Digital Commons Network^™

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 …

Critical Analysis Of Cerebrovascular Autoregulation During Repeated Head-Up Tilt., R L Hughson, M R Edwards, D D O'Leary, J K Shoemaker

Kinesiology Publications

BACKGROUND AND PURPOSE: Cerebrovascular autoregulation has been described with a phase lead of cerebral blood flow preceding changes in cerebral perfusion pressure (CPP), but there has been less focus on the effect of CPP on cerebral vascular resistance. We investigated these relations during spontaneous fluctuations (control) and repeated head-up tilt.

METHODS: Eight healthy adults were studied in supine rest and repeated tilt with 10-second supine, 10 seconds at 45 degrees head-up tilt for a total of 12 cycles. Cerebral blood flow was estimated from mean flow velocity (MFV) by transcranial Doppler ultrasound, CPP was estimated from corrected finger pressure (CPP(F)), …

Universal Snp Genotyping Assay With Fluorescence Polarization Detection, T. M. Hsu, X. Chen, S. Duan, R. D. Miller, P. Y. Kwok

Open Access Publications

The degree of fluorescence polarization (FP) of a fluorescent molecule is a reflection of its molecular weight (Mr). FP is therefore a useful detection methodfor homogeneous assays in which the starting reagents and products differ significantly in Mr. We have previously shown that FP is a good detection method for the single-base extension and the 5'-nuclease assays. In this report, we describe a universal, optimized single-base extension assay for genotyping single nucleotide polymorphisms (SNPs). This assay, which we named the template-directed dye-terminator incorporation assay with fluorescence polarization detection (FP-TDI), uses four spectrally distinct dye terminators to achieve universal assay conditions. …

The Toxoplasma Gondii Protein Rop2 Mediates Host Organelle Association With The Parasitophorous Vacuole Membrane, Anthony P. Sinai, Keith A. Joiner

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii replicates within a specialized vacuole surrounded by the parasitophorous vacuole membrane (PVM). The PVM forms intimate interactions with host mitochondria and endoplasmic reticulum (ER) in a process termed PVM–organelle association. In this study we identify a likely mediator of this process, the parasite protein ROP2. ROP2, which is localized to the PVM, is secreted from anterior organelles termed rhoptries during parasite invasion into host cells. The NH₂-terminal domain of ROP2 (ROP2hc) within the PVM is exposed to the host cell cytosol, and has characteristics of a mitochondrial targeting signal. In in vitro assays, ROP2hc is …

Comparison Of The Quantification Of Caffeine In Human Plasma By Gas Chromatography And Elisa, A. B. Carregaro, W. E. Woods, Thomas Tobin, A. Queiroz-Neto

Veterinary Science Faculty Publications

In the present study we evaluated the precision of the ELISA method to quantify caffeine in human plasma and compared the results with those obtained by gas chromatography. A total of 58 samples were analyzed by gas chromatography using a nitrogen-phosphorus detector and routine techniques. For the ELISA test, the samples were diluted to obtain a concentration corresponding to 50% of the absorbance of the standard curve. To determine whether the proximity between the I₅₀ of the standard curve and that of the sample would bring about a more precise result, the samples were divided into three blocks according …

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 …

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 …

Regulation Of The Processing Of Glucose-6-Phosphate Dehydrogenase Mrna By Nutritional Status, Batoul Amir-Ahmady, Lisa M. Salati

Faculty & Staff Scholarship

No abstract provided.

Central Chemosensitivity, Sleep, And Wakefulness, E. E. Nattie, A Li

Dartmouth Scholarship

No abstract provided.

Intimate Partner Violence Among Men And Women In South Carolina, 1998, Ann L. Coker, Christina Derrick, Julia L. Lumpkin, Robert Oldendick, R H. Potter

CRVAW Faculty Journal Articles

Few studies provide population-based estimates of intimate partner violence (IPV) for men and women, especially at the state level. IPV may result in adverse health effects for victims and perpetrators (1-3). To estimate the lifetime incidence of IPV by type of violence (e.g., physical, sexual, and perceived emotional abuse) and to explore demographic correlates of reporting IPV among men and women, the South Carolina Department of Health and Environmental Control and the University of South Carolina conducted a population-based random-digit-dialed telephone survey of adults in the state. This report summarizes the results of the survey, which indicated that approximately 25% …

Surveillance For Waterborne-Disease Outbreaks--United States, 1997-1998., Rachel S. Barwick, Deborah A. Levy, Gunther F. Craun, Michael J. Beach, Rebecca L. Calderon

Journal Articles: Epidemiology

PROBLEM/CONDITION: Since 1971, CDC and the U.S. Environmental Protection Agency (EPA) have maintained a collaborative surveillance system for collecting and periodically reporting data relating to occurrences and causes of waterborne-disease outbreaks (WBDOs).

