Medical Specialties Commons^™

Transfection Of Il-10 Expression Vectors Into Endothelial Cultures Attenuates Alpha4beta7-Dependent Lymphocyte Adhesion Mediated By Madcam-1., Makoto Sasaki, Paul Jordan, Jeff Houghton, Xianmin Meng, Makoto Itoh, Takashi Joh, J Steven Alexander

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Enhanced expression of MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is associated with the onset and progression of inflammatory bowel disease. The clinical significance of elevated MAdCAM-1 expression is supported by studies showing that immunoneutralization of MAdCAM-1, or its ligands reduce inflammation and mucosal damage in models of colitis. Interleukin-10 (IL-10) is an endogenous anti-inflammatory and immunomodulatory cytokine that has been shown to prevent inflammation and injury in several animal studies, however clinical IL-10 treatment remains insufficient because of difficulties in the route of IL-10 administration and its biological half-life. Here, we examined the ability of introducing an IL-10 expression …

Responsiveness Of Bovine Cumulus-Oocyte-Complexes (Coc) To Porcine And Recombinant Human Fsh, And The Effect Of Coc Quality On Gonadotropin Receptor And Cx43 Marker Gene Mrnas During Maturation In Vitro., Michele D Calder, Anita N Caveney, Lawrence C Smith, Andrew J Watson

Obstetrics & Gynaecology Publications

Substantially less development to the blastocyst stage occurs in vitro than in vivo and this may be due to deficiencies in oocyte competence. Although a large proportion of bovine oocytes undergo spontaneous nuclear maturation, less is known about requirements for proper cytoplasmic maturation. Commonly, supraphysiological concentrations of FSH and LH are added to maturation media to improve cumulus expansion, fertilization and embryonic development. Therefore, various concentrations of porcine FSH (pFSH) and recombinant human FSH (rhFSH) were investigated for their effect on bovine cumulus expansion in vitro. Expression of FSHr, LHr and Cx43 mRNAs was determined in cumulus-oocyte complexes to determine …

Tacrolimus As A Liver Flush Solution To Ameliorate The Effects Of Ischemia/Reperfusion Injury Following Liver Transplantation., Shawn D. St Peter, David J. Post, Manuel I. Rodriguez-Davalos, David D. Douglas, Adyr A. Moss, David C. Mulligan

Manuscripts, Articles, Book Chapters and Other Papers

The goal of this report is to evaluate in a prospective randomized fashion the effect of flushing hepatic allografts with tacrolimus before transplantation. A prospective, double-blinded, randomized trial was performed. Twenty patients receiving orthotopic liver transplants from October 2000 to October 2001 were randomized into two groups. Group 1 (active) was administered tacrolimus, 20 ng/mL, plus Plasma-lyte A (Baxter Healthcare Corp, Deerfield, IL) liver flush solution; and group 2 (placebo) was administered only Plasma-lyte A. Ischemia/reperfusion injury was assessed in both groups after transplantation by means of serum laboratory values to assess hepatocellular damage, synthetic function, and ion transport capacity. …

Effects Of Tacrolimus On Ischemia-Reperfusion Injury., Shawn D. St Peter, Adyr A. Moss, David C. Mulligan

Manuscripts, Articles, Book Chapters and Other Papers

In addition to efficacious immunosuppression for the benefit of organ transplantation, tacrolimus has diverse actions that result in amelioration of ischemia-reperfusion injury. Knowledge is accumulating rapidly on the mechanisms through which tacrolimus exerts these cytoprotective effects, including alterations in microcirculation, free radical metabolism, calcium-activated pathways, inflammatory cascades, mitochondrial stability, apoptosis, stress-response proteins, and tissue recovery. Within the nucleus, actions mediating the effects of tacrolimus appear to be dominantly influenced by interactions with the transcription factor, nuclear factor-kappaB. Because tacrolimus is a cornerstone agent in immunosuppression regimens throughout the world and knowledge of its cellular mechanisms is evolving, it is important …

Regulation Of Human Col9a1 Gene Expression. Activation Of The Proximal Promoter Region By Sox9., Ping Zhang, Sergio A. Jimenez, David G Stokes

Department of Medicine Faculty Papers

The COL9A1 gene contains two promoter regions, one driving expression of a long alpha1(IX) chain in cartilage (upstream) and one driving expression of a shorter chain in the cornea and vitreous (downstream). To determine how the chondrocyte-specific expression of the COL9A1 gene is regulated, we have begun to characterize the upstream chondrocyte-specific promoter region of the human COL9A1 gene. Transient-transfection analyses performed in rat chondrosarcoma (RCS) cells, human chondrosarcoma (HTB) cells, and NIH/3T3 cells showed that the COL9A1 promoter was active in RCS cells but not HTB or NIH/3T3 cells. Inclusion of the first intron had no effect on promoter …

