Diseases Commons^™

Immunotherapy In Hepatocellular Cancer Patients With Mild To Severe Liver Dysfunction: Adjunctive Role Of The Albi Grade, David J Pinato, Takahiro Kaneko, Anwaar Saeed, Tiziana Pressiani, Ahmed Kaseb, Yinghong Wang, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Chieh-Ju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I Abugabal, Celina Ang, Thomas U Marron, Uqba Khan, Nicola Personeni, Lorenza Rimassa, Yi-Hsiang Huang

Faculty, Staff and Students Publications

Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied …

Schizophrenia And Genomics, Tiffini Lasch

Nursing Student Class Projects (Formerly MSN)

There are several advancements in genomics under specific categories, such as cancer and autism. Mental health is one of the leading diseases to cause a significant debt burden in today's society. However, genomics has not translated well into mental health treatment. One area of focus is schizophrenia. Those with schizophrenia suffer from severe and devastating symptoms. The symptoms can lead to harsh complications. Which can make it impossible to function in everyday life. Many believe it is not just genetics alone, but also environmental factors that contribute to schizophrenia. Through large genome-wide associated studies, discoveries are being made. There have …

The Role Of Noninvasive Tests For Differentiating Nash From Nafl And Diagnosing Advanced Fibrosis Among Patients With Nafld, Maya Balakrishnan, Rohit Loomba

Faculty, Staff and Students Publications

Assessing for the presence of non-alcoholic steatohepatitis (NASH) and the presence of advanced fibrosis is vital among patients with non-alcoholic fatty liver disease (NAFLD) as each is predictive of disease outcomes. A liver biopsy is the gold standard method for doing so but is impossible to perform among all patients with NAFLD. Reliable methods for noninvasively detecting for the presence of NASH and advanced fibrosis are thus a pressing need. The search for noninvasive tests has been more successful for advanced fibrosis than for NASH. Clinical prediction models and elastography have acceptable accuracy for ruling out advanced fibrosis; when used …

Proteome Alterations In Pancreatic Ductal Adenocarcinoma, Sheng Pan, Teresa A Brentnall, Ru Chen

Faculty, Staff and Students Publications

Proteins are the essential functional biomolecules profoundly implicated in all aspects of pancreatic tumorigenesis and its progression. While common genomic factors, such as KRAS, TP53, SMAD4, and CDKN2A have been well recognized in association of pancreatic ductal adenocarcinoma (PDAC), our understanding of functional changes at the proteome level merits further investigation. Malignance associated proteome alterations can be attributed to the convoluted outcomes from genetic, epigenetic and environmental factors in initiating and progressing PDAC, and may reflect on changes in protein expressional level, structure, localization, as well as post-translational modifications (PTMs) status. The study of localized or systemic proteome alterations in …

Aromatase Inhibitors Plus Weight Loss Improves The Hormonal Profile Of Obese Hypogonadal Men Without Causing Major Side Effects, Georgia Colleluori, Rui Chen, Christie G Turin, Francesca Vigevano, Clifford Qualls, Biju Johnson, Sanjay Mediwala, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes).

Design: Randomized double-blind placebo-controlled pilot trial.

Methods: …

The Longitudinal Parallel Process Analysis Of Biomarkers Of Oxidative Stress, Symptom Clusters, And Cognitive Function In Children With Leukemia, Mary C Hooke, Daniel Hatch, Marilyn J Hockenberry, Susan Whitman, Ida Moore, David Montgomery, Kari Marano, Pauline Mitby, Michael E Scheurer, Olga Taylor, Wei Pan

Faculty, Staff and Students Publications

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system–directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster–Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar …

Natural Autoantibodies: Origin, Function And Utility For Diagnosis Of Disease, Abhirup Sarkar

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies (aAbs) by the simplest definitions have been described as antibodies against self-antigens and were exclusively associated with autoimmune diseases. Eventually, studies demonstrated that they are abundant in the blood of all human sera, regardless of age, gender, or the presence or absence of disease, and were thus named as ‘natural autoantibodies’. The underlying reason for their ubiquity has remained elusive, but we have hypothesized that they are responsible for clearing blood-borne cell and tissue debris generated under conditions of health and disease. To test this, we chose to use two widely different disease model systems, namely neurodegenerative diseases and …

