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Definition Of An Hla-Dpw2-Restricted Epitope On Ns3, Recognized By A Dengue Virus Serotype-Cross-Reactive Human Cd4+ Cd8- Cytotoxic T-Cell Clone, Ichiro Kurane, Li Chen Dai, Peter G. Livingston, Elaine Reed, Francis A. Ennis Dec 2013

Definition Of An Hla-Dpw2-Restricted Epitope On Ns3, Recognized By A Dengue Virus Serotype-Cross-Reactive Human Cd4+ Cd8- Cytotoxic T-Cell Clone, Ichiro Kurane, Li Chen Dai, Peter G. Livingston, Elaine Reed, Francis A. Ennis

Li Dai

We previously reported that the clone JK34 was cross-reactive for dengue virus types 1, 2, 3, and 4 and recognized NS3 (I. Kurane, M. A. Brinton, A. L. Samson, and F. A. Ennis, J. Virol. 65:1823-1828, 1991). In the present experiments, we defined the epitope at the amino acid level, with 93 15-mer overlapping peptides which cover the entire NS3. A peptide 4 which contains amino acids 251 to 265 of NS3 sensitized the autologous B lymphoblastoid cell line (LCL) to the lysis by JK34. The smallest peptide recognized by JK34 was a 10-mer peptide which contains amino acids 255 …


Mutation Of Human Immunodeficiency Virus Type 1 At Amino Acid 585 On Gp41 Results In Loss Of Killing By Cd8+ A24-Restricted Cytotoxic T Lymphocytes, Li Chen Dai, Kim West, Rebecca A. Littaua, Kazuo Takahashi, Francis A. Ennis Dec 2013

Mutation Of Human Immunodeficiency Virus Type 1 At Amino Acid 585 On Gp41 Results In Loss Of Killing By Cd8+ A24-Restricted Cytotoxic T Lymphocytes, Li Chen Dai, Kim West, Rebecca A. Littaua, Kazuo Takahashi, Francis A. Ennis

Li Dai

A human leukocyte antigen A24-restricted CD8+ cytotoxic T-cell clone specific for gp41 of human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 584 to 591 (YLKDQQLL, NL43 env sequence) of gp41 by using a panel of recombinant vaccinia viruses that contain truncated env genes and synthetic peptides. The clone killed autologous B-lymphoblastoid cell lines pulsed with a synthetic peptide reflecting the sequence of the IIIB and MN strains. This clone, however, failed to kill target cells pulsed with the peptides that have a mutation from Lys to Arg or Gln at …


A Prospective Study Of The Transient Decrease In Ovarian Cancer Risk Following Childbirth, Qin Liu, Mats Lambe, Inkyung Baik, Sven Cnattingius, Tomas Riman, Anders R. Ekbom, Hans-Olov Adami, Chung-Cheng Hsieh Dec 2013

A Prospective Study Of The Transient Decrease In Ovarian Cancer Risk Following Childbirth, Qin Liu, Mats Lambe, Inkyung Baik, Sven Cnattingius, Tomas Riman, Anders R. Ekbom, Hans-Olov Adami, Chung-Cheng Hsieh

Qin Liu

Epidemiologic evidence shows that the risk of ovarian cancer is decreased following childbirth. We examined the time points when the decreased risk of postpartum maternal ovarian cancer reaches the lowest point and whether the protective effect diminishes over time. A case-control study nested within the Swedish Fertility Register included 10,086 cases of epithelial ovarian cancer recorded in the Swedish Cancer Register from 1961 to 2001. From the Fertility Register, 49,249 eligible subjects matched to the cases by age were selected as controls. The analysis contrasted risk between adjacent parities through logistic regression models that included indicator variables representing each year …


Profiles Of Human Serum Antibody Responses Elicited By Three Leading Hiv Vaccines Focusing On The Induction Of Env-Specific Antibodies, Michael Vaine, Shixia Wang, Qin Liu, James Arthos, David C. Montefiori, Paul Goepfert, M. Juliana Mcelrath, Shan Lu Dec 2013

