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Antimalarial Activity Of A Cis-Terpenone, Dc Ghislaine Mayer, Maimuna Bruce, Olga Kochurova, Jennifer K. Stewart, Qibing Zhou

Biology Publications

Background

Malaria is the third most prevalent cause of infectious disease in the world. Resistance of the parasite to classical drugs makes the discovery of new and effective drugs more urgent. The oxidized derivative of hydroxy-cis terpenone (OHCT) is a synthetic molecule that is not toxic to cultured human liver cells at concentrations as high as 60 μM and inhibits activity of cytochrome P450s that metabolize many drugs.

Methods

OHCT activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum, and aP. falciparum clone that is partially resistant to artemisinin was assayed in vitro.

Results

OHCT at nanomolar …

Dna Structure Modulates The Oligomerization Properties Of The Aav Initiator Protein Rep68, Jorge Mansilla-Soto, Miran Yoon-Robarts, William J. Rice, Shailee Arya, Carlos R. Escalante, R. Michael Linden

Physiology and Biophysics Publications and Presentations

Rep68 is a multifunctional protein of the adeno-associated virus (AAV), a parvovirus that is mostly known for its promise as a gene therapy vector. In addition to its role as initiator in viral DNA replication, Rep68 is essential for site-specific integration of the AAV genome into human chromosome 19. Rep68 is a member of the superfamily 3 (SF3) helicases, along with the well-studied initiator proteins simian virus 40 large T antigen (SV40-LTag) and bovine papillomavirus (BPV) E1. Structurally, SF3 helicases share two domains, a DNA origin interaction domain (OID) and an AAA+ motor domain. The AAA+ motor domain is also …

Identification And Characterization Of Prevotella Intermedia 17 Toll-Like Receptor 2 Ligands, Jamie Feng-Hsia Yuan

Theses and Dissertations

Periodontal disease is one of the most prevalent human diseases affecting millions of individuals. Bacteria are the trigger of the host response that then results in initiation and progression of periodontal disease. The interactions between the host and the bacteria, although very complex and intricate, are not well understood. Species of gram-negative anaerobic bacteria implicated in the development of periodontal disease include Porphyromonas gingivalis and Prevotella intermedia. The goal of our study was to identify P. intermedia surface proteins interacting with TLR2 receptor. Using Cy5-labeled surface proteins we identified multiple proteins using our capture assay. The interaction of three …

Commonwealth Times 2008-09-25

Commonwealth Times, 1969-

No abstract provided.

Interneuron Subtypes Are Differentially Altered In Malformed, Epileptogenic Cortex, Amanda George

Theses and Dissertations

The propensity for seizures in patients with epilepsy is due to underlying cortical hyperexcitability, the mechanisms of which are poorly understood. Particularly difficult to treat are patients with developmental malformations of cortex. Using the freeze-lesion rat model of one such malformation, polymicrogyria, we identified, in lesioned cortex, alterations in specific interneuron subpopulations that may promote hyperexcitability. Previous studies demonstrate increased excitatory input to the paramicrogyral region. An increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from pyramidal cells has also been shown. We report an increase in sEPSCs recorded from one subtype of interneuron, the low threshold-spiking …

The Response Of Hn4 Cells To Porphyromonas Gingivalis Dna, Cheyanne Warren

Theses and Dissertations

Periodontal disease is one of the most common human diseases. Bacteria trigger the onset and progression of the disease and among them Porphyromonas gingivalis has been demonstrated to be a major etiologic agent. Although the interaction of the bacterium with the host is of major importance for the understanding of the disease mechanisms, both the host as well as the pathogen components involved in the interaction remain poorly understood. One of the bacterial components capable of eliciting a host response is unmethylated CpG DNA motifs found in bacteria. Thus, the first aim was to determine the response of oral epithelial …

Cytomegalovirus Infections Among African-Americans, Isca R. Wilms, Al M. Best, Stuart P. Adler

Pediatrics Publications

Background Since African-Americans have twice the prevalence of cytomegalovirus (CMV) infections as age-matched Caucasians we sought to determine the ages and possible sources of infection of African-American children.

