Medical Specialties Commons^™

Impact Of Pre-Stage Ii Hemodynamics And Pulmonary Artery Anatomy On 12-Month Outcomes In The Pediatric Heart Network Single Ventricle Reconstruction Trial., Ranjit Aiyagari, John F. Rhodes, Peter Shrader, Wolfgang A. Radtke, Varsha M. Bandisode, Lisa Bergersen, Matthew J. Gillespie, Robert G. Gray, Lin T. Guey, Kevin D. Hill, Russel Hirsch, Dennis W. Kim, Kyong-Jin Lee, Andrew N. Pelech, Jeremy Ringewald, Cheryl Takao, Julie A. Vincent, Richard G. Ohye, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To compare the interstage cardiac catheterization hemodynamic and angiographic findings between shunt types for the Pediatric Heart Network Single Ventricle Reconstruction trial. The trial, which randomized subjects to a modified Blalock-Taussig shunt (MBTS) or right ventricle-to-pulmonary artery shunt (RVPAS) for the Norwood procedure, demonstrated the RVPAS was associated with a smaller pulmonary artery diameter but superior 12-month transplant-free survival.

METHODS: We analyzed the pre-stage II catheterization data for the trial subjects. The hemodynamic variables and shunt and pulmonary angiographic data were compared between shunt types; their association with 12-month transplant-free survival was also evaluated.

RESULTS: Of 549 randomized subjects, …

Intimate Partner Violence After Disclosure Of Hiv Test Results Among Pregnant Women In Harare, Zimbabwe, Simukai Shamu, Christina Zarowsky, Tamara Shefer, Marleen Temmerman, Naeemah Abrahams

Obstetrics and Gynaecology, East Africa

Background: HIV status disclosure is a central strategy in HIV prevention and treatment but in high prevalence settings women test disproportionately and most often during pregnancy. This study reports intimate partner violence (IPV) following disclosure of HIV test results by pregnant women.

Methods: In this cross sectional study we interviewed 1951 postnatal women who tested positive and negative for HIV about IPV experiences following HIV test disclosure, using an adapted WHO questionnaire. Multivariate regression models assessed factors associated with IPV after disclosure and controlled for factors such as previous IPV and other known behavioural factors associated with IPV.

Results: Over …

Subgroups Of Cancer Patients With Unique Pain And Fatigue Experiences During Chemotherapy, Heeju Kim, Patrick S. Malone, Andrea M. Barsevick

Department of Medical Oncology Faculty Papers

Context. Some cancer patients experience pain and fatigue, whereas others experience only one of the two symptoms. Yet, it is not clear who experiences these unique patterns and why.

Objectives. This study aimed to identify subgroups of cancer patients with unique pain and fatigue experiences in two different chemotherapy cycles to examine how selected factors influenced subgroup membership and identify how subgroups differed in concurrently measured functional limitation outcome.

Methods. The sample included 276 patients with diverse cancer types from four U.S. sites. To investigate subgroups, latent profile analyses were performed. Multinomial logistic regression and one-way analysis of variance-type analyses …

Use Of A Melody Pulmonary Valve In Transcatheter Valve-In-Valve Replacement For Tricuspid Valve Bioprosthesis Degeneration, David M Filsoof, David F Snipelisky, Brian P Shapiro

The Texas Heart Institute Journal

Bioprosthetic heart valves can degenerate and fail over time. Repeat surgery as a means of replacement increases morbidity and mortality rates, and some patients are not candidates for reoperation. A newer treatment, percutaneous transcatheter valve-in-valve implantation, might delay or substitute for invasive procedures. We present the case of a 51-year-old woman, a poor candidate for surgery who had prosthetic tricuspid valve degeneration and stenosis. We successfully performed valve-in-valve placement of a Melody® valve, using a procedure originally intended to treat pulmonary valve conduit obstruction or regurgitation. To our knowledge, this is among the first case reports to describe the use …

Troponin Leak Associated With Drug-Induced Methemoglobinemia., Robert D. Cannon Do, Michael Wagner, Jeanne L. Jacoby Md

