Life Sciences Commons^™

Syntaxin-3 Mediates Baseline And Stimulated Mucin Secretion, Brianne Wharton

Dissertations & Theses (Open Access)

There are two rates at which airway epithelial cells secrete mucin. The low baseline rate accounts for ciliary clearance, and the high stimulated rate obstructs airways in protection from helminths or in obstructive pulmonary diseases. The exocytosis of mucins occurs via the four-helix SNARE complex. The SNARE proteins contributing helices are the vesicle-SNARE VAMP, and the target-SNAREs SNAP and Syntaxin. Coiling of the complex fuses the granule and plasma membranes to release mucins into the extracellular space. The VAMP and SNAP isoforms mediating baseline and stimulated secretion are known, but the Syntaxin (Stx) isoform remains unknown.

Three candidate exocytic Stx, …

Allergic Diseases In The Elderly, Gabriele Di Lorenzo, Marcello Melluso, Alessandro Rodolico, Aurelio Seidita

Translational Medicine @ UniSa

Recent increases in allergic diseases are thought to be caused by better hygiene, Westernized diets, air pollution, climate change, and other factors that influence host microbiota, a key player in the induction and maintenance of immunoregulatory circuits and tolerance. The increase of allergic diseases in the elderly is also related to additional factors, such as various comorbidities that may interfere with the development and the type of allergic reactions. Immunosenescence plays a central role in these reactions, altering microbiota responses and triggering inflammageing. In addition, in the elderly, there is a shift from Th1 to Th2 immunity, thus favoring allergic …

Novel Natural Compounds Derived From Tcm In The Treatment Of Food Induced Anaphylaxis, Ibrahim Musa

NYMC Student Theses and Dissertations

Food allergy is a highly prevalent disease affecting about 30 million people in the U.S. It is managed primarily by food avoidance due to lack of promising treatment options. ASHMI (anti-asthma herbal intervention) which consists of three components, Sophorae flavescentis, Ganoderma lucidum, Glycyrrhiza uralensis has been shown to inhibit allergic lung inflammation in antigen sensitized and challenged mice. In this study we isolate and identify the active compound in Sophorae flavescentis, characterized the mechanism of IgE inhibitory effect, biomarkers and potential to prevent food anaphylaxis.

To separate and identify the compounds we used column chromatography, high-performance liquid chromatography, mass …

Obesity And Asthma Risk In Indonesian Adults: Findings From The 2018 Indonesia Basic Health Research, Hoirun Nisa

Kesmas

Obesity and asthma are both global public health challenges. Mounting evidence suggests that obesity may increase asthma risk in adults; however, the association by sex remains uncertain. This study examined the association of obesity with asthma risk in Indonesian adult men and women. Data were obtained from the 2018 Indonesia Basic Health Research. The analysis included 299,837 men and 333,218 women aged ≥18 years. Asthma was identified by the self-report of a doctor’s diagnosis. Obesity was defined as a body mass index ≥30 kg/m2. A logistic regression was used for data analysis. Asthma prevalence was 2.7% (2.5% in men and …

Wheezy And Cough Asthma Phenotypes In A Cohort Of Egyptian Children: Clinical Features And Ccr3 T51c Gene Polymorphism, Magdy Mohamed Zedan, Mai Magdy Kera, Eman Omar Khashaba, Mona El Wassefy, Amal Mohamed Osman

Mansoura Medical Journal

Background: Asthma is a heterogenous disease with variable characteristic phenotypes. Correlating clinical asthma phenotypes with the underlying genotypes could pave the way for development of tailored asthma medications. Objective: The purpose of this study was to describe the clinical features of wheezy and cough asthma phenotypes and to assess the frequency of CCR3T51C gene polymorphism among Egyptian asthmatic children. Methods: A group of 60 Egyptian asthmatic children (40 wheezy phenotype and 20 cough phenotype) together with 100 controls were enrolled and analyzed for the genotypes of CCR3 T51C polymorphisms using PCR-RFLP. Serum IgE levels were determined by ELISA technique. Results: …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Effect Of Eosinophils In Purinergic Receptor P2x3 Expression In Mouse Sensory Neurons, Emily J. Mize

Student Research Symposium

P2X₃ purinoceptors are expressed by airway sensory neurons and activated by extracellular ATP released during periods of cell stress. In asthma, sensitivity to ATP is increased. Airway eosinophilia, which is common in a majority of asthmatics, increases airway sensory nerve density in mice and humans. Whether eosinophils increase neuronal P2X₃ expression in asthma is unknown.

