subject:(Curriculum in Toxicology)

University of North Carolina

1. Bhavaraju, Laya. Examination of diesel and biodiesel exhaust exposure induced disruption of arachidonic acid metabolism.

Degree: 2015, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:9dd75e93-d3fb-402c-85d6-148c4ffacce1

► Diesel combustion emissions contributes a large amount of particulate matter found in air pollution collected in high-traffic urban areas. Current epidemiology studies indicate a strong… (more)

▼ Diesel combustion emissions contributes a large amount of particulate matter found in air pollution collected in high-traffic urban areas. Current epidemiology studies indicate a strong association between traffic and increased susceptibility to adverse respiratory and cardiovascular events. Current air quality initiatives have introduced biodiesel combustion as an alternative for diesel fuel to reduce particulate emissions. Incomplete biodiesel (BD) combustion emissions particulate matter analysis has detected the presence of unique emissions components, such as fatty acid methyl esters. However, biological activity of BD exhaust emissions have yet to be studied unlike diesel exhaust. Particle extraction based cellular-response studies have challenges with collection bias and sample loss. In this research, an improved extraction method was established with both diesel and BD exhaust particle for use in cell culture exposure assessments. Critical comparisons of BD and diesel particle extractions allowed for assessment of composition based response alterations of arachidonic acid (AA) metabolism. Multiple cellular functions are regulated by AA metabolites including inflammation and vascular tone. Endothelial cells regulate vascular tone by releasing lipid signaling molecules (PGI2 and PGF2a) to signal relaxation of smooth muscle cells. Alveolar macrophages (AM) release prostaglandins (PGE2) indicating cellular inflammation response. The work in this dissertation compared in vitro responses of diesel and BD exposure with alterations to AA metabolism. We initially observed the AA metabolism changes with response to BD and diesel emission particles in AM. The significant changes in prostaglandin production and release from BD relative to diesel led to further assessment of AA metabolite production alterations in endothelial cells. The mechanistic response of BD extract was addressed with human umbilical cord endothelial cells (HUVECs) and the findings revealed a reduction in prostaglandins and prostacyclins relative to diesel exposure. The increased incorporation of AA back into the phospholipid membranes by acyltransferase was associated with BD exposure resulting in reduction of prostacyclin and prostaglandins. Cumulatively these studies, increase the depth of knowledge of diesel and BD induced disruption of AA metabolism. Thus, signifying the composition of exhaust can induce differential cellular responses of lipid mediators affecting AM inflammation signaling and the HUVECs lipid remodeling pathways. Advisors/Committee Members: Bhavaraju, Laya, Church, Frank C., Jaspers, Ilona, Taylor, Joan, Madden, Michael, Kodavanti, Urmila.

Subjects/Keywords: Toxicology; School of Medicine; Curriculum in Toxicology

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APA (6^th Edition):

Bhavaraju, L. (2015). Examination of diesel and biodiesel exhaust exposure induced disruption of arachidonic acid metabolism. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:9dd75e93-d3fb-402c-85d6-148c4ffacce1

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bhavaraju, Laya. “Examination of diesel and biodiesel exhaust exposure induced disruption of arachidonic acid metabolism.” 2015. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:9dd75e93-d3fb-402c-85d6-148c4ffacce1.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bhavaraju, Laya. “Examination of diesel and biodiesel exhaust exposure induced disruption of arachidonic acid metabolism.” 2015. Web. 21 Jan 2021.

Vancouver:

Bhavaraju L. Examination of diesel and biodiesel exhaust exposure induced disruption of arachidonic acid metabolism. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:9dd75e93-d3fb-402c-85d6-148c4ffacce1.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bhavaraju L. Examination of diesel and biodiesel exhaust exposure induced disruption of arachidonic acid metabolism. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:9dd75e93-d3fb-402c-85d6-148c4ffacce1

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

2. Wei, Darmood. Elucidating SNF5 Regulated Gene Expression in Malignant Rhabdoid Tumor Development.

Degree: 2014, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:bcca99e3-3b24-4f32-a7b1-38eb1515c585

► Malignant Rhabdoid Tumors (MRTs), a pediatric renal cancer, lack SNF5, a subunit of the SWI/SNF chromatin remodeling complex which regulates nucleosome positioning and gene expression.… (more)

▼ Malignant Rhabdoid Tumors (MRTs), a pediatric renal cancer, lack SNF5, a subunit of the SWI/SNF chromatin remodeling complex which regulates nucleosome positioning and gene expression. MRTs offer a unique model for an epigenetically driven cancer because, unlike other cancers, they often have no other detectable mutations. Recent data on SWI/SNF mutations in cancer reveal mutations of 20 SWI/SNF subunit genes across 18 different cancers. Combined, the mutation rate of SWI/SNF complex members occurs at a frequency of 19% comparable to the 26% mutation frequency of TP53. Therefore understanding the SWI/SNF complex is highly relevant in our understanding of the mechanisms of not only tumorigenesis but also to the contribution of non-genotoxic carcinogens to this process. In these dissertation studies, we focused on the role of SNF5 inactivation in the development of MRTs. We hypothesize that SNF5 loss compromises the SWI/SNF complex resulting in aberrant targeting of the SWI/SNF complex, altered gene expression and tumorigenesis. To test this notion, we re-expressed SNF5 in MRT cell lines and examined the subsequent effects in SWI/SNF complex composition and gene expression. Our results indicated that SNF5 mediates the composition of the SWI/SNF complex, and its loss potentially disrupts SWI/SNF complex variants required for differentiation. SWI/SNF subunits are post-transcriptionally regulated in an interdependent fashion for stability. The changes in SWI/SNF complex composition also alter targeting of the complex with subsequent changes in gene expression. We validated our results using two known targets of SNF5, p21 and p16, and also through the identification of 2 two novel SNF5 targets, NOXA and CCNG2. These genes are upregulated after the reconstitution of the SWI/SNF complexes with SNF5 and may play critical roles in MRT development. These data demonstrate the intricacies of chromatin regulation and our incomplete understanding of this process in tumorigenesis. Together, this body of work serves as another milestone on our path to gain a better understanding of the relationships between chromatin structure and regulation, cancer biology, and toxicology. Advisors/Committee Members: Wei, Darmood, Weissman, Bernard, Davis, Ian, Rathmell, W. Kimryn, Jaspers, Ilona, Kaufmann, William.

Subjects/Keywords: Toxicology; School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wei, D. (2014). Elucidating SNF5 Regulated Gene Expression in Malignant Rhabdoid Tumor Development. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:bcca99e3-3b24-4f32-a7b1-38eb1515c585

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wei, Darmood. “Elucidating SNF5 Regulated Gene Expression in Malignant Rhabdoid Tumor Development.” 2014. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:bcca99e3-3b24-4f32-a7b1-38eb1515c585.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wei, Darmood. “Elucidating SNF5 Regulated Gene Expression in Malignant Rhabdoid Tumor Development.” 2014. Web. 21 Jan 2021.

Vancouver:

Wei D. Elucidating SNF5 Regulated Gene Expression in Malignant Rhabdoid Tumor Development. [Internet] [Thesis]. University of North Carolina; 2014. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:bcca99e3-3b24-4f32-a7b1-38eb1515c585.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wei D. Elucidating SNF5 Regulated Gene Expression in Malignant Rhabdoid Tumor Development. [Thesis]. University of North Carolina; 2014. Available from: https://cdr.lib.unc.edu/record/uuid:bcca99e3-3b24-4f32-a7b1-38eb1515c585

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

3. Filgo, Adam. Early Life Chemical Exposures and Latent Mammary Effects in Male and Female Rats.

Degree: 2015, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:3c15ffd0-0e71-4dc9-b76f-e1827831c212

► Volatile organic compounds (VOCs) are common industrial solvents used in a number of cleaning agents and solvents. In the United States, spikes in birth defects,… (more)

▼ Volatile organic compounds (VOCs) are common industrial solvents used in a number of cleaning agents and solvents. In the United States, spikes in birth defects, infant mortality, reproductive cancers and leukemia have occurred in areas with high levels of VOCs in drinking water. My thesis is focused on the effects of a VOC mixture on mammary gland development and risk for mammary tumor formation following prenatal/perinatal exposures in a 7,12-Dimethylbenz(a)anthracene (DMBA)-induced mammary tumor rat model. To gain an understanding of the animal model used in my studies, the Harlan Sprague Dawley (HSD) rat, an atlas of mammary gland development was created for both sexes, starting at embryonic day 15.5 through postnatal day (PND) 70. In addition, prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and diethylstilbestrol were used to demonstrate delayed and accelerated mammary gland growth, respectively. This atlas of mammary gland development in the HSD rat will be a key component in understanding and interpreting effects of chemicals in this rat strain. To specifically test the VOC mixture in this rat model, time-pregnant HSD rats and their offspring were given access to water containing a mixture of VOCs at concentrations 5X, 10X and 50X times those detected in contaminated drinking water at Camp Lejeune, to determine VOC body burden in both dams and pups. Mammary gland development was found to be accelerated in both sexes at the 5X and 10X concentrations. DMBA was given to VOC-exposed animals at PND 30 and tumors were recorded and collected 26 weeks after carcinogen treatment. There was a significant trend increase in adenocarcinomas arising in a fibroadenoma with VOC exposure in the females. Additionally, two malignant tumors formed in the males in the 10X exposure group and the males that died early due to tumor burden were from the 10X exposure group. These data demonstrate the ability of the VOC mixture to accelerate mammary gland development and enhanced the risk for tumor formation following carcinogen exposure. The mixture of VOCs was active at only 5-10 fold higher levels than what Marines or their mothers might have consumed, and these low level, prenatal exposure effects deserve further attention. Advisors/Committee Members: Filgo, Adam, Fenton, Suzanne, Kaufmann, William, Weissman, Bernard, Travlos, Gregory, Troester, Melissa.

Subjects/Keywords: Toxicology; School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Filgo, A. (2015). Early Life Chemical Exposures and Latent Mammary Effects in Male and Female Rats. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:3c15ffd0-0e71-4dc9-b76f-e1827831c212

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Filgo, Adam. “Early Life Chemical Exposures and Latent Mammary Effects in Male and Female Rats.” 2015. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:3c15ffd0-0e71-4dc9-b76f-e1827831c212.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Filgo, Adam. “Early Life Chemical Exposures and Latent Mammary Effects in Male and Female Rats.” 2015. Web. 21 Jan 2021.

Vancouver:

Filgo A. Early Life Chemical Exposures and Latent Mammary Effects in Male and Female Rats. [Internet] [Thesis]. University of North Carolina; 2015. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:3c15ffd0-0e71-4dc9-b76f-e1827831c212.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Filgo A. Early Life Chemical Exposures and Latent Mammary Effects in Male and Female Rats. [Thesis]. University of North Carolina; 2015. Available from: https://cdr.lib.unc.edu/record/uuid:3c15ffd0-0e71-4dc9-b76f-e1827831c212

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

4. High, Monica Denise. A Murine Model of Genetic Determinants of RSV Disease.

Degree: 2010, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:1b32dbfb-3d96-48bc-8270-f2cf5e01b6f5

► Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in infants. Approximately 70% of infants are infected with RSV within… (more)

▼ Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in infants. Approximately 70% of infants are infected with RSV within the first year of life. Epidemiological studies show that individuals have varying severity of RSV disease, ranging from "cold-like" symptoms to death. Previous in vivo studies have suggested that RSV susceptibility is a polygenic trait; however, the specific genes regulating RSV disease have yet to be identified. The objective of this dissertation was to identify candidate genes that regulate differences in RSV disease severity between inbred mouse strains. Thirty-six inbred mouse strains were infected with a single dose of 1x106 plaque forming units of RSV or control and sacrificed 1 and 5 days post-infection (pi). Inflammatory response, lung permeability, pathology, mucus cell metaplasia, and viral load were analyzed and compared among and within all inbred strains. Using in silico haplotype association mapping, the degree of correlation between the observed phenotypic differences and the genotype of the inbred strains was used to determine candidate QTLs. RSV disease phenotypes were distributed continuously across inbred strains. Furthermore, the strain distribution patterns varied for each phenotype and time point, suggesting that multiple mechanisms influence RSV susceptibility. Correlation analysis of phenotype relatedness also suggests that the response to RSV at 1 and 5 days pi are independent. Gene expression was minimally altered by RSV infection in "non-responsive" strains (e.g. C3H/HeJ); however, gene expression did vary significantly as a result of RSV infection in responsive inbred strains (e.g. BALB/cByJ). In responsive strains the most significant change in gene expression was noted 1 day following infection when a significant number of genes were either up-regulated or down-regulated. It was determined that genes involved in antigen presentation, infection mechanisms, and inflammatory response pathways were differentially activated between responsive and non-responsive strains. Based on the expression profile and biological plausibility a few of these genes (e.g. Marco, Tlr4, Stat4, Mx1, Ccl12, Cx3cr1) were identified as candidate genes for response to RSV infection. In vivo proof-of-principle investigations confirmed the role of Cx3cr1 and Marco as candidate genes for RSV susceptibility and disease. Advisors/Committee Members: High, Monica Denise, Kleeberger, Steven R..

