Medicine and Health Sciences Commons^™

Characterization Of Conserved Properties Of Hemagglutinin Of H5n1 And Human Influenza Viruses: Possible Consequences For Therapy And Infection Control, Veljko Veljkovic, Nevena Veljkovic, Claude P. Muller, Sybille Müller, Sanja Glisic, Vladimir Perovic, Heinz Köhler

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Epidemics caused by highly pathogenic avian influenza virus (HPAIV) are a continuing threat to human health and to the world's economy. The development of approaches, which help to understand the significance of structural changes resulting from the alarming mutational propensity for human-to-human transmission of HPAIV, is of particularly interest. Here we compare informational and structural properties of the hemagglutinin (HA) of H5N1 virus and human influenza virus subtypes, which are important for the receptor/virus interaction.

RESULTS: Presented results revealed that HA proteins encode highly conserved information that differ between influenza virus subtypes H5N1, H1N1, H3N2, H7N7 and defined an …

Borrelia Burgdorferi Ebfc Defines A Newly-Identified, Widespread Family Of Bacterial Dna-Binding Proteins, Sean P. Riley, Tomasz Bykowski, Anne E. Cooley, Logan H. Burns, Kelly Babb, Catherine A. Brissette, Amy Bowman, Matthew L. Rotondi, M. Clarke Miller, Edward Demoll, Kap Lim, Michael G. Fried, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, encodes a novel type of DNA-binding protein named EbfC. Orthologs of EbfC are encoded by a wide range of bacterial species, so characterization of the borrelial protein has implications that span the eubacterial kingdom. The present work defines the DNA sequence required for high-affinity binding by EbfC to be the 4 bp broken palindrome GTnAC, where ‘n’ can be any nucleotide. Two high-affinity EbfC-binding sites are located immediately 5′ of B. burgdorferi erp transcriptional promoters, and binding of EbfC was found to alter the conformation of erp promoter DNA. Consensus EbfC-binding …

Drug Abuse Treatment Beyond Prison Walls, Carl Leukefeld, Carrie B. Oser, Jennifer Havens, Michele Staton Tindall, Jennifer Mooney, Jamieson B. Duvall, Hannah Knudsen

Behavioral Science Faculty Publications

The period surrounding release from prison is a critical time for parolees, bearing the potential for a drug-free and crime-free life in the community but also high risks for recidivism and relapse to drugs. The authors describe two projects. The first illustrates the use of a formal Delphi process to elicit and combine the expertise of treatment providers, researchers, corrections personnel, and other stakeholders in a set of statewide guidelines for facilitating re-entry. The second project is a six-session intervention to enable women to protect themselves against acquiring or transmitting HIV in their intimate relationships.

Impact Of Poor Quality Of Life On Adolescents In Rural Kentucky: A Brief Report, Hatim A. Omar, Søren Ventegodt, Joav Merrick

Pediatrics Faculty Publications

In many rural areas in Kentucky, adolescents lack the basic assets for a good quality of life, such as having caring adults, a safe place and useful activities after school. Methods: Analysis of data from middle and high school students referred to a comprehensive school based health promotion center (SBHPC). Results: From august 2006 to February 2008, a total of 382 students (200 female, 182 male, aged 12-18 years) were referred to the SBHPC for help. Only two (0.5%) students had two parents living with them and 12 (3.1%) had safe, organized after school activities. 19.9% of the total were …

Hyperglycemia And Acquired Weakness In Critically Ill Patients: Potential Mechanisms, Leigh Ann Callahan, Gerald S. Supinski

Internal Medicine Faculty Publications

Critical illness polyneuropathy/critical illness myopathy (CIP/CIM) is a major cause of mortality and long-term morbidity in critically ill patients, but the true incidence and prevalence of these syndromes are not known. Hermans and colleagues show that when intensive insulin therapy is used as part of routine clinical practice in the intensive care unit, the incidence of CIP/CIM as determined by electrophysiologic testing is reduced. Our understanding of the mechanisms responsible for inducing prolonged weakness in intensive care unit patients is limited, and the role of hyperglycemia in modulating these processes is unknown. Intensive insulin therapy currently remains the only effective …

