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Conformational Altered P53 As An Early Marker Of Oxidative Stress In Alzheimer's Disease, Laura Buizza, Giovanna Cenini, Cristina Lanni, Giulia Ferrari-Toninelli, Chiara Prandelli, Stefano Govoni, Erica Buoso, Marco Racchi, Maria Barcikowska, Maria Styczynska, Aleksandra Szybinska, D. Allan Butterfield, Maurizio Memo, Daniela Uberti

Sanders-Brown Center on Aging Faculty Publications

In order to study oxidative stress in peripheral cells of Alzheimer's disease (AD) patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD) and subjects harboured AD related mutation (ADmut), were used. Oxidative stress was evaluated measuring i) the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii) and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRD). We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut …

Hiv-1 Tat Triggers Nuclear Localization Of Zo-1 Via Rho Signaling And Camp Response Element-Binding Protein Activation, Yu Zhong, Bei Zhang, Sung Yong Eum, Michal Toborek

Neurosurgery Faculty Publications

The human immunodeficiency virus (HIV)-specific protein trans-activator of transcription (Tat) can contribute to the dysfunction of brain endothelial cells and HIV trafficking into the brain by disrupting tight junction (TJ) integrity at the blood–brain barrier (BBB) level. Specific TJ proteins, such as zonula occludens (ZO) proteins, localize not only at the cell–cell borders but are also present in the nuclei. The objective of the present study was to evaluate the mechanisms and significance of Tat-induced nuclear localization of ZO-1. Treatment of a brain endothelial cell line (hCMEC/D3 cells) with Tat resulted in a decrease in total levels of ZO-1 but …

The Role Of Ezh2 In The Regulation Of The Activity Of Matrix Metalloproteinases In Prostate Cancer Cells., Yong Jae Shin, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Degradation of the extracellular matrix (ECM), a critical step in cancer metastasis, is determined by the balance between MMPs (matrix metalloproteinases) and their inhibitors TIMPs (tissue inhibitors of metalloproteinases). In cancer cells, this balance is shifted towards MMPs, promoting ECM degradation. Here, we show that EZH2 plays an active role in this process by repressing the expression of TIMP2 and TIMP3 in prostate cancer cells. The TIMP genes are derepressed by knockdown of EZH2 expression in human prostate cancer cells but repressed by overexpression of EZH2 in benign human prostate epithelial cells. EZH2 catalyzes H3K27 trimethylation and subsequent DNA methylation …

Effect Of Spermidine On Misfolding And Interactions Of Alpha-Synuclein., Alexey V. Krasnoslobodtsev, Jie Peng, Josephat M. Asiago, Jagadish Hindupur, Jean-Christophe Rochet, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Alpha-synuclein (α-Syn) is a 140 aa presynaptic protein which belongs to a group of natively unfolded proteins that are unstructured in aqueous solutions. The aggregation rate of α-Syn is accelerated in the presence of physiological levels of cellular polyamines. Here we applied single molecule AFM force spectroscopy to characterize the effect of spermidine on the very first stages of α-Syn aggregation--misfolding and assembly into dimers. Two α-Syn variants, the wild-type (WT) protein and A30P, were studied. The two protein molecules were covalently immobilized at the C-terminus, one at the AFM tip and the other on the substrate, and intermolecular interactions …

Phylogenetic Search Through Partial Tree Mixing., Kenneth Sundberg, Mark Clement, Quinn Snell, Dan Ventura, Michael Whiting, Keith Crandall

Computational Biology Institute

BACKGROUND: Recent advances in sequencing technology have created large data sets upon which phylogenetic inference can be performed. Current research is limited by the prohibitive time necessary to perform tree search on a reasonable number of individuals. This research develops new phylogenetic algorithms that can operate on tens of thousands of species in a reasonable amount of time through several innovative search techniques.

