Digital Commons Network^™

Clock In Breast Tumorigenesis: Evidence From Genetic, Epigenetic, And Transcriptional Profiling Analyses, Richard G. Stevens

UCHC Articles - Research

As transcriptional regulators, the genes responsible for maintaining circadian rhythm exert influence in a variety of biological processes. Recently, it has been suggested that the core circadian genes may play a role in breast tumorigenesis, possibly by influencing hormone regulation or other cancer-relevant pathways. Here, we examine the role of the central circadian regulator CLOCK in breast cancer by conducting a genetic and epigenetic association study, as well as transcriptional profiling arrays and a pathway-based network analysis. Significant associations were detected between CLOCK tagging SNPs and breast cancer risk, with apparent effect modification by ER/PR status. Furthermore, hypermethylation in the …

Racial And Ethnic Disparities In Low Birth Weight Delivery Associated With Maternal Occupational Characteristics, John D. Meyer, Nicholas D. Warren, Susan T. Reisine

UCHC Articles - Research

Objectives

Work characteristics and maternal education have both been associated with low birth weight (LBW) delivery. We sought to examine the relative contribution of these two factors to LBW delivery and determine whether ethnic/racial differentials in educational attainment and work characteristics might play a role in well-described disparities in LBW.

Methods

Scores for work substantive complexity (SC) derived from the O*NET were imputed to maternal occupation for Connecticut singleton births in 2000. Risks for LBW were estimated separately for black, Hispanic, and white mothers using logistic regression controlling for maternal covariates.

Results

Using white mothers as a referent, working is …

White Matter Hyperintensities Predict Functional Decline In Voiding, Mobility And Cognition In Older Persons, Dorothy B. Wakefield, George A. Kuchel, Richard F. Kaplan, Leslie I. Wolfson

UCHC Articles - Research

Objective

To compare MRI data to functional assessments of mobility, urinary control, and cognition to determine common or distinctive features in the distribution of brain white matter hyperintensities (WMHs) associated with functional decline/impairment.

Design

Baseline data from subjects 75-89 years enrolled in a longitudinal study. Assessors and subjects were blinded to group assignment.

Participants

99 subjects were enrolled using a balanced 3×3 matrix stratified by age and mobility performance. Exclusion criteria included: medication, systemic conditions, and neurologic diseases which can compromise mobility.

Setting

Healthy community-dwelling volunteers.

Measurements

WMHs were identified using semi-automated segmentation method and regional burdens were assessed utilizing …

Prognostic Value Of Ishak Fibrosis Stage: Findings From The Halt-C Trial, Herbert L. Bonkovsky

UCHC Articles - Research

Background and Aims

Studies of the prognostic value of Ishak fibrosis stage are lacking. We utilized multi-year follow-up of the Hepatitis C Antiviral Long Term Treatment Against Cirrhosis (HALT-C) Trial to determine whether individual Ishak fibrosis stages predicted clinical outcomes in patients with chronic hepatitis C.

Methods

Baseline liver biopsies from 1,050 patients with compensated chronic hepatitis C who had failed combination peginterferon and ribavirin were reviewed by a panel of expert hepatopathologists. Fibrosis was staged with the Ishak scale (ranging from 0=no fibrosis to 6=cirrhosis). Biopsy fragmentation and length as well as number of portal tracts were recorded. We …

Memory Cd8+ T Cell Differentiation, Joshua J. Obar, Leo Lefrancois

UCHC Articles - Research

In response to infection or effective vaccination, naive antigen-specific CD8+ T cells undergo a dramatic highly orchestrated activation process. Initial encounter with an appropriately activated antigen-presenting cell leads to blastogenesis and an exponential increase in antigen-specific CD8+ T cell numbers. Simultaneously, a dynamic differentiation process occurs, resulting in formation of both primary effector and long-lived memory cells. Current findings have emphasized the heterogeneity of effector and memory cell populations with the description of multiple cellular subsets based on phenotype, function, and anatomic location. Yet, only recently have we begun to dissect the underlying factors mediating the temporal control of the …

Stroke In Women: Disparities And Outcomes, Rebecca W. Persky, Lisa Christine Turtzo, Louise D. Mccullough

