Medicine and Health Sciences Commons^™

Repression Of The Sumo-Specific Protease Senp1 Induces P53-Dependent Premature Senescence In Normal Human Fibroblasts, Kristin E. Yates, Gregory A. Korbel, Michael Shtutman, Igor Roninson, Daniel Dimaio

Faculty Publications

The proliferative lifespan of normal somatic human cells in culture terminates in a permanent growth-arrested state known as replicative senescence. In this study, we show that RNA interference-mediated repression of the genes encoding the small ubiquitin-related modifier (SUMO)-specific proteases, Senp1, Senp2, and Senp7, induced low passage primary human fibroblasts to senesce rapidly. Following Senp1 repression, we observed a global increase in sumoylated proteins and in the number and size of nuclear SUMO-containing promyelocytic leukemia (PML) bodies. SUMO/PML bodies also increased during replicative senescence. p53 transcriptional activity was enhanced towards known p53 target genes following repression of Senp1, and inhibition of …

Effect Of Progressive Mandibular Advancement On Pharyngeal Airway Size In Anesthetized Adults, Samuel T Kuna, Lee C Woodson, Daneshvari R Solanki, Oliver Esch, Donald E Frantz, Mali Mathru

Faculty, Staff and Student Publications

BACKGROUND: General anesthesia in adult humans is associated with narrowing or complete closure of the pharyngeal airway. The purpose of this study was to determine the effect of progressive mandibular advancement on pharyngeal airway size in normal adults during intravenous infusion of propofol for anesthesia.

METHODS: Magnetic resonance imaging was performed in nine normal adults during wakefulness and during propofol anesthesia. A commercially available intraoral appliance was used to manually advance the mandible. Images were obtained during wakefulness without the appliance and during anesthesia with the participants wearing the appliance under three conditions: without mandibular advancement, advancement to 50% maximum …

Molecular Processes That Handle — And Mishandle — Dietary Lipids, Kevin Jon Williams

Department of Medicine Faculty Papers

Overconsumption of lipid-rich diets, in conjunction with physical inactivity, disables and kills staggering numbers of people worldwide. Recent advances in our molecular understanding of cholesterol and triglyceride transport from the small intestine to the rest of the body provide a detailed picture of the fed/fasted and active/sedentary states. Key surprises include the unexpected nature of many pivotal molecular mediators, as well as their dysregulation — but possible reversibility — in obesity, diabetes, inactivity, and related conditions. These mechanistic insights provide new opportunities to correct dyslipoproteinemia, accelerated atherosclerosis, insulin resistance, and other deadly sequelae of overnutrition and underexertion.

The Performance Of Human Papillomavirus High-Risk Dna Testing In The Screening And Diagnostic Settings, Marylou Cárdenas-Turanzas, Graciela M Nogueras-Gonzalez, Michael E Scheurer, Karen Adler-Storthz, J L Benedet, J Robert Beck, Michele Follen, Scott B Cantor

Faculty, Staff and Student Publications

OBJECTIVE: We sought to evaluate the performance of the human papillomavirus high-risk DNA test in patients 30 years and older.

MATERIALS AND METHODS: Screening (n=835) and diagnosis (n=518) groups were defined based on prior Papanicolaou smear results as part of a clinical trial for cervical cancer detection. We compared the Hybrid Capture II (HCII) test result with the worst histologic report. We used cervical intraepithelial neoplasia (CIN) 2/3 or worse as the reference of disease. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR-), receiver operating characteristic (ROC) curves, and areas under the ROC curves for the …

Predicting Length Of Treatment For Neonatal Abstinence Syndrome In Methadone-Exposed Neonates., Neil S. Seligman, Nicole Salva, Edward J. Hayes, Kevin C. Dysart, Edward C. Pequignot, Jason K. Baxter

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: The objective of the study was to identify maternal variables predicting length of treatment for neonatal abstinence syndrome (NAS).

STUDY DESIGN: This was a retrospective cohort study of infants treated for NAS during 2000-2006 whose mothers were on methadone maintenance at delivery. Mixed-effects linear regression was used to examine the interaction of maternal and neonatal variables with length of treatment.

