Medical Specialties Commons^™

Merkel Cell Carcinoma, Cynthia L. Bartus Md, Steven Oberlender Md, Phd, Christian W. Oram Do

Department of Medicine

No abstract provided.

A Genome-Wide Methylation Study On Essential Hypertension In Young African American Males., Xiaoling Wang, Bonita Falkner, Haidong Zhu, Huidong Shi, Shaoyong Su, Xiaojing Xu, Ashok Kumar Sharma, Yanbin Dong, Frank Treiber, Bernard Gutin, Gregory Harshfield, Harold Snieder

Department of Medicine Faculty Papers

OBJECTIVE: There is emerging evidence from animal studies suggesting a key role for methylation in the pathogenesis of essential hypertension. However, to date, very few studies have investigated the role of methylation in the development of human hypertension, and none has taken a genome-wide approach. Based on the recent studies that highlight the involvement of inflammation in the development of hypertension, we hypothesize that changes in DNA methylation of leukocytes are involved in the pathogenesis of hypertension.

METHOD & RESULTS: We conducted a genome-wide methylation analysis on 8 hypertensive cases and 8 normotensive age-matched controls aged 14-23 years and performed …

Optic Neuritis Due To Toxoplasmosis: First And Only Manifestation Of Newly Diagnosed Aids, Rajesh Kumar Md, Yehia Y. Mishriki Md

Department of Medicine

No abstract provided.

Effect Of Blood Collection Practices On Emergency Department Blood Specimen Rejection Rates, Barbara K. Vernoski

UNF Graduate Theses and Dissertations

The practice of obtaining blood as part of the placement of a new peripheral venous access device (p-VAD) is a frequent practice in the emergency department (ED). Of the concerns related to this practice is the possibility of laboratory specimen rejection due to p-VAD catheter size, use of the wrong collection device, and the absence of a standardized collection process. The objective of this study, therefore, was to examine the effect of the use of evidence-based venipuncture and p-VAD blood collection protocols on the rejection rate of blood specimens drawn by staff in the adult areas of an urban academic …

Characterization Of Brer Interaction With The Bile Response Promoters Breab And Brer In Vibrio Cholerae, Francisca A. Cerda-Maira, Gabriela Kovacikova, Brooke A. Jude, Karen Skorupski, Ronald Taylor

Dartmouth Scholarship

The Vibrio cholerae BreR protein is a transcriptional repressor of the breAB efflux system operon, which encodes proteins involved in bile resistance. In a previous study (F. A. Cerda-Maira, C. S. Ringelberg, and R. K. Taylor, J. Bacteriol. 190:7441-7452, 2008), we used gel mobility shift assays to determine that BreR binds at two independent binding sites at the breAB promoter and a single site at its own promoter. Here it is shown, by DNase I footprinting and site-directed mutagenesis, that BreR is able to bind at a distal and a proximal site in the breAB promoter. However, only one of …

Recent Advances On The Use Of Structural Biology For The Design Of Novel Envelope Immunogens Of Hiv-1, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Many efforts have been made in the worldwide quest for a prophylactic HIV vaccine to end the AIDS pandemic, but none has yet succeeded. The lessons learned have repeatedly informed us that the traditional or conventional approaches directly using the pathogens or subunits will not be sufficient for an effective HIV/AIDS vaccine. Recent advances in structure-based technology have shown some promise in the quest for a better immunogen in HIV vaccine development. According to the basic binding structural relationship of an antigen and an antibody, structure-based antigen design could bring some hope for the development of an effective vaccine against …

The Highly Conserved Layer-3 Component Of The Hiv-1 Gp120 Inner Domain Is Critical For Cd4-Required Conformational Transitions, Anik Désormeaux, Mathieu Coutu, Halima Medjahed, Beatriz Pacheco, Alon Herschhorn, Christopher Gu, Shi-Hua Xiang, Youdong Mao, Joseph Sodroski, Andrés Finzi

Nebraska Center for Virology: Faculty Publications

The trimeric envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) mediates virus entry into host cells. CD4 engagement with the gp120 exterior envelope glycoprotein subunit represents the first step during HIV-1 entry. CD4-induced conformational changes in the gp120 inner domain involve three potentially flexible topological layers (layers 1, 2, and 3). Structural rearrangements between layer 1 and layer 2 have been shown to facilitate the transition of the envelope glycoprotein trimer from the unliganded to the CD4-bound state and to stabilize gp120-CD4 interaction. However, our understanding of CD4-induced conformational changes in the gp120 inner domain remains incomplete. Here, …

Analysis Of Primary Resistance Mutations To Hiv-1 Entry Inhibitors In Therapy Naive Subtype C Hiv-1 Infected Mother– Infant Pairs From Zambia, Hongyan Guo, Chang Liu, Bin Liu, Charles Wood, Xiaohong Kong

Nebraska Center for Virology: Faculty Publications

Background—Small molecular CCR5 inhibitors represent a new class of drugs for treating HIV-1 infection. The evaluation of the primary resistance mutations associated with entry inhibitors during HIV-1 perinatal transmission is required because they may have a profound impact on the clinical management in MTCT.