Incidence And Predictors Of Obstructive Coronary Artery Disease And The Role Of Cardiac Troponin Assays In Patients With Unstable Angina, Sushan Yang, Nirmanmoh Bhatia, Meng Xu, John A Mcpherson

The Texas Heart Institute Journal

In a time when cardiac troponin assays are widely used to detect myocardial injury, data remain scarce concerning the incidence and predictors of substantial obstructive coronary artery disease that causes unstable angina. This retrospective single-center study included consecutive patients hospitalized for unstable angina from January 2015 through January 2016. Patients with troponin I levels above the upper reference limit and those who did not undergo angiography were excluded. Multivariate logistic regression analysis was used to identify predictors of obstructive coronary artery disease that warranted revascularization and of major adverse cardiac events up to 6 months after discharge from the hospital. …

Biomarkers Of Dietary Omega-6 Fatty Acids And Incident Cardiovascular Disease And Mortality: An Individual-Level Pooled Analysis Of 30 Cohort Studies, Matti Marklund, Jason H. Y. Wu, Fumiaki Imamura, Liana C. Del Gobbo, Amanda Fretts, Janette De Goede, Peilin Shi, Nathan L. Tintle, Maria Wennberg, Stella Aslibekyan, Tzu-An Chen, Marcia C. De Oliveira Otto, Yoichiro Hirakawa, Helle Højmark Eriksen, Janine Kroger, Federica Laguzzi, Maria Lankinen, Rachel A. Murphy, Kiesha Prem, Cecelia Samieri, Jyrki Virtanen, Alexis C. Wood, Kerry Wong, Wei-Sin Yang, Xia Zhou, Ana Baylin, Jolanda M. A. Boer, Ingeborg A. Brouwer, Hannia Campos, Paulo H. M. Chaves, Kuo-Liong Chien, Ulf De Faire, Luc Djousse, Gudny Eiriksdottir, Naglaa El-Abbadi, Nita G. Fouruhi, J. Michael Gaziano, Johanna M. Geleijnse, Bruna Gigante, Graham Giles, Eliseo Guallar, Vilmundur Gudnason, Tamara Harris, William S. Harris, Catherine Helmer, Mai-Lis Hellenius, Allison Hodge, Frank B. Hu, Paul F. Jacques, Jan-Hakan Jansson, Anya Kalsbeek, Kay-Tee Khaw, Woon-Puay Koh, Markku Laakso, Karin Leander, Hung-Ju Lin, Lars Lind, Robert Luben, Juhua Luo, Barbara Mcknight, Jaakko Mursu, Toshiharu Ninomiya, Kim Overvad, Bruce M. Psaty, Eric Rimm, Matthias B. Schulze, David Siscovick, Michael Skjelbo Nielsen, Albert V. Smith, Brian T. Steffen, Lyn Steffen, Qi Sun, Johan Sundstrom, Michael Y. Tsai, Hugh Tunstall-Pedoe, Matti I. J. Uusitupa, Rob M. Van Dam, Jenna Veenstra, Monique Verschuren, Nick Wareham, Walter Willett, Mark Woodward, Jian-Min Yuan, Renata Micha, Rozenn N. Lemaitre, Dariush Mozaffarian, Ulf Risérus

Faculty Work Comprehensive List

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, …

Dirt, Saliva And Leprosy: Anti-Inflammatory And Anti-Infectious Effects, Helieh S. Oz

Internal Medicine Faculty Publications

Ancient Egyptians smeared a mixture of dark soil on their eyelids and believed it protected eyes from unknown forces (illness). Recent studies have proven that the dark soil across the Nile River is rich in natural compounds including lead sulfide, which in low levels, promotes the production of nitric oxide (240-fold) by keratinocytes, with strong immune stimulatory and antimicrobial properties. Current investigations reveal anti-inflammatory and anti-infectious activities—including cytokines and chemokines—in saliva, as well as its friendly microbiota, which lines the surface of the oral cavity, its protection against inflammatory and infectious organisms in the stoma and other organs, such as …

