Medical 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.

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 …

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 …

Cdx4 Dysregulates Hox Gene Expression And Generates Acute Myeloid Leukemia Alone And In Cooperation With Meis1a In A Murine Model, Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Döhner, Patricia Ernst

Dartmouth Scholarship

HOX genes have emerged as critical effectors of leukemogenesis, but the mechanisms that regulate their expression in leukemia are not well understood. Recent data suggest that the caudal homeobox transcription factors CDX1, CDX2, and CDX4, developmental regulators of HOX gene expression, may contribute to HOX gene dysregulation in leukemia. We report here that CDX4 is expressed normally in early hematopoietic progenitors and is expressed aberrantly in approximately 25% of acute myeloid leukemia (AML) patient samples. Cdx4 regulates Hox gene expression in the adult murine hematopoietic system and dysregulates Hox genes that are implicated in leukemogenesis. Furthermore, bone marrow progenitors that …

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 …

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 …

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.

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 …

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 …

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

Department of Medicine Faculty Papers

No abstract available.

Alterations In Vasodilator-Stimulated Phosphoprotein (Vasp) Phosphorylation: Associations With Asthmatic Phenotype, Airway Inflammation And Β2-Agonist Use, Annette T. Hastie, Min Wu, Gayle C. Foster, Gregory A. Hawkins, Vikas Batra, Katherine A. Rybinski, Rosemary Cirelli, James G. Zangrilli, Stephen P. Peters

Department of Medicine Faculty Papers

Background

Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this "brake" on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo β₂-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion.

Methods

Bronchial epithelium was obtained from asthmatic …

Clinical Perspectives Of Emerging Pathogens In Bleeding Disorders, Jamie Siegel

Department of Medicine Faculty Papers

As a result of immunological and nucleic-acid screening of plasma donations for transfusion-transmissible viruses, and the incorporation of viral reduction processes during plasma fractionation, coagulation-factor concentrates (CFC) are now judged safe in terms of many known infectious agents, including hepatitis B and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging pathogens could pose future threats, particularly those with blood-borne stages that are resistant to viral-inactivation steps in the manufacturing process, such as non-lipid-coated viruses. As outlined in this Review, better understanding of infectious diseases allows challenges from newly described agents of potential concern in the future to be …

A Database And Tool, Im Browser, For Exploring And Integrating Emerging Gene And Protein Interaction Data For Drosophila, Svetlana Pacifico, Guozhen Liu, Stephen Guest, Jodi R. Parrish, Farshad Fotouhi, Russell L. Finley Jr

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Biological processes are mediated by networks of interacting genes and proteins. Efforts to map and understand these networks are resulting in the proliferation of interaction data derived from both experimental and computational techniques for a number of organisms. The volume of this data combined with the variety of specific forms it can take has created a need for comprehensive databases that include all of the available data sets, and for exploration tools to facilitate data integration and analysis. One powerful paradigm for the navigation and analysis of interaction data is an interaction graph or map that represents proteins …

Transcriptional Profiling Of Degraded Rna In Cryopreserved And Fixed Tissue Samples Obtained At Autopsy, Andrew C. Haller, Deepa Kanakapalli, Rosemarie Walter, Samir Alhasan, James F. Eliason, Richard B. Everson

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Traditional multiplexed gene expression methods require well preserved, intact RNA. Such specimens are difficult to acquire in clinical practice where formalin fixation is the standard procedure for processing tissue. Even when special handling methods are used to obtain frozen tissue, there may be RNA degradation; for example autopsy samples where degradation occurs both pre-mortem and during the interval between death and cryopreservation. Although specimens with partially degraded RNA can be analyzed by qRT-PCR, these analyses can only be done individually or at low levels of multiplexing and are laborious and expensive to run for large numbers of RNA …

Identification Of Novel Functional Sequence Variants In The Gene For Peptidase Inhibitor 3, Mahboob A. Chowdhury, Helena Kuivaniemi, Roberto Romero, Samuel Edwin, Tinnakorn Chaiworapongsa, Gerard Tromp

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Peptidase inhibitor 3 (PI3) inhibits neutrophil elastase and proteinase-3, and has a potential role in skin and lung diseases as well as in cancer. Genome-wide expression profiling of chorioamniotic membranes revealed decreased expression of PI3 in women with preterm premature rupture of membranes. To elucidate the molecular mechanisms contributing to the decreased expression in amniotic membranes, the PI3 gene was searched for sequence variations and the functional significance of the identified promoter variants was studied.

Methods

Single nucleotide polymorphisms (SNPs) were identified by direct sequencing of PCR products spanning a region from 1,173 bp upstream to 1,266 bp …

K-Spmm: A Database Of Murine Spermatogenic Promoters Modules & Motifs, Yi Lu, Adrian E. Platts, G Charles Ostermeier, Stephen A. Krawetz

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Understanding the regulatory processes that coordinate the cascade of gene expression leading to male gamete development has proven challenging. Research has been hindered in part by an incomplete picture of the regulatory elements that are both characteristic of and distinctive to the broad population of spermatogenically expressed genes.

Description

K-SPMM, a database of murine Spermatogenic Promoters Modules and Motifs, has been developed as a web-based resource for the comparative analysis of promoter regions and their constituent elements in developing male germ cells. The system contains data on 7,551 genes and 11,715 putative promoter regions …

The Dynamic Proteome Of Lyme Disease Borrelia, Steven J Norris

Journal Articles

The proteome of the spirochete bacterium Borrelia burgdorferi, the tick-borne agent of Lyme disease, has been characterized by two different approaches using mass spectrometry, providing a launching point for future studies on the dramatic changes in protein expression that occur during transmission of the bacterium between ticks and mammals.

Characterization Of Hard2, A Processed Hard1 Gene Duplicate, Encoding A Human Protein N-Alpha-Acetyltransferase., Thomas Arnesen, Matthew J Betts, Frédéric Pendino, David A Liberles, Dave Anderson, Jaime Caro, Xianguo Kong, Jan E Varhaug, Johan R Lillehaug

Department of Medicine Faculty Papers

BACKGROUND: Protein acetylation is increasingly recognized as an important mechanism regulating a variety of cellular functions. Several human protein acetyltransferases have been characterized, most of them catalyzing epsilon-acetylation of histones and transcription factors. We recently described the human protein acetyltransferase hARD1 (human Arrest Defective 1). hARD1 interacts with NATH (N-Acetyl Transferase Human) forming a complex expressing protein N-terminal alpha-acetylation activity. RESULTS: We here describe a human protein, hARD2, with 81 % sequence identity to hARD1. The gene encoding hARD2 most likely originates from a eutherian mammal specific retrotransposition event. hARD2 mRNA and protein are expressed in several human cell lines. …