Medicine and Health Sciences Commons^™

X-Linked Mtmr8 Diversity And Evolutionary History Of Sub-Saharan Populations, Damian Labuda, Vania Yotova, Jean-François Lefebvre, Claudia Moreau, Gerd Utermann, Scott M. Williams

Dartmouth Scholarship

The genetic diversity within an 11 kb segment of the MTMR8 gene in a sample of 111 sub-Saharan and 49 non-African X chromosomes was investigated to assess the early evolutionary history of sub-Saharan Africans and the out-of-Africa expansion. The analyses revealed a complex genetic structure of the Africans that contributed to the emergence of modern humans. We observed partitioning of two thirds of old lineages among southern, west/central and east African populations indicating ancient population stratification predating the out of Africa migration. Age estimates of these lineages, older than coalescence times of uniparentally inherited markers, raise the question whether contemporary …

Mesenteric Vein Thrombosis In A Patient Heterozygous For Factor V Leiden And G20210a Prothrombin Genotypes., Paras Karmacharya, Madan Raj Aryal, Anthony A. Donato

Reading Hospital Internal Medicine Residency

Mesenteric venous thrombosis (MVT) is a rare but life threatening form of bowel ischemia. It is implicated in 6%-9% of all cases of acute mesenteric ischemia. The proportion of patients with primary (or idiopathic) MVT varies from 0% to 49%, with a decrease in frequency secondary to more recent availability of newer investigations for hypercoagulability. The presence of factor V Leiden (FVL) and prothrombin G20210A mutations (PGM) have been well documented in these cases. However, there have been scarce case reports describing MVT in heterozygotes of both these mutations occurring simultaneously and its implications on long term management. Our case …

Findings From The Peutz-Jeghers Syndrome Registry Of Uruguay, Asadur Tchekmedyian, Christopher I. Amos, Sherri J. Bale, Dakai Zhu, Stefan Arold, Joaquin Berrueta, Natalie Nabon, Thomas Mcgarrity

Dartmouth Scholarship

Background: Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients. Methods: Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed. Results and discussion: 25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal …

Early Diagnosis And Treatment Of Invasive Pulmonary Aspergillosis In A Patient With Cystic Fibrosis, Ricardo Alberto Mosquera, Lila Estrada, Roya Mohebpour Clements, Cindy K Jon

Student and Faculty Publications

Invasive pulmonary aspergillosis is a rare and fatal complication in patients with cystic fibrosis (CF) who lack concomitant risk factors. The few documented cases in children have all resulted in deaths during hospitalisation. We present the case of a 12-year-old boy with CF who was admitted for an exacerbation which was unresponsive to antibiotic therapy. The findings on imaging raised concerns about a possible fungal infection. As a result, voriconazole therapy was started prior to his respiratory deterioration. He was later found to be β-D glucan and Aspergillus Ag galactomannan positive confirming the suspicion for invasive pulmonary aspergillosis. Three months …

Diet And Toenail Arsenic Concentrations In A New Hampshire Population With Arsenic-Containing Water, Kathryn L. Cottingham, Roxanne Karimi, Joann F. Gruber, M Scot Zens, Vicki Sayarath, Carol L. Folt, Tracy Punshon, J. Steven Morris, Margaret R. Karagas

Dartmouth Scholarship

Background: Limited data exist on the contribution of dietary sources of arsenic to an individual's total exposure, particularly in populations with exposure via drinking water. Here, the association between diet and toenail arsenic concentrations (a long-term biomarker of exposure) was evaluated for individuals with measured household tap water arsenic. Foods known to be high in arsenic, including rice and seafood, were of particular interest.