Use Of Clopidogrel In The Reduction Of Myocardial Damage During Percutaneous Coronary Intervention, Arijit Dasgupta, Debabrata Mukherjee

Gill Heart & Vascular Institute Faculty Publications

It is estimated that approximately a quarter of patients undergoing coronary intervention may have significant post-procedural creatinine (CK)/creatinine kinase myocardial band (CK-MB) elevations and approximately half may have post-procedural troponin elevations. Current data suggest that periprocedural infarction is associated with short-, intermediate-, and long-term adverse outcomes, most notably mortality. This review examines the role of clopidogrel in decreasing periprocedural myonecrosis following percutaneous coronary intervention (PCI). Clopidogrel is an important pharmacologic agent used to reduce myocardial infarction post-coronary intervention as assessed directly by the evaluation of cardiac biomarkers and indirectly by the evaluation of short-term ischemic events. The optimal dose of …

Detection Of Cwd Prions In Urine And Saliva Of Deer By Transgenic Mouse Bioassay, Nicholas J. Haley, Davis M. Seelig, Mark D. Zabel, Glenn C. Telling, Edward A. Hoover

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chronic wasting disease (CWD) is a prion disease affecting captive and free-ranging cervids (e.g. deer, elk, and moose). The mechanisms of CWD transmission are poorly understood, though bodily fluids are thought to play an important role. Here we report the presence of infectious prions in the urine and saliva of deer with chronic wasting disease (CWD). Prion infectivity was detected by bioassay of concentrated, dialyzed urine and saliva in transgenic mice expressing the cervid PrP gene (Tg[CerPrP] mice). In addition, PrP(CWD) was detected in pooled and concentrated urine by protein misfolding cyclic amplification (PMCA). The concentration of abnormal prion protein …

Carbon Nanotube Membranes For Use In The Transdermal Treatment Of Nicotine Addiction And Opioid Withdrawal Symptoms, Caroline L. Strasinger, Nicole N. Scheff, Ji Wu, Bruce J. Hinds, Audra L. Stinchcomb

Pharmaceutical Sciences Faculty Publications

Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT) membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual's needs will increase patient compliance as well as provide much more efficient …

Multimeric Hemicellulases Facilitate Biomass Conversion, Zhanmin Fan, Kurt Wagschal, Wei Chen, Michael D. Montross, Charles C. Lee, Ling Yuan

Plant and Soil Sciences Faculty Publications

Two highly active trifunctional hemicellulases were constructed by linking the catalytic portion of a xylanase with an arabinofuranosidase and a xylosidase, using either flexible peptide linkers or linkers containing a cellulose-binding domain. The multifunctional enzymes retain the parental enzyme properties and exhibit synergistic effects in hydrolysis of natural xylans and corn stover.

Life Expectancy And Years Of Life Lost In Chronic Obstructive Pulmonary Disease: Findings From The Nhanes Iii Follow-Up Study, Robert M. Shavelle, David R. Paculdo, Scott J. Kush, David M. Mannino, David J. Strauss

Internal Medicine Faculty Publications

RATIONALE: Previous studies have demonstrated that chronic obstructive pulmonary disease (COPD) causes increased mortality in the general population. But life expectancy and the years of life lost have not been reported.

OBJECTIVES: To quantify mortality, examine how it varies with age, sex, and other risk factors, and determine how life expectancy is affected.

METHODS: We constructed mortality models using the Third National Health and Nutrition Examination Survey, adjusting for age, sex, race, and major medical conditions. We used these to compute life expectancy and the years of life lost.

