Medical Sciences Commons^™

Flavone: The Molecular And Mechanistic Study Of How A Simple Flavonoid Protects Dna From Oxidative Damage., Jennifer Dawn Dean

Electronic Theses and Dissertations

Dietary flavonoids are ubiquitous and are marketed as supplements. Characterized as antioxidants, they offer protection against a number of degenerative diseases. Flavonoid mechanics involve free radical scavenging, metal chelation, and substrate association. The skeletal structure of flavonoids is a fused ring system modified by hydroxyl, sugar, and carbohydrate additions. Flavone is a structurally simple flavonoid. Quercetin and its glycosidic analog rutin are complex structures. Using a DNA oxidation/cleavage assay, flavone reduces DNA nicking by 91%. Depending on the solvent system used, quercetin can either increase or decrease DNA oxidation. Rutin exhibits neither pro- nor antioxidant activity. The molecular interactions responsible …

The Role Of Erp57 In Hras Intracellular Trafficking And Function., Jaime Lyn Parman

Electronic Theses and Dissertations

Ras is a central player in signal transduction that mediates cellular proliferation and differentiation. Recent evidence has shown that lipid and non-lipid modified domains participate in Ras traffic and that plasma membrane association is mediated by vectorial vesicular transport from the endomembrane system. ERp57, an ER chaperone, has been shown to specifically bind farnesylated Hras but not non-farnesylated Hras. The objective of this study was to determine if ERp57 participates in Ras trafficking and function. First, the effect of ERp57 knock down by siRNA technology on Hras function was studied; there was a reduction in ERp57 cellular levels that led …

Tolerance Of The Fetus By The Maternal Immune System: Role Of Inflammatory Mediators At The Feto-Maternal Interface, Colette Kanellopoulos-Langevin, Stephane M. Caucheteux, Philippe Verbeke, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

The adaptive immune system of placental mammals has evolved to tolerate the fetus. Rejection of the fetus by adaptive immune responses is therefore a rare event, with abortion being caused more frequently by inflammation in the placenta. This review will cover recent aspects of immune privilege and the innate immune system at the feto-maternal interface, citing examples of the role played by microbial infections in fetal demise.

Effect Of Background Synaptic Activity On Excitatory-Postsynaptic Potential-Spike Coupling, Veronika Zsiros

Theses and Dissertations (ETD)

Neurons receive large amount of synaptic inputs in vivo, which may impact the coupling between EPSPs and spikes. We mimicked the in vivo synaptic activity of the cell with the dynamic clamp system. We recorded from pyramidal cells in neocortical slices in vitro to investigate how timing and probability of spike generation in response to an EPSP is affected by background synaptic conductance under these conditions. We found that near threshold, background synaptic conductance improved the precision of spike timing by reducing the depolarization-related prolongation of the EPSP. In cells with ongoing spike activity and background synaptic conductances, an …

The Relation Of Dietary Patterns To Future Survival, Health, And Cardiovascular Events In Older Adults, Paula Diehr

Paula Diehr

BACKGROUND: There have been few long-term follow-up studies of older adults who follow different dietary patterns. METHODS: We cluster-analyzed data on dietary fat, fiber, protein, carbohydrate, and calorie consumption from the U.S. Cardiovascular Health Study (mean age=73), and examined the relationship of the dietary clusters to outcomes 10 years later. RESULTS: The five clusters were named "Healthy diet" (relatively high in fiber and carbohydrate and low in fat), "Unhealthy diet" (relatively high in protein and fat, relatively low in carbohydrates and fiber); "High Calorie," "Low Calorie," and "Low 4," which was distinguished by higher alcohol consumption. The clusters were strongly …

Interleukin-10 And Pathogenesis Of Murine Ocular Toxoplasmosis, Fangli Lu, Shiguang Huang, Lloyd H. Kasper

Dartmouth Scholarship

To understand the role of interleukin-10 (IL-10) in ocular toxoplasmosis, we compared C57BL/6 (B6) and BALB/c background mice lacking a functional IL-10 gene (IL-10(-/-)) and B6 transgenic mice expressing IL-10 under the control of the IL-2 promoter. Increased cellular infiltration and necrosis were observed in the eye tissue of IL-10(-/-) mice of both the B6 and BALB/c backgrounds with associated changes in the levels of cytokines in serum. In contrast, there was no evidence of necrosis in the eye tissue from IL-10 transgenic mice following parasite exposure. Our results demonstrate that IL-10 is important in the regulation of inflammation during …

