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Functional Interplay Between The B-Box 2 And The B30.2(Spry) Domains Of Trim5Α, Xi Ling, Byeongwoon Song, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The retroviral restriction factors, TRIM5α and TRIMCyp, consist of RING and B-box 2 domains separated by a coiled coil from carboxy-terminal domains. These carboxy-terminal domains (the B30.2(SPRY) domain in TRIM5α and the cyclophilin A domain in TRIMCyp) recognize the retroviral capsid. Here we show that some B-box 2 changes in TRIM5α, but not in TRIMCyp, resulted in decreased human immunodeficiency virus (HIV-1) capsid binding. The phenotypic effects of these B-box 2 changes on the restriction of retroviral infection depended on the potency of restriction and the affinity of the TRIM5α interaction with the viral capsid, two properties specified by the …

Characterization Of Human Immunodeficiency Virus Type 1 Monomeric And Trimeric Gp120 Glycoproteins Stabilized In The Cd4-Bound State: Antigenicity, Biophysics, And Immunogenicity, Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Richard Wyatt

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations …

Georgeoral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …

Planning An Integrated Disease Surveillance And Response System: A Matrix Of Skills And Activities, Helen N. Perry, Sharon M. Mcdonnell, Wondimagegnehu Alemu, Peter Nsubuga

Dartmouth Scholarship

The threat of a global influenza pandemic and the adoption of the World Health Organization (WHO) International Health Regulations (2005) highlight the value of well-coordinated, functional disease surveillance systems. The resulting demand for timely information challenges public health leaders to design, develop and implement efficient, flexible and comprehensive systems that integrate staff, resources, and information systems to conduct infectious disease surveillance and response. To understand what resources an integrated disease surveillance and response system would require, we analyzed surveillance requirements for 19 priority infectious diseases targeted for an integrated disease surveillance and response strategy in the WHO African region.

Impact Of Antibiotic Restriction On Broad Spectrum Antibiotic Usage In The Icu Of A Developing Country, Shahla Siddiqui, Kashif Hussein, Roshan Manasia, Aijaz Samad, Nawal Salahuddin, Afia Zafar, M. Qamarul Hoda

Department of Anaesthesia

Objective: To reduce rates of nosocomial pneumonia and cost of antibiotic therapy.
Methods: By means of a policy implementation the following broad spectrum antibiotics were restricted to usage in the ICU for 72 hours: Cefepime, Meropenem, Imipenem, Tazocin, Polymixin B and Vancomycin, after an institutional based pharmacy and therapeutic committee approval. The ICU pharmacist would alert the ICU residents or consultants after 48 hours of the computer based antibiotic entry that the order would expire within hours. Telephone approval was obtained followed by a formal consultation if deemed necessary by the ID specialist or primary team. Antibiotic usage was …

Variant Merozoite Protein Expression Is Associated With Erythrocyte Invasion Phenotypes In Plasmodium Falciparum Isolates From Tanzania, A.K. Bei, C.D. Membi, J.C. Rayner, M. Mubi, B. Ngasala, A.A. Sultan, Zul Premji, M.T. Duraisingh

Pathology, East Africa

[No abstract available]

Genome Sequence Of Fusobacterium Nucleatum Subspecies Polymorphum — A Genetically Tractable Fusobacterium, Sandor E Karpathy, Xiang Qin, Jason Gioia, Huaiyang Jiang, Yamei Liu, Joseph F Petrosino, Shailaja Yerrapragada, George E Fox, Susan Kinder Haake, George M Weinstock, Sarah K Highlander

