Medical Specialties Commons^™

Conversion To Eslicarbazepine Acetate Monotherapy: A Pooled Analysis Of 2 Phase Iii Studies., Michael R Sperling, Jacqueline French, Mercedes P Jacobson, Ladislav Pazdera, Mallory Gough, Hailong Cheng, Todd Grinnell, David Blum

Department of Medicine Faculty Papers

OBJECTIVE: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy.

METHODS: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical …

Heart Rhythm Monitoring Strategies For Cryptogenic Stroke: 2015 Diagnostics And Monitoring Stroke Focus Group Report., Gregory W. Albers, Richard A. Bernstein, Johannes Brachmann, John Camm, J. Donald Easton, Peter Fromm, Shinya Goto, Christopher B. Granger, Stefan H. Hohnloser, Elaine Hylek, Amir K. Jaffer, Derk W. Krieger, Rod Passman, Jesse M. Pines, Shelby D. Reed, Peter M. Rothwell, Peter R. Kowey

Department of Medicine Faculty Papers

No abstract provided.

Lambda Red-Mediated Recombineering In The Attaching And Effacing Pathogen Escherichia Albertii., Marisa Egan, Jasmine Ramirez, Christian Xander, Chirag Upreti, Shantanu Bhatt

Department of Medicine Faculty Papers

BACKGROUND: The ability to introduce site-specific mutations in bacterial pathogens is essential towards understanding their molecular mechanisms of pathogenicity. This has been greatly facilitated by the genetic engineering technique of recombineering. In recombineering, linear double- or single-stranded DNA molecules with two terminal homology arms are electroporated into hyperrecombinogenic bacteria that express a phage-encoded recombinase. The recombinase catalyzes the replacement of the endogenous allele with the exogenous allele to generate selectable or screenable recombinants. In particular, lambda red recombinase has been instrumental in engineering mutations to characterize the virulence arsenal of the attaching and effacing (A/E) pathogens enteropathogenic Escherichia coli (EPEC), …

Cannibalism, Kuru, And Mad Cows: Prion Disease As A "Choose-Your-Own-Experiment" Case Study To Simulate Scientific Inquiry In Large Lectures., Antonio Serrano, Jeffrey Liebner, Justin K Hines

Department of Medicine Faculty Papers

Despite significant efforts to reform undergraduate science education, students often perform worse on assessments of perceptions of science after introductory courses, demonstrating a need for new educational interventions to reverse this trend. To address this need, we created An Inexplicable Disease, an engaging, active-learning case study that is unusual because it aims to simulate scientific inquiry by allowing students to iteratively investigate the Kuru epidemic of 1957 in a choose-your-own-experiment format in large lectures. The case emphasizes the importance of specialization and communication in science and is broadly applicable to courses of any size and sub-discipline of the life sciences.

Cloning And Transcriptional Activity Of The Mouse Omi/Htra2 Gene Promoter., Dan Liu, Xin Liu, Ye Wu, Wen Wang, Xin-Liang Ma, Huirong Liu

Department of Medicine Faculty Papers

HtrA serine peptidase 2 (HtrA2), also named Omi, is a pro-apoptotic protein that exhibits dramatic changes in expression levels in a variety of disorders, including ischemia/reperfusion injury, cancer, and neurodegeneration. In our study, Omi/HtrA2 protein levels were high in the heart, brain, kidney and liver, with elevated heart/brain expression in aging mice. A similar expression pattern was observed at the mRNA level, which suggests that the regulation of Omi/HtrA2 is predominately transcriptional. Promoter binding by transcription factors is the main influencing factor of transcription, and to identify specific promoter elements that contribute to the differential expression of mouse Omi/HtrA2, we …

Reduction Of Ctrp9, A Novel Anti-Platelet Adipokine, Contributes To Abnormal Platelet Activity In Diabetic Animals., Wenqing Wang, Wayne Bond Lau, Yajing Wang, Xin-Liang Ma, Rong Li