Objectives—To evaluate the primary resistance mutations to maraviroc and vicriviroc during perinatal transmission and analyze the sensitivity of Env derived from mother–infant pairs to maraviroc.

Study design—Nine MIPs infected by subtype C HIV-1 were recruited to analyze the prevalence and transmission of primary resistance mutations to maraviroc and vicriviroc. Moreover, Env derived from six MIPs were …

Early Childhood Infection Of Kaposi’S Sarcoma-Associated Herpesvirus In Zambian Households: A Molecular Analysis, Landon Olp, Danielle M. Shea, Maxine K. White, Clement Gondwe, Chipepo Kankasa, Charles Wood

Nebraska Center for Virology: Faculty Publications

Sub-Saharan Africa is endemic for Kaposi’s sarcoma-associated herpesvirus (KSHV) and there is a high rate of early childhood infection; however, the transmission sources are not well characterized. We examined household members as potential KSHV transmission sources to young children in the KSHV-endemic country of Zambia. To this end, we enrolled and followed Zambian households with at least one KSHV-seropositive child and collected longitudinal buccal swab samples. KSHV burden was evaluated and K1 sequences from the children were determined and analyzed for differences to K1 sequences from household members. The K1 sequences were also analyzed for evolution over time. We generated …

Towards Defining The Chloroviruses: A Genomic Journey Through A Genus Of Large Dna Viruses, Adrien Jeanniard, David D. Dunigan, James Gurnon, Irina V. Agarkova, Ming Kang, Jason Vitek, Garry Duncan, O William Mcclung, Megan Larsen, Jean-Michel Claverie, James L. Van Etten, Guillaume Blanc

Nebraska Center for Virology: Faculty Publications

Background: Giant viruses in the genus Chlorovirus (family Phycodnaviridae) infect eukaryotic green microalgae. The prototype member of the genus, Paramecium bursaria chlorella virus 1, was sequenced more than 15 years ago, and to date there are only 6 fully sequenced chloroviruses in public databases. Presented here are the draft genome sequences of 35 additional chloroviruses (287 – 348 Kb/319 – 381 predicted protein encoding genes) collected across the globe; they infect one of three different green algal species. These new data allowed us to analyze the genomic landscape of 41 chloroviruses, which revealed some remarkable features about these viruses. …

Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

With growing industrial interest in algae plus their critical roles in aquatic systems, the need to understand the effects of algal pathogens is increasing. We examined a model algal host–virus system, Chlorella variabilis NC64A and virus, PBCV-1. C. variabilis encodes 375 homologs to genes involved in RNA silencing and in response to virus infection in higher plants. Illumina RNA-Seq data showed that 325 of these homologs were expressed in healthy and early PBCV-1 infected (≤60 min) cells. For each of the RNA silencing genes to which homologs were found, mRNA transcripts were detected in healthy and infected cells. C. variabilis …

A Twin-Cysteine Motif In The V2 Region Of Gp120 Is Associated With Siv Envelope Trimer Stabilization, Christopher Bohl, Dane Bowder, Jesse Thompson, Levon Abrahamyan, Sandra Gonzalez-Ramirez, Youdong Mao, Joseph Sodroski, Charles Wood, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The V1 and V2 variable regions of the primate immunodeficiency viruses contribute to the trimer association domain of the gp120 exterior envelope glycoprotein. A pair of V2 cysteine residues at 183 and 191 (‘‘twin cysteines’’) is present in several simian immunodeficiency viruses, human immunodeficiency virus type 2 (HIV-2) and some SIV_cpz lineages, but not in HIV-1. To examine the role of this potentially disulfide-bonded twin-cysteine motif, the cysteine residues in the SIVmac239 envelope glycoproteins were individually and pairwise substituted by alanine residues. All of the twin-cysteine mutants exhibited decreases in gp120 association with the Env trimer, membrane-fusing activity, and …

Hiv-1 Env C2-V4 Diversification In A Slow-Progressor Infant Reveals A Flat But Rugged Fitness Landscape, S. Abigail Smith, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type-1 (HIV-1) fitness has been associated with virus entry, a process mediated by the envelope glycoprotein (Env). We previously described Env genetic diversification in a Zambian, subtype C infected, slow-progressor child (1157i) in parallel with an evolving neutralizing antibody response. Because of the role the Variable-3 loop (V3) plays in transmission, cell tropism, neutralization sensitivity, and fitness, longitudinally isolated 1157i C2-V4 alleles were cloned into HIV-1_NL4-3-eGFP and -DsRed2 infectious molecular clones. The fluorescent reporters allowed for dual-infection competitions between all patient-derived C2-V4 chimeras to quantify the effect of V3 diversification and selection on fitness. ‘Winners’ …

‘‘Megavirales’’, A Proposed New Order For Eukaryotic Nucleocytoplasmic Large Dna Viruses, Philippe Colson, Xavier De Lamballerie, Natalya Yutin, Sassan Asgari, Yves Bigot, Dennis K. Bideshi, Xiao-Wen Cheng, Brian A. Federici, James L. Van Etten, Eugene V. Koonin, Bernard La Scola, Didier Raoult

Nebraska Center for Virology: Faculty Publications

The nucleocytoplasmic large DNA viruses (NCLDVs) comprise a monophyletic group of viruses that infect animals and diverse unicellular eukaryotes. The NCLDV group includes the families Poxviridae, Asfarviridae, Iridoviridae, Ascoviridae, Phycodnaviridae, Mimiviridae and the proposed family ‘‘Marseilleviridae’’. The family Mimiviridae includes the largest known viruses, with genomes in excess of one megabase, whereas the genome size in the other NCLDV families varies from 100 to 400 kilobase pairs. Most of the NCLDVs replicate in the cytoplasm of infected cells, within so-called virus factories. The NCLDVs share a common ancient origin, as demonstrated by evolutionary reconstructions that trace approximately 50 genes encoding …

Corneal Gene Therapy: Basic Science And Translational Perspective, Rajiv R. Mohan, Jason T. Rodier, Ajay Sharma

Pharmacy Faculty Articles and Research

Corneal blindness is the third leading cause of blindness worldwide. Gene therapy is an emerging technology for corneal blindness due to the accessibility and immune-privileged nature of the cornea, ease of vector administration and visual monitoring, and ability to perform frequent noninvasive corneal assessment. Vision restoration by gene therapy is contingent upon vector and mode of therapeutic gene introduction into targeted cells/tissues. Numerous efficacious vectors, delivery techniques, and approaches have evolved in last decade for developing gene-based interventions for corneal diseases. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, …

St-Segment Elevation (Stemi) Real Time Data Feedback –A Process Of Care Initiative, Orlando E. Rivera Rn, Nainesh Patel Md, Bruce Feldman Do, Mercedes Rios-Scott Bs, David M. Richardson Md, J Patrick Kleaveland Md, David A. Cox Md, Ronald S. Freudenberger Md

Department of Medicine

No abstract provided.

Rapid Door To Balloon Time In The Treatment Of Acute St-Elevation Myocardial Infarction Is Associated With Reduced Length Of Hospital Stay, Amit Nanavati Md, David A. Cox Md, J Patrick Kleaveland Md, Orlando E. Rivera Rn, Nainesh Patel Md

Department of Medicine

No abstract provided.

Visualization And Management Of A Distally Embolized Stent After St-Elevation Myocardial Infarction, Amit Nanavati Md, Nainesh C. Patel Md

Department of Medicine

No abstract provided.

Endovascular Management Of Aortoiliac Occlusive Disease, Nitin Verma Md, Amit Nanavati Md, Bryan W. Kluck Do

Department of Medicine

No abstract provided.

Austrian Syndrome: Triad Of The Past Or Harbinger Of The Future?, Mira Mitry Md, Suzanne J. Templer Do, Stacey Smith Md, Facp, Eugene P. York Md, Facp

Department of Medicine

No abstract provided.

Secondary Cutaneous Plasmacytoma In A Patient With Multiple Myeloma, Joshua M. Levin Md, Christian W. Oram Do

Department of Medicine

No abstract provided.

Interrupted Aortic Arch In The Adult, Amit Nanavati Md, Matthew W. Martinez, Nainesh Patel Md

Department of Medicine

No abstract provided.

Pseudo Hyperphosphatemia In Multiple Myeloma, Anshul Kumar, Pradeep Dhakarwal Md, Vibha Agrawal, Tayyab Ali

Department of Medicine

No abstract provided.

Impairment Of Trkb-Psd-95 Signaling In Angelman Syndrome, Cong Cao, Mengia S. Rioult-Pedotti, Paolo Migani, Crystal J. Yu, Rakesh Tiwari, Keykavous Parang, Mark R. Spaller, Dennis J. Goebel, John Marshall

Pharmacy Faculty Articles and Research

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) …

Targeted Disruption Of Adamts16 Gene In A Rat Genetic Model Of Hypertension, Kathirvel Gopalakrishnan, Sivarajan Kumarasamy, Shakila Abdul-Majeed, Andrea L. Kalinoski, Eric E. Morgan, Amira F. Gohara, Surya M. Nauli, Wanda E. Filipiak, Thomas L. Saunders, Bina Joe

Pharmacy Faculty Articles and Research

A disintegrin-like metalloproteinase with thrombospondin motifs-16 (Adamts16) is an important candidate gene for hypertension. The goal of the present study was to further assess the candidacy of Adamts16 by targeted disruption of this gene in a rat genetic model of hypertension. A rat model was generated by manipulating the genome of the Dahl Salt-sensitive (S) rat using zinc-finger nucleases, wherein the mutant rat had a 17 bp deletion in the first exon of Adamts16, introducing a stop codon in the transcript. Systolic blood pressure (BP) of the homozygous Adamts16(mutant) rats was lower by 36 mmHg compared with the BP of …

Depletion Of Endothelial Or Smooth Muscle Cell-Specific Angiotensin Ii Type 1a Receptors Does Not Influence Aortic Aneurysms Or Atherosclerosis In Ldl Receptor Deficient Mice, Debra L. Rateri, Jessica J. Moorleghen, Victoria Knight, Anju Balakrishnan, Deborah A. Howatt, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Whole body genetic deletion of AT1a receptors in mice uniformly reduces hypercholesterolemia and angiotensin II-(AngII) induced atherosclerosis and abdominal aortic aneurysms (AAAs). However, the role of AT1a receptor stimulation of principal cell types resident in the arterial wall remains undefined. Therefore, the aim of this study was to determine whether deletion of AT1a receptors in either endothelial cells or smooth muscle cells influences the development of atherosclerosis and AAAs.

METHODOLOGY/PRINCIPAL FINDINGS: AT1a receptor floxed mice were developed in an LDL receptor -/- background. To generate endothelial or smooth muscle cell specific deficiency, AT1a receptor floxed mice were bred with …

The P2y(12) Antagonists, 2mesamp And Cangrelor, Inhibit Platelet Activation Through P2y(12)/G(I)-Dependent Mechanism, Binggang Xiang, Guoying Zhang, Hongmei Ren, Manjula Sunkara, Andrew J. Morris, T. Kent Gartner, Susan S. Smyth, Zhenyu Li

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: ADP is an important physiological agonist that induces integrin activation and platelet aggregation through its receptors P2Y(1) (Gα(q)-coupled) and P2Y(12) (Gα(i)-coupled). P2Y(12) plays a critical role in platelet activation and thrombosis. Adenosine-based P2Y(12) antagonists, 2-methylthioadenosine 5'-monophosphate triethylammonium salt hydrate (2MeSAMP) and Cangrelor (AR-C69931MX) have been widely used to demonstrate the role of P2Y(12) in platelet function. Cangrelor is being evaluated in clinical trials of thrombotic diseases. However, a recent study reported that both 2MeSAMP and Cangrelor raise intra-platelet cAMP levels and inhibit platelet aggregation through a P2Y(12)-independent mechanism.

METHODOLOGY/PRINCIPAL FINDINGS: The present work, using P2Y(12) deficient mice, sought to …

Characterization Of Beryllium As A Novel Agent To Study Cell Cycle Arrest And Cellular Senescence, Priyatham Gorjala

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cancer cells evade senescence, apoptosis, and other constraints on proliferation, often via mutation of the p53 tumor suppressor gene (TP53). Normal human lung fibroblasts have been shown to enter premature senescence upon exposure to beryllium. In these cells, BeSO₄ stabilizes p53 protein, increases p21 gene expression, induces senescence-associated β-galactosidase activity and causes cell proliferation arrest. In the present study, we have investigated whether BeSO₄ is able to induce similar effects in cancer cells that have wildtype p53. We have demonstrated that beryllium salt at low concentration can induce molecular changes in the p53 signaling pathway leading to cell …

Ccpa Regulates Arginine Biosynthesis In Staphylococcus Aureus Through Repression Of Proline Catabolism., Austin S. Nuxoll, Steven M. Halouska, Marat Sadykov, Mark L. Hanke, Kenneth W. Bayles, Tammy Kielian, Robert Powers, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of community-associated and nosocomial infections. Imperative to the success of S. aureus is the ability to adapt and utilize nutrients that are readily available. Genomic sequencing suggests that S. aureus has the genes required for synthesis of all twenty amino acids. However, in vitro experimentation demonstrates that staphylococci have multiple amino acid auxotrophies, including arginine. Although S. aureus possesses the highly conserved anabolic pathway that synthesizes arginine via glutamate, we demonstrate here that inactivation of ccpA facilitates the synthesis of arginine via the urea cycle utilizing proline as a substrate. Mutations within putA, rocD, …

Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera

Biochemistry and Microbiology

Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, …