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Neurological And Behavioral Abnormalities, Ventricular Dilatation, Altered Cellular Functions, Inflammation, And Neuronal Injury In Brains Of Mice Due To Common, Persistent, Parasitic Infection, Gretchen Hermes, James W. Ajioka, Krystyna A. Kelly, Ernest Mui, Fiona Roberts, Kristen Kasza, Thomas Mayr, Michael J. Kirisits, Robert Wollman, David J.P Ferguson, Craig W. Roberts, Jong-Hee Hwang, Toria Trendler, Richard P. Kennan, Yasuhiro Suzuki, Catherine Reardon, William F. Hickey, Lieping Chen, Rima Mcleod

Dartmouth Scholarship

Background:

Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences.

Methods:

To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. …

Role Played By Serum, A Biological Cue, In The Adherence Of Enterococcus Faecalis To Extracellular Matrix Proteins, Collagen, Fibrinogen, And Fibronectin, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

BACKGROUND: Most previous studies have found that Enterococcus faecalis isolates do not show significant adherence to fibronectin and fibrinogen.

METHODS: The influence of various conditions on E. faecalis adherence to extracellular matrix (ECM) proteins was evaluated using a radiolabeled-cell adherence assay.

RESULTS: Among the conditions studied, growth in 40% horse serum (a biological cue with potential clinical relevance) elicited adherence of all 46 E. faecalis strains tested to fibronectin and fibrinogen but not to elastin; adherence levels were independent of strain source, and adherence was eliminated by treating cells with trypsin. As previously reported, serum also elicited adherence to collagen. …

Neuromyelitis Optica Pathogenesis And Aquaporin 4, David J. Graber, Michael Levy, Douglas Kerr, William F. Wade

Dartmouth Scholarship

Neuromyelitis optica (NMO) is a severe, debilitating human disease that predominantly features immunopathology in the optic nerves and the spinal cord. An IgG1 autoantibody (NMO-IgG) that binds aquaporin 4 (AQP4) has been identified in the sera of a significant number of NMO patients, as well as in patients with two related neurologic conditions, bilateral optic neuritis (ON), and longitudinal extensive transverse myelitis (LETM), that are generally considered to lie within the NMO spectrum of diseases. NMO-IgG is not the only autoantibody found in NMO patient sera, but the correlation of pathology in central nervous system (CNS) with tissues that normally …

A Distinct Role For B1b Lymphocytes In T Cell-Independent Immunity, Kishore R. Alugupalli

Department of Microbiology and Immunology Faculty Papers

Pathogenesis of infectious disease is not only determined by the virulence of the microbe but also by the immune status of the host. Vaccination is the most effective means to control infectious diseases. A hallmark of the adaptive immune system is the generation of B cell memory, which provides a long-lasting protective antibody response that is central to the concept of vaccination. Recent studies revealed a distinct function for B1b lymphocytes, a minor subset of mature B cells that closely resembles that of memory B cells in a number of aspects. In contrast to the development of conventional B cell …

Application Of In Vivo Induced Antigen Technology (Iviat) To Bacillus Anthracis, Sean M Rollins, Amanda Peppercorn, John S Young, Melissa Drysdale, Andrea Baresch, Margaret V Bikowski, David A Ashford, Conrad P Quinn, Martin Handfield, Jeffrey D Hillman, C Rick Lyons, Theresa M Koehler, Stephen B Calderwood, Edward T Ryan

Faculty, Staff and Student Publications

In vivo induced antigen technology (IVIAT) is an immuno-screening technique that identifies bacterial antigens expressed during infection and not during standard in vitro culturing conditions. We applied IVIAT to Bacillus anthracis and identified PagA, seven members of a N-acetylmuramoyl-L-alanine amidase autolysin family, three P60 family lipoproteins, two transporters, spore cortex lytic protein SleB, a penicillin binding protein, a putative prophage holin, respiratory nitrate reductase NarG, and three proteins of unknown function. Using quantitative real-time PCR comparing RNA isolated from in vitro cultured B. anthracis to RNA isolated from BALB/c mice infected with virulent Ames strain B. anthracis, we confirmed induced …