REPORTING PERIOD COVERED: This summary includes data from January 1997 through December 1998 and a previously unreported outbreak in 1996.

DESCRIPTION OF THE SYSTEM: The surveillance system includes data regarding outbreaks associated with drinking water and recreational water. State, territorial, and local public health departments are primarily responsible for detecting and investigating WBDOs and voluntarily reporting them to CDC on a standard form.

RESULTS: During 1997-1998, a total …

A Cultivated Taste For Yeast., C Brenner

Kimmel Cancer Center Faculty Papers

The availability of complete genomic sequences of Saccharomyces cerevisiae has catalyzed a cultural change in the practice of yeast biology, providing opportunities to develop high throughput techniques to define protein function, to define drug targets, and to discover and characterize drugs.

Global Cns Gene Transfer For A Childhood Neurogenetic Enzyme Deficiency: Canavan Disease., Paola Leone, Christopher G Janson, Scott J Mcphee, Matthew J During

Department of Neurosurgery Faculty Papers

The neurogenetic prototypic disease on which we chose to test our gene therapy strategy is Canavan disease (CD). CD is an autosomal recessive leukodystrophy associated with spongiform degeneration of the brain. At present the disease is uniformly fatal in affected probands. CD is characterized by mutations in the aspartoacylase (ASPA) gene, resulting in loss of enzyme activity. In this review, recent evidence is summarized on the etiology and possible treatments for CD. In particular, we discuss two gene delivery systems representing recent advances in both viral and liposome technology: a novel cationic liposome-polymer-DNA (LPD) complex, DCChol/DOPE-protamine, as well as recombinant …

Beta- And Gamma-Catenin Mutations, But Not E-Cadherin Inactivation, Underlie T-Cell Factor/Lymphoid Enhancer Factor Transcriptional Deregulation In Gastric And Pancreatic Cancer., K Caca, F T Kolligs, X Ji, M Hayes, J Qian, Alan M. Yahanda Md, Facs, D L Rimm, J Costa, E R Fearon

PCI Publications and Projects

Adenomatous polyposis coli (APC) mutations are present in >70% of colon cancers. The APC protein binds to beta-catenin (beta-cat), a protein first identified because of its role in E-cadherin (E-cad) cell adhesion. In some colon cancers lacking APC defects, mutations in presumptive glycogen synthase kinase 3beta phosphorylation sites near the beta-cat NH2 terminus appear to render beta-cat resistant to regulation by APC and glycogen synthase kinase 3beta. In cells with APC or beta-cat defects, beta-cat is stabilized and, in turn, binds to and activates T-cell factor (Tcf)/lymphoid enhancer factor (Lef) transcription factors. To further explore the role of APC, beta-cat, …

Nebulized Nitroglycerin In Children With Pulmonary Hypertension Secondary To Congenital Heart Disease, Hatim Omar, Fangqi Gong, Mei Y. Sun, Stanley Einzig

Pediatrics Faculty Publications

Pulmonary hypertension continues to be a major cause of morbidity and mortality, despite new treatments. Since inhaled nitric oxide has been reported to be effective in some cases, we investigated using nebulized nitroglycerine to treat pulmonary hypertension in children with congenital heart disease. Four children (ages 6-72 months) with severe pulmonary hypertension secondary to congenital heart disease (all with membranous ventricular septal defect, undergoing cardiac catheterization) were given 3 cc of nebulized normal saline over 10 min as placebo control, followed by nebulized nitroglycerine (20 micrograms/Kg in 3 cc normal saline). Normal saline administration did not elicit any change, but …

The Effects Of Free Fatty Acids On Gluconeogenesis And Glycogenolysis In Normal Subjects, X Chen, N Iqbal, G Boden

