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Preface Of The Special Issue: “Recent Cmv Research”, Kayla Dufrene, Roberta L. Debiasi, Anamaris M. Colberg-Poley

Pediatrics Faculty Publications

No abstract provided.

Expression Of A Secreted Fibroblast Growth Factor Binding Protein-1 (Fgfbp1) In Angioproliferative Kaposi Sarcoma, Patricio E. Ray, Ali Al-Attar, Xue-Hui Liu, Jharna R. Das, Elena Tassi, Anton Wellstein

Pediatrics Faculty Publications

Objective: Kaposi’s sarcoma (KS) is an angioproliferative disease frequently seen in patients with the acquired immunodeficiency syndrome (AIDS). Previous studies suggest that the HIV-1 protein Tat and Fibroblast Growth Factor 2 (FGF-2) have synergistic angiogenic effects in AIDS-KS tumors. However, the mechanisms by which FGF-2 is released and activated in KS tumors are not clearly defined. We carried out this study to determine whether an FGFbinding protein (FGFBP1 or BP1) that enhances the angiogenic activity of FGF-2 is expressed in AIDS-KS tumors, and to define whether BP1, FGF-2, and HIV-Tat protein-protein interactions could play a potential clinically role in the …

Immunologic Special Forces: Anti-Pathogen Cytotoxic T-Lymphocyte Immunotherapy Following Hematopoietic Stem Cell Transplantation, Michael Keller, Catherine M. Bollard

Pediatrics Faculty Publications

Anti-pathogen adoptive T-cell immunotherapy has been proven to be highly effective in preventing or controlling viral infections following hematopoietic stem cell transplantation. Recent advances in manufacturing protocols allow an increased number of targeted pathogens, eliminate the need for viral transduction, broaden the potential donor pool to include pathogen-naïve sources, and reduce the time requirement for production. Early studies suggest that anti-fungal immunotherapy may also have clinical benefit. Future advances include further broadening of the pathogens that can be targeted and development of T-cells with resistance to pharmacologic immunosuppression.

Reactive Oxygen Species Regulate Caspase-11 Expression And Activation Of The Non-Canonical Nlrp3 Inflammasome During Enteric Pathogen Infection, Christopher R. Lupfer, Paras K. Anand, Zhiping Liu, Kate L. Stokes, Peter Vogel, Mohamed Lamkanfi, Thirumala Devi Kanneganti

College of Natural and Applied Sciences

Enteropathogenic and enterohemorrhagic bacterial infections in humans are a severe cause of morbidity and mortality. Although NOD-like receptors (NLRs) NOD2 and NLRP3 have important roles in the generation of protective immune responses to enteric pathogens, whether there is crosstalk among NLRs to regulate immune signaling is not known. Here, we show that mice and macrophages deficient in NOD2, or the downstream adaptor RIP2, have enhanced NLRP3- and caspases-11-dependent non-canonical inflammasome activation in a mouse model of enteropathogenic Citrobacter rodentium infection. Mechanistically, NOD2 and RIP2 regulate reactive oxygen species (ROS) production. Increased ROS in Rip2-deficient macrophages subsequently enhances c-Jun N-terminal kinase …

Chemical And Biological Warfare: Teaching The Forbidden At A State University, David M. Claborn, Keith Payne

College of Health and Human Services

No abstract provided.

Differential Responses Of Osteoblasts And Macrophages Upon Staphylococcus Aureus Infection, Therwa Hamza, Bingyun Li

Faculty & Staff Scholarship

Background

Staphylococcus aureus (S. aureus) is one of the primary causes of bone infections which are often chronic and difficult to eradicate. Bacteria like S. aureus may survive upon internalization in cells and may be responsible for chronic and recurrent infections. In this study, we compared the responses of a phagocytic cell (i.e. macrophage) to a non-phagocytic cell (i.e. osteoblast) upon S. aureus internalization.

Results

We found that upon internalization, S. aureus could survive for up to 5 and 7 days within macrophages and osteoblasts, respectively. Significantly more S. aureus was internalized in macrophages compared to osteoblasts and …

Factors Associated With Non-Utilization Of Child Immunization In Pakistan: Evidence From The Demographic And Health Survey 2006-07, Ayesha S. Bugvi, Rahla Rahat, Rubeena Zakar, Muhammad Z. Zakar, Florian Fischer, Muazzam Nasrullah, Riffat Manawar

Faculty & Staff Scholarship

Background

The proportion of incompletely immunized children in Pakistan varies from 37-58%, and this has recently resulted in outbreaks of measles and polio. The aim of this paper is to determine the factors associated with incomplete immunization among children aged 12-23 months in Pakistan.