Large Scale Variation In Enterococcus Faecalis Illustrated By The Genome Analysis Of Strain Og1rf, Agathe Bourgogne, Danielle A Garsin, Xiang Qin, Kavindra V Singh, Jouko Sillanpaa, Shailaja Yerrapragada, Yan Ding, Shannon Dugan-Rocha, Christian Buhay, Hua Shen, Guan Chen, Gabrielle Williams, Donna Muzny, Arash Maadani, Kristina A Fox, Jason Gioia, Lei Chen, Yue Shang, Cesar A Arias, Sreedhar R Nallapareddy, Meng Zhao, Vittal P Prakash, Shahreen Chowdhury, Huaiyang Jiang, Richard A Gibbs, Barbara E Murray, Sarah K Highlander, George M Weinstock

Faculty, Staff and Student Publications

BACKGROUND: Enterococcus faecalis has emerged as a major hospital pathogen. To explore its diversity, we sequenced E. faecalis strain OG1RF, which is commonly used for molecular manipulation and virulence studies.

RESULTS: The 2,739,625 base pair chromosome of OG1RF was found to contain approximately 232 kilobases unique to this strain compared to V583, the only publicly available sequenced strain. Almost no mobile genetic elements were found in OG1RF. The 64 areas of divergence were classified into three categories. First, OG1RF carries 39 unique regions, including 2 CRISPR loci and a new WxL locus. Second, we found nine replacements where a sequence …

Relative Contributions Of Enterococcus Faecalis Og1rf Sortase-Encoding Genes, Srta And Bps (Srtc), To Biofilm Formation And A Murine Model Of Urinary Tract Infection, Kelvin D Kemp, Kavindra V Singh, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

Deletion mutants of the two sortase genes of Enterococcus faecalis OG1RF were constructed. srtC (renamed here bps for biofilm and pilus-associated sortase) was previously shown to be necessary for the production of Ebp pili and important for biofilm formation and endocarditis. Here, we report that a srtA deletion mutant showed a small (5%) yet significant (P = 0.037) reduction in biofilm relative to OG1RF, while a DeltasrtA Deltabps double mutant showed a much greater reduction (74% versus OG1RF and 44% versus the Deltabps mutant). In a murine urinary tract infection (UTI), the 50% infective doses of both the DeltasrtA Deltabps …

The Activity Of Azithromycin Against Leishmania (Viannia) Braziliensis And Leishmania (Leishmania) Amazonensis In The Golden Hamster Model., Angel Sinagra, Concepción Luna, David Abraham, Maria Del Carmen Iannella, Adelina Riarte, Alejandro J. Krolewiecki

Department of Microbiology and Immunology Faculty Papers

New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania (Leishmania) major has been previously demonstrated. Different responses among species of Leishmania make species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis was evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with untreated controls and animals treated with meglumine antimoniate. Footpad thickness, lesion cultures and dissemination sites were analyzed. Treatment of golden hamsters with oral azithromycin at 450mg/kg had no activity against infections with Leishmania (Leishmania) amazonensis. For infections due to Leishmania (Viannia) braziliensis, …

Characterization Of The Equine 2'-5' Oligoadenylate Synthetase 1 (Oas1) And Ribonuclease L (Rnasel) Innate Immunity Genes, Jonathan J. Rios, Andrey A. Perelygin, Maureen T. Long, Teri L. Lear, Andrey A. Zharkikh, Margo A. Brinton, David L. Adelson

Veterinary Science Faculty Publications

BACKGROUND: The mammalian OAS/RNASEL pathway plays an important role in antiviral host defense. A premature stop-codon within the murine Oas1b gene results in the increased susceptibility of mice to a number of flaviviruses, including West Nile virus (WNV). Mutations in either the OAS1 or RNASEL genes may also modulate the outcome of WNV-induced disease or other viral infections in horses. Polymorphisms in the human OAS gene cluster have been previously utilized for case-control analysis of virus-induced disease in humans. No polymorphisms have yet been identified in either the equine OAS1 or RNASEL genes for use in similar case-control studies.

