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The Review - Winter/Spring 2004

Jefferson Review

In This Issue

• 3 - Message From the Dean
• 4 - Special Occasions
• 4 - TJU Partners with Villanova, St. Joseph’s and Elizabethtown
• 5 - Alumni Events
• 7 - Alumni News
• 7 - JCHP Admissions Team Grows
• 12 - JCHP Establishes Innovative Center on Aging
• 14 - Biotechnology Program Receives NIH Funding
• 14 - Summer Science Camp
• 15 - Mary E. Bowen Named to State Board of Nursing
• 15 - ASN Program Expected to Start in Fall 2004
• 16 - Nursing Grads Score High on the NCLEX
• 16 - IMPART Program Funded for Three More Years
• 16 - OT Partnership …

B-Myb Acts As A Repressor Of Human Col1a1 Collagen Gene Expression By Interacting With Sp1 And Cbf Factors In Scleroderma Fibroblasts, Lucia Cicchillitti, Sergio A. Jimenez, Arturo Sala, Biaggio Saitta

Selected Works of Sergio Jiménez, MD, MACR

We investigated the role of B-Myb, a cell-cycle-regulated transcription factor, in the expression of the alpha1 (I) pro-collagen gene (COL1A1) in scleroderma fibroblasts. Scleroderma or SSc (systemic sclerosis) is a fibrotic disease characterized by excessive production of extracellular matrix components, especially type I collagen. Northern-blot analysis showed an inverse relationship between COL1A1 mRNA expression and that of B-Myb during exponential cell growth and during quiescence in human SSc fibroblasts. Overexpression of B-Myb in SSc fibroblasts was correlated with decreased COL1A1 mRNA expression. Transient transfections localized the down-regulatory effect of B-Myb to a region containing the proximal 174 bp of the …

The Nad(P)H Oxidase Homolog Nox4 Modulates Insulin-Stimulated Generation Of H202 And Plays An Integral Role In Insulin Signal Transduction, Kalyankar Mahadev, Hiroyuki Motoshima, Xiangdong Wu, Jean Marie Ruddy, Rebecca S. Arnold, Guangjie Cheng, J. David Lambeth, Barry J. Goldstein

Department of Medicine Faculty Papers

Insulin stimulation of target cells elicits a burst of H₂O₂ that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade. The molecular mechanism coupling the insulin receptor with the cellular oxidant-generating apparatus has not been elucidated. Using reverse transcription-PCR and Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative …

Indinavir And Rifabutin Drug Interactions In Healthy Volunteers., Walter K. Kraft, Jacqueline B. Mccrea, Gregory A. Winchell, Alexandra Carides, Richard C. Lowry, Eric J. Woolf, Sandra E. Kusma, Paul J. Deutsch, Howard E Greenberg, Scott A. Waldman

Department of Medicine Faculty Papers

Two studies examined the pharmacokinetics of indinavir and rifabutin when coadministered in healthy subjects. Rifabutin, which induces the expression of cytochrome P450 (CYP) 3A, and indinavir, which inhibits that enzyme system, are frequently coadministered in patients infected with HIV. The second study was undertaken to determine if altering the dose of rifabutin coadministered with indinavir would minimize the drug interaction observed in the first study. Two studies, each with a three-period crossover design, were performed. In study 1, standard doses of rifabutin and indinavir (300 mg of rifabutin qd and 800 mg indinavir q8h) were administered as monotherapy (with placebo …

Impact Of Appropriate Pharmaceutical Therapy For Chronic Conditions On Direct Medical Costs And Workplace Productivity: A Review Of The Literature, Neil Goldfarb, Christine Weston, Christine W. Hartmann, Mirko Sikirica, Albert Crawford, Hope He, Jamie Howell, Vittorio Maio, Janice Clarke, Bhaskar Nuthulaganti, Nicole Cobb

College of Population Health Faculty Papers

This paper presents the findings of a literature review investigating the economic impact of appropriate pharmaceutical therapy in treating four prevalent chronic conditions - asthma, diabetes, heart failure, and migraine. The goal of the review was to identify high-quality studies examining the extent to which appropriate pharmaceutical therapy impacts overall medical expenditure (direct costs) and workplace productivity (indirect costs). The working hypothesis in conducting the review was that the costs of pharmaceuticals for the selected chronic conditions are offset by savings in direct and indirect costs in other areas. The literature provides evidence that appropriate drug therapy improves the health …