RESULTS: Of 204 neonates born to methadone exposed mothers, the average dose at delivery was 127 mg daily (25-340 mg) with median length of treatment 32 days (1-122 days). Trimester of initial exposure (P = .33), methadone dose at …

Design And Rationale Of A Randomized Trial Comparing The Blalock-Taussig And Right Ventricle-Pulmonary Artery Shunts In The Norwood Procedure., Richard G. Ohye, J William Gaynor, Nancy S. Ghanayem, Caren S. Goldberg, Peter C. Laussen, Peter C. Frommelt, Jane W. Newburger, Gail D. Pearson, Sarah Tabbutt, Gil Wernovsky, Lisa M. Wruck, Andrew M. Atz, Steve D. Colan, James Jaggers, Brian W. Mccrindle, Ashwin Prakash, Michael D. Puchalski, Lynn A. Sleeper, Mario P. Stylianou, Lynn Mahony, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The initial palliative procedure for patients born with hypoplastic left heart syndrome and related single right ventricle anomalies, the Norwood procedure, remains among the highest risk procedures in congenital heart surgery. The classic Norwood procedure provides pulmonary blood flow with a modified Blalock-Taussig shunt. Improved outcomes have been reported in a few small, nonrandomized studies of a modification of the Norwood procedure that uses a right ventricle-pulmonary artery shunt to provide pulmonary blood flow. Other nonrandomized studies have shown no differences between the two techniques.

METHODS: The Pediatric Heart Network designed a randomized clinical trial to compare outcomes for …

Outcomes Of Safety And Effectiveness In A Multicenter Randomized, Controlled Trial Of Whole-Body Hypothermia For Neonatal Hypoxic-Ischemic Encephalopathy, Seetha Shankaran, Athina Pappas, Abbott R Laptook, Scott A Mcdonald, Richard A Ehrenkranz, Jon E Tyson, Michelle Walsh, Ronald N Goldberg, Rosemary D Higgins, Abhik Das

Faculty, Staff and Student Publications

BACKGROUND: Whole-body hypothermia reduced the frequency of death or moderate/severe disabilities in neonates with hypoxic-ischemic encephalopathy in a randomized, controlled multicenter trial.

OBJECTIVE: Our goal was to evaluate outcomes of safety and effectiveness of hypothermia in infants up to 18 to 22 months of age.

DESIGN/METHODS: A priori outcomes were evaluated between hypothermia (n = 102) and control (n = 106) groups.

RESULTS: Encephalopathy attributable to causes other than hypoxia-ischemia at birth was not noted. Inotropic support (hypothermia, 59% of infants; control, 56% of infants) was similar during the 72-hour study intervention period in both groups. Need for blood transfusions …

Characterization Of The Inflammatory Cells In Ascending Thoracic Aortic Aneurysms In Patients With Marfan Syndrome, Familial Thoracic Aortic Aneurysms, And Sporadic Aneurysms, Rumin He, Dong-Chuan Guo, Wei Sun, Christina L Papke, Senthil Duraisamy, Anthony L Estrera, Hazim J Safi, Chul Ahn, L Maximilian Buja, Frank C Arnett, Jingwu Zhang, Yong-Jian Geng, Dianna M Milewicz

Faculty, Staff and Student Publications

OBJECTIVE: This study sought to characterize the inflammatory infiltrate in ascending thoracic aortic aneurysm in patients with Marfan syndrome, familial thoracic aortic aneurysm, or nonfamilial thoracic aortic aneurysm.

BACKGROUND: Thoracic aortic aneurysms are associated with a pathologic lesion termed "medial degeneration," which is described as a noninflammatory lesion. Thoracic aortic aneurysms are a complication of Marfan syndrome and can be inherited in an autosomal dominant manner of familial thoracic aortic aneurysm.

METHODS: Full aortic segments were collected from patients undergoing elective repair with Marfan syndrome (n = 5), familial thoracic aortic aneurysm (n = 6), and thoracic aortic aneurysms (n …