RESULTS: …

The Failed Regulatory System For Animal Imports Into The United States – And How To Fix It, Peter Jenkins

Managing Vertebrate Invasive Species

This paper provides a synopsis of the Defenders of Wildlife report entitled Broken Screens: The Regulation of Live Animal Imports in the United States, released in August 2007. That report assessed the complex federal system for regulating live wild animal imports as applied to the 2,241 non-native species that were identified in United States Fish and Wildlife Service records as being imported between 2000 and 2004, inclusive. The report describes the “coarse risk screening” conducted for those species by searching the scientific literature and United States and international databases. If one or more reliable sources indicated a species was …

The Flagellum Of Pseudomonas Aeruginosa Is Required For Resistance To Clearance By Surfactant Protein A, Shiping Zhang, Francis X. Mccormack, Roger C. Levesque, George A. O'Toole, Gee W. Lau

Dartmouth Scholarship

Surfactant protein A (SP-A) is an important lung innate immune protein that kills microbial pathogens by opsonization and membrane permeabilization. We investigated the basis of SP-A-mediated pulmonary clearance of Pseudomonas aeruginosa using genetically-engineered SP-A mice and a library of signature-tagged P. aeruginosa mutants. A mutant with an insertion into flgE, the gene that encodes flagellar hook protein, was preferentially cleared by the SP-A(+/+) mice, but survived in the SP-A(-/-) mice. Opsonization by SP-A did not play a role in flgE clearance. However, exposure to SP-A directly permeabilized and killed the flgE mutant, but not the wild-type parental strain. P. aeruginosa …

Importance Of The Ebp (Endocarditis- And Biofilm-Associated Pilus) Locus In The Pathogenesis Of Enterococcus Faecalis Ascending Urinary Tract Infection, Kavindra V Singh, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

BACKGROUND: We recently demonstrated that the ubiquitous Enterococcus faecalis ebp (endocarditis- and biofilm-associated pilus) operon is important for biofilm formation and experimental endocarditis. Here, we assess its role in murine urinary tract infection (UTI) by use of wild-type E. faecalis OG1RF and its nonpiliated, ebpA allelic replacement mutant (TX5475).

METHODS: OG1RF and TX5475 were administered transurethrally either at an ~1 : 1 ratio (competition assay) or individually (monoinfection). Kidney pairs and urinary bladders were cultured 48 h after infection. These strains were also tested in a peritonitis model.

RESULTS: No differences were observed in the peritonitis model. In mixed UTIs, …

Bovine Immune Response To Shiga-Toxigenic Escherichia Coli O157:H7., Mark A Hoffman, Christian Menge, Thomas A Casey, William Laegreid, Brad T Bosworth, Evelyn A Dean-Nystrom

Manuscripts, Articles, Book Chapters and Other Papers

Although cattle develop humoral immune responses to Shiga-toxigenic (Stx+) Escherichia coli O157:H7, infections often result in long-term shedding of these human pathogenic bacteria. The objective of this study was to compare humoral and cellular immune responses to Stx+ and Stx- E. coli O157:H7. Three groups of calves were inoculated intrarumenally, twice in a 3-week interval, with different strains of E. coli: a Stx2-producing E. coli O157:H7 strain (Stx2+ O157), a Shiga toxin-negative E. coli O157:H7 strain (Stx- O157), or a nonpathogenic E. coli strain (control). Fecal shedding of Stx2+ O157 was significantly higher than that of Stx- O157 or the …

