Anatomy Commons^™

Robustness Of A Newly Proposed Risk Schema For Lymphatic Dissemination In Endometrioid Endometrial Cancer, Danielle M. Greer, Jessica J.F. Kram, Callie M. Cox Bauer, Scott A. Kamelle

Aurora Ob/Gyn Faculty

Background: Surgical management for endometrioid endometrial cancer (EEC) includes complete lymph node dissection for all patients at risk of lymphatic dissemination. The standard risk schema, defined by Mayo Clinic, identifies low-risk patients as those with grade 1/2 EEC, myometrial invasion (MI) ≤ 50%, and tumor diameter (TD) ≤ 2 cm. We recently proposed (and published) a risk schema containing modified forms of grade, MI and TD that suggests a significant decrease in false-negative rate and need for lymphadenectomy in low-risk women.

Purpose: Evaluate robustness of our proposed schema for lymphatic dissemination risk stratification in a subsequent EEC patient cohort.

Methods: …

Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang

Katherine A. Fitzgerald

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates …

Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio

Arthur M. Mercurio

The function of vascular endothelial growth factor (VEGF) in cancer extends beyond angiogenesis and vascular permeability. Specifically, VEGF-mediated signaling occurs in tumor cells and this signaling contributes to key aspects of tumorigenesis including the self-renewal and survival of cancer stem cells (CSCs). In addition to VEGF receptor tyrosine kinases, the neuropilins (NRPs) are critical for mediating the effects of VEGF on CSCs, primarily because of their ability to impact the function of growth factor receptors and integrins. VEGF/NRP signaling can regulate the expression and function of key molecules that have been implicated in CSC function including Rho family guanosine triphosphatases …

Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA/E31-HDL. As revealed …

New Paradigms In The Treatment Of Acute Complicated And Uncomplicated Type B Aortic Dissection, Eric S. Weiss

Aurora Heart Failure / Transplant Faculty

The treatment of acute type B aortic dissection is a rapidly evolving field, due in a large part to the advent of thoracic endovascular aortic repair (TEVAR). This review will summarize the current literature on the management of both complicated and uncomplicated type B dissections, with special attention paid to emerging evidence supporting earlier aggressive treatment.

Mechanisms Of Left Ventricular Thrombus Formation In Heart Failure With Reduced Ejection Fraction: Novel Insights From Two-Dimensional Speckle Tracking Echocardiography, Dhruv Chawla, Tracy Hammonds, Tadele Mengesha, Matt Umland, Khawaja Afzal Ammar, Vinay Thohan

Aurora Heart Failure / Transplant Faculty

Background: Patients suffering from heart failure with reduced ejection fraction (HFrEF) are at increased risk for left ventricular (LV) thrombus and subsequent thromboembolism, yet anticoagulation is not routinely recommended for left ventricular ejection fraction (LVEF) alone. We sought to determine the role of two-dimensional speckle tracking echocardiography (2D-STE) to quantify regional changes in cardiac function associated with LV thrombus, which may prospectively guide anticoagulation.

Purpose: Help enable cardiovascular clinicians to use 2D-STE to evaluate regional strain patterns among patients with HFrEF with and without LV thrombus. Our results suggest that statistically lower regional longitudinal strain patterns in a well-matched cohort …

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

David Turay, MD

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It …

Fmt Placed By Colonoscopy: Systematic Review And Meta-Analysis, Nadia Huq, Veena Kumaravel, Aboud Affi, Maharaj Singh

Aurora Gastroenterology Faculty

Background: Fecal transplants are successful in the treatment of recurrent or refractory Clostridium difficile infections (CDI), but there is no consensus on the best method of instillation. Studies have shown greater success with lower gastrointestinal tract placement, but technical aspects of placement are not validated.

Purpose: This review aims to identify common traits and procedural techniques of successful fecal microbiota transplant (FMT) therapy via colonoscopy.

Methods: An electronic search was conducted using OVID Medline and PubMed for articles published from January 2010 to January 2016. The primary outcome of interest was cure by FMT placed via colonoscopy.