Serological Proteomic Screening And Evaluation Of A Recombinant Egg Antigen For The Diagnosis Of Low-Intensity Schistosoma Mansoni Infections In Endemic Area In Brazil, Vanessa Silva-Moraes, Lisa Marie Shollenberger, William Castro-Borges, Ana Lucia Teles Rabello, Donald A. Harn, Lia Carolina Soares Medeiros, Wander De Jesus Jeremias, Liliane Maria Vidal Siqueira, Caroline Stephane Salviano Pereira, Maria Luysa Camargos Pedrosa, Nathalie Bonatti Franco Almeida, Aureo Almeida, Jose Roberto Lambertucci, Nidia Francisca De Figueiredo Carneiro, Paulo Marcos Zech Coelho, Refaella Fortini Queiroz Grenfell

Biological Sciences Faculty Publications

Background

Despite decades of use of control programs, schistosomiasis remains a global public health problem. To further reduce prevalence and intensity of infection, or to achieve the goal of elimination in low-endemic areas, there needs to be better diagnostic tools to detect low-intensity infections in low-endemic areas in Brazil. The rationale for development of new diagnostic tools is that the current standard test Kato-Katz (KK) is not sensitive enough to detect low-intensity infections in low-endemic areas. In order to develop new diagnostic tools, we employed a proteomics approach to identify biomarkers associated with schistosome-specific immune responses in hopes of developing …

Bilateral Carotid Artery Stenosis Causes Unexpected Early Changes In Brain Extracellular Matrix And Blood-Brain Barrier Integrity In Mice, Jill M. Roberts, Michael E. Maniskas, Gregory J. Bix

Neuroscience Faculty Publications

Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular dementia thought to preferentially impact brain white matter. Indeed, few studies report hippocampal and cortical pathology prior to 30 days post-stenosis; though it is unclear whether those studies examined regions outside the white matter. Since changes in the blood-brain barrier (BBB) permeability precede more overt brain pathology in various diseases, we hypothesized that changes within the BBB and/or BBB-associated extracellular matrix (ECM) could occur earlier after BCAS in the hippocampus, cortex and striatum and be a precursor of longer term pathology. Here, C57Bl/6 mice underwent BCAS or sham surgeries …

Word-List Intrusion Errors Predict Progression To Mild Cognitive Impairment, Kelsey R Thomas, Joel Eppig, Emily C Edmonds, Diane M Jacobs, David J Libon, Rhoda Au, David P Salmon, Mark W Bondi, Alzheimer’S Disease Neuroimaging Initiative

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: Preclinical Alzheimer's disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI.

METHOD: Cognitively normal participants (n = 525) from the Alzheimer's Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on …

Centrilobular Emphysema And Coronary Artery Calcification: Mediation Analysis In The Spiromics Cohort, Surya P. Bhatt, Hrudaya P. Nath, Young-Il Kim, Rekha Ramachandran, Jubal R. Watts, Nina L.J. Terry, Sushil Sonavane, Swati P. Deshmane, Prescott G. Woodruff, Elizabeth C. Oelsner, Sandeep Bodduluri, Meilan K. Han, Wassim W. Labaki, J. Michael Wells, Fernando J. Martinez, R. Graham Barr, Mark T. Dransfield, Spiromics Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized to be mediated by systemic inflammation but this link has not been established.

METHODS: We included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used …

Multivariate Analysis To Identify Potential Biomarkers For Prognosis And Treatment Resistance In Head And Neck Cancer Patients, Christina Ann Wicker

Theses and Dissertations--Toxicology and Cancer Biology

It is estimated that nearly 50,000 individuals in the United States will be diagnosed with head and neck cancer in 2017 (American Cancer Society www.cancer.org). Ninety percent of oral cancers are head and neck squamous cell carcinoma (HNSCC). Major obstacles in the treatment of HNSCC are recurrence and treatment resistance, which contributes to increased mortality. Therefore, there is increased need to determine genetic alterations in HNSCC that may be ideal novel drug targets, and biomarkers to improve diagnostic and prognostic testing.

