Digital Commons Network^™

Multiple Mechanisms Of Consciousness: The Neural Correlates Of Emotional Awareness., Jayna M Amting, Steven G Greening, Derek G V Mitchell

Brain and Mind Institute Researchers' Publications

Emotional stimuli, including facial expressions, are thought to gain rapid and privileged access to processing resources in the brain. Despite this access, we are conscious of only a fraction of the myriad of emotion-related cues we face everyday. It remains unclear, therefore, what the relationship is between activity in neural regions associated with emotional representation and the phenomenological experience of emotional awareness. We used functional magnetic resonance imaging and binocular rivalry to delineate the neural correlates of awareness of conflicting emotional expressions in humans. Behaviorally, fearful faces were significantly more likely to be perceived than disgusted or neutral faces. Functionally, …

When Is Door-To-Balloon Time Critical? Analysis From The Horizons-Ami (Harmonizing Outcomes With Revascularization And Stents In Acute Myocardial Infarction) And Cadillac (Controlled Abciximab And Device Investigation To Lower Late Angioplasty Complications) Trials, Bruce R. Brodie Md, Bernard J. Gersh Mb, Chb, Dphil, Thomas D. Stuckey Md, Bernhard Witzenbichler Md, Giulio Guagliumi Md, Jan Z. Peruga Md, Dariusz Dudek Md, Cindy L. Grines Md, David A. Cox Md, Helen Parise Scd, Abhiram Prasad Md, Alexandra J. Lansky Md, Roxana Mehran Md, Gregg W. Stone Md

Department of Medicine

No abstract provided.

Warfarin Genotyping Using Three Different Platforms, Joel A. Lefferts, Mary C. Schwab, Uday B. Dandamudi, Hong-Kee Lee, Lionel D. Lewis, Gregory J. Tsongalis

Dartmouth Scholarship

Genetic testing for common variants in the CYP2C9 and VKORC1 genes may provide useful clinical information to guide dosing patients receiving oral warfarin. Specifically, the CYP2C9*2, CYP2C9*3 and either the VKORC1-1639 G>A or VKORC1 1173C>T polymorphisms can be used to help predict an approximate warfarin maintenance dose needed for a particular patient. Although clinical uptake and use of this genotyping has been slow, an increasing body of literature provides evidence of the clinical utility of supplementing traditional warfarin dosing algorithms with a pharmacogenetic approach. The availability of multiple methods for clinical genotyping provides the opportunity …

Passive Transfer Of Igg Anti-Gm1 Antibodies Impairs Peripheral Nerve Repair, Pablo H Lopez, Gang Zhang, Jiangyang Zhang, Helmar C Lehmann, John W Griffin, Ronald L Schnaar, Kazim A Sheikh

Faculty, Staff and Student Publications

Anti-GM1 antibodies are present in some patients with autoimmune neurological disorders. These antibodies are most frequently associated with acute immune neuropathy called Guillain-Barré syndrome (GBS). Some clinical studies associate the presence of these antibodies with poor recovery in GBS. The patients with incomplete recovery have failure of nerve repair, particularly axon regeneration. Our previous work indicates that monoclonal antibodies can inhibit axon regeneration by engaging cell surface gangliosides (Lehmann et al., 2007). We asked whether passive transfer of human anti-GM1 antibodies from patients with GBS modulate axon regeneration in an animal model. Human anti-GM1 antibodies were compared with other GM1 …

Control Of Catalytic Cycle By A Pair Of Analogous Trna Modification Enzymes., Thomas Christian, Georges Lahoud, Cuiping Liu, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Enzymes that use distinct active site structures to perform identical reactions are known as analogous enzymes. The isolation of analogous enzymes suggests the existence of multiple enzyme structural pathways that can catalyze the same chemical reaction. A fundamental question concerning analogous enzymes is whether their distinct active-site structures would confer the same or different kinetic constraints to the chemical reaction, particularly with respect to the control of enzyme turnover. Here, we address this question with the analogous enzymes of bacterial TrmD and its eukaryotic and archaeal counterpart Trm5. TrmD and Trm5 catalyze methyl transfer to synthesize the m1G37 base at …

