Medical Specialties Commons^™

Abdominal Intercostal Hernia: A Rare Complication After Blunt Trauma., Phi D Nguyen, B.A., Michael J. Pucci, Md, Jay S. Jenoff, Md, Scott W. Cowan, Md

Department of Surgery Gibbon Society Historical Profiles

Abdominal intercostal hernia (AIH) is uncommonly reported in the literature with only 20 cases reported to date.1–3 We report a case of a delayed incarcerated AIH secondary to blunt trauma from a motor vehicle accident in which the colon and diaphragm herniated through an associated chest defect that was repaired successfully through a transabdominal approach using primary repair of the defect in combination with onlay porcine patch reinforcement.

Nfkb Disrupts Tissue Polarity In 3d By Preventing Integration Of Microenvironmental Signals, Sabine Becker-Weimann, Gaofeng Xiong, Saori Furuta, Ju Han, Irene Kuhn, Uri-David Akavia, Dana Pe'er, Mina J. Bissell, Ren Xu

Markey Cancer Center Faculty Publications

The microenvironment of cells controls their phenotype, and thereby the architecture of the emerging multicellular structure or tissue. We have reported more than a dozen microenvironmental factors whose signaling must be integrated in order to effect an organized, functional tissue morphology. However, the factors that prevent integration of signaling pathways that merge form and function are still largely unknown. We have identified nuclear factor kappa B (NFkB) as a transcriptional regulator that disrupts important microenvironmental cues necessary for tissue organization. We compared the gene expression of organized and disorganized epithelial cells of the HMT-3522 breast cancer progression series: the non-malignant …

Phenotypic Parameters Predict Time To Normalization In Infants With Hypogammaglobulinemia., Robert C. Van Winkle, Walter W. Hauck, Stephen J. Mcgeady

Department of Pediatrics Faculty Papers

PURPOSE: Infants with recurrent infection may be found to have hypogammaglobulinemia without impaired specific antibody responses. Many will be diagnosed with transient hypogammaglobulinemia of infancy.

METHODS: This study used a parametric survival analysis of 100 infants with hypogammaglobulinemia to predict time to normalization.

RESULTS: Aggregate initial immunoglobulins (IgG + IgA + IgM), as a percentage of age-adjusted normal, predicted time to resolution: median time to resolution for the infants in the lowest quartile of aggregate levels (≤81 % of age-adjusted lower limits) was greater than 5 years, with 34 % resolving in 3 years. For infants in the highest quartile …

Neuropathy, Neuropathic Pain, And Sickle Cell Disease., Samir K. Ballas, Deepika S Darbari

Cardeza Foundation for Hematologic Research

No abstract provided.

Inverse Lichen Planus, Michael D Lee, Laurel R Schwartz

Department of Dermatology and Cutaneous Biology Faculty Papers

A Case of Inverse Lichen Planus

Lichen planus (LP) is a pruritic, papular eruption characterized by its violaceous color and polygonal shape. It is most commonly found on the flexor surfaces of the upper extremities, on the genitalia, and on the mucous membranes. We herein report a classic case of LP in an inverse distribution.

Multicenter Study Comparing Shunt Type In The Norwood Procedure For Single-Ventricle Lesions: Three-Dimensional Echocardiographic Analysis., Gerald R. Marx, Girish S. Shirali, Jami C. Levine, Lin T. Guey, James F. Cnota, Jeanne M. Baffa, William L. Border, Steve Colan, Gregory Ensing, Mark K. Friedberg, David J. Goldberg, Salim F. Idriss, J Blaine John, Wyman W. Lai, Minmin Lu, Shaji C. Menon, Richard G. Ohye, David Saudek, Pierre C. Wong, Gail D. Pearson, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The Pediatric Heart Network's Single Ventricle Reconstruction (SVR) trial randomized infants with single right ventricles (RVs) undergoing a Norwood procedure to a modified Blalock-Taussig or RV-to-pulmonary artery shunt. This report compares RV parameters in the 2 groups using 3-dimensional echocardiography.

