Digital Commons Network^™

A 2-Step Approach To Myeloablative Haploidentical Stem Cell Transplantation: A Phase 1/2 Trial Performed With Optimized T-Cell Dosing., Dolores Gross, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, John L Wagner, Beth Colombe, Patricia Cornett Farley, William O'Hara, Phyllis Flomenberg, Maria Werner-Wasik, Janet Brunner, Bijoyesh Mookerjee, Terry Hyslop, Mark Weiss, Neal Flomenberg

Department of Medical Oncology Faculty Papers

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg …

Proliferating Cell Nuclear Antigen Is Required For Loading Of The Smcx/Kmd5c Histone Demethylase Onto Chromatin., Zhihui Liang, Marc Diamond, Johanna A Smith, Matthias Schnell, René Daniel

Department of Medicine Faculty Papers

UNLABELLED: ABSTRACT:

BACKGROUND: Histone methylation is regulated by a large number of histone methyltransferases and demethylases. The recently discovered SMCX/KMD5C demethylase has been shown to remove methyl residues from lysine 4 of histone H3 (H3K4), and constitutes an important component of the regulatory element-1-silencing transcription factor (REST) protein complex. However, little is known about the cellular mechanisms that control SMCX activity and intracellular trafficking.

RESULTS: In this study, we found that small interfering RNA-mediated knockdown of proliferating cell nuclear antigen (PCNA) resulted in the reduction of the chromatin-bound SMCX fraction. We identified a PCNA-interaction protein motif (PIP box) in the …

Human Glial-Restricted Progenitor Transplantation Into Cervical Spinal Cord Of The Sod1 Mouse Model Of Als., Angelo C Lepore, John O'Donnell, Andrew S Kim, Timothy Williams, Alicia Tuteja, Mahendra S Rao, Linda L Kelley, James T Campanelli, Nicholas J Maragakis

Department of Neuroscience Faculty Papers

Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1(G93A) rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue. Our previous findings demonstrated that transplantation of rodent-derived GRPs into cervical spinal cord ventral gray matter (in order to target therapy to diaphragmatic function) resulted in therapeutic efficacy in the SOD1(G93A) rat. Those findings demonstrated the feasibility and efficacy of transplantation-based …

Zinc Supplementation As An Adjunct To Antibiotics In The Treatment Of Pneumonia In Children 2 To 59 Months Of Age, Batool A. Haider, Zohra S. Lassi, Amina Ahmed, Zulfiqar Ahmed Bhutta

Woman and Child Health

Background:Diarrhoeal disorders and acute respiratory infections (ARIs), especially pneumonia, are the most common causes of death in low-income countries. Studies evaluating the impact of zinc supplementation as an adjunct in the management of pneumonia are limited and have shown variable results.
Objectives: To evaluate zinc supplementation, as an adjunct to antibiotics, in the treatment (clinical recovery) of pneumonia in children aged two to 59 months.
Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), which contains the Cochrane Acute Respiratory Infections (ARI) Group's and the Cochrane Infectious Diseases Group's Specialised …

Comparative Immunogenicity Of Na-Gst-1 Human Hookworm Vaccine With Synthetic Glucopyranosyl Lipid Adjuvant (Gla) In Balb/C Mice, Amar R. Jariwala, Brian Keegan, Jordan L. Plieskatt, Maria Elena Bottazzi, Peter J. Hotez, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Posters and Presentations

More than 740 million people worldwide are infected with Hookworm. Hookworm infection is most prevalent in the poorest of the poor populations of the world, and has serious health effects. Hookworm infection causes blood loss leading to iron deficiency anemia and protein energy malnutrition, which results in a compromised immune response. Consequently, the target human population suffers from an increased susceptibility to infectious diseases including hookworm infection. We have developed recombinant adult hookworm vaccines against hookworm infection to break this vicious cycle. Toll-like receptor (TLR) 4 agonist are known to boost immune response in healthy and immunocompromised individuals. We believe …

Protective Cd8 Memory T Cell Responses To Mouse Melanoma Are Generated In The Absence Of Cd4 T Cell Help, Anik L. Côté, Katelyn T. Byrne, Shannon M. Steinberg, Peisheng Zhang, Mary Jo Turk

Dartmouth Scholarship

Background: We have previously demonstrated that temporary depletion of CD4 T cells in mice with progressive B16 melanoma, followed by surgical tumor excision, induces protective memory CD8 T cell responses to melanoma/melanocyte antigens. We also showed that persistence of these CD8 T cells is supported, in an antigen-dependent fashion, by concurrent autoimmune melanocyte destruction. Herein we explore the requirement of CD4 T cell help in priming and maintaining this protective CD8 T cell response to melanoma.