Control Of Catalytic Cycle By A Pair Of Analogous Trna Modification Enzymes., Thomas Christian, Georges Lahoud, Cuiping Liu, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Enzymes that use distinct active site structures to perform identical reactions are known as analogous enzymes. The isolation of analogous enzymes suggests the existence of multiple enzyme structural pathways that can catalyze the same chemical reaction. A fundamental question concerning analogous enzymes is whether their distinct active-site structures would confer the same or different kinetic constraints to the chemical reaction, particularly with respect to the control of enzyme turnover. Here, we address this question with the analogous enzymes of bacterial TrmD and its eukaryotic and archaeal counterpart Trm5. TrmD and Trm5 catalyze methyl transfer to synthesize the m1G37 base at …

Pcif1 Modulates Pdx1 Protein Stability And Pancreatic Β Cell Function And Survival In Mice, Kathryn C. Claiborn, Mira M. Sachdeva, Corey E. Cannon, David N. Groff, Jeffrey D. Singer, Doris A. Stoffers

Biology Faculty Publications and Presentations

The homeodomain transcription factor pancreatic duodenal homeobox 1 (Pdx1) is a major mediator of insulin transcription and a key regulator of the β cell phenotype. Heterozygous mutations in PDX1 are associated with the development of diabetes in humans. Understanding how Pdx1 expression levels are controlled is therefore of intense interest in the study and treatment of diabetes. Pdx1 C terminus–interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein that inhibits Pdx1 transactivation. Here, we show that Pcif1 targets Pdx1 for ubiquitination and proteasomal degradation. Silencing of Pcif1 increased Pdx1 protein levels in cultured mouse β cells, and Pcif1 …

Neural Plasticity And Treatment-Induced Recovery Of Sentence Processing In Agrammatism, Cynthia K. Thompson, Dirk B. Den Ouden, Borna Bonakdarpour, Kyla Garibaldi, Todd B. Parrish

Communication Sciences and Disorders Faculty Articles and Research

This study examined patterns of neural activation associated with treatment-induced improvement of complex sentence production (and comprehension) in six individuals with stroke-induced agrammatic aphasia, taking into account possible alterations in blood flow often associated with stroke, including delayed time-to-peak of the hemodynamic response function (HRF) and hypoperfused tissue. Aphasic participants performed an auditory verification fMRI task, processing object cleft, subject cleft, and simple active sentences, prior to and following a course of Treatment of Underlying Forms (TUF; Thompson et al., 2003), a linguistically based approach for treating aphasic sentence deficits, which targeted object relative clause constructions. The patients also were …

Deficits In Attention To Emotional Stimuli Distinguish Youth With Severe Mood Dysregulation From Youth With Bipolar Disorder., Brendan A Rich, Melissa A Brotman, Daniel P Dickstein, Derek G V Mitchell, R James R Blair, Ellen Leibenluft

Brain and Mind Institute Researchers' Publications

Studying attention in the context of emotional stimuli may aid in differentiating pediatric bipolar disorder (BD) from severe mood dysregulation (SMD). SMD is characterized by chronic irritability, arousal, and hyper-reactivity; SMD youth frequently receive a BD diagnosis although they do not meet DSM-IV criteria for BD because they lack manic episodes. We compared 57 BD (14.4 +/- 2.9 years old, 56% male), 41 SMD (12.6 +/- 2.6 years old, 66% male), and 33 control subjects (13.7 +/- 2.5 years old, 52% male) using the Emotional Interrupt task, which examines how attention is impacted by positive, negative, or neutral distracters. We …

Dopaminergic Neurons Derived From Human Induced Pluripotent Stem Cells Survive And Integrate Into 6-Ohda-Lesioned Rats., Jingli Cai, Ming Yang, Elizabeth Poremsky, Sarah Kidd, Jay S Schneider, Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

