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Inhibition Of Yeast Hexokinase By The Antimalarial Drug Artemisinin: Probing Mechanism Of Action With A Model Enzyme, Jennifer S. Spence

Biological Sciences Theses & Dissertations

A leading infectious cause of death, malaria threatens approximately half of the world's population, and drug-resistant strains of Plasmodium falciparum have created immense difficulty in chemotherapy of the disease. The artemisinin (ART) class of antimalarials may represent a powerful solution. In addition to their safety, effectiveness, and moderate cost, they are the only drugs in use for which there has been no widespread evidence of clinical resistance. The exact parasiticidal mechanism of ART is highly contested, but evidence suggests that protein alkylation may play a role in cytotoxicity. in vitro essays were performed using yeast hexokinase (HK) to demonstrate a …

Impact Of Infection Control Activities On The Rate Of Needle Stick Injuries At A Tertiary Care Hospital Of Pakistan Over A Period Of Six Years: An Observational Study., Afia Zafar, Faiza Habib, Roshan Hadwani, Muslima Ejaz, Khurshid Khowaja, Rozina Khowaja, Seema Irfan

Department of Pathology and Laboratory Medicine

Background:Accidental exposure to blood and body fluids is frequent among health care workers. They are at high risk of nosocomial transmission of blood borne pathogens due to injuries caused by used sharps. We are reporting impact of surveillance and educational program on the rate of needle stick injuries among health care workers at a tertiary care hospital in Pakistan.

Methods:

At Aga Khan University Hospital sharp injuries are reported to infection control office. To reduce these incidents a quality improvement project was inducted in the year 2005. Health care workers were educated, surveillance data from 2002 to 2007 was …

Molecular Epidemiology Of Methicillin-Resistant Staphylococcus Aureus (Mrsa), Ilene Bautista

UNLV Theses, Dissertations, Professional Papers, and Capstones

Staphylococcus aureus is a frequent cause of a myriad of infections in hospitals, healthcare facilities and community settings. It is often related to skin and soft tissue infection, but it can also cause other diseases varying from food poisoning to endocarditis and toxic shock syndrome. According to a study by Kuehnert et al. (2006) there has been a strong association between Staphylococcus aureus (S. aureus) carriage and risk factors for subsequent infections. Subsequent infection from S. aureus , including methicillin-resistant S. aureus (MRSA) infection, can be projected by looking at the presence of S. aureus nasal colonization. The purpose of …

An Evaluation Of Methicillin Resistant Staphylococcus Aureus Survival On Five Environmental Surfaces Under Two Different Humidities, With And Without The Addition Of Bovine Serum Albumin, Courtney Ann Coughenour

UNLV Theses, Dissertations, Professional Papers, and Capstones

The spread of antibiotic resistant bacteria is a major public health concern, as they result in greater healthcare costs and increased morbidity and mortality rates. Methicillin resistant Staphylococcus aureus (MRSA) is one organism of particular concern, with the number of infections increasing in epidemic proportion. Bacterial surface contamination with MRSA is significant, as it may serve as a reservoir for transmission and have negative health implications. The purpose of this study was to evaluate survival of MRSA on five environmental surface materials; glass, wood, vinyl, plastic, and cloth. The effect of relative humidity (RH) and bovine serum albumin (BSA) were …

Esat6-Induced Ifngamma And Cxcl9 Can Differentiate Severity Of Tuberculosis., Zahra Hasan, Bushra Jamil, Mussarat Ashraf, Muniba Islam, Muhammad S Yusuf, Javaid A Khan, Rabia Hussain

Department of Pathology and Laboratory Medicine

Background: Protective responses against Mycobacterium tuberculosis are dependent on appropriate T cell and macrophage activation. Mycobacterial antigen six kDa early secreted antigenic target (ESAT6) and culture filtrate protein 10 (CFP10) can detect M. tuberculosis specific IFNgamma responses. However, most studies have been performed in non-endemic regions and to study pulmonary tuberculosis (PTB). We have studied ESAT6 and CFP10 induced cytokine and chemokines responses in PTB and extrapulmonary (EPul) TB.
Methodology: IFNgamma, IL10, CXCL9 and CCL2 responses were determined using an ex vivo whole blood assay system in PTB (n = 30) and EPulTB Patients with limited (LNTB, n = …