Use Of Dried-Blood-Spot Samples And In-House Assays To Identify Antiretroviral Drug Resistance In Hiv-Infected Children In Resource-Constrained Settings, Carrie Ziemniak, Yohannes Mengistu, Andrea Ruff, Ya-Hui Chen, Leila Khaki, Abubaker Bedri, Birgitte B. Simen, Paul Palumbo

Dartmouth Scholarship

Monitoring HIV drug resistance is an important component of the World Health Organization's global HIV program. HIV drug resistance testing is optimal with commercially available clinically validated test kits using plasma; however, that type of testing may not be feasible or affordable in resource-constrained settings. HIV genotyping from dried blood spots (DBS) with noncommercial (in-house) assays may facilitate the capture of HIV drug resistance outcomes in resource-constrained settings but has had varying rates of success. With in-house assays for HIV reverse transcriptase, we evaluated the yield of genotyping DBS samples collected from HIV-infected children who were enrolled in two clinical …

The Use Of Targeted Charge-Reversal Nanoparticles (Tcrns) To Investigate Nuclear Delivery Of Fluorescent Agents To Cancer Cells: Implications For Novel Prostate And Breast Cancer Therapy, Mario Dance

Theses and Dissertations

Nanotechnology has recently emerged as a strong contributor toward research efforts to develop targeted systems of drug delivery in cancer therapy. Our work investigates the therapeutic potential of Targeted Charge-Reversal Nanoparticles (TCRNs), a novel nanoparticle with in vitro evidence of nuclear drug delivery. Using M12 prostate cancer cells, MDA-MB-231 breast cancer cells, and modified derivatives of these cell lines, we investigated the ability of Folic Acid-tagged TCRNs to deliver Nile Red and Dimethyl Indole Redfluorescent (DiR) fluorescent dyes to the nucleus of cells using confocal microscopy and in vivo biphontonic imaging using Xenogen® Technology. Confocal imaging with the SCP28 derivative …

Coordinated Regulation By Agra, Sara, And Sarr To Control Agr Expression In Staphylococcus Aureus, Dindo Reyes, Diego O. Andrey, Antoinette Monod, William L. Kelley, Gongyi Zhang, Ambrose L. Cheung

Dartmouth Scholarship

The agr locus of Staphylococcus aureus is composed of two divergent transcripts (RNAII and RNAIII) driven by the P2 and P3 promoters. The P2-P3 intergenic region comprises the SarA/SarR binding sites and the four AgrA boxes to which AgrA binds. We reported here the role of AgrA, SarA, and SarR on agr P2 and P3 transcription. Using real-time reverse transcription (RT)-PCR and promoter fusion studies with selected single, double, triple, and complemented mutants, we showed that AgrA is indispensable to agr P2 and P3 transcription, whereas SarA activates and SarR represses P2 transcription. In vitro runoff transcription assays revealed that …

Aging And Sympathetic Neurotransmission In Two Strains Of Rats That Differ In Longevity And Immune Profiles, Sam David Perez

Loma Linda University Electronic Theses, Dissertations & Projects

Age-related changes in sympathetic neurotransmission in immune organs may be associated with immunosenescence; however no causal relationship has been established. From previous studies in Fischer rats (F344), we have found that during middle age, sympathetic nerve activity (SNA) rises in the spleen followed by a decline in noradrenergic (NA) innervation. Also, increased sympathetic signaling via betaadrenergic receptor (β-AR) and reduced proliferation of lymphocytes are evident with increasing age. Although SNA progressively rises with age, effects of age on sympathetic factors may be different across rat strains. If causal relationships exist between sympathetic activity and immune function, they may be related …

