Digital Commons Network^™

Differences And Similarities In The Clinicopathological Features Of Pancreatic Neuroendocrine Tumors In China And The United States: A Multicenter Study, Li-Ming Zhu, Laura Tang, Xin-Wei Qiao, Edward M. Wolin, Nicholas N. Nissen, Deepti Dhall, Jie Chen, Lin Shen, Yihebali Chi, Yao-Zong Yuan, Qi-Wen Ben, Bin Lv, Ya-Ru Zhou, Chun-Mei Bai, Jie Chen, Yu-Li Song, Tian-Tian Song, Chong-Mei Lu, Run Yu, Yuan-Jia Chen

Markey Cancer Center Faculty Publications

The presentation, pathology, and prognosis of pancreatic neuroendocrine tumors (PNETs) in Asian patients have not been studied in large cohorts. We hypothesized that the clinicopathological features of PNETs of Chinese patients might be different from those of US patients. The objectives of this study were to address whether PNETs in Chinese patients exhibit unique clinicopathological features and natural history, and can be graded and staged using the WHO/ENETS criteria.

This is a retrospective review of medical records of patients with PNETs in multiple academic medical centers in China (7) and the United States (2). Tumor grading and staging were based …

Fracture Burden And Risk Factors In Childhood Ckd: Results From The Ckid Cohort Study., Michelle R. Denburg, Juhi Kumar, Thomas Jemielita, Ellen R. Brooks, Amy Skversky, Anthony A. Portale, Isidro B. Salusky, Bradley A. Warady, Susan L. Furth, Mary B. Leonard

Manuscripts, Articles, Book Chapters and Other Papers

Childhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence …

Genetic Loci Associated With Renal Function Measures And Chronic Kidney Disease In Children: The Pediatric Investigation For Genetic Factors Linked With Renal Progression Consortium., Matthias Wuttke, Craig S. Wong, Elke Wühl, Daniel Epting, Li Luo, Anselm Hoppmann, Anke Doyon, Yong Li, Gkdgen Consortium, Betül Sözeri, Daniela Thurn, Martin Helmstädter, Tobias B. Huber, Tom D. Blydt-Hansen, Albrecht Kramer-Zucker, Otto Mehls, Anette Melk, Uwe Querfeld, Susan L. Furth, Bradley A. Warady, Franz Schaefer, Anna Köttgen

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and therefore constitutes an important health problem. While unbiased genetic screens have identified common risk variants influencing renal function and CKD in adults, the presence and identity of such variants in pediatric CKD are unknown.

METHODS: The international Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and Cardiovascular …

Which Individual Therapist Behaviors Elicit Client Change Talk And Sustain Talk In Motivational Interviewing?, Timothy R. Apodaca, Kristina M. Jackson, Brian Borsari, Molly Magill, Richard Longabaugh, Nadine R. Mastroleo, Nancy P. Barnett

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To identify individual therapist behaviors which elicit client change talk or sustain talk in motivational interviewing sessions.

METHOD: Motivational interviewing sessions from a single-session alcohol intervention delivered to college students were audio-taped, transcribed, and coded using the Motivational Interviewing Skill Code (MISC), a therapy process coding system. Participants included 92 college students and eight therapists who provided their treatment. The MISC was used to code 17 therapist behaviors related to the use of motivational interviewing, and client language reflecting movement toward behavior change (change talk), away from behavior change (sustain talk), or unrelated to the target behavior (follow/neutral).

RESULTS: …

Endosteal Biologic Augmentation For Surgical Fixation Of Displaced Femoral Neck Fractures, Lionel E Lazaro, Jacqueline F Birnbaum, Nadja A Farshad-Amacker, David L Helfet, Hollis G Potter, Dean G Lorich

Faculty, Staff and Student Publications

OBJECTIVES: To report outcomes of a cohort with displaced femoral neck fractures (FNFs) treated with a length/angle-stable construct augmented with an endosteal fibular allograft serving as a biologic dowel.

DESIGN: Prospective.

SETTING: Level I Trauma Center.