Relationship Between Serotonin Transporter Gene Polymorphisms And Platelet Serotonin Transporter Sites Among African-American Cocaine-Dependent Individuals And Healthy Volunteers., Ashwin A. Patkar, Wade H. Berrettini, Paolo Mannelli, Raman Gopalakrishnan, Margret R. Hoehe, Louai Bilal, Stephen Weinstein, Michael J. Vergare

Department of Psychiatry and Human Behavior Faculty Papers

Alterations in the serotonin transporter (5-HTT) have been implicated in a variety of psychiatric disorders including cocaine dependence. A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) appears to influence the expression of 5-HTT in human cell lines. We investigated whether 5-HTTLPR variants were related to differences in measures of platelet 5-HTT sites in cocaine-dependent patients and healthy volunteers (controls). Polymerase chain reaction-based genotyping of a 44 base pair insertion/deletion polymorphism in 5-HTTLPR was performed in 138 cocaine-dependent African-American subjects and 60 African-American controls. This yielded a short (S) and a long (L) allele. Platelet 5-HTT sites …

Jefferson Alumni Bulletin – Volume 53, Number 2, March 2004

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Jefferson Alumni Bulletin – Volume 53, Number 2, March 2004 Mentoring: Everyday Lessons by Dean Thomas J. Nasca ’75; Page 4 Medical College Now Has an Honor Code, Established through Student Initiative; Page 6 JeffHOPE: The Light at the End of the Tunnel for Students as Well as for Patients by Lino Miele '05; Page 7 New Endowed Professorship in Otolaryngology; Page 8 The Jefferson Instructor Who Discovered REM Sleep; Page 9 Foundation Grants Support the Asthma Bus as Well as Research into HIV and Lupus; Page 14 In Memoriam: Frederick B. Wagner Jr. '41; Page 16 Jerome Sherard '81: …

All-1/Mll1, A Homologue Of Drosophila Trithorax, Modifies Chromatin And Is Directly Involved In Infant Acute Leukaemia., E Canaani, T Nakamura, T Rozovskaia, S T Smith, T Mori, C M Croce, Alexander Mazo

Kimmel Cancer Center Faculty Papers

Rearrangements of the ALL-1/MLL1 gene underlie the majority of infant acute leukaemias, as well as of therapy-related leukaemias developing in cancer patients treated with inhibitors of topoisomerase II, such as VP16 and doxorubicin. The rearrangements fuse ALL-1 to any of >50 partner genes or to itself. Here, we describe the unique features of ALL-1-associated leukaemias, and recent progress in understanding molecular mechanisms involved in the activity of the ALL-1 protein and of its Drosophila homologue TRITHORAX.

Signaling Switches And Bistability Arising From Multisite Phosphorylation In Protein Kinase Cascades., Nick I Markevich, Jan B. Hoek, Boris N. Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitogen-activated protein kinase (MAPK) cascades can operate as bistable switches residing in either of two different stable states. MAPK cascades are often embedded in positive feedback loops, which are considered to be a prerequisite for bistable behavior. Here we demonstrate that in the absence of any imposed feedback regulation, bistability and hysteresis can arise solely from a distributive kinetic mechanism of the two-site MAPK phosphorylation and dephosphorylation. Importantly, the reported kinetic properties of the kinase (MEK) and phosphatase (MKP3) of extracellular signal-regulated kinase (ERK) fulfill the essential requirements for generating a bistable switch at a single MAPK cascade level. Likewise, …

Botulinum Toxin And Other New Approaches To Migraine Therapy, Avi Ashkenazi, Stephen Silberstein

Department of Neurology Faculty Papers

The number of migraine treatments and our understanding of migraine pathophysiology are both increasing. Newer treatments are focusing on migraine prevention. Botulinum toxin (BTX) is a potent neurotoxin that has been used primarily for diseases associated with increased muscle activity. Recently the toxin was found to have antinociceptive effects that are probably independent of its muscle-relaxant action. Recent clinical trials support the efficacy of BTX type-A (and possibly also type-B) in the treatment of migraine. The anticonvulsant topiramate was recently shown to be effective for migraine prevention. With the low doses used for this indication, cognitive side effects are less …

