Digital Commons Network^™

Bicarbonate Enhances Expression Of The Endocarditis And Biofilm Associated Pilus Locus, Ebpr-Ebpabc, In Enterococcus Faecalis, Agathe Bourgogne, L Charlene Thomson, Barbara E Murray

Faculty, Staff and Student Publications

BACKGROUND: We previously identified ebpR, encoding a potential member of the AtxA/Mga transcriptional regulator family, and showed that it is important for transcriptional activation of the Enterococcus faecalis endocarditis and biofilm associated pilus operon, ebpABC. Although ebpR is not absolutely essential for ebpABC expression (100-fold reduction), its deletion led to phenotypes similar to those of an ebpABC mutant such as absence of pili at the cell surface and, consequently, reduced biofilm formation. A non-piliated ebpABC mutant has been shown to be attenuated in a rat model of endocarditis and in a murine urinary tract infection model, indicating an important participation …

Subacute Neural Stem Cell Therapy For Traumatic Brain Injury, Mikhail Bogdanov, Philip N Heacock, William Dowhan

Faculty, Staff and Student Publications

A protocol is described using lipid mutants and thiol-specific chemical reagents to study lipid-dependent and host-specific membrane protein topogenesis by the substituted-cysteine accessibility method as applied to transmembrane domains (SCAM). SCAM is adapted to follow changes in membrane protein topology as a function of changes in membrane lipid composition. The strategy described can be adapted to any membrane system.

Social Support In An Internet Weight Loss Community, Kevin O Hwang, Allison J Ottenbacher, Angela P Green, M Roseann Cannon-Diehl, Oneka Richardson, Elmer V Bernstam, Eric J Thomas

Faculty, Staff and Student Publications

Purpose: To describe social support for weight loss shared by members of a large Internet weight loss community.

Methods: We conducted a mixed-methods study with surveys (n=193) and interviews (n=13) of community members along with a content analysis of discussion forum messages (n=1924 messages). Qualitative data were analyzed for social support themes.

Results: Survey respondents were primarily white (91.4%) and female (93.8%) with mean age 37.3 years and mean body mass index 30.9. They used forums frequently, with 56.8% reading messages, 36.1% replying to messages, and 18.5% posting messages to start a discussion related to weight loss on a daily …

Treatment Strategies In Acute Myelogenous Leukemia : Investigating Hsp90 And P53 As Targets, Jennifer M. Napper

Theses, Dissertations and Capstones

Acute myelogenous leukemia (AML) is the deadliest of the lymphatic and bone marrow cancers. Patients diagnosed with AML have a five year survival rate of 23.4%. AML is characterized by an accumulation of undifferentiated and functionless myeloid precursors in the bone marrow and blood. Heat shock protein 90 (Hsp90) inhibitors, such as 17-AAG, an analog of geldanamycin (GM), are currently undergoing phase I, and II and III clinical trials for various cancers with mixed results. I found distinct responses to 17-AAG treatment among the AML cell lines tested. I also discovered two mutant TP53 alleles in Kasumi-3 cells, an AML …

Interaction Of The Mu-Opioid Receptor With Gpr177 (Wntless) Inhibits Wnt Secretion: Potential Implications For Opioid Dependence., Jay Jin, Saranya Kittanakom, Victoria Wong, Beverly A S Reyes, Elisabeth J Van Bockstaele, Igor Stagljar, Wade Berrettini, Robert Levenson

Department of Neurosurgery Faculty Papers

BACKGROUND: Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR). Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs) may help to elucidate the underlying mechanisms involved in the development of opioid dependence. RESULTS: GPR177, the mammalian ortholog of Drosophila …

Isolation And Cultivation Of Equine Corneal Keratocytes, Fibroblasts And Myofibroblasts, Dylan G. Buss, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To establish an in vitro model for the investigation of equine corneal wound healing. To accomplish this goal, a protocol to isolate and culture equine corneal keratocytes, fibroblasts and myofibroblasts was developed.

Animal material—Equine corneal buttons were aseptically harvested from healthy research horses undergoing humane euthanasia for reasons unrelated to this study. Slit-lamp biomicroscopy was performed prior to euthanasia by a board-certified veterinary ophthalmologist to ensure that all samples were harvested from horses free of anterior segment disease.

