Digital Commons Network^™

Plasticizer Interaction With The Heart: Chemicals Used In Plastic Medical Devices Can Interfere With Cardiac Electrophysiology., Rafael Jaimes, Damon Mccullough, Bryan Siegel, Luther Swift, Daniel Mcinerney, James Hiebert, Erick A Perez-Alday, Beatriz Trenor, Jiansong Sheng, Javier Saiz, Larisa G Tereshchenko, Nikki Gillum Posnack

Pediatrics Faculty Publications

BACKGROUND: Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients.

METHODS: Optical mapping of transmembrane voltage and pacing studies were performed on isolated, Langendorff-perfused rat hearts to assess cardiac electrophysiology after MEHP exposure compared with controls. MEHP dose was chosen based on reported blood concentrations after an exchange transfusion procedure.

RESULTS: Thirty-minute exposure to MEHP increased the atrioventricular node (147 …

The Current State Of Molecular Testing In The Treatment Of Patients With Solid Tumors, 2019., Wafik S El-Deiry, Richard M Goldberg, Heinz-Josef Lenz, Anthony F Shields, Geoffrey T Gibney, Antoinette R Tan, Jubilee Brown, Burton Eisenberg, Elisabeth I Heath, Surasak Phuphanich, Edward Kim, Andrew J Brenner, John L Marshall

Articles, Abstracts, and Reports

The world of molecular profiling has undergone revolutionary changes over the last few years as knowledge, technology, and even standard clinical practice have evolved. Broad molecular profiling is now nearly essential for all patients with metastatic solid tumors. New agents have been approved based on molecular testing instead of tumor site of origin. Molecular profiling methodologies have likewise changed such that tests that were performed on patients a few years ago are no longer complete and possibly inaccurate today. As with all rapid change, medical providers can quickly fall behind or struggle to find up-to-date sources to ensure he or …

Diagnosis Of Non-Small Cell Lung Cancer For Early Stage Asymptomatic Patients., Cherylle Goebel, Christopher L Louden, Robert Mckenna, Osita Onugha, Andrew Wachtel, Thomas Long

Articles, Abstracts, and Reports

BACKGROUND/AIM: In 2016 in the United States, 7 of 10 patients were estimated to die following lung cancer diagnosis. This is due to a lack of a reliable screening method that detects early-stage lung cancer. Our aim is to accurately detect early stage lung cancer using algorithms and protein biomarkers.

PATIENTS AND METHODS: A total of 1,479 human plasma samples were processed using a multiplex immunoassay platform. 82 biomarkers and 6 algorithms were explored. There were 351 NSCLC samples (90.3% Stage I, 2.3% Stage II, and 7.4% Stage III/IV).

RESULTS: We identified 33 protein biomarkers and developed a classifier using …

Pituitary Adenoma In Pediatric And Adolescent Populations, Jie Chen, Robert E Schmidt, Sonika Dahiya

Open Access Publications

Pituitary adenomas are rare in children and adolescents and although mostly benign, they can sometimes be challenging to manage due to their locally invasive nature. In this study, we examined the clinicopathologic features of 42 pituitary adenomas in patients ≤21 years of age. The youngest patient was 8 years old (median age: 18 years), and the female-to-male ratio was 1.8:1. Five patients had recurrence after resection. There was no obvious difference between the recurrent rates in the typical (11.7%) and atypical adenomas (12.5%) based on the 2004 WHO classification. However, the recurrence rate was much higher in adenomas with an …

Sentinel Vascular Access Monitoring After Endovascular Intervention Predicts Access Outcome, Lalathaksha Kumbar, Edward L. Peterson, Matthew Zaborowicz, Anatole Besarab, Jerry Yee, Gerard Zasuwa

Nephrology Articles

BACKGROUND AND OBJECTIVES: The vascular access pressure ratio test identifies dialysis vascular access dysfunction when three consecutive vascular access pressure ratios are >0.55. We tested whether the magnitude of the decline in vascular access pressure ratio 1-week post-intervention could alert of subsequent access failure.

DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The retrospective study included all vascular access procedures at one institution from March 2014 to June 2016. Data included demographics, comorbidities, vascular access features, %ΔVAPR = ((Pre-Post)/Pre] × 100% assessed within the first 2 weeks post-percutaneous transluminal balloon angioplasty, time-to-next procedure, and patency. The log-rank test compared the area under the …

Reducing Aerodynamic Drag By Adopting A Novel Road-Cycling Sprint Position, Paul F. J. Merkes, Paolo Menaspa, Chris R. Abbiss

Research outputs 2014 to 2021

Purpose:

To assess the influence of seated, standing, and forward-standing cycling sprint positions on aerodynamic drag (CdA) and the reproducibility of a field test of CdA calculated in these different positions.

Methods:

A total of 11 recreational male road cyclists rode 250 m in 2 directions at around 25, 32, and 40 km·h.

Results:

A main effect of position showed that the average CdA of the 2 d was lower for the forward-standing position (0.295 [0.059]) compared with both the seated (0.363 [0.071], P = .018) and standing positions (0.372 [0.077], P = .037). Seated and standing positions did …

Microrna-374a, -4680, And -133b Suppress Cell Proliferation Through The Regulation Of Genes Associated With Human Cleft Palate In Cultured Human Palate Cells, Akiko Suzuki, Aimin Li, Mona Gajera, Nada Abdallah, Musi Zhang, Zhongming Zhao, Junichi Iwata

Faculty, Staff and Student Publications

BACKGROUND: Cleft palate (CP) is the second most common congenital birth defect; however, the relationship between CP-associated genes and epigenetic regulation remains largely unknown. In this study, we investigated the contribution of microRNAs (miRNAs) to cell proliferation and regulation of genes involved in CP development.

METHODS: In order to identify all genes for which mutations or association/linkage have been found in individuals with CP, we conducted a systematic literature search, followed by bioinformatics analyses for these genes. We validated the bioinformatics results experimentally by conducting cell proliferation assays and miRNA-gene regulatory analyses in cultured human palatal mesenchymal cells treated with …

The Influence Of Vitamin D Supplementation On Local And Systemic Inflammatory Markers In Periodontitis Patients: A Pilot Study, Mohamed M Meghil, Lance Hutchens, Anas Raed, Neha A Multani, Mythilypriya Rajendran, Haidong Zhu, Stephen Looney, Mahmoud Elashiry, Roger M Arce, Mark E Peacock, Yanbin Dong, Christopher W Cutler

Faculty, Staff and Student Publications

OBJECTIVES: Vitamin D deficiency/insufficiency is a worldwide public health issue that has been linked to numerous inflammatory disorders, including periodontitis. There is increasing support for a role for adequate vitamin D levels in overall health. Populations with darker skin color have a higher prevalence of vitamin D deficiency/insufficiency and periodontitis. The purpose of this small pilot study was to investigate the influence of 12 weeks of 25(OH)D vitamin D supplementation (VDS) on mediators of systemic inflammation in dark-skinned, periodontitis patients.

MATERIALS AND METHODS: A total of 23 patients with moderate to severe periodontitis were randomly assigned to the vitamin D …

The Concentration Of Total Nucleated Cells In Harvested Bone Marrow For Transplantation Has Decreased Over Time., Nicole L. Prokopishyn, Brent R. Logan, Deidre M. Kiefer, Jennifer A. Sees, Pintip Chitphakdithai, Ibrahim A. Ahmed, Paolo N. Anderlini, Amer M. Beitinjaneh, Christopher Bredeson, Jan Cerny, Saurabh Chhabra, Andrew Daly, Miguel Angel Diaz, Nosha Farhadfar, Haydar A. Frangoul, Siddhartha Ganguly, Dennis A. Gastineau, Usama Gergis, Gregory A. Hale, Peiman Hematti, Rammurti T. Kamble, Kimberly A. Kasow, Hillard M. Lazarus, Jane L. Liesveld, Hemant S. Murthy, Maxim Norkin, Richard F. Olsson, Mona Papari, Bipin N. Savani, Jeffrey Szer, Edmund K. Waller, Baldeep Wirk, Jean A. Yared, Michael A. Pulsipher, Nirali N. Shah, Galen E. Switzer, Paul V. O'Donnell, Dennis L. Confer, Bronwen E. Shaw

