not increase mortality; virus titers were similar at all doses of TCDD and there was no dioxin-related effect on serum NH(3) or glucose concentrations, two prominent indicators of the altered mitochondrial oxidative metabolism typically observed in RS. A study was therefore conducted over a wider range of TCDD doses. A single injection of 0, 0.025, 0.5, or 10 micro g TCDD/kg preceded infection by 7 days; subgroups of noninfected control and highest dose group (10 micro g TCDD/kg) mice were also evaluated for biochemical and immunological endpoints on the equivalent of infection day 4 to provide baseline data. Five days after infection the same endpoints described above were evaluated. The 10 micro g TCDD/kg dose increased mortality, but once again did not increase virus titer; as in previous experiments, serum biochemistry endpoints did not support mitochondrial dysfunction. These results suggest that RS is an unlikely explanation for increased influenza mortality in TCDD-exposed mice. Rather, constituents in BALF implicate increased pulmonary inflammation as the mode of TCDD action.
- Published
- 2002
14. Proinflammatory and Th1 cytokine alterations following ultraviolet radiation enhancement of disease due to influenza infection in mice
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Mary J. Daniels, Lisa R. Copeland, MaryJane K. Selgrade, Elisabeth R. Costa, and Lisa K. Ryan
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Ultraviolet Rays ,medicine.medical_treatment ,Orthomyxoviridae ,Longevity ,Toxicology ,Virus ,Proinflammatory cytokine ,Immunocompromised Host ,Mice ,Immune system ,Th2 Cells ,Orthomyxoviridae Infections ,Immunity ,Interferon ,medicine ,Animals ,Lung ,Mice, Inbred BALB C ,integumentary system ,medicine.diagnostic_test ,biology ,Monokines ,Th1 Cells ,biology.organism_classification ,Specific Pathogen-Free Organisms ,Bronchoalveolar lavage ,Cytokine ,Influenza A virus ,Immunology ,Female ,Bronchoalveolar Lavage Fluid ,medicine.drug - Abstract
Exposure of rodents to immunosuppressive agents such as ozone, dioxin, or ultraviolet radiation (UVR) leads to increased morbidity and mortality following influenza virus infection. However, these adverse effects are not related to the suppression of virus-specific immune responses. Our laboratory showed that UVR increased the morbidity, mortality, and pathogenesis of influenza virus without affecting protective immunity to the virus, as measured by resistance to reinfection, suggesting that UVR and other immunosuppressive pollutants such as dioxin and ozone may exacerbate early responses that contribute to the pathogenesis of a primary viral infection. In the present study, we examined the mechanism of UVR-enhanced mortality in the absence of effects on virus-specific immunity and tested the hypothesis that modulation of cytokine levels was associated with increased deaths and body weight loss. BALB/c mice were exposed to 8.2 kJ/m(2) UVR and were infected 3 days later with a sublethal influenza virus infection (LD(40) of mouse-adapted Hong Kong influenza A/68, H(3)N(2)). Influx of inflammatory cells, proinflammatory cytokines, and cytokines produced by T-helper lymphocytes (Th1 and Th2) were measured in lung homogenates (LH) as well as in bronchoalveolar lavage fluid (BAL). UVR preexposure decreased the influenza-induced lymphocytic influx 5 days after infection, but did not alter macrophage and neutrophil influx into the lung, or increase virus titers significantly. Although interferon (IFN)-gamma, total interleukin (IL)-12, IL-6, and TNF-alpha were altered in mice that received UVR exposure prior to infection, no clear association was made that correlated with the UVR-induced increase in body weight loss and mortality due to influenza infection.
