Digital Commons Network^™

Antenatal Peer Support Workers And Initiation Of Breast Feeding: Cluster Randomised Controlled Trial, Christine Macarthur, Kate Jolly, Lucy Annang Ingram Phd, Nick Freemantle, Cindy-Lee Dennis, Ros Hamburger, Julia Brown, Jackie Chambers, Khalid Khan

Faculty Publications

OBJECTIVE: To assess the effectiveness of an antenatal service using community based breastfeeding peer support workers on initiation of breast feeding. DESIGN: Cluster randomised controlled trial. SETTING: Community antenatal clinics in one primary care trust in a multiethnic, deprived population. PARTICIPANTS: 66 antenatal clinics with 2511 pregnant women: 33 clinics including 1140 women were randomised to receive the peer support worker service and 33 clinics including 1371 women were randomised to receive standard care. INTERVENTION: An antenatal peer support worker service planned to comprise a minimum of two contacts with women to provide advice, information, and support from approximately 24 …

Successional Change In Phosphorus Stoichiometry Explains The Inverse Relationship Between Herbivory And Lupin Density On Mount St. Helens, Jennifer L. Apple, Michael Wink, Shannon E. Wills, John G. Bishop

Biology

Background: The average nitrogen-to-phosphorus ratio (N:P) of insect herbivores is less than that of leaves, suggesting that P may mediate plant-insect interactions more often than appreciated. We investigated whether succession-related heterogeneity in N and P stoichiometry influences herbivore performance on N-fixing lupin (Lupinus lepidus) colonizing primary successional volcanic surfaces, where the abundances of several specialist lepidopteran herbivores are inversely related to lupin density and are known to alter lupin colonization dynamics. We examined larval performance in response to leaf nutritional characteristics using gelechiid and pyralid leaf-tiers, and a noctuid leaf-cutter. Methodology/Principal Findings: We conducted four studies. First, growth of larvae …

Rationale And Design Of A Trial Of Angiotensin-Converting Enzyme Inhibition In Infants With Single Ventricle., Daphne T. Hsu, Seema Mital, Chitra Ravishankar, Renee Margossian, Jennifer S. Li, Lynn A. Sleeper, Richard V. Williams, Jami C. Levine, Brian W. Mccrindle, Andrew M. Atz, Darlene Servedio, Lynn Mahony, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors are known to improve clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology show abnormalities in ventricular function as well as poor growth. The ability of an ACE inhibitor to preserve ventricular function and improve growth in these infants is unknown.

METHODS: The Pediatric Heart Network designed a randomized, double-blind trial to compare outcomes in infants with single-ventricle physiology receiving enalapril or placebo. Neonates < or =45 days old were eligible. The primary outcome is weight-for-age Z-score at 14 months of age. Secondary outcomes include other measures of somatic growth, laboratory and functional measures of heart failure, developmental indices, measures of ventricular size and function, and the relationship of the renin-angiotensin-aldosterone system genotype to the response to enalapril. The incidence and spectrum of adverse events will also be compared between treatment groups.

RESULTS: A total of 1,245 neonates were screened and 533 (43%) were eligible. The consent rate was 43%; 230 subjects were enrolled. Parental reluctance to …

Lung Cancer In A U.S. Population With Low To Moderate Arsenic Exposure, Julia Heck

Dartmouth Scholarship

No abstract provided.

Objectively Measured Physical Activity And Its Association With Adiponectin And Other Novel Metabolic Markers: A Longitudinal Study In Children (Earlybird 38)., Bs Metcalf, An Jeffery, J Hosking, Ld Voss, N Sattar, Tj Wilkin

Peninsula Medical School

OBJECTIVE: Recent evidence suggests that, in children, traditional markers of metabolic disturbance are related only weakly to physical activity. We therefore sought to establish the corresponding relationships with newer metabolic markers. RESEARCH DESIGN AND METHODS: This was a nonintervention longitudinal study of 213 healthy children recruited from 54 schools in Plymouth, U.K. MTI accelerometers were used to make objective 7-day recordings of physical activity at ages 5 +/- 0.3 (mean +/- SD), 6, 7, and 8 years. Overall physical activity was taken as the average of the four annual time points. The metabolic markers at 8 years were adiponectin, leptin, …

