Medicine and Health Sciences Commons^™

Combinatorial Effect Of Non-Steroidal Anti-Inflammatory Drugs And Nf-Κb Inhibitors In Ovarian Cancer Therapy, Luiz F. Zerbini, Rodrigo E. Tamura, Ricardo G. Correa, Akos Czibere, Jason Coideiro, Manoj Bhasin, Fernando M. Simabuco, Yihong Wang, Xuesong Gu, Linglin Li, Devanand Sarkar, Jin-Rong Zhou, Paul B. Fisher, Towia A. Libermann

Human and Molecular Genetics Publications

Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor …

Comprehensive Gene-Based Association Study Of A Chromosome 20 Linked Region Implicates Novel Risk Loci For Depressive Symptoms In Psychotic Illness, T. Bernard Bigdeli, Brion S. Maher, Zhongming Zhao, Edwin J. C. G. Van Den Oord, Dawn L. Thiselton, Jingchun Sun, Bradley T. Webb, Richard L. Amdur, Brandon Wormley, Francis A. O'Neill, Dermot Walsh, Brien P. Riley, Kenneth S. Kendler, Ayman H. Fanous

Human and Molecular Genetics Publications

Background

Prior genomewide scans of schizophrenia support evidence of linkage to regions of chromosome 20. However, association analyses have yet to provide support for any etiologically relevant variants.

Methods

We analyzed 2988 LD-tagging single nucleotide polymorphisms (SNPs) in 327 genes on chromosome 20, to test for association with schizophrenia in 270 Irish high-density families (ISHDSF, N = 270 families, 1408 subjects). These SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Given a previous report of novel linkage with chromosome 20p using latent classes of psychotic illness in this sample, association analysis was also conducted …

Designing A Patient-Centered Personal Health Record To Promote Preventive Care, Alex H. Krist, Eric Peele, Steven H. Woolf, Stephen F. Rothemich, John F. Loomis, Daniel R. Longo, Anton J. Kuzel

Family Medicine and Population Health Publications

Background Evidence-based preventive services offer profound health benefits, yet Americans receive only half of indicated care. A variety of government and specialty society policy initiatives are promoting the adoption of information technologies to engage patients in their care, such as personal health records, but current systems may not utilize the technology's full potential.

Methods Using a previously described model to make information technology more patient-centered, we developed an interactive preventive health record (IPHR) designed to more deeply engage patients in preventive care and health promotion. We recruited 14 primary care practices to promote the IPHR to all adult patients and …

Psychometric Assessment Of Hiv/Sti Sexual Risk Scale Among Msm: A Rasch Model Approach, Jian Li, Hongjie Liu, Hui Liu, Tiejian Feng, Yumao Cai

Family Medicine and Population Health Publications

Background

Little research has assessed the degree of severity and ordering of different types of sexual behaviors for HIV/STI infection in a measurement scale. The purpose of this study was to apply the Rasch model on psychometric assessment of an HIV/STI sexual risk scale among men who have sex with men (MSM).

Methods

A cross-sectional study using respondent driven sampling was conducted among 351 MSM in Shenzhen, China. The Rasch model was used to examine the psychometric properties of an HIV/STI sexual risk scale including nine types of sexual behaviors.

Results

The Rasch analysis of the nine items met the …

Distinct Signatures Of The Immune Responses In Low Risk Versus High Risk Neuroblastoma, Madhu Gowda, Kamar Godder, Maciej Kmieciak, Andrea Worschech, Maria-Libera Ascierto, Ena Wang, Francesco M. Marincola, Masoud H. Manjili

Microbiology and Immunology Publications

Background

Over 90% of low risk (LR) neuroblastoma patients survive whereas less than 30% of high risk (HR) patients are long term survivors. Age (children younger than 18 months old) is associated with LR disease. Considering that adaptive immune system is well developed in older children, and that T cells were shown to be involved in tumor escape and progression of cancers, we sought to determine whether HR patients may tend to show a signature of adaptive immune responses compared to LR patients who tend to have diminished T-cell responses but an intact innate immune response.

