Medicine and Health Sciences Commons^™

Up-Regulation Of Interferon-A/Apobec3g Signal Pathway Potently Inactivates Hiv-1 Infectivity In Resting Cd4-T Cells, Keyang Chen, Jialing Huang, Chune Zhang, Sophia Huang, Giuseppe Nunnari, Feng-Xiang Wang, Xiangrong Tong, Ling Gao, Kristi Nikisher, Hui Zhang

Department of Medicine Faculty Papers

Poster Presentation.

Biomolecular Tuning Of Electronic Transport Properties Of Carbon Nanotubes Via Antibody Functionalization, Kasif Teker, Dr. Eric Wickstrom, Balaji Panchapakesan

Department of Biochemistry and Molecular Biology Faculty Papers

Carbon nanotubes (CNTs) are remarkable solidstate nanomaterials due to their unique electrical and mechanical properties. The electronic properties of nanotubes combined with biological molecules such as proteins could make miniature devices for biological sensing applications. In this paper, the noncovalent interaction of single-wall CNTs with antibodies is presented for its potential applications for detecting overexpressed cell surface receptors in breast cancer cells. The degree of binding of antibodies on CNTs was found to be more than 80% for an extended sampling area by confocal microscopy. The key to achieve such high degree of functionalization is due to the separation of …

Combined Effects Of Aldehyde Dehydrogenase Variants And Maternal Mitochondrial Genes On Alcohol Consumption, Yedy Israel, Maria E. Quintanilla, Amalia Sapag, Lutske Tampier

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Two lines of rats bred to differ in their voluntary alcohol consumption — the alcohol-abstaining UChA rats and the alcohol-drinking UChB rats — differ in how effectively toxic acetaldehyde is removed during alcohol metabolism. UChB animals carry efficient variants of the aldehyde dehydrogenase 2 (ALDH2) genes and have active mitochondria, resulting in fast removal of acetaldehyde. UChA animals, in contrast, carry less efficient ALDH2 variants and less active mitochondria, which result in transient elevations of acetaldehyde levels after alcohol ingestion. Cross-breeding studies have demonstrated that the presence of active mitochondria inherited from UChB females can fully abolish the reduction of …

Chemoprevention Of Breast Cancer For Women At Hgh Risk, Kathryn Chan, Gloria J. Morris

Department of Medicine Faculty Papers

Breast cancer remains the second most common cause of cancer death in the United States. Several studies have identified cohorts of women at higher than average risk to develop this disease. These are women who are exposed to high levels of endogenous or exogenous estrogens, those with a family history of breast cancer, and those who harbor benign breast disease or genetic mutations that predispose to breast cancer. In this population group, adapting a chemoprevention strategy to decrease the risk of developing overt disease is a strong consideration. To this end, tamoxifen is the most accepted agent to date. This …

Donor Tricuspid Annuloplasty During Orthotopic Heart Transplantation: Long-Term Results Of A Prospective Controlled Study, Valluvan Jeevanandum, Hyde Russell, Paul Mather, Satoshi Furukawa, Allen Anderson, Jaishankar Raman

Department of Medicine Faculty Papers

Background: Development of tricuspid regurgitation after orthotopic heart transplantation can cause heart failure along with renal and hepatic impairment and portends a poor prognosis. If tricuspid regurgitation causes significant symptoms, tricuspid valve repair or replacement is often required. This study was designed to study the effects of prophylactic tricuspid valve annuloplasty (TVA) during orthotopic heart transplantation on long-term survival, renal function, and amount of tricuspid regurgitation.

Methods: Between April 1997 and March 1998, 60 patients (aged 18 to 70 years; 22 female) randomly received either standard bicaval orthotopic heart transplantation (group STD; n = 30) or bicaval orthotopic …

Multiple Domains In Siz Sumo Ligases Contribute To Substrate Selectivity., Alison Reindle, Irina Belichenko, Gwendolyn R Bylebyl, Xiaole L Chen, Nishant Gandhi, Erica S Johnson

Department of Biochemistry and Molecular Biology Faculty Papers

Saccharomyces cerevisiae contains two Siz/PIAS SUMO E3 ligases, Siz1 and Siz2/Nfi1, and one other known ligase, Mms21. Although ubiquitin ligases are highly substrate-specific, the degree to which SUMO ligases target distinct sets of substrates is unknown. Here we show that although Siz1 and Siz2 each have unique substrates in vivo, sumoylation of many substrates can be stimulated by either protein. Furthermore, in the absence of both Siz proteins, many of the same substrates are still sumoylated at low levels. Some of this residual sumoylation depends on MMS21. Siz1 targets its unique substrates through at least two distinct domains. Sumoylation of …