Methods

Secondary analysis was conducted on nationally representative cross-sectional survey data from the Pakistan Demographic and Health Survey, 2006-07. The analysis was limited to ever-married mothers who had delivered their last child during the 23 months immediately preceding the survey (n = 2,435). ‘Complete immunization’ was defined as the child having received twelve doses of five …

Janus Devices For Gastrointestinal Drug Delivery, Young-Ah Lee

Honors Thesis Collection

No abstract provided.

Édouard Vuillard: Painting Disease And Infirmity In Fin-De-Siècle Paris, Michaela Haffner

Honors Thesis Collection

No abstract provided.

Terror Medicine As Part Of The Medical School Curriculum, L. A. Cole, K. Wagner, S. Scott, N. D. Connell, A. Cooper, C. A. Kennedy, B. Natal, S. Lamba

Journal Articles

Terror medicine, a field related to emergency and disaster medicine, focuses on medical issues ranging from preparedness to psychological manifestations specifically associated with terrorist attacks. Calls to teach aspects of the subject in American medical schools surged after the 2001 jetliner and anthrax attacks. Although the threat of terrorism persists, terror medicine is still addressed erratically if at all in most medical schools. This paper suggests a template for incorporating the subject throughout a 4-year medical curriculum. The instructional framework culminates in a short course for fourth year students, such as one recently introduced at Rutgers New Jersey Medical School, …

Distribution Of Human Papillomavirus Genotypes Among Hiv-Positive And Hiv-Negative Women In Cape Town, South Africa, A. C. Mcdonald, A. I. Tergas, L. Kuhn, L. Denny, T. C. Wright Jr.

Journal Articles

OBJECTIVE: HIV-positive women are known to be at high-risk of human papillomavirus (HPV) infection and its associated cervical pathology. Here, we describe the prevalence and distribution of HPV genotypes among HIV-positive and -negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN). METHODS: We report data on 1,371 HIV-positive women and 8,050 HIV-negative women, aged 17-65 years, recruited into three sequential studies in Cape Town, South Africa, conducted among women who had no history of cervical cancer screening recruited from the general population. All women were tested for HIV. Cervical samples were tested for high-risk HPV DNA (Hybrid …

Incidence Of Extended-Spectrum-Beta-Lactamase-Producing Escherichia Coli And Klebsiella Pneumoniae Isolates That Test Susceptible To Cephalosporins And Aztreonam By The Revised Clsi Breakpoints, C. S. Mcwilliams, S. Condon, R. M. Schwartz, C. C. Ginocchio

Journal Articles

The incidence of aztreonam and cephalosporin susceptibility, determined using the revised CLSI breakpoints, for extendedspectrum-beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates was evaluated. Our analysis showed that results for aztreonam and/or> 1 cephalosporin were reported as susceptible or intermediate for 89.2% of ESBLproducing E coli isolates (569/638 isolates) and 67.7% of ESBL-producing K. pneumoniae isolates (155/229 isolates).

Ighv1-69 B Cell Chronic Lymphocytic Leukemia Antibodies Cross-React With Hiv-1 And Hepatitis C Virus Antigens As Well As Intestinal Commensal Bacteria, K. K. Hwang, A. M. Trama, D. M. Kozink, S. L. Allen, K. R. Rai, R. Catera, X. J. Yan, C. C. Chu, N. Chiorazzi, B. F. Haynes, +12 Additional Authors

Journal Articles

IGHV1-B-cell chronic lymphocytic leukemia (B-CLL) patients expressing unmutated immunoglobulin heavy variable regions (IGHVs) use the IGHV1-69 B cell receptor (BCR) in 25% of cases. Since HIV-1 envelope gp41 antibodies also frequently use IGHV1-69 gene segments, we hypothesized that IGHV1-69 B-CLL precursors may contribute to the gp41 B cell response during HIV-1 infection. To test this hypothesis, we rescued 5 IGHV1-69 unmutated antibodies as heterohybridoma IgM paraproteins and as recombinant IgG(1) antibodies from B-CLL patients, determined their antigenic specificities and analyzed BCR sequences. IGHV1-69 B-CLL antibodies were enriched for reactivity with HIV-1 envelope gp41, influenza, hepatitis C virus E2 protein and …

