Medicine and Health Sciences Commons^™

Replication Fork Regression In Vitro By The Werner Syndrome Protein (Wrn): Holliday Junction Formation, The Effect Of Leading Arm Structure And A Potential Role For Wrn Exonuclease Activity, Amrita Machwe, Liren Xiao, Robert G Lloyd, Edward Bolt, David K. Orren

Toxicology and Cancer Biology Faculty Publications

The premature aging and cancer-prone disease Werner syndrome stems from loss of WRN protein function. WRN deficiency causes replication abnormalities, sensitivity to certain genotoxic agents, genomic instability and early replicative senescence in primary fibroblasts. As a RecQ helicase family member, WRN is a DNA-dependent ATPase and unwinding enzyme, but also possesses strand annealing and exonuclease activities. RecQ helicases are postulated to participate in pathways responding to replication blockage, pathways possibly initiated by fork regression. In this study, a series of model replication fork substrates were used to examine the fork regression capability of WRN. Our results demonstrate that WRN catalyzes …

The Association Of Lung Cancer Mortality With Income And Education In Kentucky Counties, David A. Gross

Center of Excellence in Rural Health Presentations

Lung cancer, the primary cause of cancer death in the United States, is particularly problematic in Kentucky, which has the nation’s highest rate of adult smokers. In fact, each Kentucky county exceeds the national rate for per capita lung cancer deaths. This project analyzes the relationships between lung cancer deaths, high school graduation rates, per capita personal income and adult smoking – and whether statistically significant differences exist among the variables between Kentucky’s Appalachian and non-Appalachian counties.

Human Health Risk Assessment For Aluminium, Aluminium Oxide, And Aluminium Hydroxide, Daniel Krewski, Robert A. Yokel, Evert Nieboer, David Borchelt, Joshua Cohen, Jean Harry, Sam Kacew, Joan Lindsay, Amal M. Mahfouz, Virginie Rondeau

Pharmaceutical Sciences Faculty Publications

A compendium is provided of aluminium compounds used in industrial settings, and as pharmaceuticals, food additives, cosmetics and as other household products. Most aluminium compounds are solids exhibiting high melting points. The solubility of aluminium salts is governed by pH, because the aluminium(III)-cation (Al³⁺) has a strong affinity for the hydroxide ion, which promotes precipitation. Like Mg²⁺ and Ca²⁺ ions, Al³⁺ in most situations seeks out complexing agents with oxygen-atom donor sites such as carboxylate and phosphate groups, including in biological systems. Aluminium oxides, hydroxides and oxyhydroxides occur in numerous crystallographic forms, which exhibit different …

Functional Properties Of L-Glutamate Regulation In Anesthetized And Freely Moving Mice, Kevin N. Hascup

Theses and Dissertations--Neuroscience

L-glutamate (Glu) is the predominant excitatory neurotransmitter in the mammalian central nervous system with involvement encompassing learning and memory, cognition, plasticity, and motor movement. Dysregulation of the glutamatergic system is implicated in several neurological disorders including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and amyotrophic lateral sclerosis. The mechanisms underlying these neurological disorders are not clear, but evidence suggests that abnormal Glu neurotransmission plays a role. Elevated levels of Glu in the synaptic cleft overstimulate the N-methyl-Daspartate receptor leading to excitotoxicity, which causes neuronal loss in chronic neurological diseases. What is less understood is the source for the elevated Glu levels. …

Xenobiotic Transporters In Lactating Mammary Epithelial Cells: Predictions For Drug Accumulation In Breast Milk, Philip Earle Empey

Theses and Dissertations--Pharmacy

Recent literature has established that breast cancer resistance protein (ABCG2) is upregulated during lactation and is responsible for the greater than predicted accumulation of many drugs in breast milk. The objectives of this project were (1) to investigate the role of this transporter in the reported apically-directed nitrofurantoin flux in the CIT3 cell culture model of lactation, (2) to develop a mathematical model for drug transfer into breast milk to relate initial flux rates, steady-state concentrations, efflux ratios, and in vivo milk to serum ratios (M/S) and (3) to identify xenobiotic transporters that are highly expressed, and therefore potentially important …

Evaluating If The Built Environment Has A Substantial Effect On Obesity In Fayette County, Kentucky, Will Warren

MPA/MPP/MPFM Capstone Projects

Background:

Obesity is a major health issue in the United States and Fayette County. As Fayette County has become increasingly obese, it too has had an issue of sprawl within its urban service area and beyond. Relationships between obesity and aspects of the built environment are continuing to be studied.

