Digital Commons Network^™

Safety And Tolerability Of An Ovine-Derived Polyclonal Anti-Tnfα Fab Fragment (Azd9773) In Patients With Severe Sepsis, Peter E. Morris, Brian Zeno, Andrew C. Bernard, Xiangning Huang, Steven G. Simonson, Gordon R. Bernard

Surgery Presentations

Sepsis remains a significant medical problem. TNFα is a central cytokine in sepsis pathophysiology. We conducted a phase IIa trial in patients with severe sepsis to assess the safety and tolerability of an intravenously infused ovine-derived polyclonal anti-TNFα Fab fragment (AZD9773).

The Role Of Xpg In Processing (Cag)N/(Ctg)N Dna Hairpins, Caixia Hou, Tianyi Zhang, Lei Tian, Jian Huang, Liya Gu, Guo-Min Li

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: During DNA replication or repair, disease-associated (CAG)n/(CTG)n expansion can result from formation of hairpin structures in the repeat tract of the newly synthesized or nicked DNA strand. Recent studies identified a nick-directed (CAG)n/(CTG)n hairpin repair (HPR) system that removes (CAG)n/(CTG)n hairpins from human cells via endonucleolytic incisions. Because the process is highly similar to the mechanism by which XPG and XPF endonucleases remove bulky DNA lesions during nucleotide excision repair, we assessed the potential role of XPG in conducting (CAG)n/(CTG)n HPR.

RESULTS: To determine if the XPG endonuclease is involved in (CAG)n/(CTG)n hairpin removal, two XPG-deficient cell lines (GM16024 …

Racial/Ethnic Disparities In Survival Among Men Diagnosed With Prostate Cancer In Texas, Arica L. White, Ann L. Coker, Xianglin L. Du, Katherine S. Eggleston, Melanie Williams

CRVAW Faculty Journal Articles

BACKGROUND:

To the authors' knowledge, few studies to date have examined racial differences in prostate cancer survival while controlling for socioeconomic status (SES). No such studies have examined this association in Texas, a large state with significant ethnic and racial diversity. The objective of this analysis was to determine whether racial disparities in survival for men diagnosed with prostate cancer in Texas from 1995 through 2002 remained after adjusting for SES, rural residence, and stage of disease.

METHODS:

A cohort of 87,449 men who were diagnosed with prostate cancer was identified from the Texas Cancer Registry. The SES measure was …

Semi Drivers Killed After Vehicle Rollovers, Kentucky Injury Prevention And Research Center

Kentucky Haz Alerts--Motor Vehicle

To prevent semi truck rollovers, employers should:

• Implement and enforce a seat belt safety program
• Establish and strengthen a company policy to reduce fatigue on the job

Employees should:

• Always wear a seat belt while in the vehicle
• Use correct lights during a fog
• Use proper precautions to reduce sloshing
• Reduce inadequate evasive actions

Global Gene Expression Profiles Of Subcutaneous Adipose And Muscle From Glucose-Tolerant, Insulin-Sensitive, And Insulin-Resistant Individuals Matched For Bmi, Steven C. Elbein, Philip A. Kern, Neda Rasouli, Aiwei Yao-Borengasser, Neeraj K. Sharma, Swapan K. Das

Clinical and Translational Science Faculty Publications

OBJECTIVE - To determine altered gene expression profiles in subcutaneous adipose and skeletal muscle from nondiabetic, insulin-resistant individuals compared with insulin-sensitive individuals matched for BMI.

RESEARCH DESIGN AND METHODS - A total of 62 nondiabetic individuals were chosen for extremes of insulin sensitivity (31 insulin-resistant and 31 insulin-sensitive subjects; 40 were European American and 22 were African American) and matched for age and obesity measures. Global gene expression profiles were determined and compared between ethnic groups and between insulin-resistant and insulin-sensitive participants individually and using gene-set enrichment analysis.

