Medicine and Health Sciences Commons^™

Acetaminophen Improves Protein Translational Signaling In Aged Skeletal Muscle, Miaozong Wu, Hua Liu, Jacqueline Fannin, Anjaiah Katta, Yeling Wang, Ravi Kumar Arvapalli, Satyanarayana Paturi, Sunil K. Karkala, Kevin M. Rice, Eric R. Blough

MIIR Faculty Research

Background: Age-related muscle atrophy is characterized by increased oxidative stress, diminished Akt enzymatic function, and reduced phosphorylation of the mammalian target of rapamycin (mTOR), which can be attenuated by chronic acetaminophen ingestion. Here we hypothesize that age-related impairments in Akt/ mTOR function are associated with reduced protein translational signaling, and that these changes, if present, can be attenuated by acetaminophen treatment.

Results: Compared to 6- and 27-month old animals, the expression of the mTOR-complex proteins raptor and GbL and the phosphorylation of tuberin/TSC2 (Thr1462) were reduced in the soleus muscles of very aged rats (33 months old). These changes in …

Interferon Regulatory Factor 3-Dependent Pathways Are Critical For Control Of Herpes Simplex Virus Type 1 Central Nervous System Infection, Vineet D. Menachery, Tracy J. Pasieka, David A. Leib

Dartmouth Scholarship

The initiation of the immune response at the cellular level relies on specific recognition molecules to rapidly signal viral infection via interferon (IFN) regulatory factor 3 (IRF-3)-dependent pathways. The absence of IRF-3 would be expected to render such pathways inoperative and thereby significantly affect viral infection. Unexpectedly, a previous study found no significant change in herpes simplex virus (HSV) pathogenesis in IRF-3^−/− mice following intravenous HSV type 1 (HSV-1) challenge (K. Honda, H. Yanai, H. Negishi, M. Asagiri, M. Sato, T. Mizutani, N. Shimada, Y. Ohba, A. Takaoka, N. Yoshida, and T. Taniguchi, Nature 434:772-777, 2005). In contrast, the …

Pontine Haemorrhage Due To Chondrosarcoma Of The Skull Base, Maliha Iqbal Jumani, Roomasa Channa, Sayed Nabeel Zafar, Ather Enam

Section of Neurosurgery

A young adult presented with acute weakness of right side of body and slurring of speech. An initial brain CT scan showed a pontine haemorrhage, however MRI done a few days later revealed a mass in the left parapharyngeal space. Histopathology of the mass revealed that it was a chondrosarcoma. Subsequently the patient was initially treated with chemotherapy and radiotherapy and later surgery. Skull base chondrosarcomabe is to be included in the differentials of a young patient presenting with signs consistent with pontine haemorrhage.

Using Photoactive Vitamin Nanoparticles As Photodynamic Antimicrobial Chemotherapeutic (Pact) Agents To Treat Chronic Wounds, Rahul A. Khanke

All Capstone Projects

The objective of the proposed study is to develop new materials and methods to manage microbial growth in chronic wounds using phototherapy. Chronic wounds are considered as a worldwide health problem. The most common chronic wounds can be classified into three categories: venous ulcers, diabetic ulcers, and pressure ulcers. Venous ulcers, which usually occur in the legs, account for about 70% to 90% of chronic wounds and can become infected easily. Venous ulcers are sores that develop after veins in the legs have been damaged. These ulcers can penetrate deeply into the skin. Occasionally, if a venous ulcer persists for …

Proteoglycans In Health And Disease: Novel Regulatory Signaling Mechanisms Evoked By The Small Leucine-Rich Proteoglycans., Renato V. Iozzo, Liliana Schaefer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The small leucine-rich proteoglycans (SLRPs) are involved in many aspects of mammalian biology, both in health and disease. They are now being recognized as key signaling molecules with an expanding repertoire of molecular interactions affecting not only growth factors, but also various receptors involved in controlling cell growth, morphogenesis and immunity. The complexity of SLRP signaling and the multitude of affected signaling pathways can be reconciled with a hierarchical affinity-based interaction of various SLRPs in a cell- and tissue-specific context. Here, we review this interacting network, describe new relationships of the SLRPs with tyrosine kinase and Toll-like receptors and critically …