PATIENTS: The study group consists of 27 patients with isolated FNF surgically treated by a single surgeon.

INTERVENTION: Open reduction of the femoral neck, fixed with a length- and angle-stable construct of 2 fully threaded cannulated screws augmented with an endosteal fibular allograft serving as a biologic dowel.

MAIN OUTCOME MEASUREMENTS: Clinical and radiographic outcomes of the fixation construct and the viability of both …

Assessing Knowledge Of, And Attitudes To, Hiv/Aids Among University Students In The United Arab Emirates, Dalia Haroun, Ola El Saleh, Lesley Wood, Rola Mechli, Nada Al Marzouqi, Samir Anouti

All Works

© 2016 Haroun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: The Middle East and North Africa (MENA) region is among the top two regions in the world with the fastest growing HIV epidemic. In this context, risks and vulnerability are high as the epidemic is on the rise with evidence indicating significantly increasing HIV prevalence, new HIV infections and AIDS-related deaths. Objective: The aim of the survey was to assess …

Durability Of The Starr-Edwards Heart Valve: Early Decisions Led To Successful Results, Albert Starr, Gary L Grunkemeier

The Texas Heart Institute Journal

No abstract provided.

Alternative Surgical Approach To Repairing A Giant Sinus Of Valsalva Aneurysm, Vincenzo Giambruno, Cristina Cucchietti, Calogera Pisano, Jonathan Hyde

The Texas Heart Institute Journal

We report our method of surgically repairing an unruptured giant aneurysm of the right coronary sinus of Valsalva, a lesion that caused moderate aortic regurgitation but no symptoms in a 61-year-old woman. We excised the aneurysm, reconstructed the right sinus of Valsalva with use of a patch, performed mechanical aortic valve replacement directly through the excised aneurysm's cavity, and constructed a single bypass graft to the right coronary artery. The patient was discharged from the hospital after 5 days. Twelve months postoperatively, her clinical and echocardiographic results were normal, and she was doing well. To our knowledge, our surgical approach …

Cutting The Cost Of Health Care: The Physician's Role, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

The Mosaic Mitral Valve Bioprosthesis: A Long-Term Clinical And Hemodynamic Follow-Up, Michele Celiento, Stefania Blasi, Andrea De Martino, Stefano Pratali, Aldo D Milano, Uberto Bortolotti

The Texas Heart Institute Journal

We reviewed the cases of 100 patients (mean age, 73 ± 10 yr; 64 men) who had mitral valve replacement with a Medtronic Mosaic porcine bioprosthesis from 1995 through 2011. The mean New York Heart Association (NYHA) class was 3 ± 0.7, and 52 patients were in atrial fibrillation. Prosthetic sizes were chiefly 27 mm (50 patients) and 29 mm (40 patients). Follow-up ended in December 2012 and is 97% complete, with a cumulative duration of 611 patient-years (mean duration, 6 ± 4.6 yr; maximum, 17.7 yr). The early mortality rate was 10% (6% in elective patients); late deaths occurred …

Aortic Dissection Caused By Percutaneous Coronary Intervention: 2 New Case Reports And Detailed Analysis Of 86 Previous Cases, Priyank Shah, Sharad Bajaj, Fayez Shamoon

The Texas Heart Institute Journal

Aortic dissection, a rare sequela of percutaneous coronary intervention, can be fatal when it is not recognized and treated promptly. Treatment varies from conservative management to invasive aortic repair and revascularization. We report the cases of 2 patients whose aortic dissection was caused by percutaneous coronary intervention. In addition, we present detailed analyses of 86 previously reported cases. Aortic dissection was most often seen during intervention to the right coronary artery (in 76.7% of instances). The 2 most frequently reported causes were catheter trauma (in 54% of cases) and balloon inflation (in 23.8%). The overall mortality rate was 7.1%. We …

Binomial Regression With A Misclassified Covariate And Outcome, Sheng Luo, Wenyaw Chan, Michelle A Detry, Paul J Massman, R S. Doody

