Medical Microbiology Commons^™

Anti-Herv-K (Hml-2) Capsid Antibody Responses In Hiv Elite Controllers., Miguel De Mulder, Devi Sengupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection.

Results

We developed an ELISA assay using either recombinant protein or 164 redundant “15mer” HERV-K (HML-2) Gag peptides to test sera for antibody reactivity. We identified a total of eight potential HERV-K (HML-2) Gag immunogenic domains: two on …

Improving Type And Screen Specimen Collection Prior To Elective Surgery, Nordx Blood Bank Staff, Haley Pelletier, Suneela Nayak, Stephen Tyzik, Ruth Hanselman

Maine Medical Center

To avoid delays in the availability of compatible blood for elective surgery patients requiring transfusion, a type and screen specimen should be completed at least 24 hours prior to surgery. Baseline metrics in an acute care inpatient blood bank demonstrated a significant number of cases with no type or screen completed.

The objective of this KPI was to prevent any delays in providing compatible blood products to scheduled surgical patients. Several internal and external system issues were identified as a result of a root cause analysis and a number of actions were initiated.

Outcomes have been positive. Data collection post …

Stromal Cyclin D1 Promotes Heterotypic Immune Signaling And Breast Cancer Growth, Timothy G. Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R. Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Matthew C. Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P. Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas Craig Hooper, Zuoren Yu, Aaron R. Goldman, David W. Speicher, Lisa Laury-Kleintop, Richard G. Pestell

Department of Cancer Biology Faculty Papers

The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased > 30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1^Stroma) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy. Cyclin D1^Stroma had profound effects on the breast tumor microenvironment increasing the recruitment of F4/80⁺ and CD11b⁺ macrophages and increasing …

Randomized Vitamin D Supplementation In Vitamin D Deficient Obese Children From West Virginia, Yoram Elitsur Md, Deborah L. Preston

Yoram Elitsur

Objective: Vitamin D (Vit D) deficiency is a very common problem in obese children, but clinical guidelines for maintenance or treatment have not been published for this population. The aim was to assess the benefit of 2 months Vit D supplementation given to deficient obese children from WV. Design: Vit D deficient obese children were prospectively recruited. Exclusion criteria included <8 years, and medical conditions that may affect Vit D homeostasis. Participants were randomized into two supplement groups: 5,000IU/day (Group A) or 50,000IU/week (Group B). Serum 25(OH)D levels were measured at baseline and post-treatment. Results: Sixty obese children were screened of whom 39 (65%) were deficient (<20ng/ml). Of the 39 recruited, 26 completed the study. The mean serum 25(OH)D after 2 months treatment were significantly higher in Group B (p= 0.02), but most reached normal levels (>30ng/ml). Conclusions: Two months Vit D supplementation (5000IU/day or 50,000IU/week) was sufficient to normalize 25(OH)D levels in Vit D deficient obese West Virginian children.

Helicobacter-Pylori Negative Gastritis In Children—A New Clinical Enigma, Yoram Elitsur, Deborah L. Preston

Yoram Elitsur

The decrease in the prevalence of Helicobacter pylori (Hp) infection in children in the world gave rise to a new pathological finding termed as Hp-negative gastritis. Unfortunately, the term “Hp-negative gastritis” has not been identified as a pathological process and has the status of a “second cousin”; in most publications it was never mentioned as a subject to be dealt with, but was “left over” data that was never the topic of the manuscripts’ discussions. Only recently has the topic captured the attention of the pathologists who described this phenomenon in adults, yet the pathological and/or clinical spectrum or significance …

Na/K-Atpase Signaling And Salt Sensitivity: The Role Of Oxidative Stress, Jiang Liu, Yanling Yan, Ying Nie

Yanling Yan

Other than genetic regulation of salt sensitivity of blood pressure, many factors have been shown to regulate renal sodium handling which contributes to long-term blood pressure regulation and have been extensively reviewed. Here we present our progress on the Na/K-ATPase signaling mediated sodium reabsorption in renal proximal tubules, from cardiotonic steroids-mediated to reactive oxygen species (ROS)-mediated Na/K-ATPase signaling that contributes to experimental salt sensitivity.