Antagonistic Effects Of Cellular Poly(C) Binding Proteins On Vesicular Stomatitis Virus Gene Expression, Phat X. Dinh, Lalit Beura, Debasis Panda, Anshuman Das, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Immunoprecipitation and subsequent mass spectrometry analysis of the cellular proteins from cells expressing the vesicular stomatitis virus (VSV) P protein identified the poly(C) binding protein 2 (PCBP2) as one of the P protein-interacting proteins. To investigate the role of PCBP2 in the viral life cycle, we examined the effects of depletion or overexpression of this protein on VSV growth. Small interfering RNA-mediated silencing of PCBP2 promoted VSV replication. Conversely, overexpression of PCBP2 in transfected cells suppressed VSV growth. Further studies revealed that PCBP2 negatively regulates overall viral mRNA accumulation and subsequent genome replication. Coimmunoprecipitation and immunofluorescence microscopic studies showed that …

Acute Fatty Liver Of Pregnancy: An Update On Mechanisms, Sathish Kumar Natarajan, Kavitha R. Thangaraj, Ashish Goel, C. E. Eapen, K. A. Balasubramanian, Anup Ramachandran

School of Veterinary and Biomedical Sciences: Faculty Publications

Acute fatty liver of pregnancy (AFLP), characterized by hepatic microvesicular steatosis, is a sudden catastrophic illness occurring almost exclusively in the third trimester of pregnancy. Defective fatty acid oxidation in the fetus has been shown to be associated with this disease. Since the placenta has the same genetic makeup as the fetus and as AFLP patients generally recover following delivery, we hypothesized that the placenta might be involved in pathogenesis of this disease. In an animal model of hepatic microvesicular steatosis (using sodium valproate), we found that microvesicular steatosis results in mitochondrial structural alterations and oxidative stress in subcellular organelles …

Sirolimus-Induced Pneumonitis Complicated By Pentamidine-Induced Phospholipidosis In A Renal Transplant Recipient: A Case Report., E J Filippone, J M Carson, R A Beckford, B C Jaffe, E Newman, B K Awsare, C Doria, J L Farber

Department of Medicine Faculty Papers

The proliferation signal inhibitors (PSIs)-sirolimus, everolimus, and temsirolimus-have been associated with a noninfectious pneumonitis characterized by lymphocytic alveolitis and bronciolitis obliterans with organizing pneumonia (BOOP). This condition usually occurs within the first year. Herein we presented a case of a deceased donor renal transplant with interstitial pneumonitis developing 6 years after a switch from tacrolimus to sirolimus due to chronic graft dysfunction. After the addition of intravenous pentamidine due to the suspicion of Pneumocystis pneumonia, there was marked clinical deterioration requiring intubation. Open lung biopsy revealed sirolimus-induced pulmonary toxicity (BOOP) with the additional finding of a drug-induced phospholipidosis (DIPL) that …

Characterization Of Vibrio Cholerae O1 El Tor Biotype Variant Clinical Isolates From Bangladesh And Haiti, Including A Molecular Genetic Analysis Of Virulence Genes, Mike S. Son, Christina J. Megli, Gabriela Kovacikova, Firdausi Qadri, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae serogroup O1, the causative agent of the diarrheal disease cholera, is divided into two biotypes: classical and El Tor. Both biotypes produce the major virulence factors toxin-coregulated pilus (TCP) and cholera toxin (CT). Although possessing genotypic and phenotypic differences, El Tor biotype strains displaying classical biotype traits have been reported and subsequently were dubbed El Tor variants. Of particular interest are reports of El Tor variants that produce various levels of CT, including levels typical of classical biotype strains. Here, we report the characterization of 10 clinical isolates from the International Centre for Diarrhoeal Disease Research, Bangladesh, and …

