Medicine and Health Sciences Commons^™

Intra-Tumor Heterogeneity Of Mlh1 Promoter Methylation Revealed By Deep Single Molecule Bisulfite Sequencing., Katherine E Varley, David G Mutch, Tina B Edmonston, Paul J Goodfellow, Robi D Mitra

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A single tumor may contain cells with different somatic mutations. By characterizing this genetic heterogeneity within tumors, advances have been made in the prognosis, treatment and understanding of tumorigenesis. In contrast, the extent of epigenetic intra-tumor heterogeneity and how it influences tumor biology is under-explored. We have characterized epigenetic heterogeneity within individual tumors using next-generation sequencing. We used deep single molecule bisulfite sequencing and sample-specific DNA barcodes to determine the spectrum of MLH1 promoter methylation across an average of 1000 molecules in each of 33 individual samples in parallel, including endometrial cancer, matched blood and normal endometrium. This first glimpse, …

Functional State Following The Fontan Procedure., Ismee A. Williams, Lynn A. Sleeper, Steven D. Colan, Minmin Lu, Elizabeth A. Stephenson, Jane W. Newburger, Welton M. Gersony, Meryl S. Cohen, James F. Cnota, Andrew M. Atz, Richard V. Williams, Renee Margossian, Andrew J. Powell, Mario P. Stylianou, Daphne T. Hsu, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite improvements in outcomes after completion of the Fontan circulation, long-term functional state varies. We sought to identify pre- and postoperative characteristics associated with overall function.

METHODS AND RESULTS: We analyzed data from 476 survivors with the Fontan circulation enrolled in the Pediatric Heart Network Fontan Cross-sectional Study. Mean age at creation of the Fontan circulation was 3.4 plus or minus 2.1 years, with a range from 0.7 to 17.5 years, and time since completion was 8.7 plus or minus 3.4 years, the range being from 1.1 to 17.3 years. We calculated a functional score for the survivors by …

The Time Has Come For Physicians To Take Notice: The Impact Of Psychosocial Stressors On The Heart., Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

A rapidly growing body of evidence supports a relationship between psychosocial factors and cardiovascular disease. In this article, a review of the epidemiologic and clinical research investigating this relationship concludes that psychosocial stressors can be both a cause and a consequence of cardiovascular disease events. Furthermore, recent data have shown that stress management might reduce future cardiac events in patients with cardiovascular disease. Unfortunately, the influence of psychosocial risk factors on cardiovascular disease remains underrecognized compared with traditional cardiac risk factors. Physicians and their associates should screen for psychosocial stressors and recognize potential symptoms. Consideration should be given to developing …

Comparison Of Echocardiographic And Cardiac Magnetic Resonance Imaging Measurements Of Functional Single Ventricular Volumes, Mass, And Ejection Fraction (From The Pediatric Heart Network Fontan Cross-Sectional Study)., Renee Margossian, Marcy L. Schwartz, Ashwin Prakash, Lisa Wruck, Steven D. Colan, Andrew M. Atz, Timothy J. Bradley, Mark A. Fogel, Lynne M. Hurwitz, Edward Marcus, Andrew J. Powell, Beth F. Printz, Michael D. Puchalski, Jack Rychik, Girish S. Shirali, Richard Williams, Shi-Joon Yoo, Tal Geva, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Assessment of the size and function of a functional single ventricle (FSV) is a key element in the management of patients after the Fontan procedure. Measurement variability of ventricular mass, volume, and ejection fraction (EF) among observers by echocardiography and cardiac magnetic resonance imaging (CMR) and their reproducibility among readers in these patients have not been described. From the 546 patients enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study (mean age 11.9 +/- 3.4 years), 100 echocardiograms and 50 CMR studies were assessed for measurement reproducibility; 124 subjects with paired studies were selected for comparison between modalities. Interobserver agreement …

Food Insecurity Among Homeless And Marginally Housed Individuals Living With Hiv/Aids In San Francisco, Sheri D. Weiser, David R. Bangsberg, Susan Kegeles, Kathleen Ragland, Margot B. Kushel, Edward A. Frongillo Jr.

