Medicine and Health Sciences Commons^™

Prion Disease: A Challenging Diagnosis, Jeffrey F. Spindel, Anita M. Fletcher, William T. Smith, Rodrigo Cavallazzi

The University of Louisville Journal of Respiratory Infections

Introduction: Human prion diseases are a group of rare encephalopathies resulting in rapidly progressive dementia and ultimately death. While there are no effective treatments for any form of prion disease, prompt and efficient diagnosis is essential to prevent the spread of the self-propagating protein, which may occur through aerosols, and avoid unnecessary or invasive testing. Diagnosis relies largely on physical examination, with many nonspecific findings, and laboratory testing, which has wide ranges of reported accuracy and high false positive rates with diseases such as Alzheimer’s dementia.

Methods: Patients who underwent testing for prion disease were retrospectively identified from the electronic …

Microbial Influence On Alzheimer's Disease, Ashley N. Hamby

The Cardinal Edge

No abstract provided.

The Importance Of Noncapped Viral Genomic Rna To Alphaviral Infection And Pathogenesis., Autumn Lapointe

Electronic Theses and Dissertations

Alphaviruses are mosquito-borne arboviruses that have a positive sense, single-stranded RNA genome, which are capable of causing severe disease and thus pose a significant burden to public health. During alphaviral replication, significant quantities of viral genomic RNAs that lack the canonical alphaviral 5’ cap structure are produced and packaged into viral particles, despite the fact that these noncapped genomes cannot be translated and are essentially noninfectious. The production and packaging of the noncapped genomes has been found to be true for infections across multiple vertebrate and invertebrate cell lines and alphavirus species, although the proportion of ncgRNA produced differs. Despite …

Streptococcus Anginosus Lung Infection And Empyema: A Case Report And Review Of The Literature, Nishita Tripathi, Kuldeep Ghosh, Anupama Raghuram

The University of Louisville Journal of Respiratory Infections

Streptococcus milleri group (SMG) also referred to as the Streptococcus anginosus group. These are Gram-positive, variable hemolysis, catalase negative, microaerophilic, non-motile facultative anaerobes which have been known to cause abscesses in humans. We report a case of empyema caused by Streptococcus anginosus in a patient with an unresolved pneumonia for over a month. In early October 2018, the patient presented to an emergency room with the complaints of shortness of air, productive cough, chills, subjective fever and weight loss for 4 weeks. A chest X-ray revealed a left lower lobe pneumonia. He was treated with 250 mg of azithromycin for …

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …

How Immune T-Cell Augmentation Can Help Prevent Covid-19: A Possible Nutritional Solution Using Ketogenic Lifestyle, Ravi K. Kamepalli Md,Fidsa,Cwsp

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Severity Of Disease And Mortality For Hospitalized Patients With Community-Acquired Viral Pneumonia Compared To Patients With Community-Acquired Bacterial Pneumonia, Richard Y. Kim, Thomas Chandler, Stephen P. Furmanek, Timothy Lee Wiemken, Rodrigo Cavallazzi

The University of Louisville Journal of Respiratory Infections

Background: There exists a large body of literature to help identify, diagnose, treat, and manage community-acquired pneumonia (CAP). Despite this, there is little data that directly compares the clinical syndromes and complications of pure bacterial pneumonia to pure viral pneumonia. Our study compares the clinical presentation, morbidity and mortality of viral vs. bacterial etiologies of CAP.

Methods: This was a secondary data analysis of the Community-Acquired Pneumonia Organization (CAPO) international study database. Data was collected concerning patient demographics, physical examination findings, laboratory findings, radiological findings, severity of illness, and clinical outcomes and stratified according to the two study groups, CAVP …

Coping With Chronic Fungal Rhinosinusitis: Diagnosis To Therapy, Veronica Corcino, Leslie Beavin, Shengli Lu, Ashley Ross, Carmen V. Sciortino Jr.

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Nutritional Virulence Of Legionella Pneumophila., Ashley M. Best

Electronic Theses and Dissertations

Legionella pneumophila is an environment organism that parasitizes a wide range of protozoa. Growth within the environmental host primes L. pneumophila for infection of human alveolar macrophages when contaminated aerosols are inhaled. Intracellular replication within either host requires the establishment a replicative niche, known as the Legionella-containing vacuole (LCV). Biogenesis of the LCV depends on the type IVb translocation system, the Dot/Icm, to translocation >320 effectors into the host cytosol. Effectors are responsible for preventing lysosome fusion to the LCV, recruitment of ER-derived vesicles to the LCV, and modulation of a plethora of host processes to promote the intracellular …

Inflammasome Independent Leukotriene-B4 Production Drives Crystalline Silica Induced Sterile Inflammation., Bindu Hegde