The Added Value Of Molecular Testing In Small Pancreatic Cysts, Adam D. Toll, Md, Marluce Bibbo, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background:

Cystic lesions of the pancreas (CLP) represent a relatively common pathologic entity affecting at least 1% of medical patients and represent a spectrum of lesions from inflammatory pseudocyststo malignant neoplasms. A significant percentage of these cysts are found incidentally during imaging work-up for unrelated conditions and require appropriate diagnostic testing to characterize the nature of the CLP. A multi-disciplinary approach to characterize CLP is currently used involving cytology, imaging, and cyst fluid analysis. The most recent international guidelines recommend resection of pancreatic mucinouscysts >3 cm, or smaller cysts with positive cytology, mural nodules, or symptoms.

Recent work utilized DNA …

Interesting Case Presentation: Placental Site Trophoblastic Tumor, Nicole Qualtieri, Ms, Pa (Ascp), Andrea Gadue, Mhs, Pa (Ascp)

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Case Study:

A 26 year-old female (G3P1) had a D&E in March, 2010 for a blighted ovum. The diagnosis on the uterine contents at an outside institution was placental site trophoblastic tumor. No follow up care was obtained. Four months later (July, 2010), the patient presented to her OB-GYN stating that she had missed a period and had a positive home pregnancy test. An ultrasound examination failed to identify a fetus, and the patient was referred to TJUH.

At Jefferson an MRI showed a poorly defined uterine mass that extended into the myometrium. The slides from the original D&E were …

Impact Of A Comprehensive Nutrition And Lifestyle Education Intervention On Body Weight And Health-Related Outcomes In Morbidly-Obese Hispanic-Americans Following Laparoscopic Roux-En Y Gastric Bypass, Monica Petasne Nijamkin

FIU Electronic Theses and Dissertations

As morbid obesity increasingly affects Hispanic-Americans, the incidence of Roux-en-Y gastric bypass procedures (RYGB) among this population rises. Prospective research on the impact of postoperative educational interventions focused on Hispanic-Americans is needed to prevent premature weight loss plateau, weight regain, nutritional deficiencies, and relapse of obesity-related comorbidities. This randomized-controlled study evaluated the impact of a comprehensive nutrition and lifestyle education intervention (6 biweekly postoperative sessions that incorporated motivational strategies for behavioral change) as compared to a non-comprehensive approach (printed guidelines for healthy lifestyle). The variables to consider are body weight, obesity-related comorbidities (depression, diabetes, dyslipidemia, and others), nutrient status, physical …

Effects Of Dose, Administration Route And/Or Vehicle On Decabromodiphenyl Ether (Decabde) Concentrations In Plasma Of Maternal, Fetal And Neonatal Rats And In Milk Of Maternal Rats, J. A. Biesemeier, Melissa J. Beck, H. Silberberg, N. R. Myers, J. M. Ariano, E. S. Bodle, D. W. Sved, S. Jacobi, D. G. Stump, M. Hardy, T. Stedeford

Pharmaceutical Sciences Faculty Publications

The effects of route and vehicle on blood and milk levels of decabromodiphenyl ether (DecaBDE; CASRN 1163-19-5) were investigated in the rat to assist in the design and conduct of a developmental neurotoxicity study. Blood plasma and/or milk concentrations were determined in dams, fetuses, and/or nursing pups after repeated DecaBDE administration by gavage throughout gestation or gestation and lactation using corn oil (CO) or soyaphospholipon/Lutrol F 127-water (SPL) as the vehicle. The impact of vehicle on plasma levels was also investigated in pups derived from naive dams after a single postnatal dose. This study reports for the first time fetal …