Iso-66, A Novel Inhibitor Of Macrophage Migration Inhibitory Factor, Shows Efficacy In Melanoma And Colon Cancer Models, K. Ioannou, K. F. Cheng, G. V. Crichlow, A. I. Birmpilis, E. J. Lolis, O. E. Tsitsilonis, Y. Al-Abed

Journal Articles

Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine, which possesses a contributing role in cancer progression and metastasis and, thus, is now considered a promising anticancer drug target. Many MIF-inactivating strategies have proven successful in delaying cancer growth. Here, we report on the synthesis of ISO-66, a novel, highly stable, small-molecule MIF inhibitor, an analog of ISO-1 with improved characteristics. The MIF:ISO-66 co-crystal structure demonstrated that ISO-66 ligates the tautomerase active site of MIF, which has previously been shown to play an important role in its biological functions. In vitro, ISO-66 enhanced specific and non-specific anticancer immune responses, …

Management Of Serology Negative Human Hepatic Hydatidosis (Caused By Echinococcus Granulosus) In A Young Woman From Bangladesh In A Resource-Rich Setting: A Case Report, Daniel O. Griffin, Henry J. Donaghy, Barbara Edwards

Journal Articles

Human cystic echinococcosis (hydatidosis) is a parasitic zoonosis with almost complete worldwide distribution. Echinococcus granulosus, the dog tapeworm, causes hydatidosis which accounts for 95% of human echinococcosis. Although this tapeworm is found in dogs as a definitive host and a number of intermediate hosts, humans are often infected from close contact with infected dogs. Humans are not part of the parasitic lifecycle and serve as accidental hosts. Hydatidosis is an important consideration in the differential diagnosis of hepatic cysts in individuals from endemic areas. Clinicians should be aware of the long incubation period, the high frequency of negative serological tests, …

Physician Clinical Management Strategies And Reasoning: A Cross-Sectional Survey Using Clinical Vignettes Of Eight Common Medical Admissions, K. L. Smith, S. Ashburn, J. A. Aminawung, M. Mann, J. S. Ross

Journal Articles

Background: Physicians often select clinical management strategies not strongly supported by evidence or guidelines. Our objective was to examine the likelihood of selecting, and rationale for pursuing, clinical management strategies with more or less guideline support among physicians using clinical vignettes of eight common medical admissions. Methods: We conducted a cross-sectional survey using clinical vignettes of attending physicians and housestaff at one internal medicine program in New York City. Each clinical vignette included a brief clinical scenario and a varying number of clinical management strategies: diagnostic tests, consultations, and treatments, some of which had strong evidence or guideline support (Level …

Pleural Innate Response Activator B Cells Protect Against Pneumonia Via A Gm-Csf-Igm Axis, G. F. Weber, B. G. Chousterman, I. Hilgendorf, C. S. Robbins, I. Theurl, L. M. S. Gerhardt, Y. Iwamoto, T. D. Quach, T. L. Rothstein, F. K. Swirski, +4 Additional Authors

Journal Articles

Pneumonia is a major cause of mortality worldwide and a serious problem in critical care medicine, but the immunophysiological processes that confer either protection or morbidity are not completely understood. We show that in response to lung infection, B1a B cells migrate from the pleural space to the lung parenchyma to secrete polyreactive emergency immunoglobulin M ( IgM). The process requires innate response activator (IRA) B cells, a transitional B1a-derived inflammatory subset which controls IgM production via autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. The strategic location of these cells, coupled with the capacity to produce GM-CSF-dependent IgM, ensures effective early …

Renin Modulates Hiv Replication In T Cells, N. Chandel, K. Ayasolla, X. Q. Lan, P. Rai, J. Mikulak, M. Husain, A. Malhotra, J. Mcgowan, P. C. Singhal

Journal Articles

HIV is known to subvert cellular machinery to enhance its replication. Recently, HIV has been reported to enhance TC renin expression. We hypothesized that HIV induces and maintains high renin expression to promote its own replication in TCs. Renin enhanced HIV replication in TCs in a dose-dependent manner. (P)RR-deficient TCs, as well as those lacking renin, displayed attenuated NF-B activity and HIV replication. TCs treated with renin and Hpr displayed activation of the (P)RR-PLZF protein signaling cascade. Renin, HIV, and Hpr activated the PI3K pathway. Both renin and Hpr cleaved Agt (a renin substrate) to Ang I and also cleaved …