Methods Subjects were 157 African-American healthy children and adolescents and their 113 household adults in Richmond VA. Families completed a questionnaire, provided saliva for antibody testing, and adolescents were interviewed regarding sexual activity.

Results Regardless of age CMV seropositivity was not associated with gender, breast feeding, health insurance, sexual activity, or household income, education, or size. In the final regression model, prior CMV infection in adults was over two-fold higher than in …

Genetically Engineered Live-Attenuated Cytomegalovirus (Cmv) Vaccines Improve Pregnancy Outcome In The Guinea-Pig Model Of Congenital Cmv Infection, Mark R. Schleiss, Alistair Mcgregor, Yeon Choi, Jodi Anderson, Mike Levinton, Xiaohong Cui, Michael Mcvoy

Pediatrics Publications

No abstract provided.

Inflammatory And Coagulation Biomarkers And Mortality In Patients With Hiv Infection, Lewis H. Kuller, Russell Tracy, Waldo Belloso, Stephane De Wit, Fraser Drummond, H. Clifford Lane, Bruno Ledergerber, Jens Lundgren, Jacqueline Neuhaus, Daniel Nixon, Nicholas I. Paton, James D. Neaton

Internal Medicine Publications

Background

In the Strategies for Management of Anti-Retroviral Therapy trial, all-cause mortality was higher for participants randomized to intermittent, CD4-guided antiretroviral treatment (ART) (drug conservation [DC]) than continuous ART (viral suppression [VS]).

We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways, thrombosis, and fibrinolysis.

Methods and Findings

Stored samples were used to measure six biomarkers: high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), amyloid A, amyloid P, D-dimer, and prothrombin fragment 1+2. Two studies were conducted: (1) a nested case–control study for studying biomarker associations with mortality, and (2) a study to compare DC and …

Prolonged Therapy Of Advanced Chronic Hepatitis C With Low-Dose Peginterferon, Adrian M. Di Bisceglie, Mitchell L. Shiffman, Gregory T. Everson, Karen L. Lindsay, James E. Everhart, Elizabeth C. Wright, William M. Lee, Anna S. Lok, Herbert L. Bonkovsky, Timothy R. Morgan, Marc G. Ghany, Chihiro Morishima, Kristin K. Snow, Jules L. Dienstag

VCU Health Publications

Background

In patients with chronic hepatitis C who do not have a response to antiviral treatment, the disease may progress to cirrhosis, liver failure, hepatocellular carcinoma, and death. Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain.

Methods

We conducted a randomized, controlled trial of peginterferon alfa-2a at a dosage of 90 μg per week for 3.5 years, as compared with no treatment, in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin. The patients, who were stratified according to stage of …

Dengue Virus Pathogenesis In Mouse Central Nervous System: Studies On Host Response To Dengue Virus Infection, Juliano Bordignon, Christian Probst, Ana Luiza P. Mosimann, Vanessa Stella, Daniela Pavoni, Gregory A. Buck, Paul Fawcett, Silvio M. Zanata, Lucia Noronha, Marco Krieger, Claudia Nunes Duarte Dos Santos

Microbiology and Immunology Publications

Dengue virus (DENV) causes a self-limiting fever (DF) or severe hemorrhagic fever/shock-syndrome (DHF/DSS). Recently, clinical profile of DENV infection is changing, and neurological manifestations are becoming frequent. We previously demonstrated that mutations on E and NS3 proteins may account for DENV neurovirulence for mice. To validate the involvement of the observed mutations in the appearance of neurovirulent viral phenotypes, we constructed cDNA infectious clones encompassing the observed mutations. Aiming to determine host response to infection with neurovirulent and parental strains of DENV-1, we used a Mus musculus biochip (Virginia Commonwealth University) encompassing whole mouse genome. Newborn Swiss mice were infected …

Virginia Dental Journal (Vol. 85, No. 4, 2008)

Virginia Dental Journal

No abstract provided.

