Medicine and Health Sciences Commons^™

Efficient Activation Of Reconstructed Rat Embryos By Cyclin-Dependent Kinase Inhibitors, Robin L. Webb, Kirk A. Findlay, Michael A. Green, Tina L. Beckett, M. Paul Murphy

Molecular and Cellular Biochemistry Faculty Publications

Background

Over the last decade a number of species, from farm animals to rodents, have been cloned using somatic cell nuclear transfer technology (SCNT). This technique has the potential to revolutionize the way that genetically modified animals are made. In its current state, the process of SCNT is very inefficient (<5% success rate), with several technical and biological hurdles hindering development. Yet, SCNT provides investigators with powerful advantages over other approaches, such as allowing for prescreening for the desired level of transgene expression and eliminating the excess production of undesirable wild-type animals. The rat plays a significant role in biomedical research, but SCNT has been problematic for this species. In this study, we address one aspect of the problem by evaluating methods of activation in artificially constructed rat embryos.

Principal Findings

We demonstrate that treatment with a calcium ionophore (ionomycin) combined with a variety of cyclin-dependent kinase inhibitors is an effective way to activate rat embryos. This is in contrast to methods developed for the mouse embryo, which tolerates much less specific chemical treatments. Methods developed to activate …

Dopamine Neuron Stimulating Actions Of A Gdnf Propeptide, Luke H. Bradley, Josh Fuqua, April Richardson, Jadwiga Turchan-Cholewo, Yi Ai, Kristen A. Kelps, John D. Glass, Xiuquan He, Zhiming Zhang, Richard Grondin, O. Meagan Littrell, Peter Huettl, Francois Pomerleau, Don M. Gash, Greg A. Gerhardt

Neuroscience Faculty Publications

BACKGROUND: Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), have shown great promise for protection and restoration of damaged or dying dopamine neurons in animal models and in some Parkinson's disease (PD) clinical trials. However, the delivery of neurotrophic factors to the brain is difficult due to their large size and poor bio-distribution. In addition, developing more efficacious trophic factors is hampered by the difficulty of synthesis and structural modification. Small molecules with neurotrophic actions that are easy to synthesize and modify to improve bioavailability are needed.

METHODS AND FINDINGS: Here we present the neurobiological actions of dopamine …

Use Of Parthenolide Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Xiaochen Wei

Pharmaceutical Sciences Faculty Patents

To view this abstract, please download this patent.

Eicosapentaenoic Acid Preserves Diaphragm Force Generation Following Endotoxin Administration, Gerald S. Supinski, Jonas Vanags, Leigh Ann Callahan

Internal Medicine Faculty Publications

INTRODUCTION: Infections produce severe respiratory muscle weakness, which contributes to the development of respiratory failure. An effective, safe therapy to prevent respiratory muscle dysfunction in infected patients has not been defined. This study examined the effect of eicosapentaenoic acid (EPA), an immunomodulator that can be safely administered to patients, on diaphragm force generation following endotoxin administration.

METHODS: Rats were administered the following (n = 5/group): (a) saline, (b) endotoxin, 12 mg/kg IP, (c) endotoxin + EPA (1.0 g/kg/d), and (d) EPA alone. Diaphragms were removed and measurements made of the diaphragm force-frequency curve, calpain activation, caspase activation, and protein carbonyl …

Workers Killed While Working With Forklifts, Kentucky Injury Prevention And Research Center

Kentucky Haz Alerts--Other

To prevent forklift injuries:

• Do not operate a forklift without being certified and trained.
• Forklift operators should wear their safety belts.
• Do not jump from an overturning forklift. Keep your body inside the forklift frame. Ride it out and lean in the opposite direction of the overturn.
• Do not place yourself between two forklifts.
• Do not handle loads that are heavier than the load capacity of the forklift.
• Make sure that the travel path of the forklift is clear from the floor to the height of the load being moved.
• Do not step on elevated loads.
• It is a violation …

Residential Tree Trimmers Killed While Working, Kentucky Injury Prevention And Research Center

Kentucky Haz Alerts--Falls

To prevent tree trimmer injuries:

• Tree trimming or cutting should not be performed without appropriate safety training.
• Appropriate personal protective equipment should be worn at all times while removing trees.
• All trees and limbs should be inspected for structural weakness before work commences.
• Safe work procedures should be used for climbing, felling, topping, and pruning trees.
• A jobsite hazard assessment should be performed to identify hazards so that hazards can be controlled for.

Microrna In Situ Hybridization In The Human Entorhinal And Transentorhinal Cortex, Peter T. Nelson, James Dimayuga, Bernard R. Wilfred

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) play key roles in gene expression regulation in both healthy and disease brains. To better understand those roles, it is necessary to characterize the miRNAs that are expressed in particular cell types under a range of conditions. In situ hybridization (ISH) can demonstrate cell- and lamina-specific patterns of miRNA expression that would be lost in tissue-level expression profiling. In the present study, ISH was performed with special focus on the human entorhinal cortex (EC) and transentorhinal cortex (TEC). The TEC is the area of the cerebral cortex that first develops neurofibrillary tangles in Alzheimer's disease (AD). However, the …

Arborist Dies After Fall From Tree, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Falls

A 30-year old arborist was hired by a private resident to remove trees from a yard. At approximately 5:00 PM, the arborist, along with a ground person, arrived at the residence. The arborist donned climbing spurs, and a tree climbing saddle then spoke briefly with the homeowner. With the climbing line and spurs, the arborist climbed the first tree. After trimming limbs from the tree trunk, the arborist began cutting the tree trunk one section at a time. There was a power line near the trees. The arborist was working at the fork of the tree and had cut a …

Team Semi Driver Dies After Rig Is Struck By Impaired Driver, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

During the early hours one fall morning, a husband and wife driving team were traveling west on a divided interstate highway. A concrete barrier separated the four east bound lanes from the four west bound lanes. The wife was driving while the husband was asleep in the sleeper berth. Driving conditions were dark and the pavement dry. They were traveling in the second lane from the median and there was a passenger car to the right of the semi in the third lane from the median traveling next to the front wheel well and bumper. The passenger car driver veered …

Anti-Argonaute Rip-Chip Shows That Mirna Transfections Alter Global Patterns Of Mrna Recruitment To Microribonucleoprotein Complexes, Wang-Xia Wang, Bernard R. Wilfred, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) play key roles in gene expression regulation by guiding Argonaute (AGO)-containing microribonucleoprotein (miRNP) effector complexes to target polynucleotides. There are still uncertainties about how miRNAs interact with mRNAs. Here we employed a biochemical approach to isolate AGO-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with a previously described anti-AGO antibody. Co-immunoprecipitated (co-IPed) RNAs were subjected to downstream Affymetrix Human Gene 1.0 ST microarray analysis. During rigorous validation, the "RIP-Chip" assay identified target mRNAs specifically associated with AGO complexes. RIP-Chip was performed after transfecting brain-enriched miRNAs (miR-107, miR-124, miR-128, and miR-320) and nonphysiologic control miRNA to identify …

Proteomic Analysis Of Iron Acquisition, Metabolic And Regulatory Responses Of Yersinia Pestis To Iron Starvation, Rembert Pieper, Shih-Ting Huang, Prashanth P. Parmar, David J. Clark, Hamid Alami, Robert D. Fleischmann, Robert D. Perry, Scott N. Peterson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: The Gram-negative bacterium Yersinia pestis is the causative agent of the bubonic plague. Efficient iron acquisition systems are critical to the ability of Y. pestis to infect, spread and grow in mammalian hosts, because iron is sequestered and is considered part of the innate host immune defence against invading pathogens. We used a proteomic approach to determine expression changes of iron uptake systems and intracellular consequences of iron deficiency in the Y. pestis strain KIM6+ at two physiologically relevant temperatures (26°C and 37°C).

RESULTS: Differential protein display was performed for three Y. pestis subcellular fractions. Five characterized Y. pestis …

Methods To Impair Hematologic Cancer Progenitor Cells And Compounds Related Thereto, Craig Jordan

Pharmaceutical Sciences Faculty Patents

Primitive or progenitor hematologic cancer cells have been implicated in the early stages and development of leukemia and malignant lymphoproliferative disorders, including acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and chronic lymphoid leukemia (CLL). Interleukin-3 receptor alpha chain (IL-3Rα or CD123) is strongly expressed on progenitor hematologic cancer cells, but is virtually undetectable on normal bone marrow cells. The present invention provides methods of impairing progenitor hematologic cancer (e.g., leukemia and lymphomic) cells by selectively targeting cells expressing CD123. These methods are useful in the detection and treatment of leukemias and malignant lymphoproliferative disorders. Also provided are compounds useful …

The Effect Of A Motivational Intervention On Weight Loss Is Moderated By Level Of Baseline Controlled Motivation, Kelly H. Webber, Jeanne M. Gabriele, Deborah F. Tate, Mark B. Dignan

Dietetics and Human Nutrition Faculty Publications

BACKGROUND: Clinic-based behavioral weight loss programs are effective in producing significant weight loss. A one-size-fits-all approach is often taken with these programs. It may be beneficial to tailor programs based on participants' baseline characteristics. Type and level of motivation may be an important factor to consider. Previous research has found that, in general, higher levels of controlled motivation are detrimental to behavior change while higher levels of autonomous motivation improve the likelihood of behavior modification.

METHODS: This study assessed the outcomes of two internet behavioral weight loss interventions and assessed the effect of baseline motivation levels on program success. Eighty …

Ventricular Function, Myocardial Delayed Enhancement And Patient-Reported Quality Of Life In Adolescents And Adults With Repaired Tetralogy Of Fallot, Jimmy C. Lu, Timothy B. Cotts, Prachi P. Agarwal, Anil K. Attili, Adam L. Dorfman

Internal Medicine Presentations

INTRODUCTION: In patients with repaired tetralogy of Fallot (TOF), right ventricular myocardial delayed enhancement (MDE) and diastolic dysfunction are common, and have been associated with decreased exercise capacity and increased arrhythmia. Predictors of quality of life (QOL) have not been reported in this population.

PURPOSE: We assessed the hypothesis that a greater degree of MDE in adolescents and adults with repaired TOF would correlate with diastolic dysfunction and decreased QOL.

Neural Network Model For Instruments That Store And Retrieve Sequential Information, Philip W. Landfield, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Patents

A method and design is provided for distributing and storing sets of temporally ordered information in a systematic and sequential fashion. This method is based on a model of how the brain functions in the distribution and storage of temporally ordered memories, but it can also be applied to the design of new biological, electronic or optical devices. These devices may be used in the testing and development of new therapeutic drugs, in the detection of toxic agents or impaired performance, or in the development of new industrial and consumer devices in which the orderly storage of sequential information is …

Epoxyketone-Based Immunoproteasome Inhibitors, Kyung Bo Kim, Yik Khuan Ho

Pharmaceutical Sciences Faculty Patents

An efficient new route for the preparation of dihydroeponemycin, an active eponemycin derivative, is provided, which includes the synthesis of the intermediate compound, a hydroxymethyl-substituted enone. In addition, a method is provided for synthesizing inhibitors, which includes PI′-modified analogues. These analogues selectively bind to a major immunoproteasome catalytic subunit LMP2 and inactivate its proteolytic activity in a method of treating diseases, including myeloma and other cancers, Huntington's disease and Alzheimer's disease.

A Comprehensive Approach To Obesity, Hypertension, And Mental Health Evaluation, Stefan G. Kiessling, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

The global epidemic of childhood and adolescent obesity in developing and developed countries has become a major public health concern. Given the relationship between obesity and hypertension as documented in several landmark studies, it is no surprise that, as the prevalence of obesity has increased in the pediatric population, rates of hypertension have also increased substantially. Hypertension is one of the most important risk factors for cardiovascular diseases and stroke; therefore, evaluation and initiation of appropriate treatment are extremely important in the pediatric population. Evaluation for secondary causes of hypertension, including renovascular, renoparenchymal, and endocrine disease, is the approach most …

Substance Abuse Among Adolescents, Abdel Salous, Hatim A. Omar

Pediatrics Faculty Publications

This chapter aims to provide a global perspective on substance abuse among adolescents across different cultures, and to review appropriate strategies in communicating with the adolescent population about substance abuse. Drug abuse continues to be a major public health issue in the United States, especially among adolescents. The attitude toward and involvement in drug abuse among adolescents is a complex problem shaped by multiple psychosocial parameters. Psychosocial variables such as ethnicity, and religion, and group dynamics, while deeply intertwined in shaping the cultural identity of adolescents, also deliver their impact to substance abuse in this patient population. In a society …

50 Years For The Uk College Of Medicine, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Hyperandrogenism And Obesity, Amit M. Deokar, Shawn J. Smith, Amanda J. Goodwin, Hatim A. Omar

Pediatrics Faculty Publications

This chapter has a two-fold objective. One, ti addresses the association of hyperandrogenism and obesity and the complex metabolic derangements that are part of the problem. Clinical management of these co-morbidities is challenging and complex. Second, this chapter will aid health care providers with the key features to an early diagnosis and intervention to decrease the morbidities in the short as well as long term. Method: Systematic review of articles and information on the topic of interest that were published in the last 15 years. Conclusion: Obesity and hyperandrogenism are integral parts of Metabolic Syndrome/Polycystic Ovarian Syndrome (PCOS)/Hyperandrogenism, Insulin resistance, …

Increasing Complexity: Resisting Simplification In Forensic Psychology, Diane R. Follingstad

CRVAW Faculty Journal Articles

The American Academy of Forensic Psychology annually presents a Distinguished Contribution in Forensic Psychology Award to an individual whose work has significantly moved the field forward. Dr. Follingstad received this award for decades of productive research, testimony, and public education regarding family, adolescent, and women's issues, all areas in which she has received numerous research grants over the years. Following is her acceptance speech, presented at the American Psychology-Law Association convention in Vancouver, B.C. in March 2010.