Cell replacement therapy could be an important treatment strategy for Parkinson's disease (PD), which is caused by the degeneration of dopamine neurons in the midbrain (mDA). The success of this approach greatly relies on the discovery of an abundant source of cells capable of mDAergic function in the brain. With the paucity of available human fetal tissue, efforts have increasingly focused on renewable stem cells. Human induced pluripotent stem (hiPS) cells offer great promise in this regard. If hiPS cells can be differentiated into authentic mDA neuron, hiPS could provide a potential autologous source of transplant tissue when generated from …

Human Papillomavirus And Survival Of Patients With Oropharyngeal Cancer., K Kian Ang, Jonathan Harris, Richard Wheeler, Randal Weber, David I Rosenthal, Phuc Felix Nguyen-Tân, William H Westra, Christine H Chung, Richard C Jordan, Charles Lu, Harold Kim, Rita S. Axelrod, Md, C Craig Silverman, Kevin P Redmond, Maura L Gillison

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.

METHODS: We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive …

Toxicity Of Flow Line, Durafill Vs, And Dycal To Dental Pulp Cells: Effects Of Growth Factors, Alyssa Furey, Julie Hjelmhaug, Doug Lobner

Biomedical Sciences Faculty Research and Publications

Introduction

The objective was to determine the effects of growth factor treatment on dental pulp cell sensitivity to toxicity of 2 composite restoration materials, Flow Line and Durafill VS, and a calcium hydroxide pulp capping material, Dycal.

Methods

Toxicity of the dental materials to cultures of primary dental pulp cells was determined by the MTT metabolism assay. The ability of 6 different growth factors to influence the toxicity was tested.

Results

A 24-hour exposure to either Flow Line or Durafill VS caused approximately 40% cell death, whereas Dycal exposure caused approximately 80% cell death. The toxicity of Flow Line and …

White Matter Diffusion Alterations In Normal Women At Risk Of Alzheimer's Disease, Charles D. Smith, Himachandra Chebrolu, Anders H. Andersen, David A. Powell, Mark A. Lovell, Shuling Xiong, Brian T. Gold

Neurology Faculty Publications

Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal …

Pathologically Activated Neuroprotection Via Uncompetitive Blockade Of N-Methyl-D-Aspartate Receptors With Fast Off-Rate By Novel Multifunctional Dimer Bis(Propyl)-Cognitin, Jialie Luo, Wenming Li, Yuming Zhao, Hongjun Fu, Dik-Lung Ma, Jing Tang, Chaoying Li, Robert W. Peoples, Fushun Li, Qinwen Wang, Pingbo Huang, Jun Xia, Yuanping Pang, Yifan Han

Biomedical Sciences Faculty Research and Publications

Uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists with fast off-rate (UFO) may represent promising drug candidates for various neurodegenerative disorders. In this study, we report that bis(propyl)-cognitin, a novel dimeric acetylcholinesterase inhibitor and γ-aminobutyric acid subtype A receptor antagonist, is such an antagonist of NMDA receptors. In cultured rat hippocampal neurons, we demonstrated that bis(propyl)-cognitin voltage-dependently, selectively, and moderately inhibited NMDA-activated currents. The inhibitory effects of bis(propyl)-cognitin increased with the rise in NMDA and glycine concentrations. Kinetics analysis showed that the inhibition was of fast onset and offset with an off-rate time constant of 1.9 s. Molecular docking simulations showed moderate …

Probiotic Therapy - Recruiting Old Friends To Fight New Foes, Roy D. Sleator

Department of Biological Sciences Publications

Against a backdrop of increasing antibiotic resistance, and the emergence of new and evolving pathogens, clinicians are increasingly forced to consider alternative therapies - probiotics are one such alternative.

The Vision Of Toxicity Testing In The 21st Century: Moving From Discussion To Action, Melvin E. Andersen, Daniel Krewski

Toxicology and Animal Models in Research Collection

Over the past year, a series on commentaries have appeared in the Toxicological Sciences Forum Series related to the 2007 National Research Council (NRC) publication, Toxicity Testing in the 21st Century: A Vision and A Strategy. The first article in the series provided an overview of the vision and was accompanied by an editorial by the three editors of Toxicological Sciences. During the past year, eight invited commentaries from the academic, industrial, and regulatory sectors have provided diverse perspectives on the vision, noted challenges to its implementation, and highlighted aspects of toxicity testing that were not addressed in …

The Efficacy And Safety Of Insulin-Sensitizing Drugs In Hiv-Associated Lipodystrophy Syndrome: A Meta-Analysis Of Randomized Trials, Siddharth H. Sheth, Robin J. Larson

Dartmouth Scholarship

HIV-associated lipodystrophy syndrome (HALS) is characterized by insulin resistance, abnormal lipid metabolism and redistribution of body fat. To date, there has been no quantitative summary of the effects of insulin sensitizing-agents for the treatment of this challenging problem. We searched MEDLINE, the Cochrane Library, clinical trial registries, conference proceedings and references for randomized trials evaluating rosiglitazone, pioglitazone or metformin in patients with evidence of HALS (last update December 2009). Two reviewers independently abstracted data and assessed quality using a standard form. We contacted authors for missing data and calculated weighted mean differences (WMD) and 95% confidence intervals (CI) for each …

High-Throughput Experimental Studies To Identify Mirna Targets Directly, With Special Focus On The Mammalian Brain, Peter T. Nelson, Marianthi Kiriakidou, Zissimos Mourelatos, Grace S. Tan, Mary H. Jennings, Kevin Xie, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

We review the pertinent literature on methods used in high-throughput experimental identification of microRNA (miRNA) "targets" with emphasis on neurochemical studies. miRNAs are short regulatory noncoding RNAs that play important roles in the mammalian brain. The functions of miRNAs are related to their binding of RNAs including mRNAs. Since mammalian miRNAs tend to bind to target mRNAs via imperfect complementarity, understanding exactly which target mRNAs are recognized by which specific miRNAs is a challenge. Based on early experimental evidence, a set of "binding rules" for miRNAs has been described. These have focused on the 5' "seed" region of miRNAs binding …

The Lysr-Type Virulence Activator Aphb Regulates The Expression Of Genes In Vibrio Cholerae In Response To Low Ph And Anaerobiosis, Gabriela Kovacikova, Wei Lin, Karen Skorupski

Dartmouth Scholarship

AphB is a LysR-type activator that initiates the expression of the virulence cascade in Vibrio cholerae by cooperating with the quorum-sensing-regulated activator AphA at the tcpPH promoter on the Vibrio pathogenicity island (VPI). To identify the ancestral chromosomal genes in V. cholerae regulated by AphB, we carried out a microarray analysis and show here that AphB influences the expression of a number of genes that are not associated with the VPI. One gene strongly activated by AphB is cadC, which encodes the ToxR-like transcriptional activator responsible for activating the expression of lysine decarboxylase, which plays an important role in …

Biomarkers For Aging, Philip W. Landfield, Eric M. Blalock, Kuey-Chu Chen, Thomas S. Foster

Pharmacology and Nutritional Sciences Faculty Patents

A statistical and functional correlation strategy to identify changes in cellular pathways specifically linked to impaired cognitive function with aging. Analyses using the strategy identified multiple groups of genes expressed in the hippocampi of mammals, where the genes were expressed at different levels for several ages. The aging changes in expression began before mid-life. Many of the genes were involved in specific neuronal and glial pathways with previously unrecognized relationships to aging and/or cognitive decline. These identified genes and the proteins they encode can be used as novel biomarkers of brain aging and as targets for developing treatment methods against …

Q-Ve-Oph, A Negative Control For O-Phenoxy-Conjugated Caspase Inhibitors, Benjamin Southerland, Kashmira Kulkarni-Datar, Chanel Keoni, Rebecca Bricker, William C. Grunwald Jr., Daniel M. Ketcha, Eugene Hern, David R. Cool, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

The broad-spectrum apoptosis (caspase) inhibitor, Q-VD-OPh, has been shown to have no side effects and is effective at a much lower concentration than other FMK-type caspase inhibitors. However, an appropriate negative control to use with this inhibi- tor has not been available. In this study, we developed and analyzed a new compound, based on the Q-VD-OPh backbone, which acts as a cognate negative control. To create the negative control, we substituted a glutamate residue for the aspartate residue to create Q-VE-OPh, thereby retaining the identical charge and molecular properties with only the addition of an extra –CH2 group. The purity …