- Published
- 2002
15. Suppression of allergic immune responses to house dust mite (HDM) in rats exposed to 2,3,7,8-TCDD
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M. Ian Gilmour, Mary J. Daniels, Carey B. Copeland, Robert W. Luebke, and Amy L. Lambert
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medicine.medical_specialty ,Polychlorinated Dibenzodioxins ,Lymphocyte ,Bronchoconstriction ,Spleen ,Lung injury ,Toxicology ,Immunoglobulin E ,medicine.disease_cause ,Lymphocyte Activation ,Immunocompromised Host ,Internal medicine ,Rats, Inbred BN ,medicine ,Concanavalin A ,Intubation, Intratracheal ,Respiratory Hypersensitivity ,Animals ,RNA, Messenger ,Sensitization ,House dust mite ,Mites ,medicine.diagnostic_test ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Dust ,Allergens ,biology.organism_classification ,Rats ,Bronchoalveolar lavage ,Endocrinology ,medicine.anatomical_structure ,Immunoglobulin G ,Immunology ,Allergic response ,biology.protein ,Female ,Lymph Nodes ,Bronchoalveolar Lavage Fluid - Abstract
Exposure to various xenobiotics, including oxidant gases, diesel exhaust, and certain pesticides, has been reported to exacerbate pulmonary allergic hypersensitivity responses. Increased lymphocyte proliferative responses to parasite antigens or increased antibody responses to sheep erythrocyte have also been reported in rats exposed to TCDD before infection or immunization. As a result, these studies were conducted to test the hypothesis that TCDD exposure exacerbates the allergic response to house dust mite antigen. Brown Norway rats were injected, ip, with 0, 1, 10, or 30 microg TCDD/kg 7 days before intratracheal (it) sensitization to semipurified house dust mite allergen (HDM). Fourteen days later, rats were challenged with HDM and immediate bronchospasm was measured. At this time point, plus 2 and 7 days later, inflammatory cells in bronchoalveolar lavage fluid (BALF), HDM-specific IgE levels in serum, and HDM-driven cell proliferation in bronchial lymph nodes and spleen were evaluated. TCDD exposure decreased both immediate bronchoconstriction and specific IgE synthesis after the HDM challenge; 7 days later, HDM-specific IgE responses remained suppressed. Total serum IgE levels were similar in all groups. HDM challenge alone significantly increased cellular and biochemical indicators of lung injury, both of which were suppressed by TCDD exposure. The proliferative response of lymph node cells, but not of spleen cells, to HDM was also suppressed at the highest TCDD dose, although the splenic response to Concanavalin A was elevated. It appears that early events in the response to HDM are affected by TCDD exposure, since message for IL5 was dramatically reduced 2 days after sensitization, but not after challenge. We therefore conclude that TCDD exposure suppressed, rather than enhanced the development of allergic immune responses and the expression of immune-mediated lung disease.
- Published
- 2001
16. Morphine reduces pulmonary inflammation in response to influenza infection
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Mary J. Daniels, Mary E. Coussons-Read, and M.I. Gilmour
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Male ,Pneumonia, Viral ,Anti-Inflammatory Agents ,Inflammation ,medicine.disease_cause ,Placebo ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Orthomyxoviridae Infections ,medicine ,Influenza A virus ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Lung ,L-Lactate Dehydrogenase ,Morphine ,business.industry ,Pulmonary inflammation ,Proteins ,General Medicine ,medicine.disease ,Rats ,Pneumonia ,Rats, Inbred Lew ,Immunology ,Nasal administration ,medicine.symptom ,business ,Bronchoalveolar Lavage Fluid ,medicine.drug - Abstract
The present study shows that morphine reduces the pulmonary inflammatory response to intranasal influenza virus infection in rats. Rats were infected with rat-adapted influenza virus (RAIV), which is a unique infectious agent because normal rats develop an acute pulmonary inflammatory response to RAIV and rapidly clear the virus within a few days with no mortality. Male Lewis rats were implanted with 75 mg morphine pellets or placebo pellets 72 hours prior to intranasal RAIV infection. Rats were euthanized at 2, 24, 48, 72, and 96 hours after infection. Assessment of inflammation included accumulation of inflammatory cells in the lungs, lung weight, and protein and LDH content of bronchial alveolar lavage fluid (BALF). Placebo-treated rats showed a marked inflammatory response to RAIV infection, and morphine-treated rats mounted less vigorous inflammatory responses to the infection. Taken together, these data suggest that morphine treatment impairs the inflammatory response to RAIV infection in the lungs, which is consistent with prior work demonstrating that morphine is a potent anti-inflammatory agent in other areas of the body.