METHODS AND RESULTS: Three-dimensional echocardiography studies were obtained at 10 of 15 SVR centers. Of the 549 subjects, 314 underwent 3-dimensional echocardiography studies at 1 to 4 time points (pre-Norwood, post-Norwood, pre-stage II, and 14 months) for a total of 757 3-dimensional echocardiography studies. Of these, 565 (75%) were acceptable for analysis. RV volume, mass, mass:volume ratio, ejection fraction, …

Cholera Vaccination Campaign Contributes To Improved Knowledge Regarding Cholera And Improved Practice Relevant To Waterborne Disease In Rural Haiti, Omowunmi Aibana, Molly F Franke, Jessica E Teng, Johanne Hilaire, Max Raymond, Louise C Ivers

Faculty, Staff and Student Publications

BACKGROUND: Haiti's cholera epidemic has been devastating partly due to underlying weak infrastructure and limited clean water and sanitation. A comprehensive approach to cholera control is crucial, yet some have argued that oral cholera vaccination (OCV) might result in reduced hygiene practice among recipients. We evaluated the impact of an OCV campaign on knowledge and health practice in rural Haiti.

METHODOLOGY/PRINCIPAL FINDINGS: We administered baseline surveys on knowledge and practice relevant to cholera and waterborne disease to every 10th household during a census in rural Haiti in February 2012 (N = 811). An OCV campaign occurred from May-June 2012 after …

Sternal Wound Infection Caused By Mycobacterium Chelonae., Shinya Unai, Joseph Miessau, Pawel Karbowski, Gurjyot Bajwa, Hitoshi Hirose

Department of Surgery Faculty Papers

INTRODUCTION: Sternal wound infection caused by Mycobacterium chelonae, a member of the rapidly growing nontuberculous mycobacteria (NTM), is rare and may present without signs and symptoms of systemic infection.

METHODS: We present a patient who had a M. chelonae infection of the sternum following excision of a left atrial myxoma and conducted a review of the literature from 1976 to 2013.

RESULTS: Seventy cases of NTM sternal wound infection after cardiac surgery were identified, including six outbreaks and ten sporadic cases including the present case. Thirty-four cases were isolated coronary artery bypass grafting (CABG) surgery, 16 cases were isolated valve …

Predictors Of Disease Progression In Pediatric Dilated Cardiomyopathy., Kimberly M. Molina, Peter Shrader, Steven D. Colan, Seema Mital, Renee Margossian, Lynn A. Sleeper, Girish S. Shirali, Piers Barker, Charles E. Canter, Karen Altmann, Elizabeth Radojewski, Elif Seda Selamet Tierney, Jack Rychik, Lloyd Y. Tani, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Background: Despite medical advances, children with dilated cardiomyopathy (DCM) remain at high risk of death or need for cardiac transplantation. We sought to identify predictors of disease progression in pediatric DCM.

Methods and results: The Pediatric Heart Network evaluated chronic DCM patients with prospective echocardiographic and clinical data collection during an 18-month follow-up. Inclusion criteria were age <22 years and DCM disease duration >2 months. Patients requiring intravenous inotropic/mechanical support or listed status 1A/1B for transplant were excluded. Disease progression was defined as an increase in transplant listing status, hospitalization for heart failure, intravenous inotropes, mechanical support, or death. Predictors of disease progression were identified using …

New Oral Anticoagulants Are Not Superior To Warfarin In Secondary Prevention Of Stroke Or Transient Ischemic Attacks, But Lower The Risk Of Intracranial Bleeding: Insights From A Meta-Analysis And Indirect Treatment Comparisons, Partha Sardar, Saurav Chatterjee, Wen-Chih Wu, Edgar Lichstein, Joydeep Ghosh, Shamik Aikat, Debabrata Mukherjee

Internal Medicine Faculty Publications

PURPOSE: Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).

