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Comparative Proteome Analysis Of Brucella Melitensis Vaccine Strain Rev 1 And A Virulent Strain, 16m, Michel Eschenbrenner, Mary Ann Wagner, Troy A. Horn, Jo Ann Kraycer, Cesar V. Mujer, Sue Hagius, Philip Elzer, Vito G. Delvecchio

Faculty Publications

The genus Brucella consists of bacterial pathogens that cause brucellosis, a major zoonotic disease characterized by undulant fever and neurological disorders in humans. Among the different Brucella species, Brucella melitensis is considered the most virulent. Despite successful use in animals, the vaccine strains remain infectious for humans. To understand the mechanism of virulence in B. melitensis, the proteome of vaccine strain Rev 1 was analyzed by two-dimensional gel electrophoresis and compared to that of virulent strain 16M. The two strains were grown under identical laboratory conditions. Computer-assisted analysis of the two B. melitensis proteomes revealed proteins expressed in either 16M …

Thin Laser Light Sheet Microscope For Microbial Oceanography, Eran Fuchs, Jules S. Jaffe, Richard A. Long, Farooq Azam

Faculty Publications

Despite a growing need, oceanographers are limited by existing technological constrains and are unable to observe aquatic microbes in their natural setting. In order to provide a simple and easy to implement solution for such studies, a new Thin Light Sheet Microscope (TLSM) has been developed. The TLSM utilizes a well-defined sheet of laser light, which has a narrow (23 micron) axial dimension over a 1 mm x 1 mm field of view. This light sheet is positioned precisely within the depth of field of the microscope’s objective lens. The technique thus utilizes conventional microscope optics but replaces the illumination …

Disability, Employment Policy, And The Supreme Court, Michael Ashley Stein

Faculty Publications

No abstract provided.

Glycoprotein K Specified By Herpes Simplex Virus Type 1 Is Expressed On Virions As A Golgi Complex-Dependent Glycosylated Species And Functions In Virion Entry, T. P. Foster, G. V. Rybachuk, K. G. Kousoulas

Faculty Publications

To facilitate detection of glycoprotein K (gK) specified by herpes simplex virus, a 12-amino-acid epitope tag was inserted within gK domain III. Recombinant virus gKprotC-DIII, expressing the tagged gK, was isolated. This virus formed wild-type plaques and replicated as efficiently as the wild-type KOS virus in Vero cells. Anti-protein C MAb detected high-mannose and Golgi complex-dependent glycosylated gK within cells as well as on purified virions. The gK-null virus ΔgK (gK-/-) entered Vero cells substantially more slowly than the wild-type KOS (gK+/+), while ΔgK virus grown in complementing VK302 cells (gK-/+) entered with entry kinetics similar to those of the …

Microscale Patchiness Of Bacterioplankton Assemblage Richness In Seawater, Richard A. Long, Farooq Azam

Faculty Publications

We sought to test the hypothesis that bacterial species richness and composition vary at the millimeter scale in the marine pelagic environment, in response to the heterogeneous distribution of organic matter. To test this hypothesis, it was necessary to design and test a protocol to sample, lyse and analyze (by polymerase chain reaction/denaturing gradient gel electrophoresis [PCR-DGGE]) bacterioplankton species richness in a single microliter of seawater. Significant variation in bacterial species richness was found amongst 1 μl samples. Greater species richness was seen when seawater was enriched with diatom detritus. Examination of species richness at 2 mm intervals over a …

Fusobacteriosis In Captive Wild-Caught Pronghorns (Antilocapra Americana), J. F. Edwards, D. S. Davis, T. J. Roffe, F. Ramiro-Ibañez, P. H. Elzer

Faculty Publications

An outbreak of Fusobacterium necrophorum-induced septicemia occurred in a group of 40 captive wild-caught pronghorns (Antilocapra americana). Primary pododermatitis or necrotic stomatitis progressed to produce fatal septicemia with metastatic lesions in the forestomachs, lung, liver, and cecum in 38 of the animals. Two remaining animals were euthanatized because of chronic pododermatitis. Housing the animals in a pasture previously used by bovids and heavy rains with persistence of ground water pools in the pasture were contributing factors in the pathogenesis of this outbreak.

