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Full-Text Articles in Medicine and Health Sciences
Chronic Hiv Infection Influences The Immune Response To Sars-Cov-2, Skye Opsteen
Chronic Hiv Infection Influences The Immune Response To Sars-Cov-2, Skye Opsteen
All ETDs from UAB
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global morbidity and mortality since late 2019. Many infections result in self-limited disease and recovery in 1-2 weeks. However, a subset of individuals experience more severe illness, associated with hospitalization, ventilation, and potential mortality. HIV infection is a proposed risk factor for more severe illness due to people living with HIV (PLWH) experiencing chronic immune activation and inflammation despite effective antiretroviral therapy. While there is supporting evidence showing worsened clinical outcomes in PLWH experiencing acute COVID-19, the immune response driving these outcomes is less explored. We analyzed markers of immune activation …
Exploring The Influence Of Psychosocial Stress And Inflammatory Properties Of The Diet On Cardiometabolic Risk And Gut Microbiome Health Among Young Adult Women Of Birmingham, Alabama, Rachel Olivia Knight
Exploring The Influence Of Psychosocial Stress And Inflammatory Properties Of The Diet On Cardiometabolic Risk And Gut Microbiome Health Among Young Adult Women Of Birmingham, Alabama, Rachel Olivia Knight
All ETDs from UAB
Concerning trends for obesity, diabetes, heart attacks, and obesity-related cancers, or cardiometabolic disease (CMD), are developing within the emerging and young adult/adulthood (EYA) population. Evidence supports the concept that chronic stress leads to physiologic dysregulation, reduced mental health, chronic diseases, and reduced longevity; however, these are not inevitable outcomes, and resilience or vulnerability is determined by interacting environmental and biobehavioral factors. Although CMD manifests clinically in older adulthood, disease pathophysiology begins earlier, and thus, EYA is a critical time for observation and intervention. Growing evidence indicates inflammation is a major risk factor in CMD development and may be exacerbated by …
Integrated Phenotypic And Molecular Expression Circuits In End-Stage Osteoarthritis, Devin J. Drummer
Integrated Phenotypic And Molecular Expression Circuits In End-Stage Osteoarthritis, Devin J. Drummer
All ETDs from UAB
Osteoarthritis (OA) is a debilitating, inflammatory, joint degeneration disorder, and is the most common form of arthritis. Individuals reaching end-stage OA often pursue elective total hip/knee arthroplasty (THA/TKA) to relieve pain and improve mobility and quality of life. However, approximately one third of THA/TKA patients suffer long-term mobility impairments following surgery, likely in part due to an inability to repair the damaged muscle surrounding the diseased joint. Mechanisms driving this impaired recovery remain poorly understood, therefore it is prudent to interrogate the molecular signatures in skeletal muscle at the time of surgery to provide candidate markers that may improve upon …
Early Life Stress And Barrier Dysfunction Of The Blood-Brain Barrier, Margaret Ellen Lloyd
Early Life Stress And Barrier Dysfunction Of The Blood-Brain Barrier, Margaret Ellen Lloyd
All ETDs from UAB
Early Life Stress (ELS) refers to any process or event of chronic and/or sever stress that occurs early in an individual’s development; this can be spurred by environmental or behavioral cues and helps predict inflammation later1 in life. ELS is associated with increased risk of cardiovascular disease (CVD) and other chronic conditions like depression. However, many of the physiological processes that lead to increased risk of chronic illness later in life have yet to be established or examined. The ELS mouse model is used to examine the unknown mechanistic links between childhood stress and risk for chronic disease in adulthood. …
Glycoprotein 340 Expression In Dry Eye Disease And Ocular Surface Infection, Kwaku Antwi Osei
Glycoprotein 340 Expression In Dry Eye Disease And Ocular Surface Infection, Kwaku Antwi Osei
All ETDs from UAB