Faculty, Staff and Students Publications

Misclassification occurring in either outcome variables or categorical covariates or both is a common issue in medical science. It leads to biased results and distorted disease-exposure relationships. Moreover, it is often of clinical interest to obtain the estimates of sensitivity and specificity of some diagnostic methods even when neither gold standard nor prior knowledge about the parameters exists. We present a novel Bayesian approach in binomial regression when both the outcome variable and one binary covariate are subject to misclassification. Extensive simulation results under various scenarios and a real clinical example are given to illustrate the proposed approach. This approach …

Predator Diet And Trophic Position Modified With Altered Habitat Morphology, Alexander Tewfik, Susan S. Bell, Kevin S. Mccann, Kristina Morrow

Integrative Biology Faculty and Staff Publications

Empirical patterns that emerge from an examination of food webs over gradients of environmental variation can help to predict the implications of anthropogenic disturbance on ecosystems. This “dynamic food web approach” is rarely applied at the coastal margin where aquatic and terrestrial systems are coupled and human development activities are often concentrated. We propose a simple model of ghost crab (Ocypode quadrata) feeding that predicts changing dominant prey (Emerita talpoida, Talorchestia sp., Donax variablis) along a gradient of beach morphology and test this model using a suite of 16 beaches along the Florida, USA coast. …

Diagnostic Value Of End Tidal Capnography In Patients With Hyperglycemia In The Emergency Department., Ralphe Bou Chebl, Bryan Madden, Justin Belsky, Elie Harmouche, Lenar Yessayan

Emergency Medicine Articles

BACKGROUND: Diabetic Ketoacidosis (DKA) is a potentially life-threatening emergency that requires prompt diagnosis and treatment. In paediatric populations an end tidal capnography value greater than 36 mmHg was found to be 100 % sensitive in ruling out DKA.

METHODS: A cross sectional observational study of adults ≥ 17 years of age presenting to the emergency department between January 2014 and May 2014 with glucose > 550 mg/dL. In all patients, nasal capnography and venous blood gas analysis were performed prior to any insulin or intravenous fluid administration. The diagnosis of DKA was based on the presence of anion gap metabolic acidosis, …

Assessing The Twinning Model In The Rwandan Human Resources For Health Program: Goal Setting, Satisfaction And Perceived Skill Transfer, Esperance Ndenga, Glorieuse Uwizeye, Dana R. Thomson, Eric Uwitonze, Joel Mubiligi, Bethany L. Hedt-Gauthier, Michael Wilkes, Agnes Binagwaho

Dartmouth Scholarship

Because of the shortage of health professionals, particularly in specialty areas, Rwanda initiated the Human Resources for Health (HRH) Program. In this program, faculty from United States teaching institutions (USF) "twin" with Rwandan Faculty (RF) to transfer skills. This paper assesses the twinning model, exploring USF and RF goal setting, satisfaction and perceptions of the effectiveness of skill transfer within the twinning model.

Phase Of Spontaneous Slow Oscillations During Sleep Influences Memory-Related Processing Of Auditory Cues., Laura J Batterink, Jessica D Creery, Ken A Paller

Brain and Mind Institute Researchers' Publications

UNLABELLED: Slow oscillations during slow-wave sleep (SWS) may facilitate memory consolidation by regulating interactions between hippocampal and cortical networks. Slow oscillations appear as high-amplitude, synchronized EEG activity, corresponding to upstates of neuronal depolarization and downstates of hyperpolarization. Memory reactivations occur spontaneously during SWS, and can also be induced by presenting learning-related cues associated with a prior learning episode during sleep. This technique, targeted memory reactivation (TMR), selectively enhances memory consolidation. Given that memory reactivation is thought to occur preferentially during the slow-oscillation upstate, we hypothesized that TMR stimulation effects would depend on the phase of the slow oscillation. Participants learned …

Identification Of Novel Cyclic Lipopeptides From A Positional Scanning Combinatorial Library With Enhanced Antibacterial And Antibiofilm Activities, Nina Bionda, Renee M. Fleeman, César De La Fuente-Núñez, Maria C. Rodriguez, Fany Reffuveille, Lindsey N. Shaw, Irena Pastar, Stephen C Davis, Robert E W Hancock, Predrag Cudic

