Infectious Disease Commons^™

Long-Distance Delivery Of Bacterial Virulence Factors By Pseudomonas Aeruginosa Outer Membrane Vesicles, Jennifer M. Bomberger, Daniel P. Maceachran, Bonita A. Coutermarsh, Siying Ye, George A. O'Toole, Bruce A. Stanton, Frederick M. Ausubel

Dartmouth Scholarship

Bacteria use a variety of secreted virulence factors to manipulate host cells, thereby causing significant morbidity and mortality. We report a mechanism for the long-distance delivery of multiple bacterial virulence factors, simultaneously and directly into the host cell cytoplasm, thus obviating the need for direct interaction of the pathogen with the host cell to cause cytotoxicity. We show that outer membrane–derived vesicles (OMV) secreted by the opportunistic human pathogen Pseudomonas aeruginosa deliver multiple virulence factors, including β-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif, directly into the host cytoplasm via fusion of OMV with lipid rafts in the host plasma …

Vih Y Alcohol En Arica, Chile: Percepciones De Portadores Y Profesionales, Lena Sessions

Independent Study Project (ISP) Collection

This paper investigated the relationship between alcohol consumption and HIV in Arica, Chile. The objectives of this investigation were to understand the demographics of HIV positive Ariqueños who consume alcohol, and understand their perceptions of alcohol consumption with respect to whether they believed they had a drinking problem, whether they believed that the consumption of alcohol facilitated their contracting HIV, and whether the consumption of alcohol affected their treatment. Although there is no literature that specifically addresses the topic of how HIV positive individuals who consume alcohol perceive their disease, former research suggests that a significant number (25-50%) of individuals …

Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and …

Smoking Enhances Risk For New External Genital Warts In Men, Dorothy J. Wiley, David Elashoff, Emmanuel V. Masongsong, Diane M. Harper

Dartmouth Scholarship

Repeat episodes of HPV-related external genital warts reflect recurring or new infections. No study before has been sufficiently powered to delineate how tobacco use, prior history of EGWs and HIV infection affect the risk for new EGWs. Behavioral, laboratory and examination data for 2,835 Multicenter AIDS Cohort Study participants examined at 21,519 semi-annual visits were evaluated. Fourteen percent (391/2835) of men reported or were diagnosed with EGWs at 3% (675/21,519) of study visits. Multivariate analyses showed smoking, prior episodes of EGWs, HIV infection and CD4+ T-lymphocyte count among the infected, each differentially influenced the risk for new EGWs.

Living In Rural New England Amplifies The Risk Of Depression In Patients With Hiv, Siddharth H. Sheth, Paul T. Jensen, Timothy Lahey

Dartmouth Scholarship

The importance of depression as a complication of HIV infection is increasingly understood, and people living in rural areas are at increased risk for depression. However, it is not known whether living in rural areas amplifies the risk of depression in patients with HIV. We compared the prevalence of depression between rural and metropolitan HIV patients seen at the Dartmouth-Hitchcock HIV Program in a retrospective cohort study. Using the validated Rural-Urban Commuting Area Score, we categorized patients as living in small town/rural areas, micropolitan or metropolitan towns. Then, using a multivariate logistic regression model to adjust for demographic factors that …

Dengue Fever With Hepatitis E And Hepatitis A Infection, Javed Yakoob, Wasim Jafri, Shaheer Siddiqui, Mehmood Riaz

Section of Gastroenterology

Infection with dengue viruses produces a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal haemorrhagic disease. Important risk factors include the strain and serotype of the infecting virus, as well as the age, immune status, and genetic predisposition of the patient. The teaching point in this case study was Dengue fever which occurred concomitantly with Hepatitis A and Hepatitis E virus infection.