Glycoprotein 340 (Gp340) is a 340-kDa multi-domain pattern recognition receptor (PRR) belonging to the scavenger receptor cysteine-rich superfamily of proteins. On the ocular surface, Gp340 is expressed in the tear film, lacrimal gland, cornea, and conjunctiva. By their nature, PRRs detect pathogen-associated molecular patterns (PAMPs) on microbial organisms and damage-associated molecular patterns (DAMPs) released from injured, stressed, necrotic, and apoptotic cells. This, in turn, induces the expression of nuclear factor-κB- and the interferon regulatory factor-dependent expression proinflammatory cytokines and chemokines, eliciting both innate and adaptive immune response activation. Thus, as a PRR, Gp340 has the potential to modulate microbial infection …
Hyperphosphatemia Contributes To Functional Iron Deficiency And Skeletal Muscle Wasting, Brian Anthony Czaya
Hyperphosphatemia Contributes To Functional Iron Deficiency And Skeletal Muscle Wasting, Brian Anthony Czaya
All ETDs from UAB
Chronic kidney disease (CKD) is a global health threat that increases risk of death, which is credible to both impaired renal function and a multitude of CKD- associated comorbidities such as systemic inflammation, anemia and skeletal muscle dys- function. A distinctive feature of CKD is the dysregulation of mineral metabolism, where excess serum levels of phosphate (hyperphosphatemia) and of fibroblast growth factor 23 (FGF23) are not only viewed as biomarkers for disease severity but also exert deleterious effects towards various CKD-associated pathologies. Elevated levels of FGF23 can lead to the activation of FGF receptor 4 (FGFR4) in cell types that …
The Hocl Response Of Escherichia Coli., Rhea Marie Derke
The Hocl Response Of Escherichia Coli., Rhea Marie Derke
All ETDs from UAB
Inflammatory bowel diseases (IBDs), like Chron’s disease and ulcerative colitis, affect millions of people worldwide. There are limited treatment options available for these diseases because their direct causes are unknown. IBDs are characterized by chronic inflammation of the gastrointestinal tract and changes in the composition of the gut microbiome. Enterobacteria, including Escherichia coli, bloom to high levels in the gut during inflammation and contribute to the pathology of IBDs. E. coli must tolerate high levels of antimicrobial compounds produced by the immune system to survive during persistent inflammation. A large proportion of such compounds are reactive oxygen and reactive chlorine …
Vagal Mediated Heart Rate Variability And Cognitive Impairments In Hiv-Seropositive Women, William C. Nicholson
Vagal Mediated Heart Rate Variability And Cognitive Impairments In Hiv-Seropositive Women, William C. Nicholson
All ETDs from UAB
Regardless of sufficient viral suppression, HIV exerts an ongoing inflammatory process that promotes chronic autonomic nervous system (ANS) dysfunction, accelerates physiological aging, and increases the risk of developing a spectrum of cognitive disorders (known as HIV-associated neurocognitive disorders [HAND]). Given this, identifying pathological mediators of this inflammatory response could provide insight into the mechanisms driving HAND. The vagus nerve (indexed by vagal-mediated heart rate variability [vmHRV]) could provide such a mediator as it regulates ANS activity via reciprocal cardio-neural pathways, which regulate inflammation and homeostasis. Vagal dysfunction is associated with persistent inflammatory signaling (e.g., stress or inflammatory-based disorders [such as …
The Closed Eye As A Model For Dry Eye Disease, Cameron Kenneth Postnikoff
The Closed Eye As A Model For Dry Eye Disease, Cameron Kenneth Postnikoff
All ETDs from UAB
Every night, during sleep, the tears of the closed eye become significantly more inflammatory, with a notable influx of neutrophils. Preliminary studies suggested that these neutrophils were significantly different than blood-isolated neutrophils, with an increased concentration, upregulated surface expression of inflammatory membrane receptors, but inability to respond to inflammatory stimuli. The purpose of this dissertation was to better understand the contribution of this neutrophil population to ocular surface homeostasis and dry eye disease. Chapter One presents an introduction to the tear film and ocular surface, along with an introduction to dry eye disease and neutrophil biology. Chapter One also discusses …
