Digital Commons Network^™

Development Of Dengue Dna Vaccines, Janine R. Danko, Charmagne G. Beckett, Kevin R. Porter

United States Navy: Publications

Vaccination with plasmid DNA against infectious pathogens including dengue is an active area of investigation. By design, DNA vaccines are able to elicit both antibody responses and cellular immune responses capable of mediating long-term protection. Great technical improvements have been made in dengue DNA vaccine constructs and trials are underway to study these in the clinic. The scope of this review is to highlight the rich history of this vaccine platform and the work in dengue DNA vaccines accomplished by scientists at the Naval Medical Research Center. This work resulted in the only dengue DNA vaccine tested in a clinical …

Safety And Protective Efficacy Of Ina-Inactivated Venezuelan Equine Encephalitis Virus: Implication In Vaccine Development, Anuj Sharma, Paridhi Gupta, Pamela J. Glass, Michael D. Parker, Radha K. Maheshwari

United States Army: Publications

We have previously shown that a hydrophobic alkylating compound, 1,5-iodonaphthyl-azide (INA) can efficiently inactivate the virulent strain of Venezuelan equine encephalitis virus (VEEV), V3000 in vitro. In this study, we have evaluated the safety of INA-inactivated V3000 and V3526 and the protective efficacy of INA-inactivated V3000. INA-inactivated V3000 and V3526 did not cause disease in suckling mice. RNA isolated from the INA-inactivated V3000 and V3526 was also not infectious. Immunization of adult mice with INA-inactivated V3000 induced an anti-VEEV antibody response and protected mice from virulent VEEV challenge. The protective efficacy of INA-inactivated V3000 increased with the use of adjuvants. …

The Application Of Gis And Spatiotemporal Analyses To Investigations Of Unusual Marine Mammal Strandings And Mortality Events, Stephanie A. Norman, Jessie Huggins, Tim E. Carpenter, James T. Case, Dyanna M. Lambourn, Jim Rice, John Calambokidis, Joseph K. Gaydos, M. Bradley Hanson, Deborah A. Duffield, Sandra Dubpernell, Susan Berta, Matt Klope

United States Department of Commerce: Staff Publications

In 2006–2007, an unusually high number of harbor porpoises (Phocoena phocoena) stranded along the Washington and Oregon coastlines. Spatiotemporal analyses were used to examine their ability to detect clusters of porpoise strandings during an unusualmortality event (UME) in the Pacific Northwest using stranding location data. Strandings were evaluated as two separate populations, outer coast and inland waters. The presence of global clustering was evaluated using the Knox spatiotemporal test, and the presence of local clusters was investigated using a spatiotemporal scan statistic (space–time permutation). There was evidence of global clustering, but no local clustering, supporting the hypothesis that …

Consensus-Based Reporting Standards For Diagnostic Test Accuracy Studies For Paratuberculosis In Ruminants, Ian A. Gardner, Søren S. Nielsen, Richard J. Whittington, Michael T. Collins, Douwe Bakker, Beth Harris, Srinand Sreevatsan, Jason E. Lombard, Raymond Sweeney, David L. Smith, Jerie Gavalchin, Shigetoshi Eda

Zoonotics and Wildlife Disease: Publications

The Standards for Reporting of Diagnostic Accuracy (STARD) statement was developed to encourage complete and transparent reporting of key elements of test accuracy studies in human medicine. The statement was motivated by widespread evidence of bias in test accuracy studies and the finding that incomplete or absent reporting of items in the STARD checklist was associated with overly optimistic estimates of test performance characteristics. Although STARD principles apply broadly, specific guidelines do not exist to account for unique considerations in livestock studies such as herd tests, potential use of experimental challenge studies, a more diverse group of testing purposes and …