Methods: Associations between toenail arsenic and consumption of 120 individual diet items were quantified using general linear models that also accounted for household tap water arsenic and potentially confounding factors (e.g., age, caloric intake, sex, smoking) …

Intestinal Gucy2c Prevents Tgf-Β Secretion Coordinating Desmoplasia And Hyperproliferation In Colorectal Cancer., Ahmara V Gibbons, Jieru Egeria Lin, Gilbert Won Kim, Glen P Marszalowicz, Peng Li, Brian Arthur Stoecker, Erik S Blomain, Satish Rattan, Adam E. Snook, Stephanie Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF-β secretion, activating fibroblasts through TGF-β type I receptors and Smad3 phosphorylation. In turn, activating TGF-β signaling induces fibroblasts to …

Bdnf In The Dentate Gyrus Is Required For Consolidation Of "Pattern-Separated" Memories., Pedro Bekinschtein, Brianne A Kent, Charlotte A Oomen, Gregory D Clemenson, Fred H Gage, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

Successful memory involves not only remembering information over time, but also keeping memories distinct and less confusable. The computational process for making representations for similar input patterns more distinct from each other has been referred to as "pattern separation." In this work, we developed a set of behavioral conditions that allowed us to manipulate the load for pattern separation at different stages of memory. Thus, we provide experimental evidence that a brain-derived neurotrophic factor (BDNF)-dependent pattern separation process occurs during the encoding/storage/consolidation, but not the retrieval stage of memory processing. We also found that a spontaneous increase in BDNF in …

Interictal Neurocognitive Processing Of Visual Stimuli In Migraine: Evidence From Event-Related Potentials, Marla J. S Mickleborough, Christine M. Chapman, Andreea Simina Toma, Jeremy H. M Chan, Grace Truong, Todd C. Handy

Dartmouth Scholarship

Research has established decreased sensory habituation as a defining feature in migraine, while decreased cognitive habituation has only been found with regard to cognitive assessment of the relative probability of the occurrence of a stimulus event. Our study extended the investigation of interictal habituation in migraine to include cognitive processing when viewing of a series of visually-complex images, similar to those we encounter on the internet everyday. We examined interictal neurocognitive function in migraine from a habituation perspective, using a novel paradigm designed to assess how the response to a series of images changes over time. Two groups of participants--migraineurs …

Creating A Gold Medal Olympic And Paralympics Health Care Team: A Satisfaction Survey Of The Mobile Medical Unit/Polyclinic Team Training For The Vancouver 2010 Winter Games, D Ross Brown, Behrouz Heidary, Nathaniel Bell, Leanne Appleton, Richard K. Simons, David C. Evans, S Morad Hameed, Jack Taunton, Kosar Khwaja, Michael O'Connor, Naisan Garraway, Peter Hennecke, Donna Kuipers, Tracey Taulu, Lori Quinn

Faculty Publications

BACKGROUND:

The mobile medical unit/polyclinic (MMU/PC) was an essential part of the medical services to support ill or injured Olympic or Paralympics family during the 2010 Olympic and Paralympics winter games. The objective of this study was to survey the satisfaction of the clinical staff that completed the training programs prior to deployment to the MMU.

METHODS:

Medical personnel who participated in at least one of the four training programs, including (1) week-end sessions; (2) web-based modules; (3) just-in-time training; and (4) daily simulation exercises were invited to participate in a web-based survey and comment on their level of satisfaction …

Two Phase 3, Multicenter, Randomized, Placebo-Controlled Clinical Trials Of Fampridine-Sr For Treatment Of Spasticity In Chronic Spinal Cord Injury., D. D. Cardenas, J. F. Ditunno, V. Graziani, A. B. Mclain, D. P. Lammertse, P. J. Potter, M. S. Alexander, R. Cohen, A. R. Blight

Department of Rehabilitation Medicine Faculty Papers

STUDY DESIGN: Two randomized, double-blind, placebo-controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of fampridine sustained-release tablets (fampridine-SR) 25 mg twice daily for moderate-to-severe spasticity in patients with chronic spinal cord injury (SCI).

SETTING: United States and Canada.