Dysregulation In The Central Nervous System Upon Mcmv Infection In Newborn Mice, Cathy Yea Won Sung
Dysregulation In The Central Nervous System Upon Mcmv Infection In Newborn Mice, Cathy Yea Won Sung
All ETDs from UAB
Human cytomegalovirus (HCMV) infection is a major cause of morbidity in infants and children throughout the world. Between 0.2-1.2% of all live births is infected with HCMV in the United States. Approximately 5-15% of these newborn babies will develop long-term neurological damage resulting in motor disorders, mental retardation, and sensorineural hearing loss. Although the neurological sequelae associated with congenital HCMV infections are well characterized, little is known about the pathogenesis of the damage to the central nervous system (CNS). To study the pathogenesis of congenital HCMV infection, we have developed a mouse model in which newborn mice are infected intraperitoneally …
Streptococcus Pneumoniae In The Heart Subvert The Host Response Through Biofilm-Mediated Resident Macrophage Killing, Anukul T. Shenoy
Streptococcus Pneumoniae In The Heart Subvert The Host Response Through Biofilm-Mediated Resident Macrophage Killing, Anukul T. Shenoy
All ETDs from UAB
During invasive disease, blood circulating Streptococcus pneumoniae are capable of invading the heart and forming bacteria filled cardiac microlesions. These microlesions are devoid of immune cells and disruptive of cardiac functionality. While the mechanisms underlying pneumococcal invasion of the myocardium are well-described, how the heart-invaded pneumococci evade immune detection and clearance is unknown. Since its discovery in 1881, invasive pneumococcal disease has been associated with the presence of extracellular diplococci or short chains in affected tissues. Herein, we show that heart-invaded pneumococci replicate within cellular vesicles and transition into biofilms. Although the host cell permissible for intracellular replication is yet …
Activation Of Ampk To Diminish Sepsis-Induced Lung Injury, Nathaniel Bone
Activation Of Ampk To Diminish Sepsis-Induced Lung Injury, Nathaniel Bone
All ETDs from UAB
Sepsis is the most frequent cause of death of hospitalized patients in modern ICUs. Severe infection, trauma, hemorrhage, burns, and surgery are significant causes of multi-organ injury and immune dysfunction that in turn primes for a high risk of secondary lung infections. In addition to detrimental inflammation, sepsis is linked to loss of metabolic plasticity due to mitochondrial dysfunction in immune cells and lung tissue. In particular, mitochondrial failure in lungs of critically ill septic patients is correlated with high mortality rates. We proposed that AMP-activated protein kinase (AMPK) activation, a major bioenergetic sensor and metabolic regulator, is a plausible …
The Functional Role Of Toll-Like Receptor 4 In The Renal Microcirculation., Justin Pieter Van Beusecum
The Functional Role Of Toll-Like Receptor 4 In The Renal Microcirculation., Justin Pieter Van Beusecum
All ETDs from UAB
Renal autoregulation is an intrinsic property of afferent arterioles that maintains a stable RBF, glomerular capillary pressure, and GFR, while protecting the glomeruli against fluctuations in arterial pressure. Recently it has been reported that immune system activation and inflammation have been linked to impairment of renal autoregulatory behavior. Evidence suggests that activation of toll-like receptor 4 (TLR4) plays an important role in the progression of AKI and CKD. The contributions of innate immune system activation, TLR4 and renal autoregulatory dysfunction remain unknown. This dissertation explores the novel concept that both acute and chronic TLR4 activation leads to the attenuation of …
The Role Of Macrophages In Pressure-Overload Induced Cardiac Remodeling, Bindiya Dinesh Patel
The Role Of Macrophages In Pressure-Overload Induced Cardiac Remodeling, Bindiya Dinesh Patel
All ETDs from UAB