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 …

Deregulation Of Muc4 In Gastric Adenocarcinoma: Potential Pathobiological Implication In Poorly Differentiated Non-Signet Ring Cell Type Gastric Cancer., S. Senapati, P. Chaturvedi, P. Sharma, G Venkatraman, Jane L. Meza, W. El-Rifai, H. K. Roy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is a large, heavily glycosylated transmembrane mucin, that is implicated in the pathogenesis of various types of cancers. To date, no extensive study has been done to check the expression and functional significance of MUC4 in different types of gastric adenocarcinomas. Here, we report the expression profile of MUC4 in gastric adenocarcinomas and its function in poorly differentiated gastric non-signet ring cell carcinoma (non-SRCC) type cells. Immunohistochemical analysis using tissue microarray (TMA) showed a significant difference in MUC4 expression between normal adjacent (n = 45) and gastric adenocarcinoma (n = 83; P < 0.001). MUC4 expression was not associated with tumour type, stage or with the degree of differentiation. To gain further insight into the significance of MUC4 expression in gastric non-SRCC cells, MUC4 was ectopically expressed in AGS, a poorly differentiated gastric non-signet ring cell line. The MUC4 overexpressing cells (AGS-MUC4) showed a significant increase (P < 0.005) in cell motility and a decrease in cellular aggregation as compared with the vector-transfected cells. Furthermore, in vivo tumorigenicity analysis revealed that animals transplanted with the MUC4 overexpressing cells (AGS-MUC4) had a greater incidence of tumours (83%) in comparison to empty vector control (17%). In addition, the expression of MUC4 resulted in enhanced expression of total cellular ErbB2 and phosphorylated ErbB2. In conclusion, our results showed that MUC4 is overexpressed in gastric adenocarcinoma tissues, and that it has a role in promoting aggressive properties in poorly differentiated gastric non-SRCC cells through the activation of the ErbB2 oncoprotein.

Presence Of Endometrial Adenocarcinoma In Situ In Complex Atypical Endometrial Hyperplasia Is Associated With Increased Incidence Of Endometrial Carcinoma In Subsequent Hysterectomy., Khush Mittal, Matjaz Sebenik, Cybil Irwin, Zhijije Yan, Dorota Popiolek, John Curtin, Juan Palazzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The distinction of complex atypical endometrial hyperplasia from endometrial adenocarcinoma is often problematic. Foci of back-to-back arrangement of glands or foci of cribriform arrangement of glands smaller than 2.1 mm in diameter are considered insufficient for the diagnosis of endometrial adenocarcinoma by some authors, and sufficient to be diagnosed as endometrial adenocarcinoma by other authors. We refer to these foci as endometrial adenocarcinoma in situ. In this study, we evaluated findings in subsequent hysterectomy in complex atypical endometrial hyperplasia patients with and without adenocarcinoma in situ. Follow-up findings, including the presence or absence of endometrial adenocarcinoma in the hysterectomy specimen, …

The Fgf System Has A Key Role In Regulating Vascular Integrity, Masahiro Murakami, Loc T. Nguyen, Zhen W. Zhang, Karen L. Moodie, Pater Carmellet, Radu V. Stan, Michael Simons

Dartmouth Scholarship

The integrity of the endothelial monolayer is essential to blood vessel homeostasis and active regulation of endothelial permeability. The FGF system plays important roles in a wide variety of physiologic and pathologic conditions; however, its role in the adult vasculature has not been defined. To assess the role of the FGF system in the adult endothelial monolayer, we disrupted FGF signaling in bovine aortic endothelial cells and human saphenous vein endothelial cells in vitro and in adult mouse and rat endothelial cells in vivo using soluble FGF traps or a dominant inhibitor of all FGF receptors. The inhibition of FGF …

Shift Report And Sbar: Strategies For Clinical Postconference., Fatima Ascano-Martin

Nursing | Faculty Scholarship

Conducting an effective postconference continues to be challenging because of low levels of student participation. Many students are exhausted at the end of the clinical day, which lessens their participation in postconference. In my experience, students often omit important information, such as patients’ age, sex, race, and other medical problems, during initial reports. Some have trouble providing patients’ information in an organized manner as well. The SBAR (situation-background-assessment-recommendation) communication tool can be used as a strategy to conduct clinical postconference.

Overexpression Of Matrix Metalloproteinase 9 In Tumor Epithelial Cells Correlates With Colorectal Cancer Metastasis., David S Zuzga, Ahmara Vivian Gibbons, Peng Li, Wilhelm Johannes Lubbe, Inna Chervoneva, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Colorectal cancer mortality largely reflects metastasis, the spread of the disease to distant organs. Matrix metalloproteinase 9 (MMP-9) is a key regulator of metastasis and a target for anticancer strategies in colon cancer. Here, the overexpression of MMP-9 in pure tumor epithelial, but nor stromal, cell populations was associated with metastatic progression of colorectal cancer, as defined by reverse transcriptase-polymerase chain reaction (qRT-PCR) and confirmed by immunostaining. Thus, cancer cell MMP-9 represents a novel, selective prognostic and predictive factor that may be exploited for more effective disease stage stratification and therapeutic regimen selection in patients with colorectal cancer.