Objective:

To evaluate the impact certain factors may have on the body mass index of Fayette County residents, in particular whether urban sprawl has an overriding impact on the weight of residents.

Methods:

The study area used was Fayette County, which was broken down into its fourteen zip code areas …

Preparing For The Future: An Evaluation Of Alternative Methods For Estimating The Needed Capacity Of Nursing Home Beds In Kentucky, Michelle D. Woods

MPA/MPP/MPFM Capstone Projects

Due to the aging of the generation known as “Baby Boomers”, the nation is expected to witness extraordinary growth in the total population ages 65 and over. Population projections provided by the United States Bureau of the Census suggest that this segment of the population will double in size to 72 million by the year 2030. In order to prepare for the anticipated increase elderly Americans, policy officials have been analyzing the potential effects on the nation’s long-term care system. Although Baby Boomers can expect to live longer than their predecessors, as they age, it is predicted that this generation …

Tracing The Origin Of The Recent Rise In Neuropathogenic Ehv-1, Kathryn Laura Smith

University of Kentucky Master's Theses

Equine herpesvirus type-1(EHV-1) is a complex virus known for inducing various forms of disease in horses. In recent years, the number of cases of neurological disease caused by this virus has increased. While there are a number of possible sources for this recent surge, this project set out to determine if a genotypic shift in the latent population of the virus in favor of the neuropathogenic form of EHV-1 is the basis for the recent increase in frequency of EHV-1 neurologic disease. To ascertain if such a shift has in fact occurred, 450 EHV-1 isolates were obtained from fetal tissues …

Identification And Characterization Of Ogg1 Mutations In Patients With Alzheimer's Disease, Guogen Mao, Xiaoyu Pan, Beibei Zhu, Yanbin Zhang, Fenghua Yuan, Jian Huang, Mark A. Lovell, Maxwell P. Lee, William R. Markesbery, Guo-Min Li, Liya Gu

Toxicology and Cancer Biology Faculty Publications

Patients with Alzheimer's disease (AD) exhibit higher levels of 8-oxo-guanine (8-oxoG) DNA lesions in their brain, suggesting a reduced or defective 8-oxoG repair. To test this hypothesis, this study investigated 14 AD patients and 10 age-matched controls for mutations of the major 8-oxoG removal gene OGG1. Whereas no alterations were detected in any control samples, four AD patients exhibited mutations in OGG1, two carried a common single base (C₇₉₆) deletion that alters the carboxyl terminal sequence of OGG1, and the other two had nucleotide alterations leading to single amino acid substitutions. In vitro biochemical assays revealed …

Senate Bill (Sb) 172: Governance Of Nutrition In Kentucky Public Schools: Implementation Analysis Final Report, Bill Brumbach

MPA/MPP/MPFM Capstone Projects

This report is intended to evaluate the implementation of Senate Bill (SB) 172 in Kentucky's public schools. This law requires that all schools in Kentucky implement strict nutrition standards that apply to all foods sold during the school day. This report highlights the different methods used by selected schools in implementing the requirements in SB 172. In performing my analysis, I traveled to different schools in central and southeastern Kentucky to assess how these select schools were meeting the requirements of the law. Site visits allowed me to discuss implementation strategies with school administrators and aided in my understanding of …

Expanding A General Surgery Practice: Privileges, Ambulatory Care Centers And Hospital Interactions, Julia Snow

MPA/MPP/MPFM Capstone Projects

The objective of this case study is to document the interactions between a general surgery practice group and a university medical center as the physician group establishes and seeks to expand its revenue base. The group proposes to lease or purchase a practice location where they can consult with patients and perform procedures. The practice location is near a competitive hospital, Saint Jose East. The surgeons currently have privileges at Saint Jose Hospital and request to continue the privileges.