Comparison Of Immune Correlates, Age Related Changes And Proteomic Profiling Of Healthy Individuals Receiving Influenza Vaccines, Gaurav Basu

Theses and Dissertations in Biomedical Sciences

The burden of influenza related infections is substantial, both in terms of illness, lives lost and economic impact on society. The degree of impact of influenza related infections is much higher in the elderly population where it is a leading cause of catastrophic disability; greatly affecting the quality of life of elderly persons above 65 years of age. Vaccination is the mainstay for control and prevention of influenza infections. There are two vaccine formulations that are licensed for use at present. The inactivated influenza vaccines (TIIV) which have been used for 60 years in all age groups and the new …

Long-Distance Delivery Of Bacterial Virulence Factors By Pseudomonas Aeruginosa Outer Membrane Vesicles, Jennifer M. Bomberger, Daniel P. Maceachran, Bonita A. Coutermarsh, Siying Ye, George A. O'Toole, Bruce A. Stanton, Frederick M. Ausubel

Dartmouth Scholarship

Bacteria use a variety of secreted virulence factors to manipulate host cells, thereby causing significant morbidity and mortality. We report a mechanism for the long-distance delivery of multiple bacterial virulence factors, simultaneously and directly into the host cell cytoplasm, thus obviating the need for direct interaction of the pathogen with the host cell to cause cytotoxicity. We show that outer membrane–derived vesicles (OMV) secreted by the opportunistic human pathogen Pseudomonas aeruginosa deliver multiple virulence factors, including β-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif, directly into the host cytoplasm via fusion of OMV with lipid rafts in the host plasma …

Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and …

Pathogenic Adaptation Of Intracellular Bacteria By Rewiring A Cis-Regulatory Input Function, Suzanne E. Osborne, Don Walthers, Ana M. Tomljenovic, David T. Mulder, Uma Silphaduang, Nancy Duong, Michael J. Lowden

Dartmouth Scholarship

The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a …

From Genome-Based In Silico Predictions To Ex Vivo Verification Of Leprosy Diagnosis, Annemieke Geluk, John S. Spencer, Kidist Bobosha, Maria C. V. Pessolani, Geraldo M. B. Pereira, Sayera Banu, Nadine Honore, Stephen T. Reece, Murdo Macdonald, Bishwa Raj Sapkota, Chaman Ranjit, Kees L. M. C. Franken, Martha Zewdie, Abraham Aseffa, Rabia Hussain, Mariane M. Stefani, Sang-Nae Cho, Linda Oskam, Patrick J. Brennan, Hazel M. Dockrell

Department of Pathology and Laboratory Medicine

The detection of hundreds of thousands of new cases of leprosy every year suggests that transmission of Mycobacterium leprae infection still continues. Unfortunately, tools for identification of asymptomatic disease and/or early-stage M. leprae infection (likely sources of transmission) are lacking. The recent identification of M. leprae-unique genes has allowed the analysis of human T-cell responses to novel M. leprae antigens. Antigens with the most-promising diagnostic potential were tested for their ability to induce cytokine secretion by using peripheral blood mononuclear cells from leprosy Patients and controls in five different areas where leprosy is endemic, 246 individuals from Brazil, Nepal, Bangladesh, …

Effects Of The Pathogenic Water Mold Saprolegnia Ferax On Survival Of Amphibian Larvae, John M. Romansic, Kristin A. Diez, Elise M. Higashi, James E. Johnson, Andrew R. Blaustein

All Faculty Scholarship for the College of the Sciences

Infectious diseases are a significant threat to worldwide biodiversity. Amphibian declines, a significant part of current biodiversity losses, are in many cases associated with infectious disease. Water molds are one group of pathogens affecting amphibians on a worldwide basis. Although water molds have been studied extensively for their effects on host embryos, little information is available about how they affect post-embryonic amphibians. We tested the effects of one species of water mold, Saprolegnia ferax, in a comparative study of larvae of 4 amphibian species: Pseudacris regilla (Pacific treefrog), Rana cascadae (Cascades frog), Ambystoma macrodactylum (long-toed salamander), and R. aurora (red-legged …

Molecular Coevolution Of Pacific Northwest Hantaviruses And Their Host, The Deer Mouse, Peromyscus Maniculatus, Philip Darren Jones

Dissertations and Theses

Sin Nombre virus (SNV, family Bunyaviridae, genus Hantavirus), hosted by the deer mouse, Peromyscus maniculatus (family Cricetidae, Subfamily Neotominae), is the primary etiological agent of Hantavirus pulmonary syndrome (HPS) in the western United States. HPS, with known pathogenicity only to humans and for which there is no cure or prophylaxis, affects the epithelium of the lungs by making the capillaries leaky, thereby resulting in bilateral infiltrates, and eventually leading to respiratory failure and death by drowning in approximately 38% of hospitalized patients.

In the Americas, Peromyscus has been co-evolving with hantaviruses for approximately 12–20 million years, since the first …

Failure Of E. Coli Bacteria To Induce Preterm Delivery In The Rat, Emmet Hirsch, Yana Filipovich, Roberto Romero

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

We sought to develop a model of bacterially induced preterm delivery in rats to parallel similar models in mice.

Methods

Female Sprague-Dawley rats on day 17 of gestation (normal term = 21–22 days) were inoculated into the uterus with either 2 × 10⁹ – 7 × 10¹⁰ killed E. coli organisms, 1 – 4 × 10⁸ live E. coli or sterile solution. These inoculations were made either via trans-cervical catheter or by direct intrauterine injection at laparotomy. Animals were then observed for delivery for variable periods up to term. Necropsies were performed and fetal viability …

X4 Human Immunodeficiency Virus Type 1 Gp120 Down-Modulates Expression And Immunogenicity Of Codelivered Antigens, Avi-Hai Hovav, Michael Santosuosso, Maytal Bivas-Benita, Andre Plair, Alex Cheng, Mazal Elnekave, Elda Righi, Tao Chen, Satoshi Kashiwagi, Michael W. Panas, Shi-Hua Xiang, Karina Furmanov, Norman L. Letvin, Mark C. Poznansky

Nebraska Center for Virology: Faculty Publications

In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such

as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120

protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and

future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune

response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120

alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin

in a mouse model. We found that the presence of gp120 …

Identification And Characterization Of A New Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator (Rta)- Responsive Element Involved In Rta-Mediated Transactivation, Hui-Ju Wen, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) is well established as a key transcriptional activator that regulates the KSHV life cycle from latency to lytic replication. It is expressed immediately after infection and activates a number of viral genes leading to virus replication. The RTA-responsive element (RRE) in the RTA target gene promoters is critical for RTA to mediate this transactivation. A number of non-conserved RREs have been identified in various RTA-responsive promoters, and AT-rich sequences have been proposed to serve as RTA targets, but no consensus RRE sequence has been identified so far. Two nonconserved RREs (RRE1 …

Use Of Average Mutual Information For Studying Changes In Hiv Populations, Khalid Sayood, Federico Hoffman, Charles Wood

Nebraska Center for Virology: Faculty Publications

Average mutual information (AMI) has been used in a number of applications in bioinformatics. In this paper we present its use to study genetic changes in populations; in particular populations of HIV viruses. Disease progression of HIV-1 infection in infants can be rapid resulting in death within the the first year, or slow, allowing the infant to survive beyond the first year. We study the development of rapid and slow progressing HIV population using AMI charts based on average mutual information among amino acids in the env gene from a population of 1142 clones derived from seven infants with slow …

Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and …

Host And Seasonal Effects On The Infection Dynamics Of Skrjabinoptera Phrynosoma (Ortlepp) Schulz, 1927, A Parasitic Nematode Of Horned Lizards, Kathryn Claire Hilsinger

College of Graduate Studies: Theses & Dissertations

Author's Abstract: Skrjabinoptera phrynosoma (Ortlepp) Schulz, 1927 is a common parasitic nematode of horned lizards. The life cycle of S. phrynosoma was described by Lee in 1957, but has received little attention since. The present study addressed effect of season as well as host characteristics on the infection dynamics in lizard hosts. In the Alvord Basin in southeastern Oregon, S. phrynosoma were collected from Phrynosoma platyrhinos Gerard 1852 horned lizards via stomach flushes, cloaca flushes and fecal pellet collections. Parasite load variables (number of nematodes per host, length of those nematodes, and total worm burden (ΣL)) were analyzed within three …