Analysis Of The Nucleotide Sequence Of The Guinea Pig Cytomegalovirus (Gpcmv) Genome, Mark R. Schleiss, Alistair Mcgregor, K Yeon Choi, Shailesh V. Date, Xiaohong Cui, Michael Mcvoy

Pediatrics Publications

In this report we describe the genomic sequence of guinea pig cytomegalovirus (GPCMV) assembled from a tissue culture-derived bacterial artificial chromosome clone, plasmid clones of viral restriction fragments, and direct PCR sequencing of viral DNA. The GPCMV genome is 232,678 bp, excluding the terminal repeats, and has a GC content of 55%. A total of 105 open reading frames (ORFs) of > 100 amino acids with sequence and/or positional homology to other CMV ORFs were annotated. Positional and sequence homologs of human cytomegalovirus open reading frames UL23 through UL122 were identified. Homology with other cytomegaloviruses was most prominent in the central …

The Effect Of Cell Type On The Efficacy Of Cmv Antiviral Drugs, Benjamin Meza

Theses and Dissertations

Until recently, all in vitro drug susceptibility assays of cytomegalovirus (CMV) were performed in clinically irrelevant fibroblast cells. This study sought to test if drug susceptibility was affected by cell type. MRC-5 embryonic lung fibroblasts and ARPE-19 retinal pigmented epithelial cells were infected with BADrUL131-Y4 epithelial/fibroblast tropic virus under serial concentrations of ganciclovir (GCV) or maribavir (MBV). Virus was quantified using plaque reduction, GFP fluorescence, and yield reduction. Both drugs performed less efficiently in ARPE-19 cells. A cell type effect was observed for both plaque reduction and yield reduction assays with implications for the treatment of CMV retinitis as well …

How Well Does Spirituality Predict Health Status In People Living With Hiv-Disease?, Rachel Kidd Cobb

Theses and Dissertations

Problem: The United States of America has one of the highest number of HIV infections in the world; approximately 1.3 million people in North America were living with HIV in 2007. Factors influencing HIV survival are essential to disease management and care. Research findings suggest religion and spirituality may be essential components to health and well-being in individuals with HIV-Disease. Purpose: This study was designed to determine how well spirituality predicted health status in a convenience sample of 39 adults diagnosed with HIV-Disease. Procedure: A model building approach was used to explore relationships among the five variables of the Neuman …

Characterization Of Microorganisms Of Interest To Homeland Security And Public Health Utilizing Liquid Chromatography/Mass Spectrometry, Robert A. Everley

Theses and Dissertations

Liquid chromatography/quadrupole time of flight mass spectrometry (LC/QTOF MS) utilizing electrospray ionization was employed to monitor protein expression in Escherichia coli and Shigella organisms. Automated charge state deconvolution, spectral subtraction and spectral mirroring were used to reveal subtle differences in the LC/MS data. Reproducible intact protein biomarkers were discovered based on their unique mass, retention time and relative intensity. These markers were implemented to differentiate closely related strain types, (e.g. two distinct isolates of E. coli O157:H7) and to correctly identify unknown pathogens. Notable, was the distinction of multiple serotypes of enterohaemorrhagic E. coli which cannot be distinguished by clinical …

An Scir Model Of Meningococcal Meningitis, Kalimah Vereen

Theses and Dissertations

A model for meningitis is developed by adding a class of carriers to the basic SIR model. This model is used to analyze the impact a vaccination program can have on the health of the population of epidemic prone countries. Analysis of the model shows the local stability of the disease free equilibrium, the existence of an endemic equilibrium and computation of the reproduction number, ℜ0 . Using a MATLAB program we simulate a time course of the model using parameters gathered from the World Health Organization. The numerical solution demonstrates that our reproduction number was correct. We thenconcluded that …