Results: Of the …

Assessment Of Chronic Disease To Determine Appropriateness Of Implantable Cardioverter-Defibrillator Therapy, Bilal M. Omery, Maharaj Singh, Randy S. Turkel, Robyn Shearer, Arshad Jahangir, M. Eyman Mortada, Jasbir S. Sra, Indrajit Choudhuri

Indrajit Choudhuri, MD

Background: Implantable cardioverter-defibrillator (ICD) therapy is considered appropriate when a patient is felt to have a reasonable expectation of 1-year survival. Chronic diseases have been estimated to be associated with greater than 10% annual mortality and may reduce benefits of ICD therapy. Frailty has been estimated to be associated with greater than 20% annual mortality and has been suggested to contraindicate ICD therapy.

Purpose: Determine a risk score that may identify patients in whom ICD implantation may not be appropriate.

Methods: Patients who received an ICD for primary and secondary prevention from 2008 through 2013 at the Aurora Health Care …

New Paradigms In The Treatment Of Acute Complicated And Uncomplicated Type B Aortic Dissection, Eric S. Weiss

Eric Weiss, MD, MPH

The treatment of acute type B aortic dissection is a rapidly evolving field, due in a large part to the advent of thoracic endovascular aortic repair (TEVAR). This review will summarize the current literature on the management of both complicated and uncomplicated type B dissections, with special attention paid to emerging evidence supporting earlier aggressive treatment.

The Contribution Of Individual Exercise Training Components To Clinical Outcomes In Randomised Controlled Trials Of Cardiac Rehabilitation: A Systematic Review And Meta-Regression, Bridget Abell, Paul Glasziou, Tammy Hoffmann

Paul Glasziou

Background While the clinical benefits of exercise-based cardiac rehabilitation are well established, there is extensive variation in the interventions used within these trials. It is unknown whether variations in individual components of these exercise interventions provide different relative contributions to overall clinical outcomes. This study aims to systematically examine the relationship between individual components of the exercise intervention in cardiac rehabilitation (such as intensity and frequency) and clinical outcomes for people with coronary heart disease. Methods In this systematic review, eligible trials were identified via searches of databases (PubMed, Allied and Complementary Medicine, EMBASE, PEDro, Science Citation Index Expanded, CINAHL, …

Lead Burden As A Factor For Higher Complication Rate In Patients With Implantable Cardiac Devices, Christopher Kolibash, Naoyo Mori, Jasbir Sra, Masood Akhtar, M. Eyman Mortada

Mohammad Mortada, MD, FACC, FHRS

Purpose Lead revisions have increased over the last decade. Patients who do not undergo lead extraction face an increased lead burden. Consequences of increased lead burden have not been fully defined. We sought to characterize the complication rate and outcomes in patients with sterile redundant leads. Methods We retrospectively reviewed 242 consecutive patients [mean age 74 ± 12 years; 66.9% male] who underwent lead revision that resulted in an abandoned lead from January 2005 to June 2010. Patients were placed in a cohort based on number of leads after last recorded procedure (Group A: ≤2 [n=58]; Group B: 3-4 [n=168]; …

Score Big For Decreasing Mortality: Icd Risk Score Model, Linda Francaviglia, Rachel Petersen, Maria Stone, M. Eyman Mortada

Mohammad Mortada, MD, FACC, FHRS

Background: Aurora Health Care, a system of 14 acute care hospitals in eastern Wisconsin, has been a long-time participant in the American College of Cardiology’s National Cardiovascular Data Registries, submitting data to its ICD Registry™ since 2005. Our system’s implantable cardioverter-defibrillator (ICD) procedure volume averages 930 cases annually. During 2012 we experienced an increase in in-hospital mortality/morbidity for ICD cases.

Purpose: A single-center study examining in-hospital mortality/morbidity post-ICD implant before and after changes in practice and patient selection.