Antimicrobial Effects Of Liquid Anesthetic Isoflurane On Candida Albicans, Viachaslau M. Barodka, Edward Acheampong, Garry Powell, Ludmilla Lobach, David A. Logan, Zahida Parveen, Valerie Armstead, Muhammad Mukhtar

Department of Medicine Faculty Papers

Candida albicans is a dimorphic fungus that can grow in yeast morphology or hyphal form depending on the surrounding environment. This ubiquitous fungus is present in skin and mucus membranes as a potential pathogen that under opportunistic conditions causes a series of systemic and superficial infections known as candidiasis, moniliasis or simply candidiasis. There has been a steady increase in the prevalence of candidiasis that is expressed in more virulent forms of infection. Although candidiasis is commonly manifested as mucocutaneous disease, life-threatening systemic invasion by this fungus can occur in every part of the body. The severity of candidal infections …

Bibliography Of Secondary Sources On The History Of Dermatology Iii. Books, Monographs, And Chapters In English Supplemented Through 2005., Lawrence Charles Parish, John Thorne Crissey, Jennifer L Parish, Daniel H Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

Providing supplements to the history of dermatology bibliographic record has been a continuous project for the past four decades. When the endeavor was initiated, the original authors decided that only contributions in English and those directly related to dermatology, excluding sexually transmitted diseases as such, would be indexed.

There is the perennial question of whether such a manually created bibiliographic project has a need. The obvious answer remains yes. While Index Medicus has expanded the number of journals that are indexed, the number of dermatology publications currently included by Index Medicus is just over fifty. Granted, most of the papers …

Locus Ceruleus Regulates Sensory Encoding By Neurons And Networks In Waking Animals, David M. Devilbiss, Michelle E. Page, Barry D. Waterhouse

Department of Neurosurgery Faculty Papers

Substantial evidence indicates that the locus ceruleus (LC)–norepinephrine (NE) projection system regulates behavioral state and state-dependent processing of sensory information. Tonic LC discharge (0.1–5.0 Hz) is correlated with levels of arousal and demonstrates an optimal firing rate during good performance in a sustained attention task. In addition, studies have shown that locally applied NE or LC stimulation can modulate the responsiveness of neurons, including those in the thalamus, to nonmonoaminergic synaptic inputs. Many recent investigations further indicate that within sensory relay circuits of the thalamus both general and specific features of sensory information are represented within the collective firing patterns …

Hydroxyurea And Sickle Cell Anemia: Effect On Quality Of Life, Samir K. Ballas, Franca B. Barton, Myron K. Waclawiw, Paul Swerdlow, James R. Eckman, Charles H. Pegelow, Mabel Koshy, Bruce A. Barton, Duane R. Bonds

Department of Medicine Faculty Papers

Background: The Multicenter Study of Hydroxyurea (HU) in Sickle Cell Anemia (MSH) previously showed that daily oral HU reduces painful sickle cell (SS) crises by 50% in patients with moderate to severe disease. The morbidity associated with this disease is known to have serious negative impact on the overall quality of life(QOL) of affected individuals.

Methods: The data in this report were collected from the 299 patients enrolled in the MSH. Health quality of life (HQOL) measures were assessed in the MSH as a secondary endpoint to determine if the clinical benefit of HU could translate into a measurable benefit …

High-Affinity Binding Of The Nc1 Domain Of Collagen Vii To Laminin 5 And Collagen Iv, Raymond Brittingham, Jouni Uitto, Andrzej Fertala

Department of Dermatology and Cutaneous Biology Faculty Papers

Anchoring functions of collagen VII depend on its ability to form homotypic fibrils and to bind to other macromolecules to form heterotypic complexes. Biosensor-based binding assays were employed to analyze the kinetics of the NC1 domain-mediated binding of collagen VII to laminin 5, collagen IV, and collagen I. We showed that collagen VII interacts with laminin 5 and collagen IV with Kd values of 10-9 M. In contrast, the NC1-mediated binding to collagen I was weak with a Kd value of 10-6 M. Binding assays also showed that the NC1 domain utilizes the same region to bind to both laminin …

Chronic-Alcohol Exposure Alters Igf1 Signaling In H9c2 Cells Via Changes In Pkc Delta, Richard Ila, Michele Solem