Bovine Tuberculosis In A Nebraska Herd Of Farmed Elk And Fallow Deer: A Failure Of The Tuberculin Skin Test And Opportunities For Serodiagnosis, W. Ray Waters, Gary E. Stevens, Mark A. Schoenbaum, Kathy A. Orloski, Suelee Robbe-Austerman, N. Beth Harris, S. Mark Hall, Bruce V. Thomsen, Arach J. Wilson, Roger E. Brannian, Jeffrey T. Nelson, Shawn Schafer, Javan Esfandiari, Meghan Dutton, Rena Greenwald, Konstantin P. Lyashchenko

Zoonotics and Wildlife Disease: Publications

In 2009, Mycobacterium bovis infection was detected in a herd of 60 elk (Cervus elaphus) and 50 fallow deer (Dama dama) in Nebraska, USA. Upon depopulation of the herd, the prevalence of bovine tuberculosis (TB) was estimated at ∼71–75%, based upon histopathology and culture results. Particularly with elk, gross lesions were often severe and extensive. One year ago, the majority of the elk had been tested for TB by single cervical test (SCT), and all were negative. After initial detection of a tuberculous elk in this herd, 42 of the 59 elk were tested by SCT. …

Protective Immunity To Pre-Erythrocytic Stage Malaria, Robert J. Schwenk, Thomas L. Richie

United States Army: Publications

The development of a vaccine against malaria is a major research priority given the burden of disease, death and economic loss inflicted upon the tropical world by this parasite. Despite decades of effort, however, a vaccine remains elusive. The best candidate is a subunit vaccine termed RTS,S but this provides only partial protection against clinical disease. This review examines what is known about protective immunity against pre-erythrocytic stage malaria by considering the humoral and T cell-mediated immune responses that are induced by attenuated sporozoites and by the RTS,S vaccine. On the basis of these observations a set of research priorities …

Clostridium Difficile Infections In Patients With Severe Burns, Scott J. Crabtree, Janelle L. Robertson, Kevin K. Chung, Evan M. Renz, Steven E. Wolf, Duane R. Hospenthal, Clinton K. Murray

United States Army: Publications

With improved survival in burn patients, Clostridium difficile infection (CDI) remains a significant potential complication. The incidence of, risk factors for, and outcomes of CDI in severely burned patients are poorly studied and remain unclear. This study involves retrospective case control and cohort studies using electronic medical records from February 1, 2002 to January 31, 2009 at the US Department of Defense’s only burn unit. Demographic, risk factor, and outcome data were collected for all C. difficile toxin positive patients in the burn, medical, and surgical intensive care units and the hospital’s step down unit along with an additional analysis …

A Diagnostic Approach To Pruritus, Brian V. Reamy, Christopher W. Bunt, Stacy Fletcher

United States Air Force: Publications

Pruritus can be a symptom of a distinct dermatologic condition or of an occult underlying systemic disease. Of the patients referred to a dermatologist for generalized pruritus with no apparent primary cutaneous cause, 14 to 24 percent have a systemic etiology. In the absence of a primary skin lesion, the review of systems should include evaluation for thyroid disorders, lymphoma, kidney and liver diseases, and diabetes mellitus. Findings suggestive of less serious etiologies include younger age, localized symptoms, acute onset, involvement limited to exposed areas, and a clear association with a sick contact or recent travel. Chronic or generalized pruritus, …

Distribution Of Culicoides Sonorensis (Diptera: Ceratopogonidae) In Nebraska, South Dakota, And North Dakota: Clarifying The Epidemiology Of Bluetongue Disease In The Northern Great Plains Region Of The United States, E. T. Schmidtmann, M. V. Herrero, A. L. Green, D. A. Dargatz, J. M. Rodriquez, T. E. Walton

Zoonotics and Wildlife Disease: Publications

The presence or absence of the biting midge Culicoides sonorensis Wirth & Jones (Diptera: Ceratopogonidae), a primary vector of bluetongue viruses (genus Orbivirus, family Reoviridae, BTV) in North America, was assessed on ranches and farms across the Northern Great Plains region of the United States, specifically Nebraska, South Dakota, and North Dakota, as part of a 2-yr regional study of BTV exposure among cattle. Blacklight/suction trap samples totaling 280 2-night intervals were taken at 140 aquatic sites (potential larval habitat for C. sonorensis) on 82 livestock operations (ranches and farms) that span a south-to-north gradient of expected decreasing …