Department of Medicine Faculty Papers

Platelet hyper-reactivity is a crucial cause of accelerated atherosclerosis increasing risk of thrombotic vascular events in diabetic patients. The mechanisms leading to abnormal platelet activity during diabetes are complex and not fully defined. The current study attempted to clarify the role of CTRP9, a novel adiponectin paralog, in enhanced platelet activity and determined whether CTRP9 may inhibit platelet activity. Adult male C57BL/6 J mice were randomized to receive high-fat diet (HFD) or normal diet (ND). 8 weeks after HFD, animals were sacrificed, and both plasma CTRP9 and platelet aggregation were determined. HFD-fed animals increased weight gain significantly, and became hyperglycemic …

Preparation And Biological Activity Of The Monoclonal Antibody Against The Second Extracellular Loop Of The Angiotensin Ii Type 1 Receptor, Mingming Wei, Chengrui Zhao, Suli Zhang, Li Wang, Huirong Liu, Xin-Liang Ma

Department of Medicine Faculty Papers

No abstract provided.

Anxiety And Depression In Patients With Advanced Macular Degeneration: Current Perspectives., Verena R Cimarolli, Robin J Casten, Barry W. Rovner, Vera Heyl, Silvia Sörensen, Amy Horowitz

Department of Medicine Faculty Papers

Age-related macular degeneration (AMD) - despite advances in prevention and medical treatment options - remains prevalent among older adults, often resulting in functional losses that negatively affect the mental health of older adults. In particular, the prevalence of both anxiety and depression in patients with AMD is high. Along with medical treatment options, low vision rehabilitation and AMD-specific behavioral and self-management programs have been developed and have demonstrated effectiveness in improving the mental health of AMD patients. This article reviews the prevalence of anxiety and depression in patients with advanced AMD, discusses potential mechanisms accounting for the development of depression …

Dysregulation Of The Haem-Haemopexin Axis Is Associated With Severe Malaria In A Case-Control Study Of Ugandan Children., Robyn E Elphinstone, Frank Riley, Tian Lin, Sarah Higgins, Aggrey Dhabangi, Charles Musoke, Christine Cserti-Gazdewich, Raymond F. Regan, H Shaw Warren, Kevin C Kain

Department of Medicine Faculty Papers

BACKGROUND: Malaria is associated with haemolysis and the release of plasma haem. Plasma haem can cause endothelial injury and organ dysfunction, and is normally scavenged by haemopexin to limit toxicity. It was hypothesized that dysregulation of the haem-haemopexin pathway contributes to severe and fatal malaria infections.

METHODS: Plasma levels of haemin (oxidized haem), haemopexin, haptoglobin, and haemoglobin were quantified in a case-control study of Ugandan children with Plasmodium falciparum malaria. Levels at presentation were compared in children with uncomplicated malaria (UM; n = 29), severe malarial anaemia (SMA; n = 27) or cerebral malaria (CM; n = 31), and evaluated …

A Synthetic Lethality Screen Using A Focused Sirna Library To Identify Sensitizers To Dasatinib Therapy For The Treatment Of Epithelial Ovarian Cancer., Harsh B Pathak, Yan Zhou, Geetika Sethi, Jeff Hirst, Russell J Schilder, Erica A Golemis, Andrew K Godwin

Department of Medicine Faculty Papers

Molecular targeted therapies have been the focus of recent clinical trials for the treatment of patients with recurrent epithelial ovarian cancer (EOC). The majority have not fared well as monotherapies for improving survival of these patients. Poor bioavailability, lack of predictive biomarkers, and the presence of multiple survival pathways can all diminish the success of a targeted agent. Dasatinib is a tyrosine kinase inhibitor of the Src-family kinases (SFK) and in preclinical studies shown to have substantial activity in EOC. However, when evaluated in a phase 2 clinical trial for patients with recurrent or persistent EOC, it was found to …

Vertebral Body Stapling Versus Bracing For Patients With High-Risk Moderate Idiopathic Scoliosis., Laury Cuddihy, Aina J Danielsson, Patrick J Cahill, Amer F Samdani, Harsh Grewal, John M Richmond, M J Mulcahey, John P Gaughan, M Darryl Antonacci, Randal R Betz