Procedure—Equine corneal stroma was isolated using mechanical techniques and stromal subsections were then cultured. Customized media at different culture conditions was used …

Differential Genome-Wide Array–Based Methylation Profiles In Prognostic Subsets Of Chronic Lymphocytic Leukemia, Meena Kanduri, Nicola Cahill, Hanna Göransson, Camilla Enström, Fergus Ryan, Anders Isaksson, Richard Rosenquist

Articles

Global hypomethylation and regional hypermethylation are well-known epigenetic features of cancer; however, in chronic lymphocytic leukemia (CLL), studies on genome-wide epigenetic modifications are limited. Here, we analyzed the global methylation profiles in CLL, by applying high-resolution methylation microarrays (27 578 CpG sites) to 23 CLL samples, belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets. Overall, results demonstrated significant differences in methylation patterns between these subgroups. Specifically, in IGHV unmutated CLL, we identified methylation of 7 known or candidate tumor suppressor genes (eg, VHL, ABI3, and IGSF4) as well as 8 unmethylated genes involved in …

Evaluating Children With Otitis Media For Bacteremia Or Urinary Tract Infection., Daniel Yawman, Patrick Mahar, Aaron Blumkin, Gregory P. Conners

Manuscripts, Articles, Book Chapters and Other Papers

Background. It is unclear if clinicians evaluate for concurrent bacteremia or UTI in young patients diagnosed with acute otitis media (AOM). Objectives. To describe how often, and under which circumstances, emergency providers investigate for bacteremia or UTI in 2-36 month olds with AOM. Methods. Cases of AOM were analyzed from the 2001-2004 National Hospital Ambulatory Medical Care Survey (NHAMCS)-Emergency Department dataset. Results. AOM was diagnosed in 17% of the 10,847 recorded visits of 2-36 month olds. Of these visits, laboratory testing included: CBC: 7%, Blood culture: 4%, urinalysis or urine culture: 5%, and any of these tests: 9%. Rates of …

Gbdr Regulates Pseudomonas Aeruginosa Plch And Pchp Transcription In Response To Choline Catabolites, Matthew J. Wargo, Tiffany C. Ho, Maegan J. Gross, Laurie A. Whittaker, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C, PlcH, can degrade phosphatidylcholine (PC) and sphingomyelin in eukaryotic cell membranes and extracellular PC in lung surfactant. Numerous studies implicate PlcH in P. aeruginosa virulence. The phosphorylcholine released by PlcH activity on phospholipids is hydrolyzed by a periplasmic phosphorylcholine phosphatase, PchP. Both plcH gene expression and PchP enzyme activity are positively regulated by phosphorylcholine degradation products, including glycine betaine. Here we report that the induction of plcH and pchP transcription by glycine betaine is mediated by GbdR, an AraC family transcription factor. Mutants that lack gbdR are unable to induce plcH and pchP in media …

Fluorescent Protein Markers To Tag Collagenous Proteins: The Paradigm Of Procollagen Vii, Hye J. Chung, Andrzej Steplewski, Jouni Uitto, Andrzej Fertala

Department of Dermatology and Cutaneous Biology Faculty Papers

Fluorescent proteins are powerful markers allowing tracking expression, intracellular localization, and translocation of tagged proteins but their effects on the structure and assembly of complex extracellular matrix proteins has not been investigated. Here, we analyzed the utility of fluorescent proteins as markers for procollagen VII, a triple-helical protein critical for the integrity of dermal-epidermal junction. DNA constructs encoding a red fluorescent protein-tagged wild type mini-procollagen VII α chain and green fluorescent protein-tagged α chains harboring selected mutations were genetically engineered. These DNA constructs were co-expressed in HEK-293 cells and the assembly of heterogeneous triple-helical mini-procollagen VII molecules was analyzed. Immunoprecipitation …

Carotid Artery Disease In Patients Undergoing Elective Coronary Artery Bypass Surgery, Waseem Akhtar, Ayan Sabih, Arif Ali, Mubashir Aslam, Nadeem Ahmad

Department of Radiology

OBJECTIVE: To determine frequency of carotid artery disease in patients undergoing elective coronary artery bypass grafting (CABG) using Doppler sonography.STUDY DESIGN: Observational study.

PLACE AND DURATION OF STUDY: Radiology Department, The Aga Khan University Hospital, Karachi, from January 2005 to September 2008.