Manuscripts, Articles, Book Chapters and Other Papers

Bone marrow (BM) is an essential source of hematopoietic stem cell grafts for many allogeneic hematopoietic cell transplant (HCT) recipients, including adult patients (for specific diseases and transplantation strategies) and the majority of pediatric recipient. However, since the advent of granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts, there has been a significant decrease in the use of BM in HCT, thought to be due mainly to the increased logistical challenges in harvesting BM compared with PBSCs, as well as generally no significant survival advantage of BM over PBSCs. The decreased frequency of collection has the potential to impact …

Autonomic Response In Autism Spectrum Disorder: Relationship To Social And Cognitive Functioning, Michelle A Patriquin, Elizabeth M Hartwig, Bruce H Friedman, Stephen W Porges, Angela Scarpa

Staff and Researcher Publications

Individuals with autism spectrum disorder (ASD) may exhibit chronic autonomic nervous system (ANS) hyperarousal (e.g., lower respiratory sinus arrhythmia and higher heart rate) compared to their typically developing peers, reflecting a chronic biological threat response. The sustained nature of this cardiac threat suggests tonic nervous system perception of threat in safe contexts. Herein, the cardiac literature in adult and child populations with ASD is reviewed and placed within a continuum of functioning in order to inform the relationship between cardiac response and functioning in ASD. Findings from this review support the relationship between chronic autonomic hyperarousal and emotional and behavioral …

Evaluation Of Clinical Outcomes In An Interdisciplinary Abdominal Pain Clinic: A Retrospective, Exploratory Review., Amanda D. Deacy, Craig A. Friesen, Vincent S. Staggs, Jennifer Verrill Schurman

Manuscripts, Articles, Book Chapters and Other Papers

Background: Pediatric functional gastrointestinal disorders (FGIDs) are common and well-accepted to be etiologically complex in terms of the contribution of biological, psychological, and social factors to symptom presentations. Nonetheless, despite its documented benefits, interdisciplinary treatment, designed to address all of these factors, for pediatric FGIDs remains rare. The current study hypothesized that the majority of pediatric patients seen in an interdisciplinary abdominal pain clinic (APC) would demonstrate clinical resolution of symptoms during the study period and that specific psychosocial variables would be significantly predictive of GI symptom improvement.

Aim: To evaluate outcomes with interdisciplinary treatment in pediatric patients with pain-related …

Pathologic Gene Network Rewiring Implicates Ppp1r3a As A Central Regulator In Pressure Overload Heart Failure., Pablo Cordero, Victoria N Parikh, Elizabeth T Chin, Ayca Erbilgin, Michael J Gloudemans, Ching Shang, Yong Huang, Alex C Chang, Kevin S Smith, Frederick Dewey, Kathia Zaleta, Michael Morley, Jeff Brandimarto, Nicole Glazer, Daryl Waggott, Aleksandra Pavlovic, Mingming Zhao, Christine S Moravec, W H Wilson Tang, Jamie Skreen, Christine Malloy, Sridhar Hannenhalli, Hongzhe Li, Scott Ritter, Mingyao Li, Daniel Bernstein, Andrew Connolly, Hakon Hakonarson, Aldons J Lusis, Kenneth B Margulies, Anna A Depaoli-Roach, Stephen B Montgomery, Matthew T Wheeler, Thomas Cappola, Euan A Ashley

Articles, Abstracts, and Reports

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and …

Structural Basis For The Homotypic Fusion Of Chlamydial Inclusions By The Snare-Like Protein Inca., Gino Cingolani, Michael Mccauley, Anna Lobley, Alexander J Bryer, Jordan Wesolowski, Deanna L Greco, Ravi K Lokareddy, Erik Ronzone, Juan R Perilla, Fabienne Paumet