The case study's design and methods include benchmarking and financial analysis. The results of the study are :

• Benchmarking of operating …

Molecular Mechanisms Of Olfactory Neurodegeneration, Radhika Anand Vaishnav

University of Kentucky Doctoral Dissertations

Olfactory sensory decline has been associated with normal aging as well as neurodegenerative disorders, yet the underlying mechanisms are unclear. The overall aim of this dissertation was to investigate the fundamental molecular and cellular mechanisms associated with olfactory neurodegeneration. This investigation uses an integrative approach, combining proteomics and gene expression analyses with cellular and tissuelevel characterization. Using these approaches, two model systems were investigated: 1) normally aging C57BL/6 mice of ages 1.5-, 6- and 20-months; and 2) a mouse model of elevated endogenous oxidative stress-associated neurodegeneration, namely, the Harlequin mutant mouse. The first specific aim was to test the hypothesis …

Microemulsions As Precursors To Solid Nanoparticles, Russell John Mumper, Michael Jay

Pharmaceutical Sciences Faculty Patents

The preparation of novel microemulsions to be used as precursors for solid nanoparticles is described. The microemulsion precursors consist of either alcohol-in-fluorocarbon microemulsions, liquid hydrocarbon-in-fluorocarbon microemulsions, or liquid hydrocarbon-in-water microemulsions. The formed solid nanoparticles have diameters below 200 nanometers and can be made to entrap various materials including drugs, magnets, and sensors. The solid nanoparticles can be made to target different cells in the body by the inclusion of a cell-specific targeting ligand. Methods of preparing the novel microemulsion precursors and methods to cure solid nanoparticles are provided.

Oxpat/Pat-1 Is A Ppar-Induced Lipid Droplet Protein That Promotes Fatty Acid Utilization, Nathan E. Wolins, Benjamin K. Quaynor, James R. Skinner, Anatoly Tzekov, Michelle A. Croce, Matthew C. Gropler, Vijayalakshmi Varma, Aiwei Yao-Borengasser, Neda Rasouli, Philip A. Kern, Brian N. Finck, Perry E. Bickel

Clinical and Translational Science Faculty Publications

Lipid droplet proteins of the PAT (perilipin, adipophilin, and TIP47) family regulate cellular neutral lipid stores. We have studied a new member of this family, PAT-1, and found that it is expressed in highly oxidative tissues. We refer to this protein as "OXPAT." Physiologic lipid loading of mouse liver by fasting enriches OXPAT in the lipid droplet tissue fraction. OXPAT resides on lipid droplets with the PAT protein adipophilin in primary cardiomyocytes. Ectopic expression of OXPAT promotes fatty acid-induced triacylglycerol accumulation, long-chain fatty acid oxidation, and mRNAs associated with oxidative metabolism. Consistent with these observations, OXPAT is induced in mouse …

The Lipogenic Enzymes Dgat1, Fas, And Lpl In Adipose Tissue: Effects Of Obesity, Insulin Resistance, And Tzd Treatment, Gouri Ranganathan, Resat Unal, Irina D. Pokrovskaya, Aiwei Yao-Borengasser, Bounleut Phanavanh, Beata Lecka-Czernik, Neda Rasouli, Philip A. Kern

Clinical and Translational Science Faculty Publications

Acyl-coenzyme A:diacylglycerol transferase (DGAT), fatty acid synthetase (FAS), and LPL are three enzymes important in adipose tissue triglyceride accumulation. To study the relationship of DGAT1, FAS, and LPL with insulin, we examined adipose mRNA expression of these genes in subjects with a wide range of insulin sensitivity (S_I). DGAT1 and FAS (but not LPL) expression were strongly correlated with S_I. In addition, the expression of DGAT1 and FAS (but not LPL) were higher in normal glucose-tolerant subjects compared with subjects with impaired glucose tolerance (IGT) (P < 0.005). To study the effects of insulin sensitizers, subjects with IGT were treated with pioglitazone or metformin for 10 weeks, and lipogenic enzymes were measured in adipose tissue. After pioglitazone treatment, DGAT1 expression was increased by 33 ± 10% (P < 0.05) and FAS expression increased by 63 ± 8% (P < 0.05); however, LPL expression was not altered. DGAT1, FAS, and LPL mRNA expression were not significantly changed after metformin treatment. The treatment of mice with rosiglitazone also resulted in an increase in adipose expression of DGAT1 by 2- to 3-fold, as did the treatment of 3T3 F442A adipocytes in vitro with thiazolidinediones. These data support a more global concept suggesting that adipose lipid storage functions to prevent peripheral lipotoxicity.

The Role Of Mapks In B Cell Receptor-Induced Down-Regulation Of Egr-1 In Immature B Lymphoma Cells, Jiyuan Ke, Murali Gururajan, Anupam Kumar, Alan Simmons, Lilia Turcios, Ralph Lakshman Chelvarajan, David M. Cohen, David L. Wiest, John G. Monroe, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Cross-linking of the B cell receptor (BCR) on the immature B lymphoma cell line BKS-2 induces growth inhibition and apoptosis accompanied by rapid down-regulation of the immediate-early gene egr-1. In these lymphoma cells, egr-1 is expressed constitutively and has a prosurvival role, as Egr-1-specific antisense oligonucleotides or expression of a dominant-negative inhibitor of Egr-1 also prevented the growth of BKS-2 cells. Moreover, enhancement of Egr-1 protein with phorbol 12-myristate 13-acetate or an egr-1 expression vector rescued BKS-2 cells from BCR signal-induced growth inhibition. Nuclear run-on and mRNA stability assays indicated that BCR-derived signals act at the transcriptional level to …

Navigating Adolescence With A Chronic Health Condition: A Perspective On The Psychological Effects Of Hair-An Syndrome On Adolescent Girls, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

HAIR-AN syndrome is a subphenotype of polycystic ovary syndrome and is characterized by acne, obesity, hirsutism, and acanthosis nigricans. It usually manifests in early adolescence, a time of significant developmental change in females across physical, cognitive, social, and emotional domains. We contend that adolescent development for females is difficult, even in the best of circumstances, and having a chronic health condition, like HAIR-AN syndrome, will likely impact the afflicted individual's development and psychological well-being. While many researchers have discussed the long-term health effects of HAIR-AN and similar disorders, little has been written about the potential psychological sequelae of HAIR-AN on …

A Missense Mutation In Pmel17 Is Associated With The Silver Coat Color In The Horse, Emma Brunberg, Leif Andersson, Gus Cothran, Kaj Sandberg, Sofia Mikko, Gabriella Lindgren

Veterinary Science Faculty Publications

BACKGROUND: The Silver coat color, also called Silver dapple, in the horse is characterized by dilution of the black pigment in the hair. This phenotype shows an autosomal dominant inheritance. The effect of the mutation is most visible in the long hairs of the mane and tail, which are diluted to a mixture of white and gray hairs. Herein we describe the identification of the responsible gene and a missense mutation associated with the Silver phenotype.