METHODS: Patients with incomplete chronic SCI were randomized to twice daily fampridine-SR 25 mg or placebo, with a 2-week single-blind placebo run-in, a 2-week titration, 12 weeks of stable dosing, 2 weeks of downward titration and 2 weeks of untreated follow-up. Co-primary end points were the change from baseline, averaged over the double-blind treatment period, for Ashworth score (bilateral knee flexors …

Recurrent Tissue-Specific Mtdna Mutations Are Common In Humans, David C. Samuels, Chun Li, Bingshan Li, Zhuo Song, Eric Torstenson, Hayley Boyd Clay, Antonis Rokas, Tricia A. Thornton-Wells, Jason H. Moore, Tia M. Hughes, Robert D. Hoffman, Jonathan L. Haines, Deborah G. Murdock, Douglas P. Mortlock, Scott M. Williams

Dartmouth Scholarship

Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in …

One, Two And Three-Dimensional Ultrasound Measurements Of Carotid Atherosclerosis Before And After Cardiac Rehabilitation: Preliminary Results Of A Randomized Controlled Trial., Tamas J Lindenmaier, Daniel N Buchanan, Damien Pike, Tim Hartley, Robert D Reid, J David Spence, Richard Chan, Michael Sharma, Peter L Prior, Neville Suskin, Grace Parraga

Medical Biophysics Publications

BACKGROUND: It is still not known how patients who are post-transient ischemic attack (TIA) or post-stroke might benefit from prospectively planned comprehensive cardiac rehabilitation (CCR). In this pilot evaluation of a larger ongoing randomized-controlled-trial, we evaluated ultrasound (US) measurements of carotid atherosclerosis in subjects following TIA or mild non-disabling stroke and their relationship with risk factors before and after 6-months of CCR.

METHODS: Carotid ultrasound (US) measurements of one-dimensional intima-media-thickness (IMT), two-dimensional total-plaque-area (TPA), three-dimensional total-plaque-volume (TPV) and vessel-wall-volume (VWV) were acquired before and after 6-months CCR for 39 subjects who had previously experienced a TIA and provided written informed …

Feasibility Of Improving Cone-Beam Ct Number Consistency Using A Scatter Correction Algorithm., Jun Li, Weiguang Yao, Ying Xiao, Yan Yu

Department of Medicine Faculty Papers

The study was to explore the feasibility of improving cone-beam CT (CBCT) number (corresponding to the Hounsfield units in computed tomography) consistency using a scatter-correction algorithm, with the aim of using CBCT images for treatment planning with density correction. A scatter correction algorithm was applied to a Varian OBI CBCT and an Elekta XVI CBCT, and was evaluated for improving CBCT number consistency. CBCT numbers of phantom materials were compared between images with and without bolus, which introduced additional scatter, and with and without scatter correction processing. It was observed that CBCT numbers were different in the images with and …

Sensing Charges Of The Ciona Intestinalis Voltage-Sensing Phosphatase, Carlos A. Villalba-Galea, Ludivine Frezza, Walter Sandtner, Francisco Bezanilla

School of Pharmacy Faculty Articles

Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to …

Household Wealth And Neurocognitive Development Disparities Among School-Aged Children In Nepal., Shivani A Patel, Laura E Murray-Kolb, Steven C Leclerq, Subarna K Khatry, James M. Tielsch, Joanne Katz, Parul Christian

Global Health Faculty Publications

BACKGROUND: Wealth disparities in child developmental outcomes are well documented in developed countries. We sought to (1) describe the extent of wealth-based neurocognitive development disparities and (2) examine potential mediating factors of disparities among a population-based cohort of children in rural Nepal.