Bovine Tuberculosis In A Nebraska Herd Of Farmed Elk And Fallow Deer: A Failure Of The Tuberculin Skin Test And Opportunities For Serodiagnosis, W. Ray Waters, Gary E. Stevens, Mark A. Schoenbaum, Kathy A. Orloski, Suelee Robbe-Austerman, N. Beth Harris, S. Mark Hall, Bruce V. Thomsen, Arach J. Wilson, Roger E. Brannian, Jeffrey T. Nelson, Shawn Schafer, Javan Esfandiari, Meghan Dutton, Rena Greenwald, Konstantin P. Lyashchenko

Zoonotics and Wildlife Disease: Publications

In 2009, Mycobacterium bovis infection was detected in a herd of 60 elk (Cervus elaphus) and 50 fallow deer (Dama dama) in Nebraska, USA. Upon depopulation of the herd, the prevalence of bovine tuberculosis (TB) was estimated at ∼71–75%, based upon histopathology and culture results. Particularly with elk, gross lesions were often severe and extensive. One year ago, the majority of the elk had been tested for TB by single cervical test (SCT), and all were negative. After initial detection of a tuberculous elk in this herd, 42 of the 59 elk were tested by SCT. …

Integrating Mechanistic And Polymorphism Data To Characterize Human Genetic Susceptibility For Environmental Chemical Risk Assessment In The 21st Century, Holly M. Mortensen, Susan Y. Euling

United States Environmental Protection Agency: Publications

Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be applied to account for the lack of information about susceptibility. Defining genetic susceptibility in response to environmental chemicals across human populations is an area of interest in the NAS' new paradigm of toxicity pathway-based risk assessment. Data from highthroughput/ high content (HT/HC), including -omics (e.g., genomics, transcriptomics, proteomics, metabolomics) technologies, have been integral to the identification and characterization …

Evidence Of Susceptibility To Morbillivirus Infection In Cetaceans From The United States, T. K. Rowles, L. S. Schwacke, R. S. Wells, J. T. Saliki, L. Hansen, A. Hohn, F. Townsend, R. A. Sayre, A. J. Hall

United States Department of Commerce: Staff Publications

Cetacean morbilliviruses (CeMV) are viruses that can cause mass mortalities among various odontocete species. In this study levels of “herd” immunity in cetaceans from the U.S. coast are described from the distribution and prevalence of antibodies against morbilliviruses. Neutralizing antibody titers against dolphin morbillivirus (DMV), porpoise morbillivirus (PMV), phocine distemper (PDV), and canine distemper viruses (CDV) were measured. Positive samples had higher titers against the CeMV than against the other morbilliviruses tested, indicating that although PDV or CDV can be used to investigate exposure their use may result in a higher false negative rate. The results suggest that morbillivirus did …

International Federation For Emergency Medicine Model Curriculum For Medical Student Education In Emergency Medicine, Cherri Hobgood, Venkataraman Anantharaman, Glen Bandiera, Peter Cameron, Pinchas Halperin, James Holliman, Nicholas Jouriles, Darren Kilroy, Terrence Mulligan, Andrew Singer

Uniformed Services University of the Health Sciences

There is a critical and growing need for emergency physicians and emergency medicine resources worldwide. To meet this need, physicians must be trained to deliver time-sensitive interventions and life-saving emergency care. Currently, there is no internationally recognized, standard curriculum that defines the basic minimum standards for emergency medicine education. To address this lack, the International Federation for Emergency Medicine (IFEM) convened a committee of international physicians, health professionals and other experts in emergency medicine and international emergency medicine development, to outline a curriculum for foundation training of medical students in emergency medicine. This curriculum document represents the consensus of recommendations …

The United States Army Ocular Teleconsultation Program 2004 Through 2009, Michael J. Mines, Kraig S. Bower, Charles M. Lappan, Robert A. Mazzoli, Ronald K. Poropatich

Uniformed Services University of the Health Sciences

PURPOSE: To describe the United States Army Ocular Teleconsultation program and all consultations received from its inception in July 2004 through December 2009.

