Medical Sciences Commons^™

Salicylic Acid Activates Sigma Factor B By Rsbu-Dependent And -Independent Mechanisms, Marco Palma, Arnold Bayer, Leon I. Kupferwasser, Tammy Joska, Michael R. Yeaman, Ambrose Cheung

Dartmouth Scholarship

Salicylic acid (SAL) may impact Staphylococcus aureus virulence by activating the sigB operon (rsbU-V-W-sigB), thus leading to reductions in alpha-toxin production and decreased fibronectin binding (L. I. Kupferwasser et al., J. Clin. Investig. 112:222-233, 2003). As these prior studies were performed in strain RN6390 (an rsbU mutant) and its rsbU-repaired variant, SH1000, the current investigation was designed to determine if the SAL effect occurs via rsbU- and/or rsbV-dependent pathways in an rsbU-intact S. aureus strain (FDA486). We thus quantified the transcription from two sigB-dependent promoters (asp23 and sarA P3) in FDA486 in response to SAL exposure in vitro, using isogenic …

The Acute Effects Of Nut Ingestion On Plasma Levels Of Polyphenol Compounds, Biomarkers Of Antioxidant Status, And Lipid Peroxidation, Setareh Torabian Esfahani

Loma Linda University Electronic Theses, Dissertations & Projects

Nuts are rich sources of polyphenolic compounds and nutrients, which have antioxidant capacity. To assess the acute effect of treatment diet (75% of energy from nuts (walnut or almond) and control diet (habitual diet with no nut consumption) in healthy subjects on plasma total phenol content, antioxidant capacity and plasma lipid peroxidation. Thirteen subjects participated in the crossover design study. After an overnight fast, walnut, almond and a control diet, in form of smoothies, were consumed by the study subjects. Each subject participated on three occasions one week apart, consuming one of the smoothies each time. Blood samples were obtained …

Cell-Cycle Regulatory Proteins In The Podocyte In Collapsing Glomerulopathy In Children., Tarak Srivastava, Robert E. Garola, H K. Singh

Manuscripts, Articles, Book Chapters and Other Papers

Podocyte is a terminally committed cell in G1 arrest of cell cycle, and is unable to overcome G1/S transition phase in children with minimal change disease (MCD) and classic focal segmental glomerulosclerosis (FSGS), in contrast to dysregulated proliferative phenotype of idiopathic collapsing glomerulopathy (CGN) in adults. Forty-two kidney biopsies, MCD (14), FSGS (12), CGN (4), and normal (CON) (12), were evaluated by immunohistochemistry using dual staining for expression of p27, p21, and p57, and cyclins D and A, in podocytes of children with CGN. On light microscopy, all podocytes expressed p27, whereas p21 and p57 expression was seen in a …

Expanding Access To Care Through A Resident-Initiated Hepatitis C Clinic - An Innovative Method For Incorporating Acgme Core Competencies Into The Management Of Medically Underserved Patients, Joseph L. Yozviak Do, Facp, Suzanne J. Templer Do, Erini Vasiliadis Do, Vishal Patel Md, Nicole M. Agostino Do, K Nadeem Ahmed Md, Edward Norris Md, Fapm, Charles M. Brooks Md, Eric J. Gertner Md, Mph

Department of Medicine

No abstract provided.

Circadian Rhythmicity By Autocatalysis, Arun Mehra, Christian I. Hong, Mi Shi, Jennifer J. Loros, Jay C. Dunlap, Peter Ruoff

Dartmouth Scholarship

The temperature compensated in vitro oscillation of cyanobacterial KaiC phosphorylation, the first example of a thermodynamically closed system showing circadian rhythmicity, only involves the three Kai proteins (KaiA, KaiB, and KaiC) and ATP. In this paper, we describe a model in which the KaiA- and KaiB-assisted autocatalytic phosphorylation and dephosphorylation of KaiC are the source for circadian rhythmicity. This model, based upon autocatalysis instead of transcription-translation negative feedback, shows temperature-compensated circadian limit-cycle oscillations with KaiC phosphorylation profiles and has period lengths and rate constant values that are consistent with experimental observations.

Combining An Autologous Peripheral Nervous System “Bridge” And Matrix Modification By Chondroitinase Allows Robust, Functional Regeneration Beyond A Hemisection Lesion Of The Adult Rat Spinal Cord, John D. Houle, Veronica J. Tom, Debra A. Mayes, Gail Wagoner, Napoleon Phillips, Jerry Silver

Neuroscience, Cell Biology & Physiology Faculty Publications

Chondroitinase-ABC (ChABC) was applied to a cervical level 5 (C5) dorsal quadrant aspiration cavity of the adult rat spinal cord to degrade the local accumulation of inhibitory chondroitin sulfate proteoglycans. The intent was to enhance the extension of regenerated axons from the distal end of a peripheral nerve (PN) graft back into the C5 spinal cord, having bypassed a hemisection lesion at C3. ChABC-treated rats showed (1) gradual improvement in the range of forelimb swing during locomotion, with some animals progressing to the point of raising their forelimb above the nose, (2) an enhanced ability to use the forelimb in …

Time Course Of Substance P Expression In Dorsal Root Ganglia Following Complete Spinal Nerve Transection, Wendy Weissner, Barbara J. Winterson, Alan Stuart-Tilley, Marshall Devor, Geoffrey M. Bove

Biomedical Sciences Faculty Publications

Recent evidence suggests that substance P (SP) is upregulated in primary sensory neurons following axotomy, and that this change occurs in larger neurons that do not usually produce SP. If so, this upregulation may allow normally neighboring, uninjured, and non-nociceptive dorsal root ganglion (DRG) neurons to become effective in activating pain pathways. Using immunohistochemistry, we performed a unilateral L5 spinal nerve transection upon male Wistar rats, and measured SP expression in ipsilateral L4 and L5 DRGs and contralateral L5 DRGs, at 1 to 14 days postoperatively (dpo), and in control and sham operated rats. In normal and sham operated DRGs, …

Cross-Subtype T-Cell Immune Responses Induced By A Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen†0--, Eric A. Weaver, Zhongjing Lu, Zenaido T. Camacho, Fatiha Moukdar, Hua-Xin Liao, Ben-Jiang Ma, Mark Muldoon, James Theiler, Gary J. Nabel, Norman L. Letvin, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes, Feng Gao

Nebraska Center for Virology: Faculty Publications

The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic groupMconsensus env gene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strain env immunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or C env immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide sets from …

Quantifying Gene Network Connectivity In Silico: Scalability And Accuracy Of A Modular Approach, Nirupama Yalamanchili, Daniel E. Zak, Babatunde A. Ogunnaike, James S. Schwaber, Andres Kriete, Boris N. Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Large, complex data sets that are generated from microarray experiments, create a need for systematic analysis techniques to unravel the underlying connectivity of gene regulatory networks. A modular approach, previously proposed by Kholodenko and co-workers, helps to scale down the network complexity into more computationally manageable entities called modules. A functional module includes a gene's mRNA, promoter and resulting products, thus encompassing a large set of interacting states. The essential elements of this approach are described in detail for a three-gene model network and later extended to a ten-gene model network, demonstrating scalability. The network architecture is identified by analysing …

Antioxidant Enzyme Gene Delivery To Protect From Hiv-1 Gp120-Induced Neuronal Apoptosis, Lokesh Agrawal, Jean-Pierre Louboutin, Beverly A.S. Reyes, Elisabeth J. Van Bockstaele, David S. Strayer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Human immunodeficiency virus-1 (HIV-1) infection in the central nervous system (CNS) may lead to neuronal loss and progressively deteriorating CNS function: HIV-1 gene products, especially gp120, induce free radical-mediated apoptosis. Reactive oxygen species (ROS), are among the potential mediators of these effects. Neurons readily form ROS after gp120 exposure, and so might be protected from ROS-mediated injury by antioxidant enzymes such as Cu/Zn-superoxide dismutase (SOD1) and/or glutathione peroxidase (GPx1). Both enzymes detoxify oxygen free radicals. Because they are highly efficient gene delivery vehicles for neurons, recombinant SV40-derived vectors were used for these studies. Cultured mature neurons derived from NT2 cells …

Endoscopic Sphincterotomy With Or Without Cholecystectomy For Choledocholithiasis In High Risk Surgical Patients: A Decision Analysis, Ali Siddiqui, Pradnya Mitroo, Thomas E. Kowalski, David Loren

Department of Medicine Faculty Papers

Background

Laparoscopic cholecystectomy (LC) is recommended for patients with choledocholithiasis after ERCP with sphincterotomy (ES) and stone extraction.

Aim: We designed a decision model to address whether ES alone versus ES followed by LC (ES + LC) is the optimal treatment in high-risk patients with choledocholithiasis.

Methods:

Our cohort were patients with obstructive jaundice who have undergone an ES with biliary clearance. Recurrent biliary complications over a 2-year period stratified by gallbladder status (in/out) and age-stratified surgical complication rates were obtained from the literature. Failure of therapy was defined as either recurrent symptoms or death attributed to biliary complications.

Results …

Visualization Of Intracellular Transport Of Vesicular Stomatitis Virus Nucleocapsids In Living Cells, Subash C. Das, Debasis Nayak, You Zhou, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The phosphoprotein (P) of vesicular stomatitis virus (VSV) is a subunit of the viral RNA polymerase. In previous studies, we demonstrated that insertion of 19 amino acids in the hinge region of the protein had no significant effect on P protein function. In the present study, we inserted full-length enhanced green fluorescent protein (eGFP) in frame into the hinge region of P and show that the fusion protein (PeGFP) is functional in viral genome transcription and replication, albeit with reduced activity. A recombinant vesicular stomatitis virus encoding PeGFP in place of the P protein (VSV-PeGFP), which possessed reduced growth kinetics …

Rho Kinase As A Novel Molecular Therapeutic Target For Hypertensive Internal Anal Sphincter, Satish Rattan, Marcio A.F. De Godoy, Chirag A. Patel

Department of Medicine Faculty Papers

Background & Aims: An increase in Rho kinase (ROK) activity has been associated with the agonist-induced sustained contraction of the smooth muscle, but its role in the pathophysiology of spontaneously tonic smooth muscle is not known.

Methods: Present studies examined the effects of ROK inhibitor Y 27632 in the tonic smooth muscle of the rat internal anal sphincter (IAS) vs. in the flanking phasic smooth muscle of the rectum (RSM). In addition, studies were performed to determine the relationship between the decreases in the basal IAS tone vs. the ROK activity. Confocal microscopic studies determined the cellular distribution of smooth …

Systems Analysis Of Circadian Time-Dependent Neuronal Epidermal Growth Factor Receptor Signaling, Daniel E. Zak, Haiping Hao, Rajanikanth Vadigepalli, Gregory M. Miller, Babatunde A. Ogunnaike, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Identifying the gene regulatory networks governing physiological signal integration remains an important challenge in circadian biology. Epidermal growth factor receptor (EGFR) has been implicated in circadian function and is expressed in the suprachiasmatic nuclei (SCN), the core circadian pacemaker. The transcription networks downstream of EGFR in the SCN are unknown but, by analogy to other SCN inputs, we expect the response to EGFR activation to depend on circadian timing.

Results

We have undertaken a systems-level analysis of EGFR circadian time-dependent signaling in the SCN. We collected gene-expression profiles to study how the SCN response to EGFR activation depends on …

Systems Analysis Of Circadian Time-Dependent Neuronal Epidermal Growth Factor Receptor Signaling, Daniel E. Zak, Haiping Hao, Rajanikanth Vadigepalli, Gregory M. Miller, Babatunde A. Ogunnaike, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Identifying the gene regulatory networks governing physiological signal integration remains an important challenge in circadian biology. Epidermal growth factor receptor (EGFR) has been implicated in circadian function and is expressed in the suprachiasmatic nuclei (SCN), the core circadian pacemaker. The transcription networks downstream of EGFR in the SCN are unknown but, by analogy to other SCN inputs, we expect the response to EGFR activation to depend on circadian timing.

Results

We have undertaken a systems-level analysis of EGFR circadian time-dependent signaling in the SCN. We collected gene-expression profiles to study how the SCN response to EGFR activation depends on …

Protection Against Ischemia And Reperfusion Injury, Peter R. Oeltgen, Paul D. Bishop, Mark S. Kindy, Juan A. Sanchez

Pathology and Laboratory Medicine Faculty Patents

A compound and method for using the compound to reduce injury associated with ischemia and reperfusion of mammalian organs such as the heart. The compound, either Deltorphin A and/or Dermorphin H, may be administered as part of a preconditioning strategy which reduces the extent of injury and improves organ function following cessation and restoration of blood flow. The compound may be used in preparation for planned ischemia or in a prophylactic manner in anticipation of further ischemic events.

Molecular Diagnosis Of Burkitt's Lymphoma., Sandeep S. Dave, Kai Fu, George W. Wright, Lloyd T. Lam, Philip Kluin, Evert-Jan Boerma, Timothy Greiner, Dennis D. Weisenburger, Andreas Rosenwald, German Ott, Hans-Konrad Müller-Hermelink, Randy D. Gascoyne, Jan Delabie, Lisa M. Rimsza, Rita M. Braziel, Thomas M. Grogan, Elias Campo, Elaine S. Jaffe, Bhavana J. Dave, Warren Sanger, M Bast, Julie M. Vose, James O. Armitage, Joseph M. Connors, Erlend B. Smeland, Stein Kvaloy, Harald Holte, Richard I. Fisher, Thomas P. Miller, Emilio Montserrat, Wyndham H. Wilson, Manisha Bahl, Hong Zhao, Liming Yang, John Powell, Richard Simon, Wing C. Chan, Louis M. Staudt

Journal Articles: Pathology and Microbiology

BACKGROUND: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.