Faculty, Staff and Student Publications

Fusobacterium nucleatum is a prominent member of the oral microbiota and is a common cause of human infection. F. nucleatum includes five subspecies: polymorphum, nucleatum, vincentii, fusiforme, and animalis. F. nucleatum subsp. polymorphum ATCC 10953 has been well characterized phenotypically and, in contrast to previously sequenced strains, is amenable to gene transfer. We sequenced and annotated the 2,429,698 bp genome of F. nucleatum subsp. polymorphum ATCC 10953. Plasmid pFN3 from the strain was also sequenced and analyzed. When compared to the other two available fusobacterial genomes (F. nucleatum subsp. nucleatum, and F. nucleatum subsp. vincentii) 627 open reading frames unique …

Nosocomial Buffalopoxvirus Infection, Karachi, Pakistan, Afia Zafar, Robert Swanepoel, Roger Hewson, Mazhar Nizam, Altaf Ahmed, Akhtar Husain, Antoinette Grobbelaar, Kevin Bewley, Valerie Mioulet, Barry Dowsett, Linda Easterbrook, Rumina Hasan

Department of Pathology and Laboratory Medicine

During 5 months in 2004–2005, buffalopoxvirus infection, confirmed by virus isolation and limited nucleic acid sequencing, spread between 5 burns units in Karachi, Pakistan. The outbreak was related to movement of patients between units. Control measures reduced transmission, but sporadic cases continued due to the admission of new patients with community-acquired infections.

Dengue Virus Serotype 3, Karachi, Pakistan, Bushra Jamil, Rumina Hasan, Afia Zafar, Kevin Bewley, John Chamberlain, Valerie Mioulet, Moira Rowlands, Roger Hewson

Department of Medicine

No abstract provided.

Outcomes Of Peginterferon Alfa-2a And Ribavirin Combination Therapy In A Resident-Initiated, Multidisciplinary, Hepatitis C Clinic, Nicole M. Agostino Do, Erini Vasiliadis Do, K Nadeem Ahmed Md, Suzanne J. Templer Do, Edward R. Norris Md, Fapa, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Joseph L. Yozviak Do, Facp

Department of Medicine

No abstract provided.

Association Of Putative Enteroaggregative Escherichia Coli Virulence Genes And Biofilm Production In Isolates From Travelers To Developing Countries, Jamal A Mohamed, David B Huang, Zhi-Dong Jiang, Herbert L Dupont, James P Nataro, Jaime Belkind-Gerson, Pablo C Okhuysen

Faculty, Staff and Student Publications

Enteroaggregative Escherichia coli (EAEC) is an emerging enteric pathogen that causes acute and chronic diarrhea among children, human immunodeficiency virus-infected patients, and travelers to developing regions of the world. The pathogenesis of EAEC strains involves the production of biofilm. In this study, we determined the association between presence of putative EAEC virulence genes and biofilm formation in 57 EAEC isolates (as defined by HEp-2 adherence) from travelers with diarrhea and in 18 EAEC isolates from travelers without diarrhea. Twelve nondiarrheagenic E. coli isolates from healthy travelers were used as controls. Biofilm formation was measured by using a microtiter plate assay …

Evaluation Of Immune Response To Hepatitis B Vaccine In Health Care Workers At A Tertiary Care Hospital In Pakistan: An Observational Prospective Study, Mohammad Zeeshan, Kauser Jabeen, Anita Nausheen Akbar Ali, Ailia Wilayat Ali, Saadia Z Farooqui, Vikram Mehraj, Afia Zafar

Department of Pathology and Laboratory Medicine

Background: Seroconversion rates reported after Hepatitis B virus (HBV) vaccination globally ranges from 85–90%. Health care workers (HCWs) are at high risk of acquiring HBV and non responders' rates after HBV vaccination were not reported previously in Pakistani HCWs. Therefore we evaluated immune response to HBV vaccine in HCWs at a tertiary care hospital in Karachi, Pakistan.
Methods: Descriptive observational study conducted at Aga Khan University from April 2003 to July 2004. Newly HBV vaccinated HCWs were evaluated for immune response by measuring serum Hepatitis B surface antibody (HBsAb) levels, 6 weeks post vaccination.
Results: Initially 666 employees were included …

Antimicrobial Resistance In Neisseria Gonorrhoeae And Limited Treatment Options, Afia Zafar, Kauser Jabeen

Department of Pathology and Laboratory Medicine

No abstract provided.