METHODS: Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan …

The G-Protein-Coupled Estrogen Receptor Agonist G-1 Suppresses Proliferation Of Ovarian Cancer Cells By Blocking Tubulin Polymerization., Cheng Wang, Xiangmin Lv, Chunbo He, G Hua, M-Y Tsai, John S. Davis

Journal Articles: Obstetrics & Gynecology

The G-protein-coupled estrogen receptor 1 (GPER) has recently been reported to mediate the non-genomic action of estrogen in different types of cells and tissues. G-1 (1-[4-(6-bromobenzo[1,3] dioxol-5yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone) was developed as a potent and selective agonist for GPER. G-1 has been shown to induce the expression of genes and activate pathways that facilitate cancer cell proliferation by activating GPER. Here we demonstrate that G-1 has an anticancer potential with a mechanism similar to vinca alkaloids, the commonly used chemotherapy drugs. We found that G-1 blocks tubulin polymerization and thereby interrupts microtubule assembly in ovarian cancer cells leading to the arrest of …

Predictors Of Perioperative Blood Loss In Total Joint Arthroplasty., Jai Hyung Park, Mohammad R Rasouli, S M Javad Mortazavi, Anthony T Tokarski, Mitchell G Maltenfort, Javad Parvizi

Rothman Institute Papers

UNLABELLED: UPDATE The print version of this article has errors that have been corrected in the online version of this article. In the Materials and Methods section, the sentence that reads as "During the study period, our institution offered preoperative autologous blood donation to all patients who were scheduling for total joint arthroplasty with a hemoglobin level of no less than 11 mg/dL or a hematocrit level of at least 33%." in the print version now reads as "During the study period, our institution offered preoperative autologous blood donation to all patients who were scheduling for total joint arthroplasty with …

Recommendations For High-Priority Research On Cancer-Related Fatigue In Children And Adults., Andrea M. Barsevick, Michael R. Irwin, Pamela Hinds, Andrew Miller, Ann Berger, Paul Jacobsen, Sonia Ancoli-Israel, Bryce B Reeve, Karen Mustian, Ann O'Mara, Jin-Shei Lai, Michael Fisch, David Cella

Department of Medical Oncology Faculty Papers

Over the past decades, some scientific progress has been made in understanding and treating cancer-related fatigue (CRF). However, three major problems have limited further progress: lack of agreement about measurement, inadequate understanding of the underlying biology, and problems in the conduct of clinical trials for CRF. This commentary reports the recommendations of a National Cancer Institute Clinical Trials Planning Meeting and an ongoing National Cancer Institute working group to address these problems so that high-priority research and clinical trials can be conducted to advance the science of CRF and its treatment. Recommendations to address measurement issues included revising the current …

Retinal Angiogenesis Suppression Through Small Molecule Activation Of P53, Sai H. Chavala, Younghee Kim, Laura Tudisco, Valeria Cicatiello, Till Milde, Nagaraj Kerur, Nidia Claros, Susan Yanni, Victor H. Guaiquil, William W. Hauswirth, John S. Penn, Shahin Rafii, Sandro De Falco, Thomas C. Lee, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels …

Long-Term Outcomes Of Ranibizumab Therapy For Diabetic Macular Edema: The 36-Month Results From Two Phase Iii Trials: Rise And Ride., David M. Brown, Quan Dong Nguyen, Dennis M. Marcus, David S. Boyer, Sunil Patel, Leonard Feiner, Patricio G. Schlottmann, Amy Chen Rundle, Jiameng Zhang, Roman G. Rubio, Anthony P. Adamis, Jason S. Ehrlich, J. Jill Hopkins

Journal Articles: Ophthalmology

PURPOSE: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME).

DESIGN: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection-controlled for 2 years.

PARTICIPANTS: Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥ 275 μm on optical coherence tomography.