Faculty Publications

Food insecurity is a risk factor for both HIV transmission and worse HIV clinical outcomes. We examined the prevalence of and factors associated with food insecurity among homeless and marginally housed HIV-infected individuals in San Francisco recruited from the Research on Access to Care in the Homeless Cohort. We used multiple logistic regression to determine socio-demographic and behavioral factors associated with food insecurity, which was measured using the Household Food Insecurity Access Scale. Among 250 participants, over half (53.6%) were food insecure. Higher odds of food insecurity was associated with being white, low CD4 counts, recent crack use, lack of …

R992c (P.R1192c) Substitution In Collagen Ii Alters The Structure Of Mutant Molecules And Induces The Unfolded Protein Response., Hye Jin Chung, Deborah A. Jensen, Katarzyna Gawron, Andrzej Steplewski, Andrzej Fertala

Department of Dermatology and Cutaneous Biology Faculty Papers

We investigated the molecular bases of spondyloepiphyseal dysplasia (SED) associated with the R992C (p.R1192C) substitution in collagen II. At the protein level, we analyzed the structure and integrity of mutant molecules, and at the cellular level, we specifically studied the effects of the presence of the R992C collagen II on the biological processes taking place in host cells. Our studies demonstrated that mutant collagen II molecules were characterized by altered electrophoretic mobility, relatively low thermostability, the presence of atypical disulfide bonds, and slow rates of secretion into the extracellular space. Analyses of cellular responses to the presence of the mutant …

A Functional Difficulty And Functional Pain Instrument For Hip And Knee Osteoarthritis, Alan M. Jette, Christine M. Mcdonough, Pengsheng Ni, Stephen M. Haley

Dartmouth Scholarship

The objectives of this study were to develop a functional outcome instrument for hip and knee osteoarthritis research (OA-FUNCTION-CAT) using item response theory (IRT) and computer adaptive test (CAT) methods and to assess its psychometric performance compared to the current standard in the field.

Suppression Of Rhog Activity Is Mediated By A Syndecan 4–Synectin–Rhogdi1 Complex And Is Reversed By Pkcα In A Rac1 Activation Pathway, Arye Elfenbein, John M. Rhodes, Julia Meller, Martin A. Schwartz, Michiyuki Matsuda, Michael Simons

Dartmouth Scholarship

Fibroblast growth factor 2 (FGF2) is a major regulator of developmental, pathological, and therapeutic angiogenesis. Its activity is partially mediated by binding to syndecan 4 (S4), a proteoglycan receptor. Angiogenesis requires polarized activation of the small guanosine triphosphatase Rac1, which involves localized dissociation from RhoGDI1 and association with the plasma membrane. Previous work has shown that genetic deletion of S4 or its adapter, synectin, leads to depolarized Rac activation, decreased endothelial migration, and other physiological defects. In this study, we show that Rac1 activation downstream of S4 is mediated by the RhoG activation pathway. RhoG is maintained in an inactive …

Perirhinal Cortex Contributes To Accuracy In Recognition Memory And Perceptual Discriminations., Edward B O'Neil, Anthony D Cate, Stefan Köhler

Brain and Mind Institute Researchers' Publications

The prevailing view of the medial temporal lobe (MTL) holds that its structures are dedicated to long-term declarative memory. Recent evidence challenges this position, suggesting that perirhinal cortex (PRc) in the MTL may also play a role in perceptual discriminations of stimuli with substantial visual feature overlap. Relevant neuropsychological findings in humans have been inconclusive, likely because studies have relied on patients with large and variable MTL lesions. Here, we conducted a functional magnetic resonance imaging study in healthy individuals to determine whether PRc shows a performance-related involvement in perceptual oddball judgments that is comparable to its established role in …

Improving Clinical Quality Indicators Through Electronic Health Records: It Takes More Than Just A Reminder, Dean F Sittig, Jonathan M Teich, Jerome A Osheroff, Hardeep Singh

Faculty, Staff and Student Publications

No abstract provided.