Detection Of Viruses In Human Adenoid Tissues By Use Of Multiplex Pcr, Masatoki Sato, Haijing Li, Mine R. Ikizler, Jay A. Werkhaven, John V. Williams, James D. Chappell, Yi-Wei Tang, Peter F. Wright

Dartmouth Scholarship

By PCR, we detected a high frequency of viruses in adenoids obtained from children without acute respiratory symptoms. Our results suggest that persistent/latent viral infection in the respiratory tract confounds interpretation of the association of pathogen detection by PCR with acute respiratory infection in these sources.

Interconnections Between Sigma B, Agr, And Proteolytic Activity In Staphylococcus Aureus Biofilm Maturation, Katherine J. Lauderdale, Blaise R. Boles, Ambrose L. Cheung, Alexander R. Horswill

Dartmouth Scholarship

Staphylococcus aureus is a proficient biofilm former on host tissues and medical implants. We mutagenized S. aureus strain SH1000 to identify loci essential for ica-independent mechanisms of biofilm maturation and identified multiple insertions in the rsbUVW-sigB operon. Following construction and characterization of a sigB deletion, we determined that the biofilm phenotype was due to a lack of sigma factor B (SigB) activity. The phenotype was conserved in a sigB mutant of USA300 strain LAC, a well-studied community-associated methicillin-resistant S. aureus isolate. We determined that agr RNAIII levels were elevated in the sigB mutants, and high levels of RNAIII expression are …

Ua94/6/1 Student / Alumni Personal Papers Western Kentucky University Small Collections, Wku Archives

WKU Archives Collection Inventories

Small collections of personal papers and oral histories relating to the Western Kentucky University.

Lymphomatoid Granulomatosis Masquerading As Interstitial Pneumonia In A 66-Year-Old Man: A Case Report And Review Of Literature, Ashima Makol, Kalyan Kosuri, Deimante Tamkus, Wanderley De M Calaca, Howard T. Chang

Wayne State University Associated BioMed Central Scholarship

Abstract

Lymphomatoid granulomatosis (LG) is a rare, Epstein-Barr virus (EBV)-associated systemic angiodestructive lymphoproliferative disorder that may progress to a diffuse large B cell lymphoma. Pulmonary involvement may mimic other more common lung pathologies including pneumonias. Therapeutic standards have not been established for LG, but rituximab, interferon-α2b (INF-α2b), and chemotherapy have shown to improve symptoms and long term prognosis.

We report a case of rapid respiratory deterioration in a 66-year-old man with clinical presentation, chest radiography, pulmonary function testing and high resolution computed tomography (HRCT) findings consistent with idiopathic interstitial pneumonia, but very poor response to antibiotics and low dose steroids. …

Rhizopus Necrotizing Fasciitis Of Caesarean Wound: A Rare Life Threatening Condition, Abdul Rehman Alvi, Ghina Shamsi

Section of General Surgery

Mucormycosis is a rare cause of necrotizing fasciitis in immunocompromised patients. We report a young female, who developed rhizopus necrotizing fasciitis of caesarean wound. The lady died secondary to non-responding sepsis and irreversible multi-organ failure. High index of suspicion can lead to early diagnosis by frozen section of histopathology and fungal culture technique. Aggressive surgical debridement and intravenous anti-fungal medication is the main stay of treatment. A delay in diagnosis and treatment may cause multi-organ failure leading to high mortality.

X4 Human Immunodeficiency Virus Type 1 Gp120 Down-Modulates Expression And Immunogenicity Of Codelivered Antigens, Avi-Hai Hovav, Michael Santosuosso, Maytal Bivas-Benita, Andre Plair, Alex Cheng, Mazal Elnekave, Elda Righi, Tao Chen, Satoshi Kashiwagi, Michael W. Panas, Shi-Hua Xiang, Karina Furmanov, Norman L. Letvin, Mark C. Poznansky

Nebraska Center for Virology: Faculty Publications

In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such

as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120

protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and

future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune

response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120

alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin

in a mouse model. We found that the presence of gp120 …

Identification And Characterization Of A New Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator (Rta)- Responsive Element Involved In Rta-Mediated Transactivation, Hui-Ju Wen, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) is well established as a key transcriptional activator that regulates the KSHV life cycle from latency to lytic replication. It is expressed immediately after infection and activates a number of viral genes leading to virus replication. The RTA-responsive element (RRE) in the RTA target gene promoters is critical for RTA to mediate this transactivation. A number of non-conserved RREs have been identified in various RTA-responsive promoters, and AT-rich sequences have been proposed to serve as RTA targets, but no consensus RRE sequence has been identified so far. Two nonconserved RREs (RRE1 …

Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and …

Human Ubc9 Contributes To Production Of Fully Infectious Human Immunodeficiency Virus Type 1 Virions, Tareq Jaber, Christopher R. Bohl, Gentry L. Lewis, Charles Wood, John T. West Jr., Robert A. Weldon Jr.

Nebraska Center for Virology: Faculty Publications

Ubc9 was identified as a cellular protein that interacts with the Gag protein of Mason-Pfizer monkey virus. We show here that Ubc9 also interacts with the human immunodeficiency virus type 1 (HIV-1) Gag protein and that their interaction is important for virus replication. Gag was found to colocalize with Ubc9 predominantly at perinuclear puncta. While cells in which Ubc9 expression was suppressed with RNA interference produced normal numbers of virions, these particles were 8- to 10-fold less infectious than those produced in the presence of Ubc9. The nature of this defect was assayed for dependence on Ubc9 during viral assembly, …

Thoracoscopic Decortication Vs Tube Thoracostomy With Fibrinolysis For Empyema In Children: A Prospective, Randomized Trial., Shawn D. St Peter, Kuojen Tsao, Troy L. Spilde, Scott J. Keckler, Christopher J. Harrison, Mary Anne Jackson, Susan W. Sharp, Walter S. Andrews, Douglas C. Rivard, Frank P. Morello, G W. Holcomb Iii, Daniel J. Ostlie

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Management of empyema has been debated in the literature for decades. Although both primary video-assisted thoracoscopic surgery (VATS) and tube thoracostomy with pleural instillation of fibrinolytics have been shown to result in early resolution when compared to tube thoracostomy alone, there is a lack of comparative data between these modes of management. Therefore, we conducted a prospective, randomized trial comparing VATS to fibrinolytic therapy in children with empyema.

METHODS: After Institutional Review Board approval, children defined as having empyema by either loculation on imaging or more than 10,000 white blood cells/microL were treated with VATS or fibrinolysis. Based on …

Expression Of Hpv16 E5 Produces Enlarged Nuclei And Polyploidy Through Endoreplication, Lulin Hu, Tamara A. Potapova, Shibo Li, Susannah Rankin, Gary J. Gorbsky, Peter C. Angeletti, Brian P. Ceresa

Nebraska Center for Virology: Faculty Publications

Anogenital cancers and head and neck cancers are causally-associated with infection by high-risk

human papillomavirus (HPV). The mechanism by which high-risk HPVs contribute to

oncogenesis is poorly understood. HPV16 encodes three genes (HPV16 E5, E6, and E7) that can

transform cells when expressed independently. HPV16 E6 and E7 have well-described roles

causing genomic instability and unregulated cell cycle progression. The role of HPV16 E5 in cell

transformation remains to be elucidated. Expression of HPV16 E5 results in enlarged, polyploid

nuclei that are dependent on the level and duration of HPV16 E5 expression. Live-cell imaging

data indicate these changes do not …

Human Papillomavirus 16 E5 Induces Bi-Nucleated Cell Formation By Cell-Cell Fusion, Lulin Ha, Kendra Plafker, Valeriya Vorozhoko, Rosemary E. Zuna, Marie H. Hanigan, Gary J. Gorbsky, Scott M. Plafker, Peter C. Angeletti, Brian P. Ceresa

Nebraska Center for Virology: Faculty Publications

Human Papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes – E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, …

A Comparative Study Of Hiv-1 Clade C Env Evolution In A Zambian Infant With An Infected Rhesus Macaque During Disease Progression, For Yue Tso, Federico G. Hoffmann, Damien C. Tully, Philippe Lemey, Robert A. Rasmussen, Hong Zhang, Ruth M. Ruprecht, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective—To evaluate whether HIV-1 clade C (HIV-C) envelope variations that arise during disease progression in rhesus macaque model reflect changes that occur naturally in human infection.