Measuring And Improving Health Care Quality: Nursing's Contribution To The State Of Science, Doris C. Vahey, Beth Ann Swan, Norma M. Lang, Pamela H. Mitchell

College of Nursing Faculty Papers & Presentations

Concern over the quality of health care is a recurring topic in the United States. A “state of the science” invitational conference on quality health care, titled “Measuring and Improving Health Care Quality, Towards Meaningful Solutions To Pressing Problems, Nursing’s Contribution to the State of the Science” was held April 18–20, 2002 in Philadelphia at the Annenberg Center for Public Policy, University of Pennsylvania. This conference stemmed from the work of the American Academy of Nursing (AAN) Expert Panel on Quality Health Care and had its genesis in June 1996 during the AAN Expert Panel on Quality’s Conference titled, “Outcome …

Download Full Pdf Issue-Jefferson Translations, Vol. 2, No. 1, Fall/Winter 2004-2005

Jefferson Translations

This issue includes an article on Jefferson's Heart Failure center, a highlight on Dr. Eckhart of Translational Medicine, faculty news and awards, a report on strong outcomes for liver transport team, the latest in asthma research and a master's program in human investigation.

Commentary: Teratology In The 20th Century Environmental Causes Of Congenital Malformations In Humans And How They Were Established By Harold Kalter, Robert L. Brent

The Selected Works of Robert Brent

No abstract

Utilization Of Juvenile Animals Studies To Determine The Human Effects And Risks Of Environmental Toxicants During Postnatal Developmental Stages, Robert L. Brent

The Selected Works of Robert Brent

Toxicology studies utilizing animals and in-vitro cellular or tissue preparations have been used to study the toxic effects and mechanism of action of drugs and chemicals and to determine the effective and safe dose of drugs in humans and the risk of toxicity from chemical exposures. Testing in animals could be improved if animal dosing using the mg/kg basis was abandoned and drugs and chemicals were administered to compare the effects of pharmacokinetically and toxicokinetically equivalent serum levels in the animal model and human. Since alert physicians or epidemiology studies, not animal studies have discovered most human teratogens and toxicities …

Department Of Radiology-Annual Executive Summary Report-July 1, 2003 To June 30, 2004, Vijay M. Rao, M.D.

Department of Radiology Administrative Documents and Reports

85 page Department of Radiology Annual Executive Summary Report, July 1, 2003 to June 30, 2004, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States.

Evaluation Of The Ume-21 Initiative At 18 Medical Schools Between 1999 And 2001, J. Jon Veloski, Barbara Barzansky

CRMEHC Faculty Papers

BACKGROUND: This study evaluated the processes of curricular change and the initial outcomes of the Undergraduate Medical Education for the 21st Century (UME-21) project at 18 schools.

METHODS: Site visits were conducted at eight partner schools in 1999 and 2001. Written proposals, progress reports, and final reports of 18 schools were reviewed. Senior medical students' responses to questionnaires, including the annual Association of American Medical Colleges Graduation Questionnaire and a UME-21 supplemental graduation questionnaire, were analyzed.

RESULTS: There was variation among the schools in the curriculum at baseline, in the structure of the UME-21 innovation that was introduced, and in …

Nutritional Literacy Scale, James Diamond, Phd

Nutritional Literacy Scale

Nutritional Literacy Scale developed by James Diamond, MD.

Additional documents located at bottom of page include:

• Nutritional Literacy Scale Categories
• Research article published in Nutrition Journal "Development of a reliable and construct valid measure of nutritional literacy in adults" Feb 14, 2007
• "Development of a Scale to Measure Adults' Perceptions of Health: Preliminary Findings" in Journal of Community Psychology, 2007

Download Full Pdf Issue-Jefferson Translations-Vol. 1, No. 2, Spring 2004

Jefferson Translations

This issue includes the new Center for Translational Medicine, meet Dr. Walter Koch, medical oncology grows under Dr. Flomenberg, biodefense at Jefferson, Technology Transfer gives Jeff ideas broader access and the 125th gala honoring Dr. Bernard Segal.