RESULTS - African American and European American subjects differed in 58 muscle …

Menstrual Bleeding Patterns In Adolescents Using Etonogestrel (Eng) Implant, Amit M. Deokar, Wendy Jackson, Hatim A. Omar

Pediatrics Faculty Publications

Background: Etonogestrel (ENG) implant is an effective method of contraception. The implant is designed to provide contraceptive efficacy for 3 years with a relatively quick return of fertility upon its removal. Menstrual irregularities are not uncommon on long-acting progestins and can often be the factor for discontinuation or removal. A retrospective chart analysis was done on 58 patients who chose to be on the ENG implant. Age ranged from 12 to 24 years. The cycle ranged from 1 to 17 months. The mean length of use of the implant was 10.9 months. Over the 20-month period, 13 ENG implants were …

Systematic Two-Hybrid And Comparative Proteomic Analyses Reveal Novel Yeast Pre-Mrna Splicing Factors Connected To Prp19, Liping Ren, Janel R. Mclean, Tony R. Hazbun, Stanley Fields, Craig Vander Kooi, Melanie D. Ohi, Kathleen L. Gould

Molecular and Cellular Biochemistry Faculty Publications

Prp19 is the founding member of the NineTeen Complex, or NTC, which is a spliceosomal subcomplex essential for spliceosome activation. To define Prp19 connectivity and dynamic protein interactions within the spliceosome, we systematically queried the Saccharomyces cerevisiae proteome for Prp19 WD40 domain interaction partners by two-hybrid analysis. We report that in addition to S. cerevisiae Cwc2, the splicing factor Prp17 binds directly to the Prp19 WD40 domain in a 1:1 ratio. Prp17 binds simultaneously with Cwc2 indicating that it is part of the core NTC complex. We also find that the previously uncharacterized protein Urn1 (Dre4 in Schizosaccharomyces pombe) directly …

High Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis, Chang-Guo Zhan, Fang Zheng, Wenchao Yang

Pharmaceutical Sciences Faculty Patents

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

A Brief History Of Phssr: The National Coordinating Center. Lessons From History, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Aspirin Treatment Of Mice Infected With Trypanosoma Cruzi And Implications For The Pathogenesis Of Chagas Disease, Shankar Mukherjee, Fabiana S. Machado, Huang Huang, Helieh S. Oz, Linda A. Jelicks, Cibele M. Prado, Wade Koba, Eugene J. Fine, Dazhi Zhao, Stephen M. Factor, J. Elias Collado, Louis M. Weiss, Herbert B. Tanowitz, Anthony W. Ashton

Center for Oral Health Research Faculty Publications

Chagas disease, caused by infection with Trypanosoma cruzi, is an important cause of cardiovascular disease. It is increasingly clear that parasite-derived prostaglandins potently modulate host response and disease progression. Here, we report that treatment of experimental T. cruzi infection (Brazil strain) beginning 5 days post infection (dpi) with aspirin (ASA) increased mortality (2-fold) and parasitemia (12-fold). However, there were no differences regarding histopathology or cardiac structure or function. Delayed treatment with ASA (20 mg/kg) beginning 60 dpi did not increase parasitemia or mortality but improved ejection fraction. ASA treatment diminished the profile of parasite- and host-derived circulating prostaglandins in infected …

Security Monitoring System For A Bulk Foodstuff Transport Container, Christopher Dwight Thompson, Suraj M. Alexander, William L. Christ, Brian D. Luck, James Ryan Moore, Jonathan C. Paschal, Frederick Payne, Timothy S. Stombaugh, Nasrin Tabayehnejad, Phillip C. Womble

Biosystems and Agricultural Engineering Faculty Patents

A security monitoring system provides for the secure transport of a bulk foodstuff container. The system includes an electromechanical locking mechanism allowing access by only authorized persons, a positional locator for determining the geographical position of the bulk foodstuff transport container, and a controller associated with the transport container. The controller controls operation of the electromechanical locking mechanism, stores data received from the electromechanical locking mechanism and the positional locator, and communicates with a remote data processor in near real time. A handheld user interface device is configured to control operation of the controller, to process and store data received …

Evaluation Of Immune Responses Following Infection Of Ponies With An Ehv-1 Orf1/2 Deletion Mutant, Gisela Soboll Hussey, Stephen B. Hussey, Bettina Wagner, David W. Horohov, Gerlinde R. Van De Walle, Nikolaus Osterrieder, Lutz S. Goehring, Sangeeta Rao, David P. Lunn

