Medicine and Health Sciences Commons^™

Raman Spectroscopic Analysis Of Human Skin Tissue Sections Ex-Vivo: Evaluation Of The Effects Of Tissue Processing And Dewaxing, Syed Mehmood Ali, Franck Bonnier, Ali Tfayli, Helen Lambkin, Kathleen Flynn, Vincent Mcdonagh, Claragh Healy, Thomas Lee, Fiona Lyng, Hugh Byrne

Articles

Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections, and the effects of tissue processing. Both hand and thigh sections of human cadavers were analysed in their unprocessed and formalin fixed paraffin processed (FFPP) and subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear differentiation of the stratum corneum, intermediate underlying epithelium and dermal layers for sections from both anatomical sites. The stratum corneum is seen to be relatively rich in lipidic content; the spectrum of the subjacent layers is strongly influenced by the presence of melanin, while that …

Nr2a- And Nr2b-Containing Nmda Receptors In The Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, And Contextual Fear Conditioning, Marieke R. Gilmartin, Janine L. Kwapis, Fred J. Helmstetter

Biomedical Sciences Faculty Research and Publications

Activation of N-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially regulate these two fear memories. Here we show that NR2A-containing NMDARs mediate trace, delay, and contextual fear memories, but NR2B-containing NMDARs are required only for trace conditioning, consistent with a role for PL mPFC in working memory.

Mid-Morning Break And Poster Sessions: Psychological And Physiological Responses To Gambling Cues In Pathological Gamblers, Stephen P. Sharman Mr, Eve Limbrick-Oldfield, Mike R. Aitken, Henrietta Bowden-Jones, Luke Clark

International Conference on Gambling & Risk Taking

Introduction

Gamblers experience exposure to gambling cues on a daily basis, ranging from celebrity-endorsed TV commercials, to walking past a high street bookmaker. Research on substance addictions indicates that these cues are likely to activate urges / cravings to gamble.

Wulfert et al (2005) found higher ratings of subjective excitement following a horse race with a wager on in students, Kushner et al (2008) used frequent gamblers in a simulated casino environment and found positive anticipation and positive priming increased urges to gamble, however these studies used only a single self report item to measure craving. Ashrafioun et al (2012) …

Prefrontal Neurons Of Opposite Spatial Preference Display Distinct Target Selection Dynamics., Therese Lennert, Julio C Martinez-Trujillo

Brain and Mind Institute Researchers' Publications

Neurons in the primate dorsolateral prefrontal cortex (dlPFC) of one hemisphere are selective for the location of attended targets in both visual hemifields. Whether dlPFC neurons with selectivity for opposite hemifields directly compete with each other for target selection or instead play distinct roles during the allocation of attention remains unclear. We explored this issue by recording neuronal responses in the right dlPFC of two macaques while they allocated attention to a target in one hemifield and ignored a distracter on the opposite side. Forty-nine percent of the recorded neurons were target location selective. Neurons selective for contralateral targets (58%) …

Decoding The Neural Mechanisms Of Human Tool Use., Jason P Gallivan, D Adam Mclean, Kenneth F Valyear, Jody C Culham

Brain and Mind Institute Researchers' Publications

Sophisticated tool use is a defining characteristic of the primate species but how is it supported by the brain, particularly the human brain? Here we show, using functional MRI and pattern classification methods, that tool use is subserved by multiple distributed action-centred neural representations that are both shared with and distinct from those of the hand. In areas of frontoparietal cortex we found a common representation for planned hand- and tool-related actions. In contrast, in parietal and occipitotemporal regions implicated in hand actions and body perception we found that coding remained selectively linked to upcoming actions of the hand whereas …

Database-Guided Discovery Of Potent Peptides To Combat Hiv-1 Or Superbugs., Guangshun Wang

