Medicine and Health Sciences Commons^™

A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann

Experimentation Collection

The European Union’s Registration, Evaluation and Authorisation of Chemicals (REACH) legislation mandates testing and evaluation of approximately 30,000 existing substances within a short period of time, beginning with the most widely used “high production volume” (HPV) chemicals. REACH testing requirements for the roughly 3000 HPV chemicals specify three separate tests for reproductive toxicity: two developmental toxicity studies on different animal species (OECD Test Guideline 414) and a two-generation reproduction toxicity study (OECD TG 416). These studies are highly costly in both economic and animal welfare terms. OECD TG 416 is a fertility study intended to evaluate reproductive performance of animals …

Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway, Kathleen C. Brown, Theodore R. Witte, W. Elaine Hardman, Haitao Luo, Yi C. Chen, A. Betts Carpenter, Jamie K. Lau, Piyali Dasgupta

Biochemistry and Microbiology

Background: Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays antiproliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo.

Methodology/Principal Findings: BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently …

Type 1 Diabetes Associated With Pegylated Interferon/Ribavirin Therapy In Chronic Hepatitis C, Ankush Sharma Md, Joseph L. Yozviak Do

Department of Medicine

No abstract provided.

Development Of A Functional Mri Olfactory Protocol, Jeremy Mangum

UNLV Theses, Dissertations, Professional Papers, and Capstones

Many people can spend a few days with an acute form of sinusitis, a stuffy nose, or sinus congestion that inhibits their ability to smell, but there are fourteen million Americans over the age of fifty that suffer from some form of chronic olfactory dysfunction. Some neurological disorders such as Parkinson's disease and Alzheimer's disease have demonstrated that olfactory dysfunction is a frequent and early sign. While these diseases have no known cure, there are medicines that exist to slow the progression of such debilitating illnesses. By identifying such diseases in their early stages, we can improve the quality of …

Role Of Flgt In Anchoring The Flagellum Of Vibrio Cholerae, Raquel M. Martinez, Brooke A. Jude, Thomas J. Kirn, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

Flagellar motility has long been regarded as an important virulence factor. In Vibrio cholerae, the single polar flagellum is essential for motility as well as for proper attachment and colonization. In this study, we demonstrate that the novel flagellar protein FlgT is involved in anchoring the flagellum to the V. cholerae cell. A screen for novel colonization factors by use of TnphoA mutagenesis identified flgT. An in-frame deletion of flgT established that FlgT is required for attachment, colonization, and motility. Transmission electron microscopy revealed that while the flgT mutant is capable of assembling a phenotypically normal flagellum, …

Impact Of Delay To Angioplasty In Patients With Acute Coronary Syndromes Undergoing Invasive Management : Analysis From The Acuity (Acute Catheterization And Urgent Intervention Triage Strategy) Trial, Paul Sorajja Md, Bernard J. Gersh Mb, Chb, Dphil, David A. Cox Md, Michael G. Mclaughlin Md, Peter Zimetbaum Md, Costantino Constantini Md, Thomas D. Stuckey Md, James E. Tcheng Md, Roxana Mehran Md, Alexandra J. Lansky Md, Cindy L. Grines Md, Gregg W. Stone Md

Department of Medicine

No abstract provided.

Occipital Nerve Stimulator Systems: Review Of Complications And Surgical Techniques, Steven Falowski, Dajie Wang, Arvind Sabesan, Ashwini Sharan

Department of Neurosurgery Faculty Papers

Introduction: Stimulation of the occipital nerves is becoming more widely accepted in the treatment of occipital neuritis and migraine disorders.

Objective: Presently, equipment available for spinal cord stimulation is adapted for insertion into the subcutaneous space over the occipital nerves. Many technical factors need to be reassessed to optimize the therapy.

Methods: We performed a retrospective review of patients implanted from 2003 to 2007 at a single center. We aimed to analyze the rate of surgical complications related to implantation technique. A total of 28 patients were present for analysis. Patients were followed up to 60 months with a mean …

Simple Linear Measurements Of The Normal Liver: Interobserver Agreement And Correlation With Hepatic Volume On Mri, Sachit K. Verma, Kristen Mcclure, Laurence Parker, Donald G. Mitchell, Manisha Verma, Diane Bergin

Department of Radiology Faculty Papers

OBJECTIVE. To retrospectively evaluate interobserver agreement for 4 manually determined linear hepatic measurements on magnetic resonance imaging (MRI) and correlation of these linear measurements with hepatic volume.

