Digital Commons Network^™

Structure Of Vibrio Cholerae Toxt Reveals A Mechanism For Fatty Acid Regulation Of Virulence Genes, Michael J. Lowden, Karen Skorupski, Maria Pellegrini, Michael G. Chiorazzo, Ronald K. Taylor, F. Jon Kull

Dartmouth Scholarship

Cholera is an acute intestinal infection caused by the bacterium Vibrio cholerae. In order for V. cholerae to cause disease, it must produce two virulence factors, the toxin-coregulated pilus (TCP) and cholera toxin (CT), whose expression is controlled by a transcriptional cascade culminating with the expression of the AraC-family regulator, ToxT. We have solved the 1.9 A resolution crystal structure of ToxT, which reveals folds in the N- and C-terminal domains that share a number of features in common with AraC, MarA, and Rob as well as the unexpected presence of a buried 16-carbon fatty acid, cis-palmitoleate. The finding that …

Acute Necrotizing Encephalopathy Of Childhood: A Fatal Complication Of Swine Flu, Muhammad Rehan Khan, Prem Kumar Maheshwari, Syed Asad Ali, Anwarul Haque

Department of Paediatrics and Child Health

Acute necrotizing encephalopathy of childhood (ANEC) is a rare condition characterized by the presence of multifocal symmetrical brain lesions involving mainly thalami, brainstem, cerebellum and white matter. ANEC is a serious and life threatening complication of simple viral infections. We present a case of a young child who developed this condition with classical clinical and radiological findings consistent with ANEC, secondary to swine flu (H1N1). He needed ventilatory support and had profound motor and intellectual deficit on discharge. We report this case with aim of raising awareness about this fatal complication of swine flu which has become a global health …

Ct And Mri Features Following Uterine Fibroid Embolization, Sachit Verma Md, Carin F. Gonsalves Md, Oksana H. Baltarowich Md, Donald G. Mitchell Md, Anna Lev-Toaff Md, Diane Bergin Md

Department of Radiology Faculty Papers

Uterine artery embolization (UAE) is an effective treatment for symptomaticuterine fibroids. Magnetic resonance (MR) imaging is typically employed to evaluate the uterus following UAE for fibroid infarction, size, location change, persistent enhancement, changes in adenomyosis and uterine necrosis. Variable pattern of calcification on computed tomography (CT) can differentiate embolic particles and fibroid involution. CT following UAE may be requested because of acute pelvic pain or chest discomfort or pyrexia and/or for complications that may require treatment in acute phase. Visualization of gas in uterus and uterine vessels following UAE is an expected finding that should not be misinterpreted as a …

Crystal Structure Of The Cystic Fibrosis Transmembrane Conductance Regulator Inhibitory Factor Cif Reveals Novel Active-Site Features Of An Epoxide Hydrolase Virulence Factor, Christopher D. Bahl, Christophe Morisseau, Jennifer M. Bomberger, Bruce A. Stanton, Bruce D. Hammock, George A. O'Toole, Dean R. Madden

Dartmouth Scholarship

Cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif) is a virulence factor secreted by Pseudomonas aeruginosa that reduces the quantity of CFTR in the apical membrane of human airway epithelial cells. Initial sequence analysis suggested that Cif is an epoxide hydrolase (EH), but its sequence violates two strictly conserved EH motifs and also is compatible with other alpha/beta hydrolase family members with diverse substrate specificities. To investigate the mechanistic basis of Cif activity, we have determined its structure at 1.8-A resolution by X-ray crystallography. The catalytic triad consists of residues Asp129, His297, and Glu153, which are conserved across the …

A Woman With Hiv Infection, Brain Abscesses, And Eosinophilia, Marcela Campo, Man K Phung, Rehan Ahmed, Paul Cantey, Henry Bishop, Tanvir K Bell, Carolyn Gardiner, Cesar A Arias

Faculty, Staff and Student Publications

No abstract provided.