Modeling The Optimum Duration Of Antibiotic Prophylaxis In An Anthrax Outbreak, Ron Brookmeyer, Elizabeth Johnson, Robert Bollinger

Ron Brookmeyer

A critical consideration in effective and measured public health responses to an outbreak of inhalational anthrax is the optimum duration of antibiotic prophylaxis. We develop a competing-risks model to address the duration of antibiotic prophylaxis and the incubation period that accounts for the risks of spore germination and spore clearance. The model predicts the incubation period distribution, which is confirmed by empirical data. The optimum duration of antibiotic prophylaxis depends critically on the dose of inhaled spores. At high doses, we show that exposed persons would need to remain on antibiotic prophylaxis for at least 4 months, and considerable morbidity …

Statistical Models And Bioterrorism: Application To The U.S. Anthrax Outbreak, Ron Brookmeyer, Natalie Blades

Ron Brookmeyer

In the fall of 2001 an outbreak of inhalational anthrax occurred in the United States that was the result of bioterrorism. Letters contaminated with anthrax spores were sent through the postal system. In response to the outbreak, public health officials treated over 10,000 persons with antibiotic prophylaxis in the hopes of preventing further morbidity and mortality. No persons receiving the antibiotics subsequently developed disease. The question arises as to how many cases of disease may actually have been prevented by the public health intervention of antibiotic prophylaxis. A statistical model is developed to answer this question by relating to the …

Embryonic Origins Of A Motor System: Motor Dendrites Form A Myotopic Map In Drosophila, Matthias Landgraf, Victoria Jeffrey, Miki Fujioka, James B. Jaynes, Michael Bate

Department of Biochemistry and Molecular Biology Faculty Papers

The organisational principles of locomotor networks are less well understood than those of many sensory systems, where in-growing axon terminals form a central map of peripheral characteristics. Using the neuromuscular system of the Drosophila embryo as a model and retrograde tracing and genetic methods, we have uncovered principles underlying the organisation of the motor system. We find that dendritic arbors of motor neurons, rather than their cell bodies, are partitioned into domains to form a myotopic map, which represents centrally the distribution of body wall muscles peripherally. While muscles are segmental, the myotopic map is parasegmental in organisation. It forms …

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

Molecular and Cellular Biochemistry Faculty Patents

A compound and method for using compound-D SEQ ID NO:1 to reduce injury associated with ischemia and reperfusion of mammalian organs such as the heart. The compound 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.

Incidence And Correlates Of Breast Milk Feeding In Hospitalized Preterm Infants, K. A. Espy, T. E. Senn

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

The majority of epidemiological studies of breast feeding have been conducted in healthy, fullterm infant samples. Little is known about the incidence and correlates of breast milk feeding in preterm infants, particularly in those born outside of metropolitan areas. Therefore, hospital medical charts of 151 consecutively admitted preterm infants (

Effects Of Environmental Measures On Intelligence In Young Children: Growth Curve Modeling Of Longitudinal Data, K. A. Espy, Victoria J. Molfese, L. Dilalla

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

Examined the effects of different environmental measures on individual intellectual growth patterns in 105 young children participating in a longitudinal study. Intelligence (Stanford-Binet, 4th edition) was measured at ages 3 through 6 yrs, and child's environment was assessed at age 3 years using SES data and scores on the Home Observation for Measurement of the Environment (HOME) Inventory. Growth curve analyses revealed that HOME scores exerted a constant influence on the expected composite, verbal, and nonverbal intellectual skills at each age. Only SES influenced the rate of growth, specifically nonverbal intellectual skills. The magnitudes of these effects were moderate, but …

Effects Of Neurobehavioral Assessment On Feeding And Weight Gain In Preterm Neonates, T. E. Senn, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