P2X₃ expression was quantified in vagal ganglia from wild-type (WT) mice and transgenic mice with airway eosinophilia (NJ1726), systemic eosinophilia (NJ1638), and eosinophil-deficiency (PHIL) using RNAscope in situ hybridization. Images were obtained using confocal microscopy. The percentage of P2X₃ positive pixels …

Development Of New Treatments For Asthma And Neuropathic Pain Based On Ɣ-Aminobutyric Acid A Receptor (Gabaar) Ligands, Nicolas Mark Zahn

Theses and Dissertations

The γ-aminobutyric acid A receptor (GABAAR) is a ligand-gated pentameric chloride channel consisting of several identified subunits: α1-6, β1-3, γ1-3, δ, ε, π, θ, ρ1-3.1-2 Typical arrangement of subunits consists of two α subunits, two β subunits, and one γ subunit.3 GABAARs have two binding sites for the endogenous ligand γ-aminobutyric acid (GABA), between the α and β subunits. GABAARs also have a binding site for positive allosteric modulators, such as benzodiazepines, between the α and γ subunits.4-5 Due to their ability to treat anxiety, epilepsy, insomnia, and muscle relaxation, benzodiazepines are widely prescribed pharmaceuticals.6-7 Still, adverse effects result from …

Allergy And Anaphylaxis From The Prehospital Perspective, Anthony E. Conrardy

Dissertations and Theses

Anaphylaxis is considered a severe, potentially fatal, systemic allergic reaction that occurs suddenly after contact with an allergy causing substance. It is estimated that up to 5% of the population has experienced anaphylaxis, with 1% of hospitalizations and 0.1% of emergency department patients having fatal outcomes. We characterized the population of patients encountered by the EMS agency (786 patients) that had a provider impression of “allergic reaction” and then utilized logistic regression models to estimate associations with the administration of epinephrine in the prehospital setting. Additionally, we used incident location data for all patient encounters of the EMS agency …

The Effect Of Fiber And Omega-6:Omega-3 Fatty Acid Ratio On Asthma And Asthma-Related Symptoms In An Adult U.S. Population, Korie As Nelson

Capstone Experience

Asthma is one of the most common diseases in the world affecting more than 10% of adults in many westernized countries and 339 million globally. Studies have shown a positive association between increased dietary fiber and improvement in asthma-related inflammation. Omega-3 fatty acids have also been shown to help mitigate inflammation in general. No identified studies have looked at the synergistic effect of omega-3 and omega-6 fatty acids alone and as a ratio with fiber on asthma, lung function, and respiratory morbidities. A positive association could mean that dietary interventions of fiber and fatty acids could significantly improve asthma and …

Bone Morphogenetic Proteins Modulate Mast Cell Responses During Inflammation, Jane S. Woodrow

Doctoral Dissertations

Chronic inflammatory conditions can lead to detrimental health conditions that become difficult to manage and treat. Ultimately treatment requires modulation of the critical cell types involved in pathology in order to achieve homeostasis. Mast cells, a type of innate immune cell located at areas of high antigen load, are commonly thought of as primarily pro-inflammatory, but are becoming increasingly recognized in other roles, such as wound healing, anti-inflammatory actions, and homeostatic functions. In this study we investigate the role of mast cell subtypes and inflammatory mechanisms via in vitro assays using mouse and human mast cells, as well as relate …

Genetic And Non-Genetic Factors Affecting The Expression Of Covid-19-Relevant Genes In The Large Airway Epithelium, Silva Kasela, Victor E Ortega, Molly Martorella, Suresh Garudadri, Jenna Nguyen, Elizabeth Ampleford, Anu Pasanen, Srilaxmi Nerella, Kristina L Buschur, Igor Z Barjaktarevic, R Graham Barr, Eugene R Bleecker, Russell P Bowler, Alejandro P Comellas, Christopher B Cooper, David J Couper, Gerard J Criner, Jeffrey L Curtis, Meilan K Han, Nadia N Hansel, Eric A Hoffman, Robert J Kaner, Jerry A Krishnan, Fernando J Martinez, Merry-Lynn N Mcdonald, Deborah A Meyers, Robert Paine, Stephen P Peters, Mario Castro, Loren C Denlinger, Serpil C Erzurum, John V Fahy, Elliot Israel, Nizar N Jarjour, Bruce D Levy, Xingnan Li, Wendy C Moore, Sally E Wenzel, Charles Langelier, Prescott G Woodruff, Tuuli Lappalainen, Stephanie A Christenson

Journal Articles

BACKGROUND: The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression.