Pulmonary Carcinosarcoma Initially Presenting As Invasive Aspergillosis: A Case Report Of Previously Unreported Combination, Ariyo O. Olobatoke, Doina David, Wasif Hafeez, Thien Van, Husain A. Saleh

Wayne State University Associated BioMed Central Scholarship

Abstract

Carcinosarcoma of the lung is a malignant tumor composed of a mixture of carcinoma and sarcoma elements. The carcinomatous component is most commonly squamous followed by adenocarcinoma. The sarcomatous component commonly comprises the bulk of the tumor and shows poorly differentiated spindle cell features. Foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be seen. Aspergillus pneumonia is the most common form of invasive aspergillosis and occurs mainly in patients with malignancy, immunocompromizing or debilitating diseases. Patients with Aspergillus pneumonia present with fever, cough, chest pain and occasionally hemoptysis. Tissue examination is the most reliable method for …

Continuous Infusion Of Nafcillin For Sternal Osteomyelitis In An Infant After Cardiac Surgery, Chad A. Knoderer, Jennifer L. Morris, Elaine G. Cox

Scholarship and Professional Work – COPHS

We report the use of the continuous infusion of nafcillin for the treatment of an infant who had methicillinsusceptible Staphylococcus aureus sternal osteomyelitis not responsive to traditional nafcillin dosing. The patient was successfully treated with surgical debridement and the continuous infusion of nafcillin. To our knowledge, this is the first report describing the successful use of the continuous infusion of nafcillin to treat an infant who had sternal osteomyelitis after cardiac surgery.

Prevalence Of Hepatitis B And C Viral Infections In Pakistan: Findings Of A National Survey Appealing For Effective Prevention And Control Measures, H Qureshi, K M. Bile, Rashid Jooma, S E. Alam, H U R. Afridi

Section of Neurosurgery

A prevalence survey on hepatitis B and C infections was carried out to obtain national estimates and assess epidemiological dynamics and underlying risk factors. Overall prevalence of hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) of 2.5% and 4.8%, respectively, reflected a combined infection rate of 7.6% in the general population, consistent with an ongoing high burden of chronic liver disease (CLD). There was significant association of these viral infections with a range of risk factors led by reuse of syringes. These findings validate currently implemented strategies by the national programme for the control of hepatitis viral infections, …

Referral Mechanism Improves Uptake Of Art Services For Hiv+ Fp Clients, Population Council

Reproductive Health

An operations research intervention by the Population Council in Kenya aimed to design a referral framework for linking HIV‐positive family planning (FP) clients to treatment and care in selected health facilities. The project also assessed the acceptability and effectiveness in increasing the number of eligible HIV‐positive FP clients receiving HIV care and treatment services. This summary details the effort to improve the linkage between FP services and comprehensive care centers that led to a dramatic increase in the proportions of HIV-positive clients in FP clinics who go on to receive HIV/AIDS treatment and care services at the same facility. Recommendations …

Introducing A Multi-Site Program For Early Diagnosis Of Hiv Infection Among Hiv-Exposed Infants In Tanzania, Harriet Nuwagaba-Biribonwoha, Bazghina Werq-Semo, Aziz Abdallah, Amy Cunningham, John G. Gamaliel, Sevestine Mtunga, Victoria Nankabirwa, Isaya Malisa, Luis F. Gonzalez, Charles Massambu, Denis Nash, Jessica Justman, Elaine J. Abrams

Publications and Research

Background: In Tanzania, less than a third of HIV infected children estimated to be in need of antiretroviral therapy (ART) are receiving it. In this setting where other infections and malnutrition mimic signs and symptoms of AIDS, early diagnosis of HIV among HIV-exposed infants without specialized virologic testing can be a complex process. We aimed to introduce an Early Infant Diagnosis (EID) pilot program using HIV DNA Polymerase Chain Reaction (PCR) testing with the intent of making EID nationally available based on lessons learned in the first 6 months of implementation.

