Medicine and Health Sciences Commons^™

Kallikrein Family Proteases Klk6 And Klk7 Are Potential Early Detection And Diagnostic Biomarkers For Serous And Papillary Serous Ovarian Cancer Subtypes., Ayala Tamir, Ushma Jag, Sreeja Sarojini, Craig Schindewolf, Takemi Tanaka, Rajendra Gharbaran, Hiren Patel, Anil Sood, Wei Hu, Ruzeen Patwa, Patrick Blake, Polina Chirina, Jin Oh Jeong, Heejin Lim, Andre Goy, Andrew Pecora, K Stephen Suh

Department of Medicine Faculty Papers

BACKGROUND: Early detection of ovarian cancer remains a challenge due to widespread metastases and a lack of biomarkers for early-stage disease. This study was conducted to identify relevant biomarkers for both laparoscopic and serum diagnostics in ovarian cancer.

METHODS: Bioinformatics analysis and expression screening in ovarian cancer cell lines were employed. Selected biomarkers were further validated in bio-specimens of diverse cancer types and ovarian cancer subtypes. For non-invasive detection, biomarker proteins were evaluated in serum samples from ovarian cancer patients.

RESULTS: Two kallikrein (KLK) serine protease family members (KLK6 and KLK7) were found to be significantly overexpressed relative to normal …

The New Oral Anticoagulants For The Treatment Of Venous Thromboembolism: A New Paradigm Shift In Antithrombotic Therapy., Taki Galanis, Gina Keiffer, Geno J Merli

Department of Medicine Faculty Papers

BACKGROUND: Several novel oral anticoagulants have been studied for the prevention and treatment of venous thromboembolism (VTE) in different patient populations. Clinicians will increasingly encounter scenarios in which they must choose among these and conventional anticoagulants for the treatment of this potentially fatal condition.

OBJECTIVE: To review the results of Phase III clinical trials that investigated the novel oral anticoagulants for the treatment of deep vein thrombosis and pulmonary embolism. Potential advantages and disadvantages of these anticoagulant agents with respect to each other and conventional therapy will also be explored through a case-based approach.

METHODS: A literature search in PubMed …

Adrenergic Signaling Regulates Mitochondrial Ca2+ Uptake Through Pyk2-Dependent Tyrosine Phosphorylation Of The Mitochondrial Ca2+ Uniporter., Jin O-Uchi, Bong Sook Jhun, Shangcheng Xu, Stephen Hurst, Anna Raffaello, Xiaoyun Liu, Bing Yi, Huiliang Zhang, Polina Gross, Jyotsna Mishra, Alina Ainbinder, Sarah Kettlewell, Godfrey L Smith, Robert T Dirksen, Wang Wang, Rosario Rizzuto, Shey-Shing Sheu

Department of Medicine Faculty Papers

AIMS: Mitochondrial Ca2+ homeostasis is crucial for balancing cell survival and death. The recent discovery of the molecular identity of the mitochondrial Ca2+ uniporter pore (MCU) opens new possibilities for applying genetic approaches to study mitochondrial Ca2+ regulation in various cell types, including cardiac myocytes. Basal tyrosine phosphorylation of MCU was reported from mass spectroscopy of human and mouse tissues, but the signaling pathways that regulate mitochondrial Ca2+ entry through posttranslational modifications of MCU are completely unknown. Therefore, we investigated α1-adrenergic-mediated signal transduction of MCU posttranslational modification and function in cardiac cells.

RESULTS: α1-adrenoceptor (α1-AR) signaling translocated activated proline-rich tyrosine …

Mitochondrial Ion Channels/Transporters As Sensors And Regulators Of Cellular Redox Signaling., Jin O-Uchi, Shin-Young Ryu, Bong Sook Jhun, Stephen Hurst, Shey-Shing Sheu

Department of Medicine Faculty Papers

SIGNIFICANCE: Mitochondrial ion channels/transporters and the electron transport chain (ETC) serve as key sensors and regulators for cellular redox signaling, the production of reactive oxygen species (ROS) and nitrogen species (RNS) in mitochondria, and balancing cell survival and death. Although the functional and pharmacological characteristics of mitochondrial ion transport mechanisms have been extensively studied for several decades, the majority of the molecular identities that are responsible for these channels/transporters have remained a mystery until very recently.