An Α-Helical Domain Within The Carboxyl Terminus Of Herpes Simplex Virus Type 1 (Hsv-1) Glycoprotein B (Gb) Is Associated With Cell Fusion And Resistance To Heparin Inhibition Of Cell Fusion, Timothy P. Foster, Jeff M. Melancon, Konstantin G. Kousoulas

Faculty Publications

Previous studies from our laboratory indicated that a 28-amino-acid carboxyl-terminal truncation of gB caused extensive virus-induced cell fusion (Baghian et al., 1993, J Virol 67, 2396-2401). We tested the ability of additional truncations and mutations within gB to cause cell fusion in the recently established virus-free cell fusion assay (Turner et al., 1998, J. Virol. 72, 873-875). Deletion of the carboxyl-terminal 28 amino acids of gB (gBΔ28), which removed part of the predicted α-helical structure H17b, caused extensive cell fusion. A gB truncation specified by gBΔ36, which removed the entire H17b domain, caused as much cell fusion as the gBΔ28 …

The Use Of Placebos In Clinical Trials: Responsible Research Or Unethical Practice?, Sharona Hoffman

Faculty Publications

Developments in medical research have been occurring at a rapidly increasing rate during the past two decades. Expanding budgets, augmented computer capabilities, and new research tools have all dramatically enhanced research technology. Accompanying the proliferation of medical research are increasing concerns about research risks. This article focuses on placebo-controlled clinical trials. The use of placebos enables clinical investigators to compare results from subjects taking an experimental intervention to results from a group that is receiving an inactive substance, such as a sugar pill, in order to determine the efficacy of the new medication. In recent years, some surgeons have also …

Rickettsia Felis: Molecular Characterization Of A New Member Of The Spotted Fever Group, D. H. Bouyer, J. Stenos, P. Crocquet-Valdes, C. G. Moron, V. L. Popov, J. E. Zavala-Velazquez, L. D. Foil, D. R. Stothard, A. F. Azad, D. H. Walker

Faculty Publications

In this report, placement of Rickettsia felis in the spotted fever group (SFG) rather than the typhus group (TG) of Rickettsia is proposed. The organism, which was first observed in cat fleas (Ctenocephalides felis) by electron microscopy, has not yet been reported to have been cultivated reproducibly, thereby limiting the standard rickettsial typing by serological means. To overcome this challenge, several genes were selected as targets to be utilized for the classification of R. felis. DNA from cat fleas naturally infected with R. felis was amplified by PCR utilizing primer sets specific for the 190 kDa surface antigen (rOmpA) and …

Human Immunodeficiency Virus Type 1 Quasi Species That Rebound After Discontinuation Of Highly Active Antiretroviral Therapy Are Similar To The Viral Quasi Species Present Before Initiation Of Therapy, Keith A. Crandall, Hiromi Imamichi, Ven Natarajan, Min Kang Jiang, Robin L. Dewar, Steve Berg, Arunasri Gaddam, Marjorie Bosche, Julie A. Metcalf, Richard T. Davey Jr., H. Clifford Lane

Faculty Publications

In an effort to identify the sources of the viruses that emerge after discontinuation of therapy, analyses of human immunodeficiency virus (HIV) quasi species were done for 3 patients with sustained levels of HIV RNA of <50 copies/mL for 1-3 years. The sequences found in the rebounding plasma virus were closely related to those of the actively replicating form of viruses present before the initiation of combination therapy. All quasi species found in the rebounding plasma virus were also present in proviral DNA, cell-associated RNA in peripheral blood mononuclear cells (PBMC), and virion RNA derived from PBMC coculture during periods when plasma HIV RNA levels were <50 copies/mL. These findings suggest that the rapid resurgence of plasma viremia observed after discontinuation of therapy and the viruses cocultured from PBMC are derived from a relatively stable pool of the replicating form of virus rather than from activation of a previously latent pool.