RESULTS: When compared to popular phylogenetic search algorithms, better trees are found much more quickly for large data sets. These algorithms are incorporated in the PSODA application available at http://dna.cs.byu.edu/psoda

CONCLUSIONS: The use of Partial Tree Mixing …

Control Of Interneuron Dendritic Growth Through Nrg1/Erbb4-Mediated Kalirin-7 Disinhibition., M. E. Cahill, K. A. Jones, I. Rafalovich, Z. Xie, C. S. Barros, U. Müller, P. Penzes

Peninsula Medical School

Neuregulin 1 (NRG1) is a secreted trophic factor that activates the postsynaptic erbB4 receptor tyrosine kinase. Both NRG1 and erbB4 have been repeatedly associated with schizophrenia, but their downstream targets are not well characterized. ErbB4 is highly abundant in interneurons, and NRG1-mediated erbB4 activation has been shown to modulate interneuron function, but the role for NRG1-erbB4 signaling in regulating interneuron dendritic growth is not well understood. Here we show that NRG1/erbB4 promote the growth of dendrites in mature interneurons through kalirin, a major dendritic Rac1-GEF. Recent studies have shown associations of the KALRN gene with schizophrenia. Our data point to …

Associations Of Cardiorespiratory Fitness And Fatness With Metabolic Syndrome In Rural Women With Prehypertension., Patricia A. Hageman, Carol H. Pullen, Melody A. Hertzog, Linda S. Boeckner, Susan Noble Walker

Journal Articles: Physical Therapy

BACKGROUND: This study investigated the associations of fitness and fatness with metabolic syndrome in rural women, part of a recognized US health disparities group.

METHODS: Fitness, percentage body fat, BMI, and metabolic syndrome criteria were assessed at baseline in 289 rural women with prehypertension, ages 40-69, enrolled in a healthy eating and activity community-based clinical trial for reducing blood pressure.

RESULTS: Ninety (31%) women had metabolic syndrome, of which 70% were obese by BMI (≥30 kg/m²), 100% by percentage body fat (≥30%), and 100% by revised BMI standards (≥25 kg/m²) cited in current literature. Hierarchical logistic regression models, adjusted for …

Posttraumatic Stress Disorder Prevalence And Risk Of Recurrence In Acute Coronary Syndrome Patients: A Meta-Analytic Review., D. Edmondson, S. Richardson, L. Falzon, K. W. Davidson, M. A. Mills, Y. Neria

Journal Articles

BACKGROUND: Acute coronary syndromes (ACS; myocardial infarction or unstable angina) can induce posttraumatic stress disorder (PTSD), and ACS-induced PTSD may increase patients' risk for subsequent cardiac events and mortality.

OBJECTIVE: To determine the prevalence of PTSD induced by ACS and to quantify the association between ACS-induced PTSD and adverse clinical outcomes using systematic review and meta-analysis.

DATA SOURCES: Articles were identified by searching Ovid MEDLINE, PsycINFO, and Scopus, and through manual search of reference lists.

METHODOLOGY/PRINCIPAL FINDINGS: Observational cohort studies that assessed PTSD with specific reference to an ACS event at least 1 month prior. We extracted estimates of the …

Cooperative Cluster Formation, Dna Bending And Base-Flipping By O6-Alkylguanine-Dna Alkyltransferase, Ingrid Tessmer, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

O⁶-Alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O⁶-alkylguanine and O⁴-alkylthymine adducts in DNA, protecting the genome and also contributing to the resistance of tumors to chemotherapeutic alkylating agents. AGT binds DNA cooperatively, and cooperative interactions are likely to be important in lesion search and repair. We examined morphologies of complexes on long, unmodified DNAs, using analytical ultracentrifugation and atomic force microscopy. AGT formed clusters of ≤11 proteins. Longer clusters, predicted by the McGhee–von Hippel model, were not seen even at high [protein]. Interestingly, torsional stress due to DNA unwinding has the potential to limit cluster size …

Follicle-Stimulating Hormone Is Independently Associated With Lean Mass But Not Bmd In Younger Postmenopausal Women, Margaret L Gourlay, Bonny Specker, Chenxi Li, Catherine A. Hammett-Stabler, Jordan B. Renner, Janet E Rubin

Ethel Austin Martin Program Publications

PURPOSE: Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated.
METHODS: We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the …

Antibiotics For Leptospirosis, David Brett-Major, Rodney Coldren

Journal Articles: Epidemiology

BACKGROUND: Leptospirosis has a wide-ranging clinical and public health impact. Leptospira are globally distributed. Case attack rates are as high as 1:4 to 2:5 persons in exposed populations. In some settings mortality has exceeded 10% of infected people. The benefit of antibiotic therapy in the disease has been unclear.