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

High, M. D. (2010). A Murine Model of Genetic Determinants of RSV Disease. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:1b32dbfb-3d96-48bc-8270-f2cf5e01b6f5

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

High, Monica Denise. “A Murine Model of Genetic Determinants of RSV Disease.” 2010. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:1b32dbfb-3d96-48bc-8270-f2cf5e01b6f5.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

High, Monica Denise. “A Murine Model of Genetic Determinants of RSV Disease.” 2010. Web. 21 Jan 2021.

Vancouver:

High MD. A Murine Model of Genetic Determinants of RSV Disease. [Internet] [Thesis]. University of North Carolina; 2010. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:1b32dbfb-3d96-48bc-8270-f2cf5e01b6f5.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

High MD. A Murine Model of Genetic Determinants of RSV Disease. [Thesis]. University of North Carolina; 2010. Available from: https://cdr.lib.unc.edu/record/uuid:1b32dbfb-3d96-48bc-8270-f2cf5e01b6f5

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

5. Weed, Melanie B. The impact of epidermal growth factor receptor inhibition on energy homeostasis.

Degree: 2010, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:df7baf0e-8c55-426f-875d-8a0e76c69872

► As a result of the worldwide rise in obesity and obesity-related complications such as diabetes, stroke, and cardiovascular disease, understanding the mechanisms associated with this… (more)

▼ As a result of the worldwide rise in obesity and obesity-related complications such as diabetes, stroke, and cardiovascular disease, understanding the mechanisms associated with this disease and determining treatment options is necessary. A balance between food intake and energy expenditure, through a highly integrated multi-organ system, determines body weight regulation. Signals relaying energy storage and satiety from the periphery are sent to the central nervous system (CNS) where they, along with other neuronal signals, are used to maintain this balance. Accumulating evidence suggests signaling through the epidermal growth factor receptor (EGFR) is required for normal adipocyte development; therefore understanding how this signaling contributes to excess body fat mass is necessary to unravel the mechanisms associated with obesity. Our lab has previously shown that EGFR inhibition retards adipose deposition in a diet-induced obesity (DIO) model. To further delineate the role of EGFR in DIO, we performed two studies using pharmacological and genetic mouse models with either suppressed or conditionally deleted EGFR. In the first study, wild-type male C57BL/6J mice were chronically exposed to a high-fat western diet (WD) with or without a small molecule inhibitor to the EGFR tyrosine kinase, AG1478. In a separate experiment, mice homozygous for the Egfrwa2 mutation, a constitutionally impaired EGFR tyrosine kinase, and their control littermates were also challenged with this WD. The second study aimed to understand the role of EGFR in energy homeostasis in DIO. Mice with Egfr specifically deleted in peripheral tissues (intestines and adipocytes) and in the CNS using the Egfrtm1Dwt conditional allele and the Villin-Cre, aP2-Cre, and GFAP-Cre, transgenic lines, respectively, were chronically exposed to the WD. Significantly less body weight and fat mass were observed in mice with EGFR inhibition, either pharmacologically with AG1478 or genetically in the Egfrwa2 and GFAP-Cre genetic lines. Alterations in adipocyte size, adipocyte-specific factors, food intake, energy expenditure, and clinical parameters were also observed in these mice. We conclude that alterations in energy homeostasis account for this fat mass decrease. These studies should aid in our understanding of the role of EGFR in appetite and metabolism and provide potential avenues for the treatment of obesity. Advisors/Committee Members: Weed, Melanie B., Threadgill, David W..

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Weed, M. B. (2010). The impact of epidermal growth factor receptor inhibition on energy homeostasis. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:df7baf0e-8c55-426f-875d-8a0e76c69872

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Weed, Melanie B. “The impact of epidermal growth factor receptor inhibition on energy homeostasis.” 2010. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:df7baf0e-8c55-426f-875d-8a0e76c69872.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Weed, Melanie B. “The impact of epidermal growth factor receptor inhibition on energy homeostasis.” 2010. Web. 21 Jan 2021.

Vancouver:

Weed MB. The impact of epidermal growth factor receptor inhibition on energy homeostasis. [Internet] [Thesis]. University of North Carolina; 2010. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:df7baf0e-8c55-426f-875d-8a0e76c69872.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Weed MB. The impact of epidermal growth factor receptor inhibition on energy homeostasis. [Thesis]. University of North Carolina; 2010. Available from: https://cdr.lib.unc.edu/record/uuid:df7baf0e-8c55-426f-875d-8a0e76c69872

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

6. Askew, Emily B. Mechanisms that regulate androgen receptor transcriptional activity.

Degree: 2010, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:d0d09358-5988-497d-adc7-6e64263528d3

► Testosterone (T) and dihydrotestosterone (DHT) are natural ligands for the androgen receptor (AR), an intracellular transcription factor and nuclear receptor. DHT is a more potent… (more)

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Askew, E. B. (2010). Mechanisms that regulate androgen receptor transcriptional activity. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:d0d09358-5988-497d-adc7-6e64263528d3

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Askew, Emily B. “Mechanisms that regulate androgen receptor transcriptional activity.” 2010. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:d0d09358-5988-497d-adc7-6e64263528d3.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Askew, Emily B. “Mechanisms that regulate androgen receptor transcriptional activity.” 2010. Web. 21 Jan 2021.

Vancouver:

Askew EB. Mechanisms that regulate androgen receptor transcriptional activity. [Internet] [Thesis]. University of North Carolina; 2010. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:d0d09358-5988-497d-adc7-6e64263528d3.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Askew EB. Mechanisms that regulate androgen receptor transcriptional activity. [Thesis]. University of North Carolina; 2010. Available from: https://cdr.lib.unc.edu/record/uuid:d0d09358-5988-497d-adc7-6e64263528d3

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

7. Godin, Elizabeth Anne. Magnetic resonance imaging, in situ hybridization, and immunohistochemistry-based analyses of early prenatal ethanol exposure-induced central nervous system abnormalities.

Degree: 2010, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:ad950cd6-95f8-4e9a-aa45-339d97e9dca8

► Fetal alcohol spectrum disorders (FASD), the collection of defects resulting from prenatal alcohol (ethanol) exposure, has been the subject of basic and clinical investigation for… (more)

▼ Fetal alcohol spectrum disorders (FASD), the collection of defects resulting from prenatal alcohol (ethanol) exposure, has been the subject of basic and clinical investigation for four decades, but remains a major public health problem. At the severe end of the spectrum is fetal alcohol syndrome (FAS), which is characterized by the presence of growth retardation, craniofacial anomalies, and brain deficits. The research described herein was designed to advance our knowledge regarding ethanol's insult to the developing brain, with much of it directed toward testing the hypothesis that the application of magnetic resonance-based imaging to the examination of brain morphology, regional volumes and fiber tracts in ethanol-exposed fetal mice would facilitate new discoveries. As with other teratogens, it is well known that the type and severity of abnormality induced by ethanol is dependent upon the dose, timing, and pattern of maternal exposure. For this study, the CNS dysmorphology resulting from acute gestational day (GD) 7 maternal ethanol administration was examined in fetal mice utilizing state of the art imaging techniques. This time in mouse development is consistent with that in the third week of human gestation. Magnetic resonance microscopy (MRM) allowed for linear, volumetric and 3-dimensional morphologic analyses of ethanol-induced alterations in the fetal CNS and diffusion tensor imaging (DTI) provided for assessment of fiber tract abnormalities. In addition, routine histological techniques were utilized for detailed examination of the ventromedian forebrain in ethanol-exposed embryos and fetuses. Major new findings from these studies include the following regarding the consequences of acute GD7 ethanol exposure in mice 1) cerebral cortical heterotopias are induced; a discovery that was facilitated by MRM-based analyses, 2) fiber tract abnormalities involving the corpus callosum, anterior commissure, and fornix/fimbria occur, as evidenced by DTI, 3) fiber tract abnormalities, as identified in fetal mice, persist into periadolescent stages, 4) ventral forebrain insult preferentially involving the preoptic area and medial ganglionic eminences reduces Olig2 and GABA expression and alters the morphology of somatostatin-expressing cells. Overall, the results of this work promise to aid in clinical recognition, diagnosis, and prevention of FASD. Advisors/Committee Members: Godin, Elizabeth Anne, Sulik, Kathleen K..

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Godin, E. A. (2010). Magnetic resonance imaging, in situ hybridization, and immunohistochemistry-based analyses of early prenatal ethanol exposure-induced central nervous system abnormalities. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:ad950cd6-95f8-4e9a-aa45-339d97e9dca8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Godin, Elizabeth Anne. “Magnetic resonance imaging, in situ hybridization, and immunohistochemistry-based analyses of early prenatal ethanol exposure-induced central nervous system abnormalities.” 2010. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:ad950cd6-95f8-4e9a-aa45-339d97e9dca8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Godin, Elizabeth Anne. “Magnetic resonance imaging, in situ hybridization, and immunohistochemistry-based analyses of early prenatal ethanol exposure-induced central nervous system abnormalities.” 2010. Web. 21 Jan 2021.

Vancouver:

Godin EA. Magnetic resonance imaging, in situ hybridization, and immunohistochemistry-based analyses of early prenatal ethanol exposure-induced central nervous system abnormalities. [Internet] [Thesis]. University of North Carolina; 2010. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:ad950cd6-95f8-4e9a-aa45-339d97e9dca8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Godin EA. Magnetic resonance imaging, in situ hybridization, and immunohistochemistry-based analyses of early prenatal ethanol exposure-induced central nervous system abnormalities. [Thesis]. University of North Carolina; 2010. Available from: https://cdr.lib.unc.edu/record/uuid:ad950cd6-95f8-4e9a-aa45-339d97e9dca8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

8. Smith, Lindsay Kay. Glucocorticoid regulation of microRNA expression modulates lymphocyte apoptosis.

Degree: 2010, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:8e1b427f-ab95-4941-9946-49be83b103e8

► Apoptosis of immature thymocytes is a carefully coordinated process that is controlled by the actions of pro-apoptotic and anti-apoptotic effectors. Endogenous glucocorticoids modulate immune development… (more)

▼ Apoptosis of immature thymocytes is a carefully coordinated process that is controlled by the actions of pro-apoptotic and anti-apoptotic effectors. Endogenous glucocorticoids modulate immune development and function through the induction of lymphocyte apoptosis via mechanisms requiring alterations in gene expression. Recently, short, non-coding microRNAs have been identified as key regulators of lymphocyte function, however, it is unknown whether glucocorticoids regulate non-coding microRNAs and whether this regulation contributes to lymphocyte apoptosis. This dissertation seeks to evaluate the expression and delineate the potential regulatory role of microRNAs in glucocorticoid-induced apoptosis of lymphocytes. First, this dissertation establishes a glucocorticoid-induced apoptotic signature of microRNA expression through the demonstration of prevalent repression of microRNAs and microRNA bioprocessing machinery. Furthermore, the work presented herein delineates the regulatory role of microRNAs in glucocorticoid-induced apoptosis. Global reduction of microRNA expression via Dicer depletion significantly enhanced glucocorticoid-induced apoptosis while the overexpression of specific glucocorticoid-repressed microRNAs blunted glucocorticoid induced apoptosis, suggesting a role for microRNA processors and specific microRNAs in cell life/death decisions. Finally, studies of primary thymocyte sub-populations exhibiting the distinct morphological characteristics of apoptosis identified microRNAs uniquely regulated during glucocorticoid-induced and spontaneous apoptosis. This analysis also identified the novel induction of microRNAs 223 and 451 during both apoptotic pathways. This induction occurs under conditions of ongoing Dicer depletion. The inhibition of miR-223 activity significantly enhanced glucocorticoid-induced apoptosis, suggesting an anti-apoptotic role for this microRNA. These studies elucidate the dysregulation of microRNA expression and processing during glucocorticoid-induced apoptosis and the Dicer-independent induction of apoptotic effector microRNAs in glucocorticoid-induced and spontaneously apoptotic thymocyte sub-populations. Advisors/Committee Members: Smith, Lindsay Kay, Cidlowski, John A..

