Medicine and Health Sciences Commons^™

A Model Of The Roles Of Essential Kinases In The Induction And Expression Of Late Long-Term Potentiation, Paul Smolen, Douglas A. Baxter, John H. Byrne

Faculty, Staff and Student Publications

The induction of late long-term potentiation (L-LTP) involves complex interactions among second-messenger cascades. To gain insights into these interactions, a mathematical model was developed for L-LTP induction in the CA1 region of the hippocampus. The differential equation-based model represents actions of protein kinase A (PKA), MAP kinase (MAPK), and CaM kinase II (CAMKII) in the vicinity of the synapse, and activation of transcription by CaM kinase IV (CAMKIV) and MAPK. L-LTP is represented by increases in a synaptic weight. Simulations suggest that steep, supralinear stimulus-response relationships between stimuli (e.g., elevations in [Ca(2+)]) and kinase activation are essential for translating brief …

Comparison Of Og1rf And An Isogenic Fsrb Deletion Mutant By Transcriptional Analysis: The Fsr System Of Enterococcus Faecalis Is More Than The Activator Of Gelatinase And Serine Protease, Agathe Bourgogne, Susan G Hilsenbeck, Gary M Dunny, Barbara E Murray

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The FsrABC system of Enterococcus faecalis controls the expression of gelatinase and a serine protease via a quorum-sensing mechanism, and recent studies suggest that the Fsr system may also regulate other genes important for virulence. To investigate the possibility that Fsr influences the expression of additional genes, we used transcriptional profiling, with microarrays based on the E. faecalis strain V583 sequence, to compare the E. faecalis strain OG1RF with its isogenic mutant, TX5266, an fsrB deletion mutant. We found that the presence of an intact fsrB influences expression of numerous genes throughout the growth phases tested, namely, late log to …

Bifurcation And Singularity Analysis Of A Molecular Network For The Induction Of Long-Term Memory, Hao Song, Paul Smolen, Evyatar Av-Ron, Douglas A. Baxter, John H H. Byrne

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Withdrawal reflexes of the mollusk Aplysia exhibit sensitization, a simple form of long-term memory (LTM). Sensitization is due, in part, to long-term facilitation (LTF) of sensorimotor neuron synapses. LTF is induced by the modulatory actions of serotonin (5-HT). Pettigrew et al. developed a computational model of the nonlinear intracellular signaling and gene network that underlies the induction of 5-HT-induced LTF. The model simulated empirical observations that repeated applications of 5-HT induce persistent activation of protein kinase A (PKA) and that this persistent activation requires a suprathreshold exposure of 5-HT. This study extends the analysis of the Pettigrew model by applying …

Abnormal Expression Of Rest/Nrsf And Myc In Neural Stem/Progenitor Cells Causes Cerebellar Tumors By Blocking Neuronal Differentiation, Xiaohua Su, Vidya Gopalakrishnan, Duncan Stearns, Kenneth Aldape, Fredrick F Lang, Gregory Fuller, Evan Snyder, Charles G Eberhart, Sadhan Majumder

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Medulloblastoma, one of the most malignant brain tumors in children, is thought to arise from undifferentiated neural stem/progenitor cells (NSCs) present in the external granule layer of the cerebellum. However, the mechanism of tumorigenesis remains unknown for the majority of medulloblastomas. In this study, we found that many human medulloblastomas express significantly elevated levels of both myc oncogenes, regulators of neural progenitor proliferation, and REST/NRSF, a transcriptional repressor of neuronal differentiation genes. Previous studies have shown that neither c-Myc nor REST/NRSF alone could cause tumor formation. To determine whether c-Myc and REST/NRSF act together to cause medulloblastomas, we used a …

Hepatic And Renal Cytochrome P450 Gene Regulation During Citrobacter Rodentium Infection In Wild-Type And Toll-Like Receptor 4 Mutant Mice, Terrilyn A Richardson, Melanie Sherman, Leposava Antonovic, Sean S Kardar, Henry W Strobel, Daniel Kalman, Edward T Morgan