Generation And Maintenance Of Protective Igm Responses During Intracellular Bacterial Infection, Rachael Denise Racine

Legacy Theses & Dissertations (2009 - 2024)

It is widely accepted that IgM provides the first line of defense against during microbial infection prior to the generation of high-affinity, isotype-switched antibodies, which is the hallmark of long-lived lived immunity and immunological memory. The overall objective of these studies was to address the role of IgM in the generation and maintenance of protective immunity during intracellular bacterial infection. We have identified a population of CD11clo plasmablasts that were responsible for nearly all of the antigen-specific IgM production in the spleen. Moreover, selective depletion of the CD11c-expressing B cells during acute infection resulted in a complete loss in the …

The Impact Of Environment On Virulence Of The Pathogenic Yeast Cryptococcus Gattii, Deborah Jean Springer

Legacy Theses & Dissertations (2009 - 2024)

Four serotypes of Cryptococcus are responsible for most human and animal infections. C. gattii , serotype B and C, are the primary the causative agent of cryptococcosis in immune competent individuals whilst, C. neoformans var. neoformans serotype D, and C. neoformans var. grubii serotype A are most prevalent in immunocompromised hosts world-wide. C. gattii is recognized as a species distinct from C. neoformans based on differences in clinical manifestations, morphology, biological characteristics, and environmental niche. We used the plant model Arabidopsis thaliana plants and plant derived substrates as a model to explore C. gattii interactions in its ecological niche. C. …

Identification Of B-Cell Epitopes On Domain 4 Of Anthrax Protective Antigen, Cassandra D. Kelly-Cirino

Legacy Theses & Dissertations (2009 - 2024)

Protective Antigen (PA) is the receptor binding subunit common to both Lethal (LT) and Edema (ET) toxins, which contribute to the mortality associated with Bacillus anthracis infection. While recombinant PA (rPA) is likely to be an important constituent of second generation anthrax vaccines, evaluating the effectiveness of candidate vaccines is currently difficult, because the specific B cell epitopes involved in toxin neutralization have not been completely defined. The only well characterized antibody, 14B7, has been shown to disrupt the association of PA with the anthrax toxin receptors (ATR) by binding to domain 4 of PA. I hypothesized that other domain …

Incorporation Of Membrane-Bound, Mammalian-Derived Immunomodulatory Proteins Into Influenza Whole Virus Vaccines Boosts Immunogenicity And Protection Against Lethal Challenge, Andrew S. Herbert, Lynn Heffron, Roy Sundick, Paul C. Roberts

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1), demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC). Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine.

Results

We have evaluated the immunogenicity of inactivated cytokine-bearing influenza …

Results From A Mathematical Model For Human Monocytic Ehrlichiosis, H. Gaff, L. Gross, E. Schaefer

Biological Sciences Faculty Publications

Human monocytic ehrlichiosis (Ehrlichia chaffeensis), HME, is a tick-transmitted, rickettsial disease that has recently increased substantially in the USA from 142 reported cases in 2001 to 506 reported cases in 2005 [1,2]. There have been increasing surveys of tick populations over the past 10 years that have in turn supported the development of models for tick-borne disease transmission. Resulting HME models [3] suggest the importance of metapopulation structures, landscape environment parameters and periodic climatic effects in predicting the dynamics of HME transmission and the efficacy of control efforts, such as the reduction of the tick population through acaricide …

In Step With Hiv Vaccines? A Content Analysis Of Local Recruitment Campaigns For An International Hiv Vaccine Study, Paula M. Frew, Wendy Macias, Kayshin Chan, Ashley Harding

Environmental & Global Health Faculty Research

During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the “Step …

Electroporation For The Delivery Of Dna-Based Vaccines And Immunotherapeutics: Current Clinical Developments, Angela M. Bodles-Brakhop, Richard Heller, Ruxandra Draghia-Akli