- Published
- 1999
17. Morphine Alters the Immune Response to Influenza Virus Infection in Lewis Rats
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Mary E. Coussons-Read, Mary J. Daniels, and M.I. Gilmour
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education.field_of_study ,Cellular immunity ,Lipopolysaccharide ,business.industry ,Population ,Virus ,In vitro ,Pathogenesis ,chemistry.chemical_compound ,Immune system ,chemistry ,Immunology ,Morphine ,medicine ,education ,business ,medicine.drug - Abstract
It has been well-documented that administration of opioids can alter immune function in vitro. Initial studies of chronic heroin users demonstrated that this population has decreased mitogenic responsiveness of blood lymphocytes to lipopolysaccharide, poke- weed mitogen, and concanavalin-A, suggesting an impairment of cellular immunity (1). Subsequent studies have shown that chronic heroin users also exhibit diminished T-cell E-rosetting (2), reductions in the total number of T-cells present in the peripheral blood (3), and decreases in the number of T-helper cells in the blood (4). Taken together, these studies demonstrate that chronic heroin use can alter immune function, and may thereby affect disease susceptibility and pathogenesis.
- Published
- 1998
18. Enhanced mortality and liver damage in virus-infected mice exposed to p-xylene
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Mary J. Daniels, Richard H. Jaskot, John W. Allis, Barbara L. Robinson, and MaryJane K. Selgrade
- Subjects
Ratón ,Cytomegalovirus ,Mice, Inbred Strains ,Biology ,Xylenes ,Toxicology ,medicine.disease_cause ,Isozyme ,Herpesviridae ,Virus ,Andrology ,chemistry.chemical_compound ,Mice ,Immune system ,Cytochrome P-450 Enzyme System ,Lactate dehydrogenase ,medicine ,Animals ,Analysis of Variance ,Mice, Inbred C3H ,Liver Diseases ,Body Weight ,Environmental Exposure ,Pollution ,Killer Cells, Natural ,Blood ,chemistry ,Liver ,Immunology ,Toxicity ,Cytomegalovirus Infections ,Female ,Liver function - Abstract
This study assessed effects of exposure to p-xylene, a ubiquitous air pollutant, on mice infected with murine cytomegalovirus (MCMV), a mouse model for a common human virus. It was postulated that adverse health effects could occur as a result of (1) enhanced infection due to xylene-induced immune suppression, (2) increased p-xylene toxicity due to viral suppression of cytochrome P-450 (P-450), and/or (3) additive or synergistic effects on liver function due to tissue injury by both p-xylene and MCMV. Mice were exposed to filtered air, 600 or 1200 ppm p-xylene 6 h/d for 4 d and infected with a sublethal dose of MCMV after the first exposure. No deaths occurred among uninfected, p-xylene-exposed mice or infected, air-exposed mice; 34% and 0% mortality occurred respectively in infected mice exposed to 1200 and 600 ppm p-xylene. Virus titers in the liver and splenic natural killer cell activity were unaffected by exposure to 1200 ppm p-xylene. Small but significant increases in serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase activities, indicators of liver damage, were observed at 4 d postinfection. p-Xylene exposure had no effect on these serum enzyme activities in uninfected mice, but 1200 ppm potentiated this effect in infected mice. MCMV significantly suppressed and p-xylene significantly increased total P-450 levels in the liver, but there was no significant interaction between the two. Isozymes 1A1, 2B1/B2, and 2E1 were decreased to a similar degree, suggesting that the virus does not target specific isozymes. Enhanced mortality was not due to immune suppression. While p-xylene potentiated liver damage was caused by the virus, the magnitude of serum enzyme activities indicates that this damage was not a likely cause of death. The cause of deaths is unclear, results were consistent with the hypothesis that enhanced mortality was related to enhanced xylene toxicity due to suppression of P-450, although additive or synergistic damage to tissues other than liver cannot be ruled out.