Rowan-Virtua School of Osteopathic Medicine Departmental Research

We have quantitatively determined gluconeogenesis (GNG) from all precursors, using a novel method employing 2H20 to address the question of whether changes in plasma free fatty acids (FFA) affect GNG in healthy, nonobese subjects. In the first study (n = 6), plasma FFA were lowered at 16 to 20 hours with nicotinic acid (NA) and were then allowed to rise at 20 to 24 hours (FFA rebound after administration of NA). FFA decreased from 387 microM at 16 hours to 43 microM at 20 hours, and then rebounded to 1,823 microM at 24 hours. GNG decreased from 58.1% at 16 …

Inhibition Of Fibronectin Matrix Assembly By The Heparin-Binding Domain Of Vitronectin, Denise C. Hocking, Jane Sottile, Thomas Reho, Reinhard Fässler, Paula J. Mckeown-Longo

Biology

The deposition of fibronectin into the extracellular matrix is an integrin-dependent, multistep process that is tightly regulated in order to ensure controlled matrix deposition. Reduced fibronectin deposition has been associated with altered embryonic development, tumor cell invasion, and abnormal wound repair. In one of the initial steps of fibronectin matrix assembly, the amino-terminal region of fibronectin binds to cell surface receptors, termed matrix assembly sites. The present study was undertaken to investigate the role of extracellular signals in the regulation of fibronectin deposition. Our data indicate that the interaction of cells with the extracellular glycoprotein, vitronectin, specifically inhibits matrix assembly …

Clinical Problem-Solving. Through Thick And Thin., David R. Yu, Redonda Miller, Paul F. Bray

Cardeza Foundation for Hematologic Research

No abstract provided.

Identification Of Fetal Dna And Cells In Skin Lesions From Women With Systemic Sclerosis, Carol M. Artlett, J. Bruce Smith, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

BACKGROUND: Systemic sclerosis is a disease of unknown origin which often occurs in women after their childbearing years. It has many clinical and histopathological similarities to chronic graft-versus-host disease. Recent studies indicate that fetal stem cells can survive in the maternal circulation for many years post partum. This finding suggests that fetal cells persisting in the maternal circulation or tissues could be involved in the pathogenesis of systemic sclerosis by initiating a graft-versus-host reaction.

METHODS: We used the polymerase chain reaction (PCR) to identify Y-chromosome sequences in DNA extracted from peripheral-blood cells and skin lesions from women with systemic sclerosis …

A Longitudinal Study Of Hospitalization Rates For Patients With Chronic Disease: Results From The Medical Outcomes Study., Eugene C. Nelson, Colleen A. Mchorney, Willard G. Manning, W H. Rogers

Dartmouth Scholarship

To prospectively compare inpatient and outpatient utilization rates between prepaid (PPD) and fee-for-service (FFS) insurance coverage for patients with chronic disease. Data from the Medical Outcomes Study, a longitudinal observational study of chronic disease patients conducted in Boston, Chicago, and Los Angeles.A four-year prospective study of resource utilization among 1,681 patients under treatment for hypertension, diabetes, myocardial infarction, or congestive heart failure in the practices of 367 clinicians.

Student Level Ii Fieldwork Failure: Strategies For Intervention., Sharon A. Gutman, Paula Mccreedy, Prudence Heisler

Department of Occupational Therapy Faculty Papers

OBJECTIVE: This report describes how common student communicative and behavioral characteristics that appear to predict the existence of potential problems during Level II fieldwork were identified in order to develop and implement preventative interventions during the academic curriculum at New York University (NYU). RECORD REVIEW: A record review of NYU professional-level occupational therapy students from 1986 to 1995 was completed to identify common factors among students who performed well academically but failed clinical fieldwork. Eight communicative and behavioral characteristics were identified: (a) rigidity of thinking, (b) discomfort with the ambiguity that accompanies clinical reasoning, (c) lack of psychological insight, (d) …

Surveillance For Waterborne-Disease Outbreaks -- United States, 1995-1996, Deborah A. Levy, Michelle S. Bens, Gunther F. Craun, Rebecca L. Calderon, Barbara L. Herwaldt

Journal Articles: Epidemiology

PROBLEM/CONDITION: Since 1971, CDC and the U.S. Environmental Protection Agency have maintained a collaborative surveillance system for collecting and periodically reporting data that relate to occurrences and causes of waterborne-disease outbreaks (WBDOs).

REPORTING PERIOD COVERED: This summary includes data for January 1995 through December 1996 and previously unreported outbreaks in 1994.

DESCRIPTION OF THE SYSTEM: The surveillance system includes data about outbreaks associated with drinking water and recreational water. State, territorial, and local public health departments are primarily responsible for detecting and investigating WBDOs and for voluntarily reporting them to CDC on a standard form.