Abnormal localization and overexpression of base excision repair protein and transcriptional regulator Apurinic/Apyrimidic endonuclease (APE1) has been associated with …

Serum Microrna-27b As A Screening Biomarker For Left Ventricular Hypertrophy, Yan Wang, Shuyan Chen, Yanhong Gao, Song Zhang

The Texas Heart Institute Journal

MicroRNA-27b (miR-27b) is frequently upregulated in pressure-overloaded hypertrophic hearts. The clinical implications of aberrant circulating miR-27b in the diagnosis and management of left ventricular hypertrophy warrant study. We investigated whether serum miR-27b is a biomarker for left ventricular hypertrophy (LVH).

We used stem-loop reverse-transcription quantitative polymerase chain reaction techniques to analyze serum miR-27b levels in 200 hypertensive patients with LVH, 100 hypertensive patients without LVH, and 100 healthy volunteers. We found that serum miR-27b levels were significantly higher in the hypertensive patients with LVH than in the hypertensive patients without LVH and in the healthy volunteers. Upon receiver operating characteristic …

Moonlighting Newborn Screening Markers: The Incidental Discovery Of A Second-Tier Test For Pompe Disease, Silvia Tortorelli, Jason S. Eckerman, Joseph J. Orsini, Colleen Stevens, Jeremy Hart, Patricia L. Hall, John J. Alexander, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Dietrich Matern, Piero Rinaldo

Pathology and Laboratory Medicine Faculty Publications

Purpose: To describe a novel biochemical marker in dried blood spots suitable to improve the specificity of newborn screening for Pompe disease.

Methods: The new marker is a ratio calculated between the creatine/creatinine (Cre/Crn) ratio as the numerator and the activity of acid α-glucosidase (GAA) as the denominator. Using Collaborative Laboratory Integrated Reports (CLIR), the new marker was incorporated in a dual scatter plot that can achieve almost complete segregation between Pompe disease and false-positive cases.

Results: The (Cre/Crn)/GAA ratio was measured in residual dried blood spots of five Pompe cases and was found to be elevated (range 4.41–13.26; 99%ile …

Predictors Of High-Sensitivity Cardiac Troponin T Elevation In Patients With Acute Paroxysmal Supraventricular Tachycardia And Ischemic Heart Disease, Mehdi Sayadnik, Akbar Shafiee, Yaser Jenab, Arash Jalali, Saeed Sadeghian

The Texas Heart Institute Journal

We studied the predictors and patterns of high-sensitivity cardiac troponin T (hs-cTnT) elevation in patients with paroxysmal supraventricular tachycardia (PSVT) in the presence and absence of ischemic heart disease.

During calendar year 2013, we enrolled 70 of 72 consecutive adult patients with PSVT who presented at our center within 4 hours after the onset of tachycardia. On the basis of increased hs-cTnT at either of 2 initial measurements, we divided patients into groups (hs-cTnT–positive and hs-cTnT–negative), to study the predictors of enzyme elevation. We then divided the hs-cTnT–positive patients into 2 groups—those with and those without ischemic heart disease—and compared …

Autoantibodies As Diagnostic Biomarkers For The Detection And Subtyping Of Multiple Sclerosis, Cassandra Demarshall, Eric Goldwaser, Abhirup Sarkar, George Godsey, Nimish Acharya, Umashanger Thayasivam, Benjamin Belinka, Robert Nagele

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The goal of this preliminary proof-of-concept study was to use human protein microarrays to identify blood-based autoantibody biomarkers capable of diagnosing multiple sclerosis (MS). Using sera from 112 subjects, including 51 MS subjects, autoantibody biomarkers effectively differentiated MS subjects from age- and gender-matched normal and breast cancer controls with 95.0% and 100% overall accuracy, but not from subjects with Parkinson's disease. Autoantibody biomarkers were also useful in distinguishing subjects with the relapsing-remitting form of MS from those with the secondary progressive subtype. These results demonstrate that autoantibodies can be used as noninvasive blood-based biomarkers for the detection and subtyping of …

