Medical Specialties Commons^™

Tb Research At Ut-Houston – A Review Of Cord Factor: New Approaches To Drugs, Vaccines And The Pathogenesis Of Tuberculosis, Robert L Hunter, Lisa Armitige, Chinnaswamy Jagannath, Jeffrey K Actor

Faculty, Staff and Student Publications

Tuberculosis remains a major threat as drug resistance continues to increase. Pulmonary tuberculosis in adults is responsible for 80% of clinical cases and nearly 100% of transmission of infection. Unfortunately, since we have no animal models of adult type pulmonary tuberculosis, the most important type of disease remains largely out of reach of modern science and many fundamental questions remain unanswered. This paper reviews research dating back to the 1950's providing compelling evidence that cord factor (trehalose 6,6 dimycolate [TDM]) is essential for understanding tuberculosis. However, the original papers by Bloch and Noll were too far ahead of their time …

Biological Diversity Of Prokaryotic Type Iv Secretion Systems, Cristina E Alvarez-Martinez, Peter J Christie

Faculty, Staff and Student Publications

Type IV secretion systems (T4SS) translocate DNA and protein substrates across prokaryotic cell envelopes generally by a mechanism requiring direct contact with a target cell. Three types of T4SS have been described: (i) conjugation systems, operationally defined as machines that translocate DNA substrates intercellularly by a contact-dependent process; (ii) effector translocator systems, functioning to deliver proteins or other macromolecules to eukaryotic target cells; and (iii) DNA release/uptake systems, which translocate DNA to or from the extracellular milieu. Studies of a few paradigmatic systems, notably the conjugation systems of plasmids F, R388, RP4, and pKM101 and the Agrobacterium tumefaciens VirB/VirD4 system, …

Modulation Of Outer Hair Cell Electromotility By Cochlear Supporting Cells And Gap Junctions, Ning Yu, Hong-Bo Zhao

Surgery Faculty Publications

Outer hair cell (OHC) or prestin-based electromotility is an active cochlear amplifier in the mammalian inner ear that can increase hearing sensitivity and frequency selectivity. In situ, Deiters supporting cells are well-coupled by gap junctions and constrain OHCs standing on the basilar membrane. Here, we report that both electrical and mechanical stimulations in Deiters cells (DCs) can modulate OHC electromotility. There was no direct electrical conductance between the DCs and the OHCs. However, depolarization in DCs reduced OHC electromotility associated nonlinear capacitance (NLC) and distortion products. Increase in the turgor pressure of DCs also shifted OHC NLC to the negative …

Combination Of Vandetanib, Radiotherapy, And Irinotecan In The Lovo Human Colorectal Cancer Xenograft Model., Phyllis Wachsberger, Randy Burd, Anderson Ryan, Constantine Daskalakis, Adam P. Dicker

Department of Radiation Oncology Faculty Papers

PURPOSE: The tumor growth kinetics of the human LoVo colorectal xenograft model was assessed in response to vandetanib, an orally available receptor tyrosine kinase inhibitor, radiotherapy (RT), or irinotecan (CPT-11), as single therapies and in combination. METHODS AND MATERIALS: LoVo cells were injected subcutaneously into the right hind limb (5 x 10(6) cells in 100 microL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm(3) before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3 x 3 Gy) …

Adherence To Host Extracellular Matrix And Serum Components By Enterococcus Faecium Isolates Of Diverse Origin, Meng Zhao, Jouko Sillanpää, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecium has emerged as an important cause of nosocomial infections over the last two decades. We recently demonstrated collagen type I (CI) as a common adherence target for some E. faecium isolates and a significant correlation was found to exist between acm-mediated CI adherence and clinical origin. Here, we evaluated 60 diverse E. faecium isolates for their adherence to up to 15 immobilized host extracellular matrix and serum components. Adherence phenotypes were most commonly observed to fibronectin (Fn) (20% of the 60 isolates), fibrinogen (17%) and laminin (Ln) (13%), while only one or two of the isolates adhered to …

The Production Of Antibody By Invading B Cells Is Required For The Clearance Of Rabies Virus From The Central Nervous System., D Craig Hooper, Timothy W Phares, Marzena J Fabis, Anirban Roy

Department of Cancer Biology Faculty Papers

BACKGROUND: The pathogenesis of rabies is associated with the inability to deliver immune effectors across the blood-brain barrier and to clear virulent rabies virus from CNS tissues. However, the mechanisms that facilitate immune effector entry into CNS tissues are induced by infection with attenuated rabies virus.