Sizing Up Pharmacotherapy For Obesity., Michael A. Valentino, Andre Terzic, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Obesity has increased over the last 20 years, from a condition affecting only a small portion of populations in developed countries, into a global pandemic. The impact of obesity can be appreciated in the context of the populations at risk, and it is estimated that >1 billion adults worldwide are overweight (BMI >25 kg/m2), 300 million of whom are clinically obese (BMI >30 kg/m2). In the United States, 65% of adults are overweight, and 32.2% of them are obese, a prevalence that has doubled over 20 years. In industrialized countries, obesity rates have tripled, coinciding with adoption of a Western …

The Risks And Benefits Of Long-Term Use Of Hydroxyurea In Sickle Cell Anemia: A 17.5 Year Follow-Up., M. H. Steinberg, W. F. Mccarthy, O. Castro, S. K. Ballas, F. D. Armstrong, W. Smith, K. Ataga, P. Swerdlow, A. Kutlar, L. Decastro, M. A. Waclawiw, E. Orringer, S. Jones, D. Strayhorn, W. Rosse, G. Phillips, D. Pearce, A. Johnson-Telfair, L. Daitch, P. Milner, A. Tracy, S. Valdez, G. E. Allen, J. Moshang, B. Scott, C. Bigelow, A. Anderson, V. Sabahi, T. Harrington, W. Labrousse, C. Pegelow, D. Temple, E. Case, R. Harrell, S. Childerie, S. Embury, B. Schmidt, D. Davies, Y. Saunthararajah, M. Koshy, N. Talischy-Zahed, L. Dorn, G. Pendarvis, M. Mcgee, M. Telfer, A. Davis, O. C. Onyekwere, C. Nwokolo, H. Finke, E. Perlin, J. Siteman, M. Bryan, T. Saunders, Y. Barber, P. Gascon, P. Di Paolo, S. Gargiulo, J. Eckman, E. Carter-Randall, J. H. Bailey, A. Platt, L. Waller, G. Ramirez, V. Knors, S. Hernandez, E. M. Rodriguez, E. Wilkes, E. Vichinsky, W. Hagar, C. Hoehner, E. Hackney-Stevens, S. Claster, A. Earles, K. Kleman, K. Mclaughlin, L. White, B. Maddox, L. Usry, A. Brenner, K. Williams, R. O'Brien, K. Genther, S. Shurin, B. Berman, K. Chiarucci, L. Keverline, N. Olivieri, J. Chow, M. Hui, D. Shaw, N. Lewis, M. Okam, E. Mandell, A. Palmer, K. Bridges, B. Tynan, C. Winograd, R. Bellevue, H. Dosik, M. Sheikhai, P. Ryans, H. Souffrant, B. Adler, A. Johnson-Telfair, L. Eskridge, J. Prchal, J. Braddock, T. Mcardle, T. Carlos, A. Roundtree-Schmotzer, D. Gardner

Department of Medicine Faculty Papers

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality.

Reducing The Effects Of Intracellular Accumulation Of Thermolabile Collagen Ii Mutants By Increasing Their Thermostability In Cell Culture Conditions., Katarzyna Gawron, Deborah A. Jensen, Andrzej Steplewski, Andrzej Fertala

Department of Dermatology and Cutaneous Biology Faculty Papers

Mutations in collagen II are associated with spondyloepiphyseal dysplasia, a group of heritable diseases whose common features include aberrations of skeletal growth. The mechanisms through which mutations in collagen II affect the cartilaginous tissues are complex and include both intracellular and extracellular processes. One of those mechanisms involves cellular stress caused by excessive accumulation of misfolded collagen II mutants. We investigated whether stabilizing the structure of thermolabile R789C and R992C collagen II mutants would improve their secretion from cells, thereby reducing cellular stress and apoptosis. Employing glycerol and trimethylamine N-oxide (TMAO), chemicals that increase the thermostability of collagen triple helices, …

Poor Childhood Dental Care: A Risk Factor For The Development Of Coronary Artery Disease And Potential New Target For Cad Prevention, Martin E. Matsumura Md, Taylor Trapp, Shameer Ahmed

Department of Medicine

No abstract provided.