DESIGN: Retrospective, noncomparative, consecutive case series.

METHODS: All 301 consecutive ocular teleconsultations received were reviewed. The main outcome measures were differential diagnosis, evacuation recommendations, and origination of consultation. Secondary measures included patient demographics, reason for consultation, and inclusion of clinical images.

RESULTS: The average response time was 5 hours and 41 minutes. Most consultations originated from Iraq (58.8%) and Afghanistan (18.6%). Patient care-related requests accounted for 94.7% of consultations; nonphysicians submitted 26.3% of consultations. Most patients (220/285; …

Accelerated Lymphocyte Reconstitution And Long-Term Recovery After Transplantation Of Lentiviral-Transduced Rhesus Cd34+ Cells Mobilized By G-Csf And Plerixafor, Naoya Uchida, Aylin Bonifacino, Allen E. Krouse, Mark E. Metzger, Gyorgy Csako, Agnes Lee-Stroka, Ross M. Fasano, Susan F. Leitman, Joseph J. Mattapallil, Matthew M. Hsieh, John F. Tisdale, Robert E. Donahue

Uniformed Services University of the Health Sciences

Objective. Granulocyte colony-stimulating factor (G-CSF) in combination with plerixafor produces significant mobilization of CD34⁺ cells in rhesus macaques. We sought to evaluate whether these CD34⁺ cells can stably reconstitute blood cells with lentiviral gene marking.

Materials and Methods. We performed hematopoietic stem cell transplantation using G-CSF and plerixafor-mobilized rhesus CD34⁺ cells transduced with a lentiviral vector, and these data were compared with those of G-CSF and stem cell factor mobilization.

Results. G-CSF and plerixafor mobilization resulted in CD34⁺ cell yields that were twofold higher than yields with G-CSF and stem cell factor. CD123 (interleukin-3 receptor) …

Development Of Dengue Dna Vaccines, Janine R. Danko, Charmagne G. Beckett, Kevin R. Porter

Uniformed Services University of the Health Sciences

Vaccination with plasmid DNA against infectious pathogens including dengue is an active area of investigation. By design, DNA vaccines are able to elicit both antibody responses and cellular immune responses capable of mediating long-term protection. Great technical improvements have been made in dengue DNA vaccine constructs and trials are underway to study these in the clinic. The scope of this review is to highlight the rich history of this vaccine platform and the work in dengue DNA vaccines accomplished by scientists at the Naval Medical Research Center. This work resulted in the only dengue DNA vaccine tested in a clinical …

A Recombinant Hendra Virus G Glycoprotein-Based Subunit Vaccine Protects Ferrets From Lethal Hendra Virus Challenge, Jackie Pallister, Deborah Middleton, Lin-Fa Wang, Reuben Klein, Jessica Haining, Rachel Robinson, Manabu Yamada, John White, Jean Payne, Yan-Ru Feng, Yee-Peng Chan, Christopher C. Broder

Uniformed Services University of the Health Sciences

The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in …

Safety And Immunogenicity Of An Intranasal Shigella Flexneri 2a Invaplex 50 Vaccine, Mark S. Riddle, Robert W. Kaminski, Carlos Williams, Chad Porter, Shahida Baqar, Alexis Kordis, Theron Gilliland, Joyce Lapa, Melissa Coughlin, Chris Soltis, Erica Jones, Jackie Saunders, Paul B. Keiser, Ryan T. Ranallo, Robert Gormley, Michael Nelson, K. Ross Turbyfill, David Tribble, Edwin V. Oaks

Uniformed Services University of the Health Sciences

Background: Shigella flexneri 2a lipopolysaccharide 50 is a nasally delivered subunit vaccine consisting of a macromolecular complex composed of LPS, IpaB, IpaC and IpaD. The current study examined vaccine safety and immunogenicity across a dose range and the clinical performance of a new intranasal delivery device.