Epidemiology And Outcomes Of Candidemia In 2019 Patients: Data From The Prospective Antifungal Therapy Alliance Registry., David L Horn, Dionissios Neofytos, Elias J Anaissie, Jay A Fishman, William J Steinbach, Ali J Olyaei, Kieren A Marr, Michael A Pfaller, Chi-Hsing Chang, Karen M Webster

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing.

METHODS: Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis.

RESULTS: The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher …

Modulation Of Edna Release And Degradation Affects Staphylococcus Aureus Biofilm Maturation., Ethan E. Mann, Kelly C. Rice, Blaise R. Boles, Jennifer L. Endres, Dev Ranjit, Lakshmi Chandramohan, Laura H. Tsang, Mark S. Smeltzer, Alexander R. Horswill, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

Recent studies have demonstrated a role for Staphylococcus aureus cidA-mediated cell lysis and genomic DNA release in biofilm adherence. The current study extends these findings by examining both temporal and additional genetic factors involved in the control of genomic DNA release and degradation during biofilm maturation. Cell lysis and DNA release were found to be critical for biofilm attachment during the initial stages of development and the released DNA (eDNA) remained an important matrix component during biofilm maturation. This study also revealed that an lrgAB mutant exhibits increased biofilm adherence and matrix-associated eDNA consistent with its proposed role as an …

A Truncation Mutation In Tbc1d4 In A Family With Acanthosis Nigricans And Postprandial Hyperinsulinemia, Satya Dash, Hiroyuki Sano, Justin J. Rochford, Robert K. Semple

Dartmouth Scholarship

Tre-2, BUB2, CDC16, 1 domain family member 4 (TBC1D4) (AS160) is a Rab-GTPase activating protein implicated in insulin-stimulated glucose transporter 4 (GLUT4) translocation in adipocytes and myotubes. To determine whether loss-of-function mutations in TBC1D4 might impair GLUT4 translocation and cause insulin resistance in humans, we screened the coding regions of this gene in 156 severely insulin-resistant patients. A female presenting at age 11 years with acanthosis nigricans and extreme postprandial hyperinsulinemia was heterozygous for a premature stop mutation (R363X) in TBC1D4. After demonstrating reduced expression of wild-type TBC1D4 protein and expression of the truncated protein in lymphocytes from the proband, …

A Retrospective Claims Analysis Of Combination Therapy In The Treatment Of Adult Attention-Deficit/Hyperactivity Disorder (Adhd), Gerhardt M. Pohl, David L. Van Brunt, Wenyu Ye, William W. Stoops, Joseph A. Johnston

Behavioral Science Faculty Publications

BACKGROUND: Combination therapy in managing psychiatric disorders is not uncommon. While combination therapy has been documented for depression and schizophrenia, little is known about combination therapy practices in managing attention-deficit/hyperactivity disorder (ADHD). This study seeks to quantify the combination use of ADHD medications and to understand predictors of combination therapy.

METHODS: Prescription dispensing events were drawn from a U.S. national claims database including over 80 managed-care plans. Patients studied were age 18 or over with at least 1 medical claim with a diagnosis of ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 314.0), a pharmacy claim for …

Development And Validation Of An Index Of Musculoskeletal Functional Limitations, Jeffrey N. Katz, Elizabeth A. Wright, John A. Baron, Elena Losina

Dartmouth Scholarship

While musculoskeletal problems are leading sources of disability, there has been little research on measuring the number of functionally limiting musculoskeletal problems for use as predictor of outcome in studies of chronic disease. This paper reports on the development and preliminary validation of a self administered musculoskeletal functional limitations index.

Strategic Management And Organizational Behavior In Dental Education: Reflections On Key Issues In An Environment Of Change., David G. Dunning, Timothy M. Durham, Brian M. Lange, Mert N. Aksu

Journal Articles: College of Dentistry

With issues such as shrinking revenue, access to care, faculty workloads, and graying faculty, dental schools are faced with difficult challenges that fall to dental school deans to manage. Do dental school deans have the organizational skill sets and ethical frameworks necessary to address the challenges now facing dental schools? The purpose of this article is to pose questions and suggestions regarding some of the key issues in dental colleges today and to stimulate discussion in the dental community about needed changes in dental education.

Death Receptor 5 Internalization Is Required For Lysosomal Permeabilization By Trail In Malignant Liver Cell Lines., Yuko Akazawa, Justin L. Mott, Steven F. Bronk, Nathan W. Werneburg, Alisan Kahraman, Maria Eugenia Guicciardi, Xue Wei Meng, Shigeru Kohno, Vijay H. Shah, Scott H. Kaufmann, Mark A. Mcniven, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND & AIMS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity in hepatocellular carcinoma cells is mediated by lysosomal permeabilization. Our aims were to determine which TRAIL receptor, death receptor (DR) 4 or DR5, mediates lysosomal permeabilization and assess whether receptor endocytosis followed by trafficking to lysosomes contributes in this process.

METHODS: TRAIL ligand internalization in Huh-7 cells was examined by confocal microscopy using Flag-tagged TRAIL, whereas DR4- and DR5-enhanced green fluorescent protein internalization was assessed by total internal reflection microscopy. Clathrin-dependent endocytosis was inhibited by expressing dominant negative dynamin.

RESULTS: Although Huh-7 cells express both TRAIL receptors, short hairpin RNA …

Clinical And Translational Implications Of The Caveolin Gene Family: Lessons From Mouse Models And Human Genetic Disorders., Isabelle Mercier, Jean-Francois Jasmin, Stephanos Pavlides, Carlo Minetti, Neal Flomenberg, Richard G Pestell, Philippe G Frank, Federica Sotgia, Michael P Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Here we review the clinical and translational implications of the caveolin gene family for understanding the pathogenesis of human diseases, including breast and prostate cancers, pulmonary hypertension, cardiomyopathy, diabetes, and muscular dystrophy. Detailed phenotypic analysis of caveolin knockout mice has served to highlight the crucial role of a caveolin deficiency in the pathogenesis of many human disease processes. Mutations in the human caveolin genes are associated with a number of established genetic disorders (such as breast cancer, lipodystrophy, muscular dystrophy, and cardiomyopathy), making the caveolins important and novel targets for drug development. The implementation of new strategies for caveolin replacement …

Cancer Information-Seeking Experiences: The Implications Of Hispanic Ethnicity And Spanish Language, Robin C. Vanderpool, Julie Kornfeld, Lila Finney Rutten, Linda Squiers

Health, Behavior & Society Faculty Publications

BACKGROUND: Strategies to support cancer information-seeking among Hispanics are needed.

METHODS: We analyzed data from the 2005 Health Information National Trends Survey (HINTS) to explore cancer information-seeking experiences among respondents according to ethnicity and language of interview.

RESULTS: Over 80% of Spanish-speaking Hispanics had never looked for cancer information. Compared to English-speaking respondents, Spanish-speaking Hispanics who sought cancer information indicated their search took a lot of effort (67%), was hard to understand (54%), and frustrating (42%). Spanish-speaking Hispanics noted minimal confidence in obtaining cancer information.

CONCLUSIONS: Language and cultural differences must be considered in the design, implementation, and dissemination of …

Revisiting Histidine-Dependent Acid Phosphatases: A Distinct Group Of Tyrosine Phosphatases., Suresh Veeramani, Ming-Shyue Lee, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

Although classical protein tyrosine phosphatase (PTP) superfamily members are cysteine-dependent, emerging evidence shows that many acid phosphatases (AcPs) function as histidine-dependent PTPs in vivo. These AcPs dephosphorylate phospho-tyrosine substrates intracellularly and could have roles in development and disease. In contrast to cysteine-dependent PTPs, they utilize histidine, rather than cysteine, for substrate dephosphorylation. Structural analyses reveal that active site histidine, but not cysteine, faces towards the substrate and functions as the phosphate acceptor. Nonetheless, during dephosphorylation, both histidine-dependent and cysteine-dependent PTPs use their active site arginine and aspartate for substrate binding and proton donation, respectively. Thus, we propose that they should …