Department of Biochemistry and Molecular Biology Faculty Papers

Many intracellular bacteria, including Chlamydia, establish a parasitic membrane-bound organelle inside the host cell that is essential for the bacteria's survival. Chlamydia trachomatis forms inclusions that are decorated with poorly characterized membrane proteins known as Incs. The prototypical Inc, called IncA, enhances Chlamydia pathogenicity by promoting the homotypic fusion of inclusions and shares structural and functional similarity to eukaryotic SNAREs. Here, we present the atomic structure of the cytoplasmic domain of IncA, which reveals a non-canonical four-helix bundle. Structure-based mutagenesis, molecular dynamics simulation, and functional cellular assays identify an intramolecular clamp that is essential for IncA-mediated homotypic membrane fusion during …

Intracellular Retention Of Mutant Lysyl Oxidase Leads To Aortic Dilation In Response To Increased Hemodynamic Stress, Vivian S Lee, Carmen M Halabi, Thomas J Broekelmann, Philip C Trackman, Nathan O Stitziel, Robert P Mecham

Open Access Publications

Heterozygous missense mutations in lysyl oxidase (LOX) are associated with thoracic aortic aneurysms and dissections. To assess how LOX mutations modify protein function and lead to aortic disease, we studied the factors that influence the onset and progression of vascular aneurysms in mice bearing a Lox mutation (p.M292R) linked to aortic dilation in humans. We show that mice heterozygous for the M292R mutation did not develop aneurysmal disease unless challenged with increased hemodynamic stress. Vessel dilation was confined to the ascending aorta although both the ascending and descending aortae showed changes in vessel wall structure, smooth muscle cell number and …

Assessment Of Physical Fitness After Bariatric Surgery And Its Association With Protein Intake And Type Of Cholecalciferol Supplementation, Hendrika J M Smelt, Sjaak Pouwels, Alper Celik, Adarsh Gupta, Johannes F Smulders

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Background: Several studies showed that there is a relationship between vitamin and mineral status and muscle strength. In particular this is the case for handgrip strength (HS) and vitamin D deficiency. In bariatric surgery there is a risk of decrease in muscle strength after surgery and also vitamin and mineral deficiencies are not uncommon. The aim of this study is to assess the effect of low vitamin 25 (OH) cholecalciferol levels, high dose cholecalciferol supplementation regime and protein intake on physical fitness, measured using handgrip strength (HS) and the shuttle walk run test (SWRT). Methods: For this retrospective …

Xx Sex Chromosome Complement Promotes Atherosclerosis In Mice, Yasir Alsiraj, Xuqi Chen, Sean E. Thatcher, Ryan E. Temel, Lei Cai, Eric M. Blalock, Wendy Katz, Heba M. Ali, Michael C. Petriello, Pan Deng, Andrew J. Morris, Xuping Wang, Aldons J. Lusis, Arthur P. Arnold, Karen Reue, Katherine L. Thompson, Patrick Tso, Lisa A. Cassis

Pharmacology and Nutritional Sciences Faculty Publications

Men and women differ in circulating lipids and coronary artery disease (CAD). While sex hormones such as estrogens decrease CAD risk, hormone replacement therapy increases risk. Biological sex is determined by sex hormones and chromosomes, but effects of sex chromosomes on circulating lipids and atherosclerosis are unknown. Here, we use mouse models to separate effects of sex chromosomes and hormones on atherosclerosis, circulating lipids and intestinal fat metabolism. We assess atherosclerosis in multiple models and experimental paradigms that distinguish effects of sex chromosomes, and male or female gonads. Pro-atherogenic lipids and atherosclerosis are greater in XX than XY mice, indicating …

An Integrative Cross-Omics Analysis Of Dna Methylation Sites Of Glucose And Insulin Homeostasis, Jun Liu, Elena Carnero-Montoro, Jenny Van Dongen, Samantha Lent, Ivana Nedeljkovic, Symen Ligthart, Pei-Chien Tsai, Tiphaine C. Martin, Pooja R. Mandaviya, Rick Jansen, Marjolein J. Peters, Liesbeth Duijts, Vincent W. V. Jaddoe, Henning Tiemeier, Janine F. Felix, Gonneke Willemsen, Eco J. C. De Geus, Audrey Y. Chu, Daniel Levy, Shih-Jen Hwang, Jan Bressler, Rahul Gondalia, Elias L. Salfati, Christian Herder, Bertha A. Hidalgo, Toshiko Tanaka, Ann Zenobia Moore, Rozenn N. Lemaitre, Min A. Jhun, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation …

Proteomics Standards Initiative Extended Fasta Format., Pierre-Alain Binz, Jim Shofstahl, Juan Antonio Vizcaíno, Harald Barsnes, Robert J Chalkley, Gerben Menschaert, Emanuele Alpi, Karl Clauser, Jimmy K Eng, Lydie Lane, Sean L Seymour, Luis Francisco Hernández Sánchez, Gerhard Mayer, Martin Eisenacher, Yasset Perez-Riverol, Eugene A Kapp, Luis Mendoza, Peter R Baker, Andrew Collins, Tim Van Den Bossche, Eric W Deutsch

Articles, Abstracts, and Reports

Mass-spectrometry-based proteomics enables the high-throughput identification and quantification of proteins, including sequence variants and post-translational modifications (PTMs) in biological samples. However, most workflows require that such variations be included in the search space used to analyze the data, and doing so remains challenging with most analysis tools. In order to facilitate the search for known sequence variants and PTMs, the Proteomics Standards Initiative (PSI) has designed and implemented the PSI extended FASTA format (PEFF). PEFF is based on the very popular FASTA format but adds a uniform mechanism for encoding substantially more metadata about the sequence collection as well as …

Impact Of High Volume Energy Drink Consumption On Electrocardiographic And Blood Pressure Parameters: A Randomized Trial, Sachin A. Shah, Andy H. Szeto, Raechel Farewell, Allen Shek, Dorothy Fan, Kathy N. Quach, Mouchumi Bhattacharyya, Jasmine Elmiari, Winny Chan, Kate O'Dell, Nancy Nguyen, Tracey J. Mcgaughey, Javed M. Nasir, Sanjay Kaul

School of Pharmacy Faculty Articles

Background Energy drinks have been linked to an increase in emergency room visits and deaths. We aim to determine the impact of energy drinks on electrocardiographic and hemodynamic parameters in young healthy volunteers. Methods and Results A randomized, double-masked, placebo-controlled, crossover study was conducted in healthy volunteers. Participants consumed 32 oz of either energy drink A, energy drink B, or placebo within 60 minutes on 3 study days with a 6-day washout period in between. The primary end point of QT c interval and secondary end points of QT interval, PR interval, QRS duration, heart rate, and brachial and central …

Fishermp: Fully Parallel Algorithm For Detecting Combinatorial Motifs From Large Chip-Seq Datasets., Shaoqiang Zhang, Ying Liang, Xiangyun Wang, Zhengchang Su, Yong Chen

College of Science & Mathematics Departmental Research

Detecting binding motifs of combinatorial transcription factors (TFs) from chromatin immunoprecipitation sequencing (ChIP-seq) experiments is an important and challenging computational problem for understanding gene regulations. Although a number of motif-finding algorithms have been presented, most are either time consuming or have sub-optimal accuracy for processing large-scale datasets. In this article, we present a fully parallelized algorithm for detecting combinatorial motifs from ChIP-seq datasets by using Fisher combined method and OpenMP parallel design. Large scale validations on both synthetic data and 350 ChIP-seq datasets from the ENCODE database showed that FisherMP has not only super speeds on large datasets, but also …

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Thèrése Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology Research and Scholarship

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …

Downregulation Of Cenpf Remodels Prostate Cancer Cells And Alters Cellular Metabolism., Muhammad Shahid, Minhyung Kim, Min Young Lee, Austin Yeon, Sungyong You, Hyung L Kim, Jayoung Kim

Articles, Abstracts, and Reports

Metabolic alterations in prostate cancer (PC) are associated with progression and aggressiveness. However, the underlying mechanisms behind PC metabolic functions are unknown. The authors' group recently reported on the important role of centromere protein F (CENPF), a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis, in PC MRI visibility. This study focuses on discerning the role of CENPF in metabolic perturbation in human PC3 cells. A series of bioinformatics analyses shows that CENPF is one gene that is strongly associated with aggressive PC and that its expression is positively correlated with metastasis. By identifying and reconstructing the …