OBJECTIVES: We sought to characterise the risks and benefits associated with use of antibiotic therapy in the management of leptospirosis.

SEARCH METHODS: We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded …

Examining Fatigue In Copd: Development, Validity And Reliability Of A Modified Version Of Facit-F Scale, Khaled Al-Shair, Hana Muellerova, Janelle Yorke, Stephen I. Rennard, Emiel F.M. Wouters, Nicola A. Hanania, Amir Sharafkhaneh, Jørgen Vestbo, Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Fatigue is a disruptive symptom that inhibits normal functional performance of COPD patients in daily activities. The availability of a short, simple, reliable and valid scale would improve assessment of the characteristics and influence of fatigue in COPD.

METHODS: At baseline, 2107 COPD patients from the ECLIPSE cohort completed the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale. We used well-structured classic method, the principal components analysis (PCA) and Rasch analysis for structurally examining the 13-item FACIT-F.

RESULTS: Four items were less able to capture fatigue characteristics in COPD and were deleted. PCA was applied to the remaining …

Tropical Medicine Training In The Department Of Defense, Rodney L. Coldren, David Brett-Major, Patrick W. Hickey, Eric Garges, Peter J. Weina, Paula Corrigan, Gerald Quinnan

Journal Articles: Epidemiology

No abstract provided.

Effects Of Inhaled Corticosteroids On Airway Inflammation In Chronic Obstructive Pulmonary Disease: A Systematic Review And Meta-Analysis, Rachel Jen, Stephen I. Rennard, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS) on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD.

METHODS: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment …

A Randomized Placebo-Controlled Trial Of Varenicline For Smoking Cessation Allowing Flexible Quit Dates, Stephen I. Rennard, John Hughes, Paul M. Cinciripini, Eva Kralikova, Tobias Raupach, Carmen Arteaga, Lisa B. St Aubin, Cristina Russ, The Flexible Quit Date Study Group

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication.

METHODS: In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were …

The Long And Short Of It: The Role Of Telomeres In Fetal Origins Of Adult Disease., Stephanie E Hallows, Timothy Regnault, Dean H Betts

Paediatrics Publications

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes.

Hyperpolarized 3he Functional Magnetic Resonance Imaging Of Bronchoscopic Airway Bypass In Chronic Obstructive Pulmonary Disease., Lindsay Mathew, Miranda Kirby, Donald Farquhar, Christopher Licskai, Giles Santyr, Roya Etemad-Rezai, Grace Parraga, David G Mccormack

Medical Biophysics Publications

A 73-year-old exsmoker with Global initiative for chronic Obstructive Lung Disease stage III chronic obstructive pulmonary disease underwent airway bypass (AB) as part of the Exhale Airway Stents for Emphysema (EASE) trial, and was the only EASE subject to undergo hyperpolarized 3He magnetic resonance imaging for evaluation of lung function pre- and post-AB. 3He magnetic resonance imaging was acquired twice previously (32 and eight months pre-AB) and twice post-AB (six and 12 months post-AB). Six months post-AB, his increase in forced vital capacity was

Modeling Stochastic And Spatial Heterogeneity In A Human Airway Tree To Determine Variation In Respiratory System Resistance, Del Leary, Swati A Bhatawadekar, Grace Parraga, Geoffrey N Maksym

Medical Biophysics Publications

Asthma is a variable disease with changes in symptoms and airway function over many time scales. Airway resistance (Raw) is variable and thought to reflect changes in airway smooth muscle activity, but just how variation throughout the airway tree and the influence of gas distribution abnormalities affect Raw is unclear. We used a multibranch airway lung model to evaluate variation in airway diameter size, the role of coherent regional variation, and the role of gas distribution abnormalities on mean Raw (Raw) and variation in Raw as described by the SD (SDRaw). We modified an anatomically correct airway tree, provided by …

Chest Mri In Children: Why Bother?, Amir M Owrangi, Grace Parraga

Medical Biophysics Publications

In this issue of Respirology, Montella and colleagues ask this question: How does high‐field chest MRI compare with CT of children with non‐cystic fibrosis (CF) lung disease? In an important extension of the first description of this study where they compared MRI and CT with pulmonary function measurements, the authors evaluated how widely‐used chest CT and almost never‐utilized lung MRI compare for diagnostic imaging of chronic lung disease. Here they show that high‐field (3Tesla as compared with the 1.5Tesla clinical standard) thoracic MRI has high reliability and good‐to‐excellent agreement with CT, definitively answering the important question at hand; their results …