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA (6^th Edition):

Smith, L. K. (2010). Glucocorticoid regulation of microRNA expression modulates lymphocyte apoptosis. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:8e1b427f-ab95-4941-9946-49be83b103e8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Smith, Lindsay Kay. “Glucocorticoid regulation of microRNA expression modulates lymphocyte apoptosis.” 2010. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:8e1b427f-ab95-4941-9946-49be83b103e8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Smith, Lindsay Kay. “Glucocorticoid regulation of microRNA expression modulates lymphocyte apoptosis.” 2010. Web. 21 Jan 2021.

Vancouver:

Smith LK. Glucocorticoid regulation of microRNA expression modulates lymphocyte apoptosis. [Internet] [Thesis]. University of North Carolina; 2010. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:8e1b427f-ab95-4941-9946-49be83b103e8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Smith LK. Glucocorticoid regulation of microRNA expression modulates lymphocyte apoptosis. [Thesis]. University of North Carolina; 2010. Available from: https://cdr.lib.unc.edu/record/uuid:8e1b427f-ab95-4941-9946-49be83b103e8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

9. Shannahan, Jonathan H. Susceptibility to libby amphibole-induced pulmonary disease in the cardiovascular-compromised subpopulation.

Degree: 2011, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:be3894a2-8a7d-4cd5-9408-0f32aaf3bfd0

► Human exposure to asbestos is known to cause the development of mesothelioma, asbestosis and lung cancer. Asbestos toxicity is thought to be mediated through reactive… (more)

▼ Human exposure to asbestos is known to cause the development of mesothelioma, asbestosis and lung cancer. Asbestos toxicity is thought to be mediated through reactive oxygen species (ROS) production by surface available iron (Fe). Within the lung asbestos can complex endogenous Fe possibly increasing toxicity. We hypothesized that asbsestos-induced inflammation and injury would be greater in rat models of human cardiovascular disease (CVD) with Fe-overload. We characterized the baseline pulmonary disease of normotensive Wistar Kyoto, spontaneously hypertensive (SH), and SH heart failure (SHHF) rats. SH and SHHF were found to exist with pulmonary inflammation, oxidative stress, and Fe-overload (SHHF>SH). Libby amphibole (LA) was used to examine the role of Fe in asbestos-induced toxicity. LA complexed Fe in an acellular system, which enhanced ROS production. In in vitro and in vivo models the inflammatory response to LA decreased with increased cellular and fiber-complexed Fe. The chelation of Fe from fibers and cells exacerbated LA-induced inflammation. To determine the role of increased host Fe in LA-induced inflammation, and lung pathology WKY, SH, and SHHF were intratracheally-instilled with LA (0.0, 0.25, and 1mg/rat). LA-induced neutrophilic inflammation was not exacerbated although persistent through 1-month in CVD models compared to WKY. SH and SHHF failed to increase antioxidants but increased Fe-binding proteins after LA exposure. Progressive pulmonary fibrosis was noted over 3-months in all strains, whereas the accumulation of Fe in fiber-laden macrophages occurred primarily in SHHF. At 3-months, only SHHF exposed to LA demonstrated atypical hyperplastic lesions of bronchiolar epithelial origin. Gene expression profiling at 3-months indicated baseline differences reflective of pulmonary inflammation, and immune dysregulation in CVD models. Changes in genes involved in cell-cycle control and cancer pathways correlated with atypical hyperplasia in SHHF. We concluded LA can bind Fe and produce ROS in an acellular system but this process does not exacerbate the inflammatory response in cells or animals. Furthermore, in Fe-overload conditions, more Fe accumulates at sites of fiber deposition without enhancing the inflammatory response. In the presence of baseline lung pathology, the inability to further induce inflammation in response to LA may predispose those with Fe-overload to proliferative lung pathology. Advisors/Committee Members: Shannahan, Jonathan H., Kodavanti, Urmila.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA (6^th Edition):

Shannahan, J. H. (2011). Susceptibility to libby amphibole-induced pulmonary disease in the cardiovascular-compromised subpopulation. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:be3894a2-8a7d-4cd5-9408-0f32aaf3bfd0

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shannahan, Jonathan H. “Susceptibility to libby amphibole-induced pulmonary disease in the cardiovascular-compromised subpopulation.” 2011. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:be3894a2-8a7d-4cd5-9408-0f32aaf3bfd0.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shannahan, Jonathan H. “Susceptibility to libby amphibole-induced pulmonary disease in the cardiovascular-compromised subpopulation.” 2011. Web. 21 Jan 2021.

Vancouver:

Shannahan JH. Susceptibility to libby amphibole-induced pulmonary disease in the cardiovascular-compromised subpopulation. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:be3894a2-8a7d-4cd5-9408-0f32aaf3bfd0.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shannahan JH. Susceptibility to libby amphibole-induced pulmonary disease in the cardiovascular-compromised subpopulation. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:be3894a2-8a7d-4cd5-9408-0f32aaf3bfd0

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

10. Griggs, Jennifer Lynn. The effects of diesel exhaust particles or titanium dioxide nanoparticles on pulmonary inflammation.

Degree: 2011, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:82b9ca29-bbe5-4c8b-b155-c83e33bd4d14

► Pulmonary exposure to particulate matter has been associated with development of pulmonary inflammation which can lead to pulmonary illnesses and diseases. Various cultures have turned… (more)

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Griggs, J. L. (2011). The effects of diesel exhaust particles or titanium dioxide nanoparticles on pulmonary inflammation. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:82b9ca29-bbe5-4c8b-b155-c83e33bd4d14

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Griggs, Jennifer Lynn. “The effects of diesel exhaust particles or titanium dioxide nanoparticles on pulmonary inflammation.” 2011. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:82b9ca29-bbe5-4c8b-b155-c83e33bd4d14.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Griggs, Jennifer Lynn. “The effects of diesel exhaust particles or titanium dioxide nanoparticles on pulmonary inflammation.” 2011. Web. 21 Jan 2021.

Vancouver:

Griggs JL. The effects of diesel exhaust particles or titanium dioxide nanoparticles on pulmonary inflammation. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:82b9ca29-bbe5-4c8b-b155-c83e33bd4d14.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Griggs JL. The effects of diesel exhaust particles or titanium dioxide nanoparticles on pulmonary inflammation. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:82b9ca29-bbe5-4c8b-b155-c83e33bd4d14

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

11. Marion, Tracy L. Role of bile acids and compensatory hepatic transport proteins in troglitazone-mediated hepatotoxicity.

Degree: 2011, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:c46741cd-042a-423f-837f-d17b36b00e2f

► Drug-induced hepatotoxicity is the most common reason pharmaceuticals are removed from clinical use. Understanding mechanisms of hepatotoxicity, and in vitro models to predict hepatotoxicity in… (more)

▼ Drug-induced hepatotoxicity is the most common reason pharmaceuticals are removed from clinical use. Understanding mechanisms of hepatotoxicity, and in vitro models to predict hepatotoxicity in humans, are essential for drug development and patient safety. The drug troglitazone (TRO) was removed from the market because of hepatotoxicity, but preclinical testing failed to predict toxicity in humans. One hypothesized mechanism for TRO's hepatotoxicity is impairment of bile acid (BA) transport, causing cholestasis and subsequent hepatocellular apoptosis or necrosis. The goal of this research was to demonstrate that inhibition of BA transport and compensatory transport proteins contribute to the hepatotoxicity of TRO by causing intracellular accumulation of BAs and altering the BA pool composition. In human sandwich-cultured hepatocytes (SCH) and suspended hepatocytes, TRO inhibited uptake and biliary efflux of [3H] taurocholic acid ([3H]TCA), consistent with published reports in rat SCH; however, intracellular accumulation of [3H]TCA was not observed in either species. Because BAs differ in affinity for transport proteins, it was hypothesized that TRO causes intracellular accumulation of more cytotoxic BAs, such as chenodeoxycholic acid (CDCA). Indeed, TRO caused significant intracellular accumulation of [14C]CDCA species in rat SCH. In suspended rat hepatocytes, TRO inhibited [3H]TCA uptake more potently than [14C]CDCA uptake. This differential effect on individual BA disposition was hypothesized to shift the intracellular BA pool toward more toxic species. However, 24-h exposure of rat and human SCH to TRO had no significant effect on the concentration or composition of BAs in medium, cell, or bile, although the SCH model reflected reasonably well the in vivo BA pool composition in rats and humans. TRO-sulfate (TS), the major TRO metabolite, inhibited TCA transport in plasma membrane vesicles overexpressing the efflux protein multidrug resistance-associated protein 4 (MRP4). Accumulation of TS may inhibit BA efflux and increase intrahepatic accumulation of cytotoxic BAs in susceptible patients. This may explain, in part, the idiosyncratic nature of TRO hepatotoxicity. This research indicates that preclinical drug testing should include in vitro screens for drug-induced transport inhibition of multiple BAs, not just TCA, to fully characterize the effects of a compound on BA homeostasis. Advisors/Committee Members: Marion, Tracy L., Brouwer, Kim L. R., University of North Carolina at Chapel Hill.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Marion, T. L. (2011). Role of bile acids and compensatory hepatic transport proteins in troglitazone-mediated hepatotoxicity. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:c46741cd-042a-423f-837f-d17b36b00e2f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Marion, Tracy L. “Role of bile acids and compensatory hepatic transport proteins in troglitazone-mediated hepatotoxicity.” 2011. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:c46741cd-042a-423f-837f-d17b36b00e2f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Marion, Tracy L. “Role of bile acids and compensatory hepatic transport proteins in troglitazone-mediated hepatotoxicity.” 2011. Web. 21 Jan 2021.

Vancouver:

Marion TL. Role of bile acids and compensatory hepatic transport proteins in troglitazone-mediated hepatotoxicity. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:c46741cd-042a-423f-837f-d17b36b00e2f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Marion TL. Role of bile acids and compensatory hepatic transport proteins in troglitazone-mediated hepatotoxicity. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:c46741cd-042a-423f-837f-d17b36b00e2f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

12. Horvath, Katherine M. Cigarette Smoke Alters Influenza Induced Immune Responses of the Respiratory Epithelium.

Degree: 2011, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:981de7e0-3f52-4962-8ed1-cbfae9a3e18d

► Epidemiological evidence demonstrates that smokers are at increased risk for and suffer greater morbidity and mortality from influenza infection but the mechanism underlying this susceptibility… (more)

▼ Epidemiological evidence demonstrates that smokers are at increased risk for and suffer greater morbidity and mortality from influenza infection but the mechanism underlying this susceptibility is poorly understood. Previous work from our laboratory confirmed that smokers have increased markers of influenza infection using both in vivo and in vitro models of influenza infection. In this dissertation, the differential nasal immune responses to influenza infection were explored in nonsmokers and smokers. In the in vitro model of influenza infection, nasal epithelial cells (NEC) obtained from nonsmokers and smokers were differentiated ex vivo and co-cultured with monocyte-derived dendritic cells (mono-DCs) from nonsmokers to determine the effect of cigarette smoke (CS) exposure on the ability of NEC to communicate with underlying DCs. These co-cultures were then infected with influenza A virus. Both NEC from smokers and mono-DCs co-cultured with smoker NEC had decreased expression of antiviral mediators interferon regulatory factor 7 (IRF7) and Th1 cell chemokine interferon gamma-induced protein 10 kDa (IP-10) with increased expression of Th2 chemokine thymic stromal lymphopoeitin (TSLP). Thus, CS exposure altered antiviral defense mechanisms in both NEC and mono-DCs and changed the nature of communication between these two cell types. In the in vivo model of human influenza infection, nonsmokers and smokers were administered live attenuated influenza virus (LAIV) and the resulting localized nasal immune responses were monitored using nasal lavages and nasal biopsies. Natural killer (NK) cell cytotoxic responses and chemokines important for NK cell activation were suppressed in smoker nasal lavages. This data was intriguing because 1) it was the first documentation of NK cells in the nasal lavage cell population and 2) decreased NK cell activity in smokers could contribute to delayed influenza virus clearance. These data were also the first to show that γδ T intraepithelial lymphocytes, a rare immune cell type, migrated to the nasal mucosa following LAIV inoculation in both nonsmokers and smokers. Together these data demonstrate that CS exposure suppresses NK, NEC, and DC specific immune responses of the respiratory mucosa and contribute to the mechanism of increased susceptibility to respiratory viruses observed in CS exposed populations. Advisors/Committee Members: Horvath, Katherine M., Jaspers, Ilona.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Horvath, K. M. (2011). Cigarette Smoke Alters Influenza Induced Immune Responses of the Respiratory Epithelium. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:981de7e0-3f52-4962-8ed1-cbfae9a3e18d

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Horvath, Katherine M. “Cigarette Smoke Alters Influenza Induced Immune Responses of the Respiratory Epithelium.” 2011. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:981de7e0-3f52-4962-8ed1-cbfae9a3e18d.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Horvath, Katherine M. “Cigarette Smoke Alters Influenza Induced Immune Responses of the Respiratory Epithelium.” 2011. Web. 21 Jan 2021.