RECENT ADVANCES: Recent breakthrough studies uncovered the molecular identities of the diverse array of major mitochondrial ion channels/transporters, including the mitochondrial Ca2+ uniporter pore, …

Blau Syndrome, The Prototypic Auto-Inflammatory Granulomatous Disease., Carine H Wouters, Anne Maes, Kevin P Foley, John Bertin, Carlos D Rose

Department of Medicine Faculty Papers

Blau syndrome is a monogenic disease resulting from mutations in the pattern recognition receptor NOD2, and is phenotypically characterized by the triad of granulomatous polyarthritis, dermatitis and uveitis. This paper reviews briefly the classical clinical features of the disease, as well as more recently described extra-triad symptoms. From an ongoing prospective multicenter study, we provide new data on the natural history of Blau syndrome, focusing on functional status and visual outcome. We also present an update of the range of different NOD2 mutations found in Blau syndrome as well as recent data on morphologic and immunohistochemical characteristics of the Blau …

Optimal Duration Of Holter Recordings: Is There Additional Yield From 48 Versus 24 Hours?, Amanda Trang, Md, Behzad B. Pavri, Md

Department of Medicine Faculty Papers

INTRODUCTION

• Holter monitors are often used for evaluation of palpitations, syncope, heart rate, and detection of arrhythmias
• The duration of a typical Holter recording is either 24 or 48 hours
• Little research has been targeted at determining the ideal duration of monitoring
• We examined the yield of 24 versus 48 hours of Holter monitoring

Molecular And Functional Identification Of A Mitochondrial Ryanodine Receptor In Neurons., Regina Jakob, Gisela Beutner, Virendra K Sharma, Yuntao Duan, Robert A Gross, Stephen Hurst, Bong Sook Jhun, Jin O-Uchi, Shey-Shing Sheu

Department of Medicine Faculty Papers

Mitochondrial Ca(2+) controls numerous cell functions, such as energy metabolism, reactive oxygen species generation, spatiotemporal dynamics of Ca(2+) signaling, cell growth and death in various cell types including neurons. Mitochondrial Ca(2+) accumulation is mainly mediated by the mitochondrial Ca(2+) uniporter (MCU), but recent reports also indicate that mitochondrial Ca(2+)-influx mechanisms are regulated not only by MCU, but also by multiple channels/transporters. We previously reported that ryanodine receptor (RyR), which is a one of the main Ca(2+)-release channels at endoplasmic/sarcoplasmic reticulum (SR/ER) in excitable cells, is expressed at the mitochondrial inner membrane (IMM) and serves as a part of the Ca(2+) …

Understanding The Power Of Perinatal Events And Metabolic Status In Childhood., Bonita Falkner, Julie Ingelfinger

Department of Medicine Faculty Papers

No abstract provided.

Usefulness Of Highly Sensitive Afp-L3 And Dcp In Surveillance For Hepatocellular Carcinoma In Patients With A Normal Alpha-Fetoprotein, Hie-Won Hann, Dave Li, Hiroyuki Yamada, Shinji Satomura, Robert Coben, Anthony J. Dimarino

Department of Medicine Faculty Papers

Background and aims: Early detection of Hepatocellular Carcinoma (HCC) is crucial for effective management. Incidence of HCC has increased in the United States largely attributed to hepatitis B and C virus. Lens culinaris agglutinin-reactive Alpha-Fetoprotein (AFP-L3) and Des-Gamma-Carboxy Prothrombin (DCP) are being recognized specific biomarkers for HCC.

Methods: We measured AFP-L3 and DCP in serial serum specimens of a cohort of chronic hepatitis patients on HCC surveillance and compared these markers to abdominal imaging. Among fifty patients who developed HCC during surveillance, 30 were included in the study with available sera 1-2 years before, at diagnosis and post ablation of …

Implementation Of A Residency Twitter Account To Provide Curricular Enrichment, Bryan Lebude, Md, Subhashini Appulingam Sellers, Md, Gretchen Diemer, Md, Facp

Department of Medicine Faculty Papers

Background

_{The Problem}

_{With the goals of improving patient safety and resident well-being, the ACGME’s 2011 revision of duty-hour requirements included a 16-hour limit on continuous duty hours for postgraduate year 1 (PGY-1) trainees, increased supervision for junior trainees, as well as mandated rest periods between duty hours.1 These rules place limitations on the ability of trainees to attend scheduled educational activities during standard work hours; a recent study showed a decrease in resident availability for teaching conferences compared with the 2003 duty hour regulations.2 Residency training programs must develop alternative avenues for education and encouraging inquiry outside of traditional …}