Methods: Volunteers (N = 36) were randomized to receive vaccine via the Dolphin^TM (Valois of America, Congers, New York) intranasal spray device at one of three doses (240, 480, and 690 μg) on days 0, 14, and 28. Another group (N = 8) received the 240 μg dose via pipette. Vaccine safety was …

Going Viral, Judy Diamond

World of Viruses

Science education is developing new and innovative means of communication that compete directly with global media to reach the ‘YouTube Generation’. The truly interdisciplinary team of the SEPA-funded World of Viruses project is discovering how best to spread the word.

KEY COLLABORATORS
Judy Diamond, Professor, University of Nebraska State Museum
Charles Wood, Director, Nebraska Center for Virology
Moira Rankin, President, Soundprint Media Center, Inc
Carl Zimmer, Science writer and author of WoV book of essays, A Planet of Viruses
David Uttal, Cognitive science professor, Northwestern University
Benjamin Jee, Cognitive scientist, College of Holy Cross
Tom Floyd, Comic illustrator, Nebraska Educational …

Purification Of A Recombinant Heavy Chain Fragment C Vaccine Candidate Against Botulinum Serotype C Neurotoxin [Rbontc(HC)] Expressed In Pichia Pastoris, Michael P. Dux, Jicai Huang, Rick Barent, Mehmet Inan, S. Todd Swanson, Jayanta Sinha, John T. Ross, Leonard A. Smith, Theresa J. Smith, Ian Henderson, Michael M. Meagher

United States Army: Publications

A purification process for the manufacture of a recombinant C-terminus heavy chain fragment from botulinum neurotoxin serotype C [rBoNTC(H_c)], a potential vaccine candidate, has been defined and successfully scaled-up. The rBoNTC(H_c) was produced intracellularly in Pichia pastoris X-33 using a three step fermentation process, i.e., glycerol batch phase, a glycerol fed-batch phase to achieve high cell densities, followed by a methanol induction phase. The rBoNTC(H_c) was captured from the soluble protein fraction of cell lysate using hydrophobic charge induction chromatography (HCIC; MEP HyperCel™), and then further purified using a CM 650M ion exchange chromatography …

Nematode Parasites Of Costa Rican Snakes (Serpentes) With Description Of A New Species Of Abbreviata (Physalopteridae), Charles R. Bursey, Daniel R. Brooks

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Seventy-eight snakes collected in the Area de Conservación Guanacaste, Costa Rica were necropsied: Boidae (1 species), boa constrictor, Boa constrictor; Colubridae (21 species), Ecuador sipo, Chironius grandisquamis; road guarder, Conophis lineatus; South American forest racer, Dendrophidion percarinatus; speckled racer, Drymobius margaritiferus; mimic false coral snake, Erythrolamprus mimus; blunthead tree snake, Imantodes cenchoa; western tree snake, Imantodes inornatus; banded cat-eyed snake, Leptodeira annulata; striped lowland snake, Leptodrymus pulcherrimus; Cope’s parrot snake, Leptophis depressirostris; yellow-bellied racer, Liophis epinephelus; neotropical whip snake, Masticophis mentovarius; brown vinesnake, Oxybelis aeneus; …

Plasmodium Falciparum Malaria Endemicity In Indonesia In 2010, Iqbal R.F. Elyazar, Peter W. Gething, Anand P. Patil, Hanifah Rogayah, Rita Kusriastuti, Desak M. Wismarini, Siti N. Tarmizi, J. Kevin Baird, Simon I. Hay

United States Public Health Resources

Background: Malaria control programs require a detailed understanding of the contemporary spatial distribution of infection risk to efficiently allocate resources. We used model based geostatistics (MBG) techniques to generate a contemporary map of Plasmodium falciparum malaria risk in Indonesia in 2010.