Methods: ICD implants and generator changes discharged from January 1, 2009, to December 31, 2012, were included in developing a risk model …

Efficient Immortalization Of Luminal Epithelial Cells From Human Mammary Gland By Introduction Of Simian Virus 40 Large Tumor Antigen With A Recombinant Retrovirus, Bartek J, Bartkova J, Kyprianou N, El-Nasir Lalani, Staskova Z, Shearer M, Chang S, Taylor Papadimitriou J

El Nasir Lalani

When defined in terms of markers for normal cell lineages, most invasive breast cancer cells correspond to the phenotype of the common luminal epithelial cell found in the terminal ductal lobular units. Luminal epithelial cells cultured from milk, which have limited proliferative potential, have now been immortalized by introducing the gene encoding simian virus 40 large tumor (T) antigen. Infection with a recombinant retrovirus proved to be 50-100 times more efficient than calcium phosphate transfection, and of the 17 cell lines isolated, only 5 passed through a crisis period as characterized by cessation of growth. When characterized by immunohistochemical staining …

Lead Burden As A Factor For Higher Complication Rate In Patients With Implantable Cardiac Devices, Christopher Kolibash, Naoyo Mori, Jasbir Sra, Masood Akhtar, M. Eyman Mortada

Masood Akhtar, MD, FACC, FACP, FAHA, FHRS, MACP

Purpose

Lead revisions have increased over the last decade. Patients who do not undergo lead extraction face an increased lead burden. Consequences of increased lead burden have not been fully defined. We sought to characterize the complication rate and outcomes in patients with sterile redundant leads.

Methods

We retrospectively reviewed 242 consecutive patients [mean age 74 ± 12 years; 66.9% male] who underwent lead revision that resulted in an abandoned lead from January 2005 to June 2010. Patients were placed in a cohort based on number of leads after last recorded procedure (Group A: ≤2 [n=58]; Group B: 3-4 [n=168]; …

The Mind-Body Connection: The Association Between Adolescent Locus Of Control And Indicators Of Physical Health, C. Brahler, James Cropper

C. Jayne Brahler

Locus of control (LOC) describes an individual’s generalized beliefs or expectancies that their reinforcements are under internal versus external control (1). An individual exhibits either an internal or external LOC. This study examines the link between LOC and selected health risk factors in adolescents. A convenience sample of 167 high school physical education students completed a 13-item LOC questionnaire based on Rotter’s 1966 instrument. Various anthropometric measurements, blood pressure, body mass index (BMI), and body fat were recorded on all subjects. A subsample of 61 female students received blood chemistry analysis that included a lipid profile, hemoglobin A1c (HbA1c), Apo …

Gating Of The Polycystin Ion Channel Signaling Complex In Neurons And Kidney Cells, Patrick Delmas, Surya Nauli, Xiaogang Li, Bertrand Coste, Nancy Osorio, Marcel Crest, David Brown, Jing Zhou

David C. Brown

Mutations in either polycystin-2 (PC2) or polycystin-1 (PC1) proteins cause severe, potentially lethal, kidney disorders and multiple extrarenal (including brain) disease phenotypes. PC2, a member of the transient receptor potential channel superfamily, and PC1, an orphan membrane receptor of largely unknown function, are thought to be part of a common signaling pathway. Here, we show that in rat sympathetic neurons and kidney cells, coassembly of full-length PC1 with PC2 forms a plasmalemmal ion channel signaling complex in which PC1 stimulation simultaneously activates PC2 ion channels and G(i/o)-proteins. PC2 activation occurs through a structural rearrangement of PC1, independent of G-protein activation. …

Increased Number Of Circulating Exosomes And Their Microrna Cargos Are Potential Novel Biomarkers In Alcoholic Hepatitis, Fatemeh Momen-Heravi, Banishree Saha, Karen Kodys, Donna Catalano, Abhishek Satishchandran, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: It has been well documented that alcohol and its metabolites induce injury and inflammation in the liver. However, there is no potential biomarker to monitor the extent of liver injury in alcoholic hepatitis patients. MicroRNAs (miRNAs) are a class of non-coding RNAs that are involved in various physiologic and pathologic processes. In the circulation, a great proportion of miRNAs is associated with extracellular vesicles (EVs)/exosomes. Here, we hypothesized that the exosome-associated miRNAs can be used as potential biomarkers in alcoholic hepatitis (AH).