METHODS: We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with …

Drug Therapy Problems In Asthma Identified During Pharmacist-Led Educational Interventions, Kosisochi Chinwendu Amorha, Mathew Jegbefume Okonta, Chinwe Victoria Ukwe

The Thai Journal of Pharmaceutical Sciences

Background: Drug therapy problems (DTPs) interfere with desired goals of therapy. This study evaluated DTPs in asthma identified during a pharmacist-led intervention in the asthma clinics of two Nigerian hospitals. Methods: This intervention study was conducted in the asthma clinics, University of Nigeria Teaching Hospital and Lagos University Teaching Hospital. Eligible participants were patients with asthma recruited into a pharmacist-led intervention study and followed up for 6 months. The Pharmaceutical Care Network Europe – Drug-related Problem Classification V6.2 in English (PCNE-DRP V6.2) was utilized to evaluate the DTPs. Results: Seventy-eight patients with asthma participated. A total of 158 DTPs were …

Effect Of Intrauterine Smoke Exposure On Microrna-15a Expression In Human Lung Development And Subsequent Asthma Risk., Sunita Sharma, Alvin T. Kho, Divya Chhabra, Kathleen Haley, Carrie A. Vyhlidal, R Gaedigk, J Steven Leeder, Kelan G. Tantisira, Benjamin Raby, Scott T. Weiss

Manuscripts, Articles, Book Chapters and Other Papers

Background: In utero smoke (IUS) exposure is associated with asthma susceptibility.

Objective: We sought to test the hypothesis that changes in miRNA expression by IUS exposure during human lung development is associated with asthma susceptibility.

Methods: Gene expression was profiled from 53 IUS unexposed and 51 IUS exposed human fetal lung tissues. We tested for the differential expression of miRNAs across post-conception age and by IUS using linear models with covariate adjustment. We tested the IUS-associated miRNAs for association with their gene expression targets using pair-wise inverse correlation. Using our mouse model, we investigated the persistence of the IUS-associated miRNA …

Inducible Epithelial Resistance Against Acute Viral Pneumonia And Chronic Asthma, Shradha Wali

Dissertations & Theses (Open Access)

Viral pneumonia remains a global health threat despite worldwide vaccination and therapeutic programs. The influenza pandemic of 1918 and SARS-CoV2 pandemic of 2019-2020 are cautionary reminders demanding the need for novel treatment strategies. Moreover, in addition to causing acute disease, respiratory virus infections are often complicated by chronic lung pathologies, such as asthma induction, progression, and exacerbation. We have reported that mice treated with a combination of inhaled Toll-like receptor (TLR) 2/6 and TLR 9 agonists (Pam2-ODN) to stimulate innate immunity are broadly protected against respiratory pathogens, but the mechanisms underlying this protection remain incompletely elucidated. Here, we show in …

Inducible Epithelial Resistance Against Acute Viral Pneumonia And Chronic Asthma, Shradha Wali

Dissertations & Theses (Open Access)

Viral pneumonia remains a global health threat despite worldwide vaccination and therapeutic programs. The influenza pandemic of 1918 and SARS-CoV2 pandemic of 2019-2020 are cautionary reminders demanding the need for novel treatment strategies. Moreover, in addition to causing acute disease, respiratory virus infections are often complicated by chronic lung pathologies, such as asthma induction, progression, and exacerbation. We have reported that mice treated with a combination of inhaled Toll-like receptor (TLR) 2/6 and TLR 9 agonists (Pam2-ODN) to stimulate innate immunity are broadly protected against respiratory pathogens, but the mechanisms underlying this protection remain incompletely elucidated. Here, we show in …

The Influence Of Estrogen And Glucocorticoid On Th2 Cell Survival And Transcriptional Activation Of Crth2, Jenna H. Fortunato

Electronic Thesis and Dissertation Repository

Women are more likely to have severe asthma than men. Recent data suggest this could be due to women having more circulating CD4⁺CRTh2⁺ T cells (Th2 cells). Glucocorticosteroids (GC)s are the main therapy for asthma as they inhibit cytokine production and eliminate inflammatory cells by apoptosis. The current study examined whether the female sex hormone estrogen influences the anti-inflammatory action of GC. Experiments show that ER⍺ agonist reduced GC-induced apoptosis of primary Th2 cells and enhanced GC-mediated transcriptional activation of the proximal CRTh2 promoter. Genetic variation within CRTh2 is associated with asthma and allergic phenotypes. Using constructs …

Effects Of Asthma On Lung Function, Aerobic Fitness, And Physical Activity Levels In Young Adults, Trey Deal