A Long-Term Study Of The Effects Of Antiviral Therapy On Survival Of Patients With Hbv-Associated Hepatocellular Carcinoma (Hcc) Following Local Tumor Ablation., Hie-Won Hann, Robert Coben, Daniel Brown, Laurence Needleman, Ernest Rosato, Albert Min, Richard Hann, Kyong Bin Park, Stephen Dunn, Anthony J. Dimarino

Department of Medicine Faculty Papers

The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow-up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤ 7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed …

Adiponectin Inhibits Tumor Necrosis Factor-Α-Induced Vascular Inflammatory Response Via Caveolin-Mediated Ceramidase Recruitment And Activation., Yajing Wang, Xiaoliang Wang, Wayne Bond Lau, Yuexing Yuan, David Booth, Jing-Jing Li, Rosario Scalia, Kyle Preston, Erhe Gao, Walter Koch, Xin-Liang Ma

Department of Medicine Faculty Papers

RATIONALE: Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered.

OBJECTIVE: The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory signaling.

METHODS AND RESULTS: Adiponectin significantly reduced tumor necrosis factor (TNF)α-induced intercellular adhesion molecule-1 expression and attenuated TNFα-induced oxidative/nitrative stress in human umbilical vein endothelial cells. These anti-inflammatory actions were virtually abolished by adiponectin receptor 1 (AdipoR1-), but not AdipoR2-, knockdown (KD). Treatment with adiponectin significantly increased neutral ceramidase (nCDase) activity (3.7-fold; P87% of adiponectin-induced nCDase …

The Spectrum Of Eye Disease In Hospitalized Adults Living With Hiv, 1995-2010., Christopher Miller, William Short, Md, Mph, Lorena Perez-Povis, Josephine Lontok, Christopher Fecarotta, Mengdan Liu, Jocelyn Sendecki, Katherine Belden

Department of Medicine Faculty Papers

Eye disease is a well-documented complication of HIV infection. Opportunistic infections generally comprised the majority of pre-antiretroviral therapy (ART) eye complications. With the introduction of ART, opportunistic infections diminished. However, early ART regimens were cumbersome regarding side effects and pill burden, making patient compliance difficult. Newer ART regimens are better tolerated and consist of fewer pills, theoretically making compliance easier and therapy more effective. The aim of this chart review study is to examine eye disease epidemiology in HIV patients as ART has evolved. We reviewed 222 admissions at Thomas Jefferson University Hospitals for 188 patients. These cases were divided …

Then And Now: The Progress In Hepatitis B Treatment Over The Past 20 Years., Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

The ultimate goals of treating chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC) and hepatic decompensation. Since the advent of effective antiviral drugs that appeared during the past two decades, considerable advances have been made not only in controlling hepatitis B virus (HBV) infection, but also in preventing and reducing the incidence of liver cirrhosis and HCC. Furthermore, several recent studies have suggested the possibility of reducing the incidence of recurrent or new HCC in patients even after they have developed HCC. Currently, six medications are available for HBV treatment including, interferon and five nucleoside/nucleotide analogues. In this …

Estimation Of Daily Interfractional Larynx Residual Setup Error After Isocentric Alignment For Head And Neck Radiotherapy: Quality Assurance Implications For Target Volume And Organs-At-Risk Margination Using Daily Ct On- Rails Imaging., Charles A Baron, Musaddiq J Awan, Abdallah S R Mohamed, Imad Akel, David I Rosenthal, G Brandon Gunn, Adam S Garden, Brandon A Dyer, Laurence Court, Parag R Sevak, Esengul Kocak-Uzel, Clifton D Fuller

Department of Medicine Faculty Papers

Larynx may alternatively serve as a target or organs at risk (OAR) in head and neck cancer (HNC) image-guided radiotherapy (IGRT). The objective of this study was to estimate IGRT parameters required for larynx positional error independent of isocentric alignment and suggest population-based compensatory margins. Ten HNC patients receiving radiotherapy (RT) with daily CT on-rails imaging were assessed. Seven landmark points were placed on each daily scan. Taking the most superior-anterior point of the C5 vertebra as a reference isocenter for each scan, residual displacement vectors to the other six points were calculated postisocentric alignment. Subsequently, using the first scan …