Gender Specific Differences In The Pros And Cons Of Smoking Among Current Smokers In Eastern Kentucky: Implications For Future Smoking Cessation Interventions, Dana A. Hazen, David M. Mannino, Richard Clayton

Preventive Medicine and Environmental Health Faculty Publications

This study investigated gender differences in the perceived “pros” and “cons” of smoking using the constructs of decisional balance (DB) and stage of change from the Transtheoretical Model. The population distribution for stage of change among a population-based, cross-sectional survey of 155 current smokers over 40 years was: precontemplation (22.6%), contemplation (41.9%), preparation (35.5%). Results of stepwise regression models indicated significant gender differences in DB were in the preparation stage of change; scores on the DB measure increased 3.94 points (95% CI: 1.94, 5.93) for male smokers. Interventions targeting the “pros” and “cons” of smoking may need to be gender …

Borderline Personality Disorder: An Overview Of History, Diagnosis And Treatment In Adolescents, Linah Al-Alem, Hatim A. Omar

Pharmacology and Nutritional Sciences Faculty Publications

Borderline personality disorder (BPD) is a cluster B personality disorder. It is characterized by erratic behaviors, emotional instability and one of its hallmarks is self injurious behavior, which starts in adolescence. Patients with BPD are difficult to treat, most have a history of child sexual abuse, about a quarter present with sexual abuse from a caretaker. Although personality disorders are diagnosed only in adults, BPD manifests itself in adolescence in the form of uncontrollable anger, self mutilations, dissociation and other such behaviors. Hence, there is a growing number of scientists discussing the possibility of diagnosing BPD in adolescents. Here, we …

Meeting Report: Methylmercury In Marine Ecosystems—From Sources To Seafood Consumers, Celia Y. Chen, Nancy Serrell, David C. Evers, Bethany J. Fleishman, Kathleen F. Lambert, Jeri Weiss, Robert P. Mason, Michael S. Bank

Dartmouth Scholarship

Mercury and other contaminants in coastal and open-ocean ecosystems are an issue of great concern globally and in the United States, where consumption of marine fish and shellfish is a major route of human exposure to methylmercury (MeHg). A recent National Institute of Environmental Health Sciences–Superfund Basic Research Program workshop titled “Fate and Bioavailability of Mercury in Aquatic Ecosystems and Effects on Human Exposure,” convened by the Dartmouth Toxic Metals Research Program on 15–16 November 2006 in Durham, New Hampshire, brought together human health experts, marine scientists, and ecotoxicologists to encourage cross-disciplinary discussion between ecosystem and human health scientists and …

Manufactured Aluminum Oxide Nanoparticles Decrease Expression Of Tight Junction Proteins In Brain Vasculature, Lei Chen, Robert A. Yokel, Bernhard Hennig, Michal Toborek

Pharmaceutical Sciences Faculty Publications

Manufactured nanoparticles of aluminum oxide (nano-alumina) have been widely used in the environment; however, their potential toxicity provides a growing concern for human health. The present study focuses on the hypothesis that nano-alumina can affect the blood-brain barrier and induce endothelial toxicity. In the first series of experiments, human brain microvascular endothelial cells (HBMEC) were exposed to alumina and control nanoparticles in dose- and time-responsive manners. Treatment with nano-alumina markedly reduced HBMEC viability, altered mitochondrial potential, increased cellular oxidation, and decreased tight junction protein expression as compared to control nanoparticles. Alterations of tight junction protein levels were prevented by cellular …

Intracerebral Hemorrhage For The Palliative Care Provider: What You Need To Know., B Brent Simmons, Susan M Parks