METHODS: Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser …

Generating Hypotheses About Care Needs Of High Utilizers: Lessons From Patient Interviews., Dawn B Mautner, Hauchie Pang, Jeffrey C Brenner, Judy A Shea, Kennen S Gross, Rosemary Frasso, Carolyn C Cannuscio

Department of Family & Community Medicine Faculty Papers

Informed by a largely secondary and quantitative literature, efforts to improve care and outcomes for complex patients with high levels of emergency and hospital-based health care utilization have offered mixed results. This qualitative study identifies psychosocial factors and life experiences described by these patients that may be important to their care needs. Semi-structured interviews were conducted with 19 patients of the Camden Coalition of Healthcare Providers' Care Management Team. Investigators coded transcripts using a priori and inductively-derived codes, then identified 3 key themes: (1) Early-life instability and traumas, including parental loss, unstable or violent relationships, and transiency, informed many participants' …

Outdated Dermatologic Drug Samples And Obligations To The Patient., Jordan Wang, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

CASE SCENARIO

A 37-year-old man with a slightly raised, red, scaly patch on his left arm is seen in the clinic of an academic teaching hospital by a young dermatologist. Following examination and biopsy, he is found to have squamous cell carcinoma in situ. The patient was recently laid off from work and had lost access to his health insurance. He is struggling to make ends meet for his family, so it would be difficult for him to cover any extraneous health-related expenses. Upon relaying this information to the dermatologist, the patient is provided with a full course of 5-fluorouracil …

Factors Impacting Echocardiographic Imaging After The Fontan Procedure: A Report From The Pediatric Heart Network Fontan Cross-Sectional Study., Richard V. Williams, Renee Margossian, Minmin Lu, Andrew M. Atz, Timothy J. Bradley, Michael Jay Campbell, Steven D. Colan, Dianne Gallagher, Wyman W. Lai, Gail D. Pearson, Ashwin Prakash, Girish S. Shirali, Meryl S. Cohen, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Echocardiographic image quality in Fontan survivors may be limited by a variety of factors. We sought to describe echocardiographic quality and factors associated with study quality in subjects participating in the Pediatric Heart Network Fontan Cross-Sectional Study. Echocardiograms were obtained at 7 clinical sites using a standard protocol. Quality grading and analysis were performed by a core laboratory. Univariate and multivariable modeling were performed to assess factors associated with quality and ability to obtain images sufficient for prespecified quantitative analysis. A total of 543 echocardiograms were obtained. The quality of echocardiograms improved over the duration of the study. The great …

A Study On The Geophylogeny Of Clinical And Environmental Vibrio Cholerae In Kenya, J. Kiiru, A. Mutreja, A. A. Mohamed, R. W. Kimani, J. Mwituria, R. O. Sanaya, J. Muyodi, Gunturu Revathi, J. Parkhill, N. Thomson, G. Dougan, S. Kariuki

Pathology, East Africa

Cholera remains a significant public health challenge in many sub-Saharan countries including Kenya. We have performed a combination of phylogenetic and phenotypic analysis based on whole genome DNA sequences derived from 40 environmental and 57 clinical V. cholerae from different regions of Kenya isolated between 2005 and 2010. Some environmental and all clinical isolates mapped back onto wave three of the monophyletic seventh pandemic V. cholerae El Tor phylogeny but other environmental isolates were phylogenetically very distinct. Thus, the genomes of the Kenyan V. cholerae O1 El Tor isolates are clonally related to other El Tor V. cholerae isolated elsewhere …

Molecular Signatures In Urologic Tumors, Spencer Larkin, Natasha Kyprianou

Surgery Faculty Publications

Urologic tumors continue to represent a huge fraction of cancer cases in the United States, with over 376,310 estimated new diagnoses in 2013. As with many types of tumors, urologic tumors vary greatly in their phenotype, ranging from minimally invasive to malignancies possessing great metastatic potential. The increasing need for more efficient and less invasive methods of cancer detection, as well as the ability to predict severity of the disease phenotype is readily evident--yet reliable methods remain elusive in a clinical setting today. Comprehensive panels of gene clusters are being developed toward the generation of molecular signatures in order to …

Patients With Atrial Fibrillation Undergoing Total Joint Arthroplasty Increase Hospital Burden., Vinay K Aggarwal, Eric H Tischler, Zachary D Post, Ian Kane, Fabio R Orozco, Alvin Ong

Rothman Institute Papers

BACKGROUND: More than 3 million people in the United States have atrial fibrillation, most of whom are being managed with anticoagulation therapy for life. The goal of the present study was to examine the effect of chronic anticoagulation therapy on patients with atrial fibrillation who undergo total joint arthroplasty.