Neonatal intensive care unit personnel and parents often are concerned that developmental assessment will tire preterm neonates and impair their feeding ability and subsequent weight gain. Therefore, the amount of fluid consumed by 108 preterm neonates (≤36.5 wk gestational age) was compared before and after administration of the Neurobehavioral Assessment of the Preterm Infant (NAPI). In addition, the weight gain of 35 preterm neonates who were administered the NAPI was compared with that of a matched control group of 35 preterm neonates who were not administered the NAPI. There were no differences in the amount of fluid consumed before and …

Decreasing Barriers For Teens: Evaluation Of A New Teenage Pregnancy Prevention Strategy In School-Based Clinics, Abbey C. Sidebottom, Amanda Birnbaum, Sarah S. Nafstad

Department of Public Health Scholarship and Creative Works

Sidebottom et al seek to evaluate the effects of the change in distribution systems on students' receipt of requested contraceptives and demand for contraceptive school-based clinics (SBC). The result of the study reveals that the average number of requests per student was higher under the voucher system, possibly as a consequence of expires vouchers resulting in repeated requests. The findings also suggest that SBCs could go a step further in reducing adolescents' barriers to accessing contraceptives by adopting an on-site direct delivery system..

Interpreting Hemoglobin And Water Concentration, Oxygen Saturation, And Scattering Measured In Vivo By Near-Infrared Breast Tomography, Subhadra Srinivasan, Brian W. Pogue, Shudong Jiang, Hamid Dehghani, Christine Kogel, Sandra Soho, Jennifer J. Gibson, Tor D. Tosteson, Steven P. Poplack, Keith D. Paulsen

Dartmouth Scholarship

Near-infrared spectroscopic tomography was used to measure the properties of 24 mammographically normal breasts to quantify whole-breast absorption and scattering spectra and to evaluate which tissue composition characteristics can be determined from these spectra. The absorption spectrum of breast tissue allows quantification of (i) total hemoglobin concentration, (ii) hemoglobin oxygen saturation, and (iii) water concentration, whereas the scattering spectrum provides information about the size and number density of cellular components and structural matrix elements. These property data were tested for correlation to demographic information, including subject age, body mass index, breast size, and radiographic …

Rejoinder To "“Wavelet-Based Nonparametric Modeling Of Hierarchical Functions In Colon Carcinogenesis.”, Jeffrey S. Morris, Marina Vannucci, Philip J. Brown, Raymond J. Carroll

Jeffrey S. Morris

No abstract provided.

Quality Control And Peak Finding For Proteomics Data Collected From Nipple Aspirate Fluid Using Surface Enhanced Laser Desorption And Ionization., Jeffrey S. Morris, Kevin R. Coombes, Herbert A. Fritsche, Charlotte Clarke, Jeng-Neng Chen, Keith A. Baggerly, Lian-Chun Xiao, Mien-Chie Hung, Henry M. Kuerer

Jeffrey S. Morris

Background: Recently, researchers have been using mass spectroscopy to study cancer. For use of proteomics spectra in a clinical setting, stringent quality-control procedures will be needed.

Methods: We pooled samples of nipple aspirate fluid from healthy breasts and breasts with cancer to prepare a control sample. Aliquots of the control sample were used on two spots on each of three IMAC ProteinChip® arrays (Ciphergen Biosystems, Inc.) on 4 successive days to generate 24 SELDI spectra. In 36 subsequent experiments, the control sample was applied to two spots of each ProteinChip array, and the resulting spectra were analyzed to determine how …

Imputation Of Missing Longitudinal Data: A Comparison Of Methods, Paula Diehr, Jean Mundahl Engels

Paula Diehr

BACKGROUND AND OBJECTIVES: Missing information is inevitable in longitudinal studies, and can result in biased estimates and a loss of power. One approach to this problem is to impute the missing data to yield a more complete data set. Our goal was to compare the performance of 14 methods of imputing missing data on depression, weight, cognitive functioning, and self-rated health in a longitudinal cohort of older adults. METHODS: We identified situations where a person had a known value following one or more missing values, and treated the known value as a "missing value." This "missing value" was imputed using …

Waddington’S Widget: Hsp90 And The Inheritance Of Acquired Characters, Douglas M. Ruden, Mark D. Garfinkel, Vincent E. Sollars, Xiangyi Lu

