Immunology and Infectious Disease Commons^™

Environmental Implications Of Francisella Tularensis Biofilms, Jeffrey J. Margolis '00

Doctoral Dissertations

Francisella tularensis survives in one of the widest environmental ranges of any pathogen. Numerous mammals and arthropod vectors are infected by this highly virulent organism. How this zoonotic pathogen persists outside of its many hosts remains unexplored. We aimed to examine how F. tularensis interacts with environmental surfaces, and hypothesized that biofilm formation may enable survival of this organism in nature. By understanding the role these surface-attached bacterial communities play in F. tularensis ecology, we hope to gain insight into the mechanisms of environmental persistence and transmission of this pathogen.

We identify chitin as a potential non-host niche for F. …

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 …

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 …

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 …

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 …

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 …

Host Defense Mechanisms Against Mycobacterium Tuberculosis, Laurin Nicole Holloway

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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 …

An Algorithm For Identifying Novel Targets Of Transcription Factor Families: Application To Hypoxia-Inducible Factor 1 Targets, Yue Jiang, Bojan Cukic, Donald A. Adjeroh, Heath D. Skinner, Jie Lin, Qingxi J. Shen, Bing-Hua Jiang

Electrical & Computer Engineering Faculty Research

Efficient and effective analysis of the growing genomic databases requires the development of adequate computational tools. We introduce a fast method based on the suffix tree data structure for predicting novel targets of hypoxia-inducible factor 1 (HIF-1) from huge genome databases. The suffix tree data structure has two powerful applications here: one is to extract unknown patterns from multiple strings/sequences in linear time; the other is to search multiple strings/sequences using multiple patterns in linear time. Using 15 known HIF-1 target gene sequences as a training set, we extracted 105 common patterns that all occur in the 15 training genes …

To Love Your Neighbor: A Christian Perspective On The Study Of Microbiology And Immunology, Joy Doan

Faith Learning Integration Papers

I have been blessed with enough of a sense of adventure to have experienced the awe-inspiring beauty of a rain forest at night, the top of Half Dome at Yosemite National Park, the sheer cliffs and rushing waters of the Narrows at Zion National Park, Plateau Point—which seems suspended in the Grand Canyon, and the top of a 14,000-foot peak in the Rocky Mountains of Colorado. These are the types of places about which one of the characters in Robert Pirsig’s Zen and the Art of Motorcycle Maintenance observes, “This is the hardest stuff in the world to photograph. You …

Louis Pasteur’S Views On Creation, Evolution, And The Genesis Of Germs, Alan L. Gillen, Frank Sherwin

Faculty Publications and Presentations

“There is no remembrance of men of old, and even those who are yet to come will not be remembered by those who follow.” Ecclesiastes 1:11 (NIV)

In past years revisionist historians have been rewriting the worldview of Christians who have made some of the major discoveries in biology and medicine. It appears that postmodern revisionists are rewriting history to support their agenda of a more “secular” explanation to science. The Judeo-Christian worldview is not politically correct in most universities. This is true in regard to past scientists such as Louis Pasteur who believed in creation. According to reliable, primary …

Experimental Inoculation Of House Sparrows (Passer Domesticus) With Buggy Creek Virus, Kathryn P. Huyvaert, Amy T. Moore, Nicholas A. Panella, Eric A. Edwards, Mary Bomberger Brown, Nicholas Komar, Charles R. Brown

School of Natural Resources: Faculty Publications

We performed experimental inoculations of house sparrows (Passer domesticus) with Buggy Creek virus (BCRV), a poorly known alphavirus (Togaviridae) vectored primarily by the swallow bug (Hemiptera: Cimicidae: Oeciacus vicarius) that is an ectoparasite of the cliff swallow (Petrochelidon pyrrhonota) and house sparrow. Viremias were detected by plaque assay in two of six birds on days 1–3 postinoculation; viremia was highest on day 2. Viral RNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in blood of six of 12 birds ranging from day 1 to day 15 postinoculation. Infectious BCRV was detected in …

Do Hospitalists Or Physicians With Greater Inpatient Hiv Experience Improve Hiv Care In The Era Of Highly Active Antiretroviral Therapy? Results From A Multicenter Trial Of Academic Hospitalists, John A. Schneider, Qi Zhang, Andrew Auerbach, David Gonzales, Peter Kaboli, Jeffrey Schnipper, Tosha B. Wetterneck, David L. Pitrak, David O. Meltzer

Community & Environmental Health Faculty Publications

Background. Little is known about the effect of provider type and experience on outcomes, resource use, and processes of care of hospitalized patients with human immunodeficiency virus (HIV) infection. Hospitalists are caring for this population with increasing frequency.