METHODOLOGY: Patients with known cardiovascular disease waiting for CABG surgery were enrolled for carotid artery Doppler sonography. A predefined data entry form was used for data collection. Coronary angiography findings, carotid artery findings and other associated factors were noted from medical and radiological records. Frequency and pattern of carotid artery disease along with associated risk factors were evaluated. …

Identification And Genotyping Of Bacteria From Paired Vaginal And Rectal Samples From Pregnant Women Indicates Similarity Between Vaginal And Rectal Microflora, Nabil Abdullah El Aila, Inge Tency, Geert Claeys, Hans Verstraelen, Bart Saerens, Guido Lopes Dos Santos Santiago, Ellen De Backer, Piet Cools, Marleen Temmerman, Rita Verhelst

Obstetrics and Gynaecology, East Africa

Background: The vaginal microflora is important for maintaining vaginal health and preventing infections of the reproductive tract. The rectum has been suggested as the major source for the colonisation of the vaginal econiche.

Methods: To establish whether the rectum can serve as a possible bacterial reservoir for colonisation of the vaginal econiche, we cultured vaginal and rectal specimens from pregnant women at 35-37 weeks of gestation, identified the isolates to the species level with tRNA intergenic length polymorphism analysis (tDNA-PCR) and genotyped the isolates for those subjects from which the same species was isolated simultaneously vaginally and rectally, by RAPD-analysis. …

Genotyping Of Streptococcus Agalactiae (Group B Streptococci) Isolated From Vaginal And Rectal Swabs Of Women At 35-37 Weeks Of Pregnancy, Nabil Abdullah El Aila, Inge Tency, Geert Claeys, Bart Saerens, Ellen De Backer, Marleen Temmerman, Rita Verhelst, Mario Vaneechoutte

Obstetrics and Gynaecology, East Africa

Background: Group B streptococci (GBS), or Streptococcus agalactiae, are the leading bacterial cause of meningitis and bacterial sepsis in newborns. Here we compared different culture media for GBS detection and we compared the occurrence of different genotypes and serotypes of GBS isolates from the vagina and rectum.

Methods: Streptococcus agalactiae was cultured separately from both rectum and vagina, for a total of 150 pregnant women, i) directly onto Columbia CNA agar, or indirectly onto ii) Granada agar resp. iii) Columbia CNA agar, after overnight incubation in Lim broth.

Results: Thirty six women (24%) were colonized by GBS. Of these, 19 …

The Vaginal Microflora In Relation To Gingivitis, Rutger Persson, Jane Hitti, Rita Verhelst, Mario Vaneechoutte, Rigmor Persson, Regula Hirschi, Marianne Weibel, Marilynn Rothen, Marleen Temmerman, Kathleen Paul

Obstetrics and Gynaecology, East Africa

Background: Gingivitis has been linked to adverse pregnancy outcome (APO). Bacterial vaginosis (BV) has been associated with APO. We assessed if bacterial counts in BV is associated with gingivitis suggesting a systemic infectious susceptibilty.

Methods: Vaginal samples were collected from 180 women (mean age 29.4 years, SD ± 6.8, range: 18 to 46), and at least six months after delivery, and assessed by semi-quantitative DNA-DNA checkerboard hybridization assay (74 bacterial species). BV was defined by Gram stain (Nugent criteria). Gingivitis was defined as bleeding on probing at ≥ 20% of tooth sites.

Results: A Nugent score of 0–3 (normal vaginal …

Tb Research At Ut-Houston – A Review Of Cord Factor: New Approaches To Drugs, Vaccines And The Pathogenesis Of Tuberculosis, Robert L Hunter, Lisa Armitige, Chinnaswamy Jagannath, Jeffrey K Actor

Faculty, Staff and Student Publications

Tuberculosis remains a major threat as drug resistance continues to increase. Pulmonary tuberculosis in adults is responsible for 80% of clinical cases and nearly 100% of transmission of infection. Unfortunately, since we have no animal models of adult type pulmonary tuberculosis, the most important type of disease remains largely out of reach of modern science and many fundamental questions remain unanswered. This paper reviews research dating back to the 1950's providing compelling evidence that cord factor (trehalose 6,6 dimycolate [TDM]) is essential for understanding tuberculosis. However, the original papers by Bloch and Noll were too far ahead of their time …

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Biochemistry and Microbiology

Background

Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas.