Proteomic Identification Of In Vivo Substrates For Matrix Metalloproteinases 2 And 9 Reveals A Mechanism For Resolution Of Inflammation, Kendra J Greenlee, David B Corry, David A Engler, Risë K Matsunami, Philippe Tessier, Richard G Cook, Zena Werb, Farrah Kheradmand

Faculty, Staff and Student Publications

Clearance of allergic inflammatory cells from the lung through matrix metalloproteinases (MMPs) is necessary to prevent lethal asphyxiation, but mechanistic insight into this essential homeostatic process is lacking. In this study, we have used a proteomics approach to determine how MMPs promote egression of lung inflammatory cells through the airway. MMP2- and MMP9-dependent cleavage of individual Th2 chemokines modulated their chemotactic activity; however, the net effect of complementing bronchoalveolar lavage fluid of allergen-challenged MMP2(-/-)/MMP9(-/-) mice with active MMP2 and MMP9 was to markedly enhance its overall chemotactic activity. In the bronchoalveolar fluid of MMP2(-/-)/MMP9(-/-) allergic mice, we identified several chemotactic …

Vulnerability Of Pathogenic Biofilms To Micavibrio Aeruginosavorus, Daniel Kadouri, Nel C. Venzon, George A. O'Toole

Dartmouth Scholarship

The host specificity of the gram-negative exoparasitic predatory bacterium Micavibrio aeruginosavorus was examined. M. aeruginosavorus preyed on Pseudomonas aeruginosa, as previously reported, as well as Burkholderia cepacia, Klebsiella pneumoniae, and numerous clinical isolates of these species. In a static assay, a reduction in biofilm biomass was observed as early as 3 hours after exposure to M. aeruginosavorus, and an ∼100-fold reduction in biofilm cell viability was detected following a a 24-h exposure to the predator. We observed that an initial titer of Micavibrio as low as 10 PFU/well or a time of exposure to the predator as short as 30 …

Endocarditis And Biofilm-Associated Pili Of Enterococcus Faecalis, Sreedhar R Nallapareddy, Kavindra V Singh, Jouko Sillanpää, Danielle A Garsin, Magnus Höök, Stanley L Erlandsen, Barbara E Murray

Faculty, Staff and Student Publications

Increasing multidrug resistance in Enterococcus faecalis, a nosocomial opportunist and common cause of bacterial endocarditis, emphasizes the need for alternative therapeutic approaches such as immunotherapy or immunoprophylaxis. In an earlier study, we demonstrated the presence of antibodies in E. faecalis endocarditis patient sera to recombinant forms of 9 E. faecalis cell wall-anchored proteins; of these, we have now characterized an in vivo-expressed locus of 3 genes and an associated sortase gene (encoding sortase C; SrtC). Here, using mutation analyses and complementation, we demonstrated that both the ebp (encoding endocarditis and biofilm-associated pili) operon and srtC are important for biofilm production …

Cd80 And Cd86 Control Antiviral Cd8+ T-Cell Function And Immune Surveillance Of Murine Gammaherpesvirus 68, Shinichiro Fuse, Joshua J. Obar, Sarah Bellfy, Erica K. Leung, Weijun Zhang, Edward J. Usherwood

Dartmouth Scholarship

The interactions between CD80 and CD86 on antigen-presenting cells and CD28 on T cells serve as an important costimulatory signal in the activation of T cells. Although the simplistic two-signal hypothesis has been challenged in recent years by the identification of different costimulators, this classical pathway has been shown to significantly impact antiviral humoral and cellular immune responses. How the CD80/CD86-CD28 pathway affects the control of chronic or latent infections has been less well characterized. In this study, we investigated its role in antiviral immune responses against murine gammaherpesvirus 68 (MHV-68) and immune surveillance using CD80/CD86^−/− mice. In the …