Vancouver:

Horvath KM. Cigarette Smoke Alters Influenza Induced Immune Responses of the Respiratory Epithelium. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:981de7e0-3f52-4962-8ed1-cbfae9a3e18d.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Horvath KM. Cigarette Smoke Alters Influenza Induced Immune Responses of the Respiratory Epithelium. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:981de7e0-3f52-4962-8ed1-cbfae9a3e18d

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

13. Davies, Brian Robert. Identification of novel binding targets of the SWI/SNF complex member SNF5 in malignant rhabdoid tumors.

Degree: 2011, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:70665bc8-31e6-49d1-83f5-b237e68ba809

► Malignant Rhabdoid Tumors (MRTs) show a loss of SNF5, a core subunit of the SWI/SNF chromatin remodeling complex. These cancers are genetically stable, but epigenetically… (more)

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Davies, B. R. (2011). Identification of novel binding targets of the SWI/SNF complex member SNF5 in malignant rhabdoid tumors. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:70665bc8-31e6-49d1-83f5-b237e68ba809

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Davies, Brian Robert. “Identification of novel binding targets of the SWI/SNF complex member SNF5 in malignant rhabdoid tumors.” 2011. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:70665bc8-31e6-49d1-83f5-b237e68ba809.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Davies, Brian Robert. “Identification of novel binding targets of the SWI/SNF complex member SNF5 in malignant rhabdoid tumors.” 2011. Web. 21 Jan 2021.

Vancouver:

Davies BR. Identification of novel binding targets of the SWI/SNF complex member SNF5 in malignant rhabdoid tumors. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:70665bc8-31e6-49d1-83f5-b237e68ba809.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Davies BR. Identification of novel binding targets of the SWI/SNF complex member SNF5 in malignant rhabdoid tumors. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:70665bc8-31e6-49d1-83f5-b237e68ba809

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

14. Irons, Terra D. Defining Behavioral Phenotypes Associated with Dopaminergic Nervous System Toxicity in Zebrafish Larvae.

Degree: 2011, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:bcb10a8a-1d89-4bd6-b65e-080811a56696

► Parkinson's disease and attention deficit hyperactivity disorder are motor conditions characterized by dysfunction of dopaminergic signaling in the brain. The origins of these dopamine-related movement… (more)

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Irons, T. D. (2011). Defining Behavioral Phenotypes Associated with Dopaminergic Nervous System Toxicity in Zebrafish Larvae. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:bcb10a8a-1d89-4bd6-b65e-080811a56696

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Irons, Terra D. “Defining Behavioral Phenotypes Associated with Dopaminergic Nervous System Toxicity in Zebrafish Larvae.” 2011. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:bcb10a8a-1d89-4bd6-b65e-080811a56696.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Irons, Terra D. “Defining Behavioral Phenotypes Associated with Dopaminergic Nervous System Toxicity in Zebrafish Larvae.” 2011. Web. 21 Jan 2021.

Vancouver:

Irons TD. Defining Behavioral Phenotypes Associated with Dopaminergic Nervous System Toxicity in Zebrafish Larvae. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:bcb10a8a-1d89-4bd6-b65e-080811a56696.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Irons TD. Defining Behavioral Phenotypes Associated with Dopaminergic Nervous System Toxicity in Zebrafish Larvae. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:bcb10a8a-1d89-4bd6-b65e-080811a56696

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

15. Troutman, John M. Molecular dosimetry of n7-guanine adducts in male and female mice exposed to 1,3-butadiene by inhalation.

Degree: 2011, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:8eeb2252-e3b5-4caa-b5b8-9ee05c2af885

► 1,3-Butadiene (BD) is a well-characterized carcinogen that is both an occupational and environmental hazard and an important industrial chemical widely used in the production of… (more)

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Troutman, J. M. (2011). Molecular dosimetry of n7-guanine adducts in male and female mice exposed to 1,3-butadiene by inhalation. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:8eeb2252-e3b5-4caa-b5b8-9ee05c2af885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Troutman, John M. “Molecular dosimetry of n7-guanine adducts in male and female mice exposed to 1,3-butadiene by inhalation.” 2011. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:8eeb2252-e3b5-4caa-b5b8-9ee05c2af885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Troutman, John M. “Molecular dosimetry of n7-guanine adducts in male and female mice exposed to 1,3-butadiene by inhalation.” 2011. Web. 21 Jan 2021.

Vancouver:

Troutman JM. Molecular dosimetry of n7-guanine adducts in male and female mice exposed to 1,3-butadiene by inhalation. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:8eeb2252-e3b5-4caa-b5b8-9ee05c2af885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Troutman JM. Molecular dosimetry of n7-guanine adducts in male and female mice exposed to 1,3-butadiene by inhalation. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:8eeb2252-e3b5-4caa-b5b8-9ee05c2af885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

16. Sproul, Christopher D. Biological Responses to Ultraviolet Radiation and the Effect of Intra-S Checkpoint Inhibition on Ultraviolet Radiation-Induced Mutagenesis.

Degree: 2013, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:04393838-15df-43e6-a74f-9e026ef01dd8

► Sunlight emits a spectrum of electromagnetic radiation that includes ultraviolet, visible, and infrared wavelengths. It is widely accepted that the ultraviolet radiation (UVR) component is… (more)

▼ Sunlight emits a spectrum of electromagnetic radiation that includes ultraviolet, visible, and infrared wavelengths. It is widely accepted that the ultraviolet radiation (UVR) component is responsible for the mutagenic and carcinogenic effects of sunlight. UVR is further sub-divided into three wavelength ranges: UVC (100-280 nm), UVB (280-315 nm) and UVA (315-400 nm) and each of these induce differing types and proportions of DNA damage. Despite much research, there is debate about the relative contributions from different wavelengths in initiating and promoting mutagenesis and carcinogenesis. DNA damage responses have been widely characterized using UVC, which is effectively filtered out by the Earth's atmosphere, while comparatively fewer studies have been conducted utilizing UVA and UVB. The research reported here assessed the biological outcomes of irradiating human dermal fibroblasts with UVR of different wavelengths, using DNA damage dosimetry to allow comparison between different irradiation sources. Cylobutane pyrimidine dimer (CPD) and 6-4 pyrimidine-pyrimidone photoproduct (6-4PP) densities were quantified and used as biomarkers following irradiation with lamps emitting UVA, UVB, or UVC. Comparing fluences that produced equal CPD densities, cytotoxicity, intra-S phase checkpoint response, and mutagenesis were assessed. Regardless of the source of UVR, results showed a striking similarity in the biological outcomes measured when exposures were compared on the basis of CPD dosimetry, suggesting that this UV-induced photolesion significantly contributed to the measured effect. The S-phase checkpoint response to UVR is a signaling cascade that recognizes damaged DNA or abnormal DNA structures and halts or slows new/ongoing DNA replication, potentially reducing the chance that damaged DNA will be replicated prior to its repair. Experiments reported here tested the hypothesis that this checkpoint is a protective system that reduces UVR-induced mutagenesis. Essential S-phase checkpoint components ATR or CHK1 were depleted using siRNA, or the CHK1 kinase pharmacologically inhibited using TCS2312, thereby inhibiting the S-phase checkpoint response to UVR. Subsequently, the UVR-induced mutation frequency at the HPRT locus was measured. Results showed that despite reversing the S-phase checkpoint response to UVR, the mutation frequency in the irradiated population was not increased, challenging the broadly accepted role of this signaling cascade in minimizing mutation burden. Advisors/Committee Members: Sproul, Christopher D., Cordeiro-Stone, Marila.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sproul, C. D. (2013). Biological Responses to Ultraviolet Radiation and the Effect of Intra-S Checkpoint Inhibition on Ultraviolet Radiation-Induced Mutagenesis. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:04393838-15df-43e6-a74f-9e026ef01dd8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sproul, Christopher D. “Biological Responses to Ultraviolet Radiation and the Effect of Intra-S Checkpoint Inhibition on Ultraviolet Radiation-Induced Mutagenesis.” 2013. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:04393838-15df-43e6-a74f-9e026ef01dd8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sproul, Christopher D. “Biological Responses to Ultraviolet Radiation and the Effect of Intra-S Checkpoint Inhibition on Ultraviolet Radiation-Induced Mutagenesis.” 2013. Web. 21 Jan 2021.

Vancouver:

Sproul CD. Biological Responses to Ultraviolet Radiation and the Effect of Intra-S Checkpoint Inhibition on Ultraviolet Radiation-Induced Mutagenesis. [Internet] [Thesis]. University of North Carolina; 2013. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:04393838-15df-43e6-a74f-9e026ef01dd8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sproul CD. Biological Responses to Ultraviolet Radiation and the Effect of Intra-S Checkpoint Inhibition on Ultraviolet Radiation-Induced Mutagenesis. [Thesis]. University of North Carolina; 2013. Available from: https://cdr.lib.unc.edu/record/uuid:04393838-15df-43e6-a74f-9e026ef01dd8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

17. Bauer, Rebecca N. The role of the inflammasome in the respiratory innate immune response to viruses and pollutants: insights for asthma pathogenesis.

Degree: 2014, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:a5baa79b-e6d4-4950-ad16-f1207b8018c6

► The respiratory mucosal innate immune system is composed of both structural cells, such as airway epithelial cells, and immune cells, such as macrophages, that together… (more)

▼ The respiratory mucosal innate immune system is composed of both structural cells, such as airway epithelial cells, and immune cells, such as macrophages, that together determine the appropriate immune response to inhaled stimuli. These cells use pattern recognition receptors to distinguish between harmless and harmful stimuli by recognizing conserved microbial pathogen-associated molecular patterns (PAMPs) and endogenously derived damage-associated molecular patterns (DAMPs) from damaged tissue. Inappropriate immune responses to normally innocuous stimuli underpin the pathogenesis of a number of immune disorders, including asthma, a chronic inflammatory disease of the airway typified by difficulty breathing in response to a trigger. In this dissertation, we explored the contribution of the inflammasome signaling complex to respiratory mucosal host defense against two sources of asthma exacerbation: influenza A virus infection and inhalation of the oxidant air pollutant ozone (O3). The inflammasome is an innate immune complex composed of a pattern recognition receptor, the protease caspase-1, and an adaptor protein (PYCARD) that when formed induces activation of caspase-1-mediated processing of the pro-inflammatory mediators IL-1B and IL-18 or cell death. Our results show that caspase-1 and the inflammasome contribute to the airway epithelial cell innate immune response to influenza and that this pathway is modified by asthma, suggesting a role for caspase-1 in virus-induced asthma exacerbation. Using a mouse model of allergic airway inflammation, we also show that caspase-1 may be involved in the development of allergic asthma, though its function in asthma development is complex. In the context of O3, we found increased presence of several DAMPs that may activate inflammasome signaling in the airway of healthy volunteers exposed to O3, but no evidence to suggest that inflammasome signaling strongly contributes to the innate immune response to O3. Finally, we identified a mechanism by which O3 alters the interaction between epithelial cells and macrophages leading to the accumulation of DAMPs that may activate innate immune responses in the lung. In summary, our results shed light on the function of the inflammasome in the human respiratory innate immune response to viruses and pollutants, and provide insight on the contribution of inflammasome signaling to asthma pathogenesis. Advisors/Committee Members: Bauer, Rebecca N., Jaspers, Ilona.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bauer, R. N. (2014). The role of the inflammasome in the respiratory innate immune response to viruses and pollutants: insights for asthma pathogenesis. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:a5baa79b-e6d4-4950-ad16-f1207b8018c6

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bauer, Rebecca N. “The role of the inflammasome in the respiratory innate immune response to viruses and pollutants: insights for asthma pathogenesis.” 2014. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:a5baa79b-e6d4-4950-ad16-f1207b8018c6.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bauer, Rebecca N. “The role of the inflammasome in the respiratory innate immune response to viruses and pollutants: insights for asthma pathogenesis.” 2014. Web. 21 Jan 2021.