Health, Human Performance and Recreation Undergraduate Honors Theses

Background: Asthma is one of the most commonly diagnosed conditions in the United States. Research has shown that one form of asthma, exercise-induced bronchoconstriction, is experienced by the overwhelming majority of individuals with the condition during physical activity, potentially causing fear and avoidance of physical activity in the future. Physical inactivity could have several negative health implications, including lower lung function and aerobic fitness levels. Purpose: The purpose of this study is to compare lung function, aerobic fitness, and physical activity levels between young adults with asthma to those without asthma. The hypothesis is that there will be a statistically …

Glutathionylation/Glutaredoxin Axis And The Regulation Of Epithelial Cell Plasticity And Fibroblast Activation In Airway Fibrosis, Shi Biao Chia

Graduate College Dissertations and Theses

Asthma is a complex lung disorder that affects more than 200 million people across the globe. About 10% of asthmatics have severe disease accompanied by structural airway remodeling, including subepithelial fibrosis, airway smooth muscle cell hyperplasia, goblet metaplasia, and increased vascularization. Oxidative stress has been well-linked to asthma pathogenesis; however, the precise redox mechanisms governing the pathological states are slowly being teased apart in the recent years. Protein S-glutathionylation (PSSG) is a posttranslational modification where a three amino acid-peptide, glutathione, forms a disulfide bond with reactive cysteines of a protein thereby potentially changing the protein’s biological functions. Glutaredoxins are members …

Early Detection Of Asthma Via Enhanced Resolution Of Small Airways Using Ultra-Low Frequency Impulse Oscillometry, Christopher M. Aguilar

Open Access Theses & Dissertations

Examination of lung function for diagnosis and monitoring of diseases such as chronic obstructive pulmonary disease (COPD) and asthma can be performed with a variety of pulmonary function testing (PFT) techniques. The most commonly prescribed of these procedures are spirometry and whole-body plethysmography. However, these active participation tests depend on forced breathing maneuvers, may be physically exhausting, might not produce enough information, and are susceptible to being subject-dependent. In contrast, passive PFT approaches such as the forced oscillation technique (FOT) and the impulse oscillometry system (IOS) are increasingly being utilized for measuring lung mechanics because they require only minimal participation, …

Targeting The Γ-Aminobutyric Acid A Receptor (Gabaar) To Alleviate Inflammation For Asthma And Neuropathic Pain, Amanda Nicole Nieman

Theses and Dissertations

The γ-Aminobutyric Acid A Receptor (GABAAR) is a ligand-gated, pentameric chloride channel composed of subunits that include α1-6, β1-3, γ1-3, δ, ε, π, θ, ρ1-3.1-2 The most common arrangement includes two α subunits, two β subunits, and a γ subunit.3 This receptor includes two binding sites for the endogenous ligand γ-aminobutyric acid (GABA) between the α and β subunits and a binding site between the α and γ subunit for benzodiazepines, a large family of positive allosteric modulators.4-5

Benzodiazepines are one of the most prescribed classes of pharmaceuticals to treat anxiety, insomnia, and epilepsy as well as for muscle relaxation.6-7 …

Urban Air Quality, Spring/Summer 2002, Issue 6

Sustain Magazine

No abstract provided.

Investigation Of Therapeutic Immune Cell Metabolism, Josephine Anna Tueller

Theses and Dissertations

This thesis addresses multiple approaches to investigating mechanisms of immune linked disease. There are four projects outlined below which describe the work of these investigations. First, educating students about techniques to study disease and therapies is an important area of research. Flow cytometry is a common technique in immunology and its versatility and high throughput abilities can be applied to many fields. While it is very useful, flow cytometry is a complex technique that requires training to operate and understand, and there are very few reports about administering effective training. This thesis outlines the first report of a full semester …

Bioaerosols Associated With Evaporative Cooler Use In Low-Income Homes In Semi-Arid Climates, Ashlin Elaine Cowger

Theses and Dissertations

Asthma is the leading chronic illness in children in the United States. Since children in the U.S. spend a majority of their time indoors there is an increased need to understand key sources of daily asthma triggers in the home. Bacterial endotoxin, dust mite allergens and β-D-glucan have been shown to be potent inducers of asthma attacks, and high levels of these allergens in homes can trigger attacks in those with asthma. We aim to better understand the risks to those with asthma that might be associated with evaporative cooler (EC) use in low-income homes. ECs are often promoted because …

Activation Of Toll-Like Receptor 3 Translates To Long-Term Post-Viral Lung Disease, Xinyu Wang