Methods: Plasmodium falciparum Annual Parasite Incidence (PfAPI) data (2006–2008) were used to map limits of P. falciparum transmission. A total of 2,581 community blood surveys of P. falciparum parasite rate (PfPR) were identified (1985–2009). After quality control, 2,516 were included into a national database of age-standardized 2–10 year old PfPR data (PfPR …

Radical Cure: The Case For Anti-Relapse Therapy Against All Malarias, J. Kevin Baird

United States Public Health Resources

Douglas et al [1] describe patency with Plasmodium vivax in the 63 days after treatment of malaria caused by Plasmodium falciparum in >10,000 subjects in Thailand over a 14-year period who received 25 different therapies. Therapy for acute malaria aims at the asexual stages of the organism infecting blood. Among the many blood schizontocidal drugs that achieve this therapeutic effect, none eliminate dormant stages in the liver, which are known as hypnozoites. Regardless of the species being treated, if hypnozoites are present, relapse may occur in the absence of treatment with primaquine, which is the only registered hypnozoitocide. The patients …

Landscape And Residential Variables Associated With Plague-Endemic Villages In The West Nile Region Of Uganda, Katherine Macmillan, Russell E. Enscore, Asaph Ogen- Odoi, Jeff N. Borchert, Nackson Babi, Gerald Amatre, Linda A. Atiku, Paul S. Mead, Kenneth L. Gage, Rebecca J. Eisen

United States Public Health Resources

Plague, caused by the bacteria Yersinia pestis , is a severe, often fatal disease. This study focuses on the plagueendemic West Nile region of Uganda, where limited information is available regarding environmental and behavioral risk factors associated with plague infection. We conducted observational surveys of 10 randomly selected huts within historically classified case and control villages (four each) two times during the dry season of 2006 ( N = 78 case huts and N = 80 control huts), which immediately preceded a large plague outbreak. By coupling a previously published landscape-level statistical model of plague risk with this observational survey, …

Factors Associated With Viral Rebound In Hiv-1-Infected Individuals Enrolled In A Therapeutic Hiv-1 Gag Vaccine Trial, Jonathan Z. Li, Zabrina L. Brumme, Chanson J. Brumme, Hongying Wang, John Spritzler, Michael N. Robertson, Michael M. Lederman, Mary Carrington, Bruce D. Walker, Rovert T. Schooley, Daniel R. Kuritzkes

United States Public Health Resources

Background. Human immunodeficiency virus type 1 (HIV-1) vaccines directed to the cell-mediated immune system could have a role in lowering the plasma HIV-1 RNA set point, which may reduce infectivity and delay disease progression.

Methods. Randomized, placebo-controlled trial involving HIV-1-infected participants who received a recombinant adenovirus serotype 5 (rAd5) HIV-1 gag vaccine or placebo. Sequence-based HLA typing was performed for all 110 participants who initiated analytic treatment interruption (ATI) to assess the role of HLA types previously associated with HIV prognosis. Plasma HIV-1 gag and pol RNA sequences were obtained during the ATI. Virologic endpoints and HLA groups …

Differential Microrna Regulation Of Hla-C Expression And Its Association With Hiv Control, Smita Kulkarni, Ram Savan, Ying Qi, Xiaojiang Gao, Yuko Yuki, Sara E. Bass, Maureen P. Martin, Peter Hunt, Steven G. Deeks, Amalio Telenti, Florencia Pereyra, David Goldstein, Steven Wolinsky, Bruce Walker, Howard A. Young, Mary Carrington

United States Public Health Resources

The HLA-C locus is distinct relative to the other classicalHLA class I loci in that it has relatively limited polymorphism1, lower expression on the cell surface, and more extensive ligand–receptor interactions with killer-cell immunoglobulin-like receptors. A single nucleotide polymorphism (SNP) 35 kb upstream of HLA-C (rs9264942; termed -35) associates with control of HIV, and with levels of HLA-C messenger RNA transcripts and cell-surface expression, but the mechanism underlying its varied expression is unknown. We proposed that the -35 SNP is not the causal variant for differential HLA-C expression, but rather is marking another polymorphism that directly affects levels of HLA-C. …