Profiles Of Human Serum Antibody Responses Elicited By Three Leading Hiv Vaccines Focusing On The Induction Of Env-Specific Antibodies, Michael Vaine, Shixia Wang, Qin Liu, James Arthos, David C. Montefiori, Paul Goepfert, M. Juliana Mcelrath, Shan Lu

Qin Liu

In the current report, we compared the specificities of antibody responses in sera from volunteers enrolled in three US NIH-supported HIV vaccine trials using different immunization regimens. HIV-1 Env-specific binding antibody, neutralizing antibody, antibody-dependent cell-mediated cytotoxicity (ADCC), and profiles of antibody specificity were analyzed for human immune sera collected from vaccinees enrolled in the NIH HIV Vaccine Trial Network (HVTN) Study #041 (recombinant protein alone), HVTN Study #203 (poxviral vector prime-protein boost), and the DP6-001 study (DNA prime-protein boost). Vaccinees from HVTN Study #041 had the highest neutralizing antibody activities against the sensitive virus along with the highest binding antibody …


Correlation Of Umbilical Cord Blood Hormones And Growth Factors With Stem Cell Potential: Implications For The Prenatal Origin Of Breast Cancer Hypothesis, Todd M. Savarese, William C. Strohsnitter, Hoi Pang Low, Qin Liu, Inkyung Baik, William C. Okulicz, David P. Chelmow, Pagona Lagiou, Peter J. Quesenberry, Kenneth L. Noller, Chung-Cheng Hsieh Dec 2013

Correlation Of Umbilical Cord Blood Hormones And Growth Factors With Stem Cell Potential: Implications For The Prenatal Origin Of Breast Cancer Hypothesis, Todd M. Savarese, William C. Strohsnitter, Hoi Pang Low, Qin Liu, Inkyung Baik, William C. Okulicz, David P. Chelmow, Pagona Lagiou, Peter J. Quesenberry, Kenneth L. Noller, Chung-Cheng Hsieh

Qin Liu

INTRODUCTION: Prenatal levels of mitogens may influence the lifetime breast cancer risk by driving stem cell proliferation and increasing the number of target cells, and thereby increasing the chance of mutation events that initiate oncogenesis. We examined in umbilical cord blood the correlation of potential breast epithelial mitogens, including hormones and growth factors, with hematopoietic stem cell concentrations serving as surrogates of overall stem cell potential. METHODS: We analyzed cord blood samples from 289 deliveries. Levels of hormones and growth factors were correlated with concentrations of stem cell and progenitor populations (CD34+ cells, CD34+CD38- cells, CD34+c-kit+ cells, and granulocyte-macrophage colony-forming …


A Functional Notch-Survivin Gene Signature In Basal Breast Cancer, Connie Wing-Ching Lee, Karl Simin, Qin Liu, Janet Plescia, Minakshi Guha, Ashraf Khan, Chung-Cheng Hsieh, Dario C. Altieri Dec 2013

A Functional Notch-Survivin Gene Signature In Basal Breast Cancer, Connie Wing-Ching Lee, Karl Simin, Qin Liu, Janet Plescia, Minakshi Guha, Ashraf Khan, Chung-Cheng Hsieh, Dario C. Altieri

Qin Liu

INTRODUCTION: Basal-type, or triple-negative, breast cancer (lacking estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression) is a high-risk disease for which no molecular therapies are currently available. We studied genetic signatures of basal breast cancer potentially suitable for therapeutic intervention. METHODS: We analyzed protein expression of the Notch-1 intracellular domain and survivin by immunohistochemistry in a series of basal breast cancer patients. A hierarchical clustering and overall survival analysis was carried out on a microarray mRNA database of 232 breast cancer patients. Fifteen published mRNA datasets containing estrogen receptor-negative or estrogen receptor-positive samples were subjected to meta-analysis …


Homeotic Gene Teashirt (Tsh) Has A Neuroprotective Function In Amyloid-Beta 42 Mediated Neurodegeneration., Michael M. Moran, Madhuri Kango-Singh, Amit Singh Nov 2013