Na/K-Atpase Signaling And Salt Sensitivity: The Role Of Oxidative Stress, Jiang Liu, Yanling Yan, Ying Nie

Jiang Liu

Other than genetic regulation of salt sensitivity of blood pressure, many factors have been shown to regulate renal sodium handling which contributes to long-term blood pressure regulation and have been extensively reviewed. Here we present our progress on the Na/K-ATPase signaling mediated sodium reabsorption in renal proximal tubules, from cardiotonic steroids-mediated to reactive oxygen species (ROS)-mediated Na/K-ATPase signaling that contributes to experimental salt sensitivity.

Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Monir Ejemal, Chelsea A. Rapp, William D. Thomas Jr, Eric J. Sundberg, Zhiping Weng, Yang Wang

Food for Health: Publications

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as …

April:Taci Axis Is Dispensable For The Immune Response To Rabies Vaccination., Shannon L. Haley, Evgeni P. Tzvetkov, Andrew G. Lytle, Kishore R. Alugupalli, Joseph R. Plummer, James P. Mcgettigan

Department of Microbiology and Immunology Faculty Papers

There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell …

The Global Alliance For Infections In Surgery: Defining A Model For Antimicrobial Stewardship-Results From An International Cross-Sectional Survey, M Sartelli, F Labricciosa, P Barbadoro, L Pagani, L Ansaloni, Rifat Latifi, N Shafiq, K Koike, I Kozlovska, A Kumar, L Lagunes, Rifat Latifi, J Lee, N Shafiq

NYMC Faculty Publications

BACKGROUND: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. METHODS: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global …

Revisiting Neutrophil Responses To Toll-Like Receptor 4 : Influence Of Ligand Structures And Cellular Environments., Shuvasree Sengupta

Electronic Theses and Dissertations

Neutrophils respond to bacterial LPS through Toll-like receptor 4 (TLR4), which activates or potentiates immune defensive functions and prolongs cell survival. Activation of TLR4 signaling in neutrophils is beneficial for effective clearance of LPS-bearing Gram-negative bacteria, but may also drive aberrant inflammation if not stringently regulated. The regulatory processes by which neutrophil functions are calibrated to respond appropriately to different LPS-bearing bacteria are incompletely understood. Described here are investigations that reveal an unexpected sensitivity of TLR4 in neutrophils to small changes in LPS structure typical of various Gram-negative bacteria, including those that are dangerously virulent (Escherichia coli and Salmonella …

The Feoabc Locus Of Yersinia Pestis Likely Has Two Promoters Causing Unique Iron Regulation, Lauren O'Connor, Jacqueline D. Fetherston, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The FeoABC ferrous transporter is a wide-spread bacterial system. While the feoABC locus is regulated by a number of factors in the bacteria studied, we have previously found that regulation of feoABC in Yersinia pestis appears to be unique. None of the non-iron responsive transcriptional regulators that control expression of feoABC in other bacteria do so in Y. pestis. Another unique factor is the iron and Fur regulation of the Y. pestis feoABC locus occurs during microaerobic but not aerobic growth. Here we show that this unique iron-regulation is not due to a unique aspect of the Y. pestis …

Crystal Structure Of Yersinia Pestis Virulence Factor Yfea Reveals Two Polyspecific Metal-Binding Sites, Christopher D. Radka, Lawrence J. Delucas, Landon S. Wilson, Matthew B. Lawrenz, Robert D. Perry, Stephen G. Aller

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Gram-negative bacteria use siderophores, outer membrane receptors, inner membrane transporters and substrate-binding proteins (SBPs) to transport transition metals through the periplasm. The SBPs share a similar protein fold that has undergone significant structural evolution to communicate with a variety of differentially regulated transporters in the cell. In Yersinia pestis, the causative agent of plague, YfeA (YPO2439, y1897), an SBP, is important for full virulence during mammalian infection. To better understand the role of YfeA in infection, crystal structures were determined under several environmental conditions with respect to transition-metal levels. Energy-dispersive X-ray spectroscopy and anomalous X-ray scattering data show that …