Methods: In September 2006, a molecular biology laboratory at …

Voices From The Floor (January 2010), Pcom

Voices from the Floor

No abstract provided.

Labrad : Vol 35, Issue 1 - January - February 2010, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Assessment of Osteoporosis Risk by NTx- A Biochemical Marker
• Antibodies Against Cyclic Citrullinated Peptides (Anti-CCP) Assay in Rheumatoid Arthritis
• A Disintegrin and Metallopeptidase with Thrombospondin Type 1 Motif, 13 (ADAMTS-13)
• Soluble Transferrin Receptor (sTfR)
• Diagnosis of Cryptococcal Meningitis
• Infections in Thalassaemia
• CDX-2, A Reliable Diagnostic Marker for Carcinomas of Colorectal Origin
• Radiopaque Metallic Marker Insertion in Breast Cancers Prior to Neoadjuvant/Preoperative Chemotherapy
• Meeting Reports: 10TH International Radiological Conference 2009
• Continuing Medical Education Seminar Organised by Clinical Laboratory at AKUH

Validation Of C-Reactive Protein In The Early Diagnosis Of Neonatal Sepsis In A Tertiary Care Hospital In Kenya., Rashim Kumar, Rachel Musoke, William Macharia, Gunturu Revathi

Paediatrics and Child Health, East Africa

Objective: To evaluate utility of C-reactive protein (CRP) in the early diagnosis of neonatal sepsis in a tertiary care Newborn Unit in Kenya.

Design: Cross-sectional study.

Setting: Newborn Unit, Kenyatta National Hospital.

Subjects: All neonates admitted to Newborn Unit, Kenyatta National Hospital during the study period with suspected sepsis based on specified clinical criteria.

Results: Of the 310 infants, there were 83 episodes of proven sepsis and 94 episodes of probable sepsis. Using the standard CRP cut-off value of 5 mg/dl, a sensitivity of 95.2% in proven sepsis and 98.9% for probable septic episodes were noted. In proven sepsis, a …

Chlorella Viruses Encode Most, If Not All, Of The Machinery To Glycosylate Their Glycoproteins Independent Of The Endoplasmic Reticulum And Golgi, James L. Van Etten, James Gurnon, Giane M. Yanai-Balser, David Dunigan, Michael V. Graves

Nebraska Center for Virology: Faculty Publications

In contrast to all other viruses that use the host machinery located in the endoplasmic reticulum and Golgi to glycosylate their glycoproteins, the large dsDNA-containing chlorella viruses encode most, if not all, of the components to glycosylate their major capsid proteins. Furthermore, all experimental results indicate that glycosylation occurs independent of the endoplasmic reticulum and Golgi. (Review article)

Lessons From A Career In Medicine And Education - Rani Bright, Mbbs, Justin Guthier

Voices from the Floor

No abstract provided.

Robustness Of The Healthcare Utilization Results From The Rotavirus Efficacy And Safety Trial (Rest) Evaluating The Human-Bovine (Wc3) Reassortant Pentavalent Rotavirus Vaccine (Rv5), Robbin Itzler, Gary Koch, David O. Matson, Leif Gothefors, Pierre Van Damme, Mark J. Dinubile, Penny M. Heaton

Community & Environmental Health Faculty Publications

Background: The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5) including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE). The per-protocol (PP) analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT) analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after …

Association Of Hiv Infection With Distribution And Viral Load Of Hpv Types In Kenya: A Survey With 820 Female Sex Workers, Stanley Mf Luchters, Davy Vanden Broeck, Matthew F. Chersich, Annalene Nel, Wim Delva, Kishor Mandaliya, Christophe E. Depuydt, Patricia Claeys, John-Paul Bogers, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Background: Human papillomavirus (HPV) and HIV are each responsible for a considerable burden of disease. Interactions between these infections pose substantial public health challenges, especially where HIV prevalence is high and HPV vaccine coverage low.