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Previously, we have demonstrated that chronic-alcohol exposure alters insulin-like growth factor 1 (IGF1) signaling in adult rat heart cells. This report examines the effects of alcohol in vitro on the expression of protein kinase C (PKC) alpha, delta, and epsilon using the embryonic heart cell line, H9c2, and how this may be linked to changes in IGF1 signal transduction. Western blot analyses of H9c2 protein preparations demonstrate that there are significant increases in the total protein levels of PKC delta and epsilon after 4 days exposure to alcohol, and similar increases were found after 2 and 6 days exposure. In …

Case Report: Sigmoid Schwannoma As The Lead Point For Intussusception In An Adult Patient With Neurofibromatosis, Roger Coron, Herve Boucard, Robert Richards

Department of Medicine Faculty Papers

No abstract available.

Alpha Interferon Potently Enhances The Anti-Human Immunodeficiency Virus Type 1 Activity Of Apobec3g In Resting Primary Cd4 T Cells, Keyang Chen, Jialing Huang, Chune Zhang, Sophia Huang, Guiseppe Nunnari, Feng-Xiang Wang, Xiangrong Tong, Ling Gao, Kristi Nikisher, Hui Zhang

Department of Medicine Faculty Papers

The interferon (IFN) system, including various IFNs and IFN-inducible gene products, is well known for its potent innate immunity against wide-range viruses. Recently, a family of cytidine deaminases, functioning as another innate immunity against retroviral infection, has been identified. However, its regulation remains largely unknown. In this report, we demonstrate that through a regular IFN-{alpha}/ß signal transduction pathway, IFN-{alpha} can significantly enhance the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) in human primary resting but not activated CD4 T cells and the amounts of APOBEC3G associated with a low molecular mass. Interestingly, short-time treatments of newly infected resting …

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 …

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 …

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 …

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 …

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 …

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 …

Mixed Germ Cell Sex Cord-Stromal Tumors Of The Testis And Ovary. Morphological, Immunohistochemical, And Molecular Genetic Study Of Seven Cases, Michal Michal, Tomas Vanacek, Radek Sima, Petr Mukensnabl, Ondrej Hes, Dmitry V. Kazakov, Jozef Matoska, Anna Zuntova, Vladimir Dvorak, Alexander Talerman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We present the morphological, immunohistochemical, and molecular genetic features of three cases of testicular and four cases of ovarian mixed germ cell sex cord-stromal tumors (MGSCT). The germ cells in the testicular MGSCTs morphologically differed from those in classical seminomas by lacking the typical "square off" quality of the nuclei. In contrast to the nuclei in classical seminomas, their size in testicular MGSCTs was smaller and nucleoli were inconspicuous and the cytoplasm was Periodic Acid-Schiff(PAS) negative. Quite on the contrary, the variability in the size of the nuclei of the germ cells in the testicular MGSCTs was more similar to …

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

Department of Medicine Faculty Papers

No abstract available.

The Molecular Portraits Of Breast Tumors Are Conserved Acress Microarray Platforms, Zhiyuan Hu, Cheng Fan, Daniel S. Oh, J. S. Marron, Xiaping He, Bahjat F. Qaqish, Chad Livasy, Lisa A. Carey, Evangeline Reynolds, Lynn Dressler, Andrew Nobel, Joel Parker, Matthew G. Ewend, Lynda R. Sawyer, Junyuan Wu, Yudong Liu, Rita Nanda, Maria Tretiakova, Alejandra Ruiz Orrico, Donna Dreher, Juan P. Palazzo, Laurent Perreard, Edward Nelson, Mary Mone, Heidi Hansen, Michael Mullins, John F. Quackenbush, Matthew J. Ellis, Olufunmilayo I. Olopade, Philip S. Bernard, Charles M. Perou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Validation of a novel gene expression signature in independent data sets is a critical step in the development of a clinically useful test for cancer patient risk-stratification. However, validation is often unconvincing because the size of the test set is typically small. To overcome this problem we used publicly available breast cancer gene expression data sets and a novel approach to data fusion, in order to validate a new breast tumor intrinsic list.

