Medicine and Health Sciences Commons^™

Beta Blocker Specificity: A Building Block Toward Personalized Medicine., Brent R Degeorge, Walter J Koch

Center for Translational Medicine Faculty Papers

Drugs known as beta blockers, which antagonize the beta-adrenergic receptor (beta-AR), are an important component of the treatment regimen for chronic heart failure (HF). However, a significant body of evidence indicates that genetic heterogeneity at the level of the beta(1)-AR may be a factor in explaining the variable responses of HF patients to beta blockade. In this issue of the JCI, Rochais et al. describe how a single amino acid change in beta(1)-AR alters its structural conformation and improves its functional response to carvedilol, a beta blocker currently used in the treatment of HF (see the related article beginning on …

Download Full Pdf Issue-Jefferson Translations, Vol. 3, No. 1, Spring/Summer 2007

Jefferson Translations

This issue includes an article on Dr. Squires and her work to study the effects of the HIV virus in women, clinical director forges new paths to health, Dr. Woulfe pioneers thrombosis research, resident updates, faculty news and awards and honors.

A Non-Pharmacological Intervention To Manage Behavioral And Psychological Symptoms Of Dementia And Reduce Caregiver Distress: Design And Methods Of Project Act3., Laura N Gitlin, Laraine Winter, Marie P Dennis, Walter W Hauck

Center for Applied Research on Aging and Health Research Papers

Project ACT is a randomized controlled trial designed to test the effectiveness of a non-pharmacological home-based intervention to reduce behavioral and psychological symptoms of dementia (BPSD) and caregiver distress. The study targets 272 stressed racially diverse family caregivers providing in-home care to persons with moderate stage dementia with one or more behavioral disturbances. All participants are interviewed at baseline, 4-months (main trial endpoint), and 6-months (maintenance). The four-month intervention involves up to 13 visits from an occupational therapist who works with families to problem-solve potential triggers (communication style, environmental clutter) contributing to behaviors, and instruct in strategies to reduce caregiver …

Evidence Against Roles For Phorbol Binding Protein Munc13-1, Adam Adaptor Eve-1, Or Vesicle Trafficking Phosphoproteins Munc18 Or Nsf As Phospho-State-Sensitive Modulators Of Phorbol/Pkc-Activated Alzheimer App Ectodomain Shedding., Annat F Ikin, Mirsada Causevic, Steve Pedrini, Lyndsey S Benson, Joseph D Buxbaum, Toshiharu Suzuki, Simon Lovestone, Shigeki Higashiyama, Tomas Mustelin, Robert D Burgoyne, Sam Gandy

Farber Institute for Neuroscience Faculty Papers

ABSTRACT: BACKGROUND: Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network (TGN) and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as alpha-secretase(s). However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES) responsible for regulated shedding has been challenging. Here, we examined the effects on …

Download Full Pdf Issue-Jefferson Translations, Vol. 3, No. 2, Fall 2007

Jefferson Translations

This issue includes an article on the clinical outcomes research team, an update with Dr. Most on cardiac research, a description of the hospitalist program, a visit to the sleep disorders center, faculty news and and a chief residents update.

Download Full Pdf Issue Of Thomas Jefferson University Mph Public Health Link Newsletter, Vol. 3, Iss.1, January 2007

Public Health Link

This issue includes a faculty spotlight on Dr. James Diamond and MPH program announcements.

Idiopathic Granulomatous Mastitis Masquerading As Carcinoma Of The Breast: A Case Report And Review Of The Literature., Richard Tuli, Brian J O'Hara, Janet Hines, Anne L Rosenberg

Department of Surgery Faculty Papers

BACKGROUND: Idiopathic granulomatous mastitis is an uncommon, benign entity with a diagnosis of exclusion. The typical clinical presentation of idiopathic granulomatous mastitis often mimics infection or malignancy. As a result, histopathological confirmation of idiopathic granulomatous mastitis combined with exclusion of infection, malignancy and other causes of granulomatous disease is absolutely necessary. CASE PRESENTATION: We present a case of a young woman with idiopathic granulomatous mastitis, initially mistaken for mastitis as well as breast carcinoma, and successfully treated with a course of corticosteroids. CONCLUSION: There is no clear clinical consensus regarding the ideal therapeutic management of idiopathic granulomatous mastitis. Treatment options …

Chronic Care At The Crossroads: Exploring Solutions For Chronic Care Management. Report On The Us Summit., Janice L Clarke

College of Population Health Faculty Papers

Report on the US Summit

A Turner Syndrome Neurocognitive Phenotype Maps To Xp22.3., Andrew R Zinn, David Roeltgen, Gerry Stefanatos, Purita Ramos, Frederick F Elder, Harvey Kushner, Karen Kowal, Judith L Ross