Molecular Biosciences Faculty Publications

Treating bacterial infections can be difficult due to innate or acquired resistance mechanisms, and the formation of biofilms. Cyclic lipopeptides derived from fusaricidin/LI-F natural products represent particularly attractive candidates for the development of new antibacterial and antibiofilm agents, with the potential to meet the challenge of bacterial resistance to antibiotics. A positional-scanning combinatorial approach was used to identify the amino acid residues responsible for driving antibacterial activity, and increase the potency of these cyclic lipopeptides. Screening against the antibiotic resistant ESKAPE pathogens revealed the importance of hydrophobic as well as positively charged amino acid residues for activity of this class …

Gender Representation In The Vision Sciences: A Longitudinal Study, Emily A. Cooper, Ana Radonjic

Dartmouth Scholarship

Understanding the current status and historical trends of gender representation within a research field is an important component of fostering a diverse and inclusive scientific community. Here, we report on the gender representation of a large sample of the vision science research community—the attendees of the Annual Meeting of the Vision Sciences Society (VSS). Our analysis shows that the majority of scientists at all career levels in our sample are male. This imbalance is most pronounced for the senior scientists, whereas predoctoral students are nearly balanced between the genders. Historically, the gender imbalance was larger than it is at present, …

Gap Junction Mediated Mirna Intercellular Transfer And Gene Regulation: A Novel Mechanism For Intercellular Genetic Communication, Liang Zong, Yan Zhu, Ruqiang Liang, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Intercellular genetic communication is an essential requirement for coordination of cell proliferation and differentiation and has an important role in many cellular processes. Gap junction channels possess large pore allowing passage of ions and small molecules between cells. MicroRNAs (miRNAs) are small regulatory RNAs that can regulate gene expression broadly. Here, we report that miRNAs can pass through gap junction channels in a connexin-dependent manner. Connexin43 (Cx43) had higher permeability, whereas Cx30 showed little permeability to miRNAs. In the tested connexin cell lines, the permeability to miRNAs demonstrated: Cx43 > Cx26/30 > Cx26 > Cx31 > Cx30 = Cx-null. However, consistent with a uniform …

Post-Prandial Glucose And Insulin Responses Of Hummus Alone Or Combined With A Carbohydrate Food: A Dose-Response Study, Livia S. Augustin, Laura Chiavaroli, Janice Campbell, Adish Ezatagha, Alexandra L. Jenkins, Amin Esfahani, Cyril Kendall

NYMC Faculty Publications

OBJECTIVES: Pulses are low glycemic index (GI) foods and have been associated with reduced risk of heart disease, diabetes and some cancers. However the blood glucose and insulin responses of hummus, a food containing chickpea, have not been thoroughly tested.

METHODS: Ten healthy subjects each consumed 11 breakfast study meals in randomized order over a period of 15 weeks. Hummus was consumed alone at three doses (2.7 g, 10.8 g and 25 g available carbohydrate [avCHO] portions) and with 50 g avCHO from white bread at three doses (2.7 g, 5.4 g and 10.8 g avCHO portions). The responses elicited …

Incidence And In-Hospital Mortality Of Acute Kidney Injury (Aki) And Dialysis Requiring Aki (Aki-D) After Cardiac Catheterization In The National Inpatient Sample, Jeremiah R. Brown, Michael E. Rezaee, Elizabeth L. Nichols, Emily J. Marshall, Edward D. Siew, Michael E. Matheny

Dartmouth Scholarship

Background:

Acute kidney injury (AKI) and dialysis‐requiring AKI (AKI‐D) are common, serious complications of cardiac procedures.