Arts & Sciences Electronic Theses and Dissertations

Chronic obstructive lung disease (COPD) causes substantial human and economic costs both in the US and worldwide. To identify the molecular mechanisms to allow for targeted therapies for COPD, we developed a high-fidelity mouse model of chronic lung inflammation using the natural rodent pathogen Sendai virus (SeV). While nucleic acid-sensing pattern recognition receptors are important for innate immune responses to viral pathogens, there have been few studies investigating their role in the context of chronic disease. Here we show that Toll-like receptor 3 (Tlr3) signaling is required for the development of chronic lung disease in a postviral mouse model. Activation …

Understanding The Comorbidity Of Asthma And Anxiety In Childhood: Characteristics, Vulnerabilities, And Treatment Implications, Nicole Fleischer, Elizabeth Gosch, Phil Kendall

Research Day

Introduction: Given the high incidence of asthma and anxiety comorbidity, clinicians should be informed of the unique presentation of these clients in clinical practice. Although much is known about the development and characteristics of childhood anxiety, less is known about children with anxiety and comorbid asthma.

Methods: This study, using archival data, examined the potential differences in children with comorbid asthma and anxiety compared to children with anxiety from a random controlled trial. These two groups were compared on negative self-talk, number of physical symptoms, parent anxiety, content of their worries, and presence of panic, generalized anxiety, and …

Design And Synthesis Of Achiral And Chiral Imidazodiazepine (Imdz) Gaba(A)R Subtype Selective Ligands For The Treatment Of Cns Disorders, As Well As Asthma, Guanguan Li

Theses and Dissertations

Gamma-aminobutyric acid type A receptors (GABAAR) are transmembrane pentameric ligand-gated chloride ion channels that respond to GABA, the major inhibitory neurotransmitter in the central nervous systems (CNS). The benzodiazepines (BZDs) bind at the extracellular interface of the α+γ2-subunits of GABAAR. The binding of ligands at different subunits of GABAA receptors specifically at α1-6β2/3 γ2 ion channels, can affect a wide variety of brain functions. The α1-subtype selective ion channels of GABAARs are involved in the sedative, ataxic, amnesic, anticonvulsant and addictive effects, which should be avoided, with the exception of the anticonvulsant effects, when designing ligands for this BZ allosteric …

A Study On Vitamin D Metabolic Genes Single Nucleotide Polymorphisms And Their Linkage In Adult Asthmatic Emiratis, Amneh Mohammad Al Mousa

Biology Theses

Vitamin D normal levels are vital to many biological processes including its classical role in calcium and phosphate homeostasis, and regulation of immune and non-immune cells. Vitamin D mediates its actions via the vitamin D receptor (VDR) which is expressed in most tissues of the body including the airway smooth muscle. Asthma is a syndrome of chronic inflammatory airway disease. There is a genetic and immunological link between vitamin D and asthma. In this study, we aim to investigate whether asthma and its severity were associated with single nucleotide polymorphisms (SNPs) in vitamin D metabolic genes as well as vitamin …

Resveratrol Attenuates Allergic Asthma And Associated Inflammation In The Lungs Through Regulation Of Mirna-34a That Targets Foxp3 In Mice, Esraah Alharris, Hasan Alghetaa, Ratanesh K. Seth, Saurabh Chatterjee, Narendra P. Singh, Mitzi Nagarkatti, Prakash Nagarkatti

Faculty Publications

Asthma is a chronic inflammatory disease of airways mediated by T-helper 2 (Th2) cells involving complex signaling pathways. Although resveratrol has previously been shown to attenuate allergic asthma, the role of miRNA in this process has not been studied. We investigated the effect of resveratrol on ovalbumin-induced experimental allergic asthma in mice. To that end, BALB/c mice were immunized with ovalbumin (OVA) intraperitoneally followed by oral gavage of vehicle (OVA-veh) or resveratrol (100 mg/kg body) (OVA-res). On day 7, the experimental groups received intranasal challenge of OVA followed by 7 days of additional oral gavage of vehicle or resveratrol. At …

Effects Of Ambient Air Pollution On Asthma-Related Emergency Department Visits Within The Las Vegas Metropolitan Area, Loiren E. Monardes

UNLV Theses, Dissertations, Professional Papers, and Capstones

The objective of this research was to evaluate the risk for asthma-related Emergency Department visits and their association with ambient air pollution within the Las Vegas metropolitan area. All data were aggregated by date and ZIP Code. The association was analyzed by applying the distributed lag non-linear model in an attempt to identify elevated concentrations of specific air pollutants

as triggers and their delayed effects (lag days). Relative Risk (RR) and 95% confidence intervals were produced, while adjusting for socioeconomic status. This ecological population-based study analyzed daily asthma counts of Emergency Department visits from January 1st, 2009 to December 31st, …