Homeotic Gene Teashirt (Tsh) Has A Neuroprotective Function In Amyloid-Beta 42 Mediated Neurodegeneration., Michael M. Moran, Madhuri Kango-Singh, Amit Singh

Amit Singh

Background: Alzheimer's disease (AD) is a debilitating age related progressive neurodegenerative disorder characterized by the loss of cognition, and eventual death of the affected individual. One of the major causes of AD is the accumulation of Amyloid-beta 42 (Aβ42) polypeptides formed by the improper cleavage of amyloid precursor protein (APP) in the brain. These plaques disrupt normal cellular processes through oxidative stress and aberrant signaling resulting in the loss of synaptic activity and death of the neurons. However, the detailed genetic mechanism(s) responsible for this neurodegeneration still remain elusive. Methodology/ Principle Findings: We have generated a transgenic Drosophila eye model …


Transitions, Risks, And Actions In Coronary Events--Center For Outcomes Research And Education (Trace-Core): Design And Rationale, Molly Waring, Richard Mcmanus, Jane Saczynski, Milena Anatchkova, David Mcmanus, Randolph Devereaux, Robert Goldberg, Jeroan Allison, Catarina Kiefe Nov 2013

Transitions, Risks, And Actions In Coronary Events--Center For Outcomes Research And Education (Trace-Core): Design And Rationale, Molly Waring, Richard Mcmanus, Jane Saczynski, Milena Anatchkova, David Mcmanus, Randolph Devereaux, Robert Goldberg, Jeroan Allison, Catarina Kiefe

Richard H. McManus

Background: Cardiovascular disease continues to cause significant morbidity, mortality, and impaired quality of life, with unrealized health gains from the underuse of available evidence. The Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education (TRACE-CORE) aims to advance the science of acute coronary syndromes by examining the determinants and outcomes of the quality of transition from hospital to community and by quantifying the impact of potentially modifiable characteristics associated with decreased quality of life, rehospitalization, and mortality. Methods and Results: TRACE-CORE comprises a longitudinal multiracial cohort of patients hospitalized with acute coronary syndromes, 2 research projects, …


Transitions, Risks, And Actions In Coronary Events--Center For Outcomes Research And Education (Trace-Core): Design And Rationale, Molly Waring, Richard Mcmanus, Jane Saczynski, Milena Anatchkova, David Mcmanus, Randolph Devereaux, Robert Goldberg, Jeroan Allison, Catarina Kiefe Nov 2013

Transitions, Risks, And Actions In Coronary Events--Center For Outcomes Research And Education (Trace-Core): Design And Rationale, Molly Waring, Richard Mcmanus, Jane Saczynski, Milena Anatchkova, David Mcmanus, Randolph Devereaux, Robert Goldberg, Jeroan Allison, Catarina Kiefe

Richard H. McManus

Background: Cardiovascular disease continues to cause significant morbidity, mortality, and impaired quality of life, with unrealized health gains from the underuse of available evidence. The Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education (TRACE-CORE) aims to advance the science of acute coronary syndromes by examining the determinants and outcomes of the quality of transition from hospital to community and by quantifying the impact of potentially modifiable characteristics associated with decreased quality of life, rehospitalization, and mortality. Methods and Results: TRACE-CORE comprises a longitudinal multiracial cohort of patients hospitalized with acute coronary syndromes, 2 research projects, …


Combinatorial Resistance: The Best Defense Is A Good Offense, Kevin O'Donovan Nov 2013

Combinatorial Resistance: The Best Defense Is A Good Offense, Kevin O'Donovan

Kevin O'Donovan

No abstract provided.