Department of Medicine Faculty Papers

Purpose. We report a comparison study of vertebral body stapling (VBS) versus a matched bracing cohort for immature patients with moderate (25 to 44°) idiopathic scoliosis (IS). Methods. 42 of 49 consecutive patients (86%) with IS were treated with VBS and followed for a minimum of 2 years. They were compared to 121 braced patients meeting identical inclusion criteria. 52 patients (66 curves) were matched according to age at start of treatment (10.6 years versus 11.1 years, resp. [P = 0.07]) and gender. Results. For thoracic curves 25-34°, VBS had a success rate (defined as curve progression

Notching Early Repolarization Pattern In Inferior Leads Increases Risk Of Ventricular Tachyarrhythmias In Patients With Acute Myocardial Infarction: A Meta-Analysis., Zhiwei Zhang, Konstantinos P Letsas, Yajuan Yang, Panagiotis Korantzopoulos, Guangping Li, Gan-Xin Yan, Tong Liu

Department of Medicine Faculty Papers

The aim of this of this meta-analysis was to examine the potential association between certain early repolarization (ER) characteristics and ventricular tachyarrhythmias (VTAs) in patients with acute myocardial infarction (AMI). We searched PubMed, Embase and Web of Science databases for records published until December 2014. Of the 658 initially identified records, 7 studies with a total of 1,565 patients (299 with ER and 1,266 without ER) were finally analyzed. Overall, patients with ER displayed a higher risk of VTAs following AMI compared to patients without ER [odds ratio (OR): 3.75, 95% CI: 2.62-5.37, p < 0.00001]. Subgroup analyses showed that the diagnosis of ER prior to AMI onset is a better predictor of VTAs (OR: 5.70, p < 0.00001) compared to those diagnosed after AMI onset (OR: 2.60, p = 0.00001). Remarkably, a notching morphology was a significant predictor of VTAs compared to slurring morphology (OR: 3.85, p = 0.002). Finally, an inferior ER location (OR: 8.85, p < 0.00001) was significantly associated with increased risk of VTAs in AMI patients. In conclusion, our meta-analysis suggests that ER pattern is associated with greater risk of VTAs in patients with AMI. A notched ER pattern located in inferior leads confers the highest risk for VTAs in AMI.

Tools For Economic Analysis Of Patient Management Interventions In Heart Failure Cost-Effectiveness Model: A Web-Based Program Designed To Evaluate The Cost-Effectiveness Of Disease Management Programs In Heart Failure., Shelby D. Reed, Matthew P. Neilson, Matthew Gardner, Yanhong Li, Andrew H. Briggs, Daniel E E. Polsky, Felicia L. Graham, Margaret T. Bowers, Sara C. Paul, Bradi B. Granger, Kevin A. Schulman, David J. Whellan, Barbara Riegel, Wayne C. Levy

Department of Medicine Faculty Papers

BACKGROUND: Heart failure disease management programs can influence medical resource use and quality-adjusted survival. Because projecting long-term costs and survival is challenging, a consistent and valid approach to extrapolating short-term outcomes would be valuable.

METHODS: We developed the Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model, a Web-based simulation tool designed to integrate data on demographic, clinical, and laboratory characteristics; use of evidence-based medications; and costs to generate predicted outcomes. Survival projections are based on a modified Seattle Heart Failure Model. Projections of resource use and quality of life are modeled using relationships with time-varying …

Dna-Repair Defects And Olaparib In Metastatic Prostate Cancer., Joaquin Mateo, Suzanne Carreira, Shahneen Sandhu, Susana Miranda, Helen Mossop, Raquel Perez-Lopez, Daniel Nava Rodrigues, Dan Robinson, Aurelius Omlin, Nina Tunariu, Gunther Boysen, Nuria Porta, Penny Flohr, Alexa Gillman, Ines Figueiredo, Claire Paulding, George Seed, Suneil Jain, Christy Ralph, Andrew Protheroe, Syed Hussain, Robert Jones, Tony Elliott, Ursula Mcgovern, Diletta Bianchini, Jane Goodall, Zafeiris Zafeiriou, Chris T Williamson, Roberta Ferraldeschi, Ruth Riisnaes, Bernardette Ebbs, Gemma Fowler, Desamparados Roda, Wei Yuan, Yi-Mi Wu, Xuhong Cao, Rachel Brough, Helen Pemberton, Roger A'Hern, Amanda Swain, Lakshmi P Kunju, Rosalind Eeles, Gerhardt Attard, Christopher J Lord, Alan Ashworth, Mark A Rubin, Karen E Knudsen, Felix Y Feng, Arul M Chinnaiyan, Emma Hall, Johann S De Bono

Department of Medicine Faculty Papers

BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.

METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the …

Palbociclib In Hormone-Receptor-Positive Advanced Breast Cancer., Nicholas C Turner, Cynthia Huang Bartlett, Massimo Cristofanilli

Department of Medicine Faculty Papers

No abstract provided.

Effect Of Mycophenolate Mofetil On The White Blood Cell Count And The Frequency Of Infection In Systemic Lupus Erythematosus., Ananta Subedi, Laurence S. Magder, Michelle Petri

Department of Medicine Faculty Papers

Leukopenia is a common manifestation of SLE. Addition of immunosuppressive therapy in a SLE patient who is already leukopenic is a clinical concern. It could worsen leukopenia, increase the risk of infection, or both. The aim of this study was to analyze the immediate effect of mycophenolate mofetil on the white blood cell count and the rate of infection in SLE patients. Two hundred and forty-four patients within the Hopkins Lupus Cohort who were newly started on mycophenolate mofetil were included in the study. The white blood cell count and interval infection history on the day mycophenolate mofetil was started …

Emerging Novel Therapies For Heart Failure., Anthony M Szema, Sophia Dang, Jonathan C Li

Department of Medicine Faculty Papers

Heart function fails when the organ is unable to pump blood at a rate proportional to the body's need for oxygen or when this function leads to elevated cardiac chamber filling pressures (cardiogenic pulmonary edema). Despite our sophisticated knowledge of heart failure, even so-called ejection fraction-preserved heart failure has high rates of mortality and morbidity. So, novel therapies are sorely needed. This review discusses current standard therapies for heart failure and launches an exploration into emerging novel treatments on the heels of recently-approved sacubitril and ivbradine. For example, Vasoactive Intestinal Peptide (VIP) is protective of the heart, so in the …

Chimeric Cells Of Maternal Origin Do Not Appear To Be Pathogenic In The Juvenile Idiopathic Inflammatory Myopathies Or Muscular Dystrophy., Carol M Artlett, Sihem Sassi-Gaha, Ronald C Ramos, Frederick W Miller, Lisa G Rider

Department of Medicine Faculty Papers

INTRODUCTION: Microchimeric cells have been studied for over a decade, with conflicting reports on their presence and role in autoimmune and other inflammatory diseases. To determine whether microchimeric cells were pathogenic or mediating tissue repair in inflammatory myopathies, we phenotyped and quantified microchimeric cells in juvenile idiopathic inflammatory myopathies (JIIM), muscular dystrophy (MD), and noninflammatory control muscle tissues.

METHOD: Fluorescence immunophenotyping for infiltrating cells with sequential fluorescence in situ hybridization was performed on muscle biopsies from ten patients with JIIM, nine with MD and ten controls.

RESULTS: Microchimeric cells were significantly increased in MD muscle (0.079 ± 0.024 microchimeric cells/mm(2) …

Treatment-Induced Changes In Plasma Adiponectin Do Not Reduce Urinary Albumin Excretion In The Diabetes Prevention Program Cohort., Kieren J Mather, Qing Pan, William C Knowler, Tohru Funahashi, George A Bray, Richard Arakaki, Bonita Falkner, Kumar Sharma, Barry J. Goldstein

Department of Medicine Faculty Papers

BACKGROUND AND OBJECTIVES: Molecular data suggests that adiponectin may directly regulate urinary albumin excretion. In the Diabetes Prevention Program (DPP) we measured adiponectin and albuminuria before and after intervention, and we previously reported increases in adiponectin with interventions. Here we have used the DPP dataset to test the hypothesis that treatment-related increases in adiponectin may reduce albuminuria in obesity.