Veterinary Science Faculty Publications

Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite the widespread use of vaccines. The inability to generate a protective immune response to EHV-1 vaccination or infection is thought to be due to immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products have been hypothesized as potential candidates with immunoregulatory properties. A pony infection study was performed to define immune responses to EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would have different disease and immunoregulatory effects compared to wild type EHV-1 (WT). Infection with either virus led to cytokine responses that coincided with …

Subjects With Discordant Airways Obstruction: Lost Between Spirometric Definitions Of Copd, Bernd Lamprecht, Lea Schirnhofer, Bernhard Kaiser, Sonia A. Buist, David Mannino, Michael Studnicka

Preventive Medicine and Environmental Health Faculty Publications

Background. Since the FEV1/FVC ratio declines with age, using the fixed ratio of 0.70 leads to overdiagnosis of COPD in older populations and underdiagnosis among young adults. Objective. To evaluate whether discordant obstructive cases (FEV1/FVC < 0.70 but ≥LLN) are a healthy population or have clinical features that would place them at increased risk. Methods. We used post-bronchodilator spirometry data from the population-based Austrian Burden of Obstructive Lung Disease (BOLD) study. Those with post-bronchodilator FEV1/FVC ratio

Pediatric Ethics Guidelines For Hereditary Medullary Thyroid Cancer, M. Sara Rosenthal, Douglas S. Diekema

Internal Medicine Faculty Publications

Hereditary medullary thyroid cancer is an aggressive cancer for which there is no standard effective systemic therapy, but which can be prevented through genetic screening and prophylactic thyroidectomy. Although this cancer accounts for roughly 17% of all pediatric thyroid cancers, a significant percentage of affected families do not "accept" screening, while many gene carriers delay or refuse prophylactic thyroid surgery for their children. Current genetic screening practices in medullary thyroid cancer are inadequate; more than 50% of index patients with hereditary medullary thyroid cancer present with a thyroid mass; up to 75% have distant metastasis. These proposed pediatric ethics guidelines …

Cmr Of Lv Non-Compaction Cardiomyopathy: Association Of Clinical Presentation And Prognosis With Cardiac Phenotype, Mushabbar A. Syed, Steve W. Leung, Samy Claude Elayi, Richard J. Charnigo

Internal Medicine Presentations

Left ventricular non-compaction (LVNC) is a rare congenital disorder characterized by two layered myocardium; trabeculated (non-compacted) and a non-trabeculated (compacted). LVNC is increasingly being recognized due to better imaging technology as a cause for heart failure and sudden cardiac death; however, data on clinical and imaging characteristics remains limited.

Patterns Of Microrna Expression In Normal And Early Alzheimer's Disease Human Temporal Cortex: White Matter Versus Gray Matter, Wang-Xia Wang, Qingwei Huang, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNA (miRNA) expression was assessed in human cerebral cortical gray matter (GM) and white matter (WM) in order to provide the first insights into the difference between GM and WM miRNA repertoires across a range of Alzheimer's disease (AD) pathology. RNA was isolated separately from GM and WM portions of superior and middle temporal cerebral cortex (N = 10 elderly females, postmortem interval < 4 h). miRNA profiling experiments were performed using state-of-the-art Exiqon^© LNA-microarrays. A subset of miRNAs that appeared to be strongly expressed according to the microarrays did not appear to be conventional miRNAs according to Northern blot analyses. Some well-characterized miRNAs were substantially enriched in WM …

Grazing Non-Traditional Forages, Jeff Mccutcheon

Kentucky Grazing Conference

In the Heart of America region we are blessed with perennial cool-season grasses and legumes as the bulk of our forage production. Efficiently taking advantage of that perennial production is the focus of most grazing operations. Occasionally there are times when the production from our cool- season grass and legume pasture is not sufficient. In Ohio, that is late summer and late fall through winter till early spring. Nontraditional forages could be used when cool season forages are not producing. Non-traditional forages can provide a large volume, of high-quality feed during specific times of the year.