- Published
- 1993
19. Correlation between chemical suppression of natural killer cell activity in mice and susceptibility to cytomegalovirus: rationale for applying murine cytomegalovirus as a host resistance model and for interpreting immunotoxicity testing in terms of risk of disease
- Author
-
M K Selgrade, J H Dean, and Mary J. Daniels
- Subjects
Polychlorinated Dibenzodioxins ,Chemical compound ,Ratón ,9,10-Dimethyl-1,2-benzanthracene ,Congenital cytomegalovirus infection ,G(M1) Ganglioside ,Toxicology ,medicine.disease_cause ,Herpesviridae ,Natural killer cell ,chemistry.chemical_compound ,Mice ,Cadmium Chloride ,Chlorides ,Immunity ,Betaherpesvirinae ,Nickel ,medicine ,Benzo(a)pyrene ,Animals ,Cyclophosphamide ,Cells, Cultured ,Immunity, Cellular ,Mice, Inbred C3H ,biology ,medicine.disease ,biology.organism_classification ,Pollution ,Specific Pathogen-Free Organisms ,Killer Cells, Natural ,medicine.anatomical_structure ,chemistry ,Toxicity ,Immunology ,Cytomegalovirus Infections ,Cyclosporine ,Tetradecanoylphorbol Acetate ,Female ,Disease Susceptibility ,Immunosuppressive Agents ,Cadmium - Abstract
The purpose of this study was to determine the relationship between chemical suppression of natural killer (NK) cell activity in mice and chemical effects on susceptibility to murine cytomegalovirus (MCMV) infection. The goal was to provide a rational basis for applying MCMV as a host resistance model for immunotoxicity testing and to provide risk assessors some guidance in relating suppression of NK cell activity to enhanced risk of disease. Data from studies with eight chemicals administered in various doses and by various routes were evaluated, and a significant correlation was observed between chemical suppression of virus-augmented NK cell activity and increased mortality due to MCMV infection. In contrast, effects of the same chemical treatments on spontaneous NK cell activity (i.e., basal activity in uninfected mice) did not correlate with effects of these chemicals on mortality due to MCMV. Although chemicals that suppressed spontaneous NK cell activity enhanced infection, the converse was not always true--that is, increased susceptibility to infection and suppression of virus-augmented NK cell activity were observed on three occasions when spontaneous NK cell activity was unaffected. This latter phenomenon plus the fact that for two chemicals spontaneous NK was suppressed at concentrations twofold below that which affected mortality appear to account for the poor statistical correlation. Nevertheless, the data indicate that MCMV is a useful host resistance model to be applied in immunotoxicity testing when suppression of NK cell activity has been demonstrated. However, virus-augmented activity may be a better indicator than spontaneous activity. The data also indicated that suppression of NK cell activity is predictive of increased susceptibility to infection and hence provides qualitative guidance (hazard identification) to risk assessors.
- Published
- 1992
20. Exposure to Ultraviolet Radiation Enhances Mortality and Pathology Associated with Influenza Virus Infection in Mice¶
- Author
-
Lisa R. Bishop, M. Ian Gilmour, Mary J. Daniels, Donna L. Neldon, Lisa K. Ryan, MaryJane K. Selgrade, and Denise M. Sailstad
- Subjects
Incidence (epidemiology) ,Lethal dose ,Bacterial pneumonia ,Balanced salt solution ,General Medicine ,Biology ,medicine.disease ,Biochemistry ,Virus ,Immune system ,Immunology ,medicine ,Nasal administration ,Physical and Theoretical Chemistry ,Ultraviolet radiation - Abstract
Ultraviolet radiation (UVR) causes systemic immune suppression, decreasing the delayed type and contact hypersensitivity responses in animals and humans and enhancing certain mycobacterial, parasitic and viral infections in mice. This study tests the hypothesis that prior exposure to UVR enhances influenza infections in mice. BALB/c female mice were exposed to 0–8.2 kJ/m2 of UVR. Exposed and unexposed mice were infected intranasally three days later with 150–300 plaque-forming units/mouse (lethal dose (LD)20–LD40) of mouse-adapted Hong Kong Influenza A/68 (H3N2) virus or sham infected with 50 μL Hanks' balanced salt solution/mouse. Mortality from viral infection ranged from 25–50%. UVR exposure increased virus-associated mortality in a dose-dependent manner (up to a two-fold increase at 8.2 kJ/m2). The increased mortality was not associated with bacterial pneumonia. The highest dose of UVR also accelerated the body weight loss and increased the severity and incidence of thymic atrophy associated ...