UCHC Articles - Research

Stroke is the leading cause of disability in the United States and affects 15 million people worldwide. Studies performed in various parts of the world have found differences between sexes in stroke incidence, prevalence, mortality, and outcomes. Although men are at higher risk of stroke for most age groups below age 85 years, after this age the incidence reverses dramatically, with women being much more at risk. Furthermore, recent studies suggest that women have worse recovery than men post-stroke. Many aspects of recovery may influence this outcome, including sex-specific comorbidities, aggressiveness of acute treat-ment, prevention therapies, and varying degrees of …

Role Of The Cyclooxygenase Pathway In Chemotherapy-Induced Oral Mucositis: A Pilot Study, Rajesh V. Lalla, Carol C. Pilbeam, Stephen J. Walsh, Stephen T. Sonis, Dorothy M. K. Keefe, Douglas E. Peterson

UCHC Articles - Research

Goals Oral mucositis can be a significant and dose-limiting complication of high-dose cancer therapy. Mucositis is a particularly severe problem in patients receiving myeloablative chemotherapy prior to bone marrow or hematopoetic stem cell transplant (HSCT). The cyclooxygenase (COX) pathway mediates tissue injury and pain through upregulation of pro-inflammatory prostaglandins, including prostaglandin E2 (PGE2) and prostacyclin (PGI2). The objective of this small (n=3) pilot study was to examine the role of the COX pathway in causing mucosal injury and pain in chemotherapy-induced oral mucositis. Materials and methods We collected blood, saliva, and oral mucosal biopsy specimens from three autologous …

Nonlinear Oscillations In Pain Prediction Accuracy: A Dynamical Systems Approach To Understanding Daily Pain Prediction, Howard A. Tennen

UCHC Articles - Research

Dynamical systems modeling was used to analyze fluctuations in the pain prediction process of people with rheumatoid arthritis. 170 people diagnosed with rheumatoid arthritis completed 29 consecutive days of diaries. Difference scores between pain predictions and next-day pain experience ratings provided a time series of pain prediction accuracy. Pain prediction accuracy oscillated over time. The oscillation amplitude was larger at the start of the diary than at the end, which indicates damping toward more accurate predictions. State-level psychological characteristics moderated the damping pattern such that the oscillations for patients with lower negative affect and higher pain control damped more quickly …

Functional Polymorphisms In The Serotonin 1b Receptor Gene (Htr1b) Predict Self-Reported Anger And Hostility Among Young Men, Kevin P. Jensen, Henry M. Furneaux, Howard A. Tennen, Henry R. Kranzler, Jonathan Covault

UCHC Articles - Research

Objective To examine associations between haplotypes of the serotonin 1B receptor gene and individual differences in anger and hostility. Methods Data were analyzed from a study of 361 university students (47% male). Participants were genotyped at 5 polymorphisms in the HTR1B gene (rs11568817, rs130058, rs6296, rs6297, rs13212041), including promoter and 3′UTR polymorphisms with opposite functional effects on gene expression. Participants reported their emotional states across 30 consecutive days for up to four years. Haplotype pairs were constructed statistically and assigned to a level of HTR1B expression based on the presence of the functional polymorphisms. Results Six haplotypes accounted for >97% …

Use Of Virtual Cell In Studies Of Cellular Dynamics, Leslie M. Loew, Boris M. Slepchenko

UCHC Articles - Research

The Virtual Cell (VCell) is a unique computational environment for modeling and simulation of cell biology. It has been specifically designed to be a tool for a wide range of scientists, from experimental cell biologists to theoretical biophysicists. The models created with VCell can range from the simple, to evaluate hypotheses or to interpret experimental data, to complex multi-layered models used to probe the predicted behavior of spatially resolved, highly non-linear systems. In this Chapter, we discuss modeling capabilities of VCell and demonstrate representative examples of the models published by the Virtual Cell users.

Expansion Of The Eukaryotic Proteome By Alternative Splicing, Brenton R. Graveley

UCHC Articles - Research

The collection of components required to carry out the intricate processes involved in generating and maintaining a living, breathing and, sometimes, thinking organism is staggeringly complex. Where do all of the parts come from? Early estimates stated that about 100,000 genes would be required to make up a mammal; however, the actual number is less than one-quarter of that, barely four times the number of genes in budding yeast. It is now clear that the ‘missing’ information is in large part provided by alternative splicing, the process by which multiple different functional messenger RNAs, and therefore proteins, can be synthesized …