User Centered Clinical Decision Support Tools: Adoption Across Clinician Training Level, L. J. Mccullagh, A. Sofianou, J. Kannry, D. M. Mann, T. G. Mcginn

Journal Articles

BACKGROUND: Dissemination and adoption of clinical decision support (CDS) tools is a major initiative of the Affordable Care Act's Meaningful Use program. Adoption of CDS tools is multipronged with personal, organizational, and clinical settings factoring into the successful utilization rates. Specifically, the diffusion of innovation theory implies that 'early adopters' are more inclined to use CDS tools and younger physicians tend to be ranked in this category. OBJECTIVE: This study examined the differences in adoption of CDS tools across providers' training level. PARTICIPANTS: From November 2010 to 2011, 168 residents and attendings from an academic medical institution were enrolled into …

Intracellular Hmgb1 Inhibits Inflammatory Nucleosome Release And Limits Acute Pancreatitis In Mice, R. Kang, Q. Zhang, W. Hou, Z. Yan, R. Chen, J. Bonaroti, P. Bansal, T. R. Billiar, A. Tsung, Q. Wang, D. L. Bartlett, D. C. Whitcomb, E. B. Chang, X. Zhu, H. Wang, B. Lu, K. J. Tracey, L. Cao, X. G. Fan, M. T. Lotze, H. J., 3rd Zeh, D. Tang

Journal Articles

BACKGROUND & AIMS: High mobility group box 1 (HMGB1) is an abundant protein that regulates chromosome architecture and also functions as a damage-associated molecular pattern molecule. Little is known about its intracellular roles in response to tissue injury or during subsequent local and systemic inflammatory responses. We investigated the function of Hmgb1 in mice after induction of acute pancreatitis. METHODS: We utilized a Cre/LoxP system to create mice with pancreas-specific disruption in Hmbg1 (Pdx1-Cre; HMGB1(flox/flox) mice). Acute pancreatitis was induced in these mice (HMGB1(flox/flox) mice served as controls) after injection of l-arginine or cerulein. Pancreatic tissues and acinar cells were …

Molecular Mechanism And Therapeutic Modulation Of High Mobility Group Box 1 Release And Action: An Updated Review, B. Lu, C. Wang, M. Wang, W. Li, F. P. Chen, K. J. Tracey, H. C. Wang

Journal Articles

High mobility group box 1 (HMGB1) is an evolutionarily conserved protein, and is constitutively expressed in virtually all types of cells. Infection and injury converge on common inflammatory responses that are mediated by HMGB1 secreted from immunologically activated immune cells or passively released from pathologically damaged cells. Herein we review the emerging molecular mechanisms underlying the regulation of pathogen-associated molecular patterns (PAMPs)-induced HMGB1 secretion, and summarize many HMGB1-targeting therapeutic strategies for the treatment of infection- and injury-elicited inflammatory diseases. It may well be possible to develop strategies that specifically attenuate damage-associated molecular patterns (DAMPs)-mediated inflammatory responses without compromising the PAMPs-mediated …

Patients In A Private Hospital In India Leave The Emergency Department Against Medical Advice For Financial Reasons, S. Naderi, J. R. Acerra, K. Bailey, P. Mukherji, T. Taraphdar, T. Mukherjee, A. Pal, M. F. Ward, K. Miele, M. Mathias, R. Tan, M. Kline, K. Alagappan, R. Silverman

Journal Articles

BACKGROUND: Some reports indicate financial concerns as a factor affecting ED patients leaving the acute care setting against medical advice (AMA). In India, no person is supposed to be denied urgent care because of inability to pay. Since a large proportion of the Indian health care system is financed by out-of-pocket expenses, we investigate the role of financial constraints for ED patients at a private hospital in India in leaving AMA. METHODS: A prospective ED-based cross-sectional survey of patients leaving AMA was conducted at a private hospital in India from 1 October 2010 to 31 December 2010. Descriptive statistics and …

Septic Arthritis Of A Native Knee Joint Due To Corynebacterium Striatum, L. F. Westblade, F. Shams, S. Duong, O. Tariq, A. Bulbin, W. Zhen, S. Sakaria, B. A. Ford, C. A. D. Burnham, C. C. Ginocchio, +1 Additional Author

Journal Articles

We report a case of septic arthritis of a native knee joint due to Corynebacterium striatum, a rare and unusual cause of septic arthritis of native joints. The isolate was identified by a combination of phenotypic, mass spectrometric, and nucleic acid-based assays and exhibited high-level resistance to most antimicrobials.

Cb2 Receptor Deficiency Increases Amyloid Pathology And Alters Tau Processing In A Transgenic Mouse Model Of Alzheimer's Disease, Jeremy Koppel, V. Vingtdeux, P. Marambaud, C. D'Abramo, H. Jimenez, M. Stauber, R. Friedman, P. Davies

Journal Articles

The endocannabinoid CB2 receptor system has been implicated in the neuropathology of Alzheimer's disease (AD). In order to investigate the impact of the CB2 receptor system on AD pathology, a colony of mice with a deleted CB2 receptor gene, CNR2, was established on a transgenic human mutant APP background for pathological comparison with CB2 receptor-sufficient transgenic mice. J20 APP (PDGFB-APPSwInd) mice were bred over two generations with CNR2(-/-) (Cnr2(tm1Dgen)/J) mice to produce a colony of J20 CNR2(+/+) and J20 CNR2(-/-)mice. Seventeen J20 CNR2(+/+) mice (12 females, 5 males) and 16 J20 CNR2(-/-) mice (11 females, 5 males) were killed at …

Census-Based Rapid And Accurate Metagenome Taxonomic Profiling, Amirhossein Shamsaddini, Yang Pan, W. Evan Johnson, Konstantinos Krampis, Mariya Shcheglovitova, Vahan Simonyan, Amy Zanne, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

Background

Understanding the taxonomic composition of a sample, whether from patient, food or environment, is important to several types of studies including pathogen diagnostics, epidemiological studies, biodiversity analysis and food quality regulation. With the decreasing costs of sequencing, metagenomic data is quickly becoming the preferred typed of data for such analysis.

Results

Rapidly defining the taxonomic composition (both taxonomic profile and relative frequency) in a metagenomic sequence dataset is challenging because the task of mapping millions of sequence reads from a metagenomic study to a non-redundant nucleotide database such as the NCBI non-redundant nucleotide database (nt) is a computationally intensive …

Virginia Commonwealth University Fall Commencement Program [2014], Virginia Commonwealth University

VCU Commencement Programs

No abstract provided.

Integrated Assessment Of Predicted Mhc Binding And Cross-Conservation With Self Reveals Patterns Of Viral Camouflage, Lu He, Anne S. Degroot, Andres H. Gutierrez, William D. Martin, Lenny Moise, Chris Bailey-Kellogg

Institute for Immunology and Informatics Faculty Publications

Background

Immune recognition of foreign proteins by T cells hinges on the formation of a ternary complex sandwiching a constituent peptide of the protein between a major histocompatibility complex (MHC) molecule and a T cell receptor (TCR). Viruses have evolved means of "camouflaging" themselves, avoiding immune recognition by reducing the MHC and/or TCR binding of their constituent peptides. Computer-driven T cell epitope mapping tools have been used to evaluate the degree to which particular viruses have used this means of avoiding immune response, but most such analyses focus on MHC-facing 'agretopes'. Here we set out a new means of evaluating …

Vaxcelerate Ii: Rapid Development Of A Self-Assembling Vaccine For Lassa Fever, Pierre Leblanc, Leonard Moise, Cybelle Luza, Kanawat Chantaralawan, Lynchy Lezeau, Jianping Yuan, Mary Field, Daniel Richer, Christine Boyle, William D. Martin, Jordan B. Fishman, Eric A. Berg, David Baker, Brandon Zeigler, Dale E. Mais, William Taylor, Russell Coleman, H. Shaw Warren, Jeffrey A. Gelfand, Anne S. De Groot, Timothy Brauns, Mark C. Poznansky

Institute for Immunology and Informatics Faculty Publications

Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d. A self-assembling vaccine is …

Airborne Staphylococcus Aureus In The Biology Labs At Southern Adventist University, Harrison Filler

Capstone Research Projects

Staphylococcus aureus has been of growing interest to the scientific community in recent years. It is not only easily transferred from one person to another, but its rapidly evolving antibiotic resistance has made it increasingly difficult to treat. Once thought to be a hospital-acquired disease, S. aureus is now often found in the community. Studies indicate that people and clothing can act as carriers of S. aureus not only directly, but through airborne particles. For these reasons a research experiment was designed to determine the prevalence of S. aureus in the microbiology lab and anatomy and physiology lab at Southern …

Health Department - Rowan County, Jack D. Ellis

Jack D. Ellis Rowan County History Collection

No abstract provided.