Nonsteroidal Anti-Inflammatory Drugs, Acetaminophen, Cyclooxygenase 2, And Fever, Daniel L. Simmons, David Wagner, Kenneth Westover

Faculty Publications

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used antipyretic agents that most probably exert their antifever effect by inhibiting cyclooxygenase (COX)–2. Thus, COX-2–selective drugs or null mutation of the COX-2 gene reduce or prevent fever. Acetaminophen is antipyretic and analgesic, as are NSAIDs, but it lacks the anti-inflammatory and anticoagulatory properties of these drugs. This has led to the speculation that a COX variant exists that is inhibitable by acetaminophen. An acetaminophen-inhibitable enzyme is inducible in the mouse J774.2 monocyte cell line. Induction of acetaminophen-inhibitable prostaglandin E2 synthesis parallels induction of COX-2. Thus, inhibition of pharmacologically distinct COX-2 enzyme activity by …

Beneficial And Unusual Punishment: An Argument In Support Of Prisoner Participation In Clinical Trials, Sharona Hoffman

Faculty Publications

Currently, approximately 1.8 million people are incarcerated in the United States at any given time. A disproportionately large percentage of the prisoner population has serious illnesses, such as AIDS and tuberculosis. Prisoners most often, however, are barred from participation in clinical trials, even when conventional therapy has failed, and experimental treatment might provide them with their only hope of survival.

Much of the reluctance to include prisoners in biomedical research is based on history. In the past, prisoners have been severely abused and even tortured in medical studies conducted in the Nazi death camps, Japanese prisoner camps, and correctional facilities …

Cd8+ Cytotoxic T Lymphocyte Responses To Lytic Proteins Of Human Herpes Virus 8 In Human Immunodeficiency Virus Type 1-Infected And -Uninfected Individuals, Qiong J. Wang, Frank J. Jenkins, Lisa P. Jacobson, Yuan Xiang Meng, Philip E. Pellett, Lawrence A. Kingsley, Konstantin G. Kousoulas, Abolghasem Baghian, Charles R. Rinaldo

Faculty Publications

T cell immunity to lytic proteins of herpesviruses is important in host control of infection. We have characterized the cytotoxic T lymphocyte (CTL) response to 5 human herpesvirus 8 (HHV-8) homologues of lytic proteins in HHV-8-seropositive individuals. HLA class I-restricted, CD8+ CTL responses to ≥1 HHV-8 lytic protein were detected in all 14 HHV-8-seropositive study subjects tested, with or without human immunodeficiency virus type 1 (HIV-1) infection, but not in any of 5 HHV-8-seronegative individuals. Seven of these study subjects with both HHV-8 and HIV-1 infection had greater anti-CTL reactivity to glycoprotein H (open-reading frame 22) than did the 7 …

A Multiplex Approach To Molecular Detection Of Brucella Abortus And/Or Mycobacterium Boris Infection In Cattle, Srinand Sreevatsan, Jack B. Bookout, Fidel Ringpis, Veera S. Perumaalla, Thomas A. Ficht, L. Garry Adams, Sue D. Hagius, Philip H. Elzer, Betsy J. Bricker, Girish K. Kumar, M. Rajasekhar, Srikrishna Isloor, Raj R. Barathur

Faculty Publications

A multiplex amplification and detection platform for the diagnosis of Mycobacterium bovis and Brucella abortus infection simultaneously in bovine milk and nasal secretions was developed. This system (designated the bovine pathogen detection assay [BPDA]-PCR) consists of duplex amplification of species-specific targets (a region of the BCSP31K gene of B. abortus and a repeat-sequence region in the hsp65 gene of M. bovis, respectively). This is followed by a solid-phase probe capture hybridization of amplicons for detection. On the basis of spiking experiments with normal milk, the analytical sensitivity of the assay was 800 CFU equivalents/ml of milk for B. abortus and …

Is Malnutrition Declining? An Analysis Of Changes In Levels Of Childhood Malnutrition Since 1980, Mercedes De Onis, Edward A. Frongillo Jr., Monika Blo¨ Ssner

Faculty Publications

Nutritional status is the best global indicator of well-being in children. Although many surveys of children have been conducted since the 1970s, lack of comparability between them has made it difficult to monitor trends in child malnutrition.

Cross-sectional data from 241 nationally representative surveys were analysed in a standard way to produce comparable results of low height-for-age (stunting). Multilevel modelling was applied to estimate regional and global trends from 1980 to 2005.

The prevalence of stunting has fallen in developing countries from 47% in 1980 to 33% in 2000 (i.e. by 40 million), although progress has been uneven according to …

Zooarchaeology, Susan L. Scott

Faculty Publications

No abstract provided.