Department of Emergency Medicine

Drug-induced methemoglobinemia is a well-described entity but has not been previously associated with elevated troponins in the absence of cardiac symptoms. We report a case of a patient presenting to the emergency department (ED) with complaints related to an exacerbation of her long-standing cystitis. A low pulse oximetry reading prompted an evaluation, revealing a troponin leak, which peaked at 10 hours. Her methemoglobin level was found to be elevated at 11.4%, but a preexisting anemia apparently prevented the clinical recognition of cyanosis. The methemoglobinemia was determined to be secondary to her ingestion of phenazopyridine and trimethoprim-sulfa methoxizole. Although phenazopyridine and …

Surgeon Practices And Attitudes Toward The Control Of Surgical-Site Infections In Jordan, Sara Ali Mater

Independent Study Project (ISP) Collection

The purpose of this study was to determine the attitudes and practices of Jordanian surgeons on the control of surgical-site infections, evaluated by the Center of Disease Control’s guidelines toward the prevention of surgical-site infections, in addition to gaining respondents opinions on infection control in Jordan. This study was conducted through the distribution of 75 questionnaires given to surgeons at five hospitals in Jordan. Additional insight on SSI infection control was gained through interviews with two cardiac surgeons and three infection control directors. The results of the survey were compared with the Center for Disease Control’s guide to surgical-site infection …

Rationale And Design Of The Guide-It Study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment In Heart Failure., G. Michael Felker, Tariq Ahmad, Kevin J. Anstrom, Kirkwood F. Adams, Lawton S. Cooper, Justin A. Ezekowitz, Mona Fiuzat, Nancy Houston-Miller, James L. Januzzi, Eric S. Leifer, Daniel B. Mark, Patrice Desvigne-Nickens, Gayle Paynter, Ileana L. Piña, David J. Whellan, Christopher M. O'Connor

Division of Cardiology Faculty Papers

OBJECTIVES: The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of

BACKGROUND: Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies …

Interpersonal Communication In The Context Of Dementia: Examining Family Caregivers' Appraisals And Burden, Stacy Lynn Barnes

Dissertations (1934 -)

Purpose and Objectives: The purpose of this study was to explore dementia family caregivers' appraisals of communication behaviors and strategies, and their relationships to caregiver burden. Study objectives were to investigate: 1) the relationship between frequency of dementia-related communication behaviors and caregivers' appraisals of frustration; 2) the relationship between caregivers' use of communication strategies and appraisals of helpfulness; 3) the structural relationships between communication behavior appraisal, communication strategy appraisal, problem behaviors, and caregiver burden; and 4) caregiver education level as a moderating variable of the final structural model. Methods: A written, mailed questionnaire was developed to capture dementia family caregivers' …

Palliative Care's Sacramental And Liturgical Foundations: Healthcare Formed By Faith, Hope, And Love, Darren M. Henson

Dissertations (1934 -)

Medical history identifies Dame Cicely Saunders as the founder of modern hospice and palliative care for the unique care she gave to the incurably and terminally ill. Less known is how her Christian faith, combined with her knowledge of medicine, influenced her vision. This work retrieves the Christian roots of palliative care and asserts that the practice of faith preserves the practice of medicine from succumbing to medicalized dying--a phenomenon that excessively relies on technology with the implied hope that it will ultimately conquer illnesses and even death. Efficiency and effectiveness ground modern medicine's epistemology. These concepts follow the philosophical …

Prevalence Of Hepatitis B Virus Infection Among Barbers And Their Knowledge, Attitude And Practices In The District Of Sukkur, Sindh ., Imran Naeem Abbasi, Zafar Fatmi, Muhammad Masood Kadir, Nalini Sathiakumar

Community Health Sciences

Abstract

OBJECTIVES:

Several occupations in developing countries lag behind in ensuring the safety of their workers in occupational settings. Lack of implementation of safety guidelines at workplaces can expose workers to health risks. In Pakistan, barbers are one of the un-regulated occupational groups. Low literacy, increased frequency of direct skin contact and blade/razors use can expose barbers to body fluids including blood of the customers. We conducted this study in order to determine hepatitis B virus (HBV) prevalence among barbers and their knowledge, attitude and practices in a peri-urban district of Sindh.