Vancouver:

Bauer RN. The role of the inflammasome in the respiratory innate immune response to viruses and pollutants: insights for asthma pathogenesis. [Internet] [Thesis]. University of North Carolina; 2014. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:a5baa79b-e6d4-4950-ad16-f1207b8018c6.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bauer RN. The role of the inflammasome in the respiratory innate immune response to viruses and pollutants: insights for asthma pathogenesis. [Thesis]. University of North Carolina; 2014. Available from: https://cdr.lib.unc.edu/record/uuid:a5baa79b-e6d4-4950-ad16-f1207b8018c6

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

18. Macon, Madisa. Mechanistic Pathways Underlying Low-Dose Perfluorooctanoic Acid (PFOA) Effects in Murine Mammary Tissues.

Degree: 2014, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:99cdf32b-1ce2-4ce5-ba02-7506de540d3f

► Perfluorooctanoic acid (PFOA) is a synthetic surfactant that is as a prominent environmental toxicant. Previous studies have characterized the morphological effects of prenatal PFOA exposure… (more)

▼ Perfluorooctanoic acid (PFOA) is a synthetic surfactant that is as a prominent environmental toxicant. Previous studies have characterized the morphological effects of prenatal PFOA exposure on the mammary gland at 5mg/kg/day PFOA. The goal of this project was to identify major signaling pathways involved in this effect using a mouse model at dosing exposures that overlap with human serum levels. To minimize the overt developmental toxicity of PFOA, prenatal levels were reduced and/or exposures were abbreviated to a critical window of mammary gland organogenesis, gestational days 10-17. A systems biology approach was utilized to characterize the morphological and molecular changes using microarray, RT-PCR, Western blots, immunohistochemistry, histology, whole mount analysis, mammary epithelial transplant recombination, and serum hormone analysis. Following lowdose (0.01-1.0 mg/kg/day) and abbreviated (GD 10-17) PFOA exposures, mammary glands of treated mice displayed characteristics of delayed development which persisted into adulthood. These adult morphological alterations were characterized by misdirected growth patterns, thicker collagen density, increased active TEBs, and reduced side branching of the ductal tree. Genome-wide microarray analysis of young mammary tissues revealed PFOA altered RNA post-transcriptional modification, lipid metabolism and cholesterol biosynthesis; peroxisome proliferator-activated receptor (Ppar), Wnt, and endocrine related signaling were identified as targeted signaling pathways and confirmed by RT-PCR. The majority of RNA expression changes occurred early in life yet PFOA altered protein levels of candidate gene across multiple time-points. In whole cell lysates, at PND 7 PPARγ and ERα levels were increased; at PND 21 ERα protein levels was reduced; at PND 56 PPARα and PPARγ levels were severely reduced. Results from blots coincided with IHC stained sections for ERα which were reduced at PND 21 and 56 in treated glands. Circulating testosterone levels were reduced at PND 21 and DHEA was reduced at PND 56. Altered steroid levels, differences in steroid receptor populations, and dense breasts in women are associated with increased breast cancer risk, and similar to effects observed in mouse mammary glands following PFOA exposure. Collectively, these data show that prenatal PFOA exposure alters endocrine disruption and steroid receptor expression leading to phenotypic features associated with increased breast cancer risk. Importantly, these effects were observed in mice as PFOA serum concentrations approached background levels and overlapped with reported human serum levels. Advisors/Committee Members: Macon, Madisa, Fenton, Suzanne.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Macon, M. (2014). Mechanistic Pathways Underlying Low-Dose Perfluorooctanoic Acid (PFOA) Effects in Murine Mammary Tissues. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:99cdf32b-1ce2-4ce5-ba02-7506de540d3f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Macon, Madisa. “Mechanistic Pathways Underlying Low-Dose Perfluorooctanoic Acid (PFOA) Effects in Murine Mammary Tissues.” 2014. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:99cdf32b-1ce2-4ce5-ba02-7506de540d3f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Macon, Madisa. “Mechanistic Pathways Underlying Low-Dose Perfluorooctanoic Acid (PFOA) Effects in Murine Mammary Tissues.” 2014. Web. 21 Jan 2021.

Vancouver:

Macon M. Mechanistic Pathways Underlying Low-Dose Perfluorooctanoic Acid (PFOA) Effects in Murine Mammary Tissues. [Internet] [Thesis]. University of North Carolina; 2014. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:99cdf32b-1ce2-4ce5-ba02-7506de540d3f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Macon M. Mechanistic Pathways Underlying Low-Dose Perfluorooctanoic Acid (PFOA) Effects in Murine Mammary Tissues. [Thesis]. University of North Carolina; 2014. Available from: https://cdr.lib.unc.edu/record/uuid:99cdf32b-1ce2-4ce5-ba02-7506de540d3f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

19. Szabo, David. TOXICOKINETICS AND EFFECTS OF 1,2,5,6,9,10-HEXABROMOCYCLODODECANE (HBCD) STEREOISOMERS IN MICE.

Degree: 2011, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:4abc0883-76e2-46f9-835a-cd5ad50c126e

► Despite its small contribution to global production and usage of hexabromocyclododecane, α-HBCD is the major flame -retardant diastereomer found in environmental samples and human tissue.… (more)

▼ Despite its small contribution to global production and usage of hexabromocyclododecane, α-HBCD is the major flame -retardant diastereomer found in environmental samples and human tissue. Limited toxicology studies suggest that the commercially available HBCD mixture (CM-HBCD) is a developmental reproductive and neurotoxicant, as well as an endocrine disrupter. This dissertation investigates the link between exposure and dose of the two major HBCD stereosiomers, α and γ. The thrust and novelty of this research rest on the examination of the different stereoisomers of HBCD. We hypothesized that these isomers differed in pharmacokinetic and toxicological properties and moreover could interconvert, thus conclusions based on testing the commercially-available mixture might not adequately predict the outcome of real-life exposures. To test this hypothesis and provide information essential to the human health risk assessment of HBCD, the basic toxicokinetic parameters of α-HBCD and γ-HBCD were characterized in adult mice, which included: the impact of repeated dosing on the disposition and elimination of α-HBCD and γ-HBCD and the disposition and elimination of α-HBCD and γ-HBCD in infantile mice were also investigated. Pathway analysis was performed which may shed light on the mechanisms involved in effects leading to cognitive (learning and memory) deficits. We found that in adult female mice, α-HBCD and γ-HBCD are both well absorbed, 90 and 85% respectively. Distribution is dictated by lipophilicity for α- but not for γ-HBCD. This is due to the rapid elimination of γ-HBCD by metabolism and stereoisomerization in contrast to the much slower elimination of α-HBCD, with a terminal whole -body half life of 4 days for γ-HBCD and 17 days for α-HBCD. Repeated exposure results in higher body burdens than a single exposure alone, demonstrating the potential for bioaccumulation of α-HBCD. This was not observed for γ-HBCD. α-HBCD has toxicokinetic properties similar to other POPs. Tissue distribution in developing animals is similar to adults; however, actual concentrations are higher in younger animals for both α-HBCD and γ-HBCD because of a less developed metabolism and excretion capability. A systems biology approach involving transcriptomics, proteomics, and metabolomics was used to characterize the mechanisms involved in the infantile mouse response to α-HBCD, γ-HBCD and CM-HBCD in liver and brain. Alteration in synaptic long term potentiation is a potential mechanism observed from these studies which may account for the reported developmental neurotoxicity previously observed in vivo. Overall, we have identified differences in both, the toxicokinetics and molecular effects associated with the two HBCD stereoisomers. Advisors/Committee Members: Szabo, David, Birnbaum, Linda, Thakker, Dhiren, Ball, Louise, Stapleton, Heather, Nylander-French, Leena A..

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Szabo, D. (2011). TOXICOKINETICS AND EFFECTS OF 1,2,5,6,9,10-HEXABROMOCYCLODODECANE (HBCD) STEREOISOMERS IN MICE. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:4abc0883-76e2-46f9-835a-cd5ad50c126e

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Szabo, David. “TOXICOKINETICS AND EFFECTS OF 1,2,5,6,9,10-HEXABROMOCYCLODODECANE (HBCD) STEREOISOMERS IN MICE.” 2011. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:4abc0883-76e2-46f9-835a-cd5ad50c126e.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Szabo, David. “TOXICOKINETICS AND EFFECTS OF 1,2,5,6,9,10-HEXABROMOCYCLODODECANE (HBCD) STEREOISOMERS IN MICE.” 2011. Web. 21 Jan 2021.

Vancouver:

Szabo D. TOXICOKINETICS AND EFFECTS OF 1,2,5,6,9,10-HEXABROMOCYCLODODECANE (HBCD) STEREOISOMERS IN MICE. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:4abc0883-76e2-46f9-835a-cd5ad50c126e.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Szabo D. TOXICOKINETICS AND EFFECTS OF 1,2,5,6,9,10-HEXABROMOCYCLODODECANE (HBCD) STEREOISOMERS IN MICE. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:4abc0883-76e2-46f9-835a-cd5ad50c126e

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

20. Wages, Phillip. Peroxide dependent effects in human airway epithelial cells exposed to oxidant air pollutants.

Degree: 2016, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:b542bdfd-91db-4656-810f-dc5fb1f899a3

► Air pollution is a global public health problem. The induction of oxidative stress, or the cellular response to avoid cytotoxicity due to an increase in… (more)

▼ Air pollution is a global public health problem. The induction of oxidative stress, or the cellular response to avoid cytotoxicity due to an increase in reactive oxygen species or decrease in antioxidants, is frequently cited as a mechanism of toxicity for air pollutants. In addition to the role of oxidative stress in disease, there is growing evidence that oxidative processes including the generation of reactive oxygen species is essential for normal cellular function. This dissertation provides evidence that the reactive oxygen species, hydrogen peroxide, is a key mediator in air pollutant-induced adverse cellular responses. First, it is demonstrated that the divalent metal, zinc, induces hydrogen peroxide-dependent adaptive gene expression in human airway epithelial cells. This builds upon previous work to establish that zinc-induced pro-oxidant effects and electrophilic activity are both critical in its mechanism of toxicity. We next show that the organic component, 1,2-naphthoquinone, increases protein sulfenylation of regulatory proteins via hydrogen peroxide. This is the first report that protein sulfenylation is effected by an environmentally relevant exposure, establishing a potential new mechanism of toxicity as well as a new biomarker for future studies. Finally, two approaches to utilize readouts of oxidative stress in a translational manner are discussed. Specifically, the biological basis of a genetic risk factor of a susceptible population to air pollution is explored using a primary human airway epithelial cell culture. We report that there is an intimate relationship between hydrogen peroxide and glutathione in the air pollutant-induced outcomes, and that the genetic risk factor, GSTM1-null, enhances the effect of 1,2-NQ to induce the novel readout protein sulfenylation. Furthermore, we were able to use a live cell imaging analysis of oxidative stress to rank the toxicity of fibers of importance to respiratory toxicity and show that asbestos fibers obtained from the Libby Montana Superfund Site have similar toxicity to that of crocidolite asbestos fibers. Together the data suggests a vital and important role of hydrogen peroxide in air pollutant-induced adverse responses and provides the basis to use redox-based readouts as biomarkers to improve public health. Advisors/Committee Members: Wages, Phillip, Samet, James, Weissman, Bernard, Gold, Avram, Kodavanti, Urmila, Styblo, Mirek.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wages, P. (2016). Peroxide dependent effects in human airway epithelial cells exposed to oxidant air pollutants. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:b542bdfd-91db-4656-810f-dc5fb1f899a3

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wages, Phillip. “Peroxide dependent effects in human airway epithelial cells exposed to oxidant air pollutants.” 2016. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:b542bdfd-91db-4656-810f-dc5fb1f899a3.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wages, Phillip. “Peroxide dependent effects in human airway epithelial cells exposed to oxidant air pollutants.” 2016. Web. 21 Jan 2021.