Methods: Between July 2005 and January 2006, a cross-sectional community-based survey in Mombasa, Kenya, enrolled female sex workers using snowball sampling. After interview and a gynaecological examination, blood and cervical cytology samples were taken. Quantitative real-time PCR detected HPV types and viral load measures. Prevalence of high-risk HPV was compared between HIV-infected and -uninfected women, and in women with abnormal cervical cytology, measured using conventional …

Synthesis, Antiviral And Contraceptive Activities Of Nucleoside-Sodium Cellulose Sulfate Acetate And Succinate Conjugates, Hitesh K. Agarwal, Anil Kumar, Gustavo F. Doncel, Keykavous Parang

Pharmacy Faculty Articles and Research

Chemical conjugates between sodium cellulose sulfate (CS), displaying contraceptive and HIV-entry inhibiting properties, and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), or 2',3'-dideoxy-3'-thiacytidine (3TC)) were designed to simultaneously provide contraceptive and anti-HIV activity. Two linkers, acetate and succinate, were used to conjugate the nucleoside analogs with CS. The conjugates containing cellulose sulfate-acetate (CSA) (e.g., AZT-CSA and FLT-CSA) were found to be more potent than CS and other conjugates (e.g., AZT-succinate-CS, and FLT-succinate-CS). The presence of both sulfate and the acetate groups on cellulose were critical for generating maximum anti-HIV activity. In addition to showing equal potency against wild-type …

Training Service Providers Increases Tb Screening In Postnatal Care, Population Council

Reproductive Health

This document summarizes a Population Council operations research project undertaken in collaboration with the Kenya Ministry of Health to develop and pilot-test an intervention to improve TB screening, case detection, treatment, and care among postnatal clients. The intervention demonstrated that it is feasible to use postnatal care services as a platform to increase TB screening and case detection. Training providers, giving them job-aids, and strengthening client flow within the facility also improved the overall quality of care that the clients received. The actual number of cases of TB detected was extremely low, however; thus the report recommends that the Ministry …

Introducing And Pilot-Testing The National Guidelines On Integrating The Management Of Stis/Rtis Into Reproductive Health Settings In Kenya, Wilson Liambila, Saiqa Mullick, Ian Askew, Nathalie Broutet, Bartilol Kigen, Cosmas Mutunga, Daniel Sande, Nimrod Garama, Benjamin Tsofa, Christine Awuor, Ibrahim Mohammed

Reproductive Health

This report evaluated a project in ten Kenyan health facilities. It examined the feasibility, acceptability and effect of introducing reproductive tract infection and sexually transmitted infection (RTI/STI) guidelines on the quality of care provided, and the incremental costs of integrating these services into existing reproductive health (RH) services; it also disseminated the results and lessons learnt within Kenya. Overall, the results showed that integration of activities to screen for and manage STIs/RTIs into RH services is feasible, acceptable to clients and providers, and effective in improving the range and quality of services offered to clients.

Evaluating Children With Otitis Media For Bacteremia Or Urinary Tract Infection., Daniel Yawman, Patrick Mahar, Aaron Blumkin, Gregory P. Conners

Manuscripts, Articles, Book Chapters and Other Papers

Background. It is unclear if clinicians evaluate for concurrent bacteremia or UTI in young patients diagnosed with acute otitis media (AOM). Objectives. To describe how often, and under which circumstances, emergency providers investigate for bacteremia or UTI in 2-36 month olds with AOM. Methods. Cases of AOM were analyzed from the 2001-2004 National Hospital Ambulatory Medical Care Survey (NHAMCS)-Emergency Department dataset. Results. AOM was diagnosed in 17% of the 10,847 recorded visits of 2-36 month olds. Of these visits, laboratory testing included: CBC: 7%, Blood culture: 4%, urinalysis or urine culture: 5%, and any of these tests: 9%. Rates of …