METHODOLOGY/PRINCIPAL FINDINGS: Infection of normal mice with attenuated rabies virus but not immunization with killed virus can promote the clearance of pathogenic rabies virus from the CNS. T cell activity in B cell-deficient mice can control the replication of attenuated virus in the CNS, but viral mRNA persists. Low levels of passively administered rabies …

Effects Of Genistein Following Fractionated Lung Irradiation In Mice., Andrea E Para, Andrea Bezjak, Ivan W T Yeung, Jacob Van Dyk, Richard P Hill

Oncology Publications

BACKGROUND AND PURPOSE: This study investigated protection of lung injury by genistein following fractionated doses of radiation and its effect on tumor response.

MATERIAL AND METHODS: C3H/HeJ mice were irradiated (100 kVp X-rays) with 9 fractions of 3.1 Gy over 30 days (approximately equivalent to 10 Gy single dose) and were maintained on a genistein diet ( approximately 10mg/kg). Damage was assessed over 28 weeks in lung cells by a cytokinesis block micronucleus (MN) assay and by changes in breathing rate and histology. Tumor protection was assessed using a colony assay to determine cell survival following in situ irradiation of …

Human Amniotic Fluid Stem Cells Do Not Differentiate Into Dopamine Neurons In Vitro Or After Transplantation In Vivo., Angela E Donaldson, Jingli Cai, Ming Yang, Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

Although embryonic stem (ES) cells can generate dopamine (DA) neurons that are potentially useful as a cell replacement therapy in Parkinson's disease (PD), associated ethical and practical concerns remain major stumbling blocks to their eventual use in humans. In this study, we examined human amniotic fluid stem (hAFS) cells derived from routine amniocenteses for their potential to give rise to DA neurons in vitro and following transplantation into the 6-hydroxydopamine-lesioned rat brain. We show that undifferentiated hAFS cells constitutively expressed mRNAs and proteins typical of stem cells but also cell derivatives of all three germ layers, including neural progenitors/neurons (nestin, …

Advances In Progenitor Cell Therapy Using Scaffolding Constructs For Central Nervous System Injury, Peter A Walker, Kevin R Aroom, Fernando Jimenez, Shinil K Shah, Matthew T Harting, Brijesh S Gill, Charles S Cox

Faculty, Staff and Student Publications

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Current clinical therapy is focused on optimization of the acute/subacute intracerebral milieu, minimizing continued cell death, and subsequent intense rehabilitation to ameliorate the prolonged physical, cognitive, and psychosocial deficits that result from TBI. Adult progenitor (stem) cell therapies have shown promise in pre-clinical studies and remain a focus of intense scientific investigation. One of the fundamental challenges to successful translation of the large body of pre-clinical work is the delivery of progenitor cells to the target location/organ. Classically used vehicles such as intravenous and …

Calcium Homeostasis And Cone Signaling Are Regulated By Interactions Between Calcium Stores And Plasma Membrane Ion Channels., Tamas Szikra, Peter Barabas, Theodore M. Bartoletti, Wei Huang, Abram Akopian, Wallace B. Thoreson, David Krizaj

Journal Articles: Ophthalmology

Calcium is a messenger ion that controls all aspects of cone photoreceptor function, including synaptic release. The dynamic range of the cone output extends beyond the activation threshold for voltage-operated calcium entry, suggesting another calcium influx mechanism operates in cones hyperpolarized by light. We have used optical imaging and whole-cell voltage clamp to measure the contribution of store-operated Ca(2+) entry (SOCE) to Ca(2+) homeostasis and its role in regulation of neurotransmission at cone synapses. Mn(2+) quenching of Fura-2 revealed sustained divalent cation entry in hyperpolarized cones. Ca(2+) influx into cone inner segments was potentiated by hyperpolarization, facilitated by depletion of …

Mechanisms Of Primary Axonal Damage In A Viral Model Of Multiple Sclerosis., Jayasri Das Sarma, Lawrence C. Kenyon, Susan T. Hingley, Kenneth S. Shindler

Department of Neurology Faculty Papers

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Recent studies have demonstrated that significant axonal injury also occurs in MS patients and correlates with neurological dysfunction, but it is not known whether this neuronal damage is a primary disease process, or occurs only secondary to demyelination. In the current studies, neurotropic strains of mouse hepatitis virus (MHV) that induce meningitis, encephalitis, and demyelination in the CNS, an animal model of MS, were used to evaluate mechanisms of axonal injury. The pathogenic properties of genetically engineered isogenic spike protein recombinant demyelinating and nondemyelinating strains of MHV were compared. …

