Anatomy Commons^™

Oncolytic Virotherapy Of Ovarian Cancer, Shoudong Li, Jessica Tong, Masmudur M. Rahman, Trevor G. Shepherd, Grant Mcfadden

Anatomy and Cell Biology Publications

In the past two decades, more than 20 viruses with selective tropism for tumor cells have been developed as oncolytic viruses (OVs) for treatments of a variety of malignancies. Of these viruses, eleven have been tested in human ovarian cancer models in preclinical studies. So far, nine phase I or II clinical trials have been conducted or initiated using four different types of OVs in patients with recurrent ovarian cancers. In this article, we summarize the different OVs that are being assessed as therapeutics for ovarian cancer. We also present an overview of recent advances in identification of key genetic …

Coronary Artery Remodeling In A Model Of Left Ventricular Pressure Overload Is Influenced By Platelets And Inflammatory Cells, Fanmuyi Yang, Anping Dong, Paul Mueller, Jessica Caicedo, Alyssa Moore Sutton, Juliana Odetunde, Cordelia J. Barrick, Yuri M. Klyachkin, Ahmed Abdel-Latif, Susan S. Smyth

Internal Medicine Faculty Publications

Left ventricular hypertrophy (LVH) is usually accompanied by intensive interstitial and perivascular fibrosis, which may contribute to arrhythmogenic sudden cardiac death. The mechanisms underlying the development of cardiac fibrosis are incompletely understood. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of LVH (transverse aortic constriction [TAC]). Three days after pressure overload, macrophages and T lymphocytes accumulated around and along left coronary arteries in association with luminal platelet deposition. Consistent with these histological findings, cardiac expression of IL-10 was upregulated and in the systemic circulation, …

Palmitoylation Regulates Intracellular Trafficking Of Β2 Adrenergic Receptor/Arrestin/Phosphodiesterase 4d Complexes In Cardiomyocytes, Ruijie Liu, Dayong Wang, Qian Shi, Qin Fu, Steven Hizon, Yang K. Xiang

Peer Reviewed Articles

β₂ adrenergic receptor (β₂AR) is a prototypical G-protein coupled receptor that stimulates the classic cAMP-protein kinase A (PKA) signaling pathway. Recent studies indicate that the cAMP-PKA activities are spatiotemporally regulated in part due to dynamic association of β₂AR with phosphodiesterase 4D (PDE4D), a group of cAMP degradation enzymes. Here, we demonstrate that in cardiomyocytes, palmitoylation of β₂AR, the covalent acylation of cysteine residue 341, plays a critical role in shaping subcellular cAMP-PKA activities in cardiomyocytes via regulating β₂AR association with arrestin/PDE4D. Replacing cysteine 341 on β₂AR with alanine (C341A) …

Coronary Heart Disease In Primary Care: Accuracy Of Medical History And Physical Findings In Patients With Chest Pain – A Study Protocol For A Systematic Review With Individual Patient Data, Jörg Haasenritter, Marc Aerts, Stefan Bösner, Frank Buntinx, Bernard Burnand, Lilli Herzig, J André Knottnerus, Girma Minalu, Staffan Nilsson, Walter Renier, Carol Sox, Carol Sox, Harold Sox, Norbert Donner-Banzhoff

Dartmouth Scholarship

Chest pain is a common complaint in primary care, with coronary heart disease (CHD) being the most concerning of many potential causes. Systematic reviews on the sensitivity and specificity of symptoms and signs summarize the evidence about which of them are most useful in making a diagnosis. Previous meta-analyses are dominated by studies of patients referred to specialists. Moreover, as the analysis is typically based on study-level data, the statistical analyses in these reviews are limited while meta-analyses based on individual patient data can provide additional information. Our patient-level meta-analysis has three unique aims. First, we strive to determine the …

The Neural Substrates Of Complex Argument Structure Representations: Processing “Alternating Transitivity” Verbs, Aya Meltzer-Asscher, Julia Schuchard, Dirk B. Den Ouden, Cynthia K. Thompson

Communication Sciences and Disorders Faculty Articles and Research

This study examines the neural correlates of processing verbal entries with multiple argument structures using functional magnetic resonance imaging (fMRI). We compared brain activation in response to “alternating transitivity” verbs, corresponding to two different verbal alternates—one transitive and one intransitive—and simple verbs, with only one, intransitive, thematic grid. Fourteen young healthy participants performed a lexical decision task with the two verb types. Results showed significantly greater activation in the angular and supramarginal gyri (Brodmann areas (BAs) 39 and 40) extending to the posterior superior and middle temporal gyri bilaterally, for alternating compared to simple verbs. Additional activation was detected in …