Parasite Microbiome Project: Systematic Investigation Of Microbiome Dynamics Within And Across Parasite-Host Interactions., Nolwenn M Dheilly, Daniel Bolnick, Seth Bordenstein, Paul J Brindley, Cédric Figuères, Edward C Holmes, Joaquín Martínez Martínez, Anna J Phillips, Robert Poulin, Karyna Rosario

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Understanding how microbiomes affect host resistance, parasite virulence, and parasite-associated diseases requires a collaborative effort between parasitologists, microbial ecologists, virologists, and immunologists. We hereby propose the Parasite Microbiome Project to bring together researchers with complementary expertise and to study the role of microbes in host-parasite interactions. Data from the Parasite Microbiome Project will help identify the mechanisms driving microbiome variation in parasites and infected hosts and how that variation is associated with the ecology and evolution of parasites and their disease outcomes. This is a call to arms to prevent fragmented research endeavors, encourage best practices in experimental approaches, and …

Helminth Infection-Induced Malignancy., Paul J Brindley, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infectious diseases cause more than 20% of cancers in the developing world [1]. About a dozen pathogens including Epstein-Barr virus and human T cell lymphocytotropic virus 1 are among the well-known examples. In addition, infection with several trematodes, which are eukaryotes, can cause malignancy. The International Agency for Research on Cancer categorizes infection with the fish-borne trematodes Opisthorchis viverrini and Clonorchis sinensis and the blood fluke Schistosoma haematobium as Group 1 biological carcinogens [2]. In addition to parasitism directly damaging development, health, and prosperity of infected populations, infection with these helminths leads to cholangiocarcinoma (CCA) (bile duct cancer) and squamous …

Metabolite Profiling Of Infection-Associated Metabolic Markers Of Onchocerciasis., Sasisekhar Bennuru, Sara Lustigman, David Abraham, Thomas B. Nutman

Department of Microbiology and Immunology Faculty Papers

The global efforts for onchocerciasis elimination may require additional tools (safe micro and macrofilaricidal drugs, vaccines and biomarkers) as elimination efforts move toward the "end game". Efforts toward the identification of suitable biomarkers have focused on specific protein(s) and/or nucleic acids, but metabolites present an alternative option as they have limited half-lives and are the result of combinatorial effects. In comparison to previously used methodology of LC-MS for metabolomic approaches, we used a non-targeted capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) to analyze the serum metabolic profiles of Ov-infected and -uninfected individuals (n=20). We identified 286 known metabolites (167 in the …

Isolated Candida Infection Of The Lung, Yousef Shweihat Md, James Perry, Darshana T. Shah Phd

Darshana Shah

Candida pneumonia is a rare infection of the lungs, with the majority of cases occurring secondary to hematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or skin. We report a case of a 77-year-old male who is life-long smoker with a history of rheumatoid arthritis and polymyalgia rheumatica, but did not take immunosuppressants for those conditions. Here, we present an extremely rare case of isolated pulmonary parenchymal Candida infection in the form pulmonary nodules without evidence of systemic disease which has only been described in a few previous reports.

Isolated Candida Infection Of The Lung, Yousef Shweihat Md, James Perry, Darshana T. Shah Phd

Yousef R. Shweihat

Candida pneumonia is a rare infection of the lungs, with the majority of cases occurring secondary to hematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or skin. We report a case of a 77-year-old male who is life-long smoker with a history of rheumatoid arthritis and polymyalgia rheumatica, but did not take immunosuppressants for those conditions. Here, we present an extremely rare case of isolated pulmonary parenchymal Candida infection in the form pulmonary nodules without evidence of systemic disease which has only been described in a few previous reports.

Intratracheal Instillation Of Cerium Oxide Nanoparticles Induces Hepatic Toxicity In Male Sprague-Dawley Rats, Siva Krishna Nalabotu, Madhukar Babu Kolli, William E. Triest, Jane Y. Ma, Nandini Dpk Manne, Anjaiah Katta, Hari S. Addagarla, Kevin M. Rice, Eric R. Blough

Nandini Manne

Background: Cerium oxide (CeO2) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO2 nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats. Methods and results: Compared with control animals, CeO2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO2nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and …

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Jiang Liu

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed …