Medical Sciences Commons^™

Efficacy Of Female Rat Models In Translational Cardiovascular Aging Research, Kevin M. Rice, J. C. Fannin, C. Gillette, Eric Blough

Pharmaceutical Science and Research

Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. …

Classification Of Current Anticancer Immunotherapies., Lorenzo Galluzzi, Erika Vacchelli, José-Manuel Bravo-San Pedro, Aitziber Buqué, Laura Senovilla, Elisa Elena Baracco, Norma Bloy, Francesca Castoldi, Jean-Pierre Abastado, Patrizia Agostinis, Ron N. Apte, Fernando Aranda, Maha Ayyoub, Philipp Beckhove, Jean-Yves Blay, Laura Bracci, Anne Caignard, Chiara Castelli, Federica Cavallo, Estaban Celis, Vincenzo Cerundolo, Aled Clayton, Mario P. Colombo, Lisa Coussens, Madhav V. Dhodapkar, Alexander M. Eggermont, Douglas T. Fearon, Wolf H. Fridman, Jitka Fučíková, Dmitry I. Gabrilovich, Jérôme Galon, Abhishek Garg, François Ghiringhelli, Giuseppe Giaccone, Eli Gilboa, Sacha Gnjatic, Axel Hoos, Anne Hosmalin, Dirk Jäger, Pawel Kalinski, Klas Kärre, Oliver Kepp, Rolf Kiessling, John M. Kirkwood, Eva Klein, Alexander Knuth, Claire E. Lewis, Roland Liblau, Michael T. Lotze, Enrico Lugli, Jean-Pierre Mach, Fabrizio Mattei, Domenico Mavilio, Ignacio Melero, Cornelis J. Melief, Elizabeth A. Mittendorf, Lorenzo Moretta, Adekunke Odunsi, Hideho Okada, Anna Karolina Palucka, Marcus E. Peter, Kenneth J. Pienta, Angel Porgador, George C. Prendergast, Gabriel A. Rabinovich, Nicholas P. Restifo, Naiyer Rizvi, Catherine Sautès-Fridman, Hans Schreiber, Barbara Seliger, Hiroshi Shiku, Bruno Silva-Santos, Mark J. Smyth, Daniel E. Speiser, Radek Spisek, Pramod K. Srivastava, James E. Talmadge, Eric Tartour, Sjoerd H. Van Der Burg, Benoît J. Van Den Eynde, Richard Vile, Hermann Wagner, Jeffrey S. Weber, Theresa L. Whiteside, Jedd D. Wolchok, Laurence Zitvogel, Weiping Zou, Guido Kroemer

Journal Articles: Pathology and Microbiology

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification …

Cd151-Α3Β1 Integrin Complexes Suppress Ovarian Tumor Growth By Repressing Slug-Mediated Emt And Canonical Wnt Signaling, Lauren A. Baldwin, John T. Hoff, Jason Lefringhouse, Michael Zhang, Changhe Jia, Zeyi Liu, Sonia Erfani, Hongyan Jin, Mei Xu, Qing-Bai She, John R. Van Nagell Jr., Chi Wang, Li Chen, Rina Plattner, David M. Kaetzel, Jia Luo, Michael Lu, Dava West, Chunming Liu, Fred R. Ueland, Ronny Drapkin, Binhua P. Zhou, Xiuwei H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-α3β1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or α3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by …

Mcp-1 In Colorectal Cancer: Benefits Of Exercise, Jamie Lee Mcclellan

Theses and Dissertations

The etiology of colon cancer is a complex phenomenon that involves both genetic and environmental factors. However, only about 20% have a familial basis with the largest fraction being attributed to environmental causes that can lead to chronic inflammation. Tumors associated macrophages drive the pro-inflammatory response in the tumor micro-environment and are associated with poor prognosis in certain cancers. Monocyte chemoattractant protein 1 (MCP-1) is thought to be the most important chemokine for recruitment of macrophages to the tumor microenvironment. In chapter 1, we examined the timing and magnitude of the intestinal inflammatory cytokine response in relation to tumorigenesis in …

Marine Population Connectivity: Range Boundaries And Climate Change, Rhiannon Leigh Rognstad

Theses and Dissertations

Population connectivity, particularly in open systems, is an important metric for understanding population-level processes on both ecological and evolutionary timescales. In coastal marine systems, adults are typically sedentary and dispersal occurs primarily during a larval stage when individuals are transported in ocean currents. Because coastal marine populations exist as networks of interconnected subpopulations, variation in the magnitude and extent of population connectivity can have profound effects on population dynamics and species distribution limits. Connectivity is a complex process, affected by a multitude of factors, including adult inputs and physical dispersal, which operate at multiple scales and may interact. This dissertation …

Registration Of In-Vivo To Ex-Vivo Mri Of Surgically Resected Specimens: A Pipeline For Histology To In-Vivo Registration., Maged Goubran, Sandrine De Ribaupierre, Robert R Hammond, Catherine Currie, Jorge G Burneo, Andrew G Parrent, Terry M Peters, Ali R Khan

Medical Biophysics Publications

BACKGROUND: Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to develop and evaluate a protocol for deformable image registration of in-vivo to ex-vivo resected brain specimen MRI. This protocol, in conjunction with our previous work on ex-vivo to histology registration, completes a registration pipeline for histology to in-vivo MRI, enabling voxel-based validation of novel and existing MRI techniques with histopathology.

NEW METHOD: A combination of image-based and landmark-based 3D …

Loss Of Thiol Repair Systems In Human Cataractous Lenses, Min Wei, Kui-Yi Xing, Yin-Chuan Fan, Teodosio Libondi, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. The purpose of this study was to investigate the thiol repair systems of thioltransferase (TTase) and thioredoxin (Trx) and oxidation-damaged proteins in human cataractous lenses.

METHODS. Cataractous lenses in humans (57–85 years of age) were classified into cortical, nuclear, mixed, mature, and hypermature cataract types by using a lens opacity classification system, and were obtained by extracapsular cataract extraction (ECCE) procedure. Cortical and nuclear cataracts were grouped by decreasing order of visual acuity into optical chart reading (R), counting fingers (CF), hand motion (HM), and light perception (LP). ECCE lens homogenate was analyzed for glutathione (GSH) level and enzyme …

Oligomerization, Conformational Stability And Thermal Unfolding Of Harpin, Hrpzpss And Its Hypersensitive Response-Inducing C-Terminal Fragment, C-214-Hrpzpss., Pradip K Tarafdar, Lakshmi Vasudev Vedantam, Rajeshwer S Sankhala, Pallinti Purushotham, Appa Rao Podile, Musti J Swamy

Department of Biochemistry and Molecular Biology Faculty Papers

HrpZ-a harpin from Pseudomonas syringae-is a highly thermostable protein that exhibits multifunctional abilities e.g., it elicits hypersensitive response (HR), enhances plant growth, acts as a virulence factor, and forms pores in plant plasma membranes as well as artificial membranes. However, the molecular mechanism of its biological activity and high thermal stability remained poorly understood. HR inducing abilities of non-overlapping short deletion mutants of harpins put further constraints on the ability to establish structure-activity relationships. We characterized HrpZPss from Pseudomonas syringae pv. syringae and its HR inducing C-terminal fragment with 214 amino acids (C-214-HrpZPss) using calorimetric, spectroscopic and microscopic approaches. Both …

P53 And Cancer-Associated Sialylated Glygans Are Surrogate Markers Of Cancerization Of The Bladder Associated With Schistosoma Haematobium Infection, Julio Santos, Elisabete Fernandes, Jose Alexandre Ferreira, Luis Lima, Ana Tavares, Andreia Peixoto, Beatriz Parreira, Jose Manuel Correia Da Costa, Paul J. Brindley, Carlos Lopes, Lucio L. Santos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers.

Methodology/Principal Findings

Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder …

Expression Of Suppressor Of Cytokine Signaling 1 (Socs1) Impairs Viral Clearance And Exacerbates Lung Injury During Influenza Infection., Keer Sun, Sharon Salmon, Vijaya Kumar Yajjala, Christopher Bauer, Dennis W. Metzger

Journal Articles: Pathology and Microbiology

Suppressor of cytokine signaling (SOCS) proteins are inducible feedback inhibitors of cytokine signaling. SOCS1-/- mice die within three weeks postnatally due to IFN-γ-induced hyperinflammation. Since it is well established that IFN-γ is dispensable for protection against influenza infection, we generated SOCS1-/-IFN-γ-/- mice to determine whether SOCS1 regulates antiviral immunity in vivo. Here we show that SOCS1-/-IFN-γ-/- mice exhibited significantly enhanced resistance to influenza infection, as evidenced by improved viral clearance, attenuated acute lung damage, and consequently increased survival rates compared to either IFN-γ-/- or WT animals. Enhanced viral clearance in SOCS1-/-IFN-γ-/- mice coincided with a rapid onset of adaptive immune …

Functional Lung Avoidance For Individualized Radiotherapy (Flair): Study Protocol For A Randomized, Double-Blind Clinical Trial., Douglas A Hoover, Dante Pi Capaldi, Khadija Sheikh, David A Palma, George B Rodrigues, A Rashid Dar, Edward Yu, Brian Dingle, Mark Landis, Walter Kocha, Michael Sanatani, Mark Vincent, Jawaid Younus, Sara Kuruvilla, Stewart Gaede, Grace Parraga, Brian P Yaremko

Medical Biophysics Publications

BACKGROUND: Although radiotherapy is a key component of curative-intent treatment for locally advanced, unresectable non-small cell lung cancer (NSCLC), it can be associated with substantial pulmonary toxicity in some patients. Current radiotherapy planning techniques aim to minimize the radiation dose to the lungs, without accounting for regional variations in lung function. Many patients, particularly smokers, can have substantial regional differences in pulmonary ventilation patterns, and it has been hypothesized that preferential avoidance of functional lung during radiotherapy may reduce toxicity. Although several investigators have shown that functional lung can be identified using advanced imaging techniques and/or demonstrated the feasibility and …

Ifn-Γ Causes Aplastic Anemia By Altering Hematopoietic Stem/Progenitor Cell Composition And Disrupting Lineage Differentiation, Fan Ching Lin, Megan Karwan, Bahara Saleh, Deborah L. Hodge, Tim Chan, Kimberly C. Boelte, Jonathan R. Keller, Howard A. Young

United States Public Health Resources

Aplastic anemia (AA) is characterized by hypocellular marrow and peripheral pancytopenia. Because interferon gamma (IFN-γ) can be detected in peripheral blood mononuclear cells of AA patients, it has been hypothesized that autoreactive T lymphocytes may be involved in destroying the hematopoietic stem cells. We have observed AA-like symptoms in our IFN-γ adenylate-uridylate-rich element (ARE)-deleted (del) mice, which constitutively express a low level of IFN-γ under normal physiologic conditions. Because no T-cell autoimmunity was observed, we hypothesized that IFN-γ may be directly involved in the pathophysiology of AA. In these mice, we did not detect infiltration of T cells in bone …

A Critical Analysis Of Infant Mortality In Kalamazoo County, Audrey Jensen

Honors Theses

The following is a review of the state of infant and fetal health in Kalamazoo County in the 21st century. Since infant health is a marker for the effectiveness of health care, this review will analyze the leading causes of infant mortality in Kalamazoo County. Statistical indicators show that Kalamazoo County falls below both state and national IMR averages. The leading causes of infant mortality in Kalamazoo are considered preventable infant deaths. Therefore, this review will make recommendations for the reduction of IMR through the improvement of preventative prenatal healthcare practices.

Engineered Plga Nanoparticles For Delivery Of Sirna In Mcf-7 Breast Cancer Cells, Sydney Pong, Samit Shah, Vivek Gupta

Student Scholar Symposium Abstracts and Posters

Small interfering RNAs have been an emerging medical treatment for molecular based diseases as they are capable of gene-specific knockdown. Appropriate and efficient delivery remains one of the biggest challenges in the development of siRNA as an anti-cancer treatment. Nanoparticles containing siRNA were characterized and the efficacy of various peptides in the transfection of the nanoparticles were tested. A gene silencing assay was developed in order to determine the effect of siRNA therapeutics on gene functionality in breast cancer cells.

The Effect Of Chronic Sleep Deprivation On Tumor Necrosis Factor Alpha And Bone Health In Peri-Menopausal Rats, Megan Robertson, Derek Booth, Erin Wainwright, Cody Arbuckle, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis is a common syndrome in the United States. The cessation of estrogen signaling coupled with the production of pro-inflammatory cytokines from sleep deprivation leads to an even greater risk of post-menopausal osteoporosis by creating an imbalance between osteoblasts and osteoclasts. With estrogen no longer present to regulate the concentration of osteoclasts and pro-inflammatory cytokines increasing production of osteoclasts, bone is degraded at a faster rate than it is formed. One of the most common treatments for osteoporosis is Zolendronate (a nitrogenous bisphosphonate), which decreases the number of osteoclasts in bone. This preliminary study looked at the effects on …

Accommodating Hyperaroused Information Processing In Persons At Risk For Alcoholism, Kellianne Clark, Jaclyn Cutler

Student Scholar Symposium Abstracts and Posters

In the search for the factors related to the heightened alcoholism risk in adult children of alcoholics (ACOA), it has been reported that these persons possess a high incidence of attention deficit disorders (ADD) as determined by clinical assessment instruments. However, investigations of alcoholism risk and ADD indicate that, in contrast to the hypoarousal model of ADD, the ACOA’s attention problems represent hyperarousal of attention mechanisms resulting in reduced ability to select and encode relevant information. If true, then unlike persons with ADD, clinical and cognitive assessments of ACOAs would benefit if the ACOA was provided with more time to …

Effect Of Dual Tasking On Walking Over Even And Uneven Surfaces In Functionally Independent Community Older Adults, Olajide L. Kolawole

Seton Hall University Dissertations and Theses (ETDs)

While several studies have reported a decrement in performance by older adults while walking and concurrently performing a dual task on even surfaces, to date the effects of dual tasking while walking on uneven surfaces commonly found in the community has received less attention. Thus, we sought to test the hypothesis that an incremental decrement in gait parameters will be observed, when walking on an uneven versus an even surface and furthermore, that this decrement would be dependent upon the concurrent performance of a secondary cognitive and/or motor task in functionally independent-living-community older adults.

Dynamic Gait Index assessed the subject’s …

A Randomized Noninferiority Trial Of Condensed Protocols For Genetic Risk Disclosure Of Alzheimer's Disease, Peter J. Whitehouse, Melissa Barber Butson

Faculty Scholarship

Introduction Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD. Methods A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared with condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Preplanned co-primary outcomes were anxiety and depression scales …

One Year Review Of High Flow Oxygen Delivery System Outcomes, Susan Carvin Rrt-Accs, Kenneth Miller Med, Rrt-Nps, Diane Horoski, Robert Leshko Bs,Rrt, Rita Pechulis Md, Fccp

Patient Care Services / Nursing

No abstract provided.

Free-Breathing Pulmonary (1)H And Hyperpolarized (3)He Mri: Comparison In Copd And Bronchiectasis., Dante P I Capaldi, Khadija Sheikh, Fumin Guo, Sarah Svenningsen, Roya Etemad-Rezai, Harvey O Coxson, Jonathon A Leipsic, David G Mccormack, Grace Parraga

Medical Biophysics Publications

RATIONALE AND OBJECTIVES: In this proof-of-concept demonstration, we aimed to quantitatively and qualitatively compare pulmonary ventilation abnormalities derived from Fourier decomposition of free-breathing (1)H magnetic resonance imaging (FDMRI) to hyperpolarized (3)He MRI in subjects with chronic obstructive pulmonary disease (COPD) and bronchiectasis.

MATERIALS AND METHODS: All subjects provided written informed consent to a protocol approved by a local research ethics board and Health, Canada, and they underwent MRI, computed tomography (CT), spirometry, and plethysmography during a single 2-hour visit. Semiautomated segmentation was used to generate ventilation defect measurements derived from FDMRI and (3)He MRI, and these were compared using analysis …

Sensory Abnormalities In Focal Hand Dystonia And Non-Invasive Brain Stimulation, Angelo Quartarone, Vincenzo Rizzo, Carmen Terranova, Demetrio Milardi, Daniele Bruschetta, Maria Felice Ghilardi, Paolo Girlanda

Publications and Research

It has been proposed that synchronous and convergent afferent input arising from repetitive motor tasks may play an important role in driving the maladaptive cortical plasticity seen in focal hand dystonia (FHD).This hypothesis receives support from several sources. First, it has been reported that in subjects with FHD, paired associative stimulation produces an abnormal increase in corticospinal excitability, which was not confined to stimulated muscles. These findings provide support for the role of excessive plasticity in FHD. Second, the genetic contribution to the dystonias is increasingly recognized indicating that repetitive, stereotyped afferent inputs may lead to late-onset dystonia, such as …

Analysis Of Drug Interactions With Lipoproteins By High Performance Affinity Chromatography, Matthew R. Sobansky

Department of Chemistry: Dissertations, Theses, and Student Research

High density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) are lipoproteins previously shown to bind many basic and neutral hydrophobic drugs in serum. These interactions impact the distribution, delivery, metabolism, and excretion of drugs and are important in determining drug activity, pharmacokinetics, and toxicity in the human body. Information about drug-lipoprotein interactions and the strength of these interactions can be useful in determining the distribution of drugs following administration.