METHODS: Exosomes were isolated from sera of alcohol-fed mice or pair-fed mice, and plasma of alcoholic hepatitis …

Evaluation Of Cardiac Involvement In Children With Dengue By Serial Echocardiographic Studies, Tawatchai Kirawittaya, In-Kyu Yoon, Sineewanlaya Wichit, Sharone Green, Francis A. Ennis, Robert V. Gibbons, Stephen J. Thomas, Alan L. Rothman, Siripen Kalayanarooj, Anon Srikiatkhachorn

Sharone Green

BACKGROUND: Infection with dengue virus results in a wide range of clinical manifestations from dengue fever (DF), a self-limited febrile illness, to dengue hemorrhagic fever (DHF) which is characterized by plasma leakage and bleeding tendency. Although cardiac involvement has been reported in dengue, the incidence and the extent of cardiac involvement are not well defined. METHODS AND PRINCIPAL FINDINGS: We characterized the incidence and changes in cardiac function in a prospective in-patient cohort of suspected dengue cases by serial echocardiography. Plasma leakage was detected by serial chest and abdominal ultrasonography. Daily cardiac troponin-T levels were measured. One hundred and eighty …

Assessment Of Obesity As A Cardiovascular Disease Risk Factor In A Geriatric Rural Texas Community - A Six Month Follow-Up, Alberto Coustasse Md, Mba

Alberto Coustasse, DrPH, MD, MBA, MPH

Coustasse, Alberto, Assessment of Obesity as a Cardiovascular Disease Risk Factor in a Geriatric Rural Texas Community – A Six Month Follow-up. Master of Public Health Track, Public Health Administration, December 1999, 22 pp., 9 tables, 9 illustrations, bibliography, 7 titles. The health fair approach was used as a method to establish individual and population health status baselines and to provide a mechanism to follow-up with an elderly population in a rural Texas community. A controlled trial sample of forty-four seniors was initially screened in a primary care clinic in August 1998. Patients were reevaluated at six months and results …

Osteopontin: A Bridge Between Bone And The Immune System, Ellen M. Gravallese

Ellen M. Gravallese

The molecular mechanisms underlying the putative role of osteopontin in the chronic inflammatory disease rheumatoid arthritis are unclear. A study in a murine model of arthritis now demonstrates that a specific antibody directed against the exposed osteopontin epitope SLAYGLR is capable of preventing inflammatory cell infiltration in arthritic joints.

The Role Played By Cell-Substrate Interactions In The Pathogenesis Of Osteoclast-Mediated Peri-Implant Osteolysis, Zhenxin Shen, Tania N. Crotti, Kevin P. Mchugh, Kenichiro Matsuzaki, Ellen M. Gravallese, Benjamin E. Bierbaum, Steven R. Goldring

Ellen M. Gravallese

Prosthetic wear debris-induced peri-implant osteolysis is a major cause of aseptic loosening after total joint replacement. In this condition, wear particles released from the implant components induce a granulomatous inflammatory reaction at the interface between implant and adjacent bone, leading to progressive bone resorption and loss of fixation. The present study was undertaken to characterize definitively the phenotype of osteoclast-like cells associated with regions of peri-implant focal bone resorption and to compare the phenotypic features of these cells with those of mononucleated and multinucleated cells associated with polyethylene wear particles. Peri-implant tissues were obtained from patients undergoing hip revision surgery …

Mcnamara 2014 Mmb1075 - Low Magnification Confocal Microscopy Of Tumor Angiogenesis, George Mcnamara

George McNamara

McNamara 2014 MMB1075 - Low Magnification Confocal Microscopy of Tumor Angiogenesis

Book chapter from Paddock 2014 Confocal Microscopy

Book is online at http://www.springer.com/us/book/9781588293510

Rapid Door To Balloon Time In The Treatment Of Acute St- Elevation Myocardial Infarction Meaningfully Reduces Overall Hospital Stay, Amit N. Nanavati Md, Nainesh Patel Md, Bruce Feldman Do, J Patrick Kleaveland Md, Orlando E. Rivera Rn, David A. Cox Md

Nainesh C Patel MD

No abstract provided.