Leg Ulcers In Sickle Cell Disease., Caterina P Minniti, James Eckman, Paola Sebastiani, Martin H Steinberg, Samir K. Ballas

Department of Medicine Faculty Papers

Sickle cell disease is a single amino acid molecular disorder of hemoglobin leading to its pathological polymerization, red cell rigidity that causes poor microvascular blood flow, with consequent tissue ischemia and infarction. The manifestations of this disease are protean.Among them, leg ulcers represent a particularly disabling and chronic complication, often associated with a more severe clinical course.Despite the fact that this complication has been recognized since the early times of SCD, there has been little improvement in the efficacy of its management and clinical outcome over the past 100 years. Recently, vasculopathic abnormalities involving abnormal vascular tone and activated, adhesive …

Selected Hormonal And Neurotransmitter Mechanisms Regulating, James L. Sartin, Joseph A. Daniel, Brian K. Whitlock, Robyn R. Wilborn

Faculty Publications and Other Works -- Large Animal Clinical Sciences

Appetite control is a major issue in normal growth and in suboptimal growth performance settings. A number of hormones, in particular leptin, activate or inhibit orexigenic or anorexigenic neurotransmitters within the arcuate nucleus of the hypothalamus, where feed intake regulation is integrated. Examples of appetite regulatory neurotransmitters are the stimulatory neurotransmitters neuropeptide Y (NPY), agouti-related protein (AgRP), orexin and melanin-concentrating hormone and the inhibitory neurotransmitter, melanocyte-stimulating hormone (MSH). Examination of messenger RNA (using in situ hybridization and realtime PCR) and proteins (using immunohistochemistry) for these neurotransmitters in ruminants has indicated that physiological regulation occurs in response to fasting for several …

Fast, Flexible Function-On-Scalar Regression, With An Application To Brain Development, Philip T. Reiss, Lei Huang

Philip T. Reiss

No abstract provided.

Factors Associated With The Acquisition And Severity Of Gestational Listeriosis, M. M. Suyemoto, P. A. Spears, T. S. Hamrick, J. A. Barnes, E. A. Havell, P. E. Orndorff

Osteopathic Medicine, Jerry M. Wallace School of

No abstract provided.

The Mir-15/107 Group Of Microrna Genes: Evolutionary Biology, Cellular Functions, And Roles In Human Diseases, John R. Finnerty, Wang-Xia Wang, Sébastien S. Hébert, Bernard R. Wilfred, Guogen Mao, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

The miR-15/107 group of microRNA (miRNA) gene is increasingly appreciated to serve key functions in humans. These miRNAs regulate gene expression involved in cell division, metabolism, stress response, and angiogenesis in vertebrate species. The miR-15/107 group has also been implicated in human cancers, cardiovascular disease and neurodegenerative disease, including Alzheimer's disease. Here we provide an overview of the following: (1) the evolution of miR-15/107 group member genes; (2) the expression levels of miRNAs in mammalian tissues; (3) evidence for overlapping gene-regulatory functions by different miRNAs; (4) the normal biochemical pathways regulated by miR-15/107 group miRNAs; and (5) the roles played …

Microrna-21 Dysregulates The Expression Of Mef2c In Neurons In Monkey And Human Siv/Hiv Neurological Disease., Sowmya V. Yelamanchili, A Datta Chaudhuri, L N. Chen, Huangui Xiong, Howard S. Fox

Journal Articles: Pharmacology & Experimental Neuroscience

MicroRNAs (miRNAs) play important roles in regulating a plethora of physiological and pathophysiogical processes including neurodegeneration. In both HIV associated dementia in humans and its monkey model SIV encephalitis we find miR-21, a miRNA largely known for its link to oncogenesis, to be significantly upregulated in the brain. In situ hybridization of the diseased brain sections revealed induction of miR-21 in neurons. MiR-21 can be induced in neurons by prolonged N-methyl-D-aspartic acid receptor stimulation, an excitotoxic process active in HIV and other neurodegenerative diseases. Introduction of miR-21 into human neurons leads to pathological functional defects. Furthermore, we show that miR-21 …