- Published
- 2000
21. Effects of NiCI2 and CdCI2 on Susceptibility to Murine Cytomegalovirus and Virus-Augmented Natural Killer Cell and Interferon Responses
- Author
-
MARY J. DANIELS, MARGARET G. Ménache, GARY R. BURLESON, JUDITH A. GRAHAM, and MARYJANE K. SELGRADE
- Subjects
Toxicology - Published
- 1987
22. Inhalation studies of Mt. St. Helens volcanic ash in animals
- Author
-
Margaret A. Grady, Joseph W. Illing, Mary J. Daniels, Elaine C. Grose, MaryJane K. Selgrade, and Gary E. Hatch
- Subjects
Inhalation exposure ,Lung ,Inhalation ,Phagocytosis ,technology, industry, and agriculture ,respiratory system ,Biology ,musculoskeletal system ,complex mixtures ,Biochemistry ,Andrology ,medicine.anatomical_structure ,Toxicity ,Immunology ,Alveolar macrophage ,medicine ,Respiratory system ,General Environmental Science ,Volcanic ash - Abstract
The effects of inhalation exposure of mice or rats to 9.4 mg/m3 volcanic ash, 2.5 mg/m3 SO2, or both on host defense mechanisms were assessed. Cytologic changes in pulmonary lavage fluid included an increase in percentage polymorphonuclear leukocytes due to SO2 exposure and an increase in eosinophils due to ash. SO2 and ash also produced decreases in percentage alveolar macrophages. In the case of ash-exposed animals, this decrease was offset by an increase in lymphocytes. Total cell counts and viability were not affected by any of the exposures. Pulmonary clearance mechanisms were affected in that there were both decreased alveolar macrophage phagocytic capability following ash and ash + SO2 exposures and depressed ciliary beat frequency attributable to ash exposure. None of the inhalation exposures caused increases in susceptibility to an immediate or 24 hr postexposure aerosol challenge with Streptococcus. However, intratracheal instillation of both fine- and coarse-mode volcanic ash caused slight but significant increases in mortality due to bacterial challenge 24 hr after the instillation. The phytohemagglutinin-induced blastogenic response of splenic lymphocytes from exposed animals did not differ significantly from that of control lymphocytes, although the lipopolysaccharide-induced blastogenic response was enhanced. Ash exposure had no effect on susceptibility to murine cytomegalovirus. In summary, volcanic ash alone or in combination with SO2 had only minimal effects on certain host defense mechanisms.
- Published
- 1985
23. Effect of nickel chloride on primary antibody production in the spleen
- Author
-
Mary J. Daniels, Frederick J. Miller, Donald E. Gardner, Judith A. Graham, and David L. Coffin
- Subjects
inorganic chemicals ,Pathology ,medicine.medical_specialty ,Erythrocytes ,Time Factors ,Health, Toxicology and Mutagenesis ,chemistry.chemical_element ,Spleen ,Hemolytic Plaque Technique ,Chloride ,Microbiology ,Mice ,Nickel ,medicine ,Animals ,Lymphocytes ,Sheep ,biology ,Public Health, Environmental and Occupational Health ,Organ Size ,Primary and secondary antibodies ,medicine.anatomical_structure ,chemistry ,Depression, Chemical ,Antibody Formation ,biology.protein ,Female ,Antibody formation ,medicine.drug ,Research Article - Abstract
Mice immunized intraperitoneally with sheep erythrocytes were treated with nickel chloride, a common particulate air pollutant. Primary antibody production in the spleen was examined using a hemolytic plaque technique. A negative linear dose-response relationship (p is less than 0.05) was observed between the logarithm of (plaques/10(6) cells) and the nickel concentration administered. Mice injected with 3.09 mug Ni2+/g body weight displayed lymphocyte function similar to that of control mice. However, injection of 9.26-12.34 mug Ni2+/g caused significant immunosupression (p is less than 0.05).