Journal Articles: Pathology and Microbiology

Antimicrobial peptides (AMPs), small host defense proteins, are indispensable for the protection of multicellular organisms such as plants and animals from infection. The number of AMPs discovered per year increased steadily since the 1980s. Over 2,000 natural AMPs from bacteria, protozoa, fungi, plants, and animals have been registered into the antimicrobial peptide database (APD). The majority of these AMPs (>86%) possess 11-50 amino acids with a net charge from 0 to +7 and hydrophobic percentages between 31-70%. This article summarizes peptide discovery on the basis of the APD. The major methods are the linguistic model, database screening, de novo …

Microproteinuria During Opisthorchis Viverrini Infection: A Biomarker For Advanced Renal And Hepatobiliary Pathologies From Chronic Opisthorchiasis, Prasert Saichua, Paiboon Sithithaworn, Amar R. Jariwala, David J. Diemert, Jiraporn Sithithaworn, Banchob Sripa, Thewarach Laha, Eimorn Mairiang, Chawalit Pairojkul, Maria V. Periago, Narong Khuntikeo, Jason Mulvenna, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Approximately 680 million people are at risk of infection with Opisthorchis viverrini (OV) andClonorchis sinensis, with an estimated 10 million infected with OV in Southeast Asia alone. While opisthorchiasis is associated with hepatobiliary pathologies, such as advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA), animal models of OV infection show that immune-complex glomerulonephritis is an important renal pathology that develops simultaneously with hepatobiliary pathologies. A cardinal sign of immune-complex glomerulonephritis is the urinary excretion of immunoglobulin G (IgG) (microproteinuria). In community-based studies in OV endemic areas along the Chi River in northeastern Thailand, we observed that over half of …

Cannabis And Psychosis: Transition To Psychosis, Amresh Srivastava, Kristen , Terpstra, Yves Bureau

Data and Test Instruments

Cannabis has been implicated as a risk factor for the development of schizophrenia, however, but the pathway of cannabis causing psychosis is not well understood. It appears that cannabis does not cause any structural changes per say but deficits in areas of the brain responsible for memory and emotion do show some changes. Recent studies suggest that cannabinoids such as CB1 have a pharmacological profile similar to that of atypical antipsychotic drugs. This mechanisms may involve dopamine, GABA, and glutamate neurotransmission; It is still not known if these changes are transitory or permanent, and whether or not they contribute to …

Resilience, Psychopathology And Rehospitalization, Amresh Srivastava

Data and Test Instruments

Purpose: The goal of the project was to determine why patients are being hospitalized repeatedly within an acute psychiatric facility. Past studies have found repeated hospitalization leads to economic drain, disability, poor outcome, stigma and discrimination. Repeated hospitalizations are one of the main causes of disability and dysfunction amongst the mentally ill as well as consuming more than 90 % of the mental health budget. This drain deprives consumers of a major part of allocated health resources. Identifying the potential risk factors for repeated hospitalization, interrelationships between risk factors, and vulnerability will help us take the appropriate measures to prevent …

Human Prostatic Acid Phosphatase: Structure, Function And Regulation., Sakthivel Muniyan, Nagendra K. Chaturvedi, Jennifer G. Dwyer, Chad A. Lagrange, William G. Chaney, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

Human prostatic acid phosphatase (PAcP) is a 100 kDa glycoprotein composed of two subunits. Recent advances demonstrate that cellular PAcP (cPAcP) functions as a protein tyrosine phosphatase by dephosphorylating ErbB-2/Neu/HER-2 at the phosphotyrosine residues in prostate cancer (PCa) cells, which results in reduced tumorigenicity. Further, the interaction of cPAcP and ErbB-2 regulates androgen sensitivity of PCa cells. Knockdown of cPAcP expression allows androgen-sensitive PCa cells to develop the castration-resistant phenotype, where cells proliferate under an androgen-reduced condition. Thus, cPAcP has a significant influence on PCa cell growth. Interestingly, promoter analysis suggests that PAcP expression can be regulated by NF-κB, via …

The Role Of Indoleamine 2,3-Dioxygenase In Lp-Bpm5 Murine Retroviral Disease Progression, Megan A. O'Connor, William R. Green