The Dose-Response Of Nitrous Oxide In Postoperative Nausea In Patients Undergoing Gynecologic Laparoscopic Surgery: A Preliminary Study., Boris Mraovic, Tatjana Simurina, Zdenko Sonicki, Neven Skitarelic, Tong J. Gan

Department of Anesthesiology Faculty Papers

BACKGROUND: Whether nitrous oxide (N(2)O) increases the incidence of postoperative nausea and vomiting (PONV) after laparoscopic gynecologic surgery is still controversial, which may be due to the administration of different concentrations of inspired N(2)O. We investigated whether N(2)O results in a dose-response increase in PONV. METHODS: Patients undergoing gynecologic laparoscopic surgery were randomized to receive 30% oxygen with air (G0, n = 46), 50% N(2)O with oxygen (G50, n = 46), or 70% N(2)O with oxygen (G70, n = 45). A standardized general anesthetic was used with no PONV prophylaxis. Known risk factors for PONV were controlled. Metoclopramide was used …

Myositis Ossificans Circumscripta Of The Buccinator Muscle: First Report Of A Rare Complication Of Mandibular Third Molar Extraction, Raymond L Wiggins, David Thurber, Kenneth Abramovitch, Jerry Bouquot, Nadarajah Vigneswaran

Faculty, Staff and Student Publications

No abstract provided.

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 …

Decreased Expression Of Caveolin 1 In Patients With Systemic Sclerosis: Crucial Role In The Pathogenesis Of Tissue Fibrosis., Francesco Del Galdo, Federica Sotgia, Cecilia J. De Almeida, Jean-Francois Jasmin, Megan Musick, Michael P. Lisanti, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: Recent studies have implicated caveolin 1 in the regulation of transforming growth factor beta (TGFbeta) downstream signaling. Given the crucial role of TGFbeta in the pathogenesis of systemic sclerosis (SSc), we sought to determine whether caveolin 1 is also involved in the pathogenesis of tissue fibrosis in SSc. We analyzed the expression of CAV1 in affected SSc tissues, studied the effects of lack of expression of CAV1 in vitro and in vivo, and analyzed the effects of restoration of caveolin 1 function on the fibrotic phenotype of SSc fibroblasts in vitro.

METHODS: CAV1 expression in tissues was analyzed by …

Complete Resolution Of Gastric Amyloidosis After Autologous Stem Cell Transplantation., Dinu Cherian, Kristin Braun, Neal Flomenberg, Juan P. Palazzo, David Kastenberg

Division of Gastroenterology and Hepatology Faculty Papers

A 48-year-old female with multiple myeloma (MM) and amyloidosis presented with massive upper gastrointestinal (GI) bleeding one week after autologous stem cell transplantation (autologous-SCT). Esophagogastroduodenoscopy (EGD) demonstrated necrotic, purple, pigmented, friable lesions throughout the stomach (Figure 1a), along with a bleeding ulcer in the cardia (Figure 1b, Video 1) which was successfully treated with epinephrine (1:10,000) injections. Biopsies demonstrated nodular amyloid deposition (Figures 2) which was Congo red positive. The patient had no further hematemesis and was discharged home 4 days later. Ten months after autologous-SCT, EGD revealed a normal stomach (Figure 3, Video 2) with …

Freedom For The Bulgarian Nurses And A Palestinian Doctor., Lawrence Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

On July 24, 2007, the five Bulgarian nurses and the Palestinian, unjustly accused of infecting Libyan children with the AIDS virus, were freed by the Libyan government. They had spent a tumultuous seven years in prison, much of the time on death row, having been accused of injecting the children with tainted blood they had brought with them. This was not only preposterous but also an impossibility as the particular strain of the AIDS virus had been found in Libya, two years prior. [1]

Direct Estimation Of Evoked Hemoglobin Changes By Multimodality Fusion Imaging, Theodore J. Huppert, Solomon G. Diamond, David A. Boas

Dartmouth Scholarship

In the last two decades, both diffuse optical tomography (DOT) and blood oxygen level dependent (BOLD)-based functional magnetic resonance imaging (fMRI) methods have been developed as noninvasive tools for imaging evoked cerebral hemodynamic changes in studies of brain activity. Although these two technologies measure functional contrast from similar physiological sources, i.e., changes in hemoglobin levels, these two modalities are based on distinct physical and biophysical principles leading to both limitations and strengths to each method. In this work, we describe a unified linear model to combine the complimentary spatial, temporal, and spectroscopic resolutions of concurrently measured optical tomography and fMRI …

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

Dartmouth Scholarship

No abstract provided.