Progressive Levels Of Physical Dependence To Tobacco Coincide With Changes In The Anterior Cingulum Bundle Microstructure, Wei Huang, Joseph R. Difranza, David N. Kennedy, Nanyin Zhang, Douglas M. Ziedonis, W. W. Sanouri A. Ursprung, Jean A. King Nov 2013

Progressive Levels Of Physical Dependence To Tobacco Coincide With Changes In The Anterior Cingulum Bundle Microstructure, Wei Huang, Joseph R. Difranza, David N. Kennedy, Nanyin Zhang, Douglas M. Ziedonis, W. W. Sanouri A. Ursprung, Jean A. King

Douglas M. Ziedonis

BACKGROUND: The tobacco withdrawal syndrome indicates the development of neurophysiologic dependence. Clinical evidence indicates that neurophysiologic dependence develops through a set sequence of symptom presentation that can be assessed with a new 3-item survey measure of wanting, craving, and needing tobacco, the Level of Physical Dependence (PD). This study sought to determine if advancing neurophysiologic dependence as measured by the Level of PD correlates with characteristics of white matter structure measured by Fractional Anisotropy (FA).

METHODS: Diffusion-MRI based FA and diffusion tensor imaging probabilistic tractography were used to evaluate 11 smokers and 10 nonsmokers. FA was also examined in relation …


Leica Microscope Gpu Deconvolution Stellaris Fish Dataset #1, George Mcnamara Nov 2013

Leica Microscope Gpu Deconvolution Stellaris Fish Dataset #1, George Mcnamara

George McNamara

McNamara 20131101Fri Leica widefield microscope CUDA Deconvolution Stellaris FISH probe cultured cells dataset #1.zip

A text file in the zip archive has experiment details. I am posting this online so that researchers - whether academic or commercial - can evaluate the acquired data, the Bruce and Butte 2013 Optics Express ( http://www.opticsinfobase.org/oe/fulltext.cfm?uri=oe-21-4-4766 ) deconvolution result (note: I may not have used optimal settings), and to compare these deconvolution results to other methods. If anyone generates alternative spatial deconvolution output, such as from: * SVI Huygens * Media Cy AutoQuant * Agard's ER-Decon (Arigovindan 2013 PNAS) * Vicidomini SGP GPU Deconv …


The Synergistic Effects Of Green Tea Polyphenols And Antibiotics Against Potential Pathogens, Bobak Haghjoo, Lee H. Lee, Umme Habiba, Hassan Tahir, Moe Olabi, Tin-Chun Chu Oct 2013

The Synergistic Effects Of Green Tea Polyphenols And Antibiotics Against Potential Pathogens, Bobak Haghjoo, Lee H. Lee, Umme Habiba, Hassan Tahir, Moe Olabi, Tin-Chun Chu

Tinchun Chu, Ph.D.

No abstract provided.


Diarylheptanoid From Pleuranthodium Racemigerum With In Vitro Prostaglandin E2 Inhibitory And Cytotoxic Activity, Hans Wohlmuth, Myrna Deseo, Don Brushett, Dion Thompson, Graham Macfarlane, Lesley Stevenson, David Leach Oct 2013

Diarylheptanoid From Pleuranthodium Racemigerum With In Vitro Prostaglandin E2 Inhibitory And Cytotoxic Activity, Hans Wohlmuth, Myrna Deseo, Don Brushett, Dion Thompson, Graham Macfarlane, Lesley Stevenson, David Leach

Dr Myrna A Deseo

Bioactivity-guided fractionation of an ethanolic extract of the rhizome of Pleuranthodium racemigerum, a tropical Zingiberaceae species from North-eastern Australia, resulted in the isolation and structural elucidation of 1-(4″-methoxyphenyl)-7-(4′-hydroxyphenyl)-(E)-hept-2-ene (1), a new diarylheptanoid related to curcumin. Compound 1 was a fairly potent inhibitor of prostaglandin E2 production in 3T3 murine fibroblasts (IC50 ≈ 34 μM) and also displayed moderate cytotoxicity against this cell line (IC50 = 52.8 μM). The compound also demonstrated cytotoxic activity against the P388D1 murine lymphoblast cell line (IC50 = 117.0 μM) and four human cell lines: Caco-2 colonic adenocarcinoma (IC50 = 44.8 μM), PC3 prostate adenocarcinoma (IC50 …


Prolactin And Fmri Response To Skf38393 In The Baboon, Brad D. Miller, Lauren A. Marks, Jonathan M. Koller, Blake J. Newman, G Larry Bretthorst, Kevin J. Black Oct 2013