DESIGN, SETTING, PARTICIPANTS AND METHODS: We evaluated cross-sectional correlations between plasma adiponectin and urinary albumin excretion at baseline, and the relationship of treatment-related changes in adiponectin and albuminuria. Baseline and follow-up urine albumin to creatinine ratios (ACR (albumin to creatinine ratio)) …

J-Wave Syndromes: Brugada And Early Repolarization Syndromes., Charles Antzelevitch, Gan-Xin Yan

Department of Medicine Faculty Papers

A prominent J wave is encountered in a number of life-threatening cardiac arrhythmia syndromes, including the Brugada syndrome and early repolarization syndromes. Brugada syndrome and early repolarization syndromes differ with respect to the magnitude and lead location of abnormal J waves and are thought to represent a continuous spectrum of phenotypic expression termed J-wave syndromes. Despite two decades of intensive research, risk stratification and the approach to therapy of these 2 inherited cardiac arrhythmia syndromes are still undergoing rapid evolution. Our objective in this review is to provide an integrated synopsis of the clinical characteristics, risk stratifiers, and molecular, ionic, …

Sex And Race And/Or Ethnicity Differences In Patients Undergoing Radiofrequency Ablation For Barrett's Esophagus: Results From The U.S. Rfa Registry., Sarina Pasricha, Nan Li, William J. Bulsiewicz, Richard I. Rothstein, Anthony Infantolino, Atilla Ertan, Daniel S. Camara, Evan S. Dellon, George Triadafilopoulos, Charles J. Lightdale, Ryan D. Madanick, William D. Lyday, Raman V. Muthusamy, Bergein F. Overholt, Nicholas J. Shaheen

Department of Medicine Faculty Papers

BACKGROUND: Little is known about differences in Barrett's esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA).

OBJECTIVE: We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE.

DESIGN: The U.S. RFA patient registry is a multicenter collaboration reporting processes and outcomes of care for patients treated with RFA for BE.

PATIENTS: Patients enrolled with BE.

INTERVENTIONS: RFA.

MAIN OUTCOME MEASUREMENTS: We assessed safety (stricture, bleeding, perforation, hospitalization), efficacy (complete eradication of intestinal metaplasia [CEIM]), complete eradication of dysplasia, …

The Effect Of Aspirin On Bleeding And Transfusion In Contemporary Cardiac Surgery., Jordan E Goldhammer, Gregary D. Marhefka, Constantine Daskalakis, Mark W Berguson, John E Bowen, James Diehl, Jianzhong Sun

Department of Medicine Faculty Papers

OBJECTIVE: Despite evidence that preoperative aspirin improves outcomes in cardiac surgery, recommendations for aspirin use are inconsistent due to aspirin's anti-platelet effect and concern for bleeding. The purpose of this study was to investigate preoperative aspirin use and its effect on bleeding and transfusion in cardiac surgery.

METHODS: This retrospective study involved consecutive patients (n=1571) who underwent CABG, valve, or combined CABG and valve surgery at a single center between March 2007 and July 2012. Of all patients, 728 met the inclusion criteria and were divided into two groups: those using (n=603) or not using (n=125) aspirin within 5 days …

Inflammatory Muscle Diseases., Marinos Dalakas

Department of Medicine Faculty Papers

No abstract provided.

Flattening Filter-Free Accelerators: A Report From The Aapm Therapy Emerging Technology Assessment Work Group., Ying Xiao, Stephen F Kry, Richard Popple, Ellen Yorke, Niko Papanikolaou, Sotirios Stathakis, Ping Xia, Saiful Huq, John Bayouth, James Galvin Phd, Fang-Fang Yin

Department of Medicine Faculty Papers

This report describes the current state of flattening filter-free (FFF) radiotherapy beams implemented on conventional linear accelerators, and is aimed primarily at practicing medical physicists. The Therapy Emerging Technology Assessment Work Group of the American Association of Physicists in Medicine (AAPM) formed a writing group to assess FFF technology. The published literature on FFF technology was reviewed, along with technical specifications provided by vendors. Based on this information, supplemented by the clinical experience of the group members, consensus guidelines and recommendations for implementation of FFF technology were developed. Areas in need of further investigation were identified. Removing the flattening filter …

Practical Management Of Anticoagulation In Patients With Atrial Fibrillation., Richard J Kovacs, Greg C Flaker, Sherry J Saxonhouse, John U. Doherty, Kim K Birtcher, Adam Cuker, Bruce L Davidson, Robert P Giugliano, Christopher B Granger, Amir K Jaffer, Bella H Mehta, Edith Nutescu, Kim A Williams

Department of Medicine Faculty Papers

Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, …

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 …