Seeking Causal Explanations In Social Epidemiology, Jay S. Kaufman, Richard S. Cooper

Faculty Publications

Social factors are associated with a wide variety of health outcomes. Social epidemiology has successfully used the traditional methods of surveillance and description to establish consistent relations between social factors and health status. Epidemiology as an etiologic science, however, has been largely ineffective in moving toward causal explanations for these observed patterns. Using the counterfactual approach to causal inference, the authors describe several fundamental problems that often arise when researchers seek to infer explanatory mechanisms from data on social factors. Contrasts that form standard causal effect estimates require implicit unobserved (counterfactual) quantities, because observational data provide only one exposure state …

Co-Infection With Opportunistic Pathogens Promotes Human Immunodeficiency Virus Type 1 Infection In Macrophages, Sharon M. Wahl, Teresa Greenwell-Wild, Gang Peng, Hollie Hale-Donze, Jan M. Orenstein

Faculty Publications

Human immunodeficiency virus type 1 (HIV-1) infection is dependent on susceptible host cells that express both CD4 and chemokine co-receptors. The co-receptor CCR5 is associated with primary infection by macrophage-tropic virus isolates, whereas CXCR4 is commonly associated with T cell- and dual- tropic viruses. Once infected, lymphocytes and macrophages may replicate HIV- 1 or harbor latent virus, depending on environmental factors and cellular activation. Immune activation is often associated with viremia, which is consistent with enhanced infection and viral replication in activated cells harboring virus. In this regard, opportunistic infections activate the immune system with the detrimental sequelae of enhanced …

A Comparison Of The Use Of Tympanic, Axillary, And Rectal Thermometers In Infants, Russell Wilshaw, Renea L. Beckstrand, Dawn Waid, Bruce Schaallje

Faculty Publications

This study examined the relationship between three instruments used in measuring tympanic, axillary, and rectal temperatures in infants less than 1 year of age. Temperatures were measured by Oto-temp Pedi Q tympanic thermometers, Becton Dickinson axillary thermometer, and rectal thermometers. A convience sample of 5 infants less than 90 day and 54 greater than 90 days with fever, as well as 34 infants less than 90 days and 27 infants greater than 90 days without fever were studied. Correlations of infants less than 90 days and greater 90 days of age, as well as differences between infant temperature with and …

Acute Clinical Disease In Cats Following Infection With A Pathogenic Strain Of Bartonella Henselae (Lsu16), Kathy L. O'Reilly, Rudy W. Bauer, Rebecca L. Freeland, Lane D. Foil, Keith J. Hughes, Kristen R. Rohde, Alma F. Roy, Rhett W. Stout, Patricia C. Triche

Faculty Publications

Bartonella henselae is the causative agent of human cat scratch disease as well as several serious sequelae of infections, including bacillary angiomatosis and bacillary peliosis. Conflicting reports describe the pathogenesis of B. henselae in the cat. In this study, we characterized a strain of B. henselae termed LSU16. This strain was isolated on rabbit blood agar from a naturally infected 10-month-old female cat during a recurrent episode of bacteremia. The bacterial species was confirmed by PCR- restriction fragment length polymorphism analysis. Nine cats were infected intradermally with 5 x 107 CFU of LSU16, and clinical signs, antibody responses, and bacteremia …

Patient Safety, Risk Reduction, And The Law, Larry I. Palmer

Faculty Publications

No abstract provided.

Mycobacterium Avium Complex Augments Macrophage Hiv-1 Production And Increases Ccr5 Expression, S. M. Wahl, T. Greenwell-Wild, G. Peng, H. Hale-Donze, T. M. Doherty, D. Mizel, J. M. Orenstein

Faculty Publications

Infection with HIV-1 results in pronounced immune suppression and susceptibility to opportunistic infections (OI). Reciprocally, OI augment HIV-1 replication. As we have shown for Mycobacterium avium complex (MAC) and Pneumocystis carinii, macrophages infected with opportunistic pathogens and within lymphoid tissues containing OI, exhibit striking levels of vital replication. To explore potential underlying mechanisms for increased HIV-1 replication associated with coinfection, blood monocytes were exposed to MAC antigens (MAg) or viable MAC and their levels of tumor necrosis factor α (TNFα) and HIV-1 coreceptors monitored. MAC enhanced TNFα production in vitro, consistent with its expression in coinfected lymph nodes. Using a …

Mortality Data For Sub-Saharan Africa [10], R. S. Cooper, C. Rotimi, J. Kaufman, T. Lawoyin

Faculty Publications

No abstract provided.