Methods and Results:

We evaluated 3 633 762 (17 765 214 weighted population) cardiac catheterization or percutaneous coronary intervention (PCI) hospital discharges from the nationally representative National Inpatient Sample to determine annual population incidence rates for AKI and AKI‐D in the United States from 2001 to 2011. Odds ratios for both conditions and associated in‐hospital mortality were calculated for each year in the study period using multiple logistic regression. The number of cardiac catheterization or PCI cases resulting in AKI rose almost 3‐fold from …

Association Of Dna Methylation At Cpt1a Locus With Metabolic Syndrome In The Genetics Of Lipid Lowering Drugs And Diet Network (Goldn) Study, Mithun Das, Jin Sha, Bertha Hidalgo, Stella Aslibekyan, Anh N. Do, Degui Zhi, Dianjianyi Sun, Tao Zhang, Shengxu Li, Wei Chen, Sathanur R. Srinivasan, Hemant K. Tiwari, Devin Absher, Jose M. Ordovas, Gerald S. Berenson, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10⁻⁷ was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = …

Ceramide Induces Human Hepcidin Gene Transcription Through Jak/Stat3 Pathway., Sizhao Lu, Sathish Kumar Natarajan, Justin L. Mott, Kusum K. Kharbanda, Duygu Dee Harrison-Findik

Journal Articles: Biochemistry & Molecular Biology

Changes in lipid metabolism and iron content are observed in the livers of patients with fatty liver disease. The expression of hepcidin, an iron-regulatory and acute phase protein synthesized by the liver, is also modulated. The potential interaction of lipid and iron metabolism is largely unknown. We investigated the role of lipid intermediate, ceramide in the regulation of human hepcidin gene, HAMP. Human hepatoma HepG2 cells were treated with cell-permeable ceramide analogs. Ceramide induced significant up-regulation of HAMP mRNA expression in HepG2 cells. The effect of ceramide on HAMP expression was mediated through transcriptional mechanisms because it was completely blocked …

Ceramide Induces Human Hepcidin Gene Transcription Through Jak/Stat3 Pathway., Sizhao Lu, Sathish Kumar Natarajan, Justin L. Mott, Kusum K. Kharbanda, Duygu Dee Harrison-Findik

Journal Articles: Biochemistry & Molecular Biology

Changes in lipid metabolism and iron content are observed in the livers of patients with fatty liver disease. The expression of hepcidin, an iron-regulatory and acute phase protein synthesized by the liver, is also modulated. The potential interaction of lipid and iron metabolism is largely unknown. We investigated the role of lipid intermediate, ceramide in the regulation of human hepcidin gene, HAMP. Human hepatoma HepG2 cells were treated with cell-permeable ceramide analogs. Ceramide induced significant up-regulation of HAMP mRNA expression in HepG2 cells. The effect of ceramide on HAMP expression was mediated through transcriptional mechanisms because it was completely blocked …

The Relationship Between Foot Arch Measurements And Walking Parameters In Children, Simone V. Gill, Sara Keimig, Damian Kelty-Stephen, Ya-Ching Hung, Jeremy M. Desilva

Dartmouth Scholarship

Walking mechanics are influenced by body morphology. Foot arch height is one aspect of body morphology central to walking. However, generalizations about the relationship between arch height and walking are limited due to previous methodologies used for measuring the arch and the populations that have been studied. To gain the knowledge needed to support healthy gait in children and adults, we need to understand this relationship in unimpaired, typically developing children and adults using dynamic measures. The purpose of the current study was to examine the relationship between arch height and gait in a sample of healthy children and adults …

Ehugs: Enhanced Hierarchical Unbiased Graph Shrinkage For Efficient Groupwise Registration, Guorong Wu, Xuewei Peng, Shihui Ying, Qian Wang, Pew-Thian Yap, Dan Shen, Dinggang Shen

Mathematics and Statistics Faculty Publications

Effective and efficient spatial normalization of a large population of brain images is critical for many clinical and research studies, but it is technically very challenging. A commonly used approach is to choose a certain image as the template and then align all other images in the population to this template by applying pairwise registration. To avoid the potential bias induced by the inappropriate template selection, groupwise registration methods have been proposed to simultaneously register all images to a latent common space. However, current groupwise registration methods do not make full use of image distribution information for more accurate registration. …

