Medicine and Health Sciences Commons^™

Toxoplasma Gondii Induces Granulocyte Colony-Stimulating Factor And Granulocyte-Macrophage Colony-Stimulating Factor Secretion By Human Fibroblasts: Implications For Neutrophil Apoptosis, Jacqueline Y. Channon, Kristin A. Miselis, Laurie A. Minns, Chaitali Dutta, Lloyd H. Kasper

Dartmouth Scholarship

Human neutrophils are rescued from apoptosis following incubation with once-washed, fibroblast-derived Toxoplasma gondii tachyzoites. Both infected and uninfected neutrophils are rescued, implicating a soluble mediator. In this study we investigated the origin and identity of this soluble mediator. Neutrophils were incubated either with purified tachyzoites or with conditioned medium derived from T. gondii-infected human fibroblasts. Conditioned medium was found to be a potent stimulus that delayed neutrophil apoptosis up to 72 h, whereas purified and extensively washed tachyzoites had no effect. Delayed apoptosis correlated with up-regulation of the neutrophil antiapoptotic protein, Mcl-1, and the neutrophil interleukin 3 receptor alpha subunit …

Supervised Treatment Interruption (Sti) In An Urban Hiv Clinical Practice: A Prospective Analysis, Joseph L. Yozviak Do, Facp, Peter Kouvatos Do, R Eric Doerfler Np, Cch, William C. Woodward Do

Department of Medicine

Background: In acute HIV-1 infection, STI may induce immunologic control of HIV-1 replication. Several prospective trials of STI in chronic HIV-1 infection have been less encouraging. A previously presented retrospective analysis of our patients showed that in those with a significant CD4 increase (>200 cells) on antiretroviral therapy (ART), 2 or more interruptions may significantly lower viral set point. This prospective study describes STI in a cohort of patients.

Methods: 10 patients with either a positive response to therapy interruption retrospectively or those expressing interest in the strategy who met inclusion criteria (VL BLQ on ART, good adherence, robust …

Clinical And Epidemiological Correlates Of Genotypes Within The Mycobacterium Avium Complex Defined By Restriction And Sequence Analysis Of Hsp65, Sandra C. Smole, Fionnuala Mcaleese, Jutamas Ngampasutadol, C. Fordham Von Reyn, Robert D. Arbeit

Dartmouth Scholarship

Species identification of isolates of the Mycobacterium avium complex (MAC) remains a difficult task. Although M. avium and Mycobacterium intracellulare can be identified with expensive, commercially available probes, many MAC isolates remain unresolved, including those representing Mycobacterium lentiflavum as well as other potentially undefined species. PCR restriction analysis (PRA) of the hsp65 gene has been proposed as a rapid and inexpensive approach. We applied PRA to 278 MAC isolates, including 126 from blood of human immunodeficiency virus (HIV)-infected patients, 59 from sputum of HIV-negative patients with chronic obstructive pulmonary disease, 88 from environmental sources, and 5 pulmonary isolates from …

Identification Of The Vibrio Cholerae Enterobactin Receptors Vcta And Irga: Irga Is Not Required For Virulence, Alexandra R. Mey, Elizabeth E. Wyckoff, Amanda G. Oglesby, Eva Rab, Ronald K. Taylor, Shelley M. Payne

Dartmouth Scholarship

The gram-negative enteric pathogen Vibrio cholerae requires iron for growth. V. cholerae has multiple iron acquisition systems, including utilization of heme and hemoglobin, synthesis and transport of the catechol siderophore vibriobactin, and transport of several siderophores that it does not itself make. One siderophore that V. cholerae transports, but does not make, is enterobactin. Enterobactin transport requires TonB and is independent of the vibriobactin receptor ViuA. In this study, two candidate enterobactin receptor genes, irgA (VC0475) and vctA (VCA0232), were identified by analysis of the V. cholerae genomic sequence. A single mutation in either of these genes did not significantly …

Treatment With Soluble Interleukin-15ralpha Exacerbates Intracellular Parasitic Infection By Blocking The Development Of Memory Cd8+ T Cell Response, Imtiaz A. Khan, Magali Moretto, Xiao-Qing Wei, Martha Williams, Joseph D. Schwartzman, F Y. Liew

Dartmouth Scholarship

Interferon (IFN)-γ–producing CD8⁺ T cells are important for the successful resolution of the obligate intracellular parasite Toxoplasma gondii by preventing the reactivation or controlling a repeat infection. Previous reports from our laboratory have shown that exogenous interleukin (IL)-15 treatment augments the CD8⁺ T cell response against the parasite. However, the role of endogenous IL-15 in the proliferation of activated/memory CD8⁺ T cells during toxoplasma or any other infection is unknown. In this study, we treated T. gondii immune mice with soluble IL-15 receptor α (sIL-15Rα) to block the host endogenous IL-15. The treatment markedly reduced the ability …

Enhancement Of Anti-Hiv-1 Ribozyme Activities By Rev Binding And Multimerization, Yuksel Yildiz