Evaluation Of Circulating Mirnas During Late Pregnancy In The Mare, Shavahn C. Loux, Kirsten E. Scoggin, Jason E. Bruemmer, Igor F. Canisso, Mats H. T. Troedsson, Edward L. Squires, Barry A. Ball

Veterinary Science Faculty Publications

MicroRNAs (miRNAs) are small, non-coding RNAs which are produced throughout the body. Individual tissues tend to have a specific expression profile and excrete many of these miRNAs into circulation. These circulating miRNAs may be diagnostically valuable biomarkers for assessing the presence of disease while minimizing invasive testing. In women, numerous circulating miRNAs have been identified which change significantly during pregnancy-related complications (e.g. chorioamnionitis, eclampsia, recurrent pregnancy loss); however, no prior work has been done in this area in the horse. To identify pregnancy-specific miRNAs, we collected serial whole blood samples in pregnant mares at 8, 9, 10 m of gestation …

Plasma Cross-Gestational Sphingolipidomic Analyses Reveal Potential First Trimester Biomarkers Of Preeclampsia, Aneta Dobierzewska, Sony Soman, Sebastian E Illanes, Andrew J. Morris

Saha Cardiovascular Research Center Faculty Publications

Introduction

Preeclampsia (PE) is a gestational disorder, manifested in the second half of pregnancy by maternal hypertension, proteinuria and generalized edema. PE is a major cause of maternal and fetal morbidity and mortality, accounting for nearly 40% of all premature births worldwide. Bioactive sphingolipids are emerging as key molecules involved in etiopathogenesis of PE, characterized by maternal angiogenic imbalance and symptoms of metabolic syndrome. The aim of this study was to compare the cross-gestational profile of circulating bioactive sphingolipids in maternal plasma from preeclamptic (PE) versus normotensive control (CTL) subjects with the goal of identifying sphingolipids as candidate first trimester …

Cancer Antigen 125 Is Associated With Length Of Stay In Patients With Acute Heart Failure, Hakki Kaya, Recep Kurt, Osman Beton, Ali Zorlu, Hasan Yucel, Hakan Gunes, Didem Oguz, Mehmet Birhan Yilmaz

The Texas Heart Institute Journal

Length of stay is the primary driver of heart-failure hospitalization costs. Because cancer antigen 125 has been associated with poor morbidity and mortality rates in heart failure, we investigated the relationship between admission cancer antigen 125 levels and lengths of stay in heart-failure patients. A total of 267 consecutive patients (184 men, 83 women) with acute decompensated heart failure were evaluated prospectively. The median length of stay was 4 days, and the patients were classified into 2 groups: those with lengths of stay ≤4 days and those with lengths of stay >4 days. Patients with longer lengths of stay had …

Cystatin C And Cardiac Measures In Children And Adolescents With Ckd., Tammy M. Brady, Kelly Townsend, Michael F. Schneider, Christopher Cox, Thomas Kimball, Peace Madueme, Bradley A. Warady, Susan Furth, Mark Mitsnefes

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. …

Network-Based Analysis Reveals Novel Gene Signatures In Peripheral Blood Of Patients With Chronic Obstructive Pulmonary Disease, Ma'en Obeidat, Yunlong Nie, Virginia Chen, Casey P. Shannon, Anand Kumar Andiappan, Bernett Lee, Olaf Rotzschke, Peter J. Castaldi, Craig P. Hersh, Nick Fishbane, Raymond T. Ng, Bruce Mcmanus, Bruce E. Miller, Stephen I. Rennard, Peter D. Paré, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death and there is a huge unmet clinical need to identify disease biomarkers in peripheral blood. Compared to gene level differential expression approaches to identify gene signatures, network analyses provide a biologically intuitive approach which leverages the co-expression patterns in the transcriptome to identify modules of co-expressed genes.