- Published
- 1975
24. Influence of cadmium, nickel, and chromium on primary immunity in mice
- Author
-
Judith A. Graham, E.A. Payne, Donald E. Gardner, Frederick J. Miller, and Mary J. Daniels
- Subjects
Chromium ,Time Factors ,Inorganic chemistry ,chemistry.chemical_element ,Spleen ,Injections, Intramuscular ,Biochemistry ,Mice ,Immune system ,Nickel ,medicine ,Animals ,Lung ,General Environmental Science ,Cadmium ,Dose-Response Relationship, Drug ,Inhalation ,biology ,Hydrogen-Ion Concentration ,Molecular biology ,medicine.anatomical_structure ,Solubility ,chemistry ,Metals ,Antibody Formation ,Toxicity ,biology.protein ,Environmental Pollutants ,Female ,Antibody ,Intramuscular injection - Abstract
The effects of metals on the primary humoral immune system of mice were investigated using a hemolytic plaque technique to determine the number of specific antibody-producing spleen cells. Inhalation of NiCl/sub 2/ for 2 hr resulted in a significant negative linear dose response, the lowest effective concentration tested being 250 ..mu..g of Ni/m/sup 3/. Following a 2 hr aerosol exposure to NiCl/sub 2/, the lung cleared Ni on a first-order kinetics basis. A significant reduction in the number of plaques per 10/sup 6/ cells also was observed with exposure to 190 ..mu..g of Cd/m/sup 3/. Analyses of the data from intramuscularly exposed mice indicated that concentrations greater than or equal to 3.90 ..mu..g of Ni/g body weight (as NiSO/sub 4/) and greater than or equal to 9.25 ..mu..g of Ni/g body weight (as NiCl/sub 2/) resulted in significant immunosuppression. Intramuscular treatments with NiO, CdCl/sub 2/, and CrCl/sub 3/ had no effect at the concentrations tested.
- Published
- 1978
25. Effects of NiCl2 and CdCl2 on susceptibility to murine cytomegalovirus and virus-augmented natural killer cell and interferon responses*1
- Author
-
Mary J. Daniels, Judith A. Graham, Gary R. Burleson, MaryJane K. Selgrade, and Margaret G. Ménache
- Subjects
Ratón ,Congenital cytomegalovirus infection ,Cadmium chloride ,Biology ,Toxicology ,medicine.disease ,medicine.disease_cause ,Virus ,Herpesviridae ,Natural killer cell ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Interferon ,Toxicity ,Immunology ,medicine ,medicine.drug - Abstract
Female C3HHeJ or CD-1 mice were infected with a sublethal dose of murine cytomegalovirus (MCMV) and then exposed to nickel chloride (NiCl2) or cadmium chloride (CdCl2) intramuscularly (im) or by inhalation. Effects of these treatments on disease susceptibility, virus-augmented and spontaneous natural killer (NK) cell activity, and virus induction of interferon (IFN) were determined. NiCl2 (20 mg/kg, im) enhanced mortality due to MCMV in both mouse strains, and a reduction in virus-augmented NK cell activity was seen at doses as low as 10 mg NiCl2/kg im. At 6.25 mg CdCl2/kg im there was a significant depression of NK cell activity, but there was no effect on mortality due to infection. Effects on NK activity did not appear to be due to effects on IFN production since neither of the metal treatments caused depression of this response. Neither metal when given by inhalation had any effect on these parameters.
- Published
- 1987
26. Effects of Phosgene Exposure on Bacterial, Viral, and Neoplastic Lung Disease Susceptibility in Mice
- Author
-
Mary J. Daniels, Judith A. Graham, Joseph W. Illing, Diane M. Starnes, and MaryJane K. Selgrade
- Subjects
Lung ,biology ,Inhalation ,Chemistry ,Streptococcus ,Health, Toxicology and Mutagenesis ,Cell ,Toxicology ,biology.organism_classification ,medicine.disease_cause ,Microbiology ,chemistry.chemical_compound ,medicine.anatomical_structure ,Lung disease ,Immunology ,medicine ,Alveolar macrophage ,Phosgene ,Bacteria - Abstract
In this study the effects of phosgene inhalation on host resistance models representative of bacterial, viral, and neoplastic lung diseases were assessed. A single Ch exposure to concentrations of phosgene of 0.025 ppm and above significantly enhanced mortality due to laboratory-induced aerosol infection with Streptococcus zooepidimi-cus (group C). Bacteria recovered from lavage fluid of mice exposed to 0.05 ppm for 4 h increased dramatically between 3 and 48 h post infection, while bacteria recovered from lavage fluid of air exposed mice declined to nearly undetectable levels over the same time period. Concentrations of phosgene 10-fold higher than the lowest observable effect concentration for streptococcus susceptibility had little or no effect on alveolar macrophage phagocytic activity and little or no effect on total cells recovered, viability, or differential cell counts in lavage fluid obtained shortly after exposure. A single 4-h exposure to as little as 0.025 ppm phosgene also caused a si...