Vancouver:

Wages P. Peroxide dependent effects in human airway epithelial cells exposed to oxidant air pollutants. [Internet] [Thesis]. University of North Carolina; 2016. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:b542bdfd-91db-4656-810f-dc5fb1f899a3.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wages P. Peroxide dependent effects in human airway epithelial cells exposed to oxidant air pollutants. [Thesis]. University of North Carolina; 2016. Available from: https://cdr.lib.unc.edu/record/uuid:b542bdfd-91db-4656-810f-dc5fb1f899a3

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

21. Holman, Natalie. Investigating the role of hepatocyte-derived exosomes in drug-induced liver injury.

Degree: 2016, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:b23d5a8a-894a-4150-9ece-fa32359b7160

► Drug-induced liver injury (DILI) is the primary cause of acute liver failure in the United States and is responsible for a substantial number of drug… (more)

▼ Drug-induced liver injury (DILI) is the primary cause of acute liver failure in the United States and is responsible for a substantial number of drug failures both pre- and post-market. Over 1,000 drugs have been associated with DILI and as a result, understanding the mechanisms of toxicity has proved extremely difficult. A common theme across mechanisms is the involvement of the immune system in the etiology, exacerbation, or resolution of DILI. It has become apparent that events at the hepatocyte level prior to cell death may influence immune responses and mediate the outcome of DILI. Hepatocyte-derived exosomes (HDE) may constitute one such immunomodulatory signal. HDE are constitutively released lipid-bound particles that have the unique ability to pass through fenestrations in the sinusoidal endothelium and enter the systemic circulation, potentially delivering stress signals to local and distal immune cells. The current research sought to establish HDE as mediators of early immune responses in the absence of overt DILI. We present a comprehensive analysis of the kinetics, content, and immunologic activity of HDE from primary hepatocytes stressed by sub-toxic drug exposures. To our knowledge, this is the first report of content profiling and functional analysis using primary human HDE in the context of DILI. Studies in rats, rat hepatocytes, and human hepatocytes exposed to the prototypical hepatotoxicant acetaminophen (APAP) verified changes in the RNA content of HDE prior to overt injury. Next, HDE from control- and APAP-treated primary human hepatocytes were collected for content profiling and functional analysis. The global profiles of mRNA and miRNA in HDE shifted as a result of drug exposure. Lastly, the immunologic activity of HDE was examined by exposing monocytes to HDE from control- and APAP-treated primary human hepatocytes. Differential gene expression in pathways related to immune cell function and cholesterol metabolism were observed. Functionally, APAP HDE exposure resulted in sensitization of monocytes to LPS stimulation. miRNA profiles in APAP HDE suggested that monocyte gene expression may have been mediated directly by exosomal miRNA. These results demonstrate that HDE influence immune cells before overt hepatotoxicity and highlight the mechanistic relevance of HDE in mediating DILI outcomes. Advisors/Committee Members: Holman, Natalie, LeCluyse, Edward, Watkins, Paul, LeCluyse, Edward, Watkins, Paul, Jaspers, Ilona, Kesimer, Mehmet, Key, Nigel.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Holman, N. (2016). Investigating the role of hepatocyte-derived exosomes in drug-induced liver injury. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:b23d5a8a-894a-4150-9ece-fa32359b7160

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Holman, Natalie. “Investigating the role of hepatocyte-derived exosomes in drug-induced liver injury.” 2016. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:b23d5a8a-894a-4150-9ece-fa32359b7160.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Holman, Natalie. “Investigating the role of hepatocyte-derived exosomes in drug-induced liver injury.” 2016. Web. 21 Jan 2021.

Vancouver:

Holman N. Investigating the role of hepatocyte-derived exosomes in drug-induced liver injury. [Internet] [Thesis]. University of North Carolina; 2016. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:b23d5a8a-894a-4150-9ece-fa32359b7160.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Holman N. Investigating the role of hepatocyte-derived exosomes in drug-induced liver injury. [Thesis]. University of North Carolina; 2016. Available from: https://cdr.lib.unc.edu/record/uuid:b23d5a8a-894a-4150-9ece-fa32359b7160

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

22. Suen, Alisa. ROLE OF THE SIX1 ONCOPROTEIN IN ENDOMETRIAL CANCER CAUSED BY NEONATAL XENOESTROGEN EXPOSURE.

Degree: 2017, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:e3618968-6b80-4652-b735-a98ad7704d58

► Exposure to xenoestrogens during key windows of development can lead to adverse female reproductive health outcomes, including cancer. In a classical model of latent hormonal… (more)

▼ Exposure to xenoestrogens during key windows of development can lead to adverse female reproductive health outcomes, including cancer. In a classical model of latent hormonal carcinogenesis, mice exposed neonatally to the synthetic estrogen diethylstilbestrol (DES) or the soy phytoestrogen genistein (GEN) develop endometrial carcinomas in late adulthood. However, the biological mechanisms driving carcinogenesis remain unclear. In this work, I investigated the role of the oncofetal protein sine oculis-related homeobox 1 homolog (SIX1) in endometrial carcinogenesis following neonatal xenoestrogen exposure and explored the utility of SIX1 as a biomarker in human endometrial cancer. I showed that neonatal exposure to GEN or DES causes aberrant endometrial SIX1 expression that persists with age and localizes to abnormally differentiated cell populations and all endometrial carcinomas. Further morphologic and molecular characterization revealed that mice exposed neonatally to GEN or DES exhibited three populations of abnormally differentiated SIX1-labeled endometrial epithelial cells that were associated with precursor lesions and carcinomas. These findings suggest that neonatal xenoestrogen exposure establishes unique SIX1-labeled cell populations that are associated with abnormal differentiation patterns in the endometrium and that may act as cancer progenitor cell populations. To explore the functional role of SIX1 in endometrial carcinogenesis, I used genetically engineered mouse models to investigate if SIX1 is necessary or sufficient for cancer development. I found that SIX1 was not necessary for development of xenoestrogen-induced endometrial carcinoma, but instead mediated abnormal differentiation of xenoestrogen-induced cell types. In addition, I showed that SIX1 overexpression alone is not sufficient to induce endometrial carcinoma development. I investigated the relevance of SIX1 as a human endometrial cancer biomarker and showed that a subset of human endometrial carcinoma biopsies express SIX1 and that expression is associated with late-stage disease. Together, I provide compelling evidence that although SIX1 alone does not act as a molecular driver of xenoestrogen-induced endometrial carcinogenesis, it is a biomarker for xenoestrogen exposure and for disease development, it is expressed in a potential cancer progenitor cell population in mice, and it contributes to abnormal endometrial epithelial differentiation. Advisors/Committee Members: Suen, Alisa, Williams, Carl, Fry, Rebecca, Bae-Jump, Victoria, Coleman, William, Fenton, Suzanne.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA (6^th Edition):

Suen, A. (2017). ROLE OF THE SIX1 ONCOPROTEIN IN ENDOMETRIAL CANCER CAUSED BY NEONATAL XENOESTROGEN EXPOSURE. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:e3618968-6b80-4652-b735-a98ad7704d58

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Suen, Alisa. “ROLE OF THE SIX1 ONCOPROTEIN IN ENDOMETRIAL CANCER CAUSED BY NEONATAL XENOESTROGEN EXPOSURE.” 2017. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:e3618968-6b80-4652-b735-a98ad7704d58.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Suen, Alisa. “ROLE OF THE SIX1 ONCOPROTEIN IN ENDOMETRIAL CANCER CAUSED BY NEONATAL XENOESTROGEN EXPOSURE.” 2017. Web. 21 Jan 2021.

Vancouver:

Suen A. ROLE OF THE SIX1 ONCOPROTEIN IN ENDOMETRIAL CANCER CAUSED BY NEONATAL XENOESTROGEN EXPOSURE. [Internet] [Thesis]. University of North Carolina; 2017. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:e3618968-6b80-4652-b735-a98ad7704d58.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Suen A. ROLE OF THE SIX1 ONCOPROTEIN IN ENDOMETRIAL CANCER CAUSED BY NEONATAL XENOESTROGEN EXPOSURE. [Thesis]. University of North Carolina; 2017. Available from: https://cdr.lib.unc.edu/record/uuid:e3618968-6b80-4652-b735-a98ad7704d58

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

23. Vaughan, Rachel. Biomarkers of Lung Epithelial Damage After Inhalation Injury.

Degree: 2017, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:57d36a55-b30f-4874-8394-3115d5b83ef8

► Burn and inhalation injury affects almost half a million people in the United States each year and it is one of the most complicated forms… (more)

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA (6^th Edition):

Vaughan, R. (2017). Biomarkers of Lung Epithelial Damage After Inhalation Injury. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:57d36a55-b30f-4874-8394-3115d5b83ef8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Vaughan, Rachel. “Biomarkers of Lung Epithelial Damage After Inhalation Injury.” 2017. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:57d36a55-b30f-4874-8394-3115d5b83ef8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vaughan, Rachel. “Biomarkers of Lung Epithelial Damage After Inhalation Injury.” 2017. Web. 21 Jan 2021.

Vancouver:

Vaughan R. Biomarkers of Lung Epithelial Damage After Inhalation Injury. [Internet] [Thesis]. University of North Carolina; 2017. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:57d36a55-b30f-4874-8394-3115d5b83ef8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Vaughan R. Biomarkers of Lung Epithelial Damage After Inhalation Injury. [Thesis]. University of North Carolina; 2017. Available from: https://cdr.lib.unc.edu/record/uuid:57d36a55-b30f-4874-8394-3115d5b83ef8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

24. Bowers, Emma. Harnessing Inter-Individual Variability to Identify Molecular Mechanisms Shaping Airway Epithelial Cell Transcriptional Responses to Ozone Exposure.

Degree: 2017, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:32407efc-b9cd-4bb8-a5bc-6c11fd30afc5

► Millions of people are exposed to levels of the ambient air pollutant ozone that are known to produce pulmonary inflammation; however, inflammatory responses exhibit extensive… (more)

▼ Millions of people are exposed to levels of the ambient air pollutant ozone that are known to produce pulmonary inflammation; however, inflammatory responses exhibit extensive inter-individual variability. Moreover, during multi-day exposures acute inflammatory responses are attenuated, resulting in a phenomenon known as “ozone adaptation.” The mechanisms governing these phenomena are not understood, but their identification is essential in understanding the health impacts of air pollutant exposure. The ozone-mediated induction of pro-inflammatory genes is a key step in the release of cytokines and chemokines in the airway. Thus, differences in the regulation of transcription may be a potential source of ozone inflammatory response inter-individual variability and may explain ozone adaptation. To model ozone associated transcriptional inter-individual variability, primary human bronchial epithelial cells (phBECs) were collected from different individuals, cultured at air-liquid-interface, and exposed to ozone in vitro. I then examined the expression of the chemokine IL-8, a central mediator of pulmonary inflammation, in addition to other ozone-responsive genes. I found that ozone inductions exhibited inter-individual variability and were reproducible within donors even when phBECs were collected, cultured, and exposed at different times. This suggests that ozone-responsive gene induction adheres to a set of biological rules that remain to be defined. Recent findings suggest that the MAPKs p38 and ERK1/2 mediate ozone response in phBECs, thus I investigated whether these kinases also controlled gene induction inter-individual variability. I found that phBECs with higher inductions of IL-8 are distinguished by elevated activation of ERK1/2, but not p38, following ozone exposure. Upon repeated ozone exposure, ozone-responsive gene expression was suppressed and was paralleled by decreases in ERK1/2 activation, suggesting that this may be an important adaptive mechanism. In collaboration with other scientists, I also found that epigenetic modifications at pro-inflammatory gene promoters were strongly associated with ozone-associated gene expression, suggesting that the epigenome is critical part of epithelial cell response ‘programming.’ In summary, this work identifies novel molecular mechanisms that dictate responsiveness to ozone exposure. This information can be used to refine definitions of susceptible populations and better predict health outcomes associated with air pollutant exposures. Advisors/Committee Members: Bowers, Emma, Diaz-Sanchez, David, Emanuele, Michael, Fry, Rebecca, Jaspers, Ilona, Weissman, Bernard.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bowers, E. (2017). Harnessing Inter-Individual Variability to Identify Molecular Mechanisms Shaping Airway Epithelial Cell Transcriptional Responses to Ozone Exposure. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:32407efc-b9cd-4bb8-a5bc-6c11fd30afc5

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bowers, Emma. “Harnessing Inter-Individual Variability to Identify Molecular Mechanisms Shaping Airway Epithelial Cell Transcriptional Responses to Ozone Exposure.” 2017. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:32407efc-b9cd-4bb8-a5bc-6c11fd30afc5.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bowers, Emma. “Harnessing Inter-Individual Variability to Identify Molecular Mechanisms Shaping Airway Epithelial Cell Transcriptional Responses to Ozone Exposure.” 2017. Web. 21 Jan 2021.