Biochemistry and Microbiology

Conrad Waddington published an influential model for evolution in his 1942 paper, Canalization of Development and Inheritance of Acquired Characters. In this classic, albeit controversial, paper, he proposed that an unknown mechanism exists that conceals phenotypic variation until the organism is stressed. Recent studies have proposed that the highly conserved chaperone Hsp90 could function as a “capacitor,” or an “adaptively inducible canalizer,” that masks silent phenotypic variation of either genetic or epigenetic origin. This review will discuss evidence for, and arguments against, the role of Hsp90 as a capacitor for morphological evolution, and as a key component of what …

Il-7 Enhances Peripheral T Cell Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation., Onder Alpdogan, Stephanie J Muriglan, Jeffrey M Eng, Lucy M Willis, Andrew S Greenberg, Barry J Kappel, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

We used clinically relevant murine allogeneic bone marrow transplantation (BMT) models to study the mechanisms by which IL-7 administration can improve posttransplant peripheral T cell reconstitution. After transplant we could distinguish two populations of mature donor T cells: (a) alloreactive T cells with decreased expression of CD127 (IL-7 receptor alpha chain) and (b) nonalloreactive T cells, which express CD127 and undergo homeostatic proliferation. IL-7 administration increased the homeostatic proliferation of nonalloreactive T cells, but had no effect on alloreactive T cells and the development of graft-versus-host disease. Allogeneic transplant of purified hematopoietic stem cells and adoptive transfer of thymocytes into …

Topographical Expression Of Class Ia And Class Ii Phosphoinositide 3-Kinase Enzymes In Normal Human Tissues Is Consistent With A Role In Differentiation, Soha Salama El Sheikh, Jan Domin, Prakitpunthu Tomtitchong, Paul Abel, Gordon Stamp, El-Nasir Lalani

Department of Pathology and Laboratory Medicine

Background: Growth factor, cytokine and chemokine-induced activation of PI3K enzymes constitutes the start of a complex signalling cascade, which ultimately mediates cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. The PI3K enzyme family is divided into 3 classes; class I (subdivided into IA and IB), class II (PI3K-C2α, PI3K-C2β and PI3K-C2γ) and class III PI3K. Expression of these enzymes in human tissue has not been clearly defined.

Methods: In this study, we analysed the immunohistochemical topographical expression profile of class IA (anti-p85 adaptor) and class II PI3K (PI3K-C2α and PI3K-C2β) enzymes in 104 formalin-fixed, paraffin embedded …

Wavelet-Based Nonparametric Modeling Of Hierarchical Functions In Colon Carcinogenesis., Jeffrey S. Morris, Marina Vannucci, Philip J. Brown, Raymond J. Carroll

Jeffrey S. Morris

In this article we develop new methods for analyzing the data from an experiment using rodent models to investigate the effect of type of dietary fat on O6-methylguanine-DNA-methyltransferase (MGMT), an important biomarker in early colon carcinogenesis. The data consist of observed profiles over a spatial variable contained within a two-stage hierarchy, a structure that we dub hierarchical functional data. We present a new method providing a unified framework for modeling these data, simultaneously yielding estimates and posterior samples for mean, individual, and subsample-level profiles, as well as covariance parameters at the various hierarchical levels. Our method is nonparametric in that …

Trajectories Of Health For Older Adults Over Time: Accounting Fully For Death, Paula Diehr

Paula Diehr

The process of healthy aging can best be described by plotting the trajectory of health-related variables over time. Unfortunately, graphs including data only from survivors may be misleading because they may confuse patterns of mortality with patterns of change in health. Two approaches for creating graphs that account for death in such situations are 1) to incorporate a category or value for death into the longitudinal health variable and 2) to measure time in years before death or some other event. The first approach has been applied to self-rated health (excellent to poor) and the 36-Item Short-Form Health Survey (SF-36). …

The Benefits Of Breastfeeding: An Introduction For Health Educators, Sheila G. J. Clark, Timothy J. Bungum

Environmental & Occupational Health Faculty Publications

Currently 16% of Americans breastfeed their children for at least 12 months as recommended by the AAP, which is well below the HP 2010 goal of 25%. Breastfed infants receive benefits that can improve their health throughout their lives. The benefits of breastfeeding for children include increased resistance to infectious diseases, such as gastroenteritis, respiratory tract infections, and ear infections. Breastfed children also display lower rates of chronic diseases including diabetes, obesity, asthma, and leukemia. The choice to breastfeed results in economic benefits from lower health care costs and from reduced spending on infant formula. The Healthy People 2010 targets …

