Digital Commons Network^™

Loss Of Sparc-Mediated Vegfr-1 Suppression After Injury Reveals A Novel Antiangiogenic Activity Of Vegf-A, Miho Nozaki, Eiji Sakurai, Brian J. Raisler, Judit Z. Baffi, Jassir Witta, Yuichiro Ogura, Rolf A. Brekken, E Helene Sage, Balamurali K. Ambati, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

VEGF-A promotes angiogenesis in many tissues. Here we report that choroidal neovascularization (CNV) incited by injury was increased by excess VEGF-A before injury but was suppressed by VEGF-A after injury. This unorthodox antiangiogenic effect was mediated via VEGFR-1 activation and VEGFR-2 deactivation, the latter via Src homology domain 2-containing (SH2-containing) tyrosine phosphatase-1 (SHP-1). The VEGFR-1-specific ligand placental growth factor-1 (PlGF-1), but not VEGF-E, which selectively binds VEGFR-2, mimicked these responses. Excess VEGF-A increased CNV before injury because VEGFR-1 activation was silenced by secreted protein, acidic and rich in cysteine (SPARC). The transient decline of SPARC after injury revealed a temporal …

Selective Serotonin Reuptake Inhibitors In Pediatric Depression: Is The Balance Between Benefits And Risks Favorable?, Christopher J. Kratochvil, Benedetto Vitiello, John Walkup, Graham Emslie, Bruce D. Waslick, Elizabeth B. Weller, William J. Burke, John S. March

Journal Articles: Psychiatry

Recent controversies surrounding the use of selective serotonin reuptake inhibitors (SSRIs) have highlighted the need to reassess potential benefits, as well as potential risks of this class of medications in the treatment of pediatric depression. The recent availability of data from meta-analyses of published and unpublished antidepressant trials, epidemiological studies, and the Treatment for Adolescents with Depression Study (TADS) has facilitated a reanalysis of this risk/benefit relationship. Despite reviewing similar data, various regulatory agencies have arrived at rather disparate conclusions regarding the data, resulting in continued controversy. Although all groups appear to agree that careful assessment, education regarding risks, and …

Research With Arctic Peoples: Unique Research Opportunities In Heart, Lung, Blood And Sleep Disorders. Working Group Summary And Recommendations, Sally Smith, Peter Bjerregaard, Hing Man Chan, André Corriveau, Sven Ebbesson, Ruth Etzel, Richard Fabsitz, Hakon Hakonarson, Carl Hild, Elizabeth Nobmann, Jeff Reading, Larisa Tereshchenko, T. Kue Young, Barbara Howard

Open Access Publications

Arctic peoples are spread over eight countries and comprise 3.74 million residents, of whom 9% are indigenous. The Arctic countries include Canada, Finland, Greenland (Denmark), Iceland, Norway, Russia, Sweden and the United States. Although Arctic peoples are very diverse, there are a variety of environmental and health issues that are unique to the Arctic regions, and research exploring these issues offers significant opportunities, as well as challenges. On July 28-29, 2004, the National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research co-sponsored a working group entitled "Research with Arctic Peoples: Unique Research Opportunities in Heart, Lung, …

Androgen Excess Disorders In Women: The Severe Insulin-Resistant Hyperandrogenic Syndrome, Hair-An, Kristin M. Rager, Hatim A. Omar

Pediatrics Faculty Publications

HAIR-AN syndrome (hyperandrogenism, insulin resistance, acanthosis nigricans) is a subset of the polycystic ovary syndrome, where the patients demonstrate severe insulin resistance. It is theorized that both genetic and environmental factors, such as obesity, give rise to the development of HAIR-AN. Diagnosis is primarily clinical, with laboratory values lending further support. Treatment is aimed at decreasing insulin resistance, regulating ovulation, and decreasing acne, acanthosis nigricans, and hirsutism.

Heparin Modulates The 99-Loop Of Factor Ixa: Effects On Reactivity With Isolated Kunitz-Type Inhibitor Domains, Pierre F. Neuenschwander, Stephen R. Williamson, Armen Nalian, Kimberly J. Baker-Deadmond

Faculty Publications

Reactivity of factor IXa with basic pancreatic trypsin inhibitor is enhanced by low molecular weight heparin (enoxaparin). Previous studies by us have suggested that this effect involves allosteric modulation of factor IXa. We examined the reactivity of factor IXa with several isolated Kunitz-type inhibitor domains: basic pancreatic trypsin inhibitor, the Kunitz inhibitor domain of protease Nexin-2, and the first two inhibitor domains of tissue factor pathway inhibitor. We find that enhancement of factor IXa reactivity by enoxaparin is greatest for basic pancreatic trypsin inhibitor (>10-fold), followed by the second tissue factor pathway inhibitor domain (1.7-fold) and the Kunitz inhibitor …

Tooth-Size Discrepancy And Bolton's Ratios: A Literature Review, S.A. Othman, N.W. Harradine

Research Publications (2006 to 2010)

OBJECTIVES: To review the literature on Bolton's tooth-size discrepancies (TSD) with specific attention to the prevalence of TSD, and the possible influence of different classes of malocclusion, gender and racial group. Also examined were the validity of the standard deviations from Bolton's samples as an indicator of significant TSD, methods of measurement of TSD and their reproducibility. Based on the review, suggestions are made as to how future work could be improved. RESULTS AND CONCLUSIONS: Studies have reported from 20 to 30 of people with significant tooth-size anterior discrepancies and 5-14 for overall TSD. Bolton's original sample was appropriate for …

The Speciation Of Metals In Mammals Influences Their Toxicokinetics And Toxicodynamics And Therefore Human Health Risk Assessment, Robert A. Yokel, Stephen M. Lasley, David C. Dorman

Pharmaceutical Sciences Faculty Publications

Chemical form (i.e., species) can influence metal toxicokinetics and toxicodynamics and should be considered to improve human health risk assessment. Factors that influence metal speciation (and examples) include: (1) carrier-mediated processes for specific metal species (arsenic, chromium, lead and manganese), (2) valence state (arsenic, chromium, manganese and mercury), (3) particle size (lead and manganese), (4) the nature of metal binding ligands (aluminum, arsenic, chromium, lead, and manganese), (5) whether the metal is an organic versus inorganic species (arsenic, lead, and mercury), and (6) biotransformation of metal species (aluminum, arsenic, chromium, lead, manganese and mercury). The influence of speciation on metal …

Cyanidin-3-Glucoside, A Natural Product Derived From Blackberry, Exhibits Chemopreventive And Chemotherapeutic Activity, Min Ding, Rentian Feng, Shiow Y. Wang, Linda Bowman, Yongju Lu, Yong Qian, Vincent Castranova, Bing-Hua Jiang, Xianglin Shi

Faculty & Staff Scholarship

Epidemiological data suggest that consumption of fruits and vegetables has been associated with a lower incidence of cancer. Cyanidin-3-glucoside (C3G), a compound found in blackberry and other food products, was shown to possess chemopreventive and chemotherapeutic activity in the present study. In cultured JB6 cells, C3G was able to scavenge ultraviolet B-induced *OH and O2-* radicals. In vivo studies indicated that C3G treatment decreased the number of non-malignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. Pretreatment of JB6 cells with C3G inhibited UVB- and TPA-induced transactivation of NF-kappaB and AP-1 and expression of …

Mutant Neurogenin-3 In Congenital Malabsorptive Diarrhea, Jiafang Wang, Galen Cortina, S. Vincent Wu, Robert Tran, Jang-Hyeon Cho, Ming-Jer Tsai, Travis J. Bailey, Milan Jamrich, Marvin E. Ament, William R. Treem, Ivor D. Hill, Jorge H. Vargas, George Gershman, Douglas G. Farmer, Laurie Reyen, Martin G. Martín

Biology

Background: Neurogenin-3 (NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine. The NEUROG3 gene (NEUROG3) is therefore a candidate for the cause of a newly discovered autosomal recessive disorder characterized by generalized malabsorption and a paucity of enteroendocrine cells. Methods: We screened genomic DNA from three unrelated patients with sparse enteroendocrine cells for mutations of NEUROG3. We then tested the ability of the observed mutations to alter NEUROG3 function, using in vitro and in vivo assays. Results: The patients had few intestinal enteroendocrine cells positive for chromogranin A, but they had …

An Exonic Splicing Silencer Is Involved In The Regulated Splicing Of Glucose 6-Phosphate Dehydrogenase Mrna, Wioletta Szeszel-Fedorowicz, Indrani Talukdar, Brian N. Griffith, Callee M. Walsh, Lisa M. Salati

Faculty & Staff Scholarship

No abstract provided.

No Vaccine Against Hiv Yet--Are We Not Perfectly Equipped?, Mahender Singh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Enormous effort has been devoted to the development of a vaccine against human immunodeficiency virus (HIV). But it is proving to be an unprecedented challenge to create an effective vaccine mainly due to the high genetic variability of the virus and the necessity of cytotoxic T lymphocytes (CTL) for containing the infection. Currently pursued vaccine strategies appear to induce CTL in nonhuman primate models but in the early clinical trials, these strategies fail to fully control the viral infection. New strategies that can cover the vast genetic diversity of HIV are needed for the development of a potent vaccine.

Modification Of Human Immunodeficiency Virus Type 1 Reverse Transcriptase To Target Cells With Elevated Cellular Dntp Concentrations, Varuni K. Jamburuthugoda, Pauline Chugh, Baek Kim

Biology

Retroviruses and DNA viruses utilize cellular dNTPs as substrates for their DNA polymerases during viral replication in infected cells. However, because of S phase-dependent dNTP biosynthesis, the availability of cellular dNTPs significantly varies among cell types (e.g. dividing versus nondividing cells and normal versus tumor cells). Here we tested whether alterations in the dNTP utilization efficiency and dNTP binding affinity of viral DNA polymerases can switch viral infection specificity to cell types with different dNTP concentrations. We employed an HIV-1 reverse transcriptase (RT) mutant (Q151N), which is catalytically active only at high dNTP concentrations because of its reduced dNTP binding …

Identification Of The Heparin-Binding Determinants Within Fibronectin Repeat Iii1: Role In Cell Spreading And Growth, Liqiong Gui, Katherine Wojciechowski, Candace D. Gildner, Hristina Nedelkovska, Denise C. Hocking

Biology

Fibronectins are high molecular mass glycoproteins that circulate as soluble molecules in the blood, and are also found in an insoluble, multimeric form in extracellular matrices throughout the body. Soluble fibronectins are polymerized into insoluble extracellular matrix (ECM) fibrils via a cell-dependent process. Recent studies indicate that the interaction of cells with the ECM form of fibronectin promotes actin organization and cell contractility, increases cell growth and migration, and enhances the tensile strength of artificial tissue constructs; ligation of integrins alone is insufficient to trigger these responses. Evidence suggests that the effect of ECM fibronectin on cell function is mediated …

Antisperm Immunity For Contraception, R. K. Naz

Faculty & Staff Scholarship

No abstract provided.

Interdependency Of Pharmacokinetic Parameters: A Chicken-And-Egg Problem? Not!, Reza Mehvar

Pharmacy Faculty Articles and Research

Pharmacokinetic (PK) software packages are widely used by scientists in different disciplines to estimate PK parameters. However, their use without a clear understanding of physiological parameters affecting the PK parameters and how different PK parameters are related to each other may result in erroneous interpretation of data. Often, mathematical relationships used for the estimation of PK parameters obscure the true physiological relationships among these parameters, prompting a discussion of which parameter came first and giving the appearance of the-chicken-and-the-egg dilemma. In this article, the author attempts to show how different PK parameters are related to physiological parameters and each other …

The Need For Tobacco Education: Studies Of Collegiate Dental Hygiene Patients And Faculty, Joan M. Davis Rdh, Ms, Margaret S Stockdale, Martha Cropper

Journal Articles

The need for inclusion of comprehensive tobacco control education/training for health care providers continues to be stressed in publications addressing cessation services. The dental appointment presents an excellent opportunity to provide tobacco interventions to basically healthy people on regular intervals. The purpose of this study was twofold: 1) to assess the need (stage of change and concomitant need for tobacco cessation intervention) of dental hygiene patients at a Midwest dental hygiene clinic, and 2) to assess and compare the level of tobacco intervention education currently being offered by dental hygiene educators in a Midwestern state. Patients (n=426) of a collegiate …

Resident Efficiency In A Pediatric Emergency Department., M Denise Dowd, Celeste Tarantino, Theodore M. Barnett, Laura Fitzmaurice, Jane F. Knapp

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To measure the hourly rate of patients evaluated and treated by resident physicians in an academic pediatric emergency department (PED) and examine differences in the rate by subspecialty and year of training.

METHODS: For all residents rotating in an academic, urban children's hospital PED, the rate of patients seen per hour over the course of their rotation was calculated using an electronic tracking system, EmSTAT, for calendar year 2000. Rates are reported as the mean number of patients seen per resident hour worked. Mean differences are reported for resident subspecialties (emergency medicine, pediatrics, and family practice) and postgraduate year …

Growth Factor–Induced Shedding Of Syndecan-1 Confers Glypican-1 Dependence On Mitogenic Responses Of Cancer Cells, Kan Ding, Martha Lopez-Burks, José A. Sánchez-Duran, Murray Korc, Arthur D. Lander

Dartmouth Scholarship

The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated by pancreatic and breast cancer cells, and its removal renders such cells insensitive to many growth factors. We sought to explain why the cell surface HSPG syndecan-1, which is also up-regulated by these cells and is a known growth factor coreceptor, does not compensate for glypican-1 loss. We show that the initial responses of these cells to the growth factor FGF2 are not glypican dependent, but they become so over time as FGF2 induces shedding of syndecan-1. Manipulations that retain syndecan-1 on the cell surface make long-term FGF2 responses glypican …

Principal Component Analysis For Predicting Transcription-Factor Binding Motifs From Array-Derived Data, Yunlong Liu, Matthew P Vincenti, Hiroki Yokota

Dartmouth Scholarship

The responses to interleukin 1 (IL-1) in human chondrocytes constitute a complex regulatory mechanism, where multiple transcription factors interact combinatorially to transcription-factor binding motifs (TFBMs). In order to select a critical set of TFBMs from genomic DNA information and an array-derived data, an efficient algorithm to solve a combinatorial optimization problem is required. Although computational approaches based on evolutionary algorithms are commonly employed, an analytical algorithm would be useful to predict TFBMs at nearly no computational cost and evaluate varying modelling conditions. Singular value decomposition (SVD) is a powerful method to derive primary components of a given matrix. Applying SVD …

Cortical Regions Associated With Autonomic Cardiovascular Regulation During Lower Body Negative Pressure In Humans., Derek S Kimmerly, Deborah D O'Leary, Ravi S Menon, Joseph S Gati, J Kevin Shoemaker

Kinesiology Publications

The purpose of the present study was to determine the cortical structures involved with integrated baroreceptor-mediated modulation of autonomic cardiovascular function in conscious humans independent of changes in arterial blood pressure. We assessed the brain regions associated with lower body negative pressure (LBNP)-induced baroreflex control using functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast in eight healthy male volunteer subjects. The levels of LBNP administered were 5, 15 and 35 mmHg. Heart rate (HR; representing the cardiovascular response) and LBNP (representing the baroreceptor activation level) were simultaneously monitored during the scanning period. In addition, estimated central venous pressure …

Evaluation Of Stature Development During Childhood And Adolescence In Individuals With Familial Hypophosphatemic Rickets, Mauro M. S. Borghi, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

This review was conducted to study the diagnosis, treatment, and growth progression in infants and adolescents with familial hypophosphatemic rickets. The bibliographic search was carried out utilizing the electronic databases MEDLINE, OVID, and LILACS and by direct research within the last 15 years using the keywords rickets, familial hypophosphatemia, vitamin D deficiency, stature growth, childhood, and adolescence. Article selection was done by comparing the evaluation of the growth in patients with familial hypophosphatemic rickets, including the variables that might affect them, for possible future therapeutic proposals. It is concluded that the most significant fact in the treatment of familial hypophosphatemic …

Cardiac Transplant Following Failed Fontan Or Glenn Procedures., Naveen L. Pereira, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Experts Recommend Strategies For Strengthening The Use Of Advanced Practice Nurses In Nursing Homes., Mathy Mezey, Sarah Greene Burger, Harrison G Bloom, Alice Bonner, Mary Bourbonniere, Barbara Bowers, Jeffrey B Burl, Elizabeth Capezuti, Diane Carter, Jacob Dimant, Sarah A Jerro, Susan C Reinhard, Marilyn Ter Maat

College of Nursing Faculty Papers & Presentations

In 2003, The John A. Hartford Foundation Institute for Geriatric Nursing, New York University Division of Nursing, convened an expert panel to explore the potential for developing recommendations for the caseloads of advanced practice nurses (APNs) in nursing homes and to provide substantive and detailed strategies to strengthen the use of APNs in nursing homes. The panel, consisting of nationally recognized experts in geriatric practice, education, research, public policy, and long-term care, developed six recommendations related to caseloads for APNs in nursing homes. The recommendations address educational preparation of APNs; average reimbursable APN visits per day; factors affecting APNs caseload …

Taxol-Stabilized Microtubules Can Position The Cytokinetic Furrow In Mammalian Cells, Katie Shannon, Julie C. Canman, C. Ben Moree, Jennifer S. Tirnauer, Edward D. Salmon

Biological Sciences Faculty Research & Creative Works

How microtubules act to position the plane of cell division during cytokinesis is a topic of much debate. Recently, we showed that a subpopulation of stable microtubules extends past chromosomes and interacts with the cell cortex at the site of furrowing, suggesting that these stabilized microtubules may stimulate contractility. To test the hypothesis that stable microtubules can position furrows, we used taxol to rapidly suppress microtubule dynamics during various stages of mitosis in PtK1 cells. Cells with stabilized prometaphase or metaphase microtubule arrays were able to initiate furrowing when induced into anaphase by inhibition of the spindle checkpoint. In these …

Clinical Kidney Transplantation: A 50th Anniversary Review Of The First Reported Series, Vivian Charles Mcalister

Surgery Publications

BACKGROUND: Histories of kidney transplantation rarely mention a series reported by Gordon Murray of Toronto and published by the American Journal of Surgery 50 years ago.

METHODS: The papers and biographies of Gordon Murray were reviewed in the context of knowledge at that time about renal failure management to determine their contribution to transplantation research and to current practice.

RESULTS: Murray proceeded from a unique leadership position in vascular surgery, anticoagulation therapy, and dialysis to undertake a rational series of animal experiments and human trials of kidney transplantation that led him to the practices of graft irrigation, cold storage, pelvic …

The Global Campaign (Gc) To Reduce The Burden Of Headache Worldwide. The International Team For Specialist Education (Itse)., Paolo Martelletti, Redda T Haimanot, Miguel J A Láinez, Alan M Rapoport, K Ravishankar, Fumihiko Sakai, Stephen Silberstein, Maurice Vincent, Timothy J Steiner

Department of Jefferson Headache Center Papers and Presentations

The social perception of headache, everywhere at low levels in industrialised countries, becomes totally absent in developing ones. Headache disorders came into the World Health Organization's strategic priorities after publication of the 2001 World Health Report. Among the leading causes of disability, migraine was ranked 19th for adults of both sexes together and 12th for females. The Global Campaign (GC) to Reduce the Burden of Headache Worldwide was planned by the major international headache organizations together with WHO in order to identify and remove those cultural, social and educational barriers recognised as responsible factors for the inadequate treatment of headache …

Ergonomics: Implications On Computer End-Users, Maheen Ghauri, Dr. Arshad Siddiqi

International Conference on Information and Communication Technologies

Ergonomics is the application of scientific information related to humans to the design of objects, systems and environment for human use. The objective is to apply human characteristics to the design of computer-based work environments to reduce problems of people at work. Lack of ergonomics has serious repercussions on end-users, including physical and mental illnesses. Using ergonomics to design computer-intensive environments would maximize efficiency, productivity and job satisfaction of employees. Unfortunately, in the Government Sector in Pakistan, there is no application of ergonomics in computer-based environments, and this leads to inefficiencies, errors, and safety and health issues. The purpose of …

A Brief History And Current Status Of A Dental Therapy Initiative In The United States, David A. Nash, Ron J. Nagel

Oral Health Science Faculty Publications

No abstract provided.

Basal Endothelial Nitric Oxide Release Is Preserved In Overweight And Obese Adults, Christopher A Desouza, Gary P. Van Guilder, Jared J Greiner, Derek T Smith, Greta L Hoetzer, Brian L Stauffer

Health and Nutritional Sciences Faculty Publications

OBJECTIVE: Impaired basal nitric oxide release is associated with a number of cardiovascular disorders including hypertension, arterial spasm, and myocardial infarction. We determined whether basal endothelial nitric oxide release is reduced in otherwise healthy overweight and obese adult humans.
RESEARCH METHODS AND PROCEDURES: Seventy sedentary adults were studied: 32 normal weight (BMI/m(2)), 24 overweight (BMI > or = 25 < 30 kg/m(2)), and 14 obese (BMI > or = 30 kg/m(2)). Forearm blood flow (FBF) responses to intra-arterial infusions of N(g)-monomethyl-L-arginine (5 mg/min), a nitric oxide synthase inhibitor, were used as an index of basal nitric oxide release.
RESULTS: N(g)-monomethyl-L-arginine elicited significant reductions in FBF in the normal weight …

Donepezil Effects On Mood In Patients With Schizophrenia And Schizoaffective Disorder, S Craig Risch, Michael D. Horner, Susan R. Mcgurk, Simmy Palecko, John S. Markowitz, Ziad Nahas, C. Lindsay Devane

Dartmouth Scholarship

Donepezil, 5 mg/d for 6 wk then 10 mg/d for 6 wk, and placebo daily for 12 wk in a double-blind cross-over paradigm, was added to the therapeutic regimen of 13 patients with schizophrenia or schizoaffective disorders, clinically stable on atypical antipsychotic medications. Patients had varying degrees of depressive symptoms, ranging from no depression to clinically significant depression. There was no worsening or induction of depression in individual patients or the group as a whole. In addition there was a statistically significant antidepressant effect in the group as a whole during the donepezil condition and a clinically significant antidepressant effect …