A Functional Collagen Adhesin Gene, Acm, In Clinical Isolates Of Enterococcus Faecium Correlates With The Recent Success Of This Emerging Nosocomial Pathogen, Sreedhar R Nallapareddy, Kavindra V Singh, Pablo C Okhuysen, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecium recently evolved from a generally avirulent commensal into a multidrug-resistant health care-associated pathogen causing difficult-to-treat infections, but little is known about the factors responsible for this change. We previously showed that some E. faecium strains express a cell wall-anchored collagen adhesin, Acm. Here we analyzed 90 E. faecium isolates (99% acm(+)) and found that the Acm protein was detected predominantly in clinically derived isolates, while the acm gene was present as a transposon-interrupted pseudogene in 12 of 47 isolates of nonclinical origin. A highly significant association between clinical (versus fecal or food) origin and collagen adherence (P

Contribution Of The Collagen Adhesin Acm To Pathogenesis Of Enterococcus Faecium In Experimental Endocarditis, Sreedhar R Nallapareddy, Kavindra V Singh, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecium is a multidrug-resistant opportunist causing difficult-to-treat nosocomial infections, including endocarditis, but there are no reports experimentally demonstrating E. faecium virulence determinants. Our previous studies showed that some clinical E. faecium isolates produce a cell wall-anchored collagen adhesin, Acm, and that an isogenic acm deletion mutant of the endocarditis-derived strain TX0082 lost collagen adherence. In this study, we show with a rat endocarditis model that TX0082 Deltaacm::cat is highly attenuated versus wild-type TX0082, both in established (72 h) vegetations (P < 0.0001) and for valve colonization 1 and 3 hours after infection (P or=50-fold reduction relative to an Acm producer) were found in three of these five nonadherent isolates, including the sequenced strain TX0016, by quantitative reverse transcription-PCR, indicating that acm transcription is downregulated in vitro in these isolates. However, examination of TX0016 cells obtained directly from infected rat vegetations by flow cytometry showed that Acm was present on 40% of cells grown during infection. Finally, we demonstrated a significant reduction in E. faecium collagen adherence by affinity-purified anti-Acm antibodies from E. faecium endocarditis patient sera, suggesting that Acm may be a potential immunotarget for strategies to control this emerging pathogen.

Mitochondrial Redox Signaling By P66shc Is Involved In Regulating Androgenic Growth Stimulation Of Human Prostate Cancer Cells., Suresh Veeramani, Ta-Chun Yuan, Fen-Fen Lin, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

p66Shc is shown to negatively regulate the life span in mice through reactive oxygen species (ROS) production. Recent reports, however, revealed that p66Shc protein level is significantly elevated in several human cancer tissues and growth-stimulated carcinoma cells, suggesting a mitogenic and carcinogenic role for p66Shc. In this communication, we demonstrate for the first time that p66Shc mediates androgenic growth signals in androgen-sensitive human prostate cancer cells through mitochondrial ROS production. Growth stimulation of prostate cancer cells with 5alpha-dihydrotestosterone (DHT) is accompanied by increased p66Shc level and ROS production, which is abolished by antioxidant treatments. However, antioxidant treatments do not affect …

An Sp1/Sp3 Binding Polymorphism Confers Methylation Protection, Yanis A. Boumber, Yutaka Kondo, Xuqi Chen, Lanlan Shen, Yi Guo, Carmen Tellez, Marcos R H Estécio, Saira Ahmed, Jean-Pierre J. Issa