The Pharmacokinetics Of Nebulized Nanocrystal Budesonide Suspension In Healthy Volunteers., Walter Kraft, Barry Steiger, Don Beussink, John N. Quiring, Nancy Fitzgerald, Howard E. Greenberg, Scott A. Waldman

Department of Medicine Faculty Papers

Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in patients with steroid-responsive pulmonary diseases such as asthma. The pharmacokinetics and safety of the product were compared to those of Pulmicort Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0 mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover design. All nebulized formulations were well tolerated, with no evidence of bronchospasm. Nebulization times were significantly shorter for nanobudesonide compared to Pulmicort Respules. Because of a low oral bioavailability, plasma concentration of budesonide is a good marker of lung-delivered dose. The pharmacokinetics of nanobudesonide 0.5 and 1.0 mg …

Pre-Treatment Measures Of Impulsivity, Aggression And Sensation Seeking Are Associated With Treatment Outcome For African-American Cocaine-Dependent Patients., Ashwin A. Patkar, Heather W. Murray, Paolo Mannelli, Edward Gottheil, Stephen P. Weinstein, Michael J. Vergare

Department of Psychiatry and Human Behavior Faculty Papers

We investigated whether measures of impulsivity, aggression and sensation seeking differed between cocaine-dependent subjects and controls, and whether these measures were related to treatment-outcome for cocaine patients. Pre-treatment assessments of impulsivity (Barratt Impulsivity Scale [BIS]), aggression (Buss-Durkee Hostility Inventory [BDHI]) and sensation seeking (Zuckerman Sensation Seeking Scale [SSS]) were obtained for 141 African-American cocaine-dependent patients entering a 12-week, intensive outpatient treatment program and 60 controls. The outcome measures were number of negative urine drug screens, days in treatment, dropout rates and number of treatment sessions. Cocaine patients reported significantly higher scores on the SSS, the BIS and the BDHI than …

Nuovi Approcci Terapeutici Contro Il Cancro Del Colon, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

This presentation was given in Augusta (Siracusa, Italy) for the 2004 Paul Harris Fellow Award, Rotary Foundation of Rotary International. The lecture discusses the clinical significance of the GC-C pathway and its potential as a therapeutic target for colon cancer and metastatic tumors. It underscores the importance of the dysregulation of the GC-C pathway in promoting colorectal tumorigenesis and of dietary calcium in the GC-C-mediated chemoprevention.

Questa e’ la presentazione per il Premio 2004 Paul Harris Fellow del Rotary International (Augusta, Siracusa, Italia). La dissertazione illustra l’importante significato clinico della via moleculare regulata da GC-C e dai suoi ligandi (guanilina, …

Biobehavioral Correlates Of Transfer Trauma In The Frail Elderly: Salivary Cortisol, Affect, And Cognition, Nancy A. Hodgson, Vicki Freedman, Doug A. Granger, Amy Behel

Selected Works of Nancy Hodgson, PhD

No abstract provided.

Comparison Of Pretreatment Characteristics And Treatment Outcomes For Alcohol-, Cocaine-, And Multisubstance-Dependent Patients., Ashwin A. Patkar, Charles C. Thornton, Paolo Mannelli, Kevin P. Hill, Edward Gottheil, Michael J. Vergare, Stephen P. Weinstein

Department of Psychiatry and Human Behavior Faculty Papers

We investigated whether pretreatment characteristics and measures of outcome differed for alcohol-, cocaine-, and multisubstance-dependent patients receiving outpatient substance abuse treatment. One hundred and forty substance dependent individuals (32 alcohol, 76 cocaine, and 32 multisubstance) enrolled in a 12-week outpatient treatment program were compared across measures of addiction severity, personality, and treatment-readiness at admission. In-treatment, end-of-treatment and 9-month follow-up assessments of treatment outcome were then compared across the three groups. Outcome measures included reduction in problem severity, abstinence, retention, number of sessions attended, dropout, and counselor and patient ratings of treatment benefit. At admission, the multisubstance group had a higher …