Electronic Theses and Dissertations

Silicosis is an irreversible lung inflammatory disease caused by chronic exposure to crystalline silica (CS) and is one of the most prevalent occupational diseases worldwide. Lipid chemoattractant Leukotriene B₄ (LTB₄) plays an important role in neutrophilic inflammation that drives silicosis and promotes lung cancer. Previous studies in our laboratory have demonstrated that CS-induced neutrophilic inflammation and lung tumor burden in K-ras^LA1 mice is abrogated in the LTB₄-receptor deficient mice. Another pathway whose importance is well studied in the progression of silicosis is the Nalp3 inflammasome pathway. Studies have shown inflammasome- dependent IL-1b to be …

Revisiting Neutrophil Responses To Toll-Like Receptor 4 : Influence Of Ligand Structures And Cellular Environments., Shuvasree Sengupta

Electronic Theses and Dissertations

Neutrophils respond to bacterial LPS through Toll-like receptor 4 (TLR4), which activates or potentiates immune defensive functions and prolongs cell survival. Activation of TLR4 signaling in neutrophils is beneficial for effective clearance of LPS-bearing Gram-negative bacteria, but may also drive aberrant inflammation if not stringently regulated. The regulatory processes by which neutrophil functions are calibrated to respond appropriately to different LPS-bearing bacteria are incompletely understood. Described here are investigations that reveal an unexpected sensitivity of TLR4 in neutrophils to small changes in LPS structure typical of various Gram-negative bacteria, including those that are dangerously virulent (Escherichia coli and Salmonella …

Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8, …

In Vivo Monitoring Of Therapeutic Efficacy And Virulence Profile By Bioluminescent Klebsiella Pneumoniae., Ramy Ameen Fodah

Electronic Theses and Dissertations

Klebsiella pneumoniae causes an acute respiratory infection in human with severe outcomes and high mortality rates even with antibiotic treatment. Even with its critical clinical importance, few virulence systems have been identified for K. pneumoniae limiting the development of new therapeutic strategies. Accordingly, we performed Next Generation sequencing for the strain ATCC 43816, a virulent strain in mouse respiratory disease models, and compared its genomic data with two previously sequenced strains NTUH-K2044 and MGH 78578 for the purpose of identifying genes required for colonizing host lungs. Furthermore, the virulence potential of the three K. pneumoniae strains were tested in a …

Porphyromonas Gingivalis Gingipains Induce A Pro-Inflammatory Extracellular Microenvironment : The Role Of Par-2 And Fibronectin., Jeffrey S. Marschall

Electronic Theses and Dissertations

Periodontitis is a chronic inflammatory disease that is characterized by severe tissue destruction of the gingiva and other tooth supporting structures; if left untreated, tooth loss and disintegration of the alveolar bone occurs. This chronic inflammatory state has been linked to other systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer’s disease. Porphyromonas gingivalis is the major pathogenic microbe in periodontitis. The main virulence factors of P. gingivalis are the Arg-aa and Lys-aa gingipains, which are proteolytic enzymes implicated in a plethora of activities that allow P. gingivalis to subvert the human immune system in the oral cavity …

Immunomodulation Of Myeloid-Derived Suppressor Cells By Particulate B-Glucan In Cancer., Sabrin Husein Albeituni

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we investigated the effect of dectin-1 stimulation by yeast-derived particulate β-glucan in MDSC function and differentiation in cancer. In vivo treatment of mice bearing lewis lung carcinoma and mammary cell carcinoma with particulate β-glucan decreased tumor weight and splenomegaly, and reduced the accumulation of polymorphonuclear-MDSC (PMN-MDSC) but not monocytic-MDSC (M-MDSC) in the spleen and tumor. In addition, particulate β-glucan differentially modulated the function of different MDSC subsets; it enhanced PMN-MDSC respiratory burst and apoptosis, and induced the differentiation of M-MDSC into …

The Involvement Of Beta-Catenin In The Inflammatory Response Leading To Autoimmune Diabetes Development., Arin Lee Zirnheld

Electronic Theses and Dissertations

We identified and characterized a novel defect in β-catenin expression in bone marrow derived dendritic cells (BMDC) from NOD mice, a model for human Type I diabetes. This protein is expressed at high levels throughout the lifespan of the mouse and correlates with increased pro-inflammatory cytokine production by the BMDC and IFNγ induction by T cells cocultured with the BMDC. These defects, including a similar pattern of pro-inflammatory cytokine production, are also observed in human monocytederived DC from diabetic patients. After exploring several potential mechanisms involved in the accumulation of β-catenin in NOD BMDC, we found that β-catenin is phosphorylated …

Characterization Of Seca-Sod Operon In Borrellia Burgdorferi., Tonya Lynn Nichols

Electronic Theses and Dissertations

Borrelia burgdorferi, the causative agent of Lyme disease, has been characterized as a microaerophilic spirochete. O2 consumption and utilization potentially yield reactive oxygen intermediates, such as superoxide, hydroxyl radicals, and hydrogen peroxide. This study investigated the expression of the sod gene, which encodes the only, identified oxidative defense mechanism in B. burgdorferi. Using primer extension analysis and RT-PCR, it was found that sod and secA are organized as a single transcriptional unit under the control of σ70-like promoter upstream of the secA open reading frame. Generally, gene expression decreases with increased distance from the promoter; however, secA expression was observed …