It Is More Than Just A Reproductive Healthcare Visit: Experiences From An Adolescent Medicine Clinic, Marlene B. Huff, Kimberly K. Mcclanahan, Heather A. Brown, Hatim A. Omar

Pediatrics Faculty Publications

The gynecologist may be the only physician that an adolescent depends on for primary and reproductive healthcare services. Because adolescent females often make personal healthcare decisions without the benefit of supportive parents/caregivers, it is imperative that the gynecologist understands the developmental issues encountered during this phase of life. The objective of this study is to identify cited complaints of adolescent females seeking reproductive care and, thus, provide gynecologists with needed information about the medical/mental health issues that may be encountered during routine reproductive care exams. The study group was adolescent females between the ages of 12 and 20 years old. …

Therapeutic Targeting Of Atp7b In Ovarian Carcinoma, Lingegowda S Mangala, Vesna Zuzel, Rosemarie Schmandt, Erik S Leshane, Jyotsna B Halder, Guillermo N Armaiz-Pena, Whitney A Spannuth, Takemi Tanaka, Mian M K Shahzad, Yvonne G Lin, Alpa M Nick, Christopher G Danes, Jeong-Won Lee, Nicholas B Jennings, Pablo E Vivas-Mejia, Judith K Wolf, Robert L Coleman, Zahid H Siddik, Gabriel Lopez-Berestein, Svetlana Lutsenko, Anil K Sood

Faculty, Staff and Student Publications

PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models.

EXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC).

RESULTS: ATP7A …

Interaction With Lc8 Is Required For Pak1 Nuclear Import And Is Indispensable For Zebrafish Development., Christine M Lightcap, Gabor Kari, Luis E Arias-Romero, Jonathan Chernoff, Ulrich Rodeck, John C Williams

Department of Biochemistry and Molecular Biology Faculty Papers

Pak1 (p21 activated kinase 1) is a serine/threonine kinase implicated in regulation of cell motility and survival and in malignant transformation of mammary epithelial cells. In addition, the dynein light chain, LC8, has been described to cooperate with Pak1 in malignant transformation of breast cancer cells. Pak1 itself may aid breast cancer development by phosphorylating nuclear proteins, including estrogen receptor alpha. Recently, we showed that the LC8 binding site on Pak1 is adjacent to the nuclear localization sequence (NLS) required for Pak1 nuclear import. Here, we demonstrate that the LC8-Pak1 interaction is necessary for epidermal growth factor (EGF)-induced nuclear import …

Decorin Is A Novel Antagonistic Ligand Of The Met Receptor., Silvia Goldoni, Ashley Humphries, Alexander Nyström, Sampurna Sattar, Rick T Owens, David J Mcquillan, Keith Ireton, Renato V Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a member of the small leucine-rich proteoglycan gene family, impedes tumor cell growth by down-regulating the epidermal growth factor receptor. Decorin has a complex binding repertoire, thus, we predicted that decorin would modulate the bioactivity of other tyrosine kinase receptors. We discovered that decorin binds directly and with high affinity (K(d) = approximately 1.5 nM) to Met, the receptor for hepatocyte growth factor (HGF). Binding of decorin to Met is efficiently displaced by HGF and less efficiently by internalin B, a bacterial Met ligand. Interaction of decorin with Met induces transient receptor activation, recruitment of the E3 ubiquitin ligase …

Hiv Policy: The Path Forward--A Joint Position Paper Of The Hiv Medicine Association Of The Infectious Diseases Society Of America And The American College Of Physicians., Christine Lubinski, Judith Aberg, Arlene D Bardeguez, Richard Elion, Patricia Emmanuel, Daniel Kuritzkes, Michael Saag, Kathleen E Squires, Andrea Weddle, Jennifer Rainey, M Renee Zerehi, J Fred Ralston, David A Fleming, David Bronson, Molly Cooke, Charles Cutler, Yul Ejnes, Robert Gluckman, Mark Liebow, Kenneth Musana, Mark E Mayer, Mark W Purtle, P Preston Reynolds, Lavanya Viswanathan, Kevin B Weiss, Baligh Yehia