Results

HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …

Solution Structure Of The Inhibitory Phosphorylation Domain Of Myosin Phosphatase Targeting Subunit 1., Shunsuke Mori, Ryou Iwaoka, Masumi Eto, Shin-Ya Ohki

Department of Molecular Physiology and Biophysics Faculty Papers

Cell motility, such as smooth muscle contraction and cell migration, is controlled by the reversible phosphorylation of the regulatory light chain of myosin II and other cytoskeletal proteins. Mounting evidence suggests that in smooth muscle cells and other types of cells in vertebrates, myosin phosphatase (MP) plays an important role in controlling the phosphorylation of myosin II as well as other cytoskeletal proteins, including ezrin, moesin, and radixin.1 MP is a holoenzyme consisting of a catalytic subunit of a type-1 Ser/Thr phosphatase (PP1C) delta isoform, a myosin phosphatase targeting subunit 1 (MYPT1), and an accessory subunit M21. In this ternary …

Reactive Oxygen And Nitrogen Species Induce Protein And Dna Modifications Driving Arthrofibrosis Following Total Knee Arthroplasty., Theresa A Freeman, Javad Parvizi, Craig J Della Valle, Marla J Steinbeck

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Arthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA), is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS) and nitrogen species (RNS) mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation.

RESULTS: We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed …

Medical Education Digest, Vol. 11 No. 6 (November/December 2009), Nova Southeastern University

Medical Education Digest

No abstract provided.

Chromosomal Anomalies Influence Parental Treatment Decisions In Relation To Prenatally Diagnosed Congenital Heart Disease., Sinai C. Zyblewski, Elizabeth G. Hill, Girish S. Shirali, Andrew Atz, Geoffrey Forbus, Javier Gonzalez, Anthony Hlavacek

Manuscripts, Articles, Book Chapters and Other Papers

This study aimed to identify the variables that influence parental treatment decisions after a prenatal diagnosis of congenital heart disease (CHD). The authors reviewed all cases of prenatally diagnosed structural CHD from August 1998 to December 2006 at their center. The following variables were studied as potential predictors of parental intent to treat: maternal age, race, insurance status, obstetric history, fetal gender, univentricular versus biventricular cardiac physiology, and fetal chromosomal abnormality. Uni- and multivariable logistic regression analyses were performed. In the review, 252 consecutive cases of prenatally diagnosed CHD were identified. Of these, 204 women pursued full medical treatment, whereas …

The False Promise Of Adolescent Brain Science In Juvenile Justice, Terry A. Maroney

Vanderbilt Law School Faculty Publications

Recent scientific findings about the developing teen brain have both captured public attention and begun to percolate through legal theory and practice. Indeed, many believe that developmental neuroscience contributed to the U.S. Supreme Court’s elimination of the juvenile death penalty in Roper v. Simmons. Post-Roper, scholars assert that the developmentally normal attributes of the teen brain counsel differential treatment of young offenders, and advocates increasingly make such arguments before the courts. The success of any theory, though, depends in large part on implementation, and challenges that emerge through implementation illuminate problematic aspects of the theory. This Article tests the legal …

Human Uterine Natural Killer Cells But Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection By Secretion Of Cxcl12, Teddy F. Mselle, Aexandra L. Howell, Mimi Ghosh, Charles R. Wira, Charles L. Sentman

Dartmouth Scholarship

Natural killer (NK) cells derived from the human female reproductive tract (FRT) are phenotypically and functionally distinct from those obtained from peripheral blood. Because the FRT is a primary site of human immunodeficiency virus type 1 (HIV-1) infection in women, we determined whether soluble factors secreted by uterine-derived NK (uNK) cells inhibit HIV-1 infection. Clonal populations of uNK cells were activated with interleukin-12 (IL-12) and IL-15, and conditioned media (CM) from these cultures evaluated for their ability to inhibit infection of cells by HIV-1_IIIB, HIV-1_NL4.3, and HIV-1_HC4 (X4-tropic) or HIV-1_BaL (R5-tropic) viruses. We found …

Developing A Coordinated School Health Approach To Child Obesity Prevention In Rural Appalachia: Results Of Focus Groups With Teachers, Parents, And Students, Karen E. Schetzina, William Dalton, Elizabeth F. Lowe, Nora Azzazy, Katrina Vonwerssowetz, Connie Givens, H. P. Stern

ETSU Faculty Works

INTRODUCTION:

High prevalence rates of obesity, particularly among those residing in US rural areas, and associated physical and psychosocial health consequences, direct attention to the need for effective prevention programs. The current study describes an initial step in developing a school-based obesity prevention program in rural Appalachia, USA. The program, modeled on the Centers for Disease Control and Prevention Coordinated School Health (CSH) Program, includes a community-based participatory research approach to addressing the health needs specific to this region.

METHODS:

Focus groups with teachers, parents, and 4th grade students were used to understand perceptions and school policy related to nutrition, …

Use Of Id4 For Diagnosis And Treatment Of Cancer, Dave Sb Hoon, Naoyuki Umetani

Technology Transfer - Patents

The invention relates to a method of determining whether a (73) Assignee: John Wayne Cancer Institute, human Subject is suffering from or at risk for developing Sant Monica Boulevard, CA (US) pancreatic cancer by determining the methylation level of an ID4 gene promoter or the expression level of an ID4 gene in a biological sample from a human Subject. Also disclosed are a method of analyzing the methylation level of an ID4 gene promoter or the expression level of an ID4 gene in a pancreatic cancer cell, and a method of inhibiting the methylation of an ID4 gene promoter or …

Use Of Id4 For Diagnosis And Treatment Of Cancer, Dave Hoon, Naoyuki Umetani

Technology Transfer - Patents

The invention relates to a method of determining whether a human Subject is suffering from or at risk for developing Sant Monica Boulevard, CA (US) pancreatic cancer by determining the methylation level of an ID4 gene promoter or the expression level of an ID4 gene in a biological sample from a human Subject. Also disclosed are a method of analyzing the methylation level of an ID4 gene promoter or the expression level of an ID4 gene in a pancreatic cancer cell, and a method of inhibiting the methylation of Related U.S. Application Data an ID4 gene promoter or enhancing the …

Protection Against Mucosal Shiv Challenge By Peptide And Helper-Dependent Adenovirus Vaccines, Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helperdependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5- immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than in …

Com Outlook Fall 2009, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Interventions For Autism Spectrum Disorders: State Of The Evidence, Lindsey Tweed Md, Mph, Nancy Connolly Mppm, Amy Beaulieu

Children, Youth, & Families

The number of children in Maine with Autism Spectrum Disorders (ASD) has increased significantly over the past decade. Since 2000, the number of children receiving Special Education services for ASD in Maine schools jumped from 594 to 2,231in 2008 – an increase of 276%. A recent study estimated that the total cost of caring for a person with autism over his or her lifetime can reach $3.2 million, with more than $35 billion spent collectively per year (Ganz, 2007). To conserve already scarce resources and of-fer the best possible services to children with ASD, it is necessary to identify and …

Treatment Response In Depressed Adolescents With And Without Co-Morbid Attention-Deficit/Hyperactivity Disorder In The Treatment For Adolescents With Depression Study., Christopher J. Kratochvil, Diane E. May, Susan G. Silva, Vishal Madaan, Susan E. Puumala, John F. Curry, John Walkup, Hayden Kepley, Benedetto Vitiello, John S. March

Journal Articles: Psychiatry

OBJECTIVE: In the Treatment for Adolescents with Depression Study (TADS), fluoxetine (FLX) and the combination of fluoxetine with cognitive-behavioral therapy (COMB) had superior improvement trajectories compared to pill placebo (PBO), whereas cognitive-behavioral therapy (CBT) was not significantly different from PBO. Because attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) frequently co-exist, we examined whether ADHD moderated these outcomes in TADS.

METHOD: A total of 439 adolescents with MDD, 12-17 years old, were randomized to FLX, CBT, COMB, or PBO. Random coefficients regression models examined depression improvement in 377 depressed youths without ADHD and 62 with ADHD, including 20 who were …

The Production Of Antibody By Invading B Cells Is Required For The Clearance Of Rabies Virus From The Central Nervous System., D Craig Hooper, Timothy W Phares, Marzena J Fabis, Anirban Roy

Department of Cancer Biology Faculty Papers

BACKGROUND: The pathogenesis of rabies is associated with the inability to deliver immune effectors across the blood-brain barrier and to clear virulent rabies virus from CNS tissues. However, the mechanisms that facilitate immune effector entry into CNS tissues are induced by infection with attenuated rabies virus.

METHODOLOGY/PRINCIPAL FINDINGS: Infection of normal mice with attenuated rabies virus but not immunization with killed virus can promote the clearance of pathogenic rabies virus from the CNS. T cell activity in B cell-deficient mice can control the replication of attenuated virus in the CNS, but viral mRNA persists. Low levels of passively administered rabies …