Neuroaids In Africa, Kevin Robertson, Jeff Liner, James Hakim, Jean-Louis Sankalé, Igor Grant, Scott Letendre, David Clifford, Amadou Gallo Diop, Assan Jaye, Georgette Kanmogne, Alfred Njamnshi, T. Dianne Langford, Tufa Gemechu Weyessa, Charles Wood, Mwanza Banda, Mina Hosseinipour, Ned Sacktor, Noeline Nakasuja, Paul Bangirana, Robert Paul, John Joska, Joseph Wong, Michael Boivin, Penny Holding, Betsy Kammerer, Annelies Van Rie, Prudence Ive, Avindra Nath, Kathy Lawler, Clement Adebamowo, Walter Royal Iii, Jeymohan Joseph

Nebraska Center for Virology: Faculty Publications

In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting “NeuroAIDS in Africa.” This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment. These introductory talks were followed by presentations on HAND research and clinical care in Botswana, Cameroon, Ethiopia, The Gambia, Kenya, Malawi, Nigeria, Senegal, South Africa, Uganda, …

Functional Properties Of The Hiv-1 Subtype C Envelope Glycoprotein Associated With Mother-To-Child Transmission, Hong Zhang, Marzena Rola, John T. West, Damien C. Tully, Piotr Kubis, Jun He, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the properties of viruses capable of establishing infection during perinatal transmission of HIV-1 is critical for designing effective means of limiting transmission. We previously demonstrated that the newly transmitted viruses (in infant) were more fit in growth, as imparted by their envelope glycoproteins, than those in their corresponding mothers. Here, we further characterized the viral envelope glycoproteins from six mother-infant transmission pairs and determined whether any specific envelope functions correlate with HIV-1 subtype C perinatal transmission. We found that most newly transmitted viruses were less susceptible to neutralization by their maternal plasma compared to contemporaneous maternal viruses. However, the …

Chronology And Evolution Of The Hiv-1 Subtype C Epidemic In Ethiopia, Damien C. Tully, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective—To reconstruct the onset date and evolutionary history of the HIV-1 subtype C epidemic in Ethiopia - one of the earliest recorded subtype C epidemics in the world.

Design—HIV-1 C env sequences with a known sampling year isolated from HIV-1 positive patients from Ethiopia between 1984 and 2003.

Methods—Evolutionary parameters including origin and demographic growth patterns were estimated using a Bayesian coalescent-based approach under either strict or relaxed molecular clock models.

Results—Bayesian evolutionary analysis indicated a most recent common ancestor date of 1965 with three distinct epidemic growth phases. Regression analysis of root-to-tip distances revealed a highly similar estimate for …

Enhancement Of Autophagy During Lytic Replication By The Kaposi’S Sarcoma-Associated Herpesvirus Replication And Transcription Activator, Hui-Ju Wen, Zhilong Yang, You Zhou, Charles Wood

Nebraska Center for Virology: Faculty Publications

Autophagy is one of two major degradation systems in eukaryotic cells. The degradation mechanism of autophagy is required to maintain the balance between the biosynthetic and catabolic processes and also contributes to defense against invading pathogens. Recent studies suggest that a number of viruses can evade or subvert the host cell autophagic pathway to enhance their own replication. Here, we investigated the effect of autophagy on the KSHV (Kaposi’s sarcoma-associated herpesvirus) life cycle. We found that the inhibition of autophagy reduces KSHV lytic reactivation from latency, and an enhancement of autophagy can be detected during KSHV lytic replication. In addition, …

Population Genetic Analysis Of Large Sequence Polymorphisms In Plasmodium Falciparum Blood-Stage Antigens, A.D. Ahouidi, A.K. Bei, D.E. Neafsey, O. Sarr, S. Volkman, D. Milner, J. Cox-Singh, M.U. Ferreira, O. Ndir, Zul Premji, S. Mboup, M.T. Duraisingh