Sleep Hygiene And Problem Behaviors In Snoring And Non- Snoring School-Age Children, Lisa A. Witcher, David Gozal, Dennis L. Molfese, Scott M. Salathe, Karen Spruyt, Valerie Mclaughlin Crabtree

Center for Brain, Biology, and Behavior: Faculty Publications

Objectives—The effects of sleep-disordered breathing, sleep restriction, dyssomnias, and parasomnias on daytime behavior in children have been previously assessed. However, the potential relationship(s) between sleep hygiene and children’s daytime behavior remain to be explored. The primary goal of this study was to investigate the relationship between sleep hygiene and problematic behaviors in non-snoring and habitually snoring children.

Methods—Parents of 100 5- to 8-year-old children who were reported to snore “frequently” to “almost always,” and of 71 age-, gender-, and ethnicity-matched children who were reported to never snore participated in this study. As part of a larger, ongoing study, …

Effects Of Head Position And Head-Supported Mass On Nerve Function Of The Flexor Carpi Radialis Muscle In Healthy Individuals, Bethany Lauren Shivers

Graduate Theses and Dissertations

Long-term exposure to head-supported mass (HSM) has been linked with spinal degeneration including foraminal stenosis and disc deterioration. Anecdotally, HSM has also been linked to neck and arm pain and muscle atrophy, but nerve function has not been tested specifically. The combined effect of various head positions and HSM may be sufficient to compress the nerve root in aviators and Soldiers during job performance, potentially leading to short- and long-term neuromuscular effects. The Hoffmann (H) reflex, a well-established measure of nerve function, has shown to be sensitive to changes in nerve root space which occurs with different head positions. This …

Expression And Distribution Of Thiol-Regulating Enzyme, Glutaredoxin 2 In Porcine Ocular Tissues, Bijaya Prasad Upadhyaya

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Glutaredoxin 2 (Grx2), a thiol-regulating enzyme of oxidoreductase family and a mitochondrial isozyme of glutaredoxin 1, was discovered 11 years ago in our laboratory. Grx2 is present in the lens where it shows dethiolase, peroxidase, and ascorbate recycling activities. Recently, Grx2 has also been identified to protect the mitochondrial electron transport system with anti-apoptotic function. Since other eye tissues besides the lens are rich in mitochondria and are very sensitive to oxidative stress, we speculate the presence of Grx2 therein as an important redox regulator. This study is to investigate the expression and distribution of Grx2 in ocular tissues using …

Angiogenesis In Response To Varying Fiber Size In An Electrospun Scaffold In Vivo., Damien Brown

Theses and Dissertations

Injury to the spinal cord results in partial or complete loss of sensory perception and motor function. After spinal cord injury (SCI), damaged tissue dies and a cavity will form. This cavity prevents the regeneration of tissue and any functional recovery. One way to address the cavity is the insertion of an electrospun scaffold that our lab has created. This provides a substrate for regenerating tissue to grow on, and it is thought that reestablishing the blood supply within the scaffold will allow cells necessary for regeneration to thrive. This could ultimately lead to meaningful recovery for patients who have …

Delayed Expression Of Cell Cycle Proteins Contributes To Astroglial Scar Formation And Chronic Inflammation After Rat Spinal Cord Contusion, Junfang Wu, Ahdeah Pajoohesh-Ganji, Bogdan A. Stoica, Michael Dinizo, Kelsey Guanciale, Alan I. Faden

Anatomy and Regenerative Biology Faculty Publications

Background

Traumatic spinal cord injury (SCI) induces secondary tissue damage that is associated with astrogliosis and inflammation. We previously reported that acute upregulation of a cluster of cell-cycle-related genes contributes to post-mitotic cell death and secondary damage after SCI. However, it remains unclear whether cell cycle activation continues more chronically and contributes to more delayed glial change. Here we examined expression of cell cycle-related proteins up to 4 months following SCI, as well as the effects of the selective cyclin-dependent kinase (CDKs) inhibitor CR8, on astrogliosis and microglial activation in a rat SCI contusion model.