Educating Adolescents About Puberty: What Are We Missing?, Hatim A. Omar, Darby H. Mcelderry, Rana M. Zakharia

Pediatrics Faculty Publications

Adolescents undergo significant physical and cognitive changes during their pubertal development. These changes contribute to and impact their future development. Educating adolescents at an early age about their expected development decreases the possible anxiety associated with this period of life and also helps adolescents make better choices in regards to their sexuality. In order to assess the degree of education regarding pubertal development and sexuality, we conducted a survey of late adolescents (Median age 19 years) and parents of adolescents. A total of 409 adolescents (237 females, 172 males) and 124 parents completed the survey. 14.4% of teens (36.6% of …

Platelets Stimulate Fibroblast-Mediated Contraction Of Collagen Gels, Ulrika Zagai, Karin Fredriksson, Stephen I. Rennard, Joachim Lundahl, C. Magnus Sköld

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Platelets are thought to play a role in a variety of inflammatory conditions in the lung, some of which may lead to fibrosis. In the current study we tested the hypothesis that whole platelets and platelet lysate can mediate remodelling of extracellular matrix in vitro by affecting fibroblast-mediated contraction of a collagen gel. We also sought to determine to what extent platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) contribute to this effect.

METHODS: Washed platelets, isolated from healthy blood donors, and platelet lysate (freezing and thawing), were cast together with human lung fibroblasts in three-dimensional collagen gels. …

Our Adolescents--Our Future, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

Sex Education In The Schools: What Role Does It Play?, Darby H. Mcelderry, Hatim A. Omar

Pediatrics Faculty Publications

Information regarding pubertal development, sex, pregnancy, and contraception should be provided to children and adolescents in an age-appropriate manner from parents, health care providers, and schools. This article reviews the medical literature on school sex education programs, adolescents' perception of these programs, and the role played by the media, parents, and health care professionals in sexual education of teens.

Parenting Adolescents, Sandra L. D'Angelo, Hatim A. Omar

Pediatrics Faculty Publications

The period of adolescence is often thought to be one of intense stress and turmoil. Yet many parents and teens negotiate this developmental stage without extreme family conflict and without sacrificing close relationships. This review summarizes a portion of the literature on parent-adolescent relationships, focusing on monitoring and control of adolescent behavior and parenting style. Basic principles to emphasize when working with adolescents and parents are also included.

Current Practice Regarding The Use Of Fatty Livers: A Trans-Atlantic Survey., Charles J. Imber, Shawn D. St Peter, Inigo Lopez, Lynden Guiver, Peter J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

A strong association exists between the presence of steatosis in a donor liver for transplantation and the development of primary nonfunction in the recipient. Despite this, appraisal of the donor remains one of the least scientific aspects of the transplantation process, and many centers base their practice on subjective opinion, rather than objective data. We conducted this survey to illuminate controversial issues and highlight the variation of opinion and practice policies both between and within the United Kingdom and the United States. A simple, anonymous, one-page, 10-question survey with tick-box answers was sent to every practicing liver transplant surgeon in …

Hepatic Steatosis And Its Relationship To Transplantation., Charles J. Imber, Shawn D. St Peter, Ashok Handa, Peter J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

Fatty infiltration of the liver is common in the brain-dead donor population and has a strong correlation with primary nonfunction after cold preservation, a condition that is catastrophic to liver transplant recipients. This literature review examines factors associated with the development, diagnosis, quantification, and clinical management of this difficult condition.

Effectiveness Of Current Therapy Of Bacterial Vaginosis, Petya M Andreeva, Hatim A. Omar

Pediatrics Faculty Publications

The study was conducted in order to evaluate effectiveness of the treatment of bacterial vaginosis (BV) with different therapeutic regimes according to recommendations of the World Health Organization (WHO). During a one-year period (February 2000-February 2001) the Sexually Transmitted Diseases (STD) Center was visited by 482 women aged 14-51. The diagnosis of BV was established by standard methods: Amsel's clinical criteria and Gram stain of vaginal discharge. The first-line treatment was oral Metronidazole 2 g single dose. Second line was Metronidazole 500 mg twice daily orally for 7 days or oral Clindamycin 300 mg twice daily for seven days. BV …