Department of Family & Community Medicine Faculty Papers

Intracerebral hemorrhage (ICH) makes up 10%-30% of all strokes. Palliative care providers are often asked to get involved with ICH cases to aid with development of short-term and long-term goals. Prognosis can be calculated using the ICH score (based on Glasgow Coma Score score, ICH volume, presence of intraventricular hemorrhage, age, and location of origin) or the Essen score (based on age, NIH Stroke Scale [NIHSS], and level of consciousness). Do-not-resuscitate (DNR) status is important to discuss with families. Expert consensus states DNR is appropriate if the patient has two of the following: severe stroke, life-threatening brain damage, or significant …

Improving Outcomes In Infants Of Hiv-Infected Women In A Developing Country Setting, Francine Noel, Sapna Mehta, Yuwei Zhu, Patricia De Matteis Rouzier, Abdias Marcelin, Jian R. Shi, Claudine Nolte, Linda Severe, Marie Marcelle Deschamps, Daniel W. Fitzgerald, Warren D. Johnson, Peter F. Wright, Jean W. Pape

Dartmouth Scholarship

Background: Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries.

Methods and Findings: We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given “short-course” monotherapy with antiretrovirals …

Predictors Of Emesis And Time To Goal Intake After Pyloromyotomy: Analysis From A Prospective Trial., Shawn D. St Peter, Kuojen Tsao, Susan W. Sharp, G W. Holcomb Iii, Daniel J. Ostlie

Manuscripts, Articles, Book Chapters and Other Papers

Background: Emesis after pyloromyotomy for pyloric stenosis is a common clinical phenomenon and the limiting factor in time to goal feeds. The amount of emesis that can be expected after myotomy is unknown. No data have been published that equip caregivers with the ability to understand which patients are more likely to have emesis and take longer to advance to goal feeds after pyloromyotomy. Therefore, we performed analysis of prospective data obtained from a randomized trial to determine if outcome can be predicted from preoperative or intraoperative variables.

Methods: The dataset was prospectively collected from a randomized trial comparing open …

Concept, Design And Implementation Of A Cardiovascular Gene-Centric 50 K Snp Array For Large-Scale Genomic Association Studies, Brendan J. Keating, Sam Tischfield, Sarah S. Murray, Tushar Bhangale, Thomas S. Price, Joseph T. Glessner, Luana Galver, Jeffrey C. Barrett, Struan F A Grant, Deborah N. Farlow, Hareesh R. Chandrupatla, Mark Hansen, Saad Ajmal, George J. Papanicolaou, Yiran Guo, Mingyao Li, Stephanie Derohannessian, Paul I W. De Bakker, Swneke D. Bailey, Alexandre Montpetit, Andrew C. Edmondson, Kent Taylor, Xiaowu Gai, Susanna S. Wang, Myriam Fornage, Tamim Shaikh, Leif Groop, Michael Boehnke, Alistair S. Hall, Andrew T. Hattersley, Edward Frackelton, Nick Patterson, Charleston K W Chiang, Cecelia E. Kim, Richard R. Fabsitz, Willem Ouwehand, Alkes L. Price, Patricia Munroe, Mark Caulfield, Thomas Drake, Eric Boerwinkle, David Reich, A Stephen Whitehead, Thomas P. Cappola, Nilesh J. Samani, A Jake Lusis, Eric Schadt, James G. Wilson, Wolfgang Koenig, Mark I. Mccarthy, Sekar Kathiresan, Stacey B. Gabriel, Hakon Hakonarson, Sonia S. Anand, Muredach Reilly, James C. Engert, Deborah A. Nickerson, Daniel J. Rader, Joel N. Hirschhorn, Garret A. Fitzgerald

Faculty, Staff and Student Publications

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 …

Characteristics Of A Spina Bifida Population Including North American Caucasian And Hispanic Individuals, Kit Sing Au, Phong X Tran, Chester C Tsai, Michelle R O'Byrne, Jone-Ing Lin, Alanna C Morrison, Amy W Hampson, Paul Cirino, Jack M Fletcher, Kathryn K Ostermaier, Gayle H Tyerman, Sabine Doebel, Hope Northrup

Faculty, Staff and Student Publications

BACKGROUND: Meningomyelocele (MM) is a common human birth defect. MM is a disorder of neural development caused by contributions from genes and environmental factors that result in the NTD and lead to a spectrum of physical and neurocognitive phenotypes.