Methods. Data from a natural experiment in which patients were assigned to physicians on the basis of call cycle was used to study the effects of provider type—that is, hospitalist versus non hospitalist—and HIV-specific inpatient experience on resource use, outcomes, and selected measures of processes of care at 6 academic institutions. Administrative data, inpatient interviews, 30-day follow-up interviews, and the National Death …

Molecular Characterization Of Trypanosoma Cruzi And Shed Vesicle Components Involved In Host Immunomodulation And Cell Invasion, Ernesto Satoshi Nakayasu

Open Access Theses & Dissertations

Chagas disease caused by Trypanosoma cruzi is a devastating infectious disease with millions of cases in Latin America, and recently became a public health concern in United States and Europe. Although many efforts have been made for the development of an effective immunotherapy, currently there is no human vaccine for Chagas disease. Thus, the treatment is based only on two drugs that have limited efficacy and in some cases present severe side effects. One restriction for the rational approach to develop new therapies against this disease is the limited information about the proteins, glycolipids and protein posttranslational modifications expressed by …

The Response Of Vascular Dermal Enodethial Cells To House Dust Mite Extracts, Aaron Mathew Newman

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House dust mites are microscopic arthropods that can trigger moderate allergic symptoms such as sneezing, watery eyes, itching, and wheezing in sensitized individuals. People with more serious allergies to house dust mites can develop allergic diseases like atopic dermatitis and asthma. The effects of house dust mites on allergy sufferers make house dust mites and the study of their effects on the human body of great medical and economic importance. A majority of the research that has been done on house dust mite's effects on humans has dealt with the lungs and relevant disease like asthma. Little work has been …

Human Immunodeficiency Virus-1 Productively Infects Mature Terminally Differentiated Eosinophils In Hiv/Aids Patients, Jude N. Atem

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Eosinophils express membrane CD4 protein and can bind HIV-1 glycoprotein (gp) 120. Therefore, eosinophils could serve as host cells for HIV-1 infection in vivo, especially in the late phase of the infection. In culture, HIV-1 infects eosinophil precursors and primary eosinophils. Additionally HIV-1 proviral DNA sequences have been detected in the eosinophils of some HIV-1 positive patients. Since elevated levels of eosinophils occur during HIV-1 infection and parasitic infections, it implies that co-infection of parasites and HIV-1 could cause a much greater increase in the level of potential HIV-1 susceptible eosinophils. Therefore HIV-1 infection of eosinophils could partly explain the …

The Role Of Phospholipase D (Pld) And Grb2 In Chemotaxis, Katie J. Knapek

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Phospholipase D (PLD) is an enzyme that hydrolyzes phosphatidylcholine yielding choline and phosphatidic acid. PLD is activated by mitogens (lead to cell division) and motogens (leading to cell migration). PLD is known to contribute to cellular proliferation and deregulated expression of PLD has been implicated in several human cancers. PLD has been found to play a role in leukocyte chemotaxis and adhesion as studied through the formation of chemokine gradients. We have established a model of cell migration comprising three cell lines: macrophages RAW 264.7 and LR-5 (for innate defense), and fibroblast COS-7 cells (for wound healing). COS-7 cells respond …

Giardia Lamblia: Genomic And Molecular Analyses Of Flippase, Diana Leticia Villazana-Kretzer

Open Access Theses & Dissertations

Giardia lamblia, is an intestinal protozoan parasite responsible as a major cause of water-borne intestinal infection in humans (giardiasis). It has been proposed earlier that Giardia has limited lipid synThesis ability and therefore relies on preformed lipid molecules from outside sources. It has also been proposed that lipids are taken up through passive and active transport, and giardial flippasse play a significant role in this process. This study describes the identification and characterization of a putative homologue of flippase gene from Giardia. Flippase is an enzyme that functions as a trans-bilayer transport system facilitating the flip flop diffusion of phospholipids …

Direct Inhibition Of Cdk9 Blocks Hiv-1 Replication Without Preventing T Cell Activation In Primary Human Peripheral Blood Lymphocytes, Dominic Salerno, Muneer G Hasham, Renee Marshall Demarest, Judit Garriga, Alexander Y Tsygankov, Xavier Graña

Rowan-Virtua School of Osteopathic Medicine Departmental Research

HIV-1 transcription is essential for the virus replication cycle. HIV-1 Tat is a viral transactivator that strongly stimulates the processivity of RNA polymerase II (RNAPII) via recruitment of the cyclin T1/CDK9 positive transcription elongation factor, which phosphorylates the C-terminal domain (CTD) of RNAPII. Consistently, HIV-1 replication in transformed cells is very sensitive to direct CDK9 inhibition. Thus, CDK9 could be a potential target for anti-HIV-1 therapy. A clearer understanding of the requirements for CDK9 activity in primary human T cells is needed to assess whether the CDK9-dependent step in HIV-1 transcription can be targeted clinically. We have investigated the effects …