Methods

We performed microarray …

An Immunologic Portrait Of Cancer, Maria-Libera Ascierto, Valeria De Giorgi, Qiuzhen Liu, Davide Bedognetti, Tara L. Spivey, Daniela Murtas, Lorenzo Uccellini, Ben D. Ayotte, David F. Stroncek, Lofti Chouchane, Masoud H. Manjili, Ena Wang, Francesco M. Marincola

Microbiology and Immunology Publications

The advent of high-throughput technology challenges the traditional histopathological classification of cancer, and proposes new taxonomies derived from global transcriptional patterns. Although most of these molecular re-classifications did not endure the test of time, they provided bulk of new information that can reframe our understanding of human cancer biology. Here, we focus on an immunologic interpretation of cancer that segregates oncogenic processes independent from their tissue derivation into at least two categories of which one bears the footprints of immune activation. Several observations describe a cancer phenotype where the expression of interferon stimulated genes and immune effector mechanisms reflect patterns …

Pseudomonas Aeruginosa Elastase Provides An Escape From Phagocytosis By Degrading The Pulmonary Surfactant Protein-A, Zhizhou Kuang, Yonghua Hao, Brent E. Walling, Jayme L. Jeffries, Dennis E. Ohman, Gee W. Lau

Microbiology and Immunology Publications

Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute pneumonitis in immunocompromised patients and chronic lung infections in individuals with cystic fibrosis and other bronchiectasis. Over 75% of clinical isolates of P. aeruginosa secrete elastase B (LasB), an elastolytic metalloproteinase that is encoded by the lasB gene. Previously, in vitro studies have demonstrated that LasB degrades a number of components in both the innate and adaptive immune systems. These include surfactant proteins, antibacterial peptides, cytokines, chemokines and immunoglobulins. However, the contribution of LasB to lung infection by P. aeruginosa and to inactivation of pulmonary innate immunity in vivo needs …

Identification And Phylogenetic Analysis Of Heme Synthesis Genes In Trypanosomatids And Their Bacterial Endosymbionts, João M. P. Alves, Logan Voegtly, Andrey V. Matveyev, Ana M. Lara, Flávia Maia Da Silva, Myrna G. Serrano, Gregory A. Buck, Marta M. G. Teixeira, Erney P. Camargo

Microbiology and Immunology Publications

It has been known for decades that some insect-infecting trypanosomatids can survive in culture without heme supplementation while others cannot, and that this capability is associated with the presence of a betaproteobacterial endosymbiont in the flagellate's cytoplasm. However, the specific mechanisms involved in this process remained obscure. In this work, we sequence and phylogenetically analyze the heme pathway genes from the symbionts and from their hosts, as well as from a number of heme synthesis-deficient Kinetoplastida. Our results show that the enzymes responsible for synthesis of heme are encoded on the symbiont genomes and produced in close cooperation with the …

Epistasis Between Comt And Mthfr In Maternal-Fetal Dyads Increases Risk For Preeclampsia, Lori D. Hill, Timothy P. York, Juan P. Kusanovic, Ricardo Gomez, Lindon J. Eaves, Roberto Romero, Jerome F. Strauss Iii

Obstetrics and Gynecology Publications

Preeclampsia is a leading cause of perinatal morbidity and mortality. This disorder is thought to be multifactorial in origin, with multiple genes, environmental and social factors, contributing to disease. One proposed mechanism is placental hypoxia-driven imbalances in angiogenic and anti-angiogenic factors, causing endothelial cell dysfunction. Catechol-O-methyltransferase (Comt)-deficient pregnant mice have a preeclampsia phenotype that is reversed by exogenous 2-methoxyestradiol (2-ME), an estrogen metabolite generated by COMT. 2-ME inhibits Hypoxia Inducible Factor 1α, a transcription factor mediating hypoxic responses. COMT has been shown to interact with methylenetetrahydrofolate reductase (MTHFR), which modulates the availability of S-adenosylmethionine (SAM), a COMT …

Nitric Oxide Synthase Inhibition Enhances The Antitumor Effect Of Radiation In The Treatment Of Squamous Carcinoma Xenografts, Robert J. G. Cardnell, Ross B. Mikkelsen