Dartmouth Scholarship

Indoleamine 2,3-dioxygenase (IDO) is an immunomodulatory intracellular enzyme involved in tryptophan degradation. IDO is induced during cancer and microbial infections by cytokines, ligation of co-stimulatory molecules and/or activation of pattern recognition receptors, ultimately leading to modulation of the immune response. LP-BM5 murine retroviral infection induces murine AIDS (MAIDS), which is characterized by profound and broad immunosuppression of T- and B-cell responses. Our lab has previously described multiple mechanisms regulating the development of immunodeficiency of LP-BM5-induced disease, including Programmed Death 1 (PD-1), IL-10, and T-regulatory (Treg) cells. Immunosuppressive roles of IDO have been demonstrated in other retroviral models, suggesting a possible …

Analysis Of The Role Of D2 Receptors In Methylphenidate-Induced Conditioned Place Preference., Chase M. Duty

Undergraduate Honors Theses

ADHD is one of the most commonly diagnosed disorders during adolescence. Recently, significant increases in the diagnosis of ADHD have caused the prescription of the ADHD medication methylphenidate (MPH) to increase. MPH is a psychostimulant that blocks the dopamine transporter, which is responsible for dopamine reuptake at the synapse. The blockade of the dopamine transporter results in an increase in the availability of dopamine in the synaptic cleft. This increase of dopamine accounts for the addictive properties of a MPH due to strong effects on portions of the brain’s drug-reward pathway, including the striatum and nucleus accumbens. In this study, …

Anr And Its Activation By Plch Activity In Pseudomonas Aeruginosa Host Colonization And Virulence, Angelyca A. Jackson, Maegan J. Gross, Emily F. Daniels, Thomas H. Hampton, John H. Hammond, Isabelle Vallet-Gely, Simon L. Dove, Bruce A. Stanton, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C (PlcH) degrades phosphatidylcholine (PC), an abundant lipid in cell membranes and lung surfactant. A ΔplcHR mutant, known to be defective in virulence in animal models, was less able to colonize epithelial cell monolayers and was defective in biofilm formation on plastic when grown in lung surfactant. Microarray analyses found that strains defective in PlcH production had lower levels of Anr-regulated transcripts than the wild type. PC degradation stimulated the Anr regulon in an Anr-dependent manner under conditions where Anr activity was submaximal because of the presence of oxygen. Two PC catabolites, choline and glycine …

Cytotoxic Properties Of Novel Platinum Compounds, Bbr3610-Dach And Trans-4-Nbd In Tumor Cells: Cellular Effects Of 1, 2-Dach And Nbd Ligands, Vijay Menon

Theses and Dissertations

Platinum-based chemotherapeutics are used for the treatment of a wide range of cancers and a number of attempts have been made toward developing compounds with better cellular stability and similar or enhanced cytotoxicity as compared to their predecessors. The first part of the work reported here focuses on the cellular effects of the metabolically stable dinuclear platinum compound, BBR3610-DACH. Comet assay showed this compound to form interstrand crosslinks, a highly toxic DNA lesion in HCT116 cells, at equimolar concentrations to its parental compound, BBR3610. Cell cycle studies showed that BBR3610-DACH causes G1/S and G2/M cell cycle arrest with S phase …

Polyethylenimine-Enhanced Alumina Nanoscale Adjuvant For Cancer Vaccine, Naoko Uno, Haiyan Li, Hong-Ming Hu, Jun Jiao

Student Research Symposium

Aluminum oxide nanoparticles (Al2O3 NPs) have been shown to increase the efficiency of cell-mediated immune response. Specifically, CD8 and CD4 immune response is required for T cell activation by dendritic cells. These nanoparticles, when functionalized with peptides and other molecules, can be used as vaccine in cancer treatment. In this study, Al2O3 NPs were attached to E6/E7 proteins. HPV-induced cervical cancer expresses E6/E7 antigens. E6/E7 proteins were attached using surface modification of the Al2O3 NPs; different types of molecules were tested to see which adhered the highest amount of protein and produced the strongest cell response. Protein measurements were done …

The Human Brain Processes Syntax In The Absence Of Conscious Awareness., Laura Batterink, Helen J Neville

Brain and Mind Institute Researchers' Publications

Syntax is the core computational component of language. A longstanding idea about syntactic processing is that it is generally not available to conscious access, operating autonomously and automatically. However, there is little direct neurocognitive evidence on this issue. By measuring event-related potentials while human observers performed a novel cross-modal distraction task, we demonstrated that syntactic violations that were not consciously detected nonetheless produced a characteristic early neural response pattern, and also significantly delayed reaction times to a concurrent task. This early neural response was distinct from later neural activity that was observed only to syntactic violations that were consciously detected. …

Flurbiprofen Benzyl Nitrate (Nbs-242) Inhibits The Growth Of A-431 Human Epidermoid Carcinoma Cells And Targets Β-Catenin, Niharika Nath, Xiaoping Liu, Lloydine Jacobs, Khosrow Kashfi

Publications and Research

Background: The Wnt/β-catenin/T cell factor (TCF) signaling pathway is important in the development of nonmelanoma skin cancers (NMSCs). Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are chemopreventive agents consisting of a traditional NSAID attached to an NO-releasing moiety through a chemical spacer. Previously we showed that an aromatic spacer enhanced the potency of a particular NO-NSAID compared to an aliphatic spacer.

Methods: We synthesized an NO-releasing NSAID with an aromatic spacer (flurbiprofen benzyl nitrate, NBS-242), and using the human skin cancer cell line A-431, we evaluated its effects on cell kinetics, Wnt/β-catenin, cyclin D1, and caspase-3.

Results: NBS-242 inhibited the growth of …

Vbp15, A Glucocorticoid Analogue, Is Effective At Reducing Allergic Lung Inflammation In Mice, Jesse M. Damsker, Blythe C. Dillingham, Mary C. Rose, Molly A. Balsley, Christopher R. Heier, Alan M. Watson, Erik J. Stemmy, Rosalyn A. Jurjus, Tony Huynh, Kathleen Tatem, Kitipong Uaesoontrachoon, Dana M. Berry, Angela S. Benton, Robert J. Freishtat, Eric P. Hoffman, John M. Mccall, Heather Gordish-Dressman, Stephanie L. Constant, Erica K.M. Reeves, Kanneboyina Nagaraju

Pharmacology and Physiology Faculty Publications

Asthma is a chronic inflammatory condition of the lower respiratory tract associated with airway hyperreactivity and mucus obstruction in which a majority of cases are due to an allergic response to environmental allergens. Glucocorticoids such as prednisone have been standard treatment for many inflammatory diseases for the past 60 years. However, despite their effectiveness, long-term treatment is often limited by adverse side effects believed to be caused by glucocorticoid receptor-mediated gene transcription. This has led to the pursuit of compounds that retain the anti-inflammatory properties yet lack the adverse side effects associated with traditional glucocorticoids. We have developed a novel …

Competition For Antigen Selects T Cell Responses That Undergo Memory Inflation And Maintains Clonal Dominance During Mcmv Infection, Holly Turula, Lila A. Farrington, Corinne Smith, Ann B. Hill, Christopher M Snyder

Department of Microbiology and Immunology Faculty Papers

Cytomegalovirus (CMV) establishes a life-long, persistent/latent infection. Continuous immune surveillance by CMV-specific CD8+ T cells results in their accumulation over time, a process called “memory inflation”. These “inflationary” T cells migrate systemically and comprise the largest T cell populations in humans, making CMV-based vaccines attractive. Why T cells specific for only some CMV-derived epitopes undergo inflation is unclear. We found previously that recombinant murine (M)CMV expressing the SIINFEKL peptide only induced inflation of SIINFEKL-specific T cells, in contrast to wild-type MCMV infection. We show here that:

• Co-infecting mice with viruses expressing and lacking SIINFEKL enabled T cells with multiple specificities …

Oral Transmission Of Listeria Monocytogenes In Mice Via Ingestion Of Contaminated Food, Elsa N. Bou Ghanem, Tanya Myers-Morales, Grant S. Jones, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