Department of Pediatrics Faculty Papers

BACKGROUND: Turner syndrome (TS) is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls and women with partial Xp deletions, with the neurocognitive phenotype considered a dichotomous trait. We sought to confirm our findings in a large cohort (n = 47) of adult women with partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions. METHODS: Subjects were recruited from North American genetics and …

Homocysteine Levels In Preterm Infants: Is There An Association With Intraventricular Hemorrhage? A Prospective Cohort Study., Wendy J Sturtz, Kathleen H Leef, Amy B Mackley, Shailja Sharma, Teodoro Bottiglieri, David A Paul

Department of Pediatrics Faculty Papers

BACKGROUND: The purpose of this study was to characterize total homocysteine (tHcy) levels at birth in preterm and term infants and identify associations with intraventricular hemorrhage (IVH) and other neonatal outcomes such as mortality, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and thrombocytopenia. METHODS: 123 infants < 32 weeks gestation admitted to our Level III nursery were enrolled. A group of 25 term infants were enrolled for comparison. Two blood spots collected on filter paper with admission blood drawing were analyzed by a high performance liquid chromatography (HPLC) method. Statistical analysis included ANOVA, Spearman's Rank Order Correlation and Mann-Whitney U test. RESULTS: The median tHcy was 2.75 micromol/L with an interquartile range of 1.34 - 4.96 micromol/L. There was no difference between preterm and term tHcy (median 2.76, IQR 1.25 - 4.8 micromol/L vs median 2.54, IQR 1.55 - 7.85 micromol/L, p = 0.07). There was no statistically significant difference in tHcy in 31 preterm infants with IVH compared to infants without IVH (median 1.96, IQR 1.09 - 4.35 micromol/L vs median 2.96, IQR 1.51 - 4.84 micromol/L, p = 0.43). There was also no statistically significant difference in tHcy in 7 infants with periventricular leukomalacia (PVL) compared to infants without PVL (median 1.55, IQR 0.25 - 3.45 micromol/L vs median 2.85, IQR 1.34 - 4.82 micromol/L, p = 0.07). Male infants had lower tHcy compared to female; prenatal steroids were associated with a higher tHcy. CONCLUSION: In our population of preterm infants, there is no association between IVH and tHcy. Male gender, prenatal steroids and preeclampsia were associated with differences in tHcy levels.

Department Of Pathology, Thomas Jefferson University, Identification Of Conserved Gene Expression Features Between Murine Mammary Carcinoma Models And Human Breast Tumors., Jason I Herschkowitz, Karl Simin, Victor J Weigman, Igor Mikaelian, Jerry Usary, Zhiyuan Hu, Karen E Rasmussen, Laundette P Jones, Shahin Assefnia, Subhashini Chandrasekharan, Michael G Backlund, Yuzhi Yin, Andrey I Khramtsov, Roy Bastein, John Quackenbush, Robert I Glazer, Powel H Brown, Jeffrey E Green, Levy Kopelovich, Priscilla A Furth, Juan P Palazzo, Olufunmilayo I Olopade, Philip S Bernard, Gary A Churchill, Terry Van Dyke, Charles M Perou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors. RESULTS: Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of …

Silencing Of The Pink1 Gene Expression By Conditional Rnai Does Not Induce Dopaminergic Neuron Death In Mice., Hongxia Zhou, Björn H Falkenburger, Jörg B Schulz, Kim Tieu, Zuoshang Xu, Xu Gang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Transgenic RNAi, an alternative to the gene knockout approach, can induce hypomorphic phenotypes that resemble those of the gene knockout in mice. Conditional transgenic RNAi is an attractive choice of method for reverse genetics in vivo because it can achieve temporal and spatial silencing of targeted genes. Pol III promoters such as U6 are widely used to drive the expression of RNAi transgenes in animals. Tested in transgenic mice, a Cre-loxP inducible U6 promoter drove the broad expression of an shRNA against the Pink1 gene whose loss-of-functional mutations cause one form of familial Parkinson's disease. The expression of the shRNA …

Recurrent Burner Syndrome Due To Presumed Cervical Spine Osteoblastoma In A Collision Sport Athlete - A Case Report., Ilan Elias, Michael A Pahl, Adam C Zoga, Maurice L Goins, Alexander R Vaccaro

Department of Orthopaedic Surgery Faculty Papers

We present a case of a 35-year-old active rugby player presenting with a history of recurrent burner syndrome thought secondary to an osteoblastoma involving the posterior arch of the atlas. Radiographically, the lesion had features typical for a large osteoid osteoma or osteoblastoma, including osseous expansion, peripheral sclerosis and bony hypertrophy, internal lucency, and even suggestion of a central nidus. The patient subsequently underwent an en bloc resection of the posterior atlas via a standard posterior approach. The surgery revealed very good clinical results. In this report, we will discuss in detail, the presentation, treatment, and return to play recommendations …