Loma Linda University Electronic Theses, Dissertations & Projects

To effectively apply hammerhead ribozymes as therapeutic agents it is necessary to co-localize them with the desired target. Human immunodeficiency virus type1 (HIV- 1) infectivity is dependent on env gene expression. HIV-1 Rev protein binds to a higher ordered RNA structure within the env transcript termed the Rev Binding Element (RBE). In anti-HIV gene therapy employing ribozymes to increase the co-localization of anti- HIV ribozymes with target HIV mRNAs, it has been proposed that when the native HIV- 1 RBE is appended to a ribozyme as a decoy molecule, simultaneous binding of Rev monomers to the RBE sequences in both …

Cd8+-T-Cell Immunity Against Toxoplasma Gondii Can Be Induced But Not Maintained In Mice Lacking Conventional Cd4+ T Cells, Lori Casciotti, Kenneth H. Ely, Martha E. Williams, Imtiaz A. Khan

Dartmouth Scholarship

T-cell immunity is critical for survival of hosts infected with Toxoplasma gondii. Among the cells in the T-cell population, CD8⁺ T cells are considered the major effector cells against this parasite. It is believed that CD4⁺ T cells may be crucial for induction of the CD8⁺-T-cell response against T. gondii. In the present study, CD4^−/− mice were used to evaluate the role of conventional CD4⁺ T cells in the immune response against T. gondii infection. CD4^−/− mice infected with T. gondii exhibited lower gamma interferon (IFN-γ) messages in the majority of their …

Staphylococcus Aureus Agr And Sara Functions Are Required For Invasive Infection But Not Inflammatory Responses In The Lung, Geoffrey Heyer, Shahryar Saba, Robert Adamo, William Rush, Grace Soong, Ambrose Cheung, Alice Prince

Dartmouth Scholarship

Staphylococcus aureus strains lacking agr- and sarA-dependent gene products or specific MSCRAMM (microbial surface components recognizing adhesive matrix molecules) adhesins were compared for the ability to activate inflammatory responses in the lung. The mutants were evaluated for virulence in a mouse model of pneumonia and by quantifying their ability to stimulate interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in respiratory epithelial cells. In a neonatal mouse, only strains with intact agr and sarA loci were consistently associated with invasive, fatal pulmonary infection (P < 0.001) and sarA was specifically required to cause bacteremia (P < 0.001). The agr and/or sarA mutants were, nonetheless, fully capable of producing pneumonia and were as proficient as the wild-type strain in stimulating epithelial IL-8 expression, a polymorphonuclear leukocyte chemokine, in airway cells. In contrast, agr and especially sarA mutants induced less epithelial GM-CSF expression, and MSCRAMM mutants lacking fibronectin binding proteins or clumping factor A, a ligand for fibrinogen, were unable to stimulate epithelial GM-CSF production. The ability to induce IL-8 expression was independent of the adherence properties of intact bacteria, indicating that shed and/or secreted bacterial components activate epithelial responses. While conserved staphylococcal components such as peptidoglycan are sufficient to evoke inflammation and cause pneumonia, the agr and sarA loci of S. aureus are critical for the coordination of invasive infection of the lungs.

Small Glutamine-Rich Protein/Viral Protein U–Binding Protein Is A Novel Cochaperone That Affects Heat Shock Protein 70 Activity, Peter C. Angeletti, Doriann Walker, Antonito T. Panganiban

Nebraska Center for Virology: Faculty Publications

Molecular chaperone complexes containing heat shock protein (Hsp) 70 and Hsp90 are regulated by cochaperones, including a subclass of regulators, such as Hsp70 interacting protein (Hip), C-terminus of Hsp70 interacting protein (CHIP), and Hsp70-Hsp90 organizing factor (Hop), that contain tetratricopeptide repeats (TPRs), where Hsp70 refers to Hsp70 and its nearly identical constitutive counterpart, Hsc70, together. These proteins interact with the Hsp70 to regulate adenosine triphosphatase (ATPase) and folding activities or to generate the chaperone complex. Here we provide evidence that small glutamine-rich protein/viral protein U–binding protein (SGT/UBP) is a cochaperone that negatively regulates Hsp70. By “Far-Western” and pull-down assays, SGT/UBP …

Changes In The Transmission Of Tuberculosis In New York City From 1990 To 1999, Elvin H. Geng

Elvin H Geng

Background: Over the past decade, there has been a reduction in the incidence of tuberculosis in New York City and in the United States. However, the reduction has been confined mainly to U.S.-born persons. Understanding the reasons for the lack of reduction among non–U.S.-born persons may lead to new strategies for tuberculosis control. Methods: We performed DNA fingerprinting with the IS6110 insertion sequence of the organisms isolated from patients with culture-positive tuberculosis in northern Manhattan from 1990 to 1999. The goal was to identify the strains responsible for multiple infections, presumably through recent transmission (clusters of cases), as well as …