MATERIAL AND METHODS:

Three hundred eighty-five barbers from …

Persistent At-Level Thermal Hyperalgesia And Tactile Allodynia Accompany Chronic Neuronal And Astrocyte Activation In Superficial Dorsal Horn Following Mouse Cervical Contusion Spinal Cord Injury., Jaime L Watson, Tamara J Hala, Rajarshi Putatunda, Daniel Sannie, Angelo C Lepore

Department of Neuroscience Faculty Papers

In humans, sensory abnormalities, including neuropathic pain, often result from traumatic spinal cord injury (SCI). SCI can induce cellular changes in the CNS, termed central sensitization, that alter excitability of spinal cord neurons, including those in the dorsal horn involved in pain transmission. Persistently elevated levels of neuronal activity, glial activation, and glutamatergic transmission are thought to contribute to the hyperexcitability of these dorsal horn neurons, which can lead to maladaptive circuitry, aberrant pain processing and, ultimately, chronic neuropathic pain. Here we present a mouse model of SCI-induced neuropathic pain that exhibits a persistent pain phenotype accompanied by chronic neuronal …

Svegfr-2 And Its Role In Lymphangiogenesis Modulation, Jayakrishna Ambati, Romulo J. Albuquerque

Ophthalmology and Visual Science Faculty Patents

Disclosed herein are nucleic acid molecules comprising a nucleotide sequence of sVEGF-2, proteins encoded by those sequences and antibodies that bind to the protein. Also disclosed are methods for inhibiting or enhancing expression or activity of sVEGFR-2 and methods for inhibiting graft rejection, particularly cornea graph rejection. Also described are methods for inhibiting lymphangiogenesis and lymphatic endothelial cell proliferation by administering an effective amount of sVEGFR-2 and methods for treating lymphedema by inhibiting the activity of sVEGFR-2.

Effect Of Obesity And Exercise On The Expression Of The Novel Myokines, Myonectin And Fibronectin Type Iii Domain Containing 5, Jonathan M. Peterson, Ryan Mart, Cherie E. Bond

ETSU Faculty Works

Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means to directly restore skeletal muscle glucose and lipid uptake and metabolism. However, in addition to the direct effects of skeletal muscle on glucose and lipids, there is renewed interest in the ability of skeletal muscle to coordinate metabolic activity of other tissues, such as adipose tissue and liver. The purpose of this study was to examine the effects of endurance exercise on the expression level of two novel muscle-derived secreted factors, or myokines, …

Isomir Expression Profiles In Human Lymphoblastoid Cell Lines Exhibit Population And Gender Dependencies., Phillipe Loher, Eric R Londin, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

For many years it was believed that each mature microRNA (miRNA) existed as a single entity with fixed endpoints and a 'static' and unchangeable primary sequence. However, recent evidence suggests that mature miRNAs are more 'dynamic' and that each miRNA precursor arm gives rise to multiple isoforms, the isomiRs. Here we report on our identification of numerous and abundant isomiRs in the lymphoblastoid cell lines (LCLs) of 452 men and women from five different population groups. Unexpectedly, we find that these isomiRs exhibit an expression profile that is population-dependent and gender-dependent. This is important as it indicates that the LCLs …

The Association Of Meningococcal Disease With Influenza In The United States, 1989-2009, Jessica Hartman Jacobs, Cecile Viboud, Eric Tchetgen Tchetgen, Joel Schwartz, Claudia Steiner, Lone Simonsen, Marc Lipsitch

Global Health Faculty Publications

Importance and Objective

Prior influenza infection is a risk factor for invasive meningococcal disease. Quantifying the fraction of meningococcal disease attributable to influenza could improve understanding of viral-bacterial interaction and indicate additional health benefits to influenza immunization.

Design, Setting and Participants

A time series analysis of the association of influenza and meningococcal disease using hospitalizations in 9 states from 1989–2009 included in the State Inpatient Databases from the Agency for Healthcare Research and Quality and the proportion of positive influenza tests by subtype reported to the Centers for Disease Control. The model accounts for the autocorrelation of meningococcal disease and …

Plasma Adiponectin, Clinical Factors, And Patient Outcomes During The Acute Respiratory Distress Syndrome., Allan J Walkey, Serkalem Demissie, Dilip Shah, Freddy Romero, Leah Puklin, Ross S Summer

Center for Translational Medicine Faculty Papers

OBJECTIVE: Adiponectin (APN) is an anti-inflammatory hormone derived from adipose tissue that attenuates acute lung injury in rodents. In this study, we investigated the association between circulating APN and outcomes among patients with acute respiratory distress syndrome (ARDS).