Uncoupling Scavenger Receptor A-Mediated Phagocytosis Of Bacteria From Endotoxic Shock Resistance, Eyal Amiel, Julie L. Acker, Ryan M. Collins, Brent Berwin

Dartmouth Scholarship

Unresolved infection by gram-negative bacteria can result in the potentially lethal condition known as endotoxic shock, whereby uncontrolled inflammation can lead to multiple organ failure and death of the infected host. Previous results have demonstrated that animals deficient in class A scavenger receptor (SRA), a trafficking receptor for bacteria and bacterium-derived molecules, are more susceptible to endotoxic shock. This has been proposed to be a result of impaired SRA-dependent phagocytic clearance of bacteria resulting in stronger proinflammatory stimuli. In this report, we test the hypothesis that there is an obligate reciprocal relationship between SRA-mediated phagocytosis of bacteria and susceptibility to …

Expression Of Cpi-17 In Smooth Muscle During Embryonic Development And In Neointimal Lesion Formation., Jee In Kim, Garbo D Young, Li Jin, Avril V Somlyo, Masumi Eto

Department of Molecular Physiology and Biophysics Faculty Papers

Ca(2+) sensitivity of smooth muscle (SM) contraction is determined by CPI-17, an inhibitor protein for myosin light chain phosphatase (MLCP). CPI-17 is highly expressed in mature SM cells, but the expression level varies under pathological conditions. Here, we determined the expression of CPI-17 in embryonic SM tissues and arterial neointimal lesions using immunohistochemistry. As seen in adult animals, the predominant expression of CPI-17 was detected at SM tissues on mouse embryonic sections, whereas MLCP was ubiquitously expressed. Compared with SM alpha-actin, CPI-17 expression doubled in arterial SM from embryonic day E10 to E14. Like SM alpha-actin and other SM marker …

Cardioprotective Effect Of Adiponectin Is Partially Mediated By Its Ampk-Independent Antinitrative Action., Yajing Wang, Ling Tao, Yuexing Yuan, Wayne Bond Lau, Rong Li, Bernard L. Lopez, Theodore A. Christopher, Rong Tian, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Adiponectin (APN) exerts its metabolic regulation largely through AMP-dependent protein kinase (AMPK). However, the role of AMPK in APN's antiapoptotic effect in ischemic-reperfused (I/R) adult cardiomyocytes remains incompletely understood. The present study was designed to determine the involvement of AMPK in the antiapoptotic signaling of APN. Cardiomyocytes from adult male mice overexpressing a dominant-negative alpha(2)-subunit of AMPK (AMPK-DN) or wild-type (WT) littermates were subjected to simulated I/R (SI/R) and pretreated with 2 microg/ml globular domain of APN (gAPN) or vehicle. SI/R-induced cardiomyocyte apoptosis was modestly increased in AMPK-DN cardiomyocytes (P < 0.05). Treatment with gAPN significantly reduced SI/R-induced apoptosis in WT cardiomyocytes as well as in AMPK-DN cardiomyocytes, indicating that the antiapoptotic effect of gAPN is partially AMPK independent. Furthermore, gAPN-induced endothelial nitric oxide synthase (eNOS) phosphorylation was significantly reduced in AMPK-DN cardiomyocytes, suggesting that the APN-eNOS signaling axis is impaired in AMPK-DN cardiomyocytes. Additional experiments demonstrated that treatment of AMPK-DN cardiomyocytes with gAPN reduced SI/R-induced NADPH oxidase overexpression, decreased superoxide generation, and blocked peroxynitrite formation to the same extent as that observed in WT cardiomyocytes. Collectively, our present study demonstrated that although the metabolic and eNOS activation effect of APN is largely mediated by AMPK, the superoxide-suppressing effect of APN is not mediated by AMPK, and this AMPK-independent antioxidant property of APN increased nitric oxide bioavailability and exerted significant antiapoptotic effect.

Intrauterine Growth Restriction Increases Fetal Hepatic Gluconeogenic Capacity And Reduces Messenger Ribonucleic Acid Translation Initiation And Nutrient Sensing In Fetal Liver And Skeletal Muscle., Stephanie R Thorn, Timothy Regnault, Laura D Brown, Paul J Rozance, Jane Keng, Michael Roper, Randall B Wilkening, William W Hay, Jacob E Friedman

Paediatrics Publications

Expression of key metabolic genes and proteins involved in mRNA translation, energy sensing, and glucose metabolism in liver and skeletal muscle were investigated in a late-gestation fetal sheep model of placental insufficiency intrauterine growth restriction (PI-IUGR). PI-IUGR fetuses weighed 55% less; had reduced oxygen, glucose, isoleucine, insulin, and IGF-I levels; and had 40% reduction in net branched chain amino acid uptake. In PI-IUGR skeletal muscle, levels of insulin receptor were increased 80%, whereas phosphoinositide-3 kinase (p85) and protein kinase B (AKT2) were reduced by 40%. Expression of eukaryotic initiation factor-4e was reduced 45% in liver, suggesting a unique mechanism limiting …

Acute Memory Phase Of Sevoflurane Preconditioning Is Associated With Sustained Translocation Of Protein Kinase C-Alpha And Epsilon, But Not Delta, In Isolated Guinea Pig Hearts., Chika Okusa, Masami Miyamae, Shingo Sugioka, Kazuhiro Kaneda, Yoshitaka Inamura, Anna Onishi, Naochika Domae, Junichiro Kotani, Vincent M. Figueredo

Division of Cardiology Faculty Papers

BACKGROUND AND OBJECTIVE: Anaesthetic preconditioning (APC) exerts cardioprotective effects by reducing infarct size and improving recovery of contractile function after ischaemia-reperfusion. The interval between brief exposure to volatile anaesthetic and sustained ischaemia, the acute memory phase, is dependent on intracellular signalling mediating this cardioprotection. Intramyocyte translocation of protein kinase C (PKC) is known to be a key mediator in APC. We examined the relationship between the time frame of the acute memory phase of sevoflurane preconditioning and intramyocyte translocation of PKC-alpha, delta and epsilon to the particulate fraction. METHODS: Isolated perfused guinea pig hearts were subjected to 30 min ischaemia …

Hibernation-Like State Induced By An Opioid Peptide Protects Against Experimental Stroke, Cesar V. Borlongan, Teruo Hayashi, Peter R. Oeltgen, Tsung-Ping Su, Yun Wang

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Delta opioid peptide [D-ala2,D-leU5]enkephalin (DADLE) induces hibernation in summer ground squirrels, and enhances preservation and survival of isolated or transplanted lungs and hearts. In the present study, we investigated the protective effect of DADLE in the central nervous system.

RESULTS: Adult Sprague-Dawley rats were pretreated with DADLE (4 mg/kg every 2 h x 4 injections, i.p.) or saline prior to unilateral occlusion of the middle cerebral artery (MCA). Daily behavioral tests revealed that ischemic animals treated with DADLE did not show any significant behavioral dysfunctions compared with saline-treated ischemic animals. Opioid antagonists only transiently inhibited the protective effect of …

Kinetics And Phenotype Of Vaccine-Induced Cd8+ T-Cell Responses To Toxoplasma Gondii, Kimberly A. Jordan, Emma H. Wilson, Elia D. Tait, Barbara A. Fox, David S. Roos, David J. Bzik

Dartmouth Scholarship

Multiple studies have established that the ability of CD8⁺ T cells to act as cytolytic effectors and produce gamma interferon is important in mediating resistance to the intracellular parasite Toxoplasma gondii. To better understand the generation of the antigen-specific CD8⁺ T-cell responses induced by T. gondii, mice were immunized with replication-deficient parasites that express the model antigen ovalbumin (OVA). Class I tetramers specific for SIINFEKL were used to track the OVA-specific endogenous CD8⁺ T cells. The peak CD8⁺ T-cell response was found at day 10 postimmunization, after which the frequency and numbers of antigen-specific cells …

Mitogen-Activated Protein Kinase (Mapk) Pathways Mediate Embryonic Responses To Culture Medium Osmolarity By Regulating Aquaporin 3 And 9 Expression And Localization, As Well As Embryonic Apoptosis., Christine E Bell, Nathalie M K Larivière, Patricia H Watson, Andrew J Watson

Obstetrics & Gynaecology Publications

BACKGROUND: In order to advance the development of culture conditions and increase the potential for supporting normal preimplantation embryo development in vitro, it is critical to define the mechanisms that early embryos utilize to survive in culture. We investigated the mechanisms that embryos employ in response to culture medium osmolarity. We hypothesized that mitogen-activated protein kinase (MAPK) pathways mediate responses to hyperosmotic stress by regulating Aquaporin (AQP) 3 and 9 expression as well as embryonic apoptosis.