MATERIALS AND METHODS. Hepatic linear measurements: midhepatic point craniocaudad (MHP CC), maximum CC to liver tip (Max CC), maximum transverse and MHP anteroposterior (AP) dimensions were performed on 116 patients without liver disease who had 1.5 T MR imaging of the abdomen.Linear measurements: MHP CC, Max CC, maximum transverse, MHP AP dimensions and products of CC with MHP AP dimension were correlated with hepatic volumes. Correlation analysis (Pearson product moment correlation), Student t …

Mbp-1 Upregulates Mir-29b That Represses Mcl-1, Collagens, And Matrix-Metalloproteinase-2 In Prostate Cancer Cells., Robert Steele, Justin L. Mott, Ratna B. Ray

Journal Articles: Biochemistry & Molecular Biology

c-myc promoter binding protein (MBP-1) is a multi-functional protein known to regulate expression of targets involved in the malignant phenotype. We have previously demonstrated that exogenous expression of MBP-1 inhibits prostate tumor growth, although the mechanism of growth inhibition is not well understood. We hypothesized that MBP-1 may modulate microRNA (miRNA) expression for regulation of prostate cancer cell growth. In this study, we demonstrated that exogenous MBP-1 upregulates miR-29b by 5-9 fold in prostate cancer cells as measured by real-time quantitative reverse transcription-PCR. Subsequent studies indicated that exogenous expression of miR-29b inhibited Mcl-1, COL1A1, and COL4A1. Further, a novel target …

Palmitoleate Attenuates Palmitate-Induced Bim And Puma Up-Regulation And Hepatocyte Lipoapoptosis., Yuko Akazawa, Sophie Cazanave, Justin L. Mott, Nafisa Elmi, Steven F. Bronk, Shigeru Kohno, Michael R. Charlton, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND & AIMS: Saturated free fatty acids induce hepatocyte lipoapoptosis. This lipotoxicity involves an endoplasmic reticulum stress response, activation of JNK, and altered expression and function of Bcl-2 proteins. The mono-unsaturated free fatty acid palmitoleate is an adipose-derived lipokine which suppresses free fatty acid-mediated lipotoxicity by unclear mechanisms. Herein we examined the mechanisms responsible for cytoprotection.

METHODS: We employed isolated human and mouse primary hepatocytes, and the Huh-7 and Hep 3B cell lines for these studies. Cells were incubated in presence and absence of palmitate (16:0), stearate (18:0), and or palmitoleate (16:1, n-7).

RESULTS: Palmitoleate significantly reduced lipoapoptosis by palmitate …

Paracoccidiomycosis And Hiv/Aids: A Common Problem In An Uncommon Location, Astrid Radermacher Do, Joseph L. Yozviak Do, Facp, Marcelo Gareca Md

Department of Medicine

No abstract provided.

Molecular Cross Talk Between Misfolded Proteins In Animal Models Of Alzheimer's And Prion Diseases, Rodrigo Morales, Lisbell D Estrada, Rodrigo Diaz-Espinoza, Diego Morales-Scheihing, Maria C Jara, Joaquin Castilla, Claudio Soto

Faculty, Staff and Student Publications

The central event in protein misfolding disorders (PMDs) is the accumulation of a misfolded form of a naturally expressed protein. Despite the diversity of clinical symptoms associated with different PMDs, many similarities in their mechanism suggest that distinct pathologies may cross talk at the molecular level. The main goal of this study was to analyze the interaction of the protein misfolding processes implicated in Alzheimer's and prion diseases. For this purpose, we inoculated prions in an Alzheimer's transgenic mouse model that develop typical amyloid plaques and followed the progression of pathological changes over time. Our findings show a dramatic acceleration …

Inference Of Cancer-Specific Gene Regulatory Networks Using Soft Computing Rules., Xiaosheng Wang, Osamu Gotoh

Journal Articles: Genetics, Cell Biology & Anatomy

Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One …

Motor Output Evoked By Subsaccadic Stimulation Of Primate Frontal Eye Fields., Brian D Corneil, James K Elsley, Benjamin Nagy, Sharon L Cushing

Brain and Mind Institute Researchers' Publications

In addition to its role in shifting the line of sight, the oculomotor system is also involved in the covert orienting of visuospatial attention. Causal evidence supporting this premotor theory of attention, or oculomotor readiness hypothesis, comes from the effect of subsaccadic threshold stimulation of the oculomotor system on behavior and neural activity in the absence of evoked saccades, which parallels the effects of covert attention. Here, by recording neck-muscle activity from monkeys and systematically titrating the level of stimulation current delivered to the frontal eye fields (FEF), we show that such subsaccadic stimulation is not divorced from immediate motor …

Isoform-Specific Regulation And Localization Of The Coxsackie And Adenovirus Receptor In Human Airway Epithelia, Katherine J.D.A. Excoffon, Nicholas D. Gansemer, Matthew E. Mobily, Philip H. Karp, Kalpaj R. Parekh, Joseph Zabner

Biological Sciences Faculty Publications

Adenovirus is an important respiratory pathogen. Adenovirus fiber from most serotypes co-opts the Coxsackie-Adenovirus Receptor (CAR) to bind and enter cells. However, CAR is a cell adhesion molecule localized on the basolateral membrane of polarized epithelia. Separation from the lumen of the airways by tight junctions renders airway epithelia resistant to inhaled adenovirus infection. Although a role for CAR in viral spread and egress has been established, the mechanism of initial respiratory infection remains controversial. CAR exists in several protein isoforms including two transmembrane isoforms that differ only at the carboxy-terminus (CAR^Ex7 and CAR^Ex8). We found low-level …

Distribution Of Allatostatin C-Like Immunoreactivity In The Central Nervous System Of The Copepod Crustacean Calanus Finmarchicus, Caroline H. Wilson, Andrew E. Christie

Health Sciences and Kinesiology Faculty Articles

The C-type allatostatins (C-ASTs) are a family of highly pleiotropic arthropod neuropeptides. In crustaceans, transcriptomic/mass spectral studies have identified C-ASTs in the nervous systems of many species; the cellular distributions of these peptides remain unknown. Here, the distribution of C-AST was mapped in the nervous system of the copepod Calanus finmarchicus, the major contributor to the North Atlantic’s zooplanktonic biomass; C-AST-immunopositive neurons were identified in the protocerebrum, in several peripheral ganglia associated with feeding appendages, and in the ganglia controlling the swimming legs, with immunopositive axons present throughout the ventral nerve cord. In addition, axons innervating the dorsal longitudinal …

Rbc And Wbc Fatty Acid Composition Following Consumption Of An Omega 3 Supplement: Lessons For Future Clinical Trials, Theodore R. Witte, Alexander J. Salazar, Oscar F. Ballester, W. Elaine Hardman

Biochemistry and Microbiology

Background: Results from increasing numbers of in vitro and in vivo studies have demonstrated that omega 3 fatty acids incorporated in cell culture media or in the diet of the animals can suppress the growth of cancers. When human clinical trials are initiated to determine the ability of omega 3 fatty acids to alter growth or response to chemotherapeutic interventions of cancers, it will be essential to determine the omega 3 intake of individuals in the trial to determine compliance with consumption of the supplement and to correlate with endpoints of efficacy. We wondered if the fatty acid composition of …

Efficient Activation Of Reconstructed Rat Embryos By Cyclin-Dependent Kinase Inhibitors, Robin L. Webb, Kirk A. Findlay, Michael A. Green, Tina L. Beckett, M. Paul Murphy

Molecular and Cellular Biochemistry Faculty Publications

Background

Over the last decade a number of species, from farm animals to rodents, have been cloned using somatic cell nuclear transfer technology (SCNT). This technique has the potential to revolutionize the way that genetically modified animals are made. In its current state, the process of SCNT is very inefficient (<5% success rate), with several technical and biological hurdles hindering development. Yet, SCNT provides investigators with powerful advantages over other approaches, such as allowing for prescreening for the desired level of transgene expression and eliminating the excess production of undesirable wild-type animals. The rat plays a significant role in biomedical research, but SCNT has been problematic for this species. In this study, we address one aspect of the problem by evaluating methods of activation in artificially constructed rat embryos.

Principal Findings

We demonstrate that treatment with a calcium ionophore (ionomycin) combined with a variety of cyclin-dependent kinase inhibitors is an effective way to activate rat embryos. This is in contrast to methods developed for the mouse embryo, which tolerates much less specific chemical treatments. Methods developed to activate …

Theta-Activity In Anterior Cingulate Cortex Predicts Task Rules And Their Adjustments Following Errors, Thilo Womelsdorf, Kevin Johnston, Martin Vinck, Stefan Everling

Brain and Mind Institute Researchers' Publications

Accomplishing even simple tasks depend on neuronal circuits to configure how incoming sensory stimuli map onto responses. Controlling these stimulus-response (SR) mapping rules relies on a cognitive control network comprising the anterior cingulate cortex (ACC). Single neurons within the ACC convey information about currently relevant SR mapping rules and signal unexpected action outcomes, which can be used to optimize behavioral choices. However, its functional significance and the mechanistic means of interaction with other nodes of the cognitive control network remain elusive and poorly understood. Here, we report that core aspects of cognitive control are encoded by rhythmic theta-band activity within …

Bold Signal In Both Ipsilateral And Contralateral Retinotopic Cortex Modulates With Perceptual Fading, Po-Jang Hsieh, Peter U. Tse

Dartmouth Scholarship

Under conditions of visual fixation, perceptual fading occurs when a stationary object, though present in the world and continually casting light upon the retina, vanishes from visual consciousness. The neural correlates of the consciousness of such an object will presumably modulate in activity with the onset and cessation of perceptual fading.

Method: In order to localize the neural correlates of perceptual fading, a green disk that had been individually set to be equiluminant with the orange background, was presented in one of the four visual quadrants; Subjects indicated with a button press whether or not the disk was subjectively visible …

Role Of All Of The Prrsv Glycoproteins In Protective Immune Response, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) contains the major glycoprotein, GP5, as well as three other minor glycoproteins, namely, GP2a, GP3, and GP4, on the virion envelope, all of which are required for generation of infectious virions. To study their interactions amongst each other and with the cellular receptor for PRRSV, we have cloned each of the viral glycoproteins and CD163 receptor in expression vectors and examined their expression and interaction with each other in transfected cells by co-immunoprecipitation (co-IP) assay using monospecific antibodies. Our results show that strong interaction exists between GP4 and GP5 proteins, although weak interactions …

Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman

Biochemistry and Microbiology

Background: Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring.

Methods: Female SV 129 mice were divided into two groups and placed on …

Schedule For Ct Image Guidance In Treating Prostate Cancer With Helical Tomotherapy., G Beldjoudi, S Yartsev, G Bauman, Jerry J. Battista Dr., Jacob Van Dyk

Oncology Publications

The aim of this study was to determine the effect of reducing the number of image guidance sessions and patient-specific target margins on the dose distribution in the treatment of prostate cancer with helical tomotherapy. 20 patients with prostate cancer who were treated with helical tomotherapy using daily megavoltage CT (MVCT) imaging before treatment served as the study population. The average geometric shifts applied for set-up corrections, as a result of co-registration of MVCT and planning kilovoltage CT studies over an increasing number of image guidance sessions, were determined. Simulation of the consequences of various imaging scenarios on the dose …

4 Part Research Project: Cholecystokinin, Marcie Tasker

Academic Symposium of Undergraduate Scholarship

This 4 part research paper contains information on the biological molecule Cholecystokinin. The following research discusses and presents evidence of the name, history and structure of the hormone. It also discusses the different chemical reactions Cholecystokinin has in the body, the biological roles of Cholecystokinin and the importance of Cholecystokinin focusing specifically on the unexplained obesity issue of our world.