Up-Regulation Of Interferon-A/Apobec3g Signal Pathway Potently Inactivates Hiv-1 Infectivity In Resting Cd4-T Cells, Keyang Chen, Jialing Huang, Chune Zhang, Sophia Huang, Giuseppe Nunnari, Feng-Xiang Wang, Xiangrong Tong, Ling Gao, Kristi Nikisher, Hui Zhang

Department of Medicine Faculty Papers

Poster Presentation.

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Jefferson Journal of Psychiatry

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What Investigations Are Ordered In Patients With First-Episode Psychosis?, Allan Shefrin M.D. (Pgy2), Derek Puddester M.D., Stephanie Greenham Ph.D., Lise Bisnaire Ph.D., Hazen Gandy M.D.

Jefferson Journal of Psychiatry

Psychiatrists are often left with the dilemma of which investigations to order in adolescents presenting with a first episode of psychosis. Blood work, urine studies, and neuroimaging studies were tracked in 13 adolescents admitted with a diagnosis of first-episode psychosis over a 13-month period to the Children’s Hospital of Eastern Ontario. Variation was found in the amount of investigation ordered: 85% of patients received a drug screen; 54% a CT scan; 8% an MRI; 92% a CBC with differential; 92% electrolytes. Abnormalities of CT scans were detected in 2 patients (29%); in neither case did the result lead to a …

Antibiotic Susceptibility Of Atopobium Vaginae, Ellen De Backer, Rita Verhelst, Hans Verstraelen, Geert Claeys, Gerda Verschraegen, Marleen Temmerman, Mario Vaneechoutte

Obstetrics and Gynaecology, East Africa

Background: Previous studies have indicated that a recently described anaerobic bacterium, Atopobium vaginae is associated with bacterial vaginosis (BV). Thus far the four isolates of this fastidious micro-organism were found to be highly resistant to metronidazole and susceptible for clindamycin, two antibiotics preferred for the treatment of BV.

Methods: Nine strains of Atopobium vaginae, four strains of Gardnerella vaginalis, two strains of Lactobacillus iners and one strain each of Bifidobacterium breve, B. longum, L. crispatus, L. gasseri and L. jensenii were tested against 15 antimicrobial agents using the Etest.

Results: All nine strains of A. vaginae were highly resistant to …

Treatment Of Spinal Tuberculosis: Role Of Surgical Intervention, Syed Ather Enam, Ahmed Ali Shah

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Estimation Of Blood Loss During Caesarean Section: An Audit, Fauzia A. Khan, Mueenullah Khan, Asif Ali, Ursula Chohan

Department of Anaesthesia

Objective: To evaluate the blood ordering practice and blood transfusion for Caesarean sections at our institution and to compare the estimated blood loss between anaesthetists and obstetricians.Methods: A review of 126 patients undergoing both elective and emergency Caesarean section was undertaken in 2002. Information collected included the number of blood units cross-matched preoperatively, type of surgery (emergency or elective), type of anaesthesia, parity of the patient, estimated blood loss by both anaesthetists and obstetricians, intraoperative and postoperative transfusion within 48 hours and pre and post operative haemoglobin (Hb) and haemocrit (Hct).Results: A total of 215 units were cross-matched for 126 …

Proteomic Identification Of In Vivo Substrates For Matrix Metalloproteinases 2 And 9 Reveals A Mechanism For Resolution Of Inflammation, Kendra J Greenlee, David B Corry, David A Engler, Risë K Matsunami, Philippe Tessier, Richard G Cook, Zena Werb, Farrah Kheradmand