Faculty, Staff and Student Publications

Hundreds of genes show aberrant DNA hypermethylation in cancer, yet little is known about the causes of this hypermethylation. We identified RIL as a frequent methylation target in cancer. In search for factors that influence RIL hypermethylation, we found a 12-bp polymorphic sequence around its transcription start site that creates a long allele. Pyrosequencing of homozygous tumors revealed a 2.1-fold higher methylation for the short alleles (P<0.001). Bisulfite sequencing of cancers heterozygous for RIL showed that the short alleles are 3.1-fold more methylated than the long (P<0.001). The comparison of expression levels between unmethylated long and short EBV-transformed cell lines showed no difference in expression in vivo. Electrophorectic mobility shift assay showed that the inserted region of the long allele binds Sp1 and Sp3 transcription factors, a binding that is absent in the short allele. Transient transfection of RIL allele-specific transgenes showed no effects of the additional Sp1 site on transcription early on. However, stable transfection of methylation-seeded constructs showed gradually decreasing transcription levels from the short allele with eventual spreading of de novo methylation. In contrast, the long allele showed stable levels of expression over time as measured by luciferase and approximately 2-3-fold lower levels of methylation by bisulfite sequencing (P<0.001), suggesting that the polymorphic Sp1 site protects against time-dependent silencing. Our finding demonstrates that, in some genes, hypermethylation in cancer is dictated by protein-DNA interactions at the promoters and provides a novel mechanism by which genetic polymorphisms can influence an epigenetic state.

Staphylococcus Aureus Pbp4 Is Essential For Β-Lactam Resistance In Community-Acquired Methicillin-Resistant Strains, G Memmi, S R. Filipe, M G. Pinho, Z Fu, Ambrose Cheung

Dartmouth Scholarship

Recent cases of infections caused by community-acquired methicillin-resistant Staphylococcus aureus (MRSA) (CA-MRSA) strains in healthy individuals have raised concerns worldwide. CA-MRSA strains differ from hospital-acquired MRSAs by virtue of their genomic background and increased virulence in animal models.

A Cyclin D1/Microrna 17/20 Regulatory Feedback Loop In Control Of Breast Cancer Cell Proliferation., Zuoren Yu, Chenguang Wang, Min Wang, Zhiping Li, Mathew C Casimiro, Manran Liu, Kongming Wu, James Whittle, Xiaoming Ju, Terry Hyslop, Peter Mccue, Richard G Pestell

Kimmel Cancer Center Faculty Papers

Decreased expression of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. Herein, levels of the miR-17-5p/miR-20a miRNA cluster were inversely correlated to cyclin D1 abundance in human breast tumors and cell lines. MiR-17/20 suppressed breast cancer cell proliferation and tumor colony formation by negatively regulating cyclin D1 translation via a conserved 3' untranslated region miRNA-binding site, thereby inhibiting serum-induced S phase entry. The cell cycle effect of miR-17/20 was abrogated by cyclin D1 siRNA and in cyclin D1-deficient breast cancer cells. Mammary epithelial cell-targeted cyclin D1 expression induced miR-17-5p and miR-20a expression …

Biology And Therapy Of Fibromyalgia. Evidence-Based Biomarkers For Fibromyalgia Syndrome, Dina Dadabhoy, Leslie J. Crofford, Michael Spaeth, I. Jon Russell, Daniel J. Clauw

Internal Medicine Faculty Publications

Researchers studying fibromyalgia strive to identify objective, measurable biomarkers that may identify susceptible individuals, may facilitate diagnosis, or that parallel activity of the disease. Candidate objective measures range from sophisticated functional neuroimaging to office-ready measures of the pressure pain threshold. A systematic literature review was completed to assess highly investigated, objective measures used in fibromyalgia studies. To date, only experimental pain testing has been shown to coincide with improvements in clinical status in a longitudinal study. Concerted efforts to systematically evaluate additional objective measures in research trials will be vital for ongoing progress in outcome research and translation into clinical …

Muc4 Activates Her2 Signalling And Enhances The Motility Of Human Ovarian Cancer Cells., Moorthy P. Ponnusamy, A. P. Singh, Maneesh Jain, S. Chakraborty, N. Moniaux, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

The mucin MUC4 is a high molecular weight transmembrane glycoprotein. It consists of a mucin-type subunit (MUC4alpha) and a transmembrane growth factor-like subunit (MUC4beta). The mucin MUC4 is overexpressed in many epithelial malignancies including ovarian cancer, suggesting a possible role in the pathogenesis of these cancers. In this study, we investigated the functional role of MUC4 in the human ovarian cancer cell line SKOV3. The mucin MUC4 was ectopically expressed by stable transfection, and its expression was examined by western blot and confocal microscopy analyses. The in vitro studies demonstrated an enhanced motility of MUC4-expressing SKOV3 cells compared with the …