The research presented in this dissertation uses high performance affinity chromatography (HPAC) and packed columns to study binding of the drug propranolol to immobilized lipoproteins such …

A Critical Evaluation Of The Trigger Point Phenomenon, John L. Quintner, Geoffrey M. Bove, Milton L. Cohen

Biomedical Sciences Faculty Publications

The theory of myofascial pain syndrome (MPS) caused by trigger points (TrPs) seeks to explain the phenomena of muscle pain and tenderness in the absence of evidence for local nociception. Although it lacks external validity, many practitioners have uncritically accepted the diagnosis of MPS and its system of treatment. Furthermore, rheumatologists have implicated TrPs in the pathogenesis of chronic widespread pain (fibromyalgia syndrome). We have critically examined the evidence for the existence of myofascial TrPs as putative pathological entities and for the “vicious cycles that are said to maintain them. We find that both are inventions that have no scientific …

Longitudinal Quantitative Analysis Of Gait And Balance In Friedreich's Ataxia, Jeannie B. Stephenson

USF Tampa Graduate Theses and Dissertations

Friedreich's Ataxia (FA) is an autosomal-recessive, neurodegenerative disease characterized by progressive lower extremity muscle weakness and sensory loss, balance deficits, limb and gait ataxia, and dysarthria. FA is considered a sensory ataxia because the dorsal root ganglia and spinal cord dorsal columns are involved early in the disease, whereas the cerebellum is affected later. Balance deficits and gait ataxia are often evaluated clinically and in research using clinical rating scales. Recently, quantitative tools such as the Biodex Balance System SD and the GAITRite Walkway System have become available to objectively assess balance and gait, respectively. However, there are limited studies …

Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in …

E2f4 Regulatory Program Predicts Patient Survival Prognosis In Breast Cancer, Sari S. Khaleel, Erik H. Andrews, Matthew Ung, James Direnzo, Chao Chung

Dartmouth Scholarship

Genetic and molecular signatures have been incorporated into cancer prognosis prediction and treatment decisions with good success over the past decade. Clinically, these signatures are usually used in early-stage cancers to evaluate whether they require adjuvant therapy following surgical resection. A molecular signature that is prognostic across more clinical contexts would be a useful addition to current signatures. We defined a signature for the ubiquitous tissue factor, E2F4, based on its shared target genes in multiple tissues. These target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) experiments using a probabilistic method. We then computationally calculated the regulatory activity score …

Analysis Of Clock-Regulated Genes In Neurospora Reveals Widespread Posttranscriptional Control Of Metabolic Potential, Jennifer M. M. Hurley, Arko Dasgupta, Jillian M. Emerson, Xiaoying Zhou, Carol S. Ringelberg, Nicole Knabe

Dartmouth Scholarship

Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation-based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset …

Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang

Dartmouth Scholarship

Atherosclerotic plaque localization correlates with regions of disturbed flow in which endothelial cells (ECs) align poorly, whereas sustained laminar flow correlates with cell alignment in the direction of flow and resistance to atherosclerosis. We now report that in hypercholesterolemic mice, deletion of syndecan 4 (S4−/−) drastically increased atherosclerotic plaque burden with the appearance of plaque in normally resistant locations. Strikingly, ECs from the thoracic aortas of S4−/− mice were poorly aligned in the direction of the flow. Depletion of S4 in human umbilical vein endothelial cells (HUVECs) using shRNA also inhibited flow-induced alignment in vitro, which was rescued by re-expression …

Synthesis And Characterization Of Methacrylated Hyaluronan-Based Hydrogels For Tissue Engineering, Keegan Bradley Compton

Theses and Dissertations (ETD)

Polymers have revolutionized the field of tissue engineering due to the countless possibilities of scaffolds that can be constructed from such a material. Through conjugation of other functional groups onto a polymer backbone, the mechanical properties of polymers can be controlled and has the ability to span a wide range of strengths, allowing for application in multiple tissue environments. One such polymer, hyaluronic acid (HA), is a natural polysaccharide found most abundantly in the extracellular matrix (ECM) of connective tissues with structural, lubricating, and wound healing functions in the human body; for this reason, HA has great potential for utilization …

The Mirnaome Of Opisthorchis Viverrini Induced Intrahepatic Cholangiocarcinoma, Jin Peng, Yanjun Feng, Gabriel Rinaldi, Ponlapat Yonglitthipagon, Samantha Easley, Therawach Laha, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J. Brindley, Jason P. Mulvenna, Jeffrey M. Bethony, Jordan L. Plieskatt

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer, arising in the biliary ducts that extend into the liver. The highest incidence of ICC occurs in Southeast Asia, particularly in the Mekong River Basin countries of Thailand, Laos, Cambodia, and Vietnam, where it is strongly associated with chronic infection by the food-borne liver fluke Opisthorchis viverrini (OV), one of only three eukaryote pathogens considered Group one carcinogens. Intrahepatic cholangiocarcinoma is usually diagnosed at an advanced stage, with a poor prognosis and survival often less than 24 months. Hence, biomarkers that enable the early detection of ICC would be desirable and have a …