Cardiac pressure-overload is a state of increased hemodynamic load and is initially characterized by concentric left ventricular (LV) hypertrophy, but can transition to eccentric hypertrophy and adverse LV remodeling leading to heart failure (HF). Cardiac remodeling during pressure-overload is accompanied by dysregulated collagen deposition, cardiomyocyte hypertrophy, and increased inflammatory signaling. Both clinical and preclinical studies have documented increased expression of inflammatory cytokines and leukocyte infiltration in the pressure-overloaded heart, indicating inflammatory mechanisms are active during cardiac remodeling. Despite the well-known link between leukocyte infiltration and exacerbated tissue injury, the role of innate immune cells, particularly monocytes, macrophages and dendritic cells, …
Examining Hiv-Associated Symptom Burden And Microbial Translocation In The Veterans Aging Cohort Study: A Secondary Data Analysis, Natalie Lynn Wilson
Examining Hiv-Associated Symptom Burden And Microbial Translocation In The Veterans Aging Cohort Study: A Secondary Data Analysis, Natalie Lynn Wilson
All ETDs from UAB
The pathophysiological effects of HIV infection, including inflammation, contribute to symptom burden and poor clinical outcomes. Within the gut associated lymph tissue, immune activation leads to dysfunction of the gastrointestinal epithelial barrier and subsequent movement of microbial products from the gut into the blood. The translocation of microbial products from the gut into the blood circulation has been identified as a key contributor to HIV disease progression and chronic inflammation. Chronic inflammation has been associated with various symptoms including symptoms commonly reported in HIV disease. However, it is unknown if these symptoms are associated with inflammation related to microbial translocation. …
The Role Of Mammalian Tribbles Homolog 3 (Trb3) In Macrophage Biology; Evidence For Reciprocal Regulation Of Macrophage Function In Foam Cell Formation, Dennis Steverson
The Role Of Mammalian Tribbles Homolog 3 (Trb3) In Macrophage Biology; Evidence For Reciprocal Regulation Of Macrophage Function In Foam Cell Formation, Dennis Steverson
All ETDs from UAB
Atherosclerosis is disease characterized by dysregulated lipid metabolism and chronic inflammation. Macrophages are critical to the progression of the disease and are involved in the pathophysiology at all stages of the disease. In the early stages, macrophages are responsible for fatty streak formation by becoming foam cells through lipid uptake. In the later stages, macrophages contribute to the degradation of the fibrous cap and are largely responsible for chronic inflammation in atherosclerotic plaques. Tribbles homolog 3 (TRB3) is a pseudokinase that inhibits Akt activation by blocking its phosphorylation site. TRB3 is expressed on numerous cell types in the body (pancreatic …
The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues
The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues
All ETDs from UAB
Acute kidney injury (AKI), which manifests as an abrupt decline in renal function, occurs in ~1% of all hospitalization. Ischemia reperfusion injury (IRI), a common cause of AKI, can occur in any situation where blood flow to the kidney is significantly reduced such as hypertensive crisis, cardiovascular surgery, and inevitably during renal transplantation. Mortality from AKI is up to 80% due to incomplete knowledge of the pathogenesis of IRI and the lack of an effective therapy. It is thought that cellular damage as a result of hypoxia signals the release of proinflammatory cytokines that lead to a systemic inflammatory response. …
An Investigation Of Trem-Like Transcript 2 Expression, Kimberly Anne Thomas
An Investigation Of Trem-Like Transcript 2 Expression, Kimberly Anne Thomas
All ETDs from UAB
Acute inflammation is a necessary component for the clearance of pathogens. Cells at the site of infection utilize highly conserved receptors to both recognize microbes and induce the production of pro-inflammatory stimuli. These stimuli set off a chain reaction that includes localized vasodilation, leukocyte infiltration, and tissue destruction, collectively known as inflammation. Tightly controlled, this process is protective, and can compartmentalize the damage to a defined area, but when dysregulated can be catastrophic, inducing chronic inflammation and even death. Families of innate receptors can modulate inflammatory processes, and in doing so, increase or decrease their severity, as well as tailor …