Improved Continuation Rate Of Depot-Medroxyprogesterone Acetate In Adolescent Mothers, Hatim A. Omar, Amy Fowler, Sandy D'Angelo

Pediatrics Faculty Publications

Poor compliance and high discontinuation rates of Depot-Medroxyprogesterone Acetate (DMPA) and other contraceptive methods are major factors in the continuing problem of adolescent pregnancy. In this study we attempted to determine if providing comprehensive health care for teen mothers and their babies would improve continuation rates of DMPA. Patients who started DMPA between 1/1/96 and 1/1/99 were included. Teen mothers and their babies received all their health care in this clinic, supported by State funding. Key elements regarding DMPA in this clinic were continuity of care, phone and mail reminders of appointments, free DMPA for patients without insurance, counseling at …

Circulating Testosterone And Prostate-Specific Antigen In Nipple Aspirate Fluid And Tissue Are Associated With Breast Cancer., Edward R Sauter, David S Tichansky, Inna Chervoneva, Eleftherios P Diamandis

Department of Surgery Faculty Papers

Preliminary evidence has associated testosterone and prostate-specific antigen (PSA) with breast cancer. Our objective was to determine whether a) testosterone levels in nipple aspirate fluid (NAF), serum, or breast tissue are associated with breast cancer; b) testosterone levels in serum are associated with levels in NAF; c) PSA in NAF, serum, or breast tissue is associated with breast cancer; and d) serum PSA is associated with NAF PSA levels. We obtained 342 NAF specimens from 171 women by means of a modified breast pump. Additionally, we collected 201 blood samples from 99 women and 51 tissue samples from 41 subjects …

Reduction In The Incidence Of Type 2 Diabetes With Lifestyle Intervention Or Metformin., William C. Knowler, Elizabeth Barrett-Connor, Sarah E. Fowler, Richard F. Hamman, John M. Lachin, Elizabeth A. Walker, David M. Nathan, P. G. Watson, J. T. Mendoza, K. A. Smith, J. Caro, B. Goldstein, C. Lark, L. Menefee, L. Murphy, C. Pepe, J. M. Spandorfer

Department of Medicine Faculty Papers

BACKGROUND: Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes.

METHODS: We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least …

Retrospective Analysis Of Youth Evaluated For Suicide Attempt Or Suicidal Ideation In An Emergency Room Setting, Julie Hagedorn, Hatim A. Omar

Pediatrics Faculty Publications

Suicide is the third leading cause of death in adolescents and a major contributor to morbidity in this age group. The objective of this study was to look at the demographics, major stressors and factors leading to attempting suicide as well as the methods of attempted suicide in adolescents admitted to two hospitals in a medium size city. Medical records were reviewed of adolescents admitted to two area hospitals for attempted suicide between 7/1/97-12/31/99. Coroner's data on completed suicide were also reviewed. In the study period a total of 287 persons aged 21 years or under were admitted for attempted …

Nipple Aspirate Cytology And Pathologic Parameters Predict Residual Cancer And Nodal Involvement After Excisional Breast Biopsy., E R Sauter, H Ehya, A Mammen, G Klein

Department of Surgery Faculty Papers

We previously demonstrated that abnormal nipple aspirate fluid (NAF) cytology predicted residual breast cancer (RC) and tumour size after excisional biopsy (EB), although normal NAF cytology did not exclude RC. Tumour size correlates with the risk of lymph node (LN) metastases. LN metastases provide prognostic information allowing medical and radiation oncologists to determine the need for adjuvant therapy. We hypothesized that pathologic factors known after EB, combined with NAF cytology, would predict with a high degree of accuracy the presence of RC and LN spread. NAF cytology and pathologic parameters: tumour distance from biopsy margins, multifocal and multicentric disease, sub-type …

Regulation Of Type-Ii Collagen Gene Expression During Human Chondrocyte De-Differentiation And Recovery Of Chondrocyte-Specific Phenotype In Culture Involves Sry-Type High-Mobility-Group Box (Sox) Transcription Factors, David G. Stokes, Gang Liu, Rita Dharmavaram, David Hawkins, Sonsoles Piera-Velazquez, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