Augmentation Of T Cell Expansion For Adoptive Immunotherapy By Alternate Gamma Chain Cytokines And By Gemcitabine Mediated Inhibition Of Myeloid Derived Suppressor Cells, Hanh Le

Theses and Dissertations

Successful treatment of cancer with adoptive immunotherapy (AIT) is dependent on the ability to produce large numbers of tumor-specific, functional T cells. The purpose of this thesis is to explore ways in which T cell expansion could be augmented. We have focused on exploring alternate gamma chain cytokines as stimulators of T cell proliferation and differentiation in addition to investigating the potential usefulness of gemcitabine (GEM) in abrogating the immunosuppressive effects of myeloid derived suppressor cells (MDSCs). B16 melanoma sensitized draining lymph node cells that have been activated in vitro with bryostatin-1 and ionomycin (B/I) were expanded in either IL-7/15 …

Commonwealth Times 2007-11-19

Commonwealth Times, 1969-

No abstract provided.

Commonwealth Times 2007-04-30

Commonwealth Times, 1969-

No abstract provided.

Hospital-Acquired Clostridium Difficile-Associated Disease In The Intensive Care Unit Setting: Epidemiology, Clinical Course And Outcome, Alexandre R. Marra, Michael B. Edmond, Richard P. Wenzel, Gonzalo M. L. Bearman

Internal Medicine Publications

Background Clostridium difficile-associated disease (CDAD) is a serious nosocomial infection, however few studies have assessed CDAD outcome in the intensive care unit (ICU). We evaluated the epidemiology, clinical course and outcome of hospital-acquired CDAD in the critical care setting.

Methods We performed a historical cohort study on 58 adults with a positive C. difficile cytotoxin assay result occurring in intensive care units.

Results Sixty-two percent of patients had concurrent infections, 50% of which were bloodstream infections. The most frequently prescribed antimicrobials prior to CDAD were anti-anaerobic agents (60.3%). Septic shock occurred in 32.8% of CDAD patients. The in-hospital mortality was …

Interactions Of Mtfabh With Its Substrates And Inhibitors Reveal Novel Mechanistic Insights, Sarbjot Singh Sachdeva

Theses and Dissertations

Tuberculosis emerged from its grave to be one of the deadliest diseases of the present time after recently developing a synergy with AIDS. A fatty acid condensing enzyme-mtFabH has been proposed to connect the key processes involved in biosynthesis of mycolic acids, an important component of mycobacterial cell wall. It condenses long acyl Coenzymes A (CoA; up to C20CoA) with malonyl Acyl Carrier Protein (ACP) to form the elongated β-ketoacyl-ACP which further undergoes rounds of elongation to form mero-mycolate branch of mature mycolic acids. Owing to its proposed central position in mycolic acid synthesis, mtFabH has attracted considerable attention as …

Women In Science And Engineering: Politics Of Gender, Ibironke Lawal

VCU Libraries Faculty and Staff Publications

Women are fewer than men in science and engineering, therefore, the assumption is that women generally prefer arts and humanities. But to some analysts, the reason for the low percentage of women in these careers may be due to innate mental and psychological differences between them and men. Others contend that women have the capacity to excel in any profession and that their fewness in science and engineering can be attributed to other factors. They urge educational institutions and employers to develop programs and specific policies that would allow women to strike a better balance between the demands of work …

Constraints On Breastfeeding Choices For Low Income Mothers, Carol Grace Hurst

Theses and Dissertations

The choice to breastfeed a baby is a woman's concern with impact reaching beyond each individual mother and child to longer term health and mental health outcomes for society. The U.S. government has made increasing breastfeeding rates one of its major public health goals for 2010. Breastfeeding is a health disparity issue with mothers who are poor, young, less educated or Black less likely to breastfeed. This project examined impacts of sexual perceptions of breastfeeding, social support, and work on breastfeeding choices made by a sample of low income mothers. A cross-sectional survey design was employed to examine potential barriers …