Radiation Oncology Publications

This study tests whether the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (L-NNA), combines favorably with ionizing radiation (IR) in controlling squamous carcinoma tumor growth. Animals bearing FaDu and A431 xenografts were treated with L-NNA in the drinking water. IR exposure was 10 Gy for tumor growth and survival studies and 4 Gy for ex vivoclonogenic assays. Cryosections were examined immunohistochemically for markers of apoptosis and hypoxia. Blood flow was assayed by fluorescent microscopy of tissue cryosections after i.v. injection of fluorospheres. Orally administered L-NNA for 24 hrs reduces tumor blood flow by 80% (pex vivo clonogenic assay compared to …

Applying An Empirical Hydropathic Forcefield In Refinement May Improve Low-Resolution Protein X-Ray Crystal Structures, Vishal N. Koparde, J. Neel Scarsdale, Glen E. Kellogg

Medicinal Chemistry Publications

Background

The quality of X-ray crystallographic models for biomacromolecules refined from data obtained at high-resolution is assured by the data itself. However, at low-resolution, >3.0 Å, additional information is supplied by a forcefield coupled with an associated refinement protocol. These resulting structures are often of lower quality and thus unsuitable for downstream activities like structure-based drug discovery.

Methodology

An X-ray crystallography refinement protocol that enhances standard methodology by incorporating energy terms from the HINT (Hydropathic INTeractions) empirical forcefield is described. This protocol was tested by refining synthetic low-resolution structural data derived from 25 diverse high-resolution structures, and referencing the resulting …

Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene Grin2a As A Parkinson's Disease Modifier Gene Via Interaction With Coffee, Taye H. Hamza, Honglei Chen, Erin M. Hill-Burns, Shannon L. Rhodes, Jennifer Montimurro, Denise M. Kay, Albert Tenesa, Victoria I. Kusel, Patricia Sheehan, Muthukrishnan Eaaswarkhanth, Dora Yearout, Ali Samii, John W. Roberts, Pinky Agarwal, Yvette Bordelon, Yikyung Park, Liyong Wang, Jianjun Gao, Jeffery M. Vance, Kenneth S. Kendler, Silviu-Alin Bacanu, William K. Scott, Beate Ritz, John Nutt, Stweart A. Factor, Cyrus P. Zabetian, Haydeh Payami

Psychiatry Publications

Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the …

Spag16, An Axonemal Central Apparatus Gene, Encodes A Male Germ Cell Nuclear Speckle Protein That Regulates Spag16 Mrna Expression, David R. Nagarkatti-Gude, Ruth Jaimez, Scott C. Henderson, Maria E. Teves, Zhibing Zhang, Jerome F. Strauss Iii

Biochemistry and Molecular Biology Publications

Spag16 is the murine orthologue of Chlamydomonas reinhardtii PF20, a protein known to be essential to the structure and function of the “9+2” axoneme. In Chlamydomonas, the PF20gene encodes a single protein present in the central pair of the axoneme. Loss of PF20 prevents central pair assembly/integrity and results in flagellar paralysis. Here we demonstrate that the murine Spag16 gene encodes two proteins: 71 kDa SPAG16L, which is found in all murine cells with motile cilia or flagella, and 35 kDa SPAG16S, representing the C terminus of SPAG16L, which is expressed only in male germ cells, and is …

Development Of Melanopsin-Based Irradiance Detecting Circuitry, David S. Mcneill, Catherine J. Sheely, Jennifer L. Ecker, Tudor C. Badea, Duncan Morhardt, William Guido, Samer Hattar

Anatomy and Neurobiology Publications

Background

Most retinal ganglion cells (RGCs) convey contrast and motion information to visual brain centers. Approximately 2% of RGCs are intrinsically photosensitive (ipRGCs), express melanopsin and are necessary for light to modulate specific physiological processes in mice. The ipRGCs directly target the suprachiasmatic nucleus (SCN) to photoentrain circadian rhythms, and the olivary pretectal nucleus (OPN) to mediate the pupillary light response. How and when this ipRGC circuitry develops is unknown.

Results

Here, we show that some ipRGCs follow a delayed developmental time course relative to other image-forming RGCs. Specifically, ipRGC neurogenesis extends beyond that of other RGCs, and ipRGCs begin …

Influence Of Continuous Venovenous Hemofiltration And Continuous Venovenous Hemodiafiltration On The Disposition Of Doripenem, Iolanda Cirillo, Nicole Vaccaro, Dainius Balis, Rebecca Redman, Gary R. Matzke

Pharmacotherapy and Outcomes Science Publications

The pharmacokinetics, safety, and tolerability of a single 1-hour, 500-mg intravenous infusion of doripenem were assessed in dialysis-dependent subjects with stage 5 chronic kidney disease undergoing continuous renal replacement therapy (CRRT) via 12-hour continuous venovenous hemofiltration (CVVH) (n = 6) or continuous venovenous hemodiafiltration (CVVHDF) (n = 5). Healthy volunteers were also assessed (n = 12). Concentrations of doripenem and the primary metabolite doripenem-M-1 were measured in plasma and ultrafiltrate or ultrafiltrate/dialysate by a validated liquid chromatography-tandem mass spectrometry method. In dialysis-dependent subjects, levels of systemic exposure to doripenem and doripenem-M-1 were approximately 3- and 5-fold greater, respectively, than those …

Antihypertensive Treatment Differentially Affects Vascular Sphingolipid Biology In Spontaneously Hypertensive Rats, Léon J. A. Spijkers, Ben J. A. Janssen, Jelly Nelissen, Merlijn J. P. M. T. Meens, Dayanjan Wijesinghe, Charles E. Chalfant, Jo G. R. De Mey, Astrid E. Alewijnse, Stephan L. M. Peters

Biochemistry and Molecular Biology Publications

We have previously shown that essential hypertension in humans and spontaneously hypertensive rats (SHR), is associated with increased levels of ceramide and marked alterations in sphingolipid biology. Pharmacological elevation of ceramide in isolated carotid arteries of SHR leads to vasoconstriction via a calcium-independent phospholipase A2, cyclooxygenase-1 and thromboxane synthase-dependent release of thromboxane A2. This phenomenon is almost absent in vessels from normotensive Wistar Kyoto (WKY) rats. Here we investigated whether lowering of blood pressure can reverse elevated ceramide levels and reduce ceramide-mediated contractions in SHR.

Methods and Findings

For this purpose SHR were treated for 4 weeks with the angiotensin …

Crystal Structure Of Thrombin In Complex With S-Variegin: Insights Of A Novel Mechanism Of Inhibition And Design Of Tunable Thrombin Inhibitors, Cho Yeow Koh, Sundramurthy Kumar, Maria Kazimirova, Patricia A. Nuttall, Uvaraj P. Radhakrishnan, Seongcheol Kim, Pudur Jagadeeswaran, Takayuki Imamura, Jun Mizuguchi, Sadaaki Iwanaga, Kunchithapadam Swaminathan, R. Manjunathan Kini

Biochemistry and Molecular Biology Publications

The inhibition of thrombin is one of the important treatments of pathological blood clot formation. Variegin, isolated from the tropical bont tick, is a novel molecule exhibiting a unique ‘two-modes’ inhibitory property on thrombin active site (competitive before cleavage, noncompetitive after cleavage). For the better understanding of its function, we have determined the crystal structure of the human α-thrombin:synthetic-variegin complex at 2.4 Å resolution. The structure reveals a new mechanism of thrombin inhibition by disrupting the charge relay system. Based on the structure, we have designed 17 variegin variants, differing in potency, kinetics and mechanism of inhibition. The most active …

Hypertension Is Associated With Marked Alterations In Sphingolipid Biology: A Potential Role For Ceramide, Leon J. A. Spijkers, Rob F. P. Van Den Akker, Ben J. A. Janssen, Jacques J. Debets, Jo G. R. De Mey, Erik S. G. Stroes, Bart-Jan H. Van Den Bom, Dayanjan Wijesinghe, Charles E. Chalfant, Luke Macaleese, Gert B. Eijkel, Ron M. A. Heeren, Astrid E. Alewijnse, Stephan L. M. Peters

Biochemistry and Molecular Biology Publications

Background

Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function.

Methods and Findings

In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4±0.4 and SMase: 2.1±0.1 mN/mm; n = 10), that were virtually …

Er Stress And Lipid Metabolism In Adipocytes, Beth S. Zha, Huiping Zhou

Microbiology and Immunology Publications

The role of endoplasmic reticulum (ER) stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, …

Tumor Escape And Progression Of Her-2/Neu Negative Breast Cancer Under Immune Pressure, Maciej Kmieciak, Kyle K. Payne, Michael O. Idowu, Margaret M. Grimes, Laura Graham, Maria-Libera Ascierto, Ena Wang, Xiang-Yang Wang, Harry D. Bear, Masoud H. Manjili

Microbiology and Immunology Publications

Background Emerging data from pre-clinical and clinical studies suggest that HER-2/neu-specific T cell responses could induce HER-2/neu antigen loss in the tumor cells. These data suggest that patients with HER-2/neu negative breast cancer might have had HER-2/neu positive premalignant lesions in the past that progressed to HER-2/neu negative breast cancer under HER-2/neu-specific immune pressure.

Methods We conducted a pilot study in patients with HER-2/neu positive and HER-2/neu negative breast cancers as well as a patient with ductal carcinoma in situ (DCIS). HER-2/neu expression was determined by FISH. HER-2/neu-specific T cell responses were determined by using IFN-γ ELISA. Expression of IFN-γ …

Virginia Dental Journal (Vol. 88, No. 1, 2011)

Virginia Dental Journal

No abstract provided.

3d Mapping Of The Spry2 Domain Of Ryanodine Receptor 1 By Single-Particle Cryo-Em, Alex Peralvaerz-Marin, Hanshen Tae, Phillip G. Board, Marco G. Casarotto, Angela F. Dulhunty, Montserrat Samsó

Physiology and Biophysics Publications and Presentations

The type 1 skeletal muscle ryanodine receptor (RyR1) is principally responsible for Ca2+release from the sarcoplasmic reticulum and for the subsequent muscle contraction. The RyR1 contains three SPRY domains. SPRY domains are generally known to mediate protein-protein interactions, however the location of the three SPRY domains in the 3D structure of the RyR1 is not known. Combining immunolabeling and single-particle cryo-electron microscopy we have mapped the SPRY2 domain (S1085-V1208) in the 3D structure of RyR1 using three different antibodies against the SPRY2 domain. Two obstacles for the image processing procedure; limited amount of data and signal dilution introduced by the …

Cholesterol Sensitivity Of Kir2.1 Is Controlled By A Belt Of Residues Around The Cytosolic Pore, Avia Rosenhouse-Dantsker, Diomedes E. Logothetis, Irena Levitan

Physiology and Biophysics Publications and Presentations

Abstract

Kir channels play an important role in setting the resting membrane potential and modulating membrane excitability. A common feature of several Kir channels is that they are regulated by cholesterol. Yet, the mechanism by which cholesterol affects channel function is unclear. We recently showed that the cholesterol sensitivity of Kir2 channels depends on several CD-loop residues. Here we show that this cytosolic loop is part of a regulatory site that also includes residues in the G-loop, the N-terminus, and the connecting segment between the C-terminus and the inner transmembrane helix. Together, these residues form a cytosolic belt that surrounds …

State-Dependent Camp Binding To Functioning Hcn Channels Studied By Patch-Clamp Fluorometry, Shengjun Wu, Zhanna V. Vysotskaya, Xinping Xu, Changan Xie, Qinglian Liu, Lei Zhou

Physiology and Biophysics Publications and Presentations

Abstract

One major goal of ion channel research is to delineate the molecular events from the detection of the stimuli to the movement of channel gates. For ligand-gated channels, it is challenging to separate ligand binding from channel gating. Here we studied the cyclic adenosine monophosphate (cAMP)-dependent gating in hyperpolarization-activated cAMP-regulated (HCN) channel by simultaneously recording channel opening and ligand binding, using the patch-clamp fluorometry technique with a unique fluorescent cAMP analog that fluoresces strongly in the hydrophobic binding pocket and exerts regulatory effects on HCN channels similar to those imposed by cAMP. Corresponding to voltage-dependent channel activation, we observed …

Systematic Study Of Gene Functions For Morphological Chain Formation In Streptococcus Sanguinis, Karra Evans