Grazing Goats And Cattle And Other Co-Species Grazing, Jason Tower

Kentucky Grazing Conference

Multispecies, co-species, mixed species grazing, it does not really matter what it is called they all revolve around the same premise; grazing more than one species of livestock on a given land area to improve resource use efficiencies.

Mob Grazing, High Density Grazing, Management-Intensive Grazing: What's The Difference?, Mark Kennedy

Kentucky Grazing Conference

Before we can answer that question we need to review some basic fundamentals of successful grazing management. Four goals of any sustainable grazing management strategy should be: 1) Meet the nutritional needs of livestock from standing pasture as many days as possible; 2) Optimize pasture yield, quality and persistence; 3) Maintain or enhance the natural resource base; 4) Integrate the appropriate technology and knowledge into a practical and profitable system that fits your available resources and meets your objectives. We will use these goals to compare and contrast these 2 grazing management techniques. Both techniques should be considered tools in …

Organic Dairying: Role Of Grazing, Jake Schmitz

Kentucky Grazing Conference

Certified organic and many conventional dairy farmers are using grazing techniques for a number of reasons, including building better soil, reducing feed costs, improving milk quality, and enhancing herd health. Additionally, certified organic farmers must utilize their pastures because the United States Department of Agriculture’s (USDA) organic rule requires organic cows to graze. Both the farmer and the USDA are working hard to ensure that “organic dairy” is synonymous with “grazing cows,” because the organic consumer vehemently demands dairy products from pasture-grazed livestock.

From Confinement To Grazing, Bill Payne

Kentucky Grazing Conference

A Tale of Two Businesses:

I would like share an account of a transition from a conventional dairy operation to our current Management Intensive Grazing (MIG) enterprise. In 1974, I joined my father who had been dairying on a 265 acre farm in Lincoln County, Kentucky for twenty five years. We fed our registered Holsteins corn silage and alfalfa haylage and purchased a manufactured feed. Our herd of 70 Holsteins spent most of their time on concrete. We did make an effort to allow access to an exercise lot when weather permitted. However, during most of the 1990’s we spent …

Cx3cl1 Reduces Neurotoxicity And Microglial Activation In A Rat Model Of Parkinson's Disease, Mibel M. Pabon, Adam D. Bachstetter, Charles E. Hudson, Carmelina Gemma, Paula C. Bickford

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of the neurodegeneration is unknown. Neuroinflammation has been clearly shown in Parkinson's disease and may be involved in the progressive nature of the disease. Microglia are capable of producing neuronal damage through the production of bioactive molecules such as cytokines, as well as reactive oxygen species (ROS), and nitric oxide (NO). The inflammatory response in the brain is tightly regulated at multiple levels. One form of immune regulation occurs via neurons. Fractalkine (CX3CL1), produced by neurons, suppresses the activation of microglia. CX3CL1 …

Mpges-1 Null Mice Are Resistant To Bleomycin-Induced Skin Fibrosis, Matthew R. Mccann, Roxana Monemdjou, Parisa Ghassemi-Kakroodi, Hassan Fahmi, Gemma Perez, Shangxi Liu, Xu Shi-Wen, Sunil K. Parapuram, Fumiaki Kojima, Christopher P. Denton, David J. Abraham, Johanne Martel-Pelletier, Leslie J. Crofford, Andrew Leask, Mohit Kapoor

Internal Medicine Faculty Publications

INTRODUCTION: Microsomal prostaglandin E2 synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase (COX) to specifically catalyze the conversion of prostaglandin (PG) H2 to PGE2. mPGES-1 plays a key role in inflammation, pain and arthritis; however, the role of mPGES-1 in fibrogenesis is largely unknown. Herein, we examine the role of mPGES-1 in a mouse model of skin scleroderma using mice deficient in mPGES-1.