METHODS: We retrospectively reviewed all patients undergoing aseptic primary or revision total joint arthroplasty at our facility from March 2007 to August 2011. One hundred and sixty-one patients with atrial fibrillation (Group A) were compared with 161 matched controls (Group B). A total of 112 hips and 210 knees underwent 239 …

Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell

Department of Cancer Biology Faculty Papers

The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein. Although it is known that cyclin D1 regulates estrogen receptor (ER)α transactivation using heterologous reporter systems, the in vivo biological significance of cyclin D1 to estrogen-dependent signaling, and the molecular mechanisms by which cyclin D1 is involved, are yet to be elucidated. Herein, genome-wide expression profiling conducted of 17β-estradiol-treated castrated virgin mice deleted of the Ccnd1 gene demonstrated that cyclin D1 determines estrogen-dependent gene expression for 88% of estrogen-responsive genes in vivo. In addition, expression profiling of 17β-estradiol-stimulated cyclin …

Samuel D. Gross, M.D. (1805-1884): An Innovator, Even In Death., Peter R. Bucciarelli, B.S., John C. Kairys, Md, Ernest L. Rosato, Md, Charles J. Yeo, Md, Scott W. Cowan, Md

Department of Surgery Gibbon Society Historical Profiles

Dr. Samuel Gross' contributions to the field of surgery are well known and range from numerous clinical advances to pioneering scholarship and professional activities. Dr. Gross was ceaselessly ambitious and even remarked in his autobiography that his ‘‘conviction has always been that is far better for a man to wear out than to rust out.’’1 It is through this frame of motivation that Dr. Gross lived his life.

The Effect Of Malnutrition On Patients Undergoing Elective Joint Arthroplasty., Ronald Huang, Md, Max Greenky, Bs, Glenn J. Kerr, Md, Mathew S. Austin, Md, Javad Parvizi, Md, Frcs

Rothman Institute Papers

Malnutrition has been linked to serious complications in patients undergoing elective total joint arthroplasty (TJA). This study prospectively evaluated 2,161 patients undergoing elective TJA for malnutrition as defined by either an abnormal serum albumin or transferrin. The overall incidence of malnutrition was 8.5% (184 of 2,161) and the rate of overall complications in the malnourished group was 12% as compared to 2.9% in patients with normal parameters (P55years-old undergoing TJA and is associated with a significant increase in post-operative complications.

Occupational Exposure To Hepatitis C Virus: Early T-Cell Responses In The Absence Of Seroconversion In A Longitudinal Cohort Study., Theo Heller, Jens Martin Werner, Fareed Rahman, Eishiro Mizukoshi, Yuji Sobao, Ann Marie Gordon, Arlene Sheets, Averell H. Sherker, Ellen Kessler, Kathleen S. Bean, Steven K. Herrine, M'Lou Stevens, James Schmitt, Barbara Rehermann

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: T-cell responses have been described in seronegative patients who test negative for hepatitis C virus (HCV) RNA despite frequent HCV exposure. However, the cross-sectional design of those studies did not clarify whether T cells were indeed induced by low-level HCV exposure without seroconversion or whether they resulted from regular acute infection with subsequent antibody loss.

METHODS: Over a 10-year period, our longitudinal study recruited 72 healthcare workers with documented HCV exposure. We studied viremia and antibody and T-cell responses longitudinally for 6 months.