Design, Synthesis, And Evaluation Of 10-N-Substituted Acridones As Novel Chemosensitizers In Plasmodium Falciparum, Jane X. Kelly, Martin J. Smilkstein, Roland A. Cooper, Kristin D. Lane, Robert A. Johnson, Aaron Janowsky, Rozalia A. Dodean, Rolf Winter, Michael Riscoe

Collected Faculty Scholarship

A series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for the ability to enhance the potency of quinoline drugs against multidrug-resistant (MDR) Plasmodium falciparum malaria parasites. A number of acridone derivatives, with side chains bridged three or more carbon atoms apart between the ring nitrogen and terminal nitrogen, demonstrated chloroquine (CQ)-chemosensitizing activity against the MDR strain of P. falciparum (Dd2). Isobologram analysis revealed that selected candidates demonstrated significant synergy with CQ in the CQ-resistant (CQR) parasite Dd2 but only additive (or indifferent) interaction in the CQ-sensitive …

The Plasmodium Falciparum Chloroquine Resistance Transporter, Pfcrt, Mediates The Activity Of Chloroquine-Resistance Reversal Agents In The Malaria Parasite, Kristin Lane

Biological Sciences Theses & Dissertations

Chloroquine (CQ) resistant Plasmodium falciparum is a serious problem affecting 3.2 billion people in over 100 countries today. Most endemic malarious countries are among the poorest in the world and lack the resources to replace the inexpensive and highly effective CQ. CQ resistance (CQR) reversal agents are a potentially inexpensive solution to restoring CQ efficacy. CQR reversal agents are drugs that have little to no antimalarial activity alone, but in combination with CQ, they increase dmg accumulation in the parasite and enhance the sensitivity to CQ in CQR parasites. PfCRT is a putative transporter located on the parasite digestive vacuole …

Bird Movement Predicts Buggy Creek Virus Infection In Insect Vectors, Charles R. Brown, Mary Bomberger Brown, Amy T. Moore, Nicholas Komar

School of Natural Resources: Faculty Publications

Predicting the spatial foci of zoonotic diseases is a major challenge for epidemiologists and disease ecologists. Migratory birds are often thought to be responsible for introducing some aviozoonotic pathogens such as West Nile and avian influenza viruses to a local area, but most information on how bird movement correlates with virus prevalence is anecdotal or indirect. We report that the prevalence of Buggy Creek virus (BCRV) infection in cimicid swallow bugs (Oeciacus vicarius), the principal invertebrate vector for this virus, was directly associated with the likelihood of movement by cliff swallows (Petrochelidon pyrrhonota), an amplifying host …

Ecological Correlates Of Buggy Creek Virus Infection In Oeciacus Vicarius, Southwestern Nebraska, 2004, Amy T. Moore, Eric A. Edwards, Mary Bomberger Brown, Nicholas Komar, Charles R. Brown

School of Natural Resources: Faculty Publications

Buggy Creek virus (family Togaviridae, genus Alphavirus, BCRV) is an alphavirus within the western equine encephalitis virus complex whose primary vector is the swallow bug, Oeciacus vicarius Horvath (Hemiptera: Cimicidae), an ectoparasite of the colonially nesting cliff swallow, Petrochelidon pyrrhonota, that is also a frequent host for the virus.We investigated ecological correlates of BCRV infection in 100-bug pools at 14 different swallow colony sites in southwestern Nebraska from summer 2004, by using plaque assay on Vero cells to identify cytopathic virus and reverse transcription-polymerase chain reaction to identify noncytopathic viral RNA. We found 26.7% of swallow bug pools …

Role Of Mhc Antigens And Immunoregulation In Graft Survival In Autoimmunity, Bhagirath Singh

Microbiology & Immunology Publications

Using a syngeneic islet transplantation model system we have showed that in autoimmune type 1 diabetes transplanted islets are destroyed by the host immune system unless the transplanted islets lack class I major histocompatibility complex (MHC) molecules. Alternatively, immunomodulation of the host by induction of regulatory T cells prevented the destruction of autologous islet graft. We conclude that these approaches will allow successful transplantation of autologous islets derived from the host by stem cell or other technology without immunosuppression to reverse autoimmune type 1 diabetes.