Reduction Of Sympathetic Activity Via Adrenal-Targeted Grk2 Gene Deletion Attenuates Heart Failure Progression And Improves Cardiac Function After Myocardial Infarction., Anastasios Lymperopoulos, Giuseppe Rengo, Erhe Gao, Steven N. Ebert, Gerald W. Dorn, Walter J. Koch

Department of Medicine Faculty Papers

Chronic heart failure (HF) is characterized by sympathetic overactivity and enhanced circulating catecholamines (CAs), which significantly increase HF morbidity and mortality. We recently reported that adrenal G protein-coupled receptor kinase 2 (GRK2) is up-regulated in chronic HF, leading to enhanced CA release via desensitization/down-regulation of the chromaffin cell alpha(2)-adrenergic receptors that normally inhibit CA secretion. We also showed that adrenal GRK2 inhibition decreases circulating CAs and improves cardiac inotropic reserve and function. Herein, we hypothesized that adrenal-targeted GRK2 gene deletion before the onset of HF might be beneficial by reducing sympathetic activation. To specifically delete GRK2 in the chromaffin cells …

The Conundrum Of Sensitization When Recording From Nociceptors, Geoffrey M. Bove, Andrew Dilley

Biomedical Sciences Faculty Publications

Nociceptors are sensory neurons that detect harmful, or potentially harmful, stimuli, and can become sensitized following injury or repetitive stimulation. When sensitized, nociceptors often exhibit activity in the absence of apparent or additional stimulation, called ongoing (or spontaneous) activity (OA). In this report, we provide evidence that OA in nociceptors can be caused by the stimuli typically used to identify and characterize the neuron, which must by definition be noxious and therefore potentially sensitizing. Such OA caused by the experimental methodology can confound interpretation. In our nerve inflammation model, OA can potentially arise from multiple sites, including the lesion site …

A Passive Pure Moment Protocol For Testing Spine Segments: Development And Application, Kyle David Fraysur

Theses and Dissertations (ETD)

The pure moment protocol is the accepted standard for performing in-vitro biomechanical testing of spinal devices. Published studies predominantly report range of motion and flexibility data, but information regarding the segment center of rotation is also relevant. Most current pure moment platforms are not sensitive enough to accurately calculate the instantaneous axis of rotation (IAR) for a segment throughout a bending motion. The purpose of this study was to simulate a pure moment protocol using a programmable spine robot, and use the data gathered to calculate the IAR for harvested specimen and those implanted with a constrained total disc replacement …

Il-2 Regulation Of Il-24 Expression Leads To Growth Suppression Of Melanoma Cells, Emily Jen

Dissertations and Theses (Open Access)

Melanoma is known to be highly resistant to chemotherapy. Treatment with high dose IL-2 has shown significant clinical benefit in a minority of metastatic melanoma patients and has lead to long term survival in a few cases. However, this treatment is associated with excessive multiorgan toxicities, which severely limits its use. We hypothesize that one mechanism of effective IL-2 therapy is through the direct upregulation of IL-24 production in melanoma tumors and subsequent IL-24 mediated tumor growth suppression.

Five melanoma cell lines were treated with high dose recombinant hIL-2 at 1000U/ml. Three of the cell lines (A375, WM1341, WM793) showed …

Thoracic Radiotherapy Treatment Planning With Cine Pet/Ct, Adam C. Riegel

Dissertations and Theses (Open Access)

Purpose: Respiratory motion causes substantial uncertainty in radiotherapy treatment planning. Four-dimensional computed tomography (4D-CT) is a useful tool to image tumor motion during normal respiration. Treatment margins can be reduced by targeting the motion path of the tumor. The expense and complexity of 4D-CT, however, may be cost-prohibitive at some facilities. We developed an image processing technique to produce images from cine CT that contain significant motion information without 4D-CT. The purpose of this work was to compare cine CT and 4D-CT for the purposes of target delineation and dose calculation, and to explore the role of PET in target …