Prolactin And Fmri Response To Skf38393 In The Baboon, Brad D. Miller, Lauren A. Marks, Jonathan M. Koller, Blake J. Newman, G Larry Bretthorst, Kevin J. Black

Kevin J. Black, MD

Background: This study’s goal was to provide dose-response data for a dopamine agonist in the baboon using standard methods (replicate measurements at each dose, across a range of doses), as a standard against which to subsequently validate a novel pharmacological MRI (phMRI) method. Dependent variables were functional MRI (fMRI) data from brain regions selected a priori, and systemic prolactin release. Necessary first steps included estimating the magnitude and time course of prolactin response to anesthesia alone and to various doses of agonist. These first steps (“time course studies”) were performed with three agonists, and the results were used to select …


Use Of Veterinary Records To Teach Laboratory Thinking Skills In Biology, Christopher Woolverton Oct 2013

Use Of Veterinary Records To Teach Laboratory Thinking Skills In Biology, Christopher Woolverton

Christopher J. Woolverton

No abstract provided.


Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten Oct 2013

Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten

David D Dunigan Ph. D.

With growing industrial interest in algae plus their critical roles in aquatic systems, the need to understand the effects of algal pathogens is increasing. We examined a model algal host–virus system, Chlorella variabilis NC64A and virus, PBCV-1. C. variabilis encodes 375 homologs to genes involved in RNA silencing and in response to virus infection in higher plants. Illumina RNA-Seq data showed that 325 of these homologs were expressed in healthy and early PBCV-1 infected (≤60 min) cells. For each of the RNA silencing genes to which homologs were found, mRNA transcripts were detected in healthy and infected cells. C. variabilis, …


Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass Oct 2013

Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass

Aaron P Blaisdell

Welcome to the first issue of the Journal of Evolution and Health! The Journal of Evolution and Health is the peer-reviewed, open-access journal of the Ancestral Health Society, a community of scientists, healthcare professionals, and laypersons who collaborate to understand health challenges from an evolutionary perspective.


Seizure Protection By Intrapulmonary Delivery Of Midazolam In Mice, Ashish Dhir, Dorota Zolkowska, Michael A. Rogawski Sep 2013

Seizure Protection By Intrapulmonary Delivery Of Midazolam In Mice, Ashish Dhir, Dorota Zolkowska, Michael A. Rogawski

Michael A. Rogawski

The lung provides a portal of entry that could be used to rapidly deliver anticonvulsant substances to the brain to treat seizures. In the present study, we demonstrate that midazolam, a water-soluble anticonvulsant benzodiazepine, confers potent seizure protection when administered via the intrapulmonary route. High dose (100 mg/kg) intraperitoneal midazolam induced loss-of-righting reflex in mice. Lower doses of midazolam (100–1000 μg/kg) when administered intraperitoneally did not induce loss-of-righting reflex but protected animals against pentylenetetrazol (PTZ)-induced seizures. Intrapulmonary administration of midazolam via a tracheal cannula protected against intraperitoneal PTZ seizures at lower doses. The minimal intraperitoneal and intravenous doses of midazolam …


Elasmobranch Qpcr Reference Genes: A Case Study Of Hypoxia Preconditioned Epaulette Sharks, Kalle T. Rytkönen, Gillian M. C. Renshaw, Kevin J. Ashton, Grant Williams-Pritchard, Erica H. Leder, Mikko Nikinmaa Sep 2013

Elasmobranch Qpcr Reference Genes: A Case Study Of Hypoxia Preconditioned Epaulette Sharks, Kalle T. Rytkönen, Gillian M. C. Renshaw, Kevin J. Ashton, Grant Williams-Pritchard, Erica H. Leder, Mikko Nikinmaa

Kevin Ashton

Background: Elasmobranch fishes are an ancient group of vertebrates which have high potential as model species for research into evolutionary physiology and genomics. However, no comparative studies have established suitable reference genes for quantitative PCR (qPCR) in elasmobranchs for any physiological conditions. Oxygen availability has been a major force shaping the physiological evolution of vertebrates, especially fishes. Here we examined the suitability of 9 reference candidates from various functional categories after a single hypoxic insult or after hypoxia preconditioning in epaulette shark (Hemiscyllium ocellatum).Results: Epaulette sharks were caught and exposed to hypoxia. Tissues were collected from 10 controls, 10 individuals …