- Published
- 1989
27. Comparison of the pathogenesis of murine cytomegalovirus in lung and liver following intraperitoneal or intratracheal infection
- Author
-
Judith A. Graham, Laura Saxton, MaryJane K. Selgrade, Albert M. Collier, and Mary J. Daniels
- Subjects
Human cytomegalovirus ,Lung Diseases ,Congenital cytomegalovirus infection ,Cytomegalovirus ,Biology ,Viral infection ,Virus ,Pathogenesis ,Mice ,Virology ,medicine ,Animals ,Lung ,Peritoneal Cavity ,Inoculation ,Liver Diseases ,medicine.disease ,Trachea ,medicine.anatomical_structure ,Liver ,Immunology ,Cytomegalovirus Infections ,Female ,Liver function - Abstract
SUMMARY This study compares the pathogenesis of murine cytomegalovirus (MCMV) infections following intraperitoneal (i.p.) and intratracheal (i.t.) inoculation. No deaths were seen in mice given 106 p.f.u. MCMV i.t., whereas 52% mortality occurred among animals given this dose i.p. This difference in mortality was not due to different effects on the lung, since virus titres in this organ on progressive days post-infection were similar for the two routes of inoculation and similar, minor histopathological changes were observed. In contrast, virus titres in the livers of mice inoculated i.p. were 100-fold higher than for those inoculated i.t., and histopathological changes were noticeably greater in the i.p. group. This suggests that the mortality seen following i.p. inoculation may have been due, at least in part, to effects of viral infection on liver function. Parallels between various forms of human cytomegalovirus infections and the types of infections seen following i.t. and i.p. infection with MCMV were observed.
- Published
- 1984
28. Increased susceptibility to parathion poisoning following murine cytomegalovirus infection
- Author
-
Mary J. Daniels, Joseph W. Illing, Judith A. Graham, Elaine G. Charlet, Ann L. Ralston, Margaret A. Grady, and MaryJane K. Selgrade
- Subjects
Pentobarbital ,Cytochrome ,Congenital cytomegalovirus infection ,Biology ,Toxicology ,Virus ,Microbiology ,chemistry.chemical_compound ,Mice ,Cytochrome P-450 Enzyme System ,medicine ,Parathion poisoning ,Animals ,Pharmacology ,Analysis of Variance ,Liver infection ,Parathion ,medicine.disease ,Cytomegalovirus infection ,chemistry ,Liver ,Immunology ,Cytomegalovirus Infections ,biology.protein ,Female ,medicine.drug - Abstract
In mice treated with ordinarily sublethal doses of parathion 2 to 5 days postinfection with murine cytomegalovirus (MCMV) 50 to 100% mortality was observed. These mortalities appeared to be due to a decrease in the ability of infected mice to detoxify parathion. Pentobarbital-induced sleeping time was also enhanced 3 and 6 days postinfection and cytochrome P-450 concentrations were markedly depressed in mice tested 3 days after infection. MCMV-induced effects on sensitivity to parathion and pentobarbital did not appear to be directly attributable to liver infection since concentrations of virus in the liver persisted at maximum concentrations well beyond the time when sensitivity to these compounds returned to normal. The time frame during which enhanced sensitivity to parathion and pentobarbital was observed suggests that this sensitivity may have been caused by viral-induced interferon-mediated depression of cytochrome P-450.
- Published
- 1984
29. Effects of 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene and cyclosporin A on murine cytomegalovirus infection: studies of resistance mechanisms
- Author
-
Mary J. Daniels, Gary R. Burleson, MaryJane K. Selgrade, Jack H. Dean, and L.D. Lauer
- Subjects
Time Factors ,viruses ,9,10-Dimethyl-1,2-benzanthracene ,Immunology ,DMBA ,Cyclosporins ,Pharmacology ,Biology ,Natural killer cell ,chemistry.chemical_compound ,Mice ,Immune system ,Interferon ,Cyclosporin a ,medicine ,Benzo(a)pyrene ,Animals ,Carcinogen ,7,12-Dimethylbenz[a]anthracene ,Killer Cells, Natural ,medicine.anatomical_structure ,chemistry ,Cytomegalovirus Infections ,Female ,medicine.drug ,T-Lymphocytes, Cytotoxic - Abstract
Susceptibility to murine cytomegalovirus (MCMV) was enhanced by treating B6C3F1 and CD-1 mice subcutaneously with 100 mg 7,12-dimethyl-benz[a]anthracene (DMBA)/kg fractionated over a 2 week period prior to sub-lethal infection. Virus-augmented natural killer cell (NKC) activity was depressed in B6C3F1 mice treated with 100 mg DMBA/kg, while serum interferon (IFN) levels were unaffected. Treatment with 50 mg DMBA/kg had no effect on susceptibility to virus or virus-augmented NKC activity. Susceptibility to MCMV was not affected by treating mice with 400 mg benzo[a]pyrene (B[a]P)/kg using the same exposure regimen. Virus-augmented NKC activity was suppressed in B[a]P-treated mice, but the magnitude of the suppression (18%) was much less than that for DMBA-treated mice (39%). Susceptibility to MCMV, virus-augmented NKC and IFN induction were not affected in mice treated intraperitoneally with 50 mg cyclosporin A (CSA)/kg/day for 5 days and infected on the 5th day of treatment. In contrast, enhanced susceptibility to MCMV and depressed NKC activity were observed in mice treated by the same exposure regimen on days 1-5 post infection. Susceptibility was not affected by CSA given on days 5-9 post infection. The data are useful not only because they show that DMBA and appropriately-timed CSA treatments suppress virus augmented NKC and enhance susceptibility to MCMV, but also because they help to define the relative importance of certain immune responses in defending against the infection, thus improving the usefulness of MCMV as a host resistance model for immunotoxicity testing. The data suggest that chemicals which depress NKC are likely to enhance susceptibility to MCMV, and conversely that effects on NKC should be suspected when chemical exposure enhances susceptibility to MCMV.
- Published
- 1988
30. Protein accumulation in lung lavage fluid following ozone exposure
- Author
-
Gary E. Hatch, Ping C. Hu, Mary J. Daniels, MaryJane K. Selgrade, Frederick J. Miller, Judith A. Graham, and Donald E. Gardner
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Guinea Pigs ,Biology ,Biochemistry ,Lesion ,Andrology ,Ozone ,medicine ,Animals ,Ozone exposure ,Vitamin C deficiency ,Respiratory system ,Therapeutic Irrigation ,Polyacrylamide gel electrophoresis ,Lung ,General Environmental Science ,Dose-Response Relationship, Drug ,Proteins ,Lung Lavage Fluids ,medicine.anatomical_structure ,Ascorbic Acid Deficiency ,Electrophoresis, Polyacrylamide Gel ,medicine.symptom ,Lung lavage - Abstract
Accumulation of protein in lung lavage fluid was used as an indicator of pulmonary damage following exposure of guinea pigs to O 3 . Exposure of animals to 510, 1000, or 1960 μg/m 3 (0.26, 0.51, or 1.0 ppm) of O 3 for 72 hr resulted in significantly elevated levels of lavage fluid protein when compared to that of air controls. This effect was not observed in animals exposed to 196 μg O 3 /m 3 (0.10 ppm). When exposure time was reduced to 3 hr, the O 3 -induced protein accumulation in lavage fluids was undetectable unless the time of lavage was delayed 10–15 hr following the exposure. Under these conditions, elevated protein content was seen in lung lavage fluids obtained from animals exposed to O 3 ranging from 510 to 1470 μg O 3 /m 3 (0.26-0.75 ppm) and a dose relationship between the amount of protein accumulation in the lung and the concentration of O 3 to which the animals were exposed was observed. Vitamin C deficiency did not enhance this O 3 -induced lesion in guinea pigs. The dose relationship has also been confirmed by polyacrylamide gel electrophoresis of the lavage fluids. Lung lavage fluid protein content in animals exposed to 353 μg O 3 /m 3 (0.18 ppm) for 8 hr/day for 5 or 10 consecutive days was not different from that of air controls.
- Published
- 1982
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