METHODS: Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation.

RESULTS: A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt's lymphoma. Burkitt's lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target …

Substratum As A Driver Of Variation In Periphyton Chlorophyll And Productivity In Lakes, Yvonne Vadeboncoeur

Biological Sciences Faculty Publications

Quantifying periphyton (attached algal) contributions to autotrophic production in lakes is confounded by properties of substratum that affect community biomass (as chlorophyll content) and productivity. We compared chlorophyll content and productivity of natural algal communities (phytoplankton, epipelon, epilithon, epixylon, and epiphyton) experiencing high (>10%) incident radiation in lakes in the US, Greenland, and Quebec, Canada. Chlorophyll content and productivity differed significantly among regions, but they also differed consistently among communities independent of region. Chlorophyll content of periphyton on hard substrata (rocks and wood) was positively related to water-column total P (TP), whereas chlorophyll content of algae on sediment (epipelon) …

The Role Of Cd4 T Cells In The Pathogenesis Of Murine Aids, Wen Li, William R. Green

Dartmouth Scholarship

LP-BM5, a retroviral isolate, induces a disease featuring retrovirus-induced immunodeficiency, designated murine AIDS (MAIDS). Many of the features of the LP-BM5-induced syndrome are shared with human immunodeficiency virus-induced disease. For example, CD4 T cells are critical to the development of MAIDS. In vivo depletion of CD4 T cells before LP-BM5 infection rendered genetically susceptible B6 mice MAIDS resistant. Similarly, MAIDS did not develop in B6.nude mice. However, if reconstituted with CD4 T cells, B6.nude mice develop full-blown MAIDS. Our laboratory has shown that the interaction of B and CD4 T cells that is central to MAIDS pathogenesis requires ligation of …

Effects Of Advancing Age On Er Calcium Regulation In Rat Superior Cervical Ganglia, Conwin Kodel Vanterpool

Loma Linda University Electronic Theses, Dissertations & Projects

Intracellular calcium ([Ca²⁺]i) release from endoplasmic reticulum (ER) stores plays an important role in cell signaling. These stores are rapidly refilled via voltage-gated calcium channels or spontaneously via store-operated calcium channels and subsequent pumping by ER Ca²⁺-ATPases. Calcium release is triggered by the activation of the ryanodine receptor (RyR) channels and their function is in part dependent on their expression. We analyzed the [Ca²⁺]i transients in fura 2-loaded superior cervical ganglion (SCG) cells from 6, 12, 20, and 24-month-old Fischer 344 rats for their ability to rapidly and spontaneously refill. For rapid refilling, the …

Representation Of Head-Centric Flow In The Human Motion Complex., Jeroen Goossens, Sean P Dukelow, Ravi S Menon, Tutis Vilis, Albert V Van Den Berg

Brain and Mind Institute Researchers' Publications

Recent neuroimaging studies have identified putative homologs of macaque middle temporal area (area MT) and medial superior temporal area (area MST) in humans. Little is known about the integration of visual and nonvisual signals in human motion areas compared with monkeys. Through extra-retinal signals, the brain can factor out the components of visual flow on the retina that are induced by eye-in-head and head-in-space rotations and achieve a representation of flow relative to the head (head-centric flow) or body (body-centric flow). Here, we used functional magnetic resonance imaging to test whether extra-retinal eye-movement signals modulate responses to visual flow in …

Desulfovibrio Desulfuricans G20 Tetraheme Cytochrome Structure At 1.5 A˚ And Cytochrome Interaction With Metal Complexes, Mrunalini Pattarkine, J J. Tanner, C A. Bottoms, Y H. Lee, Judy D. Wall

Faculty Works

The structure of the type I tetraheme cytochrome c3 from Desulfovibrio desulfuricans G20 was determined to 1.5 A˚ by X-ray crystallography. In addition to the oxidized form, the structure of the molybdate-bound form of the protein was determined from oxidized crystals soaked in sodium molybdate. Only small structural shifts were obtained with metal binding, consistent with the remarkable structural stability of this protein. In vitro experiments with pure cytochrome showed that molybdate could oxidize the reduced cytochrome, although not as rapidly as U(VI) present as uranyl acetate. Alterations in the overall conformation and thermostability of the metal-oxidized protein were investigated …

Recruitment Of Bad By The Chlamydia Trachomatis Vacuole Correlates With Host-Cell Survival, Philippe Verbeke, Lynn Welter-Stahl, S. Ying, J. Hansen, Georg Hacker, Toni Darville, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Chlamydiae replicate intracellularly in a vacuole called an inclusion. Chlamydial-infected host cells are protected from mitochondrion-dependent apoptosis, partly due to degradation of BH3-only proteins. The host-cell adapter protein 14-3-3β can interact with host-cell apoptotic signaling pathways in a phosphorylation-dependent manner. In Chlamydia trachomatis-infected cells, 14-3-3β co-localizes to the inclusion via direct interaction with a C. trachomatis-encoded inclusion membrane protein. We therefore explored the possibility that the phosphatidylinositol-3 kinase (PI3K) pathway may contribute to resistance of infected cells to apoptosis. We found that inhibition of PI3K renders C. trachomatis-infected cells sensitive to staurosporine-induced apoptosis, which is accompanied by mitochondrial cytochrome c …

A Universal Reference Sample Derived From Clone Vector For Improved Detection Of Differential Gene Expression, Rishi L. Khan, Gregory E. Gonye, Guang Gao, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Using microarrays by co-hybridizing two samples labeled with different dyes enables differential gene expression measurements and comparisons across slides while controlling for within-slide variability. Typically one dye produces weaker signal intensities than the other often causing signals to be undetectable. In addition, undetectable spots represent a large problem for two-color microarray designs and most arrays contain at least 40% undetectable spots even when labeled with reference samples such as Stratagene's Universal Reference RNAs^TM.

Results

We introduce a novel universal reference sample that produces strong signal for all spots on the array, increasing the average fraction of detectable …

In Vitro Expression And Purification Of Class I Mhc Molecules, Loi Cheng

Honors Scholar Theses

The major histocompatibility complex (MHC) is a gene family responsible for many critical functions of the immune system in most vertebrates. The MHC consists of three classes differentiated by their structure and function, and MHC class I encodes antigen binding proteins as well as chaperone and accessory proteins such as tapasin. The purpose of this project is to reconstitute several human MHC class I molecules in their peptide-filled and peptide-deficient forms, and to purify these proteins for biochemical study. The expressed proteins include wild type and mutant variants of the fusion protein human leukocyte antigen HLA-B*0801-fos, and human beta-2-microglobulin (β2m). …

Activation In Neural Networks Controlling Ingestive Behaviors: What Does It Mean, And How Do We Map And Measure It?, Alan Watts, Arshad Khan, Graciela Sanchez-Watts, Dawna Salter, Christina Neuner

Selected Works Temporary Series

No abstract provided.

Activation In Neural Networks Controlling Ingestive Behaviors: What Does It Mean, And How Do We Map And Measure It?, Watts, Arshad Khan, Graciela Sanchez-Watts, Dawna Salter, Christina Neuner

Departmental Papers (Biology)

No abstract provided.

The Vaccinia-Related Kinases Phosphorylate The N' Terminus Of Baf, Regulating Its Interaction With Dna And Its Retention In The Nucleus, R. Jeremy Nichols, Matthew S. Wiebe, Paula Traktman

Nebraska Center for Virology: Faculty Publications

The vaccinia-related kinases (VRKs) comprise a branch of the casein kinase family whose members are characterized by homology to the vaccinia virus B1 kinase. The VRK orthologues encoded by Caenorhabditis elegans and Drosophila melanogaster play an essential role in cell division; however, substrates that mediate this role have yet to be elucidated. VRK1 can complement the temperature sensitivity of a vaccinia B1 mutant, implying that VRK1 and B1 have overlapping substrate specificity. Herein, we demonstrate that B1, VRK1, and VRK2 efficiently phosphorylate the extreme N' terminus of the BAF protein (Barrier to Autointegration Factor). BAF binds to both DNA and …

Abdominal Pain With Rigidity Secondary To The Anti-Emetic Drug Metoclopramide, Nadeem Ullah Khan, Junaid A. Razzak

Department of Emergency Medicine

We report a case of abdominal pain with rigidity, mimicking an acute abdomen, caused by metoclopramide, a common anti-emetic drug. Extrapyramidal symptoms are commonly reported side-effects of this medication. They generally include involuntary movements of limbs, torticollis, oculogyric crisis, rhythmic protrusion of tongue, trismus, or dystonic reactions resembling tetanus, etc. Abdominal rigidity due to this medication, resembling an acute abdomen, has not been reported previously. This case report illustrates the importance of considering medication side-effects when evaluating a patient with abdominal pain and rigidity.

Gαq And Its AktIons, David M. Harris, Andrea D. Eckhart, Walter J. Koch

Department of Medicine Faculty Papers

No abstract available.