METHODS: We performed a retrospective cohort study using data and plasma samples from participants in the multicenter ARDS Network Fluid and Catheter Treatment Trial.

RESULTS: Plasma APN concentrations were measured in 816 (81.6%) trial participants at baseline and in 568 (56.8%) subjects at both baseline and day 7 after enrollment. Clinical factors associated with baseline APN levels in multivariable-adjusted models included sex, …

Development Of A Fatal Noncompressible Truncal Hemorrhage Model With Combined Hepatic And Portal Venous Injury In Normothermic Normovolemic Swine, Ujwal R. Yanala, Jason M. Johanning, Iraklis I. Pipinos, Gustavo F. Larsen, William H. Velander, Mark A. Carlson

William H. Velander Publications

Noncompressible truncal hemorrhage and brain injury currently account for most early mortality of warfighters on the battlefield. There is no effective treatment for noncompressible truncal hemorrhage, other than rapid evacuation to a surgical facility. The availability of an effective field treatment for noncompressible truncal hemorrhage could increase the number of warfighters salvaged from this frequently-lethal scenario. Our intent was to develop a porcine model of noncompressible truncal hemorrhage with a ,50% one-hour mortality so that we could develop new treatments for this difficult problem. Normovolemic normothermic domestic swine (barrows, 3 months old, 34–36 kg) underwent one of three injury types …

Intellectual And Developmental Disability: Healthcare Financing, David A. Ervin, Joav Merrick

Pediatrics Faculty Publications

The World Health Organization (WHO) estimates global spending on healthcare at $6.5 trillion, approximately 10.5% of the world’s gross domestic product. The United States’ (US) share of that spending is $2.6 trillion, essentially quadrupling since 1980. The 2010 United States Patient Protection and Affordable Care Act (PPACA), also known as Obamacare, has stimulated extensive debate over the way in which healthcare is financed, and whether or not the costs of healthcare are sustainable. Among publicly funded healthcare in the US, Medicaid and Medicare are primary sources of funding. In federal fiscal year 2012, Medicaid spending on acute health exceeded $275.4 …

Pharmacotherapy For Uveitis: Current Management And Emerging Therapy., Robert J. Barry, Quan Dong Nguyen, Richard W. Lee, Philip I. Murray, Alastair K. Denniston

Journal Articles: Ophthalmology

Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual …

Inferior Meatus Maxillary Antrostomy: Time To Revisit A Previously Abandoned Surgical Technique?, Natalie Ziegler, Bs, Alfred Marc C. Lloreta, Md, Alexander Farag, Md, Ting Ting Zhan, Phd, Gurston G. Nyquist, Md, Marc Rosen, Md

Department of Otolaryngology - Head and Neck Surgery Presentations and Grand Rounds

Background: A small subset of patients have dysfunctional maxillary sinus mucosa. These patients require more aggressive surgical treatment to allow for gravity dependent mucous drainage, intra-operative and office debridements, and the delivery of irrigations and topical treatments. The aim of this study is to examine the use of inferior meatus maxillary antrostomy (IMMA) in combination with traditional maxillary antrostomy, in this challenging patient population.

Methods: We performed a retrospective study from February, 2008 until April, 2014 with a 118 patients undergoing a total of 128 IMMA procedures. Data was gathered regarding patient demographic, prior therapy, post-operative medical therapy, IMMA patency, …

Transformation Of Human Cathelicidin Ll-37 Into Selective, Stable, And Potent Antimicrobial Compounds., Guangshun Wang, Mark L. Hanke, Biswajit Mishra, Tamara Lushnikova, Cortney E. Heim, Vinai Chittezham Thomas, Kenneth W. Bayles, Tammy Kielian

Journal Articles: Pathology and Microbiology

This Letter reports a family of novel antimicrobial compounds obtained by combining peptide library screening with structure-based design. Library screening led to the identification of a human LL-37 peptide resistant to chymotrypsin. This d-amino-acid-containing peptide template was active against Escherichia coli but not methicillin-resistant Staphylococcus aureus (MRSA). It possesses a unique nonclassic amphipathic structure with hydrophobic defects. By repairing the hydrophobic defects, the peptide (17BIPHE2) gained activity against the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species. In vitro, 17BIPHE2 could disrupt bacterial membranes and bind to DNA. In vivo, the peptide …