Potential Applications Of Curcumin And Its Novel Synthetic Analogs And Nanotechnology-Based Formulations In Cancer Prevention And Therapy., Murielle Mimeault, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Curcumin has attracted great attention in the therapeutic arsenal in clinical oncology due to its chemopreventive, antitumoral, radiosensibilizing and chemosensibilizing activities against various types of aggressive and recurrent cancers. These malignancies include leukemias, lymphomas, multiple myeloma, brain cancer, melanoma and skin, lung, prostate, breast, ovarian, liver, gastrointestinal, pancreatic and colorectal epithelial cancers. Curcumin mediates its anti-proliferative, anti-invasive and apoptotic effects on cancer cells, including cancer stem/progenitor cells and their progenies, through multiple molecular mechanisms. The oncogenic pathways inhibited by curcumin encompass the members of epidermal growth factor receptors (EGFR and erbB2), sonic hedgehog (SHH)/GLIs and Wnt/β-catenin and downstream signaling elements …

Extracellular Atp Acts On P2y2 Purinergic Receptors To Facilitate Hiv-1 Infection, Claire Séror, Marie-Therese Melki, Frederic Subra, Syed Qasim Raza, Marlene Bras, Hela Saïdi, Roberta Nardacci, Laurent Voisin, Audrey Paoletti, Frederic Law, Isabelle Martins, Alessandra Amendola, Ali A. Abdul-Sater, Fabiola Ciccosanti, Olivier Delelis, Florence Niedergang, Sylvain Thierry, Najwane Said-Sadier, Christophe Lamaze, Didier Métivier, Jerome Estaquier, Gian Maria Fimia, Laura Falasca, Rita Casetti, Nazanine Modjtahedi, Jean M. Kanellopoulos, Jean-Francois Mouscadet, David M. Ojcius, Mauro Piacentini, Marie-Lise Gougeon, Guido Kroemer, Jean-Luc Perfetini

All Dugoni School of Dentistry Faculty Articles

Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant …

Glutaredoxin 2 Prevents H2o2-Induced Cell Apoptosis By Protecting Complex I Activity In The Mitochondria, Hongli Wu, Kuiyi Xing, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin 2 (Grx2) belongs to the oxidoreductase family and is an isozyme of glutaredoxin 1 (Grx1) present in the mitochondria, however its function is not well understood. The purpose of this study is to evaluate the potential anti-apoptotic function of Grx2 by examining its ability to protect complex I in the mitochondrial electron transport system using human lens epithelial cells as a model. We found that cells treated with 200 μM hydrogen peroxide (H2O2) for 24 h exhibited decreased viability and became apoptotic with corresponding Bax up-regulation, Bcl-2 down-regulation, caspase 3 activation and mitochondrial cytochrome c leakage. Grx2 over-expression (OE) …

Enforced Expression Of Tbx1 In Fetal Thymic Epithelial Cells Antagonizes Thymus Organogenesis, Kim T. Cardenas

Dissertations and Theses (Open Access)

Enforced expression of Tbx1 in fetal thymic epithelial cells antagonizes

thymus organogenesis

Kim T. Cardenas

The thymus and parathyroid glands originate from organ-specific domains of 3rd pharyngeal pouch (PP) endoderm. At embryonic day 11.5 (E11.5), the ventral thymus and dorsal parathyroid domains can be identified by Foxn1 and Gcm2 expression respectively. Neural crest cells, (NCCs) play a role in regulating patterning of 3rd PP endoderm. In addition, pharyngeal endoderm influences fate determination via secretion of Sonic hedgehog (Shh), a morphogen required for Gcm2 expression and generation of the parathyroid domain. Gcm2 is a downstream target of the transcription factor Tbx1, …

Protection And Attachment Of Vibrio Cholerae Mediated By The Toxin-Coregulated Pilus In The Infant Mouse Model, Shelly J. Krebs, Ronald K. Taylor

Dartmouth Scholarship

Colonization of the human small intestine by Vibrio cholerae is an essential step in pathogenesis that requires the type IV toxin-coregulated pilus (TCP). To date, three functions of TCP have been characterized: it serves as the CTXΦ receptor, secretes the colonization factor TcpF, and functions in microcolony formation by mediating bacterium-bacterium interactions. Although type IV pili in other pathogenic bacteria have been characterized as playing a major role in attachment to epithelial cells, there are very few studies to suggest that TCP acts as an attachment factor. Taking this into consideration, we investigated the function of TCP in attachment to …