Theses and Dissertations

Streptococcus sanguinis is a gram-positive facultative anaerobe that is indigenous to the oral cavity and a primary colonizer of the oral cavity. It serves as a tether for the attachment of several oral bacteria that colonize the tooth surface, form dental plaque, and cause periodontal disease. Previous experiments with streptococcal strains have suggested that cellular chain morphology of streptococci may influence the competitiveness, susceptibility to phagocytosis, acidurance, and aggregation of the bacterium. The purpose of this study was to systematically determine gene functions that contribute to cellular chain length morphology in the SK36 strain of S. sanguinis. Gene functions for …

Pediatrician Perceptions Of The Patient-Centered Medical Home Model, Christopher Ray

Theses and Dissertations

The Patient-Centered Medical Home (PCMH) is an emerging model of health care designed to provide a simpler, more effective health care experience. The model places heavy emphasis on the concept of every patient having a "personal physician" who is the point of access for all health care needs and concerns. The personal physician integrates all relevant health care information to provide the patient with a holistic picture of his health. The supposed benefits of the PCMH model include an improved patient experience, increased effectiveness of care, increased efficiency of care, greater access to care, among others. Only now is evidence …

Acquired Cytogenetic Changes In Adult Twins Discordant For A History Of Childhood Sexual Abuse, Jenni Brumelle

Theses and Dissertations

The primary study aim was to evaluate the latent biological effect of childhood sexual abuse (CSA) on adults by quantifying acquired cytogenetic changes and cortisol levels in identical twins who were discordant (N=22) or concordant (N=2) for a history of CSA. Although the difference scores for cortisol values between discordant identical co-twins were not significantly different from zero, a trend was observed for the twins exposed to intercourse, the most severe form of CSA, to have a blunted cortisol awakening response. Acquired cytogenetic changes were assessed by scoring telomere lengths and somatic cell abnormality frequencies via a cytokinesis-block micronucleus (MN) …

Hiv Protease Inhibitors Trigger Lipid Metabolism Dysregulation Through Endoplasmic Reticulum Stress And Autophagy, Beth Shoshana Zha

Theses and Dissertations

HIV protease inhibitors (PI) are core components of Highly Active Antiretroviral Therapy (HAART). HIV PIs are extremely effective at suppressing viral load, but have been linked to lipodystrophy and dyslipidemia, which are major risk factors for cardiovascular disease. Recent studies indicate that activation of endoplasmic reticulum (ER) stress is an important cellular mechanism underlying HIV PI-induced dysregulation of lipid metabolism. However, the exact role of ER stress in HIV PI-associated lipodystrophy and dyslipidemia remains to be identified. Hepatocytes and adipocytes are important players in regulating lipid metabolism and the inflammatory state. Dysfunction of these two cell types is closely linked …

Synthesis, Screening And Cocrystallization Of Adenosine Based Inhibitors With Methyltransferases, Ermc' And Ksga, Matthew Baker

Theses and Dissertations

Antibiotic resistance threatens to throw mankind back into an era when infectious disease was the predominant cause of death. In an effort to mitigate this danger, we targeted ErmC’ and KsgA. Both methylate N6-adenosine of ribosomal RNA, though each serve different roles in their bacterial host. ErmC’ dimethylates A2058 on 23S rRNA, conferring resistance to MLSB antibiotics (macrolides, lincosamides, streptogramin B). KsgA aids in ribosome assembly, binding inactive 30S until dimethylating A1518/A1519 of 16S rRNA. Like most methyltransferases, ErmC’ and KsgA use cofactor S-adenosylmethionine (SAM) as their methyl source, which binds adjacent to their specific adenosine substrate. ErmC’ inhibitors could …

Biobehavioral Relationships And Health Related Quality Of Life In Persons With End Stage Renal Disease On Hemodialysis, Avis Allen

Theses and Dissertations

The study of immune status and biobehavioral measures is limited in professional nursing. The purpose of the pre-pilot study was to describe levels of cytokines prior to, during, and after dialysis, examine changes in cytokine levels from immediate pre-dialysis to immediate post-dialysis, and to compare cytokine patterns prior to and after dialysis. A within subject descriptive study was conducted as part of a larger pilot study to describe levels of cytokines prior to, during, and after dialysis, examine changes in cytokine levels from immediate pre-dialysis to immediate post-dialysis, and to compare cytokine patterns prior to and after dialysis. Serum cytokine …