Cradle To Cage: Confronting The Premature Institutionalization Of The Children Of The Incarcerated, Jen Fell

Theses and Dissertations

American prisons are swollen and distended. Over 2 million Americans sit in jail or prison today. About 2/3 of the incarcerated are parents. They parent approximately 2 million children in America today who are separated from mom or dad because of incarceration. Their children suffer from poverty, inconsistency in caregivers, separation from siblings, reduced opportunity to health and education and increased risk for substance abuse, alcoholism and incarceration themselves. Children of the incarcerated are seven times more likely than their peers to become incarcerated as adults.Many of these children are unable to visit their parents. Over half the mothers in …

Beyond The Threshold: Allusions To The ÒrìsÀ In Ana Mendieta's Silueta Series, Latricia M. January

Theses and Dissertations

The Cuban-born artist Ana Mendieta (1948-1985) created the Silueta Series during the 1970s and ‘80s. It consists of earth-body works in situ featuring the silhouette of the artist's body fashioned from mud, plants, rocks, gunpowder and other materials. Underlying the creation of the Silueta Series is Mendieta's belief that the elements are sentient and powerful beings. This perception is particularly strong in the Afro-Cuban religion Santeria, a creolized form of the Òrìsà tradition of the Yoruba of West Africa introduced to the Americas during the trans-Atlantic slave trade. While scholars have noted Mendieta's incorporation of Santeria in her art, a …

Shafer Court Connections (2006-09)

Shafer Court Connections, 1994-2010

For alumni of the Academic Campus of Virginia Commonwealth University.

Shafer Court Connections (2006-03)

Shafer Court Connections, 1994-2010

For alumni of the Academic Campus of Virginia Commonwealth University.

Knowledge And Awareness Of Congenital Cytomegalovirus Among Women, Jiyeon Jeon, Marcia Victor, Stuart P. Adler, Abigail Arwady, Gail Demmeler, Karen Fowler, Johanna Goldfarb, Harry Keyserling, Mehran Massoudi, Kristin Richards, Stephanie A. S. Staras, Michael J. Cannon

Pediatrics Publications

Background. Congenital cytomegalovirus (CMV) infection is a leading cause of disabilities in children, yet the general public appears to have little awareness of CMV. Methods. Women were surveyed about newborn infections at 7 different geographic locations. Results. Of the 643 women surveyed, 142 (22%) had heard of congenital CMV. Awareness increased with increasing levels of education (P<.0001). Women who had worked as a healthcare professional had a higher prevalence of awareness of CMV than had other women (56% versus16%, P <.0001). Women who were aware of CMV were most likely to have heard about it from a healthcare provider (54%), but most could not correctly identify modes of CMV transmission or prevention. Among common causes of birth defects and childhood illnesses, women's awareness of CMV ranked last. Conclusion. Despite its large public health burden, few women had heard of congenital CMV, and even fewer were aware of prevention strategies.

Comparison Of Severity Of Illness Scoring Systems For Patients With Nosocomial Bloodstream Infection Due To Pseudomonas Aeruginosa, Alexandre R. Marra, Gonzalo M. L. Bearman, Richard P. Wenzel, Michael B. Edmond

Internal Medicine Publications

Background

Several acute illness severity scores have been proposed for evaluating patients on admission to intensive care units but these have not been compared for patients with nosocomial bloodstream infection (nBSI). We compared three severity of illness scoring systems for predicting mortality in patients with nBSI due to Pseudomonas aeruginosa.

Methods

We performed a historical cohort study on 63 adults in intensive care units with P. aeruginosamonomicrobial nBSI.

Results

The Acute Physiology, Age, Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiologic Score (SAPS II), were calculated daily from 2 days prior …