METHODS: A multidisciplinary approach has been taken to develop a comprehensive understanding of MM through collaborative efforts from investigators specializing in genetics, development, brain imaging, and neurocognitive outcome. Patients have been recruited from five different sites: Houston and the Texas-Mexico border area; Toronto, Canada; Los Angeles, California; and Lexington, Kentucky. Genetic risk factors for MM have been assessed by genotyping and …

Molecular And Macromolecular Alterations Of Recombinant Adenoviral Vectors Do Not Resolve Changes In Hepatic Drug Metabolism During Infection, Shellie M Callahan, Piyanuch Wonganan, Maria A Croyle

Faculty, Staff and Student Publications

In this report we test the hypothesis that long-term virus-induced alterations in CYP occur from changes initiated by the virus that may not be related to the immune response. Enzyme activity, protein expression and mRNA of CYP3A2, a correlate of human CYP3A4, and CYP2C11, responsive to inflammatory mediators, were assessed 0.25, 1, 4, and 14 days after administration of several different recombinant adenoviruses at a dose of 5.7 x 1012 virus particles (vp)/kg to male Sprague Dawley rats. Wild type adenovirus, containing all viral genes, suppressed CYP3A2 and 2C11 activity by 37% and 39%, respectively within six hours. Levels fell …

Genetic Variation In Genes For The Xenobiotic-Metabolizing Enzymes Cyp1a1, Ephx1, Gstm1, Gstt1, And Gstp1 And Susceptibility To Colorectal Cancer In Lynch Syndrome, Mala Pande, Christopher I Amos, Daniel R Osterwisch, Jinyun Chen, Patrick M Lynch, Russell Broaddus, Marsha L Frazier

Faculty, Staff and Student Publications

Individuals with Lynch syndrome are predisposed to cancer due to an inherited DNA mismatch repair gene mutation. However, there is significant variability observed in disease expression likely due to the influence of other environmental, lifestyle, or genetic factors. Polymorphisms in genes encoding xenobiotic-metabolizing enzymes may modify cancer risk by influencing the metabolism and clearance of potential carcinogens from the body. In this retrospective analysis, we examined key candidate gene polymorphisms in CYP1A1, EPHX1, GSTT1, GSTM1, and GSTP1 as modifiers of age at onset of colorectal cancer among 257 individuals with Lynch syndrome. We found that subjects heterozygous for CYP1A1 I462V …

Is American Health Care Uniquely Inefficient?, Alan M. Garber, Jonathan Skinner

Dartmouth Scholarship

No abstract provided.

Muscle-Bone Relationships In The Lower Leg Of Healthy Pre-Pubertal Females And Males, Teresa L. Binkley, Bonny Specker

Ethel Austin Martin Program Publications

Muscle-bone relationships in healthy pre-pubertal children were investigated using four muscle measures as predictors of tibial strength: 66% tibia cross-sectional muscle area (CSMA) by pQCT; leg lean mass (LLM) by DXA; and muscle power (Power) and force (Force) measured during a two-footed jump. Polar strength strain index (pSSI), a calculated surrogate for bone strength at the 20% distal tibia, was obtained on 105 (54 male) self-assessed pre-pubertal children. The amount of muscle (CSMA, LLM) may influence bone strength more than muscle strength (Power, Force) during periods of rapid growth. Correlations and multiple regression partial-R values from models controlling for age, …

Integrative Medicine Research At An Academic Medical Center: Patient Characteristics And Health-Related Quality-Of-Life Outcomes., Jeffrey M Greeson, Steven Rosenzweig, Steven C Halbert, Ira S Cantor, Matthew T Keener, George C Brainard

College of Science & Mathematics Departmental Research

OBJECTIVE: To characterize patients seeking care at a university-based integrative medicine practice, and to assess short-term changes in health-related quality of life (HRQoL) associated with integrative medical treatment.

DESIGN: Prospective, observational study.

SETTING: This study was conducted at a large U.S. academic medical center affiliated with the Consortium of Academic Health Centers for Integrative Medicine.