Ideology Masquerading As Science: The Case Of Endocrine Disrupter Screening Programmes, Troy Seidle

Troy Seidle, PhD

The global move to develop novel testing methods and strategies to identify suspected endocrine disrupting chemicals offers a unique opportunity to move away from traditional animal testing paradigms in this new area of regulatory concern. Regrettably, the programmes under development, both in the USA and internationally through the OECD, have thus far failed to consider in vitro and other nonanimal test methods as more than “pre-screening” or “priority-setting” tools in a larger, animal-based testing strategy. Validation efforts to date have focused almost exclusively on the modification of existing animal tests to detect “endocrine effects”, with no demonstrable effort to promote …

Regulated Splicing Of The Alpha6 Integrin Cytoplasmic Domain Determines The Fate Of Breast Cancer Stem Cells, Hira Lal Goel, Tatiana Gritsko, Bryan Pursell, Cheng Chang, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Leslie M. Shaw, Arthur M. Mercurio

Arthur M. Mercurio

Although the alpha6beta1 integrin has been implicated in the function of breast and other cancer stem cells (CSCs), little is known about its regulation and relationship to mechanisms involved in the genesis of CSCs. We report that a CD44(high)/CD24(low) population, enriched for CSCs, is comprised of distinct epithelial and mesenchymal populations that differ in expression of the two alpha6 cytoplasmic domain splice variants: alpha6A and alpha6B. alpha6Bbeta1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by alpha6A integrins. The generation of alpha6Bbeta1 is tightly controlled and occurs as a consequence of …

Rapid Door To Balloon Time In The Treatment Of Acute St- Elevation Myocardial Infarction Meaningfully Reduces Overall Hospital Stay, Amit N. Nanavati Md, Nainesh Patel Md, Bruce Feldman Do, J Patrick Kleaveland Md, Orlando E. Rivera Rn, David A. Cox Md

Bruce A. Feldman DO

No abstract provided.

Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc

Gyongyi Szabo

BACKGROUND/AIMS: Liver diseases are common in the United States and often require liver transplantation; however, donated organs are limited and thus alternative sources for liver cells are in high demand. Embryonic stem cells (ESC) can provide a continuous and readily available source of liver cells. ESC differentiation to liver cells is yet to be fully understood and comprehensive differentiation protocols are yet to be defined. Here, we aimed to achieve human (h)ESC differentiation into mature hepatocytes using defined recombinant differentiation factors and metabolites. METHODS: Embryonic stem cell H1 line was sub-cultured on feeder layer. We induced hESCs into endodermal differentiation …

Pressure Pain Threshold Testing Demonstrates Predictive Ability In People With Acute Whiplash., David Walton

David Walton

No abstract provided.

Pkc Inhibition Increases Gap Junction Intercellular Communication And Cell Adhesion In Human Neuroblastoma, M. Morley, C. Jones, M. Sidhu, V. Gupta, S. Bernier, W. Rushlow, Daniel Belliveau

Daniel J. Belliveau

Abstract Gap junction intercellular communication and cell–cell adhesion are essential for maintaining a normal cellular phenotype, including the control of growth and proliferation. Loss of either cell–cell adhesion or communication is common in cancers, while restoration of function is associated with tumor suppression. Protein kinase C (PKC) isozymes regulate a broad spectrum of cellular functions including growth and proliferation, and their overexpression has been correlated with carcinogenesis. Consequently, PKC inhibitors are currently undergoing clinical trials as an anti-cancer agents although the precise cellular alterations induced by PKC inhibitors remain to be elucidated. In the current study, the effects of PKC …