Design, Synthesis, And Evaluation Of 10-N-Substituted Acridones As Novel Chemosensitizers In Plasmodium Falciparum, Jane X. Kelly, Martin J. Smilkstein, Roland A. Cooper, Kristin D. Lane, Robert A. Johnson, Aaron Janowsky, Rozalia A. Dodean, David J. Hinrichs, Rolf Winter, Michael Riscoe

Biological Sciences Faculty Publications

A series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for the ability to enhance the potency of quinoline drugs against multidrug-resistant (MDR) Plasmodium falciparum malaria parasites. A number of acridone derivatives, with side chains bridged three or more carbon atoms apart between the ring nitrogen and terminal nitrogen, demonstrated chloroquine (CQ)-chemosensitizing activity against the MDR strain of P. falciparum (Dd2). Isobolograrn analysis revealed that selected candidates demonstrated significant synergy with CQ in the CQ-resistant (CQR) parasite Dd2 but only additive (or indifferent) interaction in the CQ-sensitive …

Hypoxic Induction And The Role Of Hifs In The Activation Of Luciferase Constitutive Reporters In Placental Stem Cells, Diane Michelle Doran

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Hypoxia is critically important to the development of the embryo and placenta. Proper placental development is critical for normal fetal growth and embryonic survival. Abnormal placental development has been implicated in numerous obstetric complications, including preeclampsia, which affects about 7% of all pregnancies and can be fatal for both mother and baby. Rodent and murine trophoblast stem cells differentiate into three distinct cell lineages: giant cells, spongiotrophoblasts, and labyrinthine cells, which form different layers and have different functions within the placenta. Recent studies in our laboratory have focused on the invasive giant cell layer using the rodent Rcho-1 choriocarcinoma stem …

On A Multinational Assessment Of Rotavirus Disease In Europe, David O. Matson

Community & Environmental Health Faculty Publications

Rotaviruses were discovered in the 1960s in animals and in the 1970s in humans; the latter discovery was made by an intrepid group who performed duodenal biopsies on children with acute gastroenteritis (AGE) [1]. By the late 1970s, data already clearly indicated that rotavirus was the cause of the annual winter peak of AGE affecting young children, as well as a frequent cause of severe gastroenteritis in various animal species (e.g., [2–5]). Use of the retrospectroscope clarified or left as tantalizing the suggestion that rotaviruses were the cause of the annual “winter vomiting syndrome” first described in children in 1910 …

Characteristics Of A Foamy Virus-Derived Vector That Allow For Safe Autologous Gene Therapy To Correct Leukocyte Adhesion Deficiency Type 1, Ryan Matthew Mcnichol

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The hematopoeitic stem cell is a prime target for gene therapy in the attempt to correct a number of single gene inherited genetic defects that affect the immune system. In persons affected by leukocyte adhesion deficiency type 1 (LAD-1) the gene for the Beta-2 subunit of the integrin molecule is mutated. This autosomal recessive gene defect yields a phenotype with little or no beta-2 integrin expression on leukocytes. Beta-2 integrin expression is essential for leukocytes to travel from the blood to the tissues to fight infection. Persons with this disease have lowered leukocyte counts in the tissues and as a …

Hsv-1 Infection Of C3h Central Nervous System Cell Lines, Lauren Kay Van Buren

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Herpes Simplex Virus Type 1 (HSV-1) can infect the nervous system, resulting in a disease known as herpes encephalitis (HSE). Herpes encephalitis affects thousands of people each year; many cases are fatal or permanently debilitating. Approximately two thousand known cases occur in the United States each year alone (Neuroland online source). Acyclovir has been the drug of choice used to treat herpes encephalitis. Even after the administration of acyclovir, permanent neurological damage and/or death often results. Thousands of individuals would benefit by the discovery of drugs that are more effective at preventing lasting HSE damage and death. Knowledge concerning HSE …

Discovery Of New Antimicrobial Agents Using Combinatorial Chemistry, William I. Northern

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Combinatorial chemistry has become an important aspect of medicinal research due to its flexibility and the ability to produce large numbers of potential therapeutic agents. Once compounds are made, they must be screened to determine if there is any biological activity. This research project focused on developing a screening method for chemical agents produced by a graduate student in the chemistry department at Wright State University. After an acceptable screening method was found, the goal of the project was to determine if compounds produced had either antibacterial activity, antifungal activity, or both. Seven compounds exhibited biological activity. Two of these …

Detection Of Panulirus Argus Virus 1 (Pav1) In The Caribbean Spiny Lobster Using Fluorescence In Situ Hybridization (Fish), Caiwen Li, Jeffrey D. Shields, Hamish J. Small, Kimberly S. Reece, Carmony L. Hartwig, Roland A. Cooper, Robert E. Ratzlaff

Collected Faculty Scholarship

Panulirus argus Virus 1 (PaV1) is the first virus known to be pathogenic to a wild lobster. It infects the Caribbean spiny lobster P. argus from the Florida Keys, and has a predilection for juveniles. The monitoring of the virus in wild populations and study of its behavior in the laboratory require the development of reliable diagnostic tools. A sensitive and specific fluorescence in situ hybridization (FISH) assay was developed for detection of PaV1. The lower detection limit using a 110 bp DNA probe in a dot-blot hybridization for PaV1 DNA was 10 pg of cloned template PaV1 DNA and …