METHODS: We investigated household wealth-based differences in intellectual, executive and motor function of n = 1692 children aged between 7 and 9 years in Nepal. Using linear mixed models, wealth-based differences were estimated before and after controlling for child and household demographic characteristics. We further examined wealth-based differences adjusted for three sets of mediators: child nutritional status, home …

Nfkb Disrupts Tissue Polarity In 3d By Preventing Integration Of Microenvironmental Signals, Sabine Becker-Weimann, Gaofeng Xiong, Saori Furuta, Ju Han, Irene Kuhn, Uri-David Akavia, Dana Pe'er, Mina J. Bissell, Ren Xu

Markey Cancer Center Faculty Publications

The microenvironment of cells controls their phenotype, and thereby the architecture of the emerging multicellular structure or tissue. We have reported more than a dozen microenvironmental factors whose signaling must be integrated in order to effect an organized, functional tissue morphology. However, the factors that prevent integration of signaling pathways that merge form and function are still largely unknown. We have identified nuclear factor kappa B (NFkB) as a transcriptional regulator that disrupts important microenvironmental cues necessary for tissue organization. We compared the gene expression of organized and disorganized epithelial cells of the HMT-3522 breast cancer progression series: the non-malignant …

Predictors Of Disease Progression In Pediatric Dilated Cardiomyopathy., Kimberly M. Molina, Peter Shrader, Steven D. Colan, Seema Mital, Renee Margossian, Lynn A. Sleeper, Girish S. Shirali, Piers Barker, Charles E. Canter, Karen Altmann, Elizabeth Radojewski, Elif Seda Selamet Tierney, Jack Rychik, Lloyd Y. Tani, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Background: Despite medical advances, children with dilated cardiomyopathy (DCM) remain at high risk of death or need for cardiac transplantation. We sought to identify predictors of disease progression in pediatric DCM.

Methods and results: The Pediatric Heart Network evaluated chronic DCM patients with prospective echocardiographic and clinical data collection during an 18-month follow-up. Inclusion criteria were age <22 years and DCM disease duration >2 months. Patients requiring intravenous inotropic/mechanical support or listed status 1A/1B for transplant were excluded. Disease progression was defined as an increase in transplant listing status, hospitalization for heart failure, intravenous inotropes, mechanical support, or death. Predictors of disease progression were identified using …

Inverse Lichen Planus, Michael D Lee, Laurel R Schwartz

Department of Dermatology and Cutaneous Biology Faculty Papers

A Case of Inverse Lichen Planus

Lichen planus (LP) is a pruritic, papular eruption characterized by its violaceous color and polygonal shape. It is most commonly found on the flexor surfaces of the upper extremities, on the genitalia, and on the mucous membranes. We herein report a classic case of LP in an inverse distribution.

Abdominal Intercostal Hernia: A Rare Complication After Blunt Trauma., Phi D Nguyen, B.A., Michael J. Pucci, Md, Jay S. Jenoff, Md, Scott W. Cowan, Md

Department of Surgery Gibbon Society Historical Profiles

Abdominal intercostal hernia (AIH) is uncommonly reported in the literature with only 20 cases reported to date.1–3 We report a case of a delayed incarcerated AIH secondary to blunt trauma from a motor vehicle accident in which the colon and diaphragm herniated through an associated chest defect that was repaired successfully through a transabdominal approach using primary repair of the defect in combination with onlay porcine patch reinforcement.

Phenotypic Parameters Predict Time To Normalization In Infants With Hypogammaglobulinemia., Robert C. Van Winkle, Walter W. Hauck, Stephen J. Mcgeady

Department of Pediatrics Faculty Papers

PURPOSE: Infants with recurrent infection may be found to have hypogammaglobulinemia without impaired specific antibody responses. Many will be diagnosed with transient hypogammaglobulinemia of infancy.

METHODS: This study used a parametric survival analysis of 100 infants with hypogammaglobulinemia to predict time to normalization.

RESULTS: Aggregate initial immunoglobulins (IgG + IgA + IgM), as a percentage of age-adjusted normal, predicted time to resolution: median time to resolution for the infants in the lowest quartile of aggregate levels (≤81 % of age-adjusted lower limits) was greater than 5 years, with 34 % resolving in 3 years. For infants in the highest quartile …

Multicenter Study Comparing Shunt Type In The Norwood Procedure For Single-Ventricle Lesions: Three-Dimensional Echocardiographic Analysis., Gerald R. Marx, Girish S. Shirali, Jami C. Levine, Lin T. Guey, James F. Cnota, Jeanne M. Baffa, William L. Border, Steve Colan, Gregory Ensing, Mark K. Friedberg, David J. Goldberg, Salim F. Idriss, J Blaine John, Wyman W. Lai, Minmin Lu, Shaji C. Menon, Richard G. Ohye, David Saudek, Pierre C. Wong, Gail D. Pearson, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The Pediatric Heart Network's Single Ventricle Reconstruction (SVR) trial randomized infants with single right ventricles (RVs) undergoing a Norwood procedure to a modified Blalock-Taussig or RV-to-pulmonary artery shunt. This report compares RV parameters in the 2 groups using 3-dimensional echocardiography.

METHODS AND RESULTS: Three-dimensional echocardiography studies were obtained at 10 of 15 SVR centers. Of the 549 subjects, 314 underwent 3-dimensional echocardiography studies at 1 to 4 time points (pre-Norwood, post-Norwood, pre-stage II, and 14 months) for a total of 757 3-dimensional echocardiography studies. Of these, 565 (75%) were acceptable for analysis. RV volume, mass, mass:volume ratio, ejection fraction, …

Neuropathy, Neuropathic Pain, And Sickle Cell Disease., Samir K. Ballas, Deepika S Darbari

Cardeza Foundation for Hematologic Research

No abstract provided.

Cholera Vaccination Campaign Contributes To Improved Knowledge Regarding Cholera And Improved Practice Relevant To Waterborne Disease In Rural Haiti, Omowunmi Aibana, Molly F Franke, Jessica E Teng, Johanne Hilaire, Max Raymond, Louise C Ivers

Faculty and Staff Publications

BACKGROUND: Haiti's cholera epidemic has been devastating partly due to underlying weak infrastructure and limited clean water and sanitation. A comprehensive approach to cholera control is crucial, yet some have argued that oral cholera vaccination (OCV) might result in reduced hygiene practice among recipients. We evaluated the impact of an OCV campaign on knowledge and health practice in rural Haiti.

METHODOLOGY/PRINCIPAL FINDINGS: We administered baseline surveys on knowledge and practice relevant to cholera and waterborne disease to every 10th household during a census in rural Haiti in February 2012 (N = 811). An OCV campaign occurred from May-June 2012 after …

Sternal Wound Infection Caused By Mycobacterium Chelonae., Shinya Unai, Joseph Miessau, Pawel Karbowski, Gurjyot Bajwa, Hitoshi Hirose

Department of Surgery Faculty Papers

INTRODUCTION: Sternal wound infection caused by Mycobacterium chelonae, a member of the rapidly growing nontuberculous mycobacteria (NTM), is rare and may present without signs and symptoms of systemic infection.

METHODS: We present a patient who had a M. chelonae infection of the sternum following excision of a left atrial myxoma and conducted a review of the literature from 1976 to 2013.

RESULTS: Seventy cases of NTM sternal wound infection after cardiac surgery were identified, including six outbreaks and ten sporadic cases including the present case. Thirty-four cases were isolated coronary artery bypass grafting (CABG) surgery, 16 cases were isolated valve …

Edoardo Bassini (1844-1924): Father Of Modern-Day Hernia Surgery., Wei Phin Tan, B.S., Harish Lavu, Md, Ernest L. Rosato, Md, Charles J. Yeo, Md, Scott W. Cowan, Md

Department of Surgery Gibbon Society Historical Profiles

According to Roman scripture, it was Celsus who attempted the first inguinal hernia repair in history during the first century A.D. His attempts were unsuccessful and resulted in an early recurrence of the hernia, which eventually led to the patient’s death.1 Over the next two millennia, little understanding was gained regarding the anatomy of the inguinal canal. It was only in the last 100 years that major advancements in herniorrhaphy were established, thanks in large part to the work of Edoardo Bassini, who revolutionized the surgical treatment of the inguinal hernia with a technique which has become the basis of …

Epigenetic Dominance Of Prion Conformers, Eri Saijo, Hae-Eun Kang, Jifeng Bian, Kristi G. Bowling, Shawn Browning, Sehun Kim, Nora Hunter, Glenn C. Telling

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Although they share certain biological properties with nucleic acid based infectious agents, prions, the causative agents of invariably fatal, transmissible neurodegenerative disorders such as bovine spongiform encephalopathy, sheep scrapie, and human Creutzfeldt Jakob disease, propagate by conformational templating of host encoded proteins. Once thought to be unique to these diseases, this mechanism is now recognized as a ubiquitous means of information transfer in biological systems, including other protein misfolding disorders such as those causing Alzheimer's and Parkinson's diseases. To address the poorly understood mechanism by which host prion protein (PrP) primary structures interact with distinct prion conformations to influence pathogenesis, …

Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari

Dartmouth Scholarship

One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killer FLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using …

New Oral Anticoagulants Are Not Superior To Warfarin In Secondary Prevention Of Stroke Or Transient Ischemic Attacks, But Lower The Risk Of Intracranial Bleeding: Insights From A Meta-Analysis And Indirect Treatment Comparisons, Partha Sardar, Saurav Chatterjee, Wen-Chih Wu, Edgar Lichstein, Joydeep Ghosh, Shamik Aikat, Debabrata Mukherjee

Internal Medicine Faculty Publications

PURPOSE: Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).

METHODS: Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan …

Microrna-200c Modulates The Expression Of Muc4 And Muc16 By Directly Targeting Their Coding Sequences In Human Pancreatic Cancer., Prakash Radhakrishnan, Ashley M. Mohr, Paul M. Grandgenett, Maria M. Steele, Surinder K. Batra, Michael A. Hollingsworth

Journal Articles: Biochemistry & Molecular Biology

Transmembrane mucins, MUC4 and MUC16 are associated with tumor progression and metastatic potential in human pancreatic adenocarcinoma. We discovered that miR-200c interacts with specific sequences within the coding sequence of MUC4 and MUC16 mRNAs, and evaluated the regulatory nature of this association. Pancreatic cancer cell lines S2.028 and T3M-4 transfected with miR-200c showed a 4.18 and 8.50 fold down regulation of MUC4 mRNA, and 4.68 and 4.82 fold down regulation of MUC16 mRNA compared to mock-transfected cells, respectively. A significant reduction of glycoprotein expression was also observed. These results indicate that miR-200c overexpression regulates MUC4 and MUC16 mucins in pancreatic …

Pre-Diagnosis Oophorectomy, Estrogen Therapy And Mortality In A Cohort Of Women Diagnosed With Breast Cancer, Hazel B. Nichols, Amy Trentham-Dietz, Polly A. Newcomb, Kathleen M. Egan, Linda J. Titus, John M. Hampton, Kala Visvanathan

Dartmouth Scholarship

Introduction:

Pre-diagnosis oophorectomy and estrogen therapy could impact mortality due to breast cancer and cardiovascular disease (CVD) among breast cancer survivors. Elective bilateral oophorectomy at the time of hysterectomy for benign conditions is not uncommon among US women.

Methods:

We examined the association between pre-diagnosis total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) and both overall and cause-specific mortality in the Collaborative Breast Cancer Studies cohort. Medical history and prior estrogen use were collected during standardized telephone interviews. Vital status, including date and cause of death, was obtained by linkage with the National Death Index. Multivariate hazard ratios (HR) and 95% …