Sart Influences Sars Expression In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus is a gram-positive pathogen that is capable of expressing a variety of virulence proteins in response to environmental signals. Virulence protein expression in S. aureus is controlled by a network of regulatory loci including sarA and agr. The sarA/agr network is associated with the expression of cell wall-associated adhesins during exponential growth and the expression of secreted enzymes and toxins in the transition to post-exponential growth. A number of sarA homologs, including sarT and sarS, have been identified in the S. aureus genome. Previous studies have shown that sarA influences expression of both sarT and sarS in the …

Immortalized Epithelial Cells From Human Autosomal Dominant Polycystic Kidney Cysts, Mahmoud Loghman-Adham, Surya M. Nauli, Carlos E. Soto, Barbara Kariuki, Jing Zhou

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (ADPKD) is the result of mutations in one allele of the PKD1 or PKD2 genes, followed by "second hit" somatic mutations of the other allele in renal tubule cells. Continued proliferation of clonal cells originating from different nephron segments leads to cyst formation. In vitro studies of the mechanisms of cyst formation have been hampered by the scarcity of nephrectomy specimens and the limited life span of cyst-derived cells in primary culture. We describe the development of a series of immortalized epithelial cell lines from over 30 individual renal cysts obtained from 11 patients with …

Prediction Of Fetal Sheep Brain Metabolic Rate During Hypoxia And Cord Occlusion, Adam D. Hickerson

Loma Linda University Electronic Theses, Dissertations & Projects

Many investigators have observed that fetal and neonatal animals are remarkably tolerant to hypoxia compared to the adult. The precise mechanisms however are still unclear. In order to better characterize the hemodynamic and metabolic responses of the fetal brain to hypoxic stress, we have designed a mathematical model to predict tissue oxygenation and metabolic rate of the fetal brain during both moderate hypoxia and severe asphyxia.

The model is based on the Krogh cylinder concept and is similar to one previously published by our lab. Several new concepts were added including the ability to run the model over time using …

Validation Of A Serotonin Checklist In A Parkinson’S Disease Population, Kelly Diane Darby-Holder

Loma Linda University Electronic Theses, Dissertations & Projects

Although the distinctive pathological marker of Parkinson’s Disease is the progressive death of neurons that produce dopamine, there are also alterations in the production of quantities of other neurotransmitters, such as norepinephrine and serotonin that contribute to the disease. Parkinson’s Disease (PD) can be divided into two distinct classes based on the manifestation of motor symptoms, Type A and Type B Parkinson’s Disease. Type B PD patients often manifest symptoms in which serotonin deficiency plays an important role, which often includes a history of depression. Within the brain and spinal cord serotonin has wide spread projections, acting as an important …

Genome-Wide Scan For Quantitative Trait Loci Influencing Ldl Size And Plasma Triglyceride In Familial Hypertriglyceridemia, Melissa A. Austin, Karen L. Edwards, Stephanie A. Monks, Kent M. Koprowicz, John D. Brunzell, Arno G. Motulsky, Michael C. Mahaney, James E. Hixson

Kent M Koprowicz

No abstract provided.

The Virulence Activator Apha Links Quorum Sensing To Pathogenesis And Physiology In Vibrio Cholerae By Repressing The Expression Of A Penicillin Amidase Gene On The Small Chromosome, Gabriela Kovacikova, Wei Lin, Karen Skorupski

Dartmouth Scholarship

Activation of the tcpPH promoter on the Vibrio pathogenicity island by AphA and AphB initiates the Vibrio cholerae virulence cascade and is regulated by quorum sensing through the repressive action of HapR on aphA expression. To further understand how the chromosomally encoded AphA protein activates tcpPH expression, site-directed mutagenesis was used to identify the base pairs critical for AphA binding and transcriptional activation. This analysis revealed a region of partial dyad symmetry, TATGCA-N6-TNCNNA, that is important for both of these activities. Searching the V. cholerae genome for this binding site permitted the identification of a second one upstream of a …