Association Of Leukocyte Mitochondrial Dna Content With Glioma Risk: Evidence From A Chinese Case-Control Study., Jie Zhang, Deyang Li, Falin Qu, Yibing Chen, Gang Li, Hequn Jiang, Xiaojun Huang, Hushan Yang, Jinliang Xing

Department of Cancer Biology Faculty Papers

BACKGROUND: Increasing evidence suggests that alterations in mitochondrial DNA (mtDNA) content may be implicated in the tumorigenesis of several malignancies. However, the association between mtDNA content in peripheral blood lymphocytes (PBLs) and glioma risk has not been investigated.

METHODS: Real-time PCR was used to examine the mtDNA content in PBLs of 414 glioma patients and 414 matched controls in a hospital-based case-control study. The association between mtDNA content and glioma risk was evaluated using an unconditional multivariate logistic regression model.

RESULTS: We found that glioma patients exhibited a significantly higher median mtDNA content than healthy controls (0.99 vs. 0.71, P …

Abnormal White Matter Integrity Related To Head Impact Exposure In A Season Of High School Varsity Football, Elizabeth M. Davenport, Christopher T. Whitlow, Jillian E. Urban, Mark A. Espeland, Jung Youngkyoo, Daryl A. Rosenbaum, Gerard A. Gioia, Alexander K. Powers, Joel D. Stitzel, Joseph A. Maldjian

Psychiatry and Behavioral Sciences Faculty Publications

The aim of this study was to determine whether the cumulative effects of head impacts from a season of high school football produce magnetic resonance imaging (MRI) measureable changes in the brain in the absence of clinically diagnosed concussion. Players from a local high school football team were instrumented with the Head Impact Telemetry System (HITS™) during all practices and games. All players received pre- and postseason MRI, including diffusion tensor imaging (DTI). Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) was also conducted. Total impacts and risk-weighted cumulative exposure (RWE), including linear (RWE_Linear), rotational (RWE_Rotational), and …

Risk Factors For Surgical Site Infection Following Total Joint Arthroplasty., Mohammad R Rasouli, Camilo Restrepo, Mitchell Maltenfort, Phd, James J Purtill, Javad Parvizi

Rothman Institute Papers

BACKGROUND: Currently, most hospitals in the United States are obliged to report infections that occur following total joint arthroplasty to the Centers for Disease Control and Prevention through the National Healthcare Safety Network surveillance. The objective of this study was to identify the risk factors of surgical site infections that were reported to the Centers for Disease Control and Prevention from a single institution.

METHODS: For this study, 6111 primary and revision total joint arthroplasties performed from April 2010 to June 2012 were identified. Surgical site infection cases captured by infection surveillance staff on the basis of the Centers for …

Emerging Multidrug Resistance Of Methicillin-Resistant Staphylococcus Aureus In Hand Infections., Rick Tosti, Brian T Samuelsen, Samantha Bender, John R Fowler, John Gaughan, Alyssa A Schaffer, Asif M Ilyas

Rothman Institute Papers

BACKGROUND: Methicillin-resistant Staphylococcus aureus has been the most commonly identified pathogen in hand infections at urban centers, but the evolving antibiotic sensitivity profiles of methicillin-resistant Staphylococcus aureus are not known. The purposes of this study are to determine if multidrug resistance in methicillin-resistant Staphylococcus aureus is emerging and to provide current recommendations for empiric antibiotic selection for hand infections in endemic regions.

METHODS: An eight-year longitudinal, retrospective chart review was performed on all culture-positive hand infections encountered by an urban hospital from 2005 to 2012. The proportions of all major organisms were calculated for each year. Methicillin-resistant Staphylococcus aureus infections …

Activation Of C-Myc And Cyclin D1 By Jcv T-Antigen And Β-Catenin In Colon Cancer, Michael J. Ripple, Amanda Parker Struckhoff, Jimena Trillo-Tinoco, Li Li, David A. Margolin, Robin Mcgoey, Luis Del Valle