PARTICIPANTS: Seven hundred and sixty-three (763) new patients with diverse medical conditions participated in the study. Mean age was 49 years (standard deviation = 16, range = 14-93). Two thirds of patients were women and three quarters were white. The most common International Classification of …

Surrogate Markers Of Success In The Bariatric Surgery Population, Alain Ramirez

Yale Medicine Thesis Digital Library

Purpose: The purpose of this study was to examine the associations between pre-operative weight loss, weight loss programs, and clinic attendance relative to the success of gastric bypass in class II and III obese patients. Background: The increasing number of obese children and adults in the United States poses an extensive social problem in the era of managed care. Notwithstanding the stigmatization associated with obesity, the considerable health implications along with the financial burden it imposes create a formidable adversary. Surgical procedures have proved to be superior to conservative and pharmacotherapeutic interventions in the morbidly obese. Despite the overall success …

Preventing Cardiovascular Disease In Kentucky: Epidemiology, Trends, And Strategies For The Future, Sarah Sartini Rugg, Alison L. Bailey, Steven R. Browning

Internal Medicine Faculty Publications

Cardiovascular disease (CVD) is the leading cause of death in the United States despite dramatic improvements in the treatment of heart disease in recent years. Kentucky leads the nation in the prevalence of several individual risk factors for cardiovascular disease, the prevalence of multiple risk factors, and in cardiovascular mortality. While trends in the prevalence of some of these cardiac risk factors have shown improvement, others have remained unchanged or have worsened. The increased prevalence of obesity and diabetes, especially among young persons, is one of the most worrisome trends. The prevalence of smoking in Kentucky remains high, and has …

Fat Embolism Syndrome., Renu Saigal, M Mittal, A Kansal, Y Singh, P R. Kolar, Shobhit Jain

Manuscripts, Articles, Book Chapters and Other Papers

Fat embolism syndrome is a rare complication occurring in 0.5 to 2% of patients following a long bone fracture. It is believed to be caused by the toxic effects of free fatty acids. Diagnosis is clinical, based on respiratory, cerebral and dermal manifestations. Treatment is only supportive, directed mainly at maintaining respiratory functions.

Application Of Prodrugs To Inflammatory Diseases Of The Gut, Helieh S. Oz, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Oral delivery is the most common and preferred route of drug administration although the digestive tract exhibits several obstacles to drug delivery including motility and intraluminal pH profiles. The gut milieu represents the largest mucosal surface exposed to microorganisms with 10^10-12 colony forming bacteria/g of colonic content. Approximately, one third of fecal dry matter is made of bacteria/ bacterial components. Indeed, the normal gut microbiota is responsible for healthy digestion of dietary fibers (polysaccharides) and fermentation of short chain fatty acids such as acetate and butyrate that provide carbon sources (fuel) for these bacteria. Inflammatory bowel disease (IBD) results …

The Uses Of Rickets: Race, Technology, And The Politics Of Preventive Medicine In The Early Twentieth Century, M. Allison Arwady

Yale Medicine Thesis Digital Library

Rickets, the bone disease classically caused by Vitamin D deficiency, was one of the most common diseases of children 100 years ago. It has been recognized as a disease of urban living and linked to issues of race and culture for generations. This paper uses unpublished patient records from 1904 to 1909 and archival and published materials from multiple community-based trials, including the New Haven Rickets Study (1923-1926), to explore how the definition, diagnosis, and treatment of rickets shifted in the first decades of the twentieth century in the United States. Before 1910, as evidenced by patient records, neither the …

Obesity, Hypertension, And Mental Health Evaluation In Adolescents: A Comprehensive Approach, Stefan G. Kiessling, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

The global epidemic of childhood and adolescent obesity in developing and developed countries has become a major public health concern. Given the relation between obesity and hypertension as documented in several landmark studies, it is no surprise that as the prevalence of obesity has increased in the pediatric population, the rates of hypertension have also increased substantially. Hypertension is one of the most important risk factors for cardiovascular diseases and stroke; therefore, evaluation and initiation of appropriate treatment are extremely important in the pediatric population. Evaluation for secondary causes of hypertension, including renovascular, renoparenchymal, and endocrine disease is the approach …