Jefferson Alumni Bulletin – Volume 53, Number 1, December 2003

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Jefferson Alumni Bulletin – Volume 53, Number 1, December 2003 The Dean’s Column by Thomas J. Nasca ’75, Page 4 Early Anesthesia Research and Jeffersonians, Page 6 Grunwald Appointed Chair of Anesthesiology, Page 7 Marone Honored for His Involvement in Establishing the Spinal Cord Injury Center, Page 8 Alumni Are Involved in the Search for the Next University President, Page 9 The Fortunate Beneficiaries of Our Education, by Richard Wenzel ’65, Alumni Achievement Award Winner, Page 14 Reunions, Clinic Talks, the Alumni Banquet, Pages 15–32

Inadequate Physician Knowledge Of The Effects Of Diet On Blood Lipids And Lipoproteins., Mary M. Flynn, Chris N. Sciamanna, Kevin C. Vigilante

College of Population Health Faculty Papers

BACKGROUND:To assess the nutrition knowledge of physicians on the basic effects of diet on blood lipids and lipoproteins.

METHODS:Anonymous mailed dietary knowledge surveys to 6000 randomly selected physicians in the United States licensed in either Internal Medicine or Cardiology.RESULTS:Response rate: 16% (n = 639). Half of the physicians did not know that canola oil and 26% did not know olive oil were good sources of monounsaturated fat. Ninety-three percent (84% of cardiologists vs. 96% of internists; p < 0.001) did not know that a low-fat diet, in general, would increase blood triglycerides. Approximately three-quarters (70% of cardiologists vs. 77% of internists; p < 0.01) did not know a low-fat diet would decrease HDL-c and almost half (45%) thought that a low-fat diet would not change HDL-c.

CONCLUSIONS:If physicians are to implement dietary and cholesterol management guidelines, they will likely need to become more knowledgeable about nutrition.

Provider-Caregiver Interactions: Evaluation And Use Of The Therapeutic Relationship Index For Caregiver Interventions, Yeon Kyung Chee, Marie P. Dennis, Laura N. Gitlin

Center for Applied Research on Aging and Health Research Papers

No abstract provided.

Embryonic Origins Of A Motor System: Motor Dendrites Form A Myotopic Map In Drosophila, Matthias Landgraf, Victoria Jeffrey, Miki Fujioka, James B. Jaynes, Michael Bate

Department of Biochemistry and Molecular Biology Faculty Papers

The organisational principles of locomotor networks are less well understood than those of many sensory systems, where in-growing axon terminals form a central map of peripheral characteristics. Using the neuromuscular system of the Drosophila embryo as a model and retrograde tracing and genetic methods, we have uncovered principles underlying the organisation of the motor system. We find that dendritic arbors of motor neurons, rather than their cell bodies, are partitioned into domains to form a myotopic map, which represents centrally the distribution of body wall muscles peripherally. While muscles are segmental, the myotopic map is parasegmental in organisation. It forms …

Caregiver Strategy Use To Contend With Cognitive And Functional Decline In Persons With Dementia , Laura N. Gitlin, Marie P. Dennis, Walter W. Hauck, Laraine Winter, Sandy Schinfeld

Center for Applied Research on Aging and Health Research Papers

No abstract provided.

Overview, David B. Nash

College of Population Health Faculty Papers

No abstract available.

Transcriptional Inhibition Of Type I Collagen Gene Expression In Scleroderma Fibroblasts By The Antineoplastic Drug Ecteinascidin 743., Natalia Louneva, Biagio Saitta, David J Herrick, Sergio A. Jimenez

Department of Medicine Faculty Papers

We previously showed that COL1A1 expression is up-regulated at the transcriptional level in systemic sclerosis (SSc) fibroblasts and that the CCAAT-binding factor (CBF) is involved in this increased expression. Ecteinascidin 743 (ET-743) is a chemotherapeutic agent that binds with sequence specificity to the minor groove of DNA and inhibits CBF-mediated transcriptional activation of numerous genes. Therefore, we examined the effects of ET-743 on the increased COL1A1 expression in SSc fibroblasts. The drug caused a potent and dose-dependent inhibition of type I collagen biosynthesis, which reached 70-90% at 700 pM without affecting cell viability. The same drug concentration caused 60-80% reduction …