Discriminating Famous From Fictional Names Based On Lifetime Experience: Evidence In Support Of A Signal-Detection Model Based On Finite Mixture Distributions., Ben Bowles, Iain M Harlow, Melissa M Meeking, Stefan Köhler

Brain and Mind Institute Researchers' Publications

It is widely accepted that signal-detection mechanisms contribute to item-recognition memory decisions that involve discriminations between targets and lures based on a controlled laboratory study episode. Here, the authors employed mathematical modeling of receiver operating characteristics (ROC) to determine whether and how a signal-detection mechanism contributes to discriminations between moderately famous and fictional names based on lifetime experience. Unique to fame judgments is a lack of control over participants' previous exposure to the stimuli deemed "targets" by the experimenter; specifically, if they pertain to moderately famous individuals, participants may have had no prior exposure to a substantial proportion of the …

Distinct Patterns Of Functional And Effective Connectivity Between Perirhinal Cortex And Other Cortical Regions In Recognition Memory And Perceptual Discrimination., Edward B O'Neil, Andrea B Protzner, Cornelia Mccormick, D Adam Mclean, Jordan Poppenk, Anthony D Cate, Stefan Köhler

Brain and Mind Institute Researchers' Publications

Traditionally, the medial temporal lobe (MTL) is thought to be dedicated to declarative memory. Recent evidence challenges this view, suggesting that perirhinal cortex (PrC), which interfaces the MTL with the ventral visual pathway, supports highly integrated object representations in recognition memory and perceptual discrimination. Even with comparable representational demands, perceptual and memory tasks differ in numerous task demands and the subjective experience they evoke. Here, we tested whether such differences are reflected in distinct patterns of connectivity between PrC and other cortical regions, including differential involvement of prefrontal control processes. We examined functional magnetic resonance imaging data for closely matched …

Fatigue In Cerebral Palsy: A Critical Review., Laura Kristine Brunton, Charles L Rice

Physical Therapy Publications

Objective: Fatigue contributes to the deterioration or cessation of walking ability in adults with cerebral palsy (CP). However, conflict exists as to its role. Studies involving functional tasks reported increased, and earlier onset of, fatigue in CP whereas laboratory studies have reported individuals with CP to be more fatigue resistant than their peers.

Methods: A critical review of the literature related to fatigue in CP was conducted.

Results: This review describes factors that contribute to the observed fatigue resistance in laboratory tasks and how a decreased force-production in CP can result in higher energy expenditure to perform the same amount …

Clinical Investigation Of The Interface Pressure In The Trans-Tibial Socket With Dermo And Seal-In X5 Liner During Walking And Their Effect On Patient Satisfaction, S. Ali, Noor Azuan Abu Osman, N. Mortaza, A. Eshraghi, H. Gholizadeh, Wan Abu Bakar Wan Abas

Research Publications (2011 to 2015)

Background: The interface pressure between the residual limb and prosthetic socket has a significant effect on an amputee's satisfaction and comfort. Liners provide a comfortable interface by adding a soft cushion between the residual limb and the socket. The Dermo and the Seal-In X5 liner are two new interface systems and, due to their relative infancy, very little are known about their effect on patient satisfaction. The aim of this study was to compare the interface pressure with these two liners and their effect on patient satisfaction. Methods: Nine unilateral transtibial amputees participated in the study. Two prostheses were fabricated …

Neural Network Diagnostic System For Dengue Patients Risk Classification, T. Faisal, M.N. Taib, Fatimah Ibrahim

Research Publications (2011 to 2015)

With the dramatic increase of the worldwide threat of dengue disease, it has been very crucial to correctly diagnose the dengue patients in order to decrease the disease severity. However, it has been a great challenge for the physicians to identify the level of risk in dengue patients due to overlapping of the medical classification criteria. Therefore, this study aims to construct a noninvasive diagnostic system to assist the physicians for classifying the risk in dengue patients. Systematic producers have been followed to develop the system. Firstly, the assessment of the significant predictors associated with the level of risk in …