Results

A 105-tumor training set containing 26 sample pairs was used to derive a new breast tumor intrinsic gene list. This intrinsic list contained 1300 genes …

Scientific Issues Related To The Cytology Proficiency Testing Regulations, George Birdsong, Lydia Howell, Karen Atkinson, R. Marshall Austin, Marluce Bibbo, Thomas A. Bonfiglio, Diane D. Davey, Catherine Keebler, Dina Mody, Lynnette Savaloja, Jacalyn Papillo, Marianne Prey, Stephen Raab, Brenda L. Schultz, Diane Solomon

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The member organizations of the Cytology Education and Technology Consortium believe there are significant flaws in current cytology proficiency testing regulations. The most immediate needed modifications include lengthening the required testing interval, utilizing stringently validated and continuously monitored slides, changing the grading scheme, and changing the focus of the test from the individual to laboratory level testing. Integration of new computer-assisted and located-guided screening technologies into the testing protocols is necessary for the testing protocol to be compliant with the law.

Pro-Opiomelanocortin Co-Localizes With Corticotropin-Releasing Factor In Axon Terminals Of The Noradrenergic Nucleus Locus Coeruleus, Beverly A.S. Reyes, Julia D. Glaser, Ronaldo Magtoto, Elisabeth K. Van Bockstaele

Department of Neurosurgery Faculty Papers

We previously demonstrated that the opioid peptide, enkephalin, and corticotropin-releasing factor (CRF) are occasionally co-localized in individual axon terminals but more frequently converge on common dendrites in the locus coeruleus (LC). To further examine potential opioid co-transmitters in CRF afferents, we investigated the distribution of proopiomelanocortin (POMC), the precursor that yields the potent bioactive peptide, ß-endorphin, with respect to CRF immunoreactivity using immunofluorescence and immunoelectron microscopic analyses of the LC. Coronal sections were collected through the dorsal pontine tegmentum of rat brain and processed for immunocytochemical detection of POMC and CRF or tyrosine hydroxylase (TH). POMC-immunoreactive processes exhibited a distinct …

Voltage-Dependent Gating Rearrangements In The Intracellular T1-T1 Interface Of A K+ Channel., Guangyu Wang, Manuel Covarrubias

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The intracellular tetramerization domain (T1) of most eukaryotic voltage-gated potassium channels (Kv channels) exists as a "hanging gondola" below the transmembrane regions that directly control activation gating via the electromechanical coupling between the S4 voltage sensor and the main S6 gate. However, much less is known about the putative contribution of the T1 domain to Kv channel gating. This possibility is mechanistically intriguing because the T1-S1 linker connects the T1 domain to the voltage-sensing domain. Previously, we demonstrated that thiol-specific reagents inhibit Kv4.1 channels by reacting in a state-dependent manner with native Zn(2+) site thiolate groups in the T1-T1 interface; …

Cell-Signalling Dynamics In Time And Space, Boris N. Kholodenko Phd, Dsci

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The specificity of cellular responses to receptor stimulation is encoded by the spatial and temporal dynamics of downstream signalling networks. Computational models provide insights into the intricate relationships between stimuli and responses and reveal mechanisms that enable networks to amplify signals, reduce noise and generate discontinuous bistable dynamics or oscillations. These temporal dynamics are coupled to precipitous spatial gradients of signalling activities, which guide pivotal intracellular processes, but also necessitate mechanisms to facilitate signal propagation across a cell.

The Ribosome-Recycling Step: Consensus Or Controversy?, Go Hirokawa, Natalia Demeshkina, Nobuhiro Iwakura, Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosome recycling, the last step in translation, is now accepted as an essential process for prokaryotes. In 2005, three laboratories showed that ribosome-recycling factor (RRF) and elongation factor G (EF-G) cause dissociation of ribosomes into subunits, solving the long-standing problem of how this essential step of translation occurs. However, there remains ongoing controversy regarding the other actions of RRF and EF-G during ribosome recycling. We propose that the available data are consistent with the notion that RRF and EF-G not only split ribosomes into subunits but also participate directly in the release of deacylated tRNA and mRNA for the next …

Trading The Micro-World Of Combinatorial Complexity For The Macro-World Of Protein Interaction Domains, Nikolay M. Borisov, Nick I. Markevitch, Jan B. Hoek, Boris N. Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Membrane receptors and proteins involved in signal transduction display numerous binding domains and operate as molecular scaffolds generating a variety of parallel reactions and protein complexes. The resulting combinatorial explosion of the number of feasible chemical species and, hence, different states of a network greatly impedes mechanistic modeling of signaling systems. Here we present novel general principles and identify kinetic requirements that allow us to replace a mechanistic picture of all possible micro-states and transitions by a macro-description of states of separate binding sites of network proteins. This domain-oriented approach dramatically reduces computational models of cellular signaling networks by dissecting …