Virus-Induced Inflammation And Central Nervous System Development, Kate Kosmac
Virus-Induced Inflammation And Central Nervous System Development, Kate Kosmac
All ETDs from UAB
Congenital human cytomegalovirus (HCMV) infection is a complex cause of central nervous system (CNS) disease. Infection with HCMV during pregnancy results in virus transmission across the placenta and infection of the fetus. With a seroconversion rate in pregnant women between 1% and 4%, HCMV is the most frequently transmitted virus from mother to developing child. Each year between 2,000 and 4,000 infants will suffer from long-term neurologic deficits as a result of congenital infection. The well documented CNS sequelae resulting from congenital HCMV infection have described a wide range of damage without a specific set of pathologic markers for disease. …
Blood Pressure And Tobacco Exposure Among Rural Adolescents Ages 15-18, Luz Huntington-Moskos
Blood Pressure And Tobacco Exposure Among Rural Adolescents Ages 15-18, Luz Huntington-Moskos
All ETDs from UAB
High blood pressure is a prevalent precursor to cardiovascular disease. An estimated 3% of US adolescents have hypertension. In addition, prehypertension is predictive of hypertension in adolescents, with progression between these stages at approximately 7% per year. Tobacco use/exposure is strongly linked to cardiovascular risk and disease in adults. Further, rural communities have higher tobacco use prevalence and fewer community policies restricting tobacco use. Little is known about the effects of tobacco exposure on blood pressure and the mediating effects of inflammation (salivary C-reactive protein (CRP)) in rural adolescents. The purpose of this study is to determine the relationships between …
Apolipoprotein E Mimetic Peptide Improves Hdl Functionality And Inhibits Atherosclerosis Progression In Mouse Models Of Atherosclerosis, Gaurav Nayyar
Apolipoprotein E Mimetic Peptide Improves Hdl Functionality And Inhibits Atherosclerosis Progression In Mouse Models Of Atherosclerosis, Gaurav Nayyar
All ETDs from UAB
Despite major advances in diagnosis and treatment, coronary artery disease (CAD) is still the number one cause of morbidity and mortality in United States. An ideal treatment for lipid-mediated inflammatory disorders would not only reduce plasma cholesterol dramatically but also improve high density lipoproteins (HDL) function. Apolipoprotein E (apo E), a protein component of HDL and very low density lipoprotein (VLDL), is necessary for the receptor mediated hepatic uptake of apolipoprotein-B (apo B) containing remnant lipoproteins and also possesses strong anti-inflammatory properties. We hypothesized that a synthetic dual domain apo E mimetic peptide, Ac-hE18A-NH2 (a 28-residue peptide) containing receptor binding …
The Intestinal Extracellular Matix As An Innate Regulator Of Effector T-Cell Responses, Kayci Renee Huff
The Intestinal Extracellular Matix As An Innate Regulator Of Effector T-Cell Responses, Kayci Renee Huff
All ETDs from UAB
Extracellular matrix (stroma) regulation of mucosal T-cell function is incompletely understood. Here we uncovered a role for intestinal stromal products in the innate regulation of effector T-cells. Stroma-conditioned media (S-CM) derived from normal human intestinal stroma (TGF-&betahi/IL-6lo/IL-1ßlo) significantly down-regulated T-cell proliferation and IFN-&gamma production compared to S-CM derived from inflamed Crohn's mucosa (TGF-&betahi/IL-6hi/IL-1&betahi). Antibody neutralization studies showed that TGF-&beta in normal S-CM inhibited T-cell proliferation and IFN-&gamma production, whereas IL-6 plus IL-1&beta in Crohn's S-CM promoted T-cell proliferation, and the IL-1&beta alone promoted IFN-γ and IL-17 release. Importantly, stromal cells in normal tissue produce TGF-&beta and contribute to mucosal homeostasis …
A Recombinant Myeloid-Binding Adenovirus For Targeted Pulmonary Gene Therapy, Michael O. Alberti
A Recombinant Myeloid-Binding Adenovirus For Targeted Pulmonary Gene Therapy, Michael O. Alberti