A Genomic Island In Salmonella Enterica Ssp. Salamae Provides New Insights On The Genealogy Of The Locus Of Enterocyte Effacement., P Scott Chandry, Simon Gladman, Sean C Moore, Torsten Seemann, Keith A Crandall, Narelle Fegan

Computational Biology Institute

The genomic island encoding the locus of enterocyte effacement (LEE) is an important virulence factor of the human pathogenic Escherichia coli. LEE typically encodes a type III secretion system (T3SS) and secreted effectors capable of forming attaching and effacing lesions. Although prominent in the pathogenic E. coli such as serotype O157:H7, LEE has also been detected in Citrobacter rodentium, E. albertii, and although not confirmed, it is likely to also be in Shigella boydii. Previous phylogenetic analysis of LEE indicated the genomic island was evolving through stepwise acquisition of various components. This study describes a new LEE region from two …

Dimerization And Heme Binding Are Conserved In Amphibian And Starfish Homologues Of The Microrna Processing Protein Dgcr8., Rachel Senturia, Arthur Laganowsky, Ian Barr, Brooke D. Scheidemantle, Feng Guo

Natural Sciences and Mathematics | Faculty Scholarship

Human DiGeorge Critical Region 8 (DGCR8) is an essential microRNA (miRNA) processing factor that is activated via direct interaction with Fe(III) heme. In order for DGCR8 to bind heme, it must dimerize using a dimerization domain embedded within its heme-binding domain (HBD). We previously reported a crystal structure of the dimerization domain from human DGCR8, which demonstrated how dimerization results in the formation of a surface important for association with heme. Here, in an attempt to crystallize the HBD, we search for DGCR8 homologues and show that DGCR8 from Patiria miniata (bat star) also binds heme. The extinction coefficients (ε) …

Differential Expression Of Metabolic Genes In Tumor And Stromal Components Of Primary And Metastatic Loci In Pancreatic Adenocarcinoma., Nina V. Chaika, Fang Yu, Vinee Purohit, Kamiya Mehla, Audrey J. Lazenby, Dominick J. Dimaio, Judy M. Anderson, Jen Jen Yeh, Keith R. Johnson, Michael A. Hollingsworth, Pankaj K. Singh

Journal Articles: Eppley Institute

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a five-year survival rate of 6%. It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions. However, the contribution of metabolic interrelationships between tumor cells and cells of the surrounding microenvironment to the progression of cancer is not well understood. We evaluated differential expression of metabolic genes and, hence, metabolic pathways …

Interferon-Α Regulates Glutaminase 1 Promoter Through Stat1 Phosphorylation: Relevance To Hiv-1 Associated Neurocognitive Disorders., Lixia Zhao, Yunlong Huang, Changhai Tian, Lynn Taylor, Norman Curthoys, Yi Wang, Hamilton Vernon, Jialin C. Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

HIV-1 associated neurocognitive disorders (HAND) develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS), glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM) and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In …

Persistent Systemic Inflammation Is Associated With Poor Clinical Outcomes In Copd: A Novel Phenotype, Alvar Agustí, Lisa D. Edwards, Stephen I. Rennard, William Macnee, Ruth Tal-Singer, Bruce E. Miller, Jørgen Vestbo, David A. Lomas, Peter M.A. Calverley, Emiel Wouters, Courtney Crim, Julie C. Yates, Edwin K. Silverman, Harvey O. Coxson, Per Bakke, Ruth J. Mayer, Bartolome Celli, Evaluation Of Copd Longitudinally To Identify Predictive Surrogate Endpoints (Eclipse) Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).

METHODS AND FINDINGS: Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years. We found that, at baseline, 30% of …

James Marion Sims, M.D., Ll.D., Jonathan Tavares, B.S., Charles J. Yeo, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

Few physicians have been as celebrated and loathed as James Marion Sims, M.D., LL.D. Dr. Sims’ modest early life and education never could have predicted that he would one day be called the ‘‘Father of American Gynecology.’’1, 2 Lauded by contemporaries and early historians as ‘‘one of the most original and gifted of American surgeons,’’ he performed the first successful operation to correct vesicovaginal fistulas (a condition that prior to 1852 was known as the ‘‘stumbling-block of gynecology’’).1 Today, the same work that earned Dr. Sims fame, fortune, and innumerable honors has been called into question, because of the unethical …