METHODS: A weighted gene co-expression network analysis (WGCNA) was applied to peripheral blood transcriptome from 238 COPD subjects to discover co-expressed gene modules. We then determined the relationship between these modules and forced expiratory volume in 1 s (FEV …

The Impact Of Sglt2 Inhibitors, Compared With Insulin, On Diabetic Bone Disease In A Mouse Model Of Type 1 Diabetes, Kathryn M. Thrailkill, Jeffry S. Nyman, R. Clay Bunn, Sasidhar Uppuganti, Katherine L. Thompson, Charles K. Lumpkin, Evangelia Kalaitzoglou, John L. Fowlkes

Barnstable Brown Diabetes Center Faculty Publications

Skeletal co-morbidities in type 1 diabetes include an increased risk for fracture and delayed fracture healing, which are intertwined with disease duration and the presence of other diabetic complications. As such, chronic hyperglycemia is undoubtedly a major contributor to these outcomes, despite standard insulin-replacement therapy. Therefore, using the streptozotocin (STZ)-induced model of hypoinsulinemic hyperglycemia in DBA/2J male mice, we compared the effects of two glucose lowering therapies on the fracture resistance of bone and markers of bone turnover. Twelve week-old diabetic (DM) mice were treated for 9 weeks with: 1) oral canagliflozin (CANA, dose range ~10-16 mg/kg/day), an inhibitor of …

Biomarkers Of Sepsis: A Retrospective Approach, Jose M. Roberts

Williams Honors College, Honors Research Projects

Background: Biomarkers are taking the spotlight in becoming the norm for early diagnoses. Sepsis is an inflammatory disease that increases metabolic rate in children. The first biomarker is hyponatremia. Hyponatremia is a frequent electrolyte imbalance in clinical practice, often observed in children with inflammatory disease and infection. Presence of hyponatremia is associated with electrical signaling imbalances, inflammation and renal dysfunction. The clinical value of hyponatremia in pediatric patients is unknown. The C-reactive protein is a second biomarker. Its presence signifies that necrotic cells and inflammation are present.

Objectives: To evaluate the use of biomarkers in children seen in the Emergency …

Identification Of Biomarkers Associated With Rous Sarcoma Virus-Induced Tumors In Two Divergently Selected Chicken Lines, Ashley Hayden

Graduate Theses and Dissertations

Poultry has become especially important to genetic research due to breeding feasibility, short generation turnover, and ease of maintaining large populations. The discovery of virus induced cancer has paved the way for further genetic studies. Rous Sarcoma Virus (RSV) is a tumor-causing virus that infects poultry. While not prevalent today, it can serve as a model for virus-induced cancer in humans and create additional insight to marker assisted selection in poultry. Genetically selected Arkansas Progressor (AP) and Arkansas Regressor (AR) chicken lines have been established and maintained at the Arkansas Experimental Station (AES) in Fayetteville, AR. Previous research has investigated …

Kidney Disease Progression In Autosomal Recessive Polycystic Kidney Disease., Katherine M. Dell, Matthew Matheson, Erum A. Hartung, Bradley A. Warady, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To define glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in subjects with autosomal recessive polycystic kidney disease (ARPKD) and compare with 2 congenital kidney disease control groups in the Chronic Kidney Disease in Children cohort.

STUDY DESIGN: GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). Differences between study groups were examined with the Wilcoxon rank sum test.

RESULTS: Annualized GFR change in subjects …

Utility And Origin Of Blood-Based Autoantibodies For Early Detection And Diagnosis Of Neurodegenerative Diseases, Cassandra Demarshall

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. My thesis work has focused on this "cause and/or …

Copd Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry, Janice M. Leung, Virginia Chen, Zsuzsanna Hollander, Darlene Dai, Scott J. Tebbutt, Shawn D. Aaron, Kathy L. Vandemheen, Stephen I. Rennard, J. Mark Fitzgerald, Prescott G. Woodruff, Stephen C. Lazarus, John E. Connett, Harvey O. Coxson, Bruce Miller, Christoph Borchers, Bruce M. Mcmanus, Raymond T. Ng, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD.

METHODS: We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72). Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate < 0.01 and fold change >1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel …