Medicine and Health Sciences Commons^™

Genomic Loss Of Tumor Suppressor Mirna-204 Promotes Cancer Cell Migration And Invasion By Activating Akt/Mtor/Rac1 Signaling And Actin Reorganization, Saadi J. Imam, Jason R. Plyler, Hima Bansal, Suresh Prajapati, Sanjay Bansal, Jennifer Rebeles, Jeffrey S. Dome, +12 Additional Authors

Pediatrics Faculty Publications

Increasing evidence suggests that chromosomal regions containing microRNAs are functionally important in cancers. Here, we show that genomic loci encoding miR-204 are frequently lost in multiple cancers, including ovarian cancers, pediatric renal tumors, and breast cancers. MiR-204 shows drastically reduced expression in several cancers and acts as a potent tumor suppressor, inhibiting tumor metastasis in vivo when systemically delivered. We demonstrated that miR-204 exerts its function by targeting genes involved in tumorigenesis including brain-derived neurotrophic factor (BDNF), a neurotrophin family member which is known to promote tumor angiogenesis and invasiveness. Analysis of primary tumors shows that increased expression …

The Involvement Of Acidic Nucleoplasmic Dna-Binding Protein (And-1) In The Regulation Of Prereplicative Complex (Pre-Rc) Assembly In Human Cells, Yongming Li, Haijie Xiao, Christelle De Renty, Aimee Jaramillo-Lambert, Zhiyong Han, Melvin L. Depamphilis, Kristy J. Brown, Wenge Zhu

Pediatrics Faculty Publications

No abstract provided.

Post-Transfusion Purpura In An African-American Man Due To Human Platelet Antigen-5b Alloantibody: A Case Report, Filipa Lynce, Fang Yin, Kirsten Alcorn, Vera Malkovska

Pediatrics Faculty Publications

Introduction

Post-transfusion purpura is a rare immunohematological disorder characterized by severe thrombocytopenia following transfusion of blood components and induced by an alloantibody against a donor platelet antigen. It occurs primarily in women sensitized by pregnancy and is most commonly caused by anti-human platelet antigen-1a antibodies. Here, we describe what we believe to be the first documented case of an African-American man who developed post-transfusion purpura due to an anti-human platelet antigen-5b alloantibody after receiving multiple blood products.

Case presentation

A 68-year-old African-American man initially admitted with atrial flutter was started on anticoagulation treatment, which was complicated by severe hematemesis. On …

Twice-Daily Application Of Hiv Microbicides Alters The Vaginal Microbiota, Jacques Ravel, Pawel Gajer, Li Fu, Christine K. Mauck, Sara S.K. Koenig, Joyce Sakamoto, Alison A. Motsinger-Reif, Gustavo F. Doncel, Steven L. Zeichner

Pediatrics Faculty Publications

Vaginal HIV microbicides offer great promise in preventing HIV transmission, but failures of phase 3 clinical trials, in which microbicide-treated subjects had an increased risk of HIV transmission, raised concerns about endpoints used to evaluate microbicide safety. A possible explanation for the increased transmission risk is that the agents shifted the vaginal bacterial community, resulting in loss of natural protection and enhanced HIV transmission susceptibility. We characterized vaginal microbiota, using pyrosequencing of bar-coded 16S rRNA gene fragments, in samples from 35 healthy, sexually abstinent female volunteer subjects (ages 18 to 50 years) with regular menses in a repeat phase 1 …

Prevalence Of Obesity Among Young Asian-American Children, Anjali Jain, Stephanie Mitchell, Radha Chirumamilla, Jin Zhang, Ivor B. Horn, Amy Lewin, Z. Jennifer Huang

Pediatrics Faculty Publications

BACKGROUND:

Asian-American children are considered to be at low risk of obesity, but previous estimates have not distinguished between children from different Asian countries. We estimate the prevalence of obesity among Asian-American children by mother's country of origin, generational status, and family socioeconomic factors using a secondary analysis of the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B) wave III (children ∼4 years old) dataset.

METHODS:

The ECLS-B is a nationally representative study of children born in 2001 that oversampled births to Asian mothers. Asian ethnic categories included Chinese, Japanese, Filipino, Asian Indian, Korean, Vietnamese, and Other Asian/Pacific Islander. The primary outcome …

Gender Differences In The Developmental Outcomes Of Children With Congenital Cardiac Defects, Annette Majnemer, Catherine Limperopoulos, Michael Shevell, Charles Rohlicek, Bernard Rosenblatt, Chirsto Tchervenkov

Pediatrics Faculty Publications

Objective: This study compares the developmental and functional outcomes at school entry between boys and girls born with a congenital cardiac defect who required early surgical correction.

Study design: A prospective cohort of 94 children, including 49 percent boys, were followed up to 5 years of age and assessed for developmental progress. Developmental measures included Wechsler Preschool and Primary Scale of Intelligence – cognitive; Peabody Picture Vocabulary Test – receptive language; Peabody Developmental Motor Scale – motor; and Child Behaviour Checklist – behaviour. Measures of function included the Vineland Adaptive Behavior Scale and Functional Independence Measure for Children (WeeFIM).

Results: …

Feasibility Of Implementing Pulse Oximetry Screening For Congenital Heart Disease In A Community Hospital., Elizabeth A. Bradshaw, Sandra Cuzzi, S. C. Kiernan, N. Nagel, Jeffrey A. Becker, Gerard R. Martin

Pediatrics Faculty Publications

Objective:

Pulse oximetry has been recognized as a promising screening tool for critical congenital heart disease (CCHD). The aim of this research was to study the feasibility of implementation in a community hospital setting.

Study Design:

Meetings were conducted to determine an implementation plan. Pulse oximetry was performed on the right hand and foot after 24h of age. Newborns with a saturation 95% or a 3% difference were considered to have a positive screen. Screening barriers, screening time and ability to effectively screen all eligible newborns were noted.

Result:

From January 2009 through May 2010, of 6841 eligible newborns, 6745 …

Use Of Quantitative Membrane Proteomics Identifies A Novel Role Of Mitochondria In Healing Injured Muscles., Nimisha Sharma, Sushma Medikayala, Sree Rayavarapu, Kristy J. Brown, Yetrib Hathout, Jyoti K. Jaiswal, Aurelia Defour

Pediatrics Faculty Publications

Skeletal muscles are proficient at healing from a variety of injuries. Healing occurs in two phases, early and late phase. Early phase involves healing the injured sarcolemma and restricting the spread of damage to the injured myofiber. Late phase of healing occurs a few days postinjury and involves interaction of injured myofibers with regenerative and inflammatory cells. Of the two phases, cellular and molecular processes involved in the early phase of healing are poorly understood. We have implemented an improved sarcolemmal proteomics approach together with in vivo labeling of proteins with modified amino acids in mice to study acute changes …

Parent-Clinician Communication Intervention During End-Of-Life Decision Making For Children With Incurable Cancer., Pamela S. Hinds, Linda L. Oakes, Judy Hicks, Brent Powell, Deo K. Srivastava, Justin N. Baker, Sheri L. Spunt, Nancy K. West, Wayne L. Furman

Pediatrics Faculty Publications

Background: In this single-site study, we evaluated the feasibility of a parent-clinician communication intervention designed to: identify parents' rationale for the phase I, do-not-resuscitate (DNR), or terminal care decision made on behalf of their child with incurable cancer; identify their definition of being a good parent to their ill child; and provide this information to the child's clinicians in time to be of use in the family's care.