During ex vivo growth as monolayer cultures, chondrocytes proliferate and undergo a process of de-differentiation. This process involves a change in morphology and a change from expression of chondrocyte-specific genes to that of genes that are normally expressed in fibroblasts. Transfer of the monolayer chondrocyte culture to three-dimensional culture systems induces the cells to re-acquire a chondrocyte-specific phenotype and produce a cartilaginous-like tissue in vitro. We investigated mechanisms involved in the control of the de-differentiation and re-differentiation process in vitro. De-differentiated chondrocytes re-acquired their chondrocyte-specific phenotype when cultured on poly-(2-hydroxyethyl methacrylate) (polyHEMA) as assayed by morphology, reverse transcriptase PCR of …

Role Of Protein Kinase C-Delta In The Regulation Of Collagen Gene Expression In Scleroderma Fibroblasts, Sergio A. Jimenez, Svetlana Gaidarova, Biagio Saitta, Nora Sandorfi, David J. Herrich, Joan C. Rosenbloom, Umberto Kucich, William R. Abrams, Joel Rosenbloom

Selected Works of Sergio Jiménez, MD, MACR

Working with cultured dermal fibroblasts derived from control individuals and patients with systemic sclerosis (SSc), we have examined the effects of protein kinase C-delta (PKC-delta) on type I collagen biosynthesis and steady-state levels of COL1A1 and COL3A1 mRNAs. Rottlerin, a specific inhibitor of PKC-delta, exerted a powerful, dose-dependent inhibition of type I and type III collagen gene expression in normal and SSc cells. Optimal rottlerin concentrations caused a 70-90% inhibition of type I collagen production, a >80% reduction in COL1A1 mRNA, and a >70% reduction in COL3A1 mRNA in both cell types. In vitro nuclear transcription assays and transient transfections …

Internet Facilitation Of Opioid Dependence., D Z Lieberman

Psychiatry and Behavioral Sciences Faculty Publications

No abstract provided.

An Open-Label Trial Of Tomoxetine In Pediatric Attention Deficit Hyperactivity Disorder., Christopher J. Kratochvil, Daryl Bohac, Martin Harrington, Natalie Baker, Diane E. May, William J. Burke

Journal Articles: Psychiatry

OBJECTIVE: To collect pilot data assessing the safety, tolerability, and efficacy of tomoxetine, a nonstimulant norepinephrine enhancer, in pediatric attention deficit hyperactivity disorder (ADHD).

METHODS: An open-label trial of tomoxetine in pediatric ADHD was conducted as part of a multisite clinical trial. Following a baseline assessment, an ascending dose titration was completed during 10 weekly visits.

RESULTS: Ten subjects were enrolled at baseline, with eight completing the study. Seven of the eight remaining subjects met efficacy criteria. Significant decreases in symptom severity ratings by parents and study investigators were found. The medication was well tolerated, with transient appetite suppression the …

Association Of Viral Genome With Graft Loss In Children After Cardiac Transplantation., Girish S. Shirali, J Ni, R E. Chinnock, J K. Johnston, G L. Rosenthal, N E. Bowles, J A. Towbin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The survival of recipients of cardiac allografts is limited by rejection, lymphoproliferative disease, and coronary vasculopathy. The purpose of this study in children who had received heart transplants was to evaluate the cardiac allografts for myocardial viral infections and to determine whether the presence of viral genome in the myocardium correlates with rejection, coronary vasculopathy, or graft loss.

METHODS: We enrolled heart-transplant recipients 1 day to 18 years old who were undergoing evaluation for possible rejection and coronary vasculopathy. Endomyocardial-biopsy specimens were evaluated for evidence of rejection with the use of standard criteria and were analyzed for the presence …

Regulation Of Blastocyst Formation., A J Watson, L C Barcroft

Obstetrics & Gynaecology Publications

Preimplantation or pre-attachment development encompasses the "free"-living period of mammalian embryogenesis, which directs development of the zygote through to the blastocyst stage. Blastocyst formation is essential for implantation, establishment of pregnancy and is a principal determinant of embryo quality prior to embryo transfer. Cavitation (blastocyst formation) is driven by the expression of specific sets of gene products that direct the acquisition of cell polarity within the trophectoderm, which is both the first epithelium of development and the outer cell layer encircling the inner cell mass of the blastocyst. Critical gene families controlling these events include: the E-cadherin-catenin cell adhesion family, …

Impact Of Smoking On The Outcome Of Anterior Cervical Arthrodesis With Interbody Or Strut-Grafting., Alan Hilibrand, Mark A. Fye, Sanford E. Emery, Mark A. Palumbo, Henry H. Bohlman

Rothman Institute Papers

BACKGROUND: An increased rate of pseudarthrosis has been documented following posterolateral lumbar spine grafting in patients who smoke. This same relationship has been assumed for anterior cervical interbody grafting, but to our knowledge it has never been proven. This study compared the long-term radiographic and clinical results of smokers and nonsmokers who had undergone arthrodesis with autogenous bone graft following multi-level anterior cervical decompression for the treatment of cervical radiculopathy or myelopathy, or both.