Pathology, East Africa

Plasmodium falciparum, the causative agent of human malaria, invades host erythrocytes using several proteins on the surface of the invasive merozoite, which have been proposed as potential vaccine candidates. Members of the multi-gene PfRh family are surface antigens that have been shown to play a central role in directing merozoites to alternative erythrocyte receptors for invasion. Recently, we identified a large structural polymorphism, a 0.58 Kb deletion, in the C-terminal region of the PfRh2b gene, present at a high frequency in parasite populations from Senegal. We hypothesize that this region is a target of humoral immunity. Here, by analyzing 371 …

Acute Transfusion Reactions Encountered In Patients At A Tertiary Care Center, Safoorah Khalid, Mohammad Usman, Mohammad Khurshid

Section of Haematology/Oncology

Objective: To determine the frequency and type of Acute Transfusion Reactions (ATRs) occurring in inpatients, reported to the transfusion service at Aga Khan University Hospital, Karachi, Pakistan.
Methods: This was a three years and seven months (from January 2005 till July 2008) retrospective review of all the transfusion reactions that were reported to the transfusion service at Aga Khan University Hospital, Karachi, Pakistan. All the reactions were clinically evaluated by the blood bank physician. Transfusion reactions occurring during or within four hours after transfusion were evaluated and classified by standard and recognized definitions defined by American Association of …

Identification Of A Novel Cytokine Inducible Stat5 Phosphoserine Site (Ps193) That Positively Regulates Its Transcriptional Activity And Is Found Constitutively Activated In Certain Hematopoietic Cancers, Abhisek Mitra

Open Access Theses & Dissertations

Hematological malignancies such as leukemia and lymphoma, can develop from aberrant changes in the cell signaling molecules to drive their uncontrolled cellular proliferation and differentiation. Activation, maturation, expansion and differentiation of T cells are critically regulated by the dynamics of various transcription factors activated by a variety of cytokines. Additionally, multiple effector molecules that mediate these T cells dependent signals include the JAK (Janus Kinase)-STAT (Signal transducer and activator of transcription) cascade. These signaling proteins are activated in response to a broad array of cytokines. Constitutively activated JAKs and STATs have been described in several T cell malignancies. A growing …

Population Pharmacokinetics And Pharmacodynamics Of Artemether And Lumefantrine During Combination Treatment In Children With Uncomplicated Falciparum Malaria In Tanzania, S.F. Hietala, A. Martensson, B. Ngasala, S. Dahlstrom, N. Lindegardh, A. Annerberg, Zul Premji, A. Farnert, P. Gil, A. Bjorkman, M. Ashton

Pathology, East Africa

The combination of artemether (ARM) and lumefantrine is currently the first-line treatment of uncomplicated falciparum malaria in mainland Tanzania. While the exposure to lumefantrine has been associated with the probability of adequate clinical and parasitological cure, increasing exposure to artemether and the active metabolite dihydroartemisinin (DHA) has been shown to decrease the parasite clearance time. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine in African children with uncomplicated malaria. In addition to drug concentrations and parasitemias from 50 Tanzanian children with falciparum malaria, peripheral parasite densities from 11 asymptomatic children were …

Hepatic Failure, Neonatal Hemochromatosis And Porto-Pulmonary Hypertension In A Newborn With Trisomy 21 - A Case Report, Erin Neil, Josef Cortez, Aparna Joshi, Erawati V. Bawle, Janet Poulik, Mark Zilberman, Mohammad F. El-Baba, Beena G. Sood

Wayne State University Associated BioMed Central Scholarship

Abstract

Liver failure in neonates is a rare but often fatal disease. Trisomy 21 is not usually associated with significant infantile liver disease. If present, hepatic dysfunction in an infant with Trisomy 21 is likely to be attributed to transient myeloproliferative disorder with hepatic infiltration by hematopoietic elements and may be associated with secondary hemosiderosis. A less commonly recognized cause of liver failure in neonates with Trisomy 21 is neonatal hemochromatosis (NH); this association has been reported in nine cases of Trisomy 21 in literature. NH is a rare, severe liver disease of intra-uterine onset that is characterized by neonatal …