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Citrobacter rodentium is the rodent equivalent of human enteropathogenic Escherichia coli infection. This study investigated regulation of hepatic and renal cytochrome P450 (P450) mRNAs, hepatic P450 proteins, cytokines, and acute phase proteins during C. rodentium infection. Female C3H/HeOuJ (HeOu) and C3H/HeJ (HeJ) mice [which lack functional toll-like receptor 4 (TLR4)] were infected with C. rodentium by oral gavage and sacrificed 6 days later. Hepatic CYP4A10 and 4A14 mRNAs were decreased in HeOu mice (

Functional Analysis Of The Amine Substrate Specificity Domain Of Pepper Tyramine And Serotonin N-Hydroxycinnamoyltransferases, Sei Kang, Kiyoon Kang, Gap Chae Chung, Doil Choi, Atsushi Ishihara, Dong-Sun Lee, Kyoungwhan Back

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Pepper (Capsicum annuum) serotonin N-hydroxycinnamoyltransferase (SHT) catalyzes the synthesis of N-hydroxycinnamic acid amides of serotonin, including feruloylserotonin and p-coumaroylserotonin. To elucidate the domain or the key amino acid that determines the amine substrate specificity, we isolated a tyramine N-hydroxycinnamoyltransferase (THT) gene from pepper. Purified recombinant THT protein catalyzed the synthesis of N-hydroxycinnamic acid amides of tyramine, including feruloyltyramine and p-coumaroyltyramine, but did not accept serotonin as a substrate. Both the SHT and THT mRNAs were found to be expressed constitutively in all pepper organs. Pepper SHT and THT, which have primary sequences that are 78% identical, were used as models …

Translational Regulation Of Nuclear Gene Cox4 Expression By Mitochondrial Content Of Phosphatidylglycerol And Cardiolipin In Saccharomyces Cerevisiae, Xuefeng Su, William Dowhan

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Previous results indicated that translation of four mitochondrion-encoded genes and one nucleus-encoded gene (COX4) is repressed in mutants (pgs1Delta) of Saccharomyces cerevisiae lacking phosphatidylglycerol and cardiolipin. COX4 translation was studied here using a mitochondrially targeted green fluorescence protein (mtGFP) fused to the COX4 promoter and its 5' and 3' untranslated regions (UTRs). Lack of mtGFP expression independent of carbon source and strain background was established to be at the translational level. The translational defect was not due to deficiency of mitochondrial respiratory function but was rather caused directly by the lack of phosphatidylglycerol and cardiolipin in mitochondrial membranes. Reintroduction of …

Application Of Cognitive Engineering Principles To The Redesign Of A Dichotomous Identification Key For Parasitology, Kimberly A. Smith-Akins, Sharon Mclane, Thomas M. Craig, Todd R. Johnson

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Dichotomous identification keys are used throughout biology for identification of plants, insects, and parasites. However, correct use of identification keys can be difficult as they are not usually intended for novice users who may not be familiar with the terminology used or with the morphology of the organism being identified. Therefore, we applied cognitive engineering principles to redesign a parasitology identification key for the Internet. We addressed issues of visual clutter and spatial distance by displaying a single question couplet at a time and by switching to the appropriate next couplet after the user made a choice. Our analysis of …

A Time-Motion Study Of Registered Nurses’ Workflow In Intensive Care Unit Remote Monitoring, Zhihua Tang, Janine Mazabob, Liza Weavind, Eric Thomas, Todd R. Johnson

Faculty, Staff and Student Publications

Utilizing advanced information technology, Intensive Care Unit (ICU) remote monitoring allows highly trained specialists to oversee a large number of patients at multiple sites on a continuous basis. In the current research, we conducted a time-motion study of registered nurses’ work in an ICU remote monitoring facility. Data were collected on seven nurses through 40 hours of observation. The results showed that nurses’ essential tasks were centered on three themes: monitoring patients, maintaining patients’ health records, and managing technology use. In monitoring patients, nurses spent 52% of the time assimilating information embedded in a clinical information system and 15% on …

Using Citation Data To Improve Retrieval From Medline, Elmer V Bernstam, Jorge R Herskovic, Yindalon Aphinyanaphongs, Constantin F Aliferis, Madurai G Sriram, William R Hersh

Faculty, Staff and Student Publications

OBJECTIVE: To determine whether algorithms developed for the World Wide Web can be applied to the biomedical literature in order to identify articles that are important as well as relevant. DESIGN AND MEASUREMENTS A direct comparison of eight algorithms: simple PubMed queries, clinical queries (sensitive and specific versions), vector cosine comparison, citation count, journal impact factor, PageRank, and machine learning based on polynomial support vector machines. The objective was to prioritize important articles, defined as being included in a pre-existing bibliography of important literature in surgical oncology. RESULTS Citation-based algorithms were more effective than noncitation-based algorithms at identifying important articles. …

The Earliest Dipodomyine Heteromyid In North America And The Phylogenetic Relationships Of Geomorph Rodent, Steven J Norris

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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.

Mapping Concepts In Medical Error Taxonomies, Min Zhu, Yong Huang, Yang Gong, Juliana J. Brixey, Jiajie Zhang, James P. Turley

Faculty, Staff and Student Publications

No abstract provided.

Construction Of Improved Temperature-Sensitive And Mobilizable Vectors And Their Use For Constructing Mutations In The Adhesin-Encoding Acm Gene Of Poorly Transformable Clinical Enterococcus Faecium Strains, Sreedhar R Nallapareddy, Kavindra V Singh, Barbara E Murray

Faculty, Staff and Student Publications

Inactivation by allelic exchange in clinical isolates of the emerging nosocomial pathogen Enterococcus faecium has been hindered by lack of efficient tools, and, in this study, transformation of clinical isolates was found to be particularly problematic. For this reason, a vector for allelic replacement (pTEX5500ts) was constructed that includes (i) the pWV01-based gram-positive repAts replication region, which is known to confer a high degree of temperature intolerance, (ii) Escherichia coli oriR from pUC18, (iii) two extended multiple-cloning sites located upstream and downstream of one of the marker genes for efficient cloning of flanking regions for double-crossover mutagenesis, (iv) transcriptional terminator …

Dose-Response Characteristics Of Methylphenidate On Locomotor Behavior And On Sensory Evoked Potentials Recorded From The Vta, Nac, And Pfc In Freely Behaving Rats, Pamela B Yang, Alan C Swann, Nachum Dafny

Faculty, Staff and Student Publications

BACKGROUND: Methylphenidate (MPD) is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC).

METHODS: The present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg) on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto …

Chronic Exposure To Mdma (Ecstasy) Elicits Behavioral Sensitization In Rats But Fails To Induce Cross-Sensitization To Other Psychostimulants, Gunjan M Modi, Pamela B Yang, Alan C Swann, Nachum Dafny

Faculty, Staff and Student Publications

BACKGROUND: The recreational use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) among adolescents and young adults has become increasingly prevalent in recent years. While evidence suggests that the long-term consequences of MDMA use include neurodegeneration to serotonergic and, possibly, dopaminergic pathways, little is known about susceptibility, such as behavioral sensitization, to MDMA.

METHODS: The objectives of this study were to examine the dose-response characteristics of acute and chronic MDMA administration in rats and to determine whether MDMA elicits behavioral sensitization and whether it cross-sensitizes with amphetamine and methylphenidate. Adult male Sprague-Dawley rats were randomly divided into three MDMA dosage groups (2.5 mg/kg, 5.0 …

Hispanic Physicians' Tobacco Intervention Practices: A Cross-Sectional Survey Study, Francisco G. Soto Mas, Richard L. Papenfuss, Holly E. Jacobson, Chiehwen E. Hsu, William M. Kane

Faculty, Staff and Student Publications

Background U.S. Hispanic physicians constitute a considerable professional collective, and they may be most suited to attend to the health education needs of the growing U.S. Hispanic population. These educational needs include tobacco use prevention and smoking cessation. However, there is a lack of information on Hispanic physicians' tobacco intervention practices, their level of awareness and use of cessation protocols, and the type of programs that would best address their tobacco training needs. The purpose of this study was to assess the tobacco intervention practices and training needs of Hispanic physicians.

Methods Data was collected through a validated survey instrument …

Stress Levels, Psychological Symptoms, And C-Reactive Protein Levels In Covid-19: A Cross-Sectional Study, Jian Zhang, Wei Li, Hideo Hoshi, Stephen L Mills, Stephen C Massey

Faculty, Staff and Student Publications

The correlation between cholinergic sensitivity and the level of stratification for ganglion cells was examined in the rabbit retina. As examples, we have used ON or OFF alpha ganglion cells and ON/OFF directionally selective (DS) ganglion cells. Nicotine, a cholinergic agonist, depolarized ON/OFF DS ganglion cells and greatly enhanced their firing rates but it had modest excitatory effects on ON or OFF alpha ganglion cells. As previously reported, we conclude that DS ganglion cells are the most sensitive to cholinergic drugs. Confocal imaging showed that ON/OFF DS ganglion cells ramify precisely at the level of the cholinergic amacrine cell dendrites, …

Activation Of Src Kinase Lyn By The Kaposi Sarcoma-Associated Herpesvirus K1 Protein: Implications For Lymphomagenesis, Om Prakash, O Rama Swamy, Xiochang Peng, Zhen-Ya Tang, Li Li, Janet E Larson, J Craig Cohen, Javed Gill, Gist Farr, Suizhao Wang, Felipe Samaniego

Faculty, Staff and Student Publications

The K1 gene of Kaposi sarcoma-associated herpesvirus (KSHV) encodes a transmembrane glycoprotein bearing a functional immunoreceptor tyrosine-based activation motif (ITAM). Previously, we reported that the K1 protein induced plasmablastic lymphomas in K1 transgenic mice, and that these lymphomas showed enhanced Lyn kinase activity. Here, we report that systemic administration of the nuclear factor kappa B (NF-kappaB) inhibitor Bay 11-7085 or an anti-vascular endothelial growth factor (VEGF) antibody significantly reduced K1 lymphoma growth in nude mice. Furthermore, in KVL-1 cells, a cell line derived from a K1 lymphoma, inhibition of Lyn kinase activity by the Src kinase inhibitor PP2 decreased VEGF …

Cart: An Hrs/Actinin-4/Berp/Myosin V Protein Complex Required For Efficient Receptor Recycling, Qing Yan, Wei Sun, Pekka Kujala, Yasmin Lotfi, Thomas A Vida, Andrew J Bean

Faculty, Staff and Student Publications

Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The …

A Web Services Architecture For Umls Knowledge Sources, Parsa Mirhaji, Narendra Kunapareddy, Yanko Michea, Arunkumar Srinivasan

Faculty, Staff and Student Publications

A web service is a collection of industry standards to enable reusability of services and interoperability of heterogeneous applications. The UMLS Knowledge Source (UMLSKS) Server provides remote access to the UMLSKS and related resources. We propose a Web Services Architecture that encapsulates UMLSKS-API and makes it available in distributed and heterogeneous environments. This is the first step towards intelligent and automatic UMLS services discovery and invocation by computer systems in distributed environments such as web.

Interruptions In Workflow For Rns In A Level One Trauma Center, Juliana J. Brixey, David J. Robinson, Zhihua Tang, Todd R. Johnson, Jiajie Zhang, James P. Turley

Faculty, Staff and Student Publications

An understanding of interruptions in healthcare is important for the design, implementation, and evaluation of health information systems and for the management of clinical workflow and medical errors. The purpose of this study is to identify and classify the types of interruptions experienced by Emergency Department(ED) nurses working in a Level One Trauma Center. This was an observational field study of Registered Nurses (RNs) employed in a Level One Trauma Center using the shadowing method. Results of the study indicate that nurses were both recipients and initiators of interruptions. Telephones, pagers, and face-to-face conversations were the most common sources of …

The Relationship Between Future Orientation And Street Substance Use Among Texas Alternative School Students, R J Peters, Susan R Tortolero, Regina Jones Johnson, Robert C Addy, Christine M Markham, S Liliana Escobar-Chaves, Holly Lewis, George S Yacoubian

Faculty, Staff and Student Publications

Self-reported substance use data were collected from 963 alternative school students in grades 7-12 who were surveyed through the Safer Choices 2 study in Houston, Texas. Data were collected between October 2000 and March 2001. Logistic regression analyses indicated that lower levels of future orientation was significantly associated (OR = 0.88, 95% CI = 0.81-0.97) with thirty-day substance use after controlling for age and gender. In addition, lower levels of future orientation was found to have a significant association with students' lifetime substance use (OR = 0.93, 95% CI = 0.87-.99) after controlling for age, race, and gender. While the …

Using Technology To Teach Technology: Design And Evaluation Of Bilingual Online Physician Education About Electronic Medical Records, Sarah R. Edmonson, Adol Esquivel, Pallavi Mokkarala, Craig W. Johnson, Cynthia L. Phelps

Faculty, Staff and Student Publications

The "EMR Tutorial" is designed to be a bilingual online physician education environment about electronic medical records. After iterative assessment and redesign, the tutorial was tested in two groups: U.S. physicians and Mexican medical students. Split-plot ANOVA revealed significantly different pre-test scores in the two groups, significant cognitive gains for the two groups overall, and no significant difference in the gains made by the two groups. Users rated the module positively on a satisfaction questionnaire.

Comparison Of Accuracy Captured By Different Controlled Languages In Oral Pathology Diagnoses, Jung-Wei Chen, Catherine Flaitz, Todd Johnson

Faculty, Staff and Student Publications

This project was comparing the accuracy of capturing the oral pathology diagnoses among different coding systems. 55 diagnoses were selected for comparison among 5 coding systems. The results of accuracy in capturing oral diagnoses are: AFIP (96.4%), followed by Read 99 (85.5%), SNOMED 98 (74.5%), ICD-9 (43.6%), and CDT-3 (14.5%). It shows that the currently used coding systems, ICD-9 and CDT-3, were inadequate, whereas the AFIP coding system captured the majority of oral diagnoses. In conclusion, the most commonly used medical and dental coding systems lack terms for the diagnosis of oral and dental conditions.

Genetic Networks Controlling Retinal Injury, Felix R Vazquez-Chona, Amna N Khan, Chun K Chan, Anthony N Moore, Pramod K Dash, M Rosario Hernandez, Lu Lu, Elissa J Chesler, Kenneth F Manly, Robert W Williams, Eldon E Geisert

Faculty, Staff and Student Publications

PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury.

METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases.

RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription …

Prime-Boost Vaccination With Plasmid And Adenovirus Gene Vaccines Control Her2/Neu+ Metastatic Breast Cancer In Mice, Xiaoyan Wang, Jian-Ping Wang, Xiao-Mei Rao, Janet E Price, Heshan S Zhou, Lawrence B Lachman

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INTRODUCTION: Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu+ cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models.

METHODS: The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad …

Predicting Childhood Sexual Or Physical Abuse: A Logistic Regression Geo-Mapping Approach To Prevention, Roland K. Tadoum, Kamila Smolij, Michelle A. Lyn, Craig W. Johnson

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This study investigates the degree to which gender, ethnicity, relationship to perpetrator, and geomapped socio-economic factors significantly predict the incidence of childhood sexual abuse, physical abuse and non- abuse. These variables are then linked to geographic identifiers using geographic information system (GIS) technology to develop a geo-mapping framework for child sexual and physical abuse prevention.

Guideview: Structured Multi-Modal Delivery Of Clinical Guidelines, M Sriram Iyengar, Subhajit Sarkar, Kira Bacal, Gregory Defouw, Phyllis Mcculley, Victor Hurst

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GuideView is a system designed for structured, multi-modal delivery of clinical guidelines. Clinical instructions are presented simultaneously in voice, text, pictures or video or animations. Users navigate using mouse-clicks and voice commands. An evaluation study performed at a medical simulation laboratory found that voice and video instructions were rated highly.

Using Incomplete Citation Data For Medline Results Ranking, Jorge R Herskovic, Elmer V Bernstam

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Information overload is a significant problem for modern medicine. Searching MEDLINE for common topics often retrieves more relevant documents than users can review. Therefore, we must identify documents that are not only relevant, but also important. Our system ranks articles using citation counts and the PageRank algorithm, incorporating data from the Science Citation Index. However, citation data is usually incomplete. Therefore, we explore the relationship between the quantity of citation information available to the system and the quality of the result ranking. Specifically, we test the ability of citation count and PageRank to identify "important articles" as defined by experts …

Persuasive Email Messages For Patient Communication, Muhammad Walji, Kathy Johnson-Throop, Todd Johnson, Elmer Bernstam, Jiajie Zhang

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To improve health and reduce costs, we need to encourage patients to make better health care decisions. Since email is widely available, it may be useful for patient-directed interventions. However, we know little about how the contents of an email message can influence a health-related decision. We propose a model to understand how patients may process persuasive email messages.