Comparison Of Adenoviruses As Oncolytics And Cancer Vaccines In An Immunocompetent B Cell Lymphoma Model, Eric A. Weaver, Christopher Y. Chen, Shannon M. May, Mary E. Barry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We have screened human adenoviruses (Ads) for oncolytic activity against a variety of mouse and hamster cell lines and have found a number that are susceptible to a variety of Ad serotypes. A20 lymphoma is derived from BALB/c mice and is susceptible to infection and killing by a variety of human Ads. A20 is also a suitable cancer vaccine model, because these cells express a unique immunoglobulin variable region that can be targeted by vaccination. To compare Ads as cancer vaccines versus Ads as oncolytics, A20 tumors were initiated in immunocompetent BALB/c mice. Mice immunized with first-generation Ad5 expressing the …

Regulation Of Cytosolic Phospholipase A2 (Cpla2) And Its Association With Cell Proliferation In Human Lens Epithelial Cells, Yin Wang, Kui-Yi Xing, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. To investigate the molecular mechanism for cytosolic phospholipase A2 (cPLA2) regulation and its association to platelet-derived growth factor (PDGF)-induced cell proliferation.

METHODS. cPLA2 was examined using human lens epithelial (HLE) B3 cells. Reactive oxygen species (ROS) generation induced by PDGF was analyzed by luminescence assay. Cell proliferation was measured by cell counting and by BrdU assay. Human cPLA2 gene was cloned via RT-PCR followed by sitedirected mutagenesis to construct HLE B3 cells expressing either inactive cPLA2 enzyme with S228A mutation (S228A), or cPLA2 truncated at the calcium-binding C2 domain (C2D). Activity of cPLA2 was measured by arachidonic acid (AA) …

Emerging Dynamics Of Human Campylobacteriosis In Southern Ireland, Susan Bullman, Daniel Corcoran, James O'Leary, Derry O'Hare, Brigid Lucey, Roy D. Sleator

Department of Biological Sciences Publications

Infections with Campylobacter spp. pose a significant health burden worldwide. The significance of Campylobacter jejuni/Campylobacter coli infection is well appreciated but the contribution of non-C. jejuni/C. coli spp. to human gastroenteritis is largely unknown. In this study, we employed a two-tiered molecular study on 7194 patient faecal samples received by the Microbiology Department in Cork University Hospital during 2009. The first step, using EntericBio® (Serosep), a multiplex PCR system, detected Campylobacter to the genus level. The second step, utilizing Campylobacter species-specific PCR identified to the species level. A total of 340 samples were confirmed as Campylobacter genus positive, 329 of …

Generation Of A Kupffer Cell-Evading Adenovirus For Systemic And Liver-Directed Gene Transfer, Reeti Khare, Shannon M. May, Francesco Vetrini, Eric A. Weaver, Donna Palmer, Amanda Rosewell, Nathan Grove, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated >10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to …

Caspase-1 Dependent Il-1Β Secretion Is Critical For Host Defense In A Mouse Model Of Chlamydia Pneumoniae Lung Infection, Kenichi Shimada, Timothy R. Crother, Justin Karlin, Shuang Chen, Norika Chiba, V. Krishnan Ramanujan, Laurent Vergnes, David M. Ojcius, Moshe Arditi

All Dugoni School of Dentistry Faculty Articles

Chlamydia pneumoniae (CP) is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory disorders. Caspase-1 is a key component of the ‘inflammasome’, and is required to cleave pro-IL-1β to bioactive IL-1β. Here we demonstrate for the first time a critical requirement for IL-1β in response to CP infection. Caspase-1^−/− mice exhibit delayed cytokine production, defective clearance of pulmonary bacteria and higher mortality in response to CP infection. Alveolar macrophages harbored increased bacterial numbers due to reduced iNOS levels in Caspase-1^−/− mice. Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice …

Multilaboratory Evaluation Of Real-Time Pcr Tests For Hepatitis B Virus Dna Quantification, Angela M. Caliendo, Alexander Valsamakis, James W. Bremer, Andrea Ferreira-Gonzalez, Suzanne Granger, Linda Sabatini, Gregory J. Tsongalis

Dartmouth Scholarship

The performance characteristics of four different assays for hepatitis B virus (HBV) quantification were assessed: the Abbott RealTime HBV IUO, the Roche Cobas AmpliPrep/Cobas TaqMan HBV test, the Roche Cobas TaqMan HBV test with HighPure system, and the Qiagen artus HBV TM ASR. Limit of detection (LOD), linear range, reproducibility, and agreement were determined using a serially diluted plasma sample from a single chronically infected subject. Each assay was tested by at least three laboratories. The LOD of the RealTime and two TaqMan assays was approximately 1.0 log₁₀ IU/ml; for artus HBV (which used the lowest volume of extracted …

Immune Evasion Of Porcine Reproductive And Respiratory Syndrome Virus Through Glycan Shielding Involves Both Glycoprotein 5 As Well As Glycoprotein 3, Hiep Vu, Byungjoon Kwon, Kyoung-Jin Yoon, William W. Laegreid, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Passive administration of porcine reproductive and respiratory syndrome virus (PRRSV) neutralizing antibodies (NAbs) can effectively protect pigs against PRRSV infection. However, after PRRSV infection, pigs typically develop a weak and deferred NAb response. One major reason for such a meager NAb response is the phenomenon of glycan shielding involving GP5, a major glycoprotein carrying one major neutralizing epitope. We describe here a type II PRRSV field isolate (PRRSV-01) that is highly susceptible to neutralization and induces an atypically rapid, robust NAb response in vivo. Sequence analysis shows that PRRSV-01 lacks two N-glycosylation sites, normally present in wild-type (wt) PRRSV strains, …

Potency Testing For Ntd Vaccines: Determining Relative Potency For The Na-Gst-1 Human Hookworm Vaccine, Amar R. Jariwala, Brian Keegan, Pavithra Raghavendra, Jordan L. Plieskatt, Maria Elena Bottazzi, Peter J. Hotez, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Posters and Presentations

Over the next decade, a new generation of vaccines will target the neglected tropical diseases (NTDs) . The goal of most NTD vaccines will be to reduce the morbidity and decrease the chronic debilitating nature of these often-forgotten infections - outcomes that are hard to measure in the traditional potency-testing paradigm . The absence of measurable correlates of protection, a lack of permissive animal models for lethal infection, and a lack of clinical indications that do not include the induction of sterilizing immunity required us to reconsider the traditional bioassay methods for determining vaccine potency . Owing to these limitations, …

Hypervirulent Chlamydia Trachomatis Clinical Strain Is A Recombinant Between Lymphogranuloma Venereum (L(2)) And D Lineages, Naraporn Somboonna, Raymond Wan, David M. Ojcius, Matthew A. Pettengill, Sandeep J. Joseph, Alexander Chang, Ray Hsu, Timothy D. Read, Deborah Dean

All Dugoni School of Dentistry Faculty Articles

Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L₂/434 and outbreak strain L₂b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L₂c, isolated from an MSM with severe hemorrhagic proctitis. L₂c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, …

Characterization Of The Sigma Factor Proteins And The Dna Binding Protein Euo Of Chlamydia, Cory L. Blackwell

Theses and Dissertations (ETD)

Chlamydia spp. are prokaryotic obligate intracellular pathogens with a unique, biphasic developmental cycle in which an infectious, extracellular form termed the elementary body (EB) interconverts with a metabolically active intracellular reticulate body (RB) within host cells. Subsets of genes are differentially expressed during the developmental cycle, and these genes are believed to be responsible for the transitions between the EB and RB forms. The goal of these studies was to explore two potential mechanisms that may function in regulating developmental cycle stage‑specific gene expression in chlamydiae: a cascade of sigma factor expression and the binding of the early stage protein …

Impact Of Adjuvants On The Antibody Responses To Pre-Pandemic H5n1 Influenza Vaccines, Ali Hassan Ellebedy

Theses and Dissertations (ETD)

Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to transmit among humans. Since their emergence in 1996, human infections with highly pathogenic avian influenza A (H5N1) viruses presented a serious public health challenge. Additionally, H5N1 viruses caused significant agricultural and economic losses in the communities it has affected. Human infections with these viruses are rare but when they occur, these infections are highly fatal. A greater public health concern stems from the rapid evolution displayed by these viruses so far, which in turn might result in viruses …