Initial Management Of Meningiomas: Analysis Of The National Cancer Database, Catherine R. Garcia, Stacey A. Slone, Monica Chau, Janna H. Neltner, Thomas A. Pittman, John L. Villano

Neurology Faculty Publications

BACKGROUND: Meningiomas are the most common central nervous system tumor. We describe current trends in treatment and survival using the largest cancer dataset in the United States.

METHODS: We analyzed the National Cancer Database from 2004 to 2014, for all patients with diagnosis of meningioma.

RESULTS: 201,765 cases were analyzed. Patients were most commonly White (81.9%) females (73.2%) with a median age of 64 years. Fifty percent of patients were diagnosed by imaging. Patients were reported as grade I (24.9%), grade II (5.0%), grade III (0.7%), or unknown WHO grade (69.4%). Patients diagnosed by imaging were older, received treatment in …

Special Considerations For Clinical Trials In Fibrodysplasia Ossificans Progressiva (Fop)., Edward C Hsiao, Maja Di Rocco, Amanda Cali, Michael Zasloff, Mona Al Mukaddam, Robert J Pignolo, Zvi Grunwald, Coen Netelenbos, Richard Keen, Genevieve Baujat, Matthew A Brown, Tae-Joon Cho, Carmen De Cunto, Patricia Delai, Nobuhiko Haga, Rolf Morhart, Christiaan Scott, Keqin Zhang, Robert J Diecidue, Clive S Friedman, Fredrick S Kaplan, Elisabeth M W Eekhoff

Department of Anesthesiology Faculty Papers

Clinical trials for orphan diseases are critical for developing effective therapies. One such condition, fibrodysplasia ossificans progressiva (FOP; MIM#135100), is characterized by progressive heterotopic ossification (HO) that leads to severe disability. Individuals with FOP are extremely sensitive to even minor traumatic events. There has been substantial recent interest in clinical trials for novel and urgently-needed treatments for FOP. The International Clinical Council on FOP (ICC) was established in 2016 to provide consolidated and coordinated advice on the best practices for clinical care and clinical research for individuals who suffer from FOP. The Clinical Trials Committee of the ICC developed a …

Developmental Expression Of The Cytosolic Sulfotransferases In Human Liver., Sarah Dubaisi, Joseph A. Caruso, R Gaedigk, Carrie A. Vyhlidal, Philip C. Smith, Ronald N. Hines, Thomas A. Kocarek, Melissa Runge-Morris

Manuscripts, Articles, Book Chapters and Other Papers

The liver is the predominant organ of metabolism for many endogenous and foreign chemicals. Cytosolic sulfotransferases (SULTs) catalyze the sulfonation of drugs and other xenobiotics, as well as hormones, neurotransmitters, and sterols, with consequences that include enhanced drug elimination, hormone inactivation, and procarcinogen bioactivation. SULTs are classified into six gene families, but only SULT1 and SULT2 enzymes are expressed in human liver. We characterized the developmental expression patterns of SULT1 and SULT2 mRNAs and proteins in human liver samples using reverse transcription quantitative polymerase chain reaction (RT-qPCR), RNA sequencing, and targeted quantitative proteomics. Using a set of prenatal, infant, and …

Genetic Approaches To Metabolic Bone Diseases, Fadil M Hannan, Paul J Newey, Michael P Whyte, Rajesh V Thakker

Open Access Publications

Metabolic bone diseases comprise a diverse group of disorders characterized by alterations in skeletal homeostasis, and are often associated with abnormal circulating concentrations of calcium, phosphate or vitamin D metabolites. These diseases commonly have a genetic basis and represent either a monogenic disorder due to a germline or somatic single gene mutation, or an oligogenic or polygenic disorder that involves variants in more than one gene. Germline single gene mutations causing Mendelian diseases typically have a high penetrance, whereas the genetic variations causing oligogenic or polygenic disorders are each associated with smaller effects with additional contributions from environmental factors. Recognition …