Long-Lasting Attenuation Of Amygdala-Kindled Seizures After Convection-Enhanced Delivery Of Botulinum Neurotoxins A And B Into The Amygdala In Rats, Maciej Gasior, Rebecca Tang, Michael A. Rogawski Aug 2013

Long-Lasting Attenuation Of Amygdala-Kindled Seizures After Convection-Enhanced Delivery Of Botulinum Neurotoxins A And B Into The Amygdala In Rats, Maciej Gasior, Rebecca Tang, Michael A. Rogawski

Michael A. Rogawski

Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. Here we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully-kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-min period by convection enhanced delivery (CED). Electrographic (EEG) and behavioral …


Development And Characterization Of A Severe Acute Respiratory Syndrome-Associated Coronavirus-Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis In Mice, Thomas Greenough, Gregory Babcock, Anjeanette Roberts, Hector Hernandez, William Thomas, Jennifer Coccia, Robert Graziano, Mohan Srinivasan, Israel Lowy, Robert Finberg, Kanta Subbarao, Leatrice Vogel, Mohan Somasundaran, Katherine Luzuriaga, John Sullivan, Donna Ambrosino Aug 2013

Development And Characterization Of A Severe Acute Respiratory Syndrome-Associated Coronavirus-Neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis In Mice, Thomas Greenough, Gregory Babcock, Anjeanette Roberts, Hector Hernandez, William Thomas, Jennifer Coccia, Robert Graziano, Mohan Srinivasan, Israel Lowy, Robert Finberg, Kanta Subbarao, Leatrice Vogel, Mohan Somasundaran, Katherine Luzuriaga, John Sullivan, Donna Ambrosino

William D Thomas Jr

BACKGROUND: Severe acute respiratory syndrome (SARS) remains a significant public health concern after the epidemic in 2003. Human monoclonal antibodies (MAbs) that neutralize SARS-associated coronavirus (SARS-CoV) could provide protection for exposed individuals. METHODS: Transgenic mice with human immunoglobulin genes were immunized with the recombinant major surface (S) glycoprotein ectodomain of SARS-CoV. Epitopes of 2 neutralizing MAbs derived from these mice were mapped and evaluated in a murine model of SARS-CoV infection. RESULTS: Both MAbs bound to S glycoprotein expressed on transfected cells but differed in their ability to block binding of S glycoprotein to Vero E6 cells. Immunoprecipitation analysis revealed …


Treatment With Monoclonal Antibodies Against Clostridium Difficile Toxins, Israel Lowy, Deborah Molrine, Brett Leav, Barbara Blair, Roger Baxter, Dale Gerding, Geoffrey Nichol, William Thomas, Mark Leney, Susan Sloan, Catherine Hay, Donna Ambrosino Aug 2013

Treatment With Monoclonal Antibodies Against Clostridium Difficile Toxins, Israel Lowy, Deborah Molrine, Brett Leav, Barbara Blair, Roger Baxter, Dale Gerding, Geoffrey Nichol, William Thomas, Mark Leney, Susan Sloan, Catherine Hay, Donna Ambrosino

William D Thomas Jr

BACKGROUND: New therapies are needed to manage the increasing incidence, severity, and high rate of recurrence of Clostridium difficile infection.

METHODS: We performed a randomized, double-blind, placebo-controlled study of two neutralizing, fully human monoclonal antibodies against C. difficile toxins A (CDA1) and B (CDB1). The antibodies were administered together as a single infusion, each at a dose of 10 mg per kilogram of body weight, in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin. The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo.