Methods: Sixty-two parents of 58 children and 126 clinicians participated. Within 72 hours after the treatment decision, parents responded to 6 open-ended interview questions and completed a 10-item questionnaire about the end-of-life …

Secretome Survey Of Human Plexiform Neurofibroma Derived Schwann Cells Reveals A Secreted Form Of The Rarres1 Protein., Hui-Ling Chen, Haeri Seol, Kristy J. Brown, Heather Gordish-Dressman, D. Ashley Hill, Vittorio Gallo, Roger J. Packer, Yetrib Hathout

Pediatrics Faculty Publications

To bring insights into neurofibroma biochemistry, a comprehensive secretome analysis was performed on cultured human primary Schwann cells isolated from surgically resected plexiform neurofibroma and from normal nerve tissue. Using a combination of SDS-PAGE and high precision LC-MS/MS, 907 proteins were confidently identified in the conditioned media of Schwann cell cultures combined. Label free proteome profiling revealed consistent release of high levels of 22 proteins by the four biological replicates of NF1 Schwann cell cultures relative to the two normal Schwann cell cultures. Inversely, 9 proteins displayed decreased levels in the conditioned media of NF1 relative to normal Schwann cells. …

Case Report: Rapid Spontaneous Recovery From Severe Hypothyroidism In 2 Teenage Girls., Paul B. Kaplowitz

Pediatrics Faculty Publications

Background

While it is recognized that patients sometimes recover from autoimmune hypothyroidism, little is known about how rapidly this may occur.

Case reports

Two 13 year old girls had severe primary hypothyroidism (total T4 14.2 nmol/L with TSH 468 miU/L and total T4 7.7 nmol/L with TSH 183 miU/L) accompanied by goiter and positive thyroid peroxidase antibodies. There were delays in starting thyroid hormone replacement, and complete reversal of hypothyroidism was documented within 2 months in both cases. One of the girls had recurrence of severe hypothyroidism after being euthyroid for 18 months.

Review of literature

There are few published …

Time-Series Model To Predict Impact Of H1n1 Influenza On A Children's Hospital., Michael C. Spaeder, Jonathan R. Stroud, Xiaoyan Song

Pediatrics Faculty Publications

The spring of 2009 witnessed the emergence of a novel influenza A(H1N1) virus resulting in the first influenza pandemic since 1968. In autumn of 2010, the 2009 novel H1N1 influenza strain re-emerged. We performed a retrospective time-series analysis of all patients with laboratory-confirmed H1N1 influenza who presented to our institution during 2009. Cases of influenza were assembled into 3-day aggregates and forecasting models of H1N1 influenza incidence were created. Forecasting estimates of H1N1 incidence for the 2010–2011 season were compared to actual values for our institution to assess model performance. Ninety-five percent confidence intervals calculated around our model's forecasts were …

Significant Differences In Markers Of Oxidant Injury Between Idiopathic And Bronchopulmonary-Dysplasia-Associated Pulmonary Hypertension In Children, Kimberly B. Vera, Donald Moore, English Flack, Michael Liske, Marshall Summar

Pediatrics Faculty Publications

While oxidant stress is elevated in adult forms of pulmonary hypertension (PH), levels of oxidant stress in pediatric PH are unknown. The objective of this study is to measure F₂-isoprostanes, a marker of oxidant stress, in children with idiopathic pulmonary hypertension (IPH) and PH due to bronchopulmonary dysplasia (BPD). We hypothesized that F₂-isoprostanes in pediatric IPH and PH associated with BPD will be higher than in controls. Plasma F₂-isoprostanes were measured in pediatric PH patients during clinically indicated cardiac catheterization and compared with controls. F₂-Isoprostane levels were compared between IPH, PH due …

Survival Motor Neuron Protein Deficiency Impairs Myotube Formation By Altering Myogenic Gene Expression And Focal Adhesion Dynamics, Katherine V. Bricceno, Tara Martinez, Evgenia Leikina, Stephanie Duguez, Terence A. Partridge, Leonid V. Chernomordik, Kenneth H. Fischbeck, Charlotte J. Sumner, Barrington G. Burnett

Pediatrics Faculty Publications

While spinal muscular atrophy (SMA) is characterized by motor neuron degeneration, it is unclear whether and how much survival motor neuron (SMN) protein deficiency in muscle contributes to the pathophysiology of the disease. There is increasing evidence from patients and SMA model organisms that SMN deficiency causes intrinsic muscle defects. Here we investigated the role of SMN in muscle development using muscle cell lines and primary myoblasts. Formation of multinucleate myotubes by SMN-deficient muscle cells is inhibited at a stage preceding plasma membrane fusion. We found increased expression and reduced induction of key muscle development factors, such as MyoD and …

Overlap Subtype Of Chronic Graft-Versus-Host Disease Is Associated With An Adverse Prognosis, Functional Impairment, And Inferior Patient-Reported Outcomes: A Chronic Graft-Versus-Host Disease Consortium Study, Joseph Pidala, Georgia Vogelsang, Paul Martin, Xiaoyu Chai, Barry Storer, Steven Pavletic, Daniel Weisdorf, Madan Jagasia, Corey Cutler, Jeanne Palmer, David Jacobsohn, Sally Arai, Stephanie J. Lee

Pediatrics Faculty Publications

Background

The National Institutes of Health Consensus Conference proposed the term “overlap” graft-versus-host disease to describe the situation when both acute and chronic graft-versus-host disease are present.

Design and Methods

We examined whether the overlap subtype of graft-versus-host disease was associated with a different prognosis, functional limitations, or patient-reported outcomes compared to “classic” chronic graft-versus-host disease without any acute features.

Results

Prospective data were collected from 427 patients from nine centers. Patients were classified as having overlap (n=352) or classic chronic (n=75) graft-versus-host disease based on reported organ involvement. Overlap …

Transcriptional Regulation Of N-Acetylglutamate Synthase, Sandra Kirsch Heibel, Giselle Yvette Lopez, Maria Panglao, Sonal Sodha, Leonardo Marino-Ramirez, Mendel Tuchman, Ljubica Caldovic

Pediatrics Faculty Publications

The urea cycle converts toxic ammonia to urea within the liver of mammals. At least 6 enzymes are required for ureagenesis, which correlates with dietary protein intake. The transcription of urea cycle genes is, at least in part, regulated by glucocorticoid and glucagon hormone signaling pathways. N-acetylglutamate synthase (NAGS) produces a unique cofactor, N-acetylglutamate (NAG), that is essential for the catalytic function of the first and rate-limiting enzyme of ureagenesis, carbamyl phosphate synthetase 1 (CPS1). However, despite the important role of NAGS in ammonia removal, little is known about the mechanisms of its regulation. We identified two regions of high …

Mechanisms Of Fetal Programming In Hypertension., John E. Jones, Julie A. Jurgens, Sarah A. Evans, Riley C. Ennis, Van Anthony Villar, Pedro A. Jose

Pediatrics Faculty Publications

Events that occur in the early fetal environment have been linked to long-term health and lifespan consequences in the adult. Intrauterine growth restriction (IUGR), which may occur as a result of nutrient insufficiency, exposure to hormones, or disruptions in placental structure or function, may induce the fetus to alter its developmental program in order to adapt to the new conditions. IUGR may result in a decrease in the expression of genes that are responsible for nephrogenesis as nutrients are rerouted to the development of more essential organs. Fetal survival under these conditions often results in low birth weight and a …

Physiologically Based Pharmacokinetic Modeling In Pediatric Drug Development: A Clinician's Request For A More Integrated Approach., Karel M. Allegaert, Anne Smits, John N. Van Den Anker

Pediatrics Faculty Publications

No abstract provided.

Hypertension-Related Gene Polymorphisms Of G-Protein-Coupled Receptor Kinase 4 Are Associated With Nt-Probnp Concentration In Normotensive Healthy Adults, Junichi Yatabe, Midori S. Yatabe, Minoru Yoneda, Robin A. Felder, Pedro A. Jose, Hironobu Sanada

Pediatrics Faculty Publications

G protein-coupled receptor kinase 4 (GRK4) with activating polymorphisms desensitize the natriuric renal tubular D1 dopamine receptor, and these GRK4 polymorphisms are strongly associated with salt sensitivity and hypertension. Meanwhile, N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful in detecting slight volume expansion. However, relations between hypertension-related gene polymorphisms including GRK4 and cardiovascular indices such as NT-proBNP are not clear, especially in healthy subjects. Therefore, various hypertension-related polymorphisms and cardiovascular indices were analyzed in 97 normotensive, healthy Japanese adults. NT-proBNP levels were significantly higher in subjects with two or more GRK4 polymorphic alleles. Other hypertension-related gene polymorphisms, such as those …

Hiv-1 Resistant Cdk2-Knockdown Macrophage-Like Cells Generated From 293t Cell-Derived Human Induced Pluripotent Stem Cells, Marina Jerebtsova, Namita Kumari, Min Xu, Gustavo Brito Alvim De Melo, Xiaomei Niu, Kuan-Teh Jeang, Sergei Nekhai

Pediatrics Faculty Publications

A major challenge in studies of human diseases involving macrophages is low yield and heterogeneity of the primary cells and limited ability of these cells for transfections and genetic manipulations. To address this issue, we developed a simple and efficient three steps method for somatic 293T cells reprogramming into monocytes and macrophage-like cells. First, 293T cells were reprogrammed into induced pluripotent stem cells (iPSCs) through a transfection-mediated expression of two factors, Oct-4 and Sox2, resulting in a high yield of iPSC. Second, the obtained iPSC were differentiated into monocytes using IL-3 and M-CSF treatment. And third, monocytes were differentiated into …

Evaluation Of Sedimentation Rate Methodology Reveals An Unusual Pediatric Subpopulation With Lupus Or Lupus-Like Syndrome And Hemolytic Anemia, Edward C. Wong, Deborah Yuan, Claas Hinze, Lawrence Jung

Pediatrics Faculty Publications

Purpose

Sedimentaion rate is often used to manage pediatric patients with rheumatologic disease. Most management decisions are dependent on studies which have used Wintrobe or Westergren sedimentation rate methodologies. However, these methods suffer from the need for relatively large amounts of blood and long turn-around times. Determination of sedimentation rate using laser kinetic rate determination has allowed calibration to Westergren methods, low volume of blood needed for testing and very rapid results. We sought to compare the Wintrobe method to the ESR Stat method (kinetic method; HemaTechnologies, Lebanon NJ) to determine suitability of the ESR Stat method for patient testing. …

The Test Characteristics Of Head Circumference Measurements For Pathology Associated With Head Enlargement: A Retrospective Cohort Study, Carrie Daymont, Moira Zabel, Chris Feudtner, David M. Rubin

Pediatrics Faculty Publications

Background

The test characteristics of head circumference (HC) measurement percentile criteria for the identification of previously undetected pathology associated with head enlargement in primary care are unknown.

Methods

Electronic patient records were reviewed to identify children age 3 days to 3 years with new diagnoses of intracranial expansive conditions (IEC) and metabolic and genetic conditions associated with macrocephaly (MGCM). We tested the following HC percentile threshold criteria: ever above the 95th, 97th, or 99.6thpercentile and ever crossing 2, 4, or 6 increasing major percentile lines. The Centers for Disease Control and World Health Organization growth curves were used, as well …

Reasons For Low Pandemic H1n1 2009 Vaccine Acceptance Within A College Sample, Russell D. Ravert, Linda Y. Fu

Pediatrics Faculty Publications

This study examined health beliefs associated with novel influenza A (H1N1) immunization among US college undergraduates during the 2009-2010 pandemic. Undergraduates (ages 18–24 years) from a large Midwestern University were invited to complete an online survey during March, 2010, five months after H1N1 vaccines became available. Survey items measured H1N1 vaccine history and H1N1-related attitudes based on the health belief literature. Logistic regression was used to identify attitudes associated with having received an H1N1 vaccine, and thematic analysis of student comments was conducted to further understand influences on vaccine decisions. Among the 296 students who participated in the survey, 15.2% …