L. monocytogenes are facultative intracellular bacterial pathogens that cause food borne infections in humans. Very little is known about the gastrointestinal phase of listeriosis due to the lack of a small animal model that closely mimics human disease. This paper describes a novel mouse model for oral transmission of L. monocytogenes. Using this model, mice fed L. monocytogenes-contaminated bread have a discrete phase of gastrointestinal infection, followed by varying degrees of systemic spread in susceptible (BALB/c/By/J) or resistant (C57BL/6) mouse strains. During the later stages of the infection, dissemination to the gall bladder and brain is observed. The …

Determinants Of Abuse-Related Effects Of Monoamine Releasers In Rats, Clayton T. Bauer

Theses and Dissertations

Monoamine releasers constitute a class of compounds that promote release of dopamine, serotonin, and/or norepinephrine. These compounds have a range of different uses in the medical setting, including treatment of attention deficit hyperactivity disorder, narcolepsy, and obesity. A major limitation of many of these compounds (i.e. amphetamine, methamphetamine, phenmetrazine) is their propensity for abuse; however, not all monoamine releasers are abused (i.e. fenfluramine). The goal of this dissertation was to examine pharmacological determinants of abuse-related effects produced by monoamine releasers in two preclinical assays in rats: intracranial self-stimulation (ICSS) and drug discrimination. First, this work confirmed and expanded upon previous …

Effects Of Mu Opioid Receptor Agonists On Intracranial Self-Stimulation In The Absence And Presence Of “Pain” In Rats, Ahmad Altarifi

Theses and Dissertations

Pain is a significant health problem. Mu opioid receptor agonists are used clinically as analgesics, but their use is constrained by high abuse liability. Intracranial self-stimulation (ICSS) is a preclinical behavioral procedure that has been used to assess abuse potential of opioids, and drug-induced facilitation of ICSS is interpreted as an abuse-related effect. ICSS can also be used as a behavioral baseline to detect affective dimensions of pain. Specifically, pain-related depression of ICSS can model pain-related depression of behavior and mood, and drug-induced blockade of pain-related ICSS depression can serve as a measure of affective analgesia. This dissertation used mu …

Estimating The Impact Of Lost To Follow-Up On Breast Cancer Patients' Disease-Free Survival, Debbie Yan Qun Huang

Statistics

Background The 5-year survival rate for patients with breast cancer is much higher than patients with other types of cancer. Due to this longer survival period, breast cancer patients also tend to have increased rates of lost to follow-up, when compared to other cancers. When a patient becomes lost, the occurrence of distant metastasis cannot be reliably ascertained, unless the patient had a breast cancer-specific (BC) death. The impact of lost patients on recurrence rates and disease-free survival (DFS) was explored in breast cancer patients seen at the City of Hope from 1997 to 2012.

Methods Female breast cancer patients …

Diabetic Db/Db Mice Exhibit Central Nervous System And Peripheral Molecular Alterations As Seen In Neurological Disorders., A. Ernst, Ajaykumar Narayan Sharma, Khalid M. Elased, P. C. Guest, H. Rahmoune, S. Bahn

Pharmacology and Toxicology Faculty Publications

The db/db mouse is a widely used preclinical model in diabetes research. Recent studies have shown that these mice also display aspects of psychosis and depression-like behaviors as seen in some psychiatric disorders. Here, we have performed multiplex immunoassay and liquid chromatography mass spectrometry profiling of the plasma and brain samples from db/db and control mice to identify altered pathways, which could be related to these behavioral abnormalities. This is the first study to carry out profiling of the brain proteome in this model. Plasma from the db/db mice had increased levels of leptin and insulin, decreased levels of peptide …

Effect Of Coconut Oil On Ulcerative Colitis In The Mouse Model, Pranav Chandra Alok

Masters Theses & Specialist Projects

Ulcerative colitis (UC) is a chronic disease of the colon or large intestine that causes inflammation and ulceration of the inner lining of the colon and rectum. In patients with ulcerative colitis, the body’s immune system overreacts and the body mistakes food, bacteria or other internal materials in the colon for an invading substance. The immune system attacks the material, thus irritating the colon. Limited knowledge of inflammatory conditions coupled with a narrow range of therapeutic options necessitates investigating the role of natural products. This study describes the effect of natural coconut oil on chemically-induced acute and chronic disease in …