Faculty, Staff and Student Publications

Clearance of allergic inflammatory cells from the lung through matrix metalloproteinases (MMPs) is necessary to prevent lethal asphyxiation, but mechanistic insight into this essential homeostatic process is lacking. In this study, we have used a proteomics approach to determine how MMPs promote egression of lung inflammatory cells through the airway. MMP2- and MMP9-dependent cleavage of individual Th2 chemokines modulated their chemotactic activity; however, the net effect of complementing bronchoalveolar lavage fluid of allergen-challenged MMP2(-/-)/MMP9(-/-) mice with active MMP2 and MMP9 was to markedly enhance its overall chemotactic activity. In the bronchoalveolar fluid of MMP2(-/-)/MMP9(-/-) allergic mice, we identified several chemotactic …

Child Health And Survival In The Eastern Mediterranean Region, Zulfiqar A. Bhutta, Asim Belgaumi, Rab Mohammad Abdur, Zein Karrar, Mohamed Khashaba, Nezha Mouane

Department of Paediatrics and Child Health

No abstract provided.

Treatment Of Spinal Tuberculosis: Role Of Surgical Intervention, Ather Enam, Ahmed Ali Shah

Section of Neurosurgery

The treatment of tuberculosis of the spine (Pott's disease) is essentially conservative and a vast majority of patients can be successfully managed on antituberculo us therapy (ATT) alone.1 Surgery is indicated in a few specific cases where deformity of spine, pain, or neurological compromise is becoming a serious issue. In cases where surgery is indicated the benefits are almost immediate and excellent. Tuberculosis (TB) is one of the leading causes of infectious disease-related deaths in under-developed countries and it has had a resurgence in developed countries as well. The most common site of bony dissemination of this disease is in …

Transcutaneous Immunization With Toxin-Coregulated Pilin A Induces Protective Immunity Against Vibrio Cholerae O1 El Tor Challenge In Mice, Julianne E. Rollenhagen, Anuj Kalsy, Francisca Cerda, Manohar John

Dartmouth Scholarship

Toxin-coregulated pilin A (TcpA) is the main structural subunit of a type IV bundle-forming pilus of Vibrio cholerae, the cause of cholera. Toxin-coregulated pilus is involved in formation of microcolonies of V. cholerae at the intestinal surface, and strains of V. cholerae deficient in TcpA are attenuated and unable to colonize intestinal surfaces. Anti-TcpA immunity is common in humans recovering from cholera in Bangladesh, and immunization against TcpA is protective in murine V. cholerae models. To evaluate whether transcutaneously applied TcpA is immunogenic, we transcutaneously immunized mice with 100 mug of TcpA or TcpA with an immunoadjuvant (cholera toxin [CT], …

Psychiatric Outcomes In A Resident-Run, Multidisciplinary, Hepatitis C Clinic (Poster), Nicole M. Agostino Do, Edward Norris Md, Fapm, Joseph L. Yozviak Do, Facp, Suzanne J. Templer Do, Charles M. Brooks Md, Eric J. Gertner Md, Mph, Michael Kaufmann Md

Department of Medicine

No abstract provided.

A Survey Of Primary Care Residents Regarding Knowledge Of Hepatitis C, Joseph L. Yozviak Do, Facp, Erini Vasiliadis Do, Sharon R. Kimmel Phd, Mha, Suzanne J. Templer Do, Margaret Hoffman-Terry Md, Facp

Department of Medicine

No abstract provided.