RESULTS: Segregation data on the Silver locus (Z) were obtained within one half-sib family that consisted of a heterozygous Silver colored stallion with 34 …

Aluminum Bioavailability From The Approved Food Additive Leavening Agent Acidic Sodium Aluminum Phosphate, Incorporated Into A Baked Good, Is Lower Than From Water, Robert A. Yokel, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

There are estimates of oral aluminum (Al) bioavailability from drinking water, but little information on Al bioavailability from foods. Foods contribute ∼95% and drinking water 1–2% of the typical human's daily Al intake. The objectives were to estimate oral Al bioavailability from a representative food containing the food additive acidic sodium aluminum phosphate (acidic SALP), a leavening agent in baked goods. Rats were acclimated to a special diet that resulted in no stomach contents 14 h after its withdrawal. They were trained to rapidly consume a biscuit containing 1.5% acidic SALP. Oral Al bioavailability was then determined from a biscuit …

Stress, Coping, Social Support, And Prostate Cancer Risk Among Older African American And Caucasian Men, Ann L. Coker, Maureen Sanderson, Gary L. Ellison, Mary Kay Fadden

CRVAW Faculty Journal Articles

Objectives: While psychosocial stress and high effort coping have been associated with reduced immune function, no epidemiologic study has addressed psychological stress and risk of prostate cancer. The purpose of this analysis was to investigate the association between stress, coping, social support, and risk of prostate cancer among older men (age 65–79 years). Design: Population-based case-control study in South Carolina.

Participants: Cases were 400 incident, histologically confirmed prostate cancer cases identified through the South Carolina Central Cancer Registry between 1999 and 2001 (70.6% response rate). Controls were 385 men identified through the 1999 Health Care Financing Administration Medicare beneficiary file …

Victims Struck Out By Logging, Kentucky Injury Prevention And Research Center

Kentucky Haz Alerts--Tractors/Logging

To prevent injuries while felling trees:

• Loggers should attend the Kentucky Master Logger program for training and education regarding Occupational Safety and Health Administration logging standards and safety procedures.
• A “pre-job safety plan” should be developed for each job site and the plan should be reviewed prior to each day on the site.
• Proper notching and directional felling techniques should be utilized when felling trees.
• Develop a felling plan for each tree prior to felling that includes escape route, dead or hanging branches, vines, and nearby trees.

Lipin Expression Is Attenuated In Adipose Tissue Of Insulin-Resistant Human Subjects And Increases With Peroxisome Proliferator-Activated Receptor Γ Activation, Aiwei Yao-Borengasser, Neda Rasouli, Vijayalakshmi Varma, Lesliie M. Miles, Bounleut Phanavanh, Tasha Starks, Jack Phan, Horace J. Spencer Iii, Robert E. Mcgehee Jr., Karen Reue, Philip A. Kern

Clinical and Translational Science Faculty Publications

Lipin-α and -β are the alternatively spliced gene products of the Lpin1 gene, whose product lipin is required for adipocyte differentiation. Lipin deficiency causes lipodystrophy, fatty liver, and insulin resistance in mice, whereas adipose tissue lipin overexpression results in increased adiposity but improved insulin sensitivity. To assess lipin expression and its relation to insulin resistance in humans, we examined lipin-α and -β mRNA levels in subjects with normal or impaired glucose tolerance. We found higher expression levels of both lipin isoforms in lean, insulin-sensitive subjects. When compared with normal glucose-tolerant subjects, individuals with impaired glucose tolerance were more insulin resistant, …

Comparative Analysis Of Vertebrate Eif2ak2 (Pkr) Genes And Assignment Of The Equine Gene To Eca15q24-Q25 And The Bovine Gene To Bta11q12-Q15, Andrey A. Perelygin, Teri L. Lear, Andrey A. Zharkikh, Margo A Brinton

Veterinary Science Faculty Publications

The structures of the canine, rabbit, bovine and equine EIF2AK2 genes were determined. Each of these genes has a 5' non-coding exon as well as 15 coding exons. All of the canine, bovine and equine EIF2AK2 introns have consensus donor and acceptor splice sites. In the equine EIF2AK2 gene, a unique single nucleotide polymorphism that encoded a Tyr329Cys substitution was detected. Regulatory elements predicted in the promoter region were conserved in ungulates, primates, rodents, Afrotheria (elephant) and Insectifora (shrew). Western clawed frog and fugu EIF2AK2 gene sequences were detected in the USCS Genome Browser and compared to those of other …

Design And Implementation Of The Domestic Violence Services In Rural Clinics Intervention, Ann L. Coker, Paige H. Smith, Vicki C. Flerx, Daniel J. Whitaker, Mary Kay Fadden, Melinda Williams

CRVAW Faculty Book Chapters

No abstract provided.