Bioelectrics Publications

Electroporation (EP) has been used in basic research for the past 25 years to aid in the transfer of DNA into cells in vitro. EP in vivo enhances transfer of DNA vaccines and therapeutic plasmids to the skin, muscle, tumors, and other tissues resulting in high levels of expression, often with serological and clinical benefits. the recent interest in nonviral gene transfer as treatment options for a vast array of conditions has resulted in the refinement and optimization of EP technology. current research has revealed that EP can be successfully used in many species, including humans. clinical trials are …

Protection Of Macrophages J774a.1 By Purine Nucleoside Analogues From Bacillus Anthracis Mediated Necrosis, Zadkiel R. Alvarez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Eight years after the lamentable anthrax attacks, major scientific effort continues to be done, in order to stop imminent acts of bioterrorism. Innovative ways of therapy against the anthrax disease are being investigated. B. anthracis, the etiological agent of the infection, has a dormant stage in its life cycle known as the endospore. When conditions become favorable spores germinate, transforming into vegetative bacteria. In inhalational anthrax, the most fatal manifestation of the disease, spores enter the organism through the respiratory track, and are phagocytosized by alveolar macrophages of the lungs. Spores are able to sense nutrient availability, activating their germination …

Molecular Characterization Of Gastroenteritis Viruses Among Equines And Porcines In Southern Ireland From 2005-2007., P. J, Collins

Theses

Rotaviruses are a major cause of gastroenteritis in humans and animals. To date, seven serogroups (A to G) of rotavirus have been determined. Group A Rotaviruses (GARVs) are enteric pathogens, causing acute watery dehydrating diarrhea in various host species, including birds and mammals. Rotaviruses account for ~611,000 child deaths each year, mainly in developing countries. Likewise, rotavirus-associated enteritis is a major problem in young calves, weaning and post-weaning piglets and foals. Vaccines against the most important serologic group of rotaviruses (GARVs) are available for the prevention of rotavirus diseases in cows and horses, and, more recently, they have been made …

The Detection And Analysis Of Selected Pathogens In The Water Supply Of Dairy Cohort Herds., Niall Drummond

Theses

The issue of food safety is a growing concern to Irish agriculture and to the food industry. In the last twenty years, many novel pathogens, which can cause concern to the food industry, have been identified. Organisms such as Verocytotoxigenic Escherichia coli (VTEC) cause hemorrhagic colitis and Haemolytic Uremic Syndrome (HUS), which is the major cause of acute renal failure in children in many countries, and it’s presence in food is a cause of growing concern. Other pathogens causing concern are those implicated as causative agents of Acute Gastroenteritis (AGE) and these can be bacterial, viral and parasitic organisms.

Consumption …

Host Defense Mechanisms Against Mycobacterium Tuberculosis, Laurin Nicole Holloway

Browse all Theses and Dissertations

Mycobacterium tuberculosis is one of the world's most infectious diseases. Approximately 2 million people die each year from Mycobacterium tuberculosis infection and one-third of the world's population remains infected. For decades research has focused on uncovering the tactics used by Mycobacterium tuberculosis to evade host immune responses and defense mechanisms used to fight tuberculosis infection. The following review focuses on the host defense mechanisms used to combat Mycobacterium tuberculosis with an emphasis placed on the roles that Toll-like receptors (TLRs), T cells (gamma delta, CD4, CD8), and macrophages play in mounting the innate and adaptive immune responses necessary to eradicate …

Characterization Of A Monothiol Glutaredoxin Encoded By Chlorella Virus Pbcv-1, Lisa A. Fitzgerald, Yuanzheng Zhang, Gentry L. Lewis, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Annotation of the 330-kb Chlorella virus PBCV-1 genome identified a 237 nucleotide gene (a438l) that codes for a protein with ~35% amino acid identity to glutaredoxins (Grx) found in other organisms. The PBCV-1 protein resembles classical Grxs in both size (9 kDa) and location of the active site (N-terminus). However, the PBCV-1 Grx is unusual because it contains a monothiol active site (CPYS) rather than the typical dithiol active site (CPYC). To examine this unique active site, four sitespecific mutants (CPYC, CPYA, SPYC, and SPYS) were constructed to determine if the N-terminal cysteine is necessary for enzyme activity. …