Design—An infant macaque was infected with SHIV-1157i, an R5 tropic clade C SHIV (SHIV-C) which expresses a primary HIV-C envelope derived from an infected human infant, and monitored over a five-year period. Genetic variation of the V1-V5 envelope region, which is the main target for humoral immune responses, derived from the infected macaque and infant was examined.

Methods—V1-V5 envelope region were cloned and sequenced from longitudinal PBMC samples collected from the infected macaque and …

Use Of Average Mutual Information For Studying Changes In Hiv Populations, Khalid Sayood, Federico Hoffman, Charles Wood

Nebraska Center for Virology: Faculty Publications

Average mutual information (AMI) has been used in a number of applications in bioinformatics. In this paper we present its use to study genetic changes in populations; in particular populations of HIV viruses. Disease progression of HIV-1 infection in infants can be rapid resulting in death within the the first year, or slow, allowing the infant to survive beyond the first year. We study the development of rapid and slow progressing HIV population using AMI charts based on average mutual information among amino acids in the env gene from a population of 1142 clones derived from seven infants with slow …

Protection Against Mucosal Shiv Challenge By Peptide And Helper-Dependent Adenovirus Vaccines, Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helper- dependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5- immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than …

Topical Application Of Entry Inhibitors As "Virustats" To Prevent Sexual Transmission Of Hiv Infection, Michael M. Lederman, Robin L.P. Jump, Heather A. Pilch-Cooper, Scott F. Sieg

Faculty Scholarship

With the continuing march of the AIDS epidemic and little hope for an effective vaccine in the near future, work to develop a topical strategy to prevent HIV infection is increasingly important. This stated, the track record of large scale "microbicide" trials has been disappointing with nonspecific inhibitors either failing to protect women from infection or even increasing HIV acquisition. Newer strategies that target directly the elements needed for viral entry into cells have shown promise in non-human primate models of HIV transmission and as these agents have not yet been broadly introduced in regions of highest HIV prevalence, they …

Effects Of Shielding Adenoviral Vectors With Polyethylene Glycol On Vector-Specific And Vaccine-Mediated Immune Responses, Eric A. Weaver, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Many individuals have been previously exposed to human adenovirus serotype 5 (Ad5). This prior immunity has long been known to hinder its use for gene therapy and as a gene-based vaccine. Given these immunogenicity problems, we have tested whether polyethylene glycol (PEG) can blunt immune effects against Ad5 during systemic and mucosal vaccination. Ad5 vectors were covalently modified with 5-, 20-, and 35-kDa linear PEG polymers and evaluated for their ability to produce immune responses against transgene antigen products and the vector itself. We show that shielding Ad5 with different-sized PEGs generally reduces transduction and primary antibody responses by the …

Impact Of Afghan Refugees On The Infectious Disease Profile Of Pakistan: Beyond Economy, Ali Jawaid, Abdul Mueed Zafar, Syed Faisal Mahmood

Department of Medicine

No abstract provided.