RESULTS: For the period 1995-1996, …

Determinants Of Antepartum Human Immunodeficiency Virus Testing In A Non-Medicaid Obstetric Population., E Cardonick, S Daly, M Dooley, K Elles, N S Silverman

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To determine voluntary human immunodeficiency virus (HIV) testing rates and factors influencing testing in a private obstetric practice.

METHODS: Antepartum patients were offered HIV testing after completing a self-assessment questionnaire. Perceived risks and demographics were correlated with testing rates.

RESULTS: Overall, 348/600 (58%) women consented to HIV testing. In a univariate analysis, patients with "any" perceived risk(s) were more likely to be tested. Single women and those with an at-risk partner(s) or a history of sexually transmitted disease (STD) were more likely to desire testing. These factors remained independently associated with voluntary testing in a multivariate regression model. No …

Occupational Therapy's Link To Vocational Reeducation, 1910-1925., Sharon A. Gutman

Department of Occupational Therapy Faculty Papers

The development of occupational therapy is rooted in early 20th century medical reform. During the early 1910s, several members of the medical profession, human service workers, and the larger American society were increasingly disturbed by medical practices that did not consider the individual's personal experience of disability. Occupational therapy was developed, in part, out of this desire to provide persons with treatment that helped them to function in their communities despite their disability. Early occupational therapy leaders envisioned the fledgling profession as a societal service capable of assisting persons with disabilities to return to both work and community life. Vocational …

Detection And Characterization Of Sp1 Binding Activity In Human Chondrocytes And Its Alterations During Chondrocyte Dedifferentiation., Rita M. Dharmavaram, Gang Liu, Sheryl D. Mowers, Sergio A. Jimenez

Department of Medicine Faculty Papers

We have detected DNA binding activity for a synthetic oligonucleotide containing an Sp1 consensus sequence in nuclear extracts from human chondrocytes. Changes in the levels of Sp1 oligonucleotide binding activity were examined in nuclear extracts from freshly isolated human chondrocytes, from chondrocytes that had been cultured under conditions that allowed the maintenance of a chondrocyte-specific phenotype on plastic dishes coated with the hydrogel poly(2-hydroxyethyl methacrylate), and from chondrocytes induced to dedifferentiate into fibroblast-like cells by passage in monolayer culture on plastic substrata. It was observed that Sp1 binding was 2-3-fold greater in nuclear extracts from dedifferentiated chondrocytes than in nuclear …

The Optimal Fontan Connection: A Growing Extracardiac Lateral Tunnel With Pedicled Pericardium., S R. Gundry, A J. Razzouk, M J. Del Rio, Girish S. Shirali, L L. Bailey

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The concept of a lateral tunnel for the Fontan operation is now widely accepted. Most lateral tunnels are constructed intraatrially with the use of aortic crossclamping. Construction of extracardiac lateral tunnels with the use of homografts or other nonviable tubes eliminates aortic crossclamping but lacks growth potential in length or width. The native pericardium, which is "sealed" posteriorly along the pulmonary artery, atrium, and inferior vena cava, could be turned down onto the right atrium to form a viable extracardiac lateral tunnel.

METHODS: We designed and successfully constructed extracardiac lateral tunnels using viable autologous pericardium, pedicled on its lateral …

Anticoagulation And Elective Surgery., J. Spandorfer, G. Merli

Department of Medicine Faculty Papers

No abstract provided.

Mirizzi Syndrome Type Ii: Is Laparoscopic Cholecystectomy Justified?, D C Desai, R D Smink

Department of Surgery Faculty Papers

Mirizzi syndrome type II is an uncommon cause of obstructive jaundice caused by an inflammatory response to an impacted gallstone in Hartmann's pouch or the cystic duct with a resultant cholecystocholedochal fistula. Two cases of Mirizzi syndrome type II are presented. Clinically only one patient had jaundice and endoscopic retrograde cholangiopancreatogram (ERCP) established a preoperative diagnosis of Mirizzi syndrome. The other patient's diagnosis of Mirizzi syndrome was made intraoperatively. It is important to properly identify the anatomy at the time of surgery to avoid compromising the common bile duct. Operative treatment of Mirizzi syndrome type II includes laparoscopic or open …

Choosing Ignorance In The Manufacture Of Toxic Products , Wendy E. Wagner

Cornell Law Review

No abstract provided.