METHODS: Real-time reverse transcription and polymerase chain reaction and whole-mount immunofluorescence were used to determine the relative mRNA levels and protein localization patterns of …

Clinical And Translational Implications Of The Caveolin Gene Family: Lessons From Mouse Models And Human Genetic Disorders., Isabelle Mercier, Jean-Francois Jasmin, Stephanos Pavlides, Carlo Minetti, Neal Flomenberg, Richard G Pestell, Philippe G Frank, Federica Sotgia, Michael P Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Here we review the clinical and translational implications of the caveolin gene family for understanding the pathogenesis of human diseases, including breast and prostate cancers, pulmonary hypertension, cardiomyopathy, diabetes, and muscular dystrophy. Detailed phenotypic analysis of caveolin knockout mice has served to highlight the crucial role of a caveolin deficiency in the pathogenesis of many human disease processes. Mutations in the human caveolin genes are associated with a number of established genetic disorders (such as breast cancer, lipodystrophy, muscular dystrophy, and cardiomyopathy), making the caveolins important and novel targets for drug development. The implementation of new strategies for caveolin replacement …

Prion Protein Glycosylation Is Not Required For Strain-Specific Neurotropism, Justin R. Piro, Brent T. Harris, Koren Nishina, Claudio Soto, Rodrigo Morales, Judy R. Rees, Surachai Supattapone

Dartmouth Scholarship

In this study, we tested the hypothesis that the glycosylation of the pathogenic isoform of the prion protein (PrP^Sc) might encode the selective neurotropism of prion strains. We prepared unglycosylated cellular prion protein (PrP^C) substrate molecules from normal mouse brain by treatment with PNGase F and used reconstituted serial protein cyclic misfolding amplification reactions to produce RML and 301C mouse prions containing unglycosylated PrP^Sc molecules. Both RML- and 301C-derived prions containing unglycosylated PrP^Sc molecules were infectious to wild-type mice, and neuropathological analysis showed that mice inoculated with these samples maintained strain-specific patterns of PrP …

Intravenous Inoculation Of A Bat-Associated Rabies Virus Causes Lethal Encephalopathy In Mice Through Invasion Of The Brain Via Neurosecretory Hypothalamic Fibers., Mirjam A R Preuss, Marie-Luise Faber, Gene S Tan, Michael Bette, Bernhard Dietzschold, Eberhard Weihe, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

The majority of rabies virus (RV) infections are caused by bites or scratches from rabid carnivores or bats. Usually, RV utilizes the retrograde transport within the neuronal network to spread from the infection site to the central nervous system (CNS) where it replicates in neuronal somata and infects other neurons via trans-synaptic spread. We speculate that in addition to the neuronal transport of the virus, hematogenous spread from the site of infection directly to the brain after accidental spill over into the vascular system might represent an alternative way for RV to invade the CNS. So far, it is unknown …

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

Physical And Functional Interaction Between The Dopamine Transporter And The Synaptic Vesicle Protein Synaptogyrin-3, Loreto A Egaña, Rolando A Cuevas, Tracy B Baust, Leonardo A Parra, Rehana K Leak, Sarah Hochendoner, Karina Peña, Marisol Quiroz, Weimin C Hong, Mario M Dorostkar, Roger Janz, Harald H Sitte, Gonzalo E Torres

Faculty, Staff and Student Publications

Uptake through the dopamine transporter (DAT) represents the primary mechanism used to terminate dopaminergic transmission in brain. Although it is well known that dopamine (DA) taken up by the transporter is used to replenish synaptic vesicle stores for subsequent release, the molecular details of this mechanism are not completely understood. Here, we identified the synaptic vesicle protein synaptogyrin-3 as a DAT interacting protein using the split ubiquitin system. This interaction was confirmed through coimmunoprecipitation experiments using heterologous cell lines and mouse brain. DAT and synaptogyrin-3 colocalized at presynaptic terminals from mouse striatum. Using fluorescence resonance energy transfer microscopy, we show …

An Adrenal Beta-Arrestin 1-Mediated Signaling Pathway Underlies Angiotensin Ii-Induced Aldosterone Production In Vitro And In Vivo., Anastasios Lymperopoulos, Giuseppe Rengo, Carmela Zincarelli, Jihee Kim, Stephen Soltys, Walter J Koch

Center for Translational Medicine Faculty Papers

Aldosterone produces a multitude of effects in vivo, including promotion of postmyocardial infarction adverse cardiac remodeling and heart failure progression. It is produced and secreted by the adrenocortical zona glomerulosa (AZG) cells after angiotensin II (AngII) activation of AngII type 1 receptors (AT(1)Rs). Until now, the general consensus for AngII signaling to aldosterone production has been that it proceeds via activation of G(q/11)-proteins, to which the AT(1)R normally couples. Here, we describe a novel signaling pathway underlying this AT(1)R-dependent aldosterone production mediated by beta-arrestin-1 (betaarr1), a universal heptahelical receptor adapter/scaffolding protein. This pathway results in sustained ERK activation and subsequent …

Recent Trends In Soft-Tissue Infection Imaging., Nicholas Petruzzi, Md, Nylla Shanthly, Mbbs, Drm, Mathew L. Thakur, Phd

Department of Radiation Oncology Faculty Papers

This article discusses the current techniques and future directions of infection imaging with particular attention to respiratory, central nervous system, abdominal, and postoperative infections. The agents currently in use localize to areas of infection and inflammation. An infection-specific imaging agent would greatly improve the utility of scintigraphy in imaging occult infections. The superior spatial resolution of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and its lack of reliance on a functional immune system, gives this agent certain advantages over the other radiopharmaceuticals. In respiratory tract infection imaging, an important advancement would be the ability to quantitatively delineate lung inflammation, allowing one to …

Accumulation Of Rhodopsin In Late Endosomes Triggers Photoreceptor Cell Degeneration, Yashodhan Chinchore, Amitavo Mitra, Patrick J. Dolph, Norbert Perrimon

Dartmouth Scholarship

Progressive retinal degeneration is the underlying feature of many human retinal dystrophies. Previous work using Drosophila as a model system and analysis of specific mutations in human rhodopsin have uncovered a connection between rhodopsin endocytosis and retinal degeneration. In these mutants, rhodopsin and its regulatory protein arrestin form stable complexes, and endocytosis of these complexes causes photoreceptor cell death. In this study we show that the internalized rhodopsin is not degraded in the lysosome but instead accumulates in the late endosomes. Using mutants that are defective in late endosome to lysosome trafficking, we were able to show that rhodopsin accumulates …

Facilitated Monocyte-Macrophage Uptake And Tissue Distribution Of Superparmagnetic Iron-Oxide Nanoparticles., Arnaud Beduneau, Zhiya Ma, Cassi B. Grotepas, Alexander Kabanov, Barrett E. Rabinow, Nan Gong, R. Lee Mosley, Huanyu Dou, Michael D. Boska, Howard Gendelman

Journal Articles: Radiology

BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery.

METHODS: Monocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was …

Multimodality Education For Airway Endoscopy Skill Development., Ellen S. Deutsch, Thomas Christenson, Joseph Curry, Jobayer Hossain, Karen Zur, Ian Jacobs

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: Airway endoscopy is a difficult skill to master. A unique practicum was designed to help otolaryngology residents develop endoscopy skills. The learning modalities included lectures, an animal laboratory, high-fidelity manikins, virtual bronchoscopy simulation, and standardized patients. This study compares the relative subjective value of these learning modalities for skill development and realism. METHODS: Participants used a Likert scale (1=disagree to 5=agree) and open responses to anonymously rate the efficacy of 5 learning modalities for teaching airway management, endoscopy skills, and clinical leadership and for providing a realistic experience. RESULTS: The results in 2007 were uniformly positive, with mean scores …

Enhanced Estrogen-Induced Proliferation In Obese Rat Endometrium, Qian Zhang, Qi Shen, Joseph Celestino, Michael R Milam, Shannon N Westin, Robin A Lacour, Larissa A Meyer, Gregory L Shipley, Peter J A Davies, Lei Deng, Adrienne S Mccampbell, Russell R Broaddus, Karen H Lu

Faculty, Staff and Student Publications

OBJECTIVE: We tested the hypothesis that the proliferative estrogen effect on the endometrium is enhanced in obese vs lean animals.

STUDY DESIGN: Using Zucker fa/fa obese rats and lean control, we examined endometrial cell proliferation and the expression patterns of certain estrogen-regulated proproliferative and antiproliferative genes after short-term treatment with estradiol.

RESULTS: No significant morphologic/histologic difference was seen between the obese rats and the lean rats. Estrogen-induced proproliferative genes cyclin A and c-Myc messenger RNA expression were significantly higher in the endometrium of obese rats compared with those of the lean control. Expression of the antiproliferative gene p27Kip1 was suppressed …