Ligand-Signaled Upregulation Of Enterococcus Faecalis Ace Transcription, A Mechanism For Modulating Host-E Faecalis Interaction, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecalis, the third most frequent cause of bacterial endocarditis, appears to be equipped with diverse surface-associated proteins showing structural-fold similarity to the immunoglobulin-fold family of staphylococcal adhesins. Among the putative E. faecalis surface proteins, the previously characterized adhesin Ace, which shows specific binding to collagen and laminin, was detectable in surface protein preparations only after growth at 46 degrees C, mirroring the finding that adherence was observed in 46 degrees C, but not 37 degrees C, grown E. faecalis cultures. To elucidate the influence of different growth and host parameters on ace expression, we investigated ace expression using E. …

Lack Of Il-15 Results In The Suboptimal Priming Of Cd4+ T Cell Response Against An Intracellular Parasite, Crescent L. Combe, Magali M. Moretto, Joseph D. Schwartzman, Jason P. Gigley, David J. Bzik, Imtiaz A. Khan

Dartmouth Scholarship

IFN-gamma-producing CD4+ T cells, although important for protection against acute Toxoplasma gondii infection, can cause gut pathology, which may prove to be detrimental for host survival. Here we show that mice lacking IL-15 gene develop a down-regulated IFN-gamma-producing CD4+ T cell response against the parasite, which leads to a reduction in gut necrosis and increased level of survival against infection. Moreover, transfer of immune CD4+ T cells from WT to IL-15-/- mice reversed inhibition of gut pathology and caused mortality equivalent to levels of parental WT mice. Down-regulated CD4+ T cell response in the absence of IL-15, manifested as reduced …

Cutaneous And Presumed Visceral Leishmaniasis In A Soldier Deployed To Afghanistan, James P. Woodrow, Joshua D. Hartzell, Jim Czarnik, David Brett-Major, Glenn Wortmann

Journal Articles: Epidemiology

Leishmaniasis has been frequently diagnosed in US military personnel returning from duty in Southwest Asia. The majority of cases have demonstrated cutaneous disease, although a few cases of visceral disease have been documented. We present the case of an immunocompetent, HIV-negative, US Army soldier who suffered both visceral and cutaneous manifestations of leishmaniasis after returning from deployment in Afghanistan. Overlap of cutaneous and visceral involvement is rare and has not been reported in our cohort. Latent Plasmodium vivax infection may have been an exacerbating cofactor. We discuss this case and present a review of the literature.

Sal-Site: Integrating New And Existing Ambystomatid Salamander Research And Informational Resources, Jeramiah J. Smith, Srikrishna Putta, John A. Walker, D. Kevin Kump, Amy K. Samuels, James R. Monaghan, David W. Weisrock, Chuck Staben, S. Randal Voss

Biology Faculty Publications

Salamanders of the genus Ambystoma are a unique model organism system because they enable natural history and biomedical research in the laboratory or field. We developed Sal-Site to integrate new and existing ambystomatid salamander research resources in support of this model system. Sal-Site hosts six important resources: 1) Salamander Genome Project: an information-based web-site describing progress in genome resource development, 2) Ambystoma EST Database: a database of manually edited and analyzed contigs assembled from ESTs that were collected from A. tigrinum tigrinum and A. mexicanum, 3) Ambystoma Gene Collection: a database containing full-length protein-coding sequences, 4) Ambystoma Map and Marker …

Tcpf Is A Soluble Colonization Factor And Protective Antigen Secreted By El Tor And Classical O1 And O139 Vibrio Cholerae Serogroups, Thomas J. Kirn, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae causes diarrhea by colonizing the human small bowel and intoxicating epithelial cells. Colonization is a required step in pathogenesis, and strains defective for colonization are significantly attenuated. The best-characterized V. cholerae colonization factor is the toxin-coregulated pilus (TCP). It has been demonstrated that TCP is required for V. cholerae colonization in both humans and mice. TCP enhances bacterial interactions that allow microcolony formation and thereby promotes survival in the intestine. We have recently discovered that the TCP biogenesis apparatus also serves as a secretion system, mediating the terminal step in the extracellular secretion pathway of TcpF. TcpF was …