Methods

Adult male rats were …

Alcohol Exposure Alters Mouse Lung Inflammation In Response To Inhaled Dust., Michael L. Mccaskill, Debra J. Romberger, Jane M. Devasure, Jessica Boten, Joseph H. Sisson, Kristina L. Bailey, Jill A. Poole, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs) are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE) collected from a CAFO results in the activation of protein kinase C (PKC), elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6), and the development of …

Intermediate-Term Mortality And Cardiac Transplantation In Infants With Single-Ventricle Lesions: Risk Factors And Their Interaction With Shunt Type., James S. Tweddell, Lynn A. Sleeper, Richard G. Ohye, Ismee A. Williams, Lynn Mahony, Christian Pizarro, Victoria L. Pemberton, Peter C. Frommelt, Scott M. Bradley, James F. Cnota, Jennifer Hirsch, Paul M. Kirshbom, Jennifer S. Li, Nancy Pike, Michael Puchalski, Chitra Ravishankar, Jeffrey P. Jacobs, Peter C. Laussen, Brian W. Mccrindle, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The study objective was to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that might favor the modified Blalock-Taussig shunt or a right ventricle-to-pulmonary artery shunt.

METHODS: We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors.

RESULTS: Data from 549 subjects (follow-up, 2.7 ± 0.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated …

An Analysis Of The Myocardial Transcriptome In A Mouse Model Of Cardiac Dysfunction With Decreased Cholinergic Neurotransmission, Ashbeel Roy, Aline Lara, Diogo Guimaraes, Rita Pires, Eneas R. Gomes, David E. Carter, Marcus V. Gomez, Silvia Guatimosim, Vania F. Prado, Marco A. M. Prado, Robert Gros

Anatomy and Cell Biology Publications

Autonomic dysfunction is observed in many cardiovascular diseases and contributes to cardiac remodeling and heart disease. We previously reported that a decrease in the expression levels of the vesicular acetylcholine transporter (VAChT) in genetically-modified homozygous mice (VAChT KDHOM) leads to decreased cholinergic tone, autonomic imbalance and a phenotype resembling cardiac dysfunction. In order to further understand the molecular changes resulting from chronic long-term decrease in parasympathetic tone, we undertook a transcriptome-based, microarray-driven approach to analyze gene expression changes in ventricular tissue from VAChT KDHOM mice. We demonstrate that a decrease in cholinergic tone is associated with alterations in gene expression …

Prevalence Of Streptococci And Increased Polymicrobial Diversity Associated With Cystic Fibrosis Patient Stability, L. M. Filkins, T. H. Hampton, A. H. Gifford, M. J. Gross, D. A. Hogan, M. L. Sogin, H. G. Morrison, B. J. Paster, G. A. O'Toole

Dartmouth Scholarship

Diverse microbial communities chronically colonize the lungs of cystic fibrosis patients. Pyrosequencing of amplicons for hypervariable regions in the 16S rRNA gene generated taxonomic profiles of bacterial communities for sputum genomic DNA samples from 22 patients during a state of clinical stability (outpatients) and 13 patients during acute exacerbation (inpatients). We employed quantitative PCR (qPCR) to confirm the detection of Pseudomonas aeruginosa and Streptococcus by the pyrosequencing data and human oral microbe identification microarray (HOMIM) analysis to determine the species of the streptococci identified by pyrosequencing. We show that outpatient sputum samples have significantly higher bacterial diversity than inpatients, but …

Mice Deficient In Gem Gtpase Show Abnormal Glucose Homeostasis Due To Defects In Beta-Cell Calcium Handling, Jenny E. Gunton, Mary Sisavanh, Rebecca A. Stokes, Jon Satin, Leslie S. Satin, Min Zhang, Sue M. Liu, Weikang Cai, Kim Cheng, Gregory J. Cooney, D. Ross Laybutt, Trina So, Juan-Carlos Molero, Shane T. Grey, Douglas A. Andres, Michael S. Rolph, Charles R. Mackay

Physiology Faculty Publications

AIMS AND HYPOTHESIS: Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.