School of Medicine Faculty Publications

During the last decade, mounting evidence has implicated the human neurotropic virus JC virus in the pathology of colon cancer. However, the mechanisms of JC virus-mediated oncogenesis are still not fully determined. One candidate to mediate these effects is the viral early transcriptional product T-Antigen, which has the ability to inactivate cell cycle regulatory proteins such as p53. In medulloblastomas, T-Antigen has been shown to bind the Wnt signaling pathway protein β-catenin; however, the effects of this interaction on downstream cell cycle regulatory proteins remain unknown. In light of these observations, we investigated the association of T-Antigen and nuclear β-catenin …

Two Classes Of Nucleic Acid Translocation Motors: Rotation And Revolution Without Rotation, Peixuan Guo, Ian Grainge, Zhengyi Zhao, Mario Vieweger

Markey Cancer Center Faculty Publications

Biomotors are extensively involved in biological processes including cell mitosis, bacterial binary fission, DNA replication, DNA repair, homologous recombination, Holliday junction resolution, RNA transcription, and viral genome packaging. Traditionally, they were classified into two categories including linear and rotation motors. In 2013, a third class of motor by revolution mechanism without rotation was discovered. In this issue of "Structure and mechanisms of nanomotors in the cells", four comprehensive reviews are published to address the latest advancements of the structure and motion mechanism of a variety of biomotors in archaea, animal viruses, bacteria, and bacteriophages.

Circulating Tumor Cells As Early Predictors Of Metastatic Spread In Breast Cancer Patients With Limited Metastatic Dissemination., Mario Giuliano, Antonio Giordano, Summer Jackson, Ugo De Giorgi, Michal Mego, Evan N Cohen, Hui Gao, Simone Anfossi, Beverly C Handy, Naoto T Ueno, Ricardo H Alvarez, Sabino De Placido, Vicente Valero, Gabriel N Hortobagyi, James M Reuben, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

IntroductionTraditional factors currently used for prognostic stratification do not always predict adequately treatment response and disease evolution in advanced breast cancer patients. Therefore, the use of blood-based markers, such as circulating tumor cells (CTCs), represents a promising complementary strategy for disease monitoring. In this retrospective study, we explored the role of CTC counts as predictors of disease evolution in breast cancer patients with limited metastatic dissemination.Methods492 advanced breast cancer patients who had a CTC count assessed by CellSearch prior to starting a new line of systemic therapy were eligible for this analysis. Using the threshold of 5 cells/7.5 mL of …

Acetylation-Defective Mutant Of Pparγ Is Associated With Decreased Lipid Synthesis In Breast Cancer Cells., Lifeng Tian, Chenguang Wang, Fred K Hagen, Michael Gormley, Sankar Addya, Raymond Soccio, Mathew C Casimiro, Jie Zhou, Michael J Powell, Ping Xu, Haiteng Deng, Anthony A Sauve, Richard Pestell

Department of Cancer Biology Faculty Papers

In our prior publications we characterized a conserved acetylation motif (K(R)xxKK) of evolutionarily related nuclear receptors. Recent reports showed that peroxisome proliferator activated receptor gamma (PPARγ) deacetylation by SIRT1 is involved in delaying cellular senescence and maintaining the brown remodeling of white adipose tissue. However, it still remains unknown whether lysyl residues 154 and 155 (K154/155) of the conserved acetylation motif (RIHKK) in Pparγ1 are acetylated. Herein, we demonstrate that Pparγ1 is acetylated and regulated by both endogenous TSA-sensitive and NAD-dependent deacetylases. Acetylation of lysine 154 was identified by mass spectrometry (MS) while deacetylation of lysine 155 by SIRT1 was …

Nuclear Factor Of Activated T-Cells 5 Increases Intestinal Goblet Cell Differentiation Through An Mtor/Notch Signaling Pathway, Yuning Zhou, Qingding Wang, Heidi L. Weiss, B. Mark Evers

Markey Cancer Center Faculty Publications

The intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis that is regulated by multiple signaling pathways. Previously, we have shown that the nuclear factor of activated T-cells 5 (NFAT5) is involved in the regulation of intestinal enterocyte differentiation. Here we show that treatment with sodium chloride (NaCl), which activates NFAT5 signaling, increased mTORC1 repressor regulated in development and DNA damage response 1 (REDD1) protein expression and inhibited mTOR signaling; these alterations were attenuated by knockdown of NFAT5. Knockdown of NFAT5 activated mammalian target of rapamycin (mTOR) signaling and significantly inhibited REDD1 mRNA expression and protein expression. Consistently, …