Morphological Study Of Emulsion-Assisted Cholesterol Precipitation Processes, Vuk Uskoković

Pharmacy Faculty Articles and Research

Crystallization of cholesterol in chemical conditions that involve the presence of emulsions of three different types of surface active agents—cationic, anionic, and nonionic—was investigated by means of scanning and transmission electron microscopic analyses. In contrast with the previous attempts to modify the typical plate- and needle-shaped character of biaxially grown cholesterol crystals, the present study indicates that spherical templates of fine emulsion droplets may impose spherical morphologies to cholesterol particles nucleated within.

Antifolate Modulators Of Amp-Activated Protein Kinase Signaling As Cancer Therapeutics, Scott Rothbart

Theses and Dissertations

Since its discovery, it was appreciated that the antifolate pemetrexed had multiple targets within folate metabolism. This laboratory was instrumental in showing that pemetrexed elicited its primary action as a thymidylate synthase inhibitor. Unusual for an antifolate, pemetrexed showed significant clinical activity against malignant pleural mesothelioma and non-small cell lung cancer. Accordingly, the FDA recently issued first-line approvals for pemetrexed in these diseases, leading us to question whether the effects of pemetrexed on other folate-dependent targets could explain this atypical clinical activity of the drug. Studies in this dissertation showed that in addition to thymidylate synthase inhibition, pemetrexed was also …

Hepatitis C Virus Core-Derived Peptides Inhibit Genotype 1b Viral Genome Replication Via Interaction With Ddx3x, Chaomin Sun, Cara T. Pager, Guangxiang Luo, Peter Sarnow, Jamie H. D. Cate

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The protein DDX3X is a DEAD-box RNA helicase that is essential for the hepatitis C virus (HCV) life cycle. The HCV core protein has been shown to bind to DDX3X both in vitro and in vivo. However, the specific interactions between these two proteins and the functional importance of these interactions for the HCV viral life cycle remain unclear. We show that amino acids 16-36 near the N-terminus of the HCV core protein interact specifically with DDX3X both in vitro and in vivo. Replication of HCV replicon NNeo/C-5B RNA (genotype 1b) is significantly suppressed in HuH-7-derived cells expressing green fluorescent …

Sialic Acid Transport And Catabolism Are Cooperatively Regulated By Siar And Crp In Nontypeable Haemophilus Influenzae, Jason W. Johnston, Haider Shamsulddin, Anne-Frances Miller, Michael A. Apicella

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: The transport and catabolism of sialic acid, a critical virulence factor for nontypeable Haemophilus influenzae, is regulated by two transcription factors, SiaR and CRP.

RESULTS: Using a mutagenesis approach, glucosamine-6-phosphate (GlcN-6P) was identified as a co-activator for SiaR. Evidence for the cooperative regulation of both the sialic acid catabolic and transport operons suggested that cooperativity between SiaR and CRP is required for regulation. cAMP was unable to influence the expression of the catabolic operon in the absence of SiaR but was able to induce catabolic operon expression when both SiaR and GlcN-6P were present. Alteration of helical phasing supported …

Association Between Chronic Liver And Colon Inflammation During The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jason Anthony Brandon, Jacqueline Perez-Rodriguez, C. Darrell Jennings, Donald A. Cohen, Vishal J. Sindhava, Subbarao Bondada, Alan M. Kaplan, J. Scott Bryson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The murine model of cyclosporine A (CsA)-induced syngeneic graft-versus-host disease (SGVHD) is a bone marrow (BM) transplantation model that develops chronic colon inflammation identical to other murine models of CD4⁺ T cell-mediated colitis. Interestingly, SGVHD animals develop chronic liver lesions that are similar to the early peribiliary inflammatory stages of clinical chronic liver disease, which is frequently associated with inflammatory bowel disease (IBD). Therefore, studies were initiated to investigate the chronic liver inflammation that develops in the SGVHD model. To induce SGVHD, mice were lethally irradiated, reconstituted with syngeneic BM, and treated with CsA. All of the SGVHD animals …