Pressure Distribution Over The Palm During Falls On The Outstretched Hands, Woochol J. Choi, Stephen N. Robinovitch

Physical Therapy Faculty Articles and Research

"Over 90% of wrist fractures are caused by falls on the outstretched hands (Palvanen et al., Osteoporos Int, 2000). Along with bone strength, fracture risk depends on the magnitude and distribution of force to soft and hard tissues during impact. In the current study, we examined how pressure distribution over the palm during a fall is affected by impact configuration, body mass index (BMI), palmer soft tissue thickness, and a 5 mm thick foam pad (simulating a protective glove)."

Transgenic Rat Model Of Neurodegeneration Caused By Mutation In The Tdp Gene., Hongxia Zhou, Cao Huang, Han Chen, Dian Wang, Carlisle P Landel, Pedro Yuxing Xia, Robert Bowser, Yong-Jian Liu, Xu Gang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

TDP-43 proteinopathies have been observed in a wide range of neurodegenerative diseases. Mutations in the gene encoding TDP-43 (i.e., TDP) have been identified in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobe degeneration associated with motor neuron disease. To study the consequences of TDP mutation in an intact system, we created transgenic rats expressing normal human TDP or a mutant form of human TDP with a M337V substitution. Overexpression of mutant, but not normal, TDP caused widespread neurodegeneration that predominantly affected the motor system. TDP mutation reproduced ALS phenotypes in transgenic rats, as seen by progressive degeneration of motor neurons …

P66shc--A Longevity Redox Protein In Human Prostate Cancer Progression And Metastasis : P66shc In Cancer Progression And Metastasis., Mythilypriya Rajendran, Paul Thomes, Li Zhang, Suresh Veeramani, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

p66Shc, a 66 kDa proto-oncogene Src homologous-collagen homologue (Shc) adaptor protein, is classically known in mediating receptor tyrosine kinase signaling and recently identified as a sensor to oxidative stress-induced apoptosis and as a longevity protein in mammals. The expression of p66Shc is decreased in mice and increased in human fibroblasts upon aging and in aging-related diseases, including prostate cancer. p66Shc protein level correlates with the proliferation of several carcinoma cells and can be regulated by steroid hormones. Recent advances point that p66Shc protein plays a role in mediating cross-talk between steroid hormones and redox signals by serving as a common …

Sharing Neurological Expertise: Development Of A High Risk Obstetrical Course, Maureen T. Smith Msn, Rn, Cnrn

Patient Care Services / Nursing

No abstract provided.

Cell-Type Specific Distribution Of Chloride Transporters In The Rat Suprachiasmatic Nucleus, Michael A. Belenky, Patricia J. Sollars, David B. Mount, Seth L. Alper, Yosef Yarom, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

The suprachiasmatic nucleus (SCN) is a circadian oscillator and biological clock. Cell-to-cell communication is important for synchronization among SCN neuronal oscillators and the great majority of SCN neurons use γ-aminobutyric acid (GABA) as a neurotransmitter, the principal inhibitory neurotransmitter in the adult central nervous system. Acting via the ionotropic GABAA receptor, a chloride ion channel, GABA typically evokes inhibitory responses in neurons via Cl− influx. Within the SCN GABA evokes both inhibitory and excitatory responses although the mechanism underlying GABA-evoked excitation in the SCN is unknown. GABA-evoked depolarization in immature neurons in several regions of the brain is a function …

Azi-Isoflurane, A Photolabel Analog Of The Commonly Used Inhaled General Anesthetic Isoflurane., Roderic G Eckenhoff, Jin Xi, Motomu Shimaoka, Aditya Bhattacharji, Manuel Covarrubias, William P Dailey

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Volatility and low-affinity hamper an ability to define molecular targets of the inhaled anesthetics. Photolabels have proven to be a useful approach in this regard, although none have closely mimicked contemporary drugs. We report here the synthesis and validation of azi-isoflurane, a compound constructed by adding a diazirinyl moiety to the methyl carbon of the commonly used general anesthetic isoflurane. Azi-isoflurane is slightly more hydrophobic than isoflurane, and more potent in tadpoles. This novel compound inhibits Shaw2 K(+) channel currents similarly to isoflurane and binds to apoferritin with enhanced affinity. Finally, when irradiated at 300 nm, azi-isoflurane adducts to residues …