RESULTS: All healthcare workers remained negative for HCV RNA and antibodies. However, 48% developed proliferative T-cell …

Sessile Serrated Adenomas In The Proximal Colon Are Likely To Be Flat, Large And Occur In Smokers, Tarun Rustagi, Priya Rangasamy, Matthew Myers, Melinda Sanders, Haleh Vaziri, George Y. Wu, John W. Birk, Petr Protiva, Joseph C. Anderson

Dartmouth Scholarship

Aim: To examine the epidemiology and the morphology of the proximal sessile serrated adenomas (SSAs).

Methods: We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007 to April 2011. Data collected included: age, gender, ethnicity, body mass index, diabetes, smoking, family history of colorectal cancer, aspirin, and statin use. We collected data on morphology of SSAs including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). We also compared proximal SSAs to proximal tubular adenomas detected during same time period.

Spinal Anesthesia: Should Everyone Receive A Urinary Catheter?: A Randomized, Prospective Study Of Patients Undergoing Total Hip Arthroplasty., Adam G Miller, James Mckenzie, Max Greenky, Erica Shaw, Kishor Gandhi, William J Hozack, Javad Parvizi

Rothman Institute Papers

BACKGROUND: The objective of this randomized prospective study was to determine whether a urinary catheter is necessary for all patients undergoing total hip arthroplasty under spinal anesthesia.

METHODS: Consecutive patients undergoing total hip arthroplasty under spinal anesthesia were randomized to treatment with or without insertion of an indwelling urinary catheter. All patients received spinal anesthesia with 15 to 30 mg of 0.5% bupivacaine. The catheter group was subjected to a standard postoperative protocol, with removal of the indwelling catheter within forty-eight hours postoperatively. The experimental group was monitored for urinary retention and, if necessary, had straight catheterization up to two …

Spinal Anesthesia: Should Everyone Receive A Urinary Catheter?: A Randomized, Prospective Study Of Patients Undergoing Total Hip Arthroplasty., Adam G Miller, Md, James Mckenzie, Bs, Max Greenky, Ba, Erica Shaw, Rnp, Kishor Gandhi, Md, William J Hozack, Md, Javad Parvizi, Md, Frcs

Rothman Institute Papers

BACKGROUND: The objective of this randomized prospective study was to determine whether a urinary catheter is necessary for all patients undergoing total hip arthroplasty under spinal anesthesia.

METHODS: Consecutive patients undergoing total hip arthroplasty under spinal anesthesia were randomized to treatment with or without insertion of an indwelling urinary catheter. All patients received spinal anesthesia with 15 to 30 mg of 0.5% bupivacaine. The catheter group was subjected to a standard postoperative protocol, with removal of the indwelling catheter within forty-eight hours postoperatively. The experimental group was monitored for urinary retention and, if necessary, had straight catheterization up to two …

A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness Of Staphylococcus Epidermidis During Β-Lactam Stress., Vinai Chittezham Thomas, Lauren C. Kinkead, Ashley Janssen, Carolyn R. Schaeffer, Keith M. Woods, Jill K. Lindgren, Jonathan M. Peaster, Sujata S. Chaudhari, Marat Sadykov, Joselyn Jones, Sameh M. Mohamadi Abdelghani, Matthew C. Zimmerman, Kenneth W. Bayles, Greg A. Somerville, Paul D. Fey

Journal Articles: Pathology and Microbiology

A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these …

Coupling S100a4 To Rhotekin Alters Rho Signaling Output In Breast Cancer Cells, Min Chen, Anne R. Bresnick, Kathleen L. O'Connor

Markey Cancer Center Faculty Publications

Rho signaling is increasingly recognized to contribute to invasion and metastasis. In this study, we discovered that metastasis-associated protein S100A4 interacts with the Rho-binding domain (RBD) of Rhotekin, thus connecting S100A4 to the Rho pathway. Glutathione S-transferase pull-down and immunoprecipitation assays demonstrated that S100A4 specifically and directly binds to Rhotekin RBD, but not the other Rho effector RBDs. S100A4 binding to Rhotekin is calcium-dependent and uses residues distinct from those bound by active Rho. Interestingly, we found that S100A4 and Rhotekin can form a complex with active RhoA. Using RNA interference, we determined that suppression of both S100A4 and …