Mgra Represses Biofilm Formation In Staphylococcus Aureus, Maria P. Trotonda, Sandeep Tamber, Guido Memmi, Ambrose L. Cheung

Dartmouth Scholarship

MgrA is a pleiotropic regulator that controls autolysis, virulence, and efflux pump activity in Staphylococcus aureus. We recently found that mgrA mutants of strains RN6390, SH1000, and MW2 also displayed enhanced biofilm formation compared with their respective parents. The biofilms formed by mgrA mutants of RN6390 and MW2 are independent of sigB and ica loci, two genetic elements that have been previously associated with biofilm formation in S. aureus. Biofilms formed by mgrA mutants are dependent on the expression of surface proteins mediated by the sortase gene srtA. Extracellular DNA was also a crucial component of the early biofilm of …

Fluoroquinolones For Treating Typhoid And Paratyphoid Fever (Enteric Fever), Durrane Thaver, Anita K. M. Zaidi, Julia A. Critchley, Asma Azmatullah, Syed Ali Madni, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Background: Fluoroquinolones are recommended as first-line therapy for typhoid and paratyphoid fever (enteric fever), but how they compare with other antibiotics and different fluoroquinolones is unclear.
Objectives: To evaluate fluoroquinolone antibiotics for treating enteric fever in children and adults compared with other antibiotics, different fluoroquinolones, and different durations of fluoroquinolone treatment.
Search strategy: In November 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 4), MEDLINE, EMBASE, LILACS, mRCT, conference proceedings, and reference lists.
Selection criteria: Randomized controlled trials of fluoroquinolones in people with blood or bone marrow culture-confirmed enteric fever.
Data collection …

Range For Normal Body Temperature In The General Population Of Pakistan., Mehreen Adhi, Rabia Hasan, Fatima Noman, Syed Faisal Mahmood, Anwar Naqvi, Adib-Ul-Hasan Rizv

Department of Medicine

OBJECTIVES:

To determine the range for normal body temperature in the general population of Pakistan and to determine if any age, sex and ambient temperature related variations exist in body temperature. Moreover, to compare how much axillary temperature differs from oral temperature measurements.

METHODS:

Oral as well as left and right axillary temperature recordings were made using an ordinary mercury-in-glass thermometer in 200 healthy individuals accompanying patients at various clinics at the Sindh Institute of Urology and Transplantation (SIUT) between mid-May to mid-June 2006. Data analysis was done using Epi Info version 3.3.

RESULTS:

The range for Normal Oral Temperatures …

Answering The Cdc's Call For Universal Hiv Testing: Assesing The Impact On A Tertiary Care Referral Center Via A Blinded Seroprevalence Study, Margaret Hoffman-Terry Md, Facp, K Nadeem Ahmed Md, Joseph L. Yozviak Do, Facp, Sherrine Eid Mph, Timothy J. Friel Md, Kimberly A. Pacella, Luther Rhodes Iii Md

Department of Medicine

No abstract provided.

Intravenous Inoculation Of Silver-Haired Bat Rabies Virus, But Not Of A Canine Strain, Elicits Lethal Encephalophathy In Mice By Fast Brain Invasion Via Neurosecretory Hypothalamic Fibers, Mirjam Ar Preuss, Marie-Luise Faber, Gene S. Tan, Bernhard Dietzschold, Matthias J. Schnell, Eberhard Weihe

Department of Microbiology and Immunology Faculty Papers

No abstract provided.

Changing Patterns And Outcome Of Dengue Infection; Report From A Tertiary Care Hospital In Pakistan, Mohammad Wasay, Roomasa Channa, Maliha Jumani, Afia Zafar

Department of Medicine

Objective: To identify predictors of outcome in patients with Dengue Infections at a tertiary care hospital and to analyze that if pattern of Dengue infection is changing in the past two years.

Methods: We reviewed 225 cases of confirmed dengue virus infection. The diagnosis was confirmed by presence of IgM antibodies against Dengue by ELISA in addition to fever according to WHO criteria.

Results: From years 2000-2004, 30(73%) had Dengue Fever (DF), 10(24%) had Dengue Haemorrhagic Fever (DHF) and 1(2.4%) had Dengue shock syndrome (DSS) while after 2005, 107(58%) had DF, 71(39%) had DHF and 6(3%) had DSS. Six …