Hiv-1 Adaptation To Nk-Cell-Mediated Immune Pressure, Galit Alter, David Heckerman, Arne Schneidewind, Lena Fadda, Carl M. Kadie, Jonathan M. Carlson, Cesar Oniangue-Ndza, Maureen Martin, Bin Li, Salim I. Khakoo, Mary Carrington, Todd M. Allen, Marcus Altfeld

United States Public Health Resources

Natural killer (NK) cells have an important role in the control of viral infections, recognizing virally infected cells through a variety of activating and inhibitory receptors. Epidemiological and functional studies have recently suggested that NK cells can also contribute to the control of HIV-1 infection through recognition of virally infected cells by both activating and inhibitory killer immunoglobulin-like receptors (KIRs). However, it remains unknown whether NK cells can directly mediate antiviral immune pressure in vivo in humans. Here we describe KIR-associated amino-acid polymorphisms in the HIV-1 sequence of chronically infected individuals, on a population level. We show that these KIR-associated …

Hla-A*3101 And Carbamazepine-Induced Hypersensitivity Reactions In Europeans, Mark Mccormack, Ana Alfirevic, Stephane Bourgeois, John J. Farrell, Dalia Kasperavičiūtė, Mary Carrington, Graeme J. Sills, Tony Marson, Xiaoming Jia, Paul I. W. De Bakker, Krishna Chinthapalli, Mariam Molokhia, Michael R. Johnson, Gerard D. O'Connor, Elijah Chaila, Saud Alhusaini, B. Kevin Park, Chantal Depondt, Sanjay M. Sisodiya, David B. Goldstein, Panos Deloukas, Norman Delanty, Gianpiero L. Cavalleri, Munir Pirmohamed, Werner Pichler, Kevin V. Shianna, Rodney A. Radtke, Massimo Pandolfo

United States Public Health Resources

Background

Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese and other Asian populations but not in European populations.

Methods

We performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine- induced maculopapular exanthema, and 3987 control subjects, all of European descent. We tested for an association between disease and HLA alleles through proxy single-nucleotide polymorphisms and imputation, confirming associations by high-resolution …

Persistent Infection Or Successive Reinfection Of Deer Mice With Bartonella Vinsonii Subsp. Arupensis, Ying Bai, Charles H. Calisher, Michael Y. Kosoy, J. Jeffrey Root, Jeffrey B. Doty

United States Public Health Resources

Bartonella infections are common in rodents. From 1994 to 2006, longitudinal studies of a rodent community, consisting mainly of deer mice (Peromyscus maniculatus), were conducted in southwestern Colorado to study hantaviruses. Blood samples from deer mice captured one or more times during the period 2003 to 2006 (n = 737) were selected to study bartonellae in deer mice. Bartonellae were found to be widely distributed in that population, with an overall prevalence of 82.4% (607/737 mice). No correlation was found between bartonella prevalence and deer mouse weight or sex. Persistent or successive infections with bartonellae were observed …

Comparison Of Genomic And Proteomic Data In Recurrent Airway Obstruction Affected Horses Using Ingenuity Pathway Analysis®, Julien Racine, Vinzenz Gerber, Marybeth Miskovic Feutz, C. Paige Riley, Jiri Adamec, June E. Swinburne, Laurent L. Couetil

Department of Biochemistry: Faculty Publications

Background: Recurrent airway obstruction (RAO) is a severe chronic respiratory disease affecting horses worldwide, though mostly in the Northern hemisphere. Environmental as well as genetic factors strongly influence the course and prognosis of the disease. Research has been focused on characterization of immunologic factors contributing to inflammatory responses, on genetic linkage analysis, and, more recently, on proteomic analysis of airway secretions from affected horses. The goal of this study was to investigate the interactions between eight candidate genes previously identified in a genetic linkage study and proteins expressed in bronchoalveolar lavage fluid (BALF) collected from healthy and RAO-affected horses. The …