MEASUREMENTS AND MAIN RESULTS: Pulmonary function testing classified patients as having …

Trends In Mental Health Of An Adolescent Medicine Clinic Patient Population, Abdel Salous, Linah Al-Alem, Hatim A. Omar

Pediatrics Faculty Publications

The correlation between exposure to forms of violence and development of mental disorders in victims is well established. The purpose of this paper was to identify mental health problems in an adolescent medicine clinic population in Lexington, KY and to investigate potential correlation of mental disorders with psychosocial factors. Data were gathered from the charts of 169 adolescent clinic patients (age 10-22) seen in the clinic for mental health care and analyzed using Excel. Of the patient population, 68% were urban, whereas 32% were rural. In terms of gender, 40% of the patients were male and 60% were female, 80% …

Discovering The Complexities Of Adolescent Compliance To Treatment, Megan Song, Hatim A. Omar

Pediatrics Faculty Publications

To explore the challenges faced in enhancing adolescent treatment compliance and to understand the roles of key players in this endeavor: the adolescent, parent and healthcare provider. Obtaining compliance from adolescents requires collaboration from the adolescent, caregiver and provider and depends on well-established relationships between each person in the triad: adolescent-provider, adolescent-caregiver, and caregiver-provider. Ensuring and improving adherence to treatment by adolescents is a challenging task but crucial to overall health outcomes. It requires the collaboration of the adolescent, parent and physician to create the optimal treatment plan, specifically tailored to the adolescent. For the clinician, maintaining good communication and …

Integral And Peripheral Association Of Proteins And Protein Complexes With Yersinia Pestis Inner And Outer Membranes, Rembert Pieper, Shih-Ting Huang, David J. Clark, Jeffrey M. Robinson, Hamid Alami, Prashanth P. Parmar, Moo-Jin Suh, Srilatha Kuntumalla, Christine L. Bunai, Robert D. Perry, Robert D. Fleischmann, Scott N. Peterson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Yersinia pestis proteins were sequentially extracted from crude membranes with a high salt buffer (2.5 M NaBr), an alkaline solution (180 mM Na2CO3, pH 11.3) and membrane denaturants (8 M urea, 2 M thiourea and 1% amidosulfobetaine-14). Separation of proteins by 2D gel electrophoresis was followed by identification of more than 600 gene products by MS. Data from differential 2D gel display experiments, comparing protein abundances in cytoplasmic, periplasmic and all three membrane fractions, were used to assign proteins found in the membrane fractions to three protein categories: (i) integral membrane proteins and peripheral membrane proteins with low solubility in …

Semi-Truck Driver Dies After Striking A Bridge Abutment, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

At approximately 11:45 PM on a spring night in 2008, a semi-tractor driver accompanied by a driver trainee began his route from a warehouse loading dock in Kentucky. The driver departed with a single axle day cab pulling a 28’ refrigerated trailer loaded with detergent, refrigerated and frozen foods.

An hour later, the semi driver was driving in the right hand northbound lane on a four-lane interstate when he came upon a crash scene. A southbound mini-van had been struck by another vehicle, crossed the median, and had come to rest across the right hand northbound lane. To avoid striking …

Dna Instability In Replicating Huntington's Disease Lymphoblasts, Milena Cannella, Vittorio Maglione, Tiziana Martino, Giuseppe Ragona, Luigi Frati, Guo-Min Li, Ferdinando Squitieri

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The expanded CAG repeat in the Huntington's disease (HD) gene may display tissue-specific variability (e.g. triplet mosaicism) in repeat length, the longest mutations involving mitotic (germ and glial cells) and postmitotic (neurons) cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths.

RESULTS: Although most lymphoblastoid cell lines …

The Future (Or Lack Of Future) Of Personalized Prescription In Psychiatry, Jose De Leon

Psychiatry Faculty Publications

Rapid technological advances in genetics have created conceptual chaos regarding the genetics of drug response. Terms for differing concepts are used interchangeably: pharmacogenetics with pharmacogenomics, personalized medicine with personalized prescription. Biomarker has many definitions. The author prefers the concept of personalized prescription and uses it with implications beyond pharmacogenetics by considering all scientific information valid for prescribing medication. Genetics may not be crucial for all drugs. In this comprehensive view, clinicians must consider genetic, environmental and personal variables when prescribing medication and incorporate some basic pharmacological principles: (1) safety and efficacy, (2) pharmacokinetics and pharmacodynamics, (3) therapeutic window and prescriber's …

Identification Of A Potent Herbal Molecule For The Treatment Of Breast Cancer, Srinivas Koduru, Srinivasan Sowmyalakshmi, Raj Kumar, Rohini Gomathinayagam, Jürgen Rohr, Chendil Damodaran

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.

METHODS: To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER+)-MCF-7 and estrogen-receptor negative (ER-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.

RESULTS: PDBD inhibits cell viability of ER+ and ER- BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting …

The Role Of Nf-Κb In Pparα-Mediated Hepatocarcinogenesis, Howard P. Glauert, Karen Calfee-Mason, Yixin Li, Vani Nilakantan, Michelle L. Twaroski, Job Tharappel, Brett T. Spear

Graduate Center for Nutritional Sciences Faculty Publications

In this review, the role of NF-kappaB in the induction of hepatocarcinogenesis by peroxisome proliferators is examined. The administration of peroxisome proliferators for more than a three-day period leads to the activation of NF-kappaB in the livers of rats and mice. On the other hand, peroxisome proliferator activated receptor-alpha (PPARalpha) activation in non-hepatic tissues can lead to the inhibition of NF-kappaB activation. Several lines of evidence support the hypothesis that the activation of NF-kappaB by peroxisome proliferators in the liver is mediated by oxidative stress. The role of NF-kappaB in peroxisome proliferator-induced hepatocarcinogenesis has been examined using NF-kappaB knockout models. …

Early Activities For Public Health Pbrns, Glen P. Mays

UKCPHSSR Research Briefs and Reports

Launching a successful public health practice-based research network requires a planned approach to developing the necessary infrastructure, relationships, and scientific direction.

Hyperandrogenism And Obesity: Ominous Co-Morbidities, Amit M. Deokar, Shawn J. Smith, Amanda J. Goodwin, Hatim A. Omar

Pediatrics Faculty Publications

This review has a two-fold objective. One, it 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 article 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, …

Overweight Children And Adolescents: Impact On Psychological And Social Development, 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 as 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 …

Violence Against Women Raises Risk Of Cervical Cancer, Ann L. Coker, Claudia Hopenhayn, Christopher P. Desimone, Heather M. Bush, Leslie Crofford

CRVAW Faculty Journal Articles

Background: An emerging literature suggests that violence against women (VAW), particularly sexual violence, may increase the risk of acquiring a sexually transmitted infection (STI) and, therefore, may be associated with cervical cancer development. The purpose of this cross-sectional analysis was to determine if women who had experienced violence had higher prevalence rates of invasive cervical cancer.

Methods: Women aged 18–88 who joined the Kentucky Women’s Health Registry (2006–2007) and completed a questionnaire were included in the sample. Multivariate logistic regression analyses were used to adjust odds ratio (OR) for confounders (e.g., age, education, current marital status, lifetime illegal drug use, …

Hpv Vaccine Acceptance Among Latina Mothers By Hpv Status, Maureen Sanderson, Ann L. Coker, Katherine S. Eggleston, Maria E. Fernandez, Concepcion D. Arrastia, Mary Kay Fadden

CRVAW Faculty Journal Articles

Objective: We investigated whether Latina mothers who were and were not human papillomavirus (HPV) positive differed in their knowledge and acceptance of the HPV vaccine for their children.

Methods: We conducted a cross–sectional survey among women aged 18–64 years between April 2007 and April 2008. Data collectors conducted in-person interviews in community clinics with 215 HPV-negative women and 190 HPV-positive women (with respective response rates of 64% and 84%). Most (83%) HPV-positive women were recruited at dysplasia clinics. Although no HPV-negative women were recruited at dysplasia clinics, they were recruited at other low-income public and private clinics.

Results: After adjustment …

Breast Cancer Screening In Women Exposed In Utero To Diethylstilbestrol, Elizabeth A. Camp, Ann L. Coker, Stanley J. Robboy, Kenneth L. Noller, Karen J. Goodman, Linda T. Titus-Ernstoff, Elizabeth E. Hatch, Arthur L. Herbst, Rebecca Troisi, Raymond H. Kaufman, Ervin Adam

CRVAW Faculty Journal Articles

Purpose: To determine if women exposed in utero to