Effects Of Estradiol On Lipopolysaccharide And Pam3cys Stimulation Of Ccl20/Macrophage Inflammatory Protein 3 Alpha And Tumor Necrosis Factor Alpha Production By Uterine Epithelial Cells In Culture, Mardi A. Crane-Godreau, Charles R. Wira

Dartmouth Scholarship

We have previously demonstrated that rat uterine epithelial cells (UEC) produce CCL20/macrophage inflammatory protein 3 alpha (MIP3alpha) and tumor necrosis factor alpha (TNF-alpha) in response to live and heat-killed Escherichia coli and to the pathogen-associated molecular patterns (PAMP) lipopolysaccharide (LPS) and Pam3Cys. To determine whether estradiol (E2) modulates PAMP-induced CCL20/MIP3alpha and TNF-alpha secretion, primary cultures of rat UEC were incubated with E2 for 24 h and then treated with LPS or Pam3Cys or not treated for an additional 12 h. E2 inhibited the constitutive secretion of TNF-alpha and CCL20/MIP3alpha into culture media. Interestingly, E2 pretreatment enhanced CCL20/MIP3alpha secretion due to …

Composite Genome Map And Recombination Parameters Derived From Three Archetypal Lineages Of Toxoplasma Gondii, Asis Khan, Sonya Taylor, Chunlei Su, Aaron J. Mackey, Jon Boyle, Robert Cole, Darius Glover, Keliang Tang, Ian T. Paulsen, Matt Berriman, John C. Boothroyd, Elmer K. Pfefferkorn, J P. Dubey, James W. Ajioka, David S. Roos, John C. Wootton, David Sibley

Dartmouth Scholarship

Toxoplasma gondii is a highly successful protozoan parasite in the phylum Apicomplexa, which contains numerous animal and human pathogens. T.gondii is amenable to cellular, biochemical, molecular and genetic studies, making it a model for the biology of this important group of parasites. To facilitate forward genetic analysis, we have developed a high-resolution genetic linkage map for T.gondii . The genetic map was used to assemble the scaffolds from a 10X shotgun whole genome sequence, thus defining 14 chromosomes with markers spaced at ∼300 kb intervals across the genome. Fourteen chromosomes were identified comprising a total genetic size of ∼592 cM …

Rna Polymerase Ii Synthesizes Antisense Rna In Plasmodium Falciparum, Kevin T. Militello, Vishal Patel, Anne-Danielle Chessler, Julia K. Fisher, Jacob M. Kasper, Anusha Gunasekera, Dyann F. Wirth

Biology

The recent identification of antisense RNA in the transcriptomes of many eukaryotes has generated enormous interest. The presence of antisense RNA in Plasmodium falciparum, the causative agent of severe malaria, remains controversial. Elucidation of the mechanism of antisense RNA in P. falciparum synthesis is critical in order to demonstrate the origin and function of these transcripts. Therefore, a systematic analysis of antisense and sense RNA synthesis was performed using direct labeling experiments. Nuclear run on experiments with single-stranded DNA probes demonstrated that antisense RNA is synthesized in the nucleus at several genomic loci. Antisense RNA synthesis is sensitive to the …

A Vibrio Cholerae Classical Tcpa Amino Acid Sequence Induces Protective Antibody That Binds An Area Hypothesized To Be Important For Toxin-Coregulated Pilus Structure, Ronald K. Taylor, Thomas J. Kirn, Michael D. Meeks, Terri K. Wade, William F. Wade

Dartmouth Scholarship

Vibrio cholerae is a gram-negative bacterium that has been associated with cholera pandemics since the early 1800s. Whole-cell, killed, and live-attenuated oral cholera vaccines are in use. We and others have focused on the development of a subunit cholera vaccine that features standardized epitopes from various V. cholerae macromolecules that are known to induce protective antibody responses. TcpA protein is assembled into toxin-coregulated pilus (TCP), a type IVb pilus required for V. cholerae colonization, and thus is a strong candidate for a cholera subunit vaccine. Polypeptides (24 to 26 amino acids) in TcpA that can induce protective antibody responses have …