Lung Cancer Risk Test Trial: Study Design, Participant Baseline Characteristics, Bronchoscopy Safety, And Establishment Of A Biospecimen Repository, E. L. Crawford, Albert M. Levin, F. Safi, Mei Lu, A. Baugh, X. Zhang, J. Yeo, S. A. Khuder, A. M. Boulos, P. Nana-Sinkam, P. P. Massion, D. A. Arenberg, D. Midthun, P. J. Mazzone, S. D. Nathan, R. Wainz, G. Silvestri, J. Tita, J. C. Willey

Public Health Sciences Articles

BACKGROUND: The Lung Cancer Risk Test (LCRT) trial is a prospective cohort study comparing lung cancer incidence among persons with a positive or negative value for the LCRT, a 15 gene test measured in normal bronchial epithelial cells (NBEC). The purpose of this article is to describe the study design, primary endpoint, and safety; baseline characteristics of enrolled individuals; and establishment of a bio-specimen repository.

METHODS/DESIGN: Eligible participants were aged 50-90 years, current or former smokers with 20 pack-years or more cigarette smoking history, free of lung cancer, and willing to undergo bronchoscopic brush biopsy for NBEC sample collection. NBEC, …

Imaging Tumour Cell Heterogeneity Following Cell Transplantation Into Optically Clear Immune-Deficient Zebrafish, Qin Tang, John C. Moore, Myron S. Ignatius, Inês M. Tenente, Madeline N. Hayes, Elaine G. Garcia, Nora Torres Yordán, Caitlin Bourque, Shuning He, Jessica S. Blackburn, A. Thomas Look, Yariv Houvras, David M. Langenau

Molecular and Cellular Biochemistry Faculty Publications

Cancers contain a wide diversity of cell types that are defined by differentiation states, genetic mutations and altered epigenetic programmes that impart functional diversity to individual cells. Elevated tumour cell heterogeneity is linked with progression, therapy resistance and relapse. Yet, imaging of tumour cell heterogeneity and the hallmarks of cancer has been a technical and biological challenge. Here we develop optically clear immune-compromised rag2^E450fs (casper) zebrafish for optimized cell transplantation and direct visualization of fluorescently labelled cancer cells at single-cell resolution. Tumour engraftment permits dynamic imaging of neovascularization, niche partitioning of tumour-propagating cells in embryonal rhabdomyosarcoma, emergence of clonal …

Mir494 Reduces Renal Cancer Cell Survival Coinciding With Increased Lipid Droplets And Mitochondrial Changes, Punashi Dutta, Edward Haller, Arielle Sharp, Meera Nanjundan

Molecular Biosciences Faculty Publications

Background: miRNAs can regulate cellular survival in various cancer cell types. Recent evidence implicates the formation of lipid droplets as a hallmark event during apoptotic cell death response. It is presently unknown whether MIR494, located at 14q32 which is deleted in renal cancers, reduces cell survival in renal cancer cells and if this process is accompanied by changes in the number of lipid droplets.

Methods: 769-P renal carcinoma cells were utilized for this study. Control or MIR494 mimic was expressed in these cells following which cell viability (via crystal violet) and apoptotic cell numbers (via Annexin V/PI staining) were …

H2ax Deficiency Is Associated With Erythroid Dysplasia And Compromised Haematopoietic Stem Cell Function, Baobing Zhao, Timothy L. Tan, Yang Mei, Jing Yang, Yiting Yu, Amit Verma, Ying Liang, Juehua Gao, Peng Ji

Toxicology and Cancer Biology Faculty Publications

Myelodysplastic syndromes (MDS) are clonal disorders of haematopoiesis characterised by dysplastic changes of major myeloid cell lines. However, the mechanisms underlying these dysplastic changes are poorly understood. Here, we used a genetically modified mouse model and human patient data to examine the physiological roles of H2AX in haematopoiesis and how the loss of H2AX contributes to dyserythropoiesis in MDS. H2AX knockout mice showed cell-autonomous anaemia and erythroid dysplasia, mimicking dyserythropoiesis in MDS. Also, dyserythropoiesis was increased in MDS patients with the deletion of chromosome 11q23, where H2AX is located. Although loss of H2AX did not affect the early stage of …