Will The Stork Return To Europe And Japan? Understanding Fertility Within Developed Nations, James Feyrer, Bruce Sacerdote, Ariel Dora Stern

Dartmouth Scholarship

We seek to explain the differences in fertility rates across high-income countries by focusing on the interaction between the increasing status of women in the workforce and their status in the household, particularly with regards to child care and home production. We observe three distinct phases in women's status generated by the gradual increase in women's workforce opportunities. In the earliest phase, characteristic of the 1950s and 1960s in the United States, women earn low wages relative to men and are expected to shoulder all of the child care at home. As a result, most women specialize in home production …

Developing "Human Functioning And Rehabilitation Research" From The Comprehensive Perspective., Gerold Stucki, Jan Dietrich Reinhardt, Gunnar Grimby, John Melvin

Department of Rehabilitation Medicine Faculty Papers

With the International Classification of Functioning, Disability and Health (ICF) the World Health Organization (WHO) has prepared the ground for a comprehensive understanding of Human Functioning and Rehabilitation Research, integrating the biomedical perspective on impairment with the social model of disability. This poses a number of old and new challenges regarding the enhancement of adequate research capacity. Here we will summarize approaches to address these challenges with respect to 3 areas: the organization of Human Functioning and Rehabilitation Research into distinct scientific fields, the development of suitable academic training programmes and the building of university centres and collaboration networks.

Nicotinamide Riboside Kinase Structures Reveal New Pathways To Nad+, Wolfram Tempel, Wael M. Rabeh, Katrina L. Bogan, Peter Belenky, Marzena Wojcik, Heather F. Seidle, Lyudmila Nedyalkova, Tianle Yang, Anthony A. Sauve, Hee-Won Park, Charles Brenner

Dartmouth Scholarship

The eukaryotic nicotinamide riboside kinase (Nrk) pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize …

Effects Of Atomoxetine On Growth In Children With Attention-Deficit/Hyperactivity Disorder Following Up To Five Years Of Treatment., Thomas J. Spencer, Christopher J. Kratochvil, R. Bart Sangal, Keith E. Saylor, Charles E. Bailey, David W. Dunn, Daniel A. Geller, Charles D. Casat, Robert S. Lipetz, Rakesh Jain, Jeffrey H. Newcorn, Dustin D. Ruff, Peter D. Feldman, Amanda J. Furr, Albert J. Allen

Journal Articles: Psychiatry

OBJECTIVE: To examine the effects on growth of long-term pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), we present findings from an ongoing 5-year study of the efficacy and safety of treatment with atomoxetine.

METHODS: North American patients, 6-17 years old at study entry (N = 1,312) and with Diagnostic and Statistical Manual of Mental Disorders,4th edition (DSM-IV) ADHD, were studied under open-label atomoxetine treatment. Sixty-one were studied up to 5 years.

RESULTS: After 1 month's treatment, patients weighed less than expected from their starting percentiles relative to population norms, with a maximum shortfall at 15 months and a return to expected …

Selective Repression Of Retinoic Acid Target Genes By Rip140 During Induced Tumor Cell Differentiation Of Pluripotent Human Embryonal Carcinoma Cells, Kelly C. Heim, Kristina A. White, Dexin Deng, Craig R. Tomlinson, Jason Moore, Sarah Freemantle, Michael Spinella

Dartmouth Scholarship

The use of retinoids as anti-cancer agents has been limited due to resistance and low efficacy. The dynamics of nuclear receptor coregulation are incompletely understood. Cell-and context-specific activities of nuclear receptors may be in part due to distinct coregulator complexes recruited to distinct subsets of target genes. RIP140 (also called NRIP1) is a ligand-dependent corepressor that is inducible with retinoic acid (RA). We had previously shown that RIP140 limits RA induced tumor cell differentiation of embryonal carcinoma; the pluriopotent stem cells of testicular germ cell tumors. This implies that RIP140 represses key genes required for RA-mediated tumor cell differentiation. Identification …