Mir-107 Is Reduced In Alzheimer's Disease Brain Neocortex: Validation Study, Peter T. Nelson, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

MiR-107 is a microRNA (miRNA) that we reported previously to have decreased expression in the temporal cortical gray matter early in the progression of Alzheimer's disease (AD). Here we study a new group of well-characterized human temporal cortex samples (N=19). MiR-107 expression was assessed, normalized to miR-124 and let-7a. Correlation was observed between decreased miR-107 expression and increased neuritic plaque counts (P< 0.05) and neurofibrillary tangle counts (P< 0.02) in adjacent brain tissue. Adjusted miR-107 and BACE1 mRNA levels tended to correlate negatively (trend with regression P< 0.07). In sum, miR-107 expression tends to be lower relative to other miRNAs as AD progresses.

Parenting Adolescents, Sandra D'Angelo, Hatim A. Omar

Pediatrics Faculty Publications

The period of adolescence is often thought to be one of intense stress and turmoil. Yet many parents and teens negotiate this developmental stage without extreme family conflict and without sacrificing close relationships. This review summarizes a portion of the literature on parent-adolescent relationships, focusing on monitoring and control of adolescent behavior and parenting style. Basic principles to emphasize when working with adolescents and parents are also included.

A Policy And Intervention For Overweight Children And Adolescents, Kimberly K. Mcclanahan, Marlene B. Huff, Hatim A. Omar

Pediatrics Faculty Publications

The global epidemic of childhood and adolescent overweight has become a major public health concern. Not only are these youth more likely to become obese adults, and thus more prone to obesity-related diseases than their non overweight peers, they are also likely to suffer emotional and social effects associated with overweight. Overweight in youth has been linked to depression, low self-esteem, eating disorders, negative body image, and stigma. It appears to be bi-directional in nature, with overweight sometimes predicting certain psychological effects and psychosocial issues sometimes predicting overweight. Effective assessment and treatment of psychological and mental health issues in overweight …

Collection And Preparation Of Milk Samples For Microbiological Culturing, Jeffrey M. Bewley, Robert J. Harmon, Stephan Locke

Agriculture and Natural Resources Publications

In developing individual farm mastitis control and treatment strategies, it is often necessary to characterize the types of bacteria that are present on your farm. To answer this question, a microbiological analysis, or milk culture, must be performed on milk samples collected from cows showing clinical or subclinical signs of mastitis. Results of the milk cultures will help identify which bacteria are causing the mastitis. In turn, this information can be used to alter mastitis control, prevention, and treatment options to fit your herd’s conditions.

During an investigation of a herd dealing with high somatic cell counts or a high …

On Why The Dental Therapists' "Movement" In The United States Should Focus On Children--Not Adults, David A. Nash

Oral Health Science Faculty Publications

No abstract provided.

Mental Health And Chronic Disease, Marlene B. Huff, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

By 2015, worldwide, 1.2 billion children aged 5-14 years will have some kind of significant chronic disease. Although scientific evidence indicates that children with chronic illness have more mental health issues than their healthy peers, many controversies and gaps in the literature exist. It is imperative that an understanding of the effects of chronic illness upon the mental health status of children and adolescents be undertaken. This chapter uses a biopsychosocial perspective to investigate the connection between chronic illness and mental health. The intent of the chapter is to suggest ways that medical and mental health professionals can provide services …

Youth Suicide Prevention In Rural Kentucky, Hatim A. Omar

Pediatrics Faculty Publications

Youth suicide continues to be one of the leading causes of death in the United States. Nation wide it is the third leading cause of death in the 10-24 year old age group. The rate of suicide varies somewhat from state to state. In the state of Kentucky, youth suicide is the second leading cause of death. This article describes a grass roots, community based program for youth suicide prevention and its impact on the community. The Stop Youth Suicide Campaign was launched in 2000 and included more than 30 local agencies. This program worked through public education, education of …

Pregnancy And Abortion, Shawn J. Smith, Amit M. Deokar, Hatim A. Omar

Pediatrics Faculty Publications

The role of caring for a pregnant adolescent can be rewarding, but it also possess unique challenges. A significant number of adolescent pregnancies are unintended and therefore providing comprehensive counseling is important even before the initiation of sexual activity. By understanding the risk factors the patient may further be provided delivery of appropriate health prevention/promotion services. It is also important for the health provider to continue to be an integral part of the life of the teenager and her child for an optimal development and growth.

The Female Athlete, Dilip R. Patel, Donald E. Greydanus, Hatim A. Omar

Pediatrics Faculty Publications

The female athlete has today became an accepted part of sports in elementary school, junior high, senior high, and college. This chapter covers various aspects of the prepubertal and pubertal female athlete. An historical perspective will be presented and selected comments provided on psychological and physiologic aspects of the female athlete. Concepts of adolescent gynecology are reviewed, including breast concerns and menstrual dilemmas in relation to sports activity. Exercise during pregnancy is also considered. Iron deficiency anemia and stress urinary incontinence