Amputation Injuries Due To Forklifts, Kentucky Injury Prevention And Research Center

Kentucky Haz Alerts--Other

To prevent injuries from forklifts while working:

• Before you operate a forklift, make sure that you are trained and certified.
• Remember if you are on a sit-down type forklift, and it starts to over-turn, lean in the opposite direction, stay with the forklift; don’t jump.
• When operating a forklift on site, slow the truck and sound the horn at cross aisles, exits, and other employee traverse points.
• Before dismounting, set the parking brake, lower the forks or lifting carriage, and neutralize controls.

From Healing The Whole Person: An Argument For Therapeutic Touch As A Complement To Traditional Medical Practice, Marlene B. Huff, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

The growing popularity and use of therapeutic touch (TT) is an issue that has generated controversy and concern within the medical community. While anecdotal and traditional scientific evidence suggest that TT would be an advantageous addition for clinics and hospitals to include in their armamentarium of complementary interventions within the realm of traditional medicine, TT has not become widely available in the U.S. One reason for the lack of availability may be the dearth of conclusive scientific support for TT's efficacy and, therefore, its inclusion in clinic and hospital treatment planning would give it the appearance of legitimate practice, which …

Pregnant Teenager Involvement In Sexual Activity And The Social Context, Maria José Carvalho Sant'anna, Júlia Kerr Catunda, Kepler Alencar Mendes Carvalho, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

Pregnancy during adolescence represents a challenge to society as a whole. Its incidence is increasing and brings about social and medical consequences to both the teen mothers and their children. The purpose of this study was to evaluate pregnant teenager involvement in sexual activity and the social context. The group studied comprised 152 pregnant teenagers attending the Department of Pediatrics, Santa Casa de Sao Paulo (SCSP) General Hospital. All information was analyzed. The age at first intercourse was 14.2 years and the average period between first intercourse and pregnancy was 1.4 years. Most pregnancies (75%) were neither planned nor wanted, …

Murine Monoclonal Anti-Idiotype Antibody 3h1 Sequences For Human Carcinoembryonic Antigen, Malaya Chatterjee, Heinz Köhler, Sunil K. Chatterjee, Kenneth A. Foon

Microbiology, Immunology and Molecular Genetics Faculty Patents

This invention provides compositions derived from the sequences encoding the variable light and/or variable heavy regions of monoclonal anti-idiotype antibody 3H1 and methods for using these compositions.

Chain-Modified Pyridino-N Substituted Nicotine Compounds For Use In The Treatment Of Cns Pathologies, Peter A. Crooks, Linda Dwoshin, Rui Xu, Joshua T. Ayers

Pharmaceutical Sciences Faculty Patents

Compounds for treating abuse of nicotinic receptor agonists, addiction to psychostimulant drugs, addiction to opiates, addiction to alcohol, addiction to tobacco products, addiction to nicotine, schizophrenia and related diseases, depression and related conditions, Alzheimer's disease, Parkinson's disease, irritable bowel syndrome, and colitis. The compounds competitively inhibit central nervous system acting nicotinic receptor agonists and act at the putative α3β2* and α4β2 neuronal nicotinic receptors in the central nervous system.

Long Acting, Reversible Veterinary Sedative And Analgesic And Method Of Use, Thomas Tobin

Veterinary Science Faculty Patents

A veterinary composition comprising a guanidine derivative, e.g., guanabenz or guanabenz acetate is provided which produces a rapid acting and long lasting sedative and analgesic effect in a subject animal that is selectively reversible. The use of guanabenz in the horse provides for a safe, effective, long lasting and rapidly reversible sedative and analgesic which can be used on the standing animal. Methods of use of the compositions of the invention are also provided.