Effects Of Hypothyroidism On Cell Proliferation And Neuroblasts In The Hippocampal Dentate Gyrus In A Rat Model Of Type 2 Diabetes, Sun Shin Yi, In Koo Hwang, Ji Won Choi, Moo-Ho Won, Je Kyung Seong, Yeo Sung Yoon

Biomedical Sciences Faculty Research and Publications

We observed how the hypothyroid state affects diabetic states and modifies cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG). For this, 0.03% methimazole, an anti-thyroid drug, was administered to 7-week-old, pre-diabetic Zucker diabetic fatty (ZDF) rats by drinking water for 5 weeks, and the animals were sacrificed at 12 weeks of age. At this age, corticosterone levels were significantly increased in the ZDF rats compared to those in the control (Zucker lean control, ZLC) rats. Methimazole (methi) treatment in the ZDF rats (ZDF-methi rats) significantly decreased corticosterone levels and diabetes-induced hypertrophy of adrenal glands. In the DG, …

Health Benefits Of Increased Walking For Sedentary, Generally Healthy Older Adults: Using Longitudinal Data To Approximate An Intervention Trial, Paula Diehr

Paula Diehr

BACKGROUND: Older adults are often advised to walk more, but randomized trials have not conclusively established the benefits of walking in this age group. Typical analyses based on observational data may have biased results. Here, we propose a "limited-bias," more interpretable estimate of the health benefits to sedentary healthy older adults of walking more, using longitudinal data from the Cardiovascular Health Study. METHODS: The number of city blocks walked per week, collected annually, was classified as sedentary (<7 blocks per>week), somewhat active, or active (>or=28). Analysis was restricted to persons sedentary and healthy in the first 2 years. In Year …

Molecular Requirements For Ethanol Differential Allosteric Modulation Of Ligand-Gated Ion Channels Based On Selective G Beta Gamma Modulation, Gonzalo E. Yevenes, Gustavo Moraga-Cid, Ariel Avila, Leonardo Guzman, Maximiliano Figueroa, Robert W. Peoples, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

It is now believed that the allosteric modulation produced by ethanol in glycine receptors (GlyRs) depends on alcohol binding to discrete sites within the protein structure. Thus, the differential ethanol sensitivity of diverse GlyR isoforms and mutants was explained by the presence of specific residues in putative alcohol pockets. Here, we demonstrate that ethanol sensitivity in two LGIC members, the GlyR adult alpha1 and embryonic alpha2 subunits, can be modified through selective mutations that rescued or impaired Gbetagamma modulation. Even though that both isoforms were able to physically interact with Gbetagamma, only the alpha1 GlyR was functionally modulated by Gbetagamma …

Distinct Macrophage Subpopulations Regulate Viral Encephalitis But Not Viral Clearance In The Cns, Christina D. Steel, Woong-Ki Kim, Larry Sanford, Laurie Wellman, Sandra Burnett, Nico Van Rooijen, Rochard P. Ciavarra

Biological Sciences Faculty Publications

Intranasal application of vesicular stomatitis virus (VSV) induces acute encephalitis characterized by a pronounced myeloid and T cell infiltrate. The role of distinct phagocytic populations on VSV encephalitis was therefore examined in this study. Ablation of peripheral macrophages did not impair VSV encephalitis or viral clearance from the brain, whereas, depletion of splenic marginal dendritic cells impaired this response and enhanced morbidity/mortality. Selective depletion of brain perivascular macrophages also suppressed this response without altering viral clearance. Thus, two anatomically distinct phagocytic populations regulate VSV encephalitis in a non-redundant fashion although neither population is essential for viral clearance in the CNS. …

Identification Of Thioaptamer Ligand Against E-Selectin: Potential Application For Inflamed Vasculature Targeting., Aman P Mann, Anoma Somasunderam, René Nieves-Alicea, Xin Li, Austin Hu, Anil K Sood, Mauro Ferrari, David G Gorenstein, Takemi Tanaka

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Active targeting of a drug carrier to a specific target site is crucial to provide a safe and efficient delivery of therapeutics and imaging contrast agents. E-selectin expression is induced on the endothelial cell surface of vessels in response to inflammatory stimuli but is absent in the normal vessels. Thus, E-selectin is an attractive molecular target, and high affinity ligands for E-selectin could be powerful tools for the delivery of therapeutics and/or imaging agents to inflamed vessels. In this study, we identified a thiophosphate modified aptamer (thioaptamer, TA) against E-selectin (ESTA-1) by employing a two-step selection strategy: a recombinant protein-based …

A Role For The Histone Deacetylase Hdac4 In The Life-Cycle Of Hiv-1-Based Vectors., Johanna A Smith, Jennifer Yeung, Gary D Kao, René Daniel

Department of Medicine Faculty Papers

HIV-1 integration is mediated by the HIV-1 integrase protein, which joins 3'-ends of viral DNA to host cell DNA. To complete the integration process, HIV-1 DNA has to be joined to host cell DNA also at the 5'-ends. This process is called post-integration repair (PIR). Integration and PIR involve a number of cellular co-factors. These proteins exhibit different degrees of involvement in integration and/or PIR. Some are required for efficient integration or PIR. On the other hand, some reduce the efficiency of integration. Finally, some are involved in integration site selection. We have studied the role of the histone deacetylase …

Quantification Of Localized Brain Iron Sources Using Magnetic Resonance Phase, Grant Alexander Mcauley

Loma Linda University Electronic Theses, Dissertations & Projects

Brain microbleeds (BMB), often present in cerebrovascular and neurodegenerative diseases and neurotrauma, are associated with both chronic and acute illness of significant social and economic impact. Because BMB present a source of potentially cyctotoxic iron to the brain proportional to the amount of extravasated blood, non-invasive quantification of this iron pool is potentially valuable both to assess tissue risk and as a biomarker to monitor disease progression, treatment efficacy, and inform treatment. Past efforts to quantify brain iron have focused on distributed (e.g., anatomical) brain regions. However, BMB represent localized sources of iron deposition. In addition, conventional "magnitude" MR images …

Bpab, A Novel Protein Encoded By The Lyme Disease Spirochete's Cp32 Prophages, Binds To Erp Operator 2 Dna, Logan H. Burns, Claire A. Adams, Sean P. Riley, Brandon L. Jutras, Amy Bowman, Alicia M. Chenail, Anne E. Cooley, Laura A. Haselhorst, Alisha M. Moore, Kelly Babb, Michael G. Fried, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi produces Erp outer surface proteins throughout mammalian infection, but represses their synthesis during colonization of vector ticks. A DNA region 5′ of the start of erp transcription, Operator 2, was previously shown to be essential for regulation of expression. We now report identification and characterization of a novel erp Operator 2-binding protein, which we named BpaB. erp operons are located on episomal cp32 prophages, and a single bacterium may contain as many as 10 different cp32s. Each cp32 family member encodes a unique BpaB protein, yet the three tested cp32-encoded BpaB alleles all bound to the same DNA …

Creating A Lymphedema Wellness Culture, Nancy Kinzli Ms, Otr/L, Clt-Lana

Department of Medicine

No abstract provided.

Ranolazine Is Effective For Acute Or Chronic Ischemic Dysfunction With Heart Failure, Sudip Nanda Md, Facp, Matthew W. Martinez Md, Tanujit Dey Phd

Department of Medicine

No abstract provided.