METHODS: One hundred and ninety patients were followed clinically and radiographically for at least two years (range, two to fifteen years). Fifty-nine of the patients had …

Clumping Factor A Mediates Binding Of Staphylococcus Aureus To Human Platelets, Ian R. Siboo, Ambrose L. Cheung, Arnold S. Bayer, Paul M. Sullam

Dartmouth Scholarship

The direct binding of bacteria to platelets may be an important virulence mechanism in the pathogenesis of infective endocarditis. We have previously described Staphylococcus aureus strain PS12, a Tn551-derived mutant of strain ISP479, with reduced ability to bind human platelets in vitro. When tested in an animal model of endocarditis, the PS12 strain was less virulent than its parental strain, as measured by bacterial densities in endocardial vegetations and incidence of systemic embolization. We have now characterized the gene disrupted in PS12 and its function in platelet binding. DNA sequencing, Southern blotting, and PCR analysis indicate that PS12 contained two …

Induction Of Beta3-Integrin Gene Expression By Sustained Activation Of The Ras-Regulated Raf-Mek-Extracellular Signal-Regulated Kinase Signaling Pathway., Douglas Woods, Holly Cherwinski, Eleni Venetsanakos, Arun Bhat, Stephan Gysin, Martine Humbert, Paul F. Bray, Vicki L. Saylor, Martin Mcmahon

Cardeza Foundation for Hematologic Research

Alterations in the expression of integrin receptors for extracellular matrix (ECM) proteins are strongly associated with the acquisition of invasive and/or metastatic properties by human cancer cells. Despite this, comparatively little is known of the biochemical mechanisms that regulate the expression of integrin genes in cells. Here we demonstrate that the Ras-activated Raf-MEK-extracellular signal-regulated kinase (ERK) signaling pathway can specifically control the expression of individual integrin subunits in a variety of human and mouse cell lines. Pharmacological inhibition of MEK1 in a number of human melanoma and pancreatic carcinoma cell lines led to reduced cell surface expression of alpha6- and …

Estrogen Protects Against The Synergistic Toxicity By Hiv Proteins, Methamphetamine And Cocaine, Jadwiga Turchan, Caroline Anderson, Kurt F. Hauser, Qinmiao Sun, Jiayou Zhang, Ying Liu, Phyllis M. Wise, Inna Kruman, William Maragos, Mark P. Mattson, Rosemarie Booze, Avindra Nath

Neurology Faculty Publications

BACKGROUND: Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness. To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat.

RESULTS: Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by …

Department Of Radiation Oncology And Kimmel Cancer Center, Thomas Jefferson University, The Intronic G13964c Variant In P53 Is Not A High-Risk Mutation In Familial Breast Cancer In Australia., Anna Marsh, Amanda B Spurdle, Bruce C Turner, Sian Fereday, Heather Thorne, Gulietta M Pupo, Graham J Mann, John L Hopper, Joseph F Sambrook, Georgia Chenevix-Trench

Department of Radiation Oncology Faculty Papers

BACKGROUND: Mutations in BRCA1 and BRCA2 account for approximately 50% of breast cancer families with more than four affected cases, whereas exonic mutations in p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently reported that an intronic variant of p53--G13964C--occurred in three out of 42 (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic' breast cancer control individuals (P = 0.0003). If this relatively frequent occurrence of G13964C in familial breast cancer and absence in control individuals were confirmed, then this would suggest that the G13964C variant plays a role in …

Synaptopodin Expression In Idiopathic Nephrotic Syndrome Of Childhood., Tarak Srivastava, Robert E. Garola, J M. Whiting, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Synaptopodin is a proline-rich protein intimately associated with actin microfilaments present in the podocytes' foot processes. We investigated for synaptopodin expression in children with idiopathic nephrotic syndrome (INS), including minimal change disease (MCD), diffuse mesangial hypercellularity (DMH), and focal segmental glomerulosclerosis (FSGS); in children with congenital nephrotic syndrome of the Finnish type (CNF); and in normal kidney tissue. In particular, we examined whether an association exists between synaptopodin expression in podocyte cells and the response to steroids in INS, and whether synaptopodin expression can predict FSGS upon the initial kidney biopsy in children who progress from MCD or DMH …