All ETDs from UAB
Inflammation and airway destruction are hallmarks of many debilitating lung diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), acute lung injury (ALI), and cancer. Gene-based therapeutic interventions that modulate this pathologic inflammatory response are likely to reduce the progressive destruction to lung airways. In this regard, a number of strategies have been evaluated for targeting the pul-monary vasculature; particularly those based on serotype 5 Adenovirus (Ad5). The ad-vantages of Ad over other vector systems include: in vivo stability, low oncogenic poten-tial, and large packaging capacity. Yet, specific and efficient gene delivery to the lung has been hampered …
A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison
A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison
All ETDs from UAB
Chronic neutrophilic inflammation is a hallmark of numerous pulmonary diseases. It is commonly associated with declining lung function, collagen turnover, and increased protease activity. Our laboratory has recently published several articles describing a biologically active collagen breakdown product, proline-glycine-proline (PGP) and its more active amino-terminus acetylated form, N-α-PGP. PGP acts via classical chemokine receptors CXCR1 and 2 to draw neutrophils (PMNs) into sites of inflammation in what is potentially a feed-forward mechanism of disease. The tri-peptide appears to be a bio-marker in certain clinical diseases like cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The present work first details …
Effects Of Daily Versus 30-Day Continuous Contact Lens Wear On Tear Cytokine Levels, Lucy Ebunoluwa Kehinde
Effects Of Daily Versus 30-Day Continuous Contact Lens Wear On Tear Cytokine Levels, Lucy Ebunoluwa Kehinde
All ETDs from UAB
The purpose of this investigation was to determine if 30 days of continuous contact lens wear produces a different ocular inflammatory response compared to 30 days of daily wear of Bausch & Lomb® PureVisionTM silicone hydrogel contact lenses. Eighty-five individuals wore these lenses for 30 days continuously in one eye and daily in the contralateral eye. Relative concentrations of 27 cytokines were measured in tear samples collected from the subjects using cytometric bead-based assays. Clinical tests were also conducted to correlate changes in cytokine levels to changes in clinical profiles. This study contributes to a greater understanding of the impact …
The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng
The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng
All ETDs from UAB
Zinc is an essential cation for life that is involved in numerous physiology and pathophysiology processes. Despite its wide use as a cytoprotective agent in medications, its cellular and molecular mechanisms of action have not been well established. In order to define the potential therapeutic benefit of zinc, I used several Cystic Fibrosis (CF) and non-CF human airway epithelial cell lines as models in my studies. Extracellular zinc caused release calcium from the endoplasmic reticulum though zinc-sensitive Gq-coupled receptor(s) that may subsequently modulate ion channels. In addition, zinc also exhibited anti-inflammatory effects. Zinc inhibited pro-inflammatory molecular TNFα-induced cytokine and chemokine …
Protective Mechanisms Of Apoa-I Mimetic Peptide Action In Sepsis-Induced Tissue Injury, Zhenghao Zhang
Protective Mechanisms Of Apoa-I Mimetic Peptide Action In Sepsis-Induced Tissue Injury, Zhenghao Zhang
All ETDs from UAB
Sepsis is among the top ten causes of death in the US, and it is associated with severe inflammatory tissue damage and organ dysfunction. Reduced plasma high density lipoprotein (HDL) is associated with increased mortality in septic patients. Since raising plasma apolipoprotein (apo) A-I and HDL may reduce sepsis complications, we tested the hypothesis that the apoA-I mimetic peptide 4F confers similar protective effects in two animal models of sepsis, and explored the possible mechanisms. In endotoxemic rats, inflammatory mediators were significantly induced while blood pressure was significantly reduced by 6hr. The impaired arterial response to vasoconstrictors was related to …