Apolipoprotein E Associated With Reconstituted High-Density Lipoprotein-Like Particles Is Protected From Aggregation., Ellen Hubin, Philip B Verghese, Nico Van Nuland, Kerensa Broersen

Open Access Publications

Apolipoprotein E (APOE) genotype determines Alzheimer's disease (AD) susceptibility, with the APOE ε4 allele being an established risk factor for late-onset AD. The ApoE lipidation status has been reported to impact amyloid-beta (Aβ) peptide metabolism. The details of how lipidation affects ApoE behavior remain to be elucidated. In this study, we prepared lipid-free and lipid-bound ApoE particles, mimicking the high-density lipoprotein particles found in vivo, for all three isoforms (ApoE2, ApoE3, and ApoE4) and biophysically characterized them. We find that lipid-free ApoE in solution has the tendency to aggregate in vitro in an isoform-dependent manner under near-physiological conditions and that …

The Man With 2 Hearts: 25 Years From Heterotopic To Orthotopic Heart Transplantation, Elizabeth L Godfrey, Michael L Kueht, Abbas Rana, O H Frazier

The Texas Heart Institute Journal

Substantial technological advances in mechanical circulatory support have caused a shift in the management of end-stage heart failure. From the 1970s through the 1990s, heterotopic heart transplantation was routinely performed in patients in whom orthotopic transplantation was likely to fail. Heterotopic heart transplantation is now performed less often because modern mechanical circulatory assist devices are routinely used as bridges to orthotopic transplantation; regardless, the operation has helped numerous patients who would not otherwise have received adequate allografts. We describe the case of a man with idiopathic nonischemic cardiomyopathy who, at age 17, was given an ABO- and size-matched heterotopic allograft …

Points-To-Consider On The Return Of Results In Epigenetic Research., Stephanie O M Dyke, Katie M. Saulnier, Charles Dupras, Amy P. Webster, Karen Maschke, Mark Rothstein, Reiner Siebert, Jörn Walter, Stephan Beck, T Pastinen, Yann Joly

Manuscripts, Articles, Book Chapters and Other Papers

As epigenetic studies become more common and lead to new insights into health and disease, the return of individual epigenetic results to research participants, in particular in large-scale epigenomic studies, will be of growing importance. Members of the International Human Epigenome Consortium (IHEC) Bioethics Workgroup considered the potential ethical, legal, and social issues (ELSI) involved in returning epigenetic research results and incidental findings in order to produce a set of 'Points-to-consider' (P-t-C) for the epigenetics research community. These P-t-C draw on existing guidance on the return of genetic research results, while also integrating the IHEC Bioethics Workgroup's ELSI research on …

Abcb1 Snp Predicts Outcome In Patients With Acute Myeloid Leukemia Treated With Gemtuzumab Ozogamicin: A Report From Children's Oncology Group Aaml0531 Trial., Roya Rafiee, Lata Chauhan, Todd A. Alonzo, Yi-Cheng Wang, Ahlam Elmasry, Michael R. Loken, Jessica Pollard, Richard Aplenc, Susana Raimondi, Betsy A. Hirsch, Irwin D. Bernstein, A S. Gamis, Soheil Meshinchi, Jatinder K. Lamba

Manuscripts, Articles, Book Chapters and Other Papers

Gemtuzumab-ozogamicin (GO), a humanized-anti-CD33 antibody linked with the toxin-calicheamicin-γ is a reemerging and promising drug for AML. Calicheamicin a key element of GO, induces DNA-damage and cell-death once the linked CD33-antibody facilitates its uptake. Calicheamicin efflux by the drug-transporter PgP-1 have been implicated in GO response thus in this study, we evaluated impact of ABCB1-SNPs on GO response. Genomic-DNA samples from 942 patients randomized to receive standard therapy with or without addition of GO (COG-AAML0531) were genotyped for ABCB1-SNPs. Our most interesting results show that for rs1045642, patients with minor-T-allele (CT/TT) had better outcome as compared to patients with CC …