Major Histocompatibility Complex Class I- And Ii-Deficient Knock-Out Mice Are Resistant To Primary But Susceptible To Secondary Eimeria Papillata Infections, Marco L. Schito, Bill Chobotar, John R. Barta

Faculty Publications

Two distinct mechanisms seem to function in reducing oocyst output during Eimeria papillata infections in mice. For naive mice, immunity was afforded by a T-cell-independent gamma-interferon (IFN-γ) response mediated by natural killer (NK) cells. On reinfection, resistance was associated with T-cells and, to a lesser extent, perforin. To determine if antigen presentation with major histocompatibility complex (MHC) molecules was required to control oocyst production by NK cells during primary infection or by T-cells during secondary infection, mutant mice that lacked H2-IAβb (Aβb(-/-)) or β2-microglobulin (β2m(-/-)) were used. Since MHC molecules are required for the maturation of αβ T-cells, Aβb(-/-) and …

Cryptococcus Neoformans Chemotyping By Quantitative Analysis Of H-1 Nuclear Magnetic Resonance Spectra Of Glucuronoxylomannans With A Computer-Simulated Artificial Neural Network, Robert Cherniak, Homayoun Valafar, Laura C. Morris, Faramarz Valafar

Faculty Publications

The complete assignment of the proton chemical shifts obtained by nuclear magnetic resonance (NMR) spectroscopy of de-O-acetylated glucuronoxylomannans (GXMs) from Cryptococcus neoformanspermitted the high-resolution determination of the total structure of any GXM. Six structural motifs based on an α-(1→3)-mannotriose substituted with variable quantities of 2-O-β- and 4-O-β-xylopyranosyl and 2-O-β-glucopyranosyluronic acid were identified. The chemical shifts of only the anomeric protons of the mannosyl residues served as structure reporter groups (SRG) for the identification and quantitation of the six triads present in any GXM. The assigned protons for the mannosyl residues resonated at clearly …

Hypertension Treatment And Control In Sub-Saharan Africa: The Epidemiological Basis For Policy, Richard S. Cooper, Charles N. Rotimi, Jay S. Kauftnan, Walinjom F.T. Muna, George A. Mensah

Faculty Publications

No abstract provided.

Emergence Of Western Diseases In The Tropical World: The Experience With Chronic Cardiovascular Diseases, Terrence Forrester, Richard S. Cooper, David Weatherall

Faculty Publications

Our knowledge of the disease burden components of tropical populations is fragmentary. Historically, the infectious diseases have been emphasized but, as some populations have undergone socio-economic changes, vital statistics have described a change in the pattern of disease. The picture is of a decline in infectious and a rise in chronic non-communicable disease. We focus here on the emergence of chronic cardiovascular diseases, and use hypertension as the paradigmic example. Early blood pressure surveys showed a virtual absence of hypertension among rural Africans and moderate prevalences in the Caribbean. Prevalence was highest among US and UK blacks. In a recent …

Landscape Change And Livestock In Sixteenth-Century New Spain: The Archival Data Base, Andrew Sluyter

Faculty Publications

Despite the wealth of Mexican archival data pertinent to understanding the ecological interaction between livestock and landscape during the sixteenth century in New Spain, some fundamental methodological issues persist in the use of the mercedes, or land grants. The degree of completeness of the extant mercedes record and the de facto areal extents of the cattle and sheep estancias both remain uncertain. A cartographic method applied to mercedes for the central Veracruz lowlands addresses those issues and suggests a general method for rigorous analysis of the data base. That method demonstrates that the extant mercedes provide a nearly complete record …

The Htra Stress Response Protease Contributes To Resistance Of Brucella Abortus To Killing By Murine Phagocytes, Philip H. Elzer, Robert W. Phillips, Gregory T. Robertson, R. Martin Roop

Faculty Publications

Compared with virulent Brucella abortus 2308, the isogenic htrA mutant PHE1 shows decreased resistance to killing by cultured murine neutrophils and macrophages and significant attenuation during the early stages of infection in the BALB/c mouse model. These findings further define the contributions of the htrA gene product to the pathogenesis of B. abortus infections.

Test Wars: Mandatory Hiv Testing, Women, And Their Children, Michelle Oberman

Faculty Publications

No abstract provided.