RESULTS: …


Human Monoclonal Antibodies Directed Against Toxins A And B Prevent Clostridium Difficile-Induced Mortality In Hamsters, Gregory Babcock, Teresa Broering, Hector Hernandez, Robert Mandell, Katherine Donahue, Naomi Boatright, Anne Stack, Israel Lowy, Robert Graziano, Deborah Molrine, Donna Ambrosino, William Thomas Aug 2013

Human Monoclonal Antibodies Directed Against Toxins A And B Prevent Clostridium Difficile-Induced Mortality In Hamsters, Gregory Babcock, Teresa Broering, Hector Hernandez, Robert Mandell, Katherine Donahue, Naomi Boatright, Anne Stack, Israel Lowy, Robert Graziano, Deborah Molrine, Donna Ambrosino, William Thomas

William D Thomas Jr

Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea, and recent outbreaks of strains with increased virulence underscore the importance of identifying novel approaches to treat and prevent relapse of Clostridium difficile-associated diarrhea (CDAD). CDAD pathology is induced by two exotoxins, toxin A and toxin B, which have been shown to be cytotoxic and, in the case of toxin A, enterotoxic. In this report we describe fully human monoclonal antibodies (HuMAbs) that neutralize these toxins and prevent disease in hamsters. Transgenic mice carrying human immunoglobulin genes were used to isolate HuMAbs that neutralize the cytotoxic effects of either toxin …


Identification Of A Human Monoclonal Antibody To Replace Equine Diphtheria Anti-Toxin For The Treatment Of Diphtheria, Leila M. Sevigny, Brian J. Booth, Kirk J. Rowley, Brett A. Leav, Peter S. Cheslock, Kerry A. Garrity, Susan Sloan, Gregory J. Babcock, William D. Thomas, Mark Klempner, Yang Wang Aug 2013

Identification Of A Human Monoclonal Antibody To Replace Equine Diphtheria Anti-Toxin For The Treatment Of Diphtheria, Leila M. Sevigny, Brian J. Booth, Kirk J. Rowley, Brett A. Leav, Peter S. Cheslock, Kerry A. Garrity, Susan Sloan, Gregory J. Babcock, William D. Thomas, Mark Klempner, Yang Wang

William D Thomas Jr

Diphtheria anti-toxin (DAT) has been used to treat Corynebacterium diphtheriae infection for over one hundred years. While the global incidence of diphtheria has declined in the 20th century, the disease remains endemic in many parts of the world and significant outbreaks still occur. Diphtheria anti-toxin is an equine polyclonal antibody with considerable side effects that is in critically short supply globally. A safer, more readily available alternative to DAT would be desirable. In the current study, we cloned human monoclonal antibodies (HuMabs) directly from antibody secreting cells of human volunteers immunized with Td vaccine. We isolated a diverse panel of …


Amino Acids 270 To 510 Of The Severe Acute Respiratory Syndrome Coronavirus Spike Protein Are Required For Interaction With Receptor, Gregory Babcock, Diana Esshaki, William Thomas, Donna Ambrosino Aug 2013

Amino Acids 270 To 510 Of The Severe Acute Respiratory Syndrome Coronavirus Spike Protein Are Required For Interaction With Receptor, Gregory Babcock, Diana Esshaki, William Thomas, Donna Ambrosino

William D Thomas Jr

A novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), has recently been identified as the causative agent of severe acute respiratory syndrome (SARS). SARS-CoV appears similar to other coronaviruses in both virion structure and genome organization. It is known for other coronaviruses that the spike (S) glycoprotein is required for both viral attachment to permissive cells and for fusion of the viral envelope with the host cell membrane. Here we describe the construction and expression of a soluble codon-optimized SARS-CoV S glycoprotein comprising the first 1,190 amino acids of the native S glycoprotein (S(1190)). The codon-optimized and native S glycoproteins …


Therapy With A Severe Acute Respiratory Syndrome-Associated Coronavirus-Neutralizing Human Monoclonal Antibody Reduces Disease Severity And Viral Burden In Golden Syrian Hamsters, Anjeanette Roberts, William Thomas, Jeannette Guarner, Elaine Lamirande, Gregory Babcock, Thomas Greenough, Leatrice Vogel, Norman Hayes, John Sullivan, Sherif Zaki, Kanta Subbarao, Donna Ambrosino Aug 2013

Therapy With A Severe Acute Respiratory Syndrome-Associated Coronavirus-Neutralizing Human Monoclonal Antibody Reduces Disease Severity And Viral Burden In Golden Syrian Hamsters, Anjeanette Roberts, William Thomas, Jeannette Guarner, Elaine Lamirande, Gregory Babcock, Thomas Greenough, Leatrice Vogel, Norman Hayes, John Sullivan, Sherif Zaki, Kanta Subbarao, Donna Ambrosino

William D Thomas Jr

BACKGROUND: Immunotherapy with monoclonal antibodies (MAbs) offers safe interventions for the prevention of infection in patients after organ transplantation and for the treatment of cancers and autoimmune diseases. MAb 201 is a severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-specific MAb that prevents establishment of viral replication in vitro and prevents viral replication in vivo when administered prophylactically. The efficacy of MAb 201 in the treatment of SARS was evaluated in golden Syrian hamsters, an animal model that supports SARS-CoV replication to high levels and displays severe pathological changes associated with infection, including pneumonitis and pulmonary consolidation. METHODS: Golden Syrian hamsters that …


Therapeutic Approaches To Aggressive Carcinomas Based On A Novel Vegf/Neuropilin Autocrine Pathway, Hira Lal Goel, Arthur M. Mercurio Aug 2013

Therapeutic Approaches To Aggressive Carcinomas Based On A Novel Vegf/Neuropilin Autocrine Pathway, Hira Lal Goel, Arthur M. Mercurio

Arthur M. Mercurio

Summary: Autocrine VEGF signaling in tumor cells contributes to de-differentiation and function of tumor initiating/stem cells. NRP2 is the nexus of a signaling pathway that promotes de-differentiation and sustains tumor initiating/stem sells. Anti-NRP2 therapy is worth pursuing, especially for high-grade cancers. Therapeutic Abs are available. This presentation was part of the retreat mini-symposium entitled: Biomarker Discovery and Targeted Therapeutics in Cancer.


Fibre: Male Participants Not Getting Enough, Rebecca Thorne, Jane O'Shea, Qingsheng Zhang, Linda Tapsell, Marijka Batterham, Karen Charlton Aug 2013

Fibre: Male Participants Not Getting Enough, Rebecca Thorne, Jane O'Shea, Qingsheng Zhang, Linda Tapsell, Marijka Batterham, Karen Charlton

Qingsheng Zhang

A regular intake of dietary fibre has been associated with a number of health benefits. Consuming a high fibre diet may significantly lower the risk of developing heart disease, stroke, hypertension, diabetes and obesity (Anderson et al, 2009). Foods high in fibre such as fruit, vegetables, legumes and wholegrains are regularly included in diets targeting weight loss as they are low in fat, sugar and salt and contain a number of vitamins and minerals. Participants in trials using healthy background diets may increase their fibre intake in addition to the study variables. The aim of this study was to report …


Start Date May Predict Attrition 6 Months Into A 12mth Dietary Intervention Weight Loss Trial, Jane O'Shea, Linda Tapsell, Marijka Batterham, Karen Charlton, Yasmine Probst, Rebecca Thorne, Qingsheng Zhang, Holley Jones Aug 2013

Start Date May Predict Attrition 6 Months Into A 12mth Dietary Intervention Weight Loss Trial, Jane O'Shea, Linda Tapsell, Marijka Batterham, Karen Charlton, Yasmine Probst, Rebecca Thorne, Qingsheng Zhang, Holley Jones

Qingsheng Zhang

Participant recruitment is a difficult and time consuming aspect of clinical trials, often resulting in delays and budget overruns. Having reached recruitment targets the next challenge is participant retention. Some weight-loss studies have attrition rates around 60% which may introduce bias in the results. It may be possible to reduce attrition rates if known predictors can be found but to date few studies produced consistent results. The aim of this exploratory study was to determine whether start date could be a predictor of attrition for participants involved in the SMART weight loss clinical trial (ACTRN12608000425392). Recruitment for the trial occurred …