Department of Medicine Faculty Papers

Executive Summary

The American College of Physicians (ACP) and the Infectious Diseases Society of America (IDSA) have jointly published 3 policy statements on AIDS, the first in 1986 [1], the second in 1988 [2], and the third in 1994 [3]. In 2001, the IDSA created the HIV Medicine Association (HIVMA), and this updated policy paper is a collaboration between the ACP and the HIVMA of the IDSA. Since the last statement, many new developments call for the need to reexamine and update our policies relating to HIV infection. First, there have been major advances …

A Gene Expression Predictor Of Response To Egfr-Targeted Therapy Stratifies Progression-Free Survival To Cetuximab In Kras Wild-Type Metastatic Colorectal Cancer, Justin M. Balko, Esther P. Black

Pharmaceutical Sciences Faculty Publications

BACKGROUND: The anti-EGFR monoclonal antibody cetuximab is used in metastatic colorectal cancer (CRC), and predicting responsive patients garners great interest, due to the high cost of therapy. Mutations in the KRAS gene occur in ~40% of CRC and are a negative predictor of response to cetuximab. However, many KRAS-wildtype patients do not benefit from cetuximab. We previously published a gene expression predictor of sensitivity to erlotinib, an EGFR inhibitor. The purpose of this study was to determine if this predictor could identify KRAS-wildtype CRC patients who will benefit from cetuximab therapy.

METHODS: Microarray data from 80 metastatic CRC patients subsequently …

A Novel Codon Insert In Protease Of Clade B Hiv Type 1., Parris S Jordan, Art Poon, Joseph Eron, Kathleen Squires, Caroline Ignacio, Douglas D Richman, Davey M Smith

Division of Infectious Diseases and Environmental Medicine Faculty Papers

A novel combination of three codon inserts in the pol coding region of HIV-1 RNA was identified in a highly antiretroviral experienced study subject with HIV-1 infection. A one codon insert was observed in the protease region between codon 40 and 41 simultaneously with a two codon insert present in the reverse transcriptase region at codon 69.

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

Identification Of Single Nucleotide Polymorphisms In The P21 (Cdkn1a) Gene And Correlations With Longevity In The Italian Population, Silvia Gravina, Francesco Lescai, Gregory Hurteau, Graham J. Brock, Anna Saramaki, Stefano Salvioli, Claudio Franceschi, Igor Roninson

Faculty Publications

Longevity in humans is determined by multiple environmental and genetic factors. We have investigated possible associations between longevity and Single Nucleotide Polymorphisms (SNPs) in the p21 (CDKN1A) gene, a stress-inducible senescence-associated cell cycle inhibitor, expression of which upregulates genes implicated in several age-related diseases. By sequencing the promoter and exons of p21 in genomic DNA of ten individuals over 90 years old, we have identified 30 SNPs, many of which had not been previously characterized. A cluster of minor alleles within the -4547/-3489 bp region did not alter the basal activity or p53 responsiveness of the p21 promoter. We then …

The Physician's Response To Climate Change., Mona Sarfaty, Safiya Abouzaid

Department of Family & Community Medicine Faculty Papers

Climate change will have an effect on the health and well-being of the populations cared for by practicing physicians. The anticipated medical effects include heat- and cold-related deaths, cardiovascular illnesses, injuries and mental harms from extreme weather events, respiratory illnesses caused by poor air quality, infectious diseases that emanate from contaminated food, water, or spread of disease vectors, the injuries caused by natural disasters, and the mental harm associated with social disruption. Within several years, such medical problems are likely to reach the doorsteps of many physicians. In the face of this reality, physicians should assume their traditional roles as …