Endocarditis And Biofilm-Associated Pili Of Enterococcus Faecalis, Sreedhar R Nallapareddy, Kavindra V Singh, Jouko Sillanpää, Danielle A Garsin, Magnus Höök, Stanley L Erlandsen, Barbara E Murray

Faculty, Staff and Student Publications

Increasing multidrug resistance in Enterococcus faecalis, a nosocomial opportunist and common cause of bacterial endocarditis, emphasizes the need for alternative therapeutic approaches such as immunotherapy or immunoprophylaxis. In an earlier study, we demonstrated the presence of antibodies in E. faecalis endocarditis patient sera to recombinant forms of 9 E. faecalis cell wall-anchored proteins; of these, we have now characterized an in vivo-expressed locus of 3 genes and an associated sortase gene (encoding sortase C; SrtC). Here, using mutation analyses and complementation, we demonstrated that both the ebp (encoding endocarditis and biofilm-associated pili) operon and srtC are important for biofilm production …

Prophylaxis And Therapy Of Inhalational Anthrax By A Novel Monoclonal Antibody To Protective Antigen That Mimics Vaccine-Induced Immunity, Laura Vitale, Diann Blanset, Israel Lowy, Thomas O'Neill, Joel Goldstein, Stephen F. Little, Gerard P. Andrews, Gary Dorough, Ronald K. Taylor, Tibor Keler

Dartmouth Scholarship

The neutralizing antibody response to the protective antigen (PA) component of anthrax toxin elicited by approved anthrax vaccines is an accepted correlate for vaccine-mediated protection against anthrax. We reasoned that a human anti-PA monoclonal antibody (MAb) selected on the basis of superior toxin neutralization activity might provide potent protection against anthrax. The fully human MAb (also referred to as MDX-1303 or Valortim) was chosen from a large panel of anti-PA human MAbs generated using transgenic mice immunized with recombinant PA solely on the basis of in vitro anthrax toxin neutralization. This MAb was effective in prophylactic and postsymptomatic treatment of …

Clinical Characteristics Of Pulmonary Tuberculosis In Adult Pakistani Patients With Co-Existing Diabetes Mellitus, A Jabbar, S F. Hussain, A A. Khan

Section of Pulmonary & Critical Care

A review was made of the records of all patients with pulmonary tuberculosis and diabetes mellitus admitted over a 5-year period to a teaching hospital in Karachi, Pakistan. Among 42358 patients, the total number with both tuberculosis and diabetes was 173. The prevalence of tuberculosis in diabetic patients was 10-times higher than in non-diabetic patients and prevalence increased with duration of diabetes. The lower lung field was most frequently involved, followed by the upper and middle. Bilateral involvement was seen in half and an associated pleural effusion in one-third of the patients. Cavitating lesions were seen in 32% of men …

Cd80 And Cd86 Control Antiviral Cd8+ T-Cell Function And Immune Surveillance Of Murine Gammaherpesvirus 68, Shinichiro Fuse, Joshua J. Obar, Sarah Bellfy, Erica K. Leung, Weijun Zhang, Edward J. Usherwood

Dartmouth Scholarship

The interactions between CD80 and CD86 on antigen-presenting cells and CD28 on T cells serve as an important costimulatory signal in the activation of T cells. Although the simplistic two-signal hypothesis has been challenged in recent years by the identification of different costimulators, this classical pathway has been shown to significantly impact antiviral humoral and cellular immune responses. How the CD80/CD86-CD28 pathway affects the control of chronic or latent infections has been less well characterized. In this study, we investigated its role in antiviral immune responses against murine gammaherpesvirus 68 (MHV-68) and immune surveillance using CD80/CD86^−/− mice. In the …

Ligand-Signaled Upregulation Of Enterococcus Faecalis Ace Transcription, A Mechanism For Modulating Host-E Faecalis Interaction, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecalis, the third most frequent cause of bacterial endocarditis, appears to be equipped with diverse surface-associated proteins showing structural-fold similarity to the immunoglobulin-fold family of staphylococcal adhesins. Among the putative E. faecalis surface proteins, the previously characterized adhesin Ace, which shows specific binding to collagen and laminin, was detectable in surface protein preparations only after growth at 46 degrees C, mirroring the finding that adherence was observed in 46 degrees C, but not 37 degrees C, grown E. faecalis cultures. To elucidate the influence of different growth and host parameters on ace expression, we investigated ace expression using E. …