Jefferson Alumni Bulletin – Volume 56, Number 1, Winter 2007

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Jefferson Alumni Bulletin – Volume 56, Number 1, Winter 2006 Dean’s Column: The One Hundred and One Fund; Page 2 Findings: Gleevec Revisited, Less Radiation Effective in Fighting Brain Tumors Saving Hearing, High Glucose before Surgery Increases Risk of Complications, Prognosis Indicates “Dachshund” Gene Reverts Cancer Genes to Normal; Page 4 On Campus; Page 8 Leaders Among Us; Page 14 Jefferson Gala; Page 24 In Memoriam; Page 26 Class Notes; Page 28 By The Numbers: Jefferson Leads the Way; Page 33

Up-Regulation Of Interferon-A/Apobec3g Signal Pathway Potently Inactivates Hiv-1 Infectivity In Resting Cd4-T Cells, Keyang Chen, Jialing Huang, Chune Zhang, Sophia Huang, Giuseppe Nunnari, Feng-Xiang Wang, Xiangrong Tong, Ling Gao, Kristi Nikisher, Hui Zhang

Department of Medicine Faculty Papers

Poster Presentation.

The Diagnosis Of Adrenal Insufficiency In The Critically Ill Patient: Does It Really Matter?, Paul E. Marik

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

No abstract provided.

Multiple Domains In Siz Sumo Ligases Contribute To Substrate Selectivity., Alison Reindle, Irina Belichenko, Gwendolyn R Bylebyl, Xiaole L Chen, Nishant Gandhi, Erica S Johnson

Department of Biochemistry and Molecular Biology Faculty Papers

Saccharomyces cerevisiae contains two Siz/PIAS SUMO E3 ligases, Siz1 and Siz2/Nfi1, and one other known ligase, Mms21. Although ubiquitin ligases are highly substrate-specific, the degree to which SUMO ligases target distinct sets of substrates is unknown. Here we show that although Siz1 and Siz2 each have unique substrates in vivo, sumoylation of many substrates can be stimulated by either protein. Furthermore, in the absence of both Siz proteins, many of the same substrates are still sumoylated at low levels. Some of this residual sumoylation depends on MMS21. Siz1 targets its unique substrates through at least two distinct domains. Sumoylation of …

Download Full Pdf Issue Of Thomas Jefferson University Mph Public Health Link Newsletter, Vol. 2, Iss. 8, November/December 2006

Public Health Link

Vol. 2, Iss. 8 includes a faculty spotlight on Mona Sarfaty, an article on Richard Wender becoming President of the American Cancer Society and Jefferson presenters at the upcoming American Public Health Association meeting.

Patient Education In Glaucoma: What Do Patients Know About Glaucoma?, Vital Paulino Costa, George L Spaeth, Maura Smith, Cordelia Uddoh, José Paulo Cabral Vasconcellos, Newton Kara-José

Wills Eye Hospital Papers

PURPOSE: To evaluate the knowledge glaucoma patients have about their disease and its treatment.

METHODS: One hundred and eighty-three patients were interviewed at the Glaucoma Service of Wills Eye Hospital (Philadelphia, USA, Group 1) and 100 at the Glaucoma Service of University of Campinas (Campinas, Brazil, Group 2). An informal, relaxed atmosphere was created by the interviewer before asking a list of 18 open-ended questions.

RESULTS: In Group 1, 44% of the 183 patients did not have an acceptable idea about what glaucoma is, 30% did not know the purpose of the medications they were taking, 47% were not aware …

Download Full Pdf Issue Of Thomas Jefferson University Mph Public Health Link Newsletter, Vol. 2, Iss. 7, October 2006

Public Health Link

Vol. 2, Iss. 7 includes a description of the The Albert Schweitzer Fellowship, a faculty spotlight on the Thomas Jefferson University and the Rwanda Healing Project and new course offerings for the spring.

Jefferson Alumni Bulletin – Volume 55, Number 3, Fall 2006

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Jefferson Alumni Bulletin – Volume 55, Number 3, Fall 2006

Dean’s Column: The Ties that Bind; Page 2

Findings: Gene Mutation Potentially Involved in Breast Cancer Initiation, New Potential Drug Targets for Metastatic Breast Cancer, “Miracle” Cancer Drug Can Be Toxic; Page 4

On Campus; Page 6

Global Initiative: Jefferson Abroad, Page 10

Into Africa: An International Health Elective; Page 16

JUREI: World Class, Right At Home; Page 17

You’re In The Military, Then…And Now; Page 18

Alumni Weekend; Page 22

Class Notes; Page 24

In Memoriam; Page 31

Giving; Page 32

By The Numbers: Jefferson in the World; Page …

Malignant Melanoma Metastacizing To The Thyroid Gland: A Case Report And Review Of The Literature, Brian Kung, Saba Aftab, Moira Wood, David Rosen

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Oral presentation 2006 AAO-H&NS Annual Meeting

Toronto, Canada September 17-20, 2006.