METHODS: Wild type (WT) and mPGES-1 null mice were subjected to the bleomycin model of cutaneous skin scleroderma. mPGES-1 expressions in scleroderma fibroblasts and in fibroblasts derived from bleomycin-exposed mice were assessed by Western …

The Differential Effect Of Toxoplasma Gondii Infection On The Stability Of Bcl2-Family Members Involves Multiple Activities, John Cherrington Carmen, Anthony Peter Sinai

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The regulation of mitochondrial permeability, a key event in the initiation of apoptosis is governed by the opposing actions of the pro- and anti-apoptotic members of the BCL2-family of proteins. The BCL2-family can be classified further based on the number of BCL-homology (BH) domains they encode. Pathogen mediated modulation of BCL2-family members play a significant role in their ability to affect the apoptotic pathways in the infected host cell. The protozoan parasite Toxoplasma gondii establishes a profound blockade of apoptosis noted by a requirement for host NFκB activity and correlating with the selective degradation of pro-apoptotic BCL2-family members. In this …

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation And Cause Cell Cycle Arrest In A Pparγ Independent Manner, Linah Al-Alem, R. Chase Southard, Michael W. Kilgore, Thomas E. Curry

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Peroxisome Proliferator Activated Receptor gamma (PPARγ) agonists, such as the thiazolinediones (TZDs), have been studied for their potential use as cancer therapeutic agents. We investigated the effect of four TZDs--Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio)--on ovarian cancer cell proliferation, PPARγ expression and PPAR luciferase reporter activity. We explored whether TZDs act in a PPARγ dependent or independent manner by utilizing molecular approaches to inhibit or overexpress PPARγ activity.

PRINCIPAL FINDINGS: Treatment with CGZ or TGZ for 24 hours decreased proliferation in three ovarian cancer cell lines, Ovcar3, CaOv3, and Skov3, whereas Rosi and Pio had no …

Public Health Services And Systems Research: A Common Meeting Ground, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Membrane Potentials, Synaptic Responses, Neuronal Circuitry, Neuromodulation And Muscle Histology Using The Crayfish: Student Laboratory Exercises, Brittany Baierlein, Alison L. Thurow, Harold L. Atwood, Robin L. Cooper

Biology Faculty Publications

The purpose of this report is to help develop an understanding of the effects caused by ion gradients across a biological membrane. Two aspects that influence a cell's membrane potential and which we address in these experiments are: (1) Ion concentration of K⁺ on the outside of the membrane, and (2) the permeability of the membrane to specific ions. The crayfish abdominal extensor muscles are in groupings with some being tonic (slow) and others phasic (fast) in their biochemical and physiological phenotypes, as well as in their structure; the motor neurons that innervate these muscles are correspondingly different in …

Increased Mitochondrial Calcium Sensitivity And Abnormal Expression Of Innate Immunity Genes Precede Dopaminergic Defects In Pink1-Deficient Mice, Ravi S. Akundi, Zhenyu Huang, Joshua Eason, Jignesh D. Pandya, Lianteng Zhi, Wayne A. Cass, Patrick G. Sullivan, Hansruedi Büeler

Neuroscience Faculty Publications

BACKGROUND: PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²⁺ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice.

METHODS AND FINDINGS: Purified brain mitochondria of ^Pink1⁻/⁻ mice showed impaired Ca²⁺ storage capacity, resulting in increased Ca²⁺ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. …

Land Surveyor Struck And Killed By Passenger Vehicle, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

One late fall day in 2009, at approximately 3:30 PM, two land surveyors had completed surveying tasks for the day and were walking north, on opposites sides of a two-lane rural state highway. They were returning surveying equipment to the company truck. Surveyor 1, company owner, was walking with traffic on the east side of the road, in the grass, a few feet to the right of the pavement. Surveyor 2 was walking on the edge of the pavement on the west side of the road. Both men were on the road on the blind side of a hill and …

Municipal Solid Waste Collector Dies After Falling From Solid Waste Vehicle Hopper Area, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

On a spring day in 2010, a 41 year-old male, solid waste collector, was riding in the hopper area of a solid waste truck when he fell out and struck his head on the pavement. He was riding in the hopper area because the step he usually rode, located at the rear driver side, was broken. Another worker rode the rear step on the passenger side of the vehicle, and a third worker, the driver, drove. After approaching a stop, the driver looked into the rearview mirror and saw the decedent on the pavement. The driver stopped the truck, and …