Vancouver:

Bowers E. Harnessing Inter-Individual Variability to Identify Molecular Mechanisms Shaping Airway Epithelial Cell Transcriptional Responses to Ozone Exposure. [Internet] [Thesis]. University of North Carolina; 2017. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:32407efc-b9cd-4bb8-a5bc-6c11fd30afc5.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bowers E. Harnessing Inter-Individual Variability to Identify Molecular Mechanisms Shaping Airway Epithelial Cell Transcriptional Responses to Ozone Exposure. [Thesis]. University of North Carolina; 2017. Available from: https://cdr.lib.unc.edu/record/uuid:32407efc-b9cd-4bb8-a5bc-6c11fd30afc5

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

25. Henriquez Coria, Andres. OZONE-INDUCED LUNG INJURY AND INFLAMMATION ARE MODULATED BY CIRCULATING STRESS HORMONES.

Degree: 2017, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:8d81df74-fe9f-46ed-b00d-3cd2efe6fdd3

► Air pollution has been associated with a wide-range of health effects. Pulmonary effects of acute ozone inhalation have been widely characterized in humans and animals.… (more)

▼ Air pollution has been associated with a wide-range of health effects. Pulmonary effects of acute ozone inhalation have been widely characterized in humans and animals. These include decrements in lung function, neutrophilic inflammation, and increased epithelial permeability. Ozone has also been shown to induce cardiovascular, neurological, metabolic and immune effects. It is believed that the “spillover” of bioactive lung-derived molecules to the circulation is responsible for extra-pulmonary effects of ozone. Our lab has recently shown that ozone, in addition to pulmonary effects, induces widespread systemic metabolic and immune effects in rats and humans. Importantly, these systemic changes are associated with increased circulating stress hormones, such as corticosterone and epinephrine, which are known to be involved in the “fight-or-flight” response. In our intervention study, we noted that extra-pulmonary but also pulmonary effects of ozone were dramatically reduced in adrenalectomized rats, indicating that circulating stress hormones contributed to all ozone effects. Since neuroendocrine stress response targets two essential survival processes, metabolic and immune, in this project we characterized in detail how pulmonary immune response and injury are influenced by the enhanced release of circulating stress hormones after ozone inhalation. In the first study, we demonstrated that the circulating stress hormones act at a transcriptional level to change gene expression after ozone exposure since global pulmonary gene changes induced by ozone exposure were attenuated in adrenalectomized rats. These ozone-induced expression changes depicted similarity to those predicted by glucocorticoid and adrenergic receptor activation, suggesting the contribution of stress hormones in mediating transcriptional effects. In our second round of studies, we demonstrated that by blocking endogenous stress hormone signaling adrenergic and glucocorticoid receptor antagonists, ozone-induced lung injury and inflammation were reduced in a receptor-specific manner (i.e. β adrenergic blocker inhibited lung neutrophilia while glucocorticoid receptor blocker caused lymphopenia). These results validated the role of stress hormones as bona fide circulating mediators acting directly on the lungs, and provided insights on the role of corticosterone versus epinephrine as individual modulators of ozone effects. In the third study, we combined surgical and pharmacological approaches, and demonstrated that the ozone-injury and inflammation phenotypes can be restored in adrenalectomized rats by providing exogenous glucocorticoid and β-adrenergic receptor agonists. These findings demonstrated unequivocally that stress hormones are the key systemic mediators of ozone-induced lung injury and innate immune effects. Thus, we show that circulating stress hormones, released from adrenal glands in response to ozone exposure, through their effects on β-adrenergic and glucocorticoid receptors, mediate most known pulmonary injury and innate… Advisors/Committee Members: Henriquez Coria, Andres, Kodavanti, Urmila, Fry, Rebecca, Ghio, Andrew, Jaspers, Ilona, Peden, David.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA (6^th Edition):

Henriquez Coria, A. (2017). OZONE-INDUCED LUNG INJURY AND INFLAMMATION ARE MODULATED BY CIRCULATING STRESS HORMONES. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:8d81df74-fe9f-46ed-b00d-3cd2efe6fdd3

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Henriquez Coria, Andres. “OZONE-INDUCED LUNG INJURY AND INFLAMMATION ARE MODULATED BY CIRCULATING STRESS HORMONES.” 2017. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:8d81df74-fe9f-46ed-b00d-3cd2efe6fdd3.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Henriquez Coria, Andres. “OZONE-INDUCED LUNG INJURY AND INFLAMMATION ARE MODULATED BY CIRCULATING STRESS HORMONES.” 2017. Web. 21 Jan 2021.

Vancouver:

Henriquez Coria A. OZONE-INDUCED LUNG INJURY AND INFLAMMATION ARE MODULATED BY CIRCULATING STRESS HORMONES. [Internet] [Thesis]. University of North Carolina; 2017. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:8d81df74-fe9f-46ed-b00d-3cd2efe6fdd3.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Henriquez Coria A. OZONE-INDUCED LUNG INJURY AND INFLAMMATION ARE MODULATED BY CIRCULATING STRESS HORMONES. [Thesis]. University of North Carolina; 2017. Available from: https://cdr.lib.unc.edu/record/uuid:8d81df74-fe9f-46ed-b00d-3cd2efe6fdd3

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

26. Jones, Shannon Zenia. The Identification of Novel Mechanisms to Regulate B cell Responses During Adaptive Immunity.

Degree: 2012, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:574f1a68-0b2c-4abf-b2ba-04f861ad2c68

► Initiation of the germinal center reaction during T-dependent adaptive immune responses gives rise to long-lived plasma cells (PCs) that produce high affinity, class switched antibodies.… (more)

▼ Initiation of the germinal center reaction during T-dependent adaptive immune responses gives rise to long-lived plasma cells (PCs) that produce high affinity, class switched antibodies. It also produces memory B cells to ensure a rapid, high affinity response to future pathogen exposure. Long-lived antibody and memory B cell responses underlie the success of vaccines and provide the host with durable, long-lasting protection from infectious disease. Although, the formation and maintenance of memory B cells and plasma cells are of critical importance, the mechanisms regulating these processes are poorly understood. Our lab has been interested in understanding the role of dendritic cells in regulating the germinal center reaction and adaptive immune response. We found that the formation of antigen/antibody immune complexes stimulate dendritic cells, through CD16 (FcgRIII), to secrete BAFF, a cytokine required initiation and maintenance of the germinal center as well as the formation of memory B cells. Specifically, our results indicate that DC-derived BAFF initially impacts the formation of T follicular helper cells, which are critical in seeding and initiating the germinal center response. Studies show that upon immunization with a T-dependent antigen, mice that lack CD16 expression, as well as mice lacking BAFF production by hematopoeitic cells, display reduced numbers of T follicular helper cells, and as consequence, reduced germinal center number and size. Correlated with this deficit in germinal centers, these mice also display attenuated secondary immune responses, and fewer numbers of antigen-experienced memory B cells. This suggests that DCs and BAFF play a key role in germinal center dynamics and subsequent memory B cell formation and function. Collectively, our data highlight an additional role for BAFF in the initiation and maintenance of T-dependent adaptive immune responses. Advisors/Committee Members: Jones, Shannon Zenia, Vilen, Barbara J., University of North Carolina at Chapel Hill.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA (6^th Edition):

Jones, S. Z. (2012). The Identification of Novel Mechanisms to Regulate B cell Responses During Adaptive Immunity. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:574f1a68-0b2c-4abf-b2ba-04f861ad2c68

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jones, Shannon Zenia. “The Identification of Novel Mechanisms to Regulate B cell Responses During Adaptive Immunity.” 2012. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:574f1a68-0b2c-4abf-b2ba-04f861ad2c68.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jones, Shannon Zenia. “The Identification of Novel Mechanisms to Regulate B cell Responses During Adaptive Immunity.” 2012. Web. 21 Jan 2021.

Vancouver:

Jones SZ. The Identification of Novel Mechanisms to Regulate B cell Responses During Adaptive Immunity. [Internet] [Thesis]. University of North Carolina; 2012. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:574f1a68-0b2c-4abf-b2ba-04f861ad2c68.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jones SZ. The Identification of Novel Mechanisms to Regulate B cell Responses During Adaptive Immunity. [Thesis]. University of North Carolina; 2012. Available from: https://cdr.lib.unc.edu/record/uuid:574f1a68-0b2c-4abf-b2ba-04f861ad2c68

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

27. Gibbs-Flournoy, Eugene. Examination of the Adverse Effects of Exposure to Gaseous and Particulate Oxidant Air Pollutants in Human Airway Epithelial Cells.

Degree: 2013, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:c35e6feb-4fcb-47a3-afdb-70ed6164466f

► Human exposure to ambient air pollution is a pervasive global public health problem. Ambient levels of air pollutants, such as particulate matter and ozone, are… (more)

▼ Human exposure to ambient air pollution is a pervasive global public health problem. Ambient levels of air pollutants, such as particulate matter and ozone, are associated with multiple adverse health effects, including increases in the incidence of morbidity and mortality. The underlying mechanism(s) responsible for the adverse effects of most air pollutants is not well understood. However, oxidative stress has been implicated as being a major contributor to the mechanism of toxic action of numerous gaseous and particulate air pollutants. The lungs serve as the primary route of exposure for air pollutants, making cells of the respiratory epithelia principal targets for many of the toxicological outcomes of air pollution exposure. The concentrations of gaseous and particulate matter (PM) air pollutants are primary determinants of the pulmonary toxicity resultant from air pollutant exposure. The study of oxidative responses to air pollutant exposure requires that a number of methodological challenges be overcome. The studies of this dissertation purposely address these challenges in the following manner: 1) Development and implementation of imaging methodologies for the investigation of effects resulting from particulate and gaseous air pollutant exposure to Human Airway Epithelial Cells (HAEC); 2) Examination of the cellular mechanisms that underlie oxidative stress responses to air pollution exposures in HAEC using live cell imaging methodologies; and 3) Examination of factors that mediate air pollution-induced changes in intracellular redox status. The major features of this body of work were able to validate and establish significant methodologies for examining the interaction of nano-scaled particulates with cellular environments, and observe oxidative alterations in the intracellular redox environment of oxidant-exposed cells in real-time. Moreover, these findings reveal that exposure to oxidative air pollutants, such as ozone, induces a profound increase in the intracellular glutathione redox potential of human airway epithelial cells that is indicative of an oxidant-dependent impairment of redox homeostasis in the cell. Cumulatively, this work advances current toxicological knowledge regarding the spatiotemporal interaction of gaseous and particulate air pollutants with cellular environments, while producing effective methodologies for the assessment of implications resulting from air pollutant exposure. Furthermore, the methodologies described herein can be used in broader toxicological applications assessing similar endpoints from other types of xenobiotic exposures. Advisors/Committee Members: Gibbs-Flournoy, Eugene, Samet, James.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gibbs-Flournoy, E. (2013). Examination of the Adverse Effects of Exposure to Gaseous and Particulate Oxidant Air Pollutants in Human Airway Epithelial Cells. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:c35e6feb-4fcb-47a3-afdb-70ed6164466f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gibbs-Flournoy, Eugene. “Examination of the Adverse Effects of Exposure to Gaseous and Particulate Oxidant Air Pollutants in Human Airway Epithelial Cells.” 2013. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:c35e6feb-4fcb-47a3-afdb-70ed6164466f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gibbs-Flournoy, Eugene. “Examination of the Adverse Effects of Exposure to Gaseous and Particulate Oxidant Air Pollutants in Human Airway Epithelial Cells.” 2013. Web. 21 Jan 2021.