Algorithms And A Software Application For The Discovery Of Heparin-Binding Proteins For Chemical Analysis, Christopher Dempewolf

Computer Science and Computer Engineering Undergraduate Honors Theses

Heparin is a biological molecule that plays a vital role in anticoagulation. As such, it is used for the prevention of blood clotting in a variety of medical disorders. However, it is easily contaminated with foreign substances, and this can prove fatal for a person receiving heparin. In order to prevent this, proteins that easily bind to heparin need to be added to the solution. Then, the unwanted substances can easily be filtered out. Certain sequences or patterns of amino acids are known to have a high probability of binding to heparin. Thus, proteins that contain large numbers of these …

Three-Dimensional Segmentation Of Three-Dimensional Ultrasound Carotid Atherosclerosis Using Sparse Field Level Sets., E Ukwatta, J Yuan, D Buchanan, B Chiu, J Awad, W Qiu, G Parraga, A Fenster

Medical Biophysics Publications

PURPOSE: Three-dimensional ultrasound (3DUS) vessel wall volume (VWV) provides a 3D measurement of carotid artery wall remodeling and atherosclerotic plaque and is sensitive to temporal changes of carotid plaque burden. Unfortunately, although 3DUS VWV provides many advantages compared to measurements of arterial wall thickening or plaque alone, it is still not widely used in research or clinical practice because of the inordinate amount of time required to train observers and to generate 3DUS VWV measurements. In this regard, semiautomated methods for segmentation of the carotid media-adventitia boundary (MAB) and the lumen-intima boundary (LIB) would greatly improve the time to train …

Polypharmacy In Elderly: A Cautious Trail To Tread, Saniya Raghib Sabzwari, Waris Qidwai, Seema Bhanji

Department of Family Medicine

Polypharmacy has now increasingly come into focus as the recipient of healthcare in old age worldwide. In elderly it is associated with frequent adverse drug reactions (ADRs) and drug-drug interactions resulting in significant morbidity. Geriatrics is still an emerging specialty in South Asia, especially in Pakistan, where multiple reasons for polypharmacy exist. An extensive literature review of articles using key words like \'polypharmacy,\' \'elderly\' was conducted. The recently updated Beers Criteria of classification of inappropriate drugs in the elderly was reviewed in detail. Articles of relevance to polypharmacy and evaluation of guidelines for appropriate interventions to minimise inappropriate drug prescribing …

Influence Of Genetic Variation On Birth Defects In Caenorhabditis Elegans, Daniel Robert Kepple

Renée Crown University Honors Thesis Projects - All

In my Renee Crown Honors Capstone project, I studied how genetic variation influences birth defects that cause death in C. elegans embryos. I performed high-throughput hatching assay experiments of recombinant inbred advance intercross lines of C. elegans. These lines are genetically distinct from each other. I found significant variation in birth defects causing embryo death in these recombinant inbred advanced intercross lines. My results give evidence that gene interaction may play a significant role in causing birth defects resulting in death. My data also provides a starting point for studies making statistical arguments linking these birth defects to specific …

The Effect Of Nerve Growth Factor (Ngf) Incorporation Into Swine Intestinal Submucosa (Sis) Suture Material On The Healing Process In Gastrocnemius Muscle, Nicole K. Alexander

PCOM Biomedical Studies Student Scholarship

The repair of gastrocnemius muscle incisions were evaluated histologically in a rat model. Comparisons were made between carbon dioxide laser and scalpel incisions closed with sutures prepared from Swine Intestinal Submucosa (SIS) with and without added Nerve Growth Factor. This study was conducted in conjunction with two other studies, one comparing epidermal repair and the other comparing kinesthetic changes post-operatively in the same animal model. Thirty-five days post-surgery the animals were euthanized and an area of muscular tissue encompassing the operative site was excised and evaluated microscopically for the following: presence of macrophages, integrity of the muscle, leukocytes present within …