METHODS: Gem-deficient mice were generated and their metabolic phenotype characterised by in …

Non-Typeable Haemophilus Influenzae Decreases Cilia Beating Via Protein Kinase Cε., Kristina L. Bailey, Tricia D. Levan, Daniel A. Yanov, Jacqueline A. Pavlik, Jane M. Devasure, Joseph H. Sisson, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Haemophilus influenzae infection of the nasal epithelium has long been associated with observations of decreased nasal ciliary beat frequency (CBF) and injury to the ciliated epithelium. Previously, we have reported that several agents that slow CBF also have the effect of activating protein kinase C epsilon (PKCε) activity in bronchial epithelial cells. The subsequent auto-downregulation of PKCε or the direct inhibition of PKCε leads to the specific detachment of the ciliated cells.

METHODS: Primary cultures of ciliated bovine bronchial epithelial cells were exposed to filtered conditioned media supernatants from non-typeable H. influenzae (NTHi) cultures. CBF and motile points were …

Composition Of The Adult Digestive Tract Bacterial Microbiome Based On Seven Mouth Surfaces, Tonsils, Throat And Stool Samples, Nicola Segata, Susan Kinder Haake, Peter Mannon, Katherine P. Lemon, Levi Waldron, Dirk Gevers, Curtis Huttenhower, Jacques Izard

Publications and Research

Background: To understand the relationship between our bacterial microbiome and health, it is essential to define the microbiome in the absence of disease. The digestive tract includes diverse habitats and hosts the human body’s greatest bacterial density. We describe the bacterial community composition of ten digestive tract sites from more than 200 normal adults enrolled in the Human Microbiome Project, and metagenomically determined metabolic potentials of four representative sites.

Results: The microbiota of these diverse habitats formed four groups based on similar community compositions: buccal mucosa, keratinized gingiva, hard palate; saliva, tongue, tonsils, throat; sub- and supra-gingival plaques; and stool. …

Endogenous Dynorphin Protects Against Neurotoxin-Elicited Nigrostriatal Dopaminergic Neuron Damage And Motor Deficits In Mice, Qingshan Wang, Eun-Joo Shin, Xuan-Khanh Thi Nguyen, Quan Li, Jae-Hyung Bach, Guoying Bing, Won-Ki Kim, Hyoung-Chun Kim, Jau-Shyong Hong

Neuroscience Faculty Publications

BACKGROUND: The striato-nigral projecting pathway contains the highest concentrations of dynorphin in the brain. The functional role of this opioid peptide in the regulation of mesencephalic dopaminergic (DAergic) neurons is not clear. We reported previously that exogenous dynorphin exerts potent neuroprotective effects against inflammation-induced dopaminergic neurodegeneration in vitro. The present study was performed to investigate whether endogenous dynorphin has neuroprotective roles in vivo.

METHODS: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (MA), two commonly used neurotoxins in rodent models of Parkinson's disease, were administered to wild-type (Dyn⁺/⁺) and prodynorphin-deficient mice (Dyn⁻/⁻). We examined dopaminergic neurotoxicity by using an automated video tracking system, HPLC, …

Melanoma Induction By Ultraviolet A But Not Ultraviolet B Radiation Requires Melanin Pigment, Frances P. Noonan, M. Raza Zaidi, Agnieszka Wolnicka-Glubisz, Miriam R. Anver, Jesse Bahn, Anastas Popratiloff, +9 Additional Authors

Anatomy and Regenerative Biology Faculty Publications

Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear. Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses. We show that melanoma induction by ultraviolet A (320–400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes. In contrast, ultraviolet B radiation (280–320 nm) initiates melanoma in a pigment-independent manner associated with direct ultraviolet B DNA damage. Thus, we identified two ultraviolet wavelength-dependent pathways for the induction of …

Muscle Contraction Duration And Fibre Recruitment Influence Blood Flow And Vo2 Independent Of Contractile Work During Steady-State Exercise In Humans, Jennifer C. Richards, Anne R. Crecelius, Brett S. Kirby, Dennis G. Larson, Frank A. Dinenno

Health and Sport Science Faculty Publications

We tested the hypothesis that, among conditions of matched contractile work, shorter contraction durations and greater muscle fibre recruitment result in augmented skeletal muscle blood flow and oxygen consumption (O2) during steady-state exercise in humans. To do so, we measured forearm blood flow (FBF; Doppler ultrasound) during 4 minutes of rhythmic handgrip exercise in 24 healthy young adults and calculated forearm O2 via blood samples obtained from a catheter placed in retrograde fashion into a deep vein draining the forearm muscle. In Protocol 1 (n = 11), subjects performed rhythmic isometric handgrip exercise at mild and moderate intensities under conditions …