Objectives: The thyroid gland is a relatively uncommon site for secondary malignancy. Even lesscommon is metastasis of malignant melanoma to the thyroid gland. We present a case of malignantmelanoma metastatic to the thyroid gland presenting as thyroid enlargement.

Study Design: This is a case report which utilizes chart review, intraoperative photographs,radiographic images, and pathology slides.

Methods: A 68 year old patient with no prior evidence of primary skin melanoma presented witha neck mass which tested positive for melanoma. A year and a half following modified radical neckdissection, the patient …

Download Full Pdf Issue Of Thomas Jefferson University Mph Public Health Link Newsletter, Vol. 2, Iss. 6, September 2006

Public Health Link

Vol. 2, Iss. 6 of the MPH Public Health Link highlights faculty member Vic Spain, the formal announcement of national accreditation for Jefferson Master of Science Program in Public Health and new course offerings for the Spring.

Peritoneal Perfusion With Oxygenated Perfluorocarbon Augments Systemic Oxygenation., Shamus R Carr, Joshua P Cantor, Atul S Rao, Thiru V Lakshman, Joshua E Collins, Joseph S Friedberg

Department of Surgery Faculty Papers

BACKGROUND: Despite maximal ventilatory support, many patients die from hypoxia in the setting of potentially reversible pulmonary failure. There remains a pressing need for additional pulmonary supportive care measures, especially techniques that do not require systemic anticoagulation. The objective of our experiments was to determine whether systemic oxygenation could be increased in a large animal, with induced hypoxia, by perfusing the abdominal cavity with oxygenated perfluorocarbons.

METHODS: Fifteen pigs with a mean (+/- SD) weight of 45 +/- 5 kg were intubated and rendered hypoxic by ventilating them with a blend of nitrogen and oxygen to achieve subatmospheric concentrations of …

Jefferson Alumni Bulletin – Volume 55, Number 2, Summer 2006

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

Jefferson Alumni Bulletin – Volume 55, Number 2, Summer 2006 Dean’s Column: A Complex Undertaking; Page 3 Construction Begins on Innovative Breast Care Center; Page 4 Clues to How Molecular Gatekeepers Work; Page 5 A Tie Between Obesity and Alzheimer’s Disease; Page 6 Fighting Artificial Implant Infections; Page 7 Reducing Radiation’s Side Effects; Page 8 Developing a New Vascular Bypass Graft; Page 8 On Campus: Dicker to Direct Translational Research Program; Page 9 Parents Day; Page 12 Class Notes; Page 13 Swatl Shah, MD’95 Rebuilds After Katrina; Page 19 Match Day 2006; Page 23 Special Center Section: Alumni Weekend

Download Full Pdf Issue Of Thomas Jefferson University Mph Public Health Link, Vol. 2, Iss.5, June 2006

Public Health Link

Vol. 2, Iss.5 of the MPH Public Health Link newsletter highlights recent graduate, Charbel Haber.

2006 Commencement For Jefferson College Of Health Professions And Jefferson College Of Graduate Studies

Jefferson College of Nursing Commencements

No abstract provided.

Download Full Pdf Issue Of Thomas Jefferson University Mph Public Health Link, Vol. 2, Iss.4, May 2006

Public Health Link

Vol. 2, Iss. 4 of Public Health Link newsletter includes a summary of the retreat to the Franklin Institute, SAPHE's public health week award luncheon and thesis presenters.

Download Full Pdf Issue Of Thomas Jefferson University Public Health Link, Vol. 2, Iss.3, April 2006

Public Health Link

Vol. 2, Iss. 3 of Public Health Link includes spotlight on Richard Wender, MD from the Department of Family and Community Medicine at Thomas Jefferson University. Also includes National Public Health Week and thesis presentations.

Voltage-Dependent Gating Rearrangements In The Intracellular T1-T1 Interface Of A K+ Channel., Guangyu Wang, Manuel Covarrubias

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The intracellular tetramerization domain (T1) of most eukaryotic voltage-gated potassium channels (Kv channels) exists as a "hanging gondola" below the transmembrane regions that directly control activation gating via the electromechanical coupling between the S4 voltage sensor and the main S6 gate. However, much less is known about the putative contribution of the T1 domain to Kv channel gating. This possibility is mechanistically intriguing because the T1-S1 linker connects the T1 domain to the voltage-sensing domain. Previously, we demonstrated that thiol-specific reagents inhibit Kv4.1 channels by reacting in a state-dependent manner with native Zn(2+) site thiolate groups in the T1-T1 interface; …