Cd4+ T Cells In The Pathogenesis Of Murine Ocular Toxoplasmosis, Fangli Lu, Shiguang Huang, Lloyd H. Kasper

Dartmouth Scholarship

The role of CD4⁺ T cells in the pathogenesis of ocular toxoplasmosis was investigated in murine models utilizing inbred C57BL/6 mice deficient either in CD4⁺, CD8⁺, or B cells (μMT). Severe necrosis and inflammation with replicating parasites were observed in the eyes of control mice after primary ocular infection, and near-normal histology with few tachyzoites was observed in the eyes of mice immunized intraperitoneally with the avirulent ts-4 strain followed by intraocular challenge with the RH strain of Toxoplasma gondii. In contrast, mild inflammation without evidence of necrosis associated with increased parasite burdens were …

Epidemiologic And Environmental Investigation Of A Recreational Water Outbreak Caused By Two Genotypes Of Cryptosporidium Parvum In Ohio In 2000, Els Mathieu, Deborah A. Levy, Fran Veverka, Mary-Kay Parrish, John Sarisky, Nancy Shapiro, Stephanie Johnston, Thomas Handzel, Allen Hightower, Lihua Xiao, Yeuk-Mui Lee, Steve York, Michael Arrowood, Robin Lee, Jeffrey L. Jones

Journal Articles: Epidemiology

In August 2000, the Ohio Department of Health requested assistance to investigate a cryptosporidiosis outbreak with more than 700 clinical case-patients. An epidemiologic and environmental investigation was conducted. Stool specimens, pool water, and sand filter samples were analyzed. A community-based case-control study showed that the main risk factor was swimming in pool A (odds ratio [OR] = 42, 95% confidence interval [CI] = 12.3-144.9). This was supported by results of polymerase chain reaction (PCR) analysis, which showed the presence of both the human and bovine genotypes of Cryptosporidium parvum in case-patients and samples from the filter of pool A. A …

Medical Training Using Simulation: Toward Fewer Animals And Safer Patients, Jonathan Balcombe

Experimentation Collection

This paper presents the current status of computer-based simulation in medicine. Recent technological advances have enabled this field to emerge from esoteric explorations in academic laboratories to commercially available simulators designed to train users to perform medical procedures from start to finish. Today, more than a dozen companies are producing virtual reality simulators and interactive manikins for training in endoscopy, laparoscopy, anaesthesia, trauma management, angiography, and needle insertion. For many of these procedures, thousands of animals are still being used in training. Yet simulation has many advantages that can transcend scientific, ethical, economic and logistical problems that arise when using …

Inactivation Of A Bacterial Virulence Pheromone By Phagocyte-Derived Oxidants: New Role For The Nadph Oxidase In Host Defense, Jacob M. Rothfork, Graham S. Timmins, Michael N. Harris, Xian Chen, Aldons J. Lusis, Michael Otto, Ambrose L. Cheung, Hattie D. Gresham

Dartmouth Scholarship

Quorum sensing triggers virulence factor expression in medically important bacterial pathogens in response to a density-dependent increase in one or more autoinducing pheromones. Here, we show that phagocyte-derived oxidants target these autoinducers for inactivation as an innate defense mechanism of the host. In a skin infection model, expression of phagocyte NADPH oxidase, myeloperoxidase, or inducible nitric oxide synthase was critical for defense against a quorum-sensing pathogen, Staphylococcus aureus, but not for defense against a quorum sensing-deficient mutant. A virulence-inducing peptide of S. aureus was inactivated in vitro and in vivo by reactive oxygen and nitrogen intermediates, including HOCl and ONOO(-). …