Vancouver:

Gibbs-Flournoy E. Examination of the Adverse Effects of Exposure to Gaseous and Particulate Oxidant Air Pollutants in Human Airway Epithelial Cells. [Internet] [Thesis]. University of North Carolina; 2013. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:c35e6feb-4fcb-47a3-afdb-70ed6164466f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gibbs-Flournoy E. Examination of the Adverse Effects of Exposure to Gaseous and Particulate Oxidant Air Pollutants in Human Airway Epithelial Cells. [Thesis]. University of North Carolina; 2013. Available from: https://cdr.lib.unc.edu/record/uuid:c35e6feb-4fcb-47a3-afdb-70ed6164466f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

28. Snow, Samantha Jean. Ultrafine Particles Alter Endothelial Phenotype Through Oxidant Signaling.

Degree: 2013, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:9b309ef2-a0e8-4e11-bd0e-3fce7631a807

► Mechanisms that underlie the strong association between air pollution exposure and cardiovascular (CV) morbidity and mortality remain unknown. Particulate matter (PM) is a major component… (more)

▼ Mechanisms that underlie the strong association between air pollution exposure and cardiovascular (CV) morbidity and mortality remain unknown. Particulate matter (PM) is a major component of air pollution and ultrafine (UF) particles, which are the smallest diameter particle, are of particular importance in CV dysfunction caused by exposure to air pollution. UF particles can deposit in the heavily vascularized region of the lung and the soluble components of UF particles (soluble UF) are able to cross from the lung into the circulation and adversely affect cells of the vasculature such as endothelial cells. Endothelial cell activation, as characterized by an increase in reactive oxygen species (ROS) production, initiation of coagulation, and induction in inflammation, is a pathophysiological mechanism that could link inhaled air pollutants to vascular dysfunction. This project will test the hypothesis that soluble UF cause altered endothelial cell phenotype through activation of oxidant signaling that mediates procoagulant and proinflammatory responses. EA cells, an immortalized endothelial cell line, and primary human coronary artery endothelial cells (HCAEC) were assessed for their production of ROS, procoagulant activity, and proinflammatory responses following exposure to non-cytotoxic doses of soluble UF. We show that exposure to soluble UF results in immediate increases in extra- and intracellular H2O2 production from NADPH oxidase (NOX) enzymes in endothelial cells. Furthermore, soluble UF PM increased the expression of proinflammatory mediators and induced endothelial procoagulant activity via a tissue factor (TF)-dependent mechanism. Pretreatment with antioxidants and NOX inhibitors attenuated the soluble UF-induced upregulation of the procoagulant protein TF, the proinflammatory cytokine IL-1β, and the oxidant stress-inducible protein HO-1, linking the procoagulant and proinflammatory responses to ROS formation from NOX enzymes. These novel findings provide mechanistic insight into the endothelial dysfunction and enhanced thrombosis that underly increased risk for CV morbidity and mortality associated with air pollution exposure. Advisors/Committee Members: Snow, Samantha Jean, Carraway, Martha.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Snow, S. J. (2013). Ultrafine Particles Alter Endothelial Phenotype Through Oxidant Signaling. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:9b309ef2-a0e8-4e11-bd0e-3fce7631a807

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Snow, Samantha Jean. “Ultrafine Particles Alter Endothelial Phenotype Through Oxidant Signaling.” 2013. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:9b309ef2-a0e8-4e11-bd0e-3fce7631a807.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Snow, Samantha Jean. “Ultrafine Particles Alter Endothelial Phenotype Through Oxidant Signaling.” 2013. Web. 21 Jan 2021.

Vancouver:

Snow SJ. Ultrafine Particles Alter Endothelial Phenotype Through Oxidant Signaling. [Internet] [Thesis]. University of North Carolina; 2013. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:9b309ef2-a0e8-4e11-bd0e-3fce7631a807.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Snow SJ. Ultrafine Particles Alter Endothelial Phenotype Through Oxidant Signaling. [Thesis]. University of North Carolina; 2013. Available from: https://cdr.lib.unc.edu/record/uuid:9b309ef2-a0e8-4e11-bd0e-3fce7631a807

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

29. Perez, Christina Margaret. The Role of Hypoxia in Air Pollutant-Induced Cardiovascular Dysfunction.

Degree: 2013, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:2f503bb3-78a0-454f-aa1e-aa00d6e1ed7f

► Diesel exhaust (DE) is a major contributor to traffic-related urban air pollution and has been associated with cardiovascular dysfunction in humans, especially susceptible individuals. DE… (more)

▼ Diesel exhaust (DE) is a major contributor to traffic-related urban air pollution and has been associated with cardiovascular dysfunction in humans, especially susceptible individuals. DE is a complex pollutant consisting of particles and toxic gases such as acrolein. Although the mechanisms that mediate adverse cardiovascular health effects are unclear, epidemiological evidence has linked exposure to air pollution to drops in blood oxygen saturation, suggesting that hypoxia may play a role. Acute and repeated hypoxia is associated with carotid body-mediated cardiovascular effects which overtime lead to hypertension and predisposition to cardiac arrhythmia. Thus, my overarching hypothesis for this dissertation project is that air pollutant-induced hypoxia mediates the adverse cardiovascular effects of air pollution exposure. To test this hypothesis, we 1) characterized the impacts of short-term exposure to DE on cardiovascular physiology in rats, 2) characterized the cardiovascular response to exposure to the DE component acrolein, and determined if acrolein exposure increases the risk of adverse cardiovascular responses to a cardiac stressor (i.e, hypoxic atmosphere) in hypertensive rats, and 3) determined if inhibition of the sensory response to hypoxia attenuated air-pollutant-induced cardiovascular dysfunction. Exposure to DE caused PR prolongation and ST depression, a marker of myocardial ischemia, only in hypertensive rats exposed to the gaseous components of DE. Because the gaseous components appeared to be driving the responses, studies were conducted to assess the effects of acrolein. Exposure to acrolein caused increases in heart rate and blood pressure. These responses were confined to the hypertensive rat, and subsequent stress testing with hypoxic atmosphere (10% FiO2) confirmed enhanced sensitivity with increased diastolic blood pressure in the hypertensive rat. We also found that acrolein exposure significantly decreased arterial pO2, and carotid body inhibition prevented acrolein-induced blood pressure increases and impaired contractility responses in hypertensive rats. This suggests that air pollutants may cause hypoxia and that the cardiac responses following pollutant exposure may be mediated by the carotid body. This research describes a novel mechanism that mediates the adverse cardiovascular effects of air pollutant exposure and fills important data gaps in our understanding of air pollution-induced cardiovascular dysfunction. Advisors/Committee Members: Perez, Christina Margaret, Farraj, Aimen K..

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Perez, C. M. (2013). The Role of Hypoxia in Air Pollutant-Induced Cardiovascular Dysfunction. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:2f503bb3-78a0-454f-aa1e-aa00d6e1ed7f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Perez, Christina Margaret. “The Role of Hypoxia in Air Pollutant-Induced Cardiovascular Dysfunction.” 2013. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:2f503bb3-78a0-454f-aa1e-aa00d6e1ed7f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Perez, Christina Margaret. “The Role of Hypoxia in Air Pollutant-Induced Cardiovascular Dysfunction.” 2013. Web. 21 Jan 2021.

Vancouver:

Perez CM. The Role of Hypoxia in Air Pollutant-Induced Cardiovascular Dysfunction. [Internet] [Thesis]. University of North Carolina; 2013. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:2f503bb3-78a0-454f-aa1e-aa00d6e1ed7f.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Perez CM. The Role of Hypoxia in Air Pollutant-Induced Cardiovascular Dysfunction. [Thesis]. University of North Carolina; 2013. Available from: https://cdr.lib.unc.edu/record/uuid:2f503bb3-78a0-454f-aa1e-aa00d6e1ed7f

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of North Carolina

30. Currier, Jenna. Novel Biomarkers for the Risk Assessment of Exposure to Arsenic in Drinking Water.

Degree: 2013, University of North Carolina

URL: https://cdr.lib.unc.edu/record/uuid:ca54006e-7b76-4da5-8579-5e2bbe21b42a

► The toxic methylated trivalent metabolites of inorganic arsenic (iAs), methylarsonite (MAsIII) and dimethylarsinite (DMAsIII), play an important role in the etiology of As-induced diseases, including… (more)

▼ The toxic methylated trivalent metabolites of inorganic arsenic (iAs), methylarsonite (MAsIII) and dimethylarsinite (DMAsIII), play an important role in the etiology of As-induced diseases, including diabetes mellitus. However, the rapid oxidation of DMAsIII and, to a lesser extent, MAsIII leads to difficulties in the analysis of these metabolites in biological samples and assessment of the risk associated with As exposure. The goal of this project was to determine if a recently optimized analytical technique, hydride generation-cryotrapping-atomic absorption spectroscopy (HG-CT-AAS), can be used to quantitate trivalent As species in complex biological matrices, and determine whether concentrations of these species in biological systems can predict susceptibility to the diabetogenic effects of As exposure. First, we established that HG-CT-AAS is suitable for the quantification of MAsIII and DMAsIII and that these species are relatively stable in cells and tissues. We then used HG-CT-AAS to compare As speciation in tissues of wild-type (WT) mice that methylate As and mice null for As (3+ oxidation state) methyltransferase (As3mt-KO), the key enzyme in the pathway for As methylation, focusing on tissues regulating glucose homeostasis, including liver, pancreas, skeletal muscle, and adipose tissue. In WT mice, MAsIII and DMAsIII were extensively retained in these tissues, while iAsIII and iAsV were predominantly retained in tissues of As3mt-KO mice. Lastly, we used HG-CT-inductively coupled plasma-mass spectrometry, which provides lower detection limits, to examine concentrations of tri- and pentavalent As species retained in bladder exfoliated cells (BECs) recovered from individuals exposed to iAs in drinking water, and determined associations between the concentrations of As species in BECs and urine and the individual risk of developing diabetes. As species retained in BECs were positively correlated with other markers of exposure. More importantly, iAsIII and MAsIII retained in BECs were positively associated with risk of diabetes. Taken together, this work demonstrates the robustness of the optimized HG-CT-based techniques for the oxidation state specific analysis of As species in a variety of biological samples, and provides the first evidence that measurements of trivalent arsenicals in these samples can provide sensitive markers for assessment of health risks associated with iAs exposure. Advisors/Committee Members: Currier, Jenna, Styblo, Miroslav.

Subjects/Keywords: School of Medicine; Curriculum in Toxicology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Currier, J. (2013). Novel Biomarkers for the Risk Assessment of Exposure to Arsenic in Drinking Water. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:ca54006e-7b76-4da5-8579-5e2bbe21b42a

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Currier, Jenna. “Novel Biomarkers for the Risk Assessment of Exposure to Arsenic in Drinking Water.” 2013. Thesis, University of North Carolina. Accessed January 21, 2021. https://cdr.lib.unc.edu/record/uuid:ca54006e-7b76-4da5-8579-5e2bbe21b42a.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Currier, Jenna. “Novel Biomarkers for the Risk Assessment of Exposure to Arsenic in Drinking Water.” 2013. Web. 21 Jan 2021.

Vancouver:

Currier J. Novel Biomarkers for the Risk Assessment of Exposure to Arsenic in Drinking Water. [Internet] [Thesis]. University of North Carolina; 2013. [cited 2021 Jan 21]. Available from: https://cdr.lib.unc.edu/record/uuid:ca54006e-7b76-4da5-8579-5e2bbe21b42a.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Currier J. Novel Biomarkers for the Risk Assessment of Exposure to Arsenic in Drinking Water. [Thesis]. University of North Carolina; 2013. Available from: https://cdr.lib.unc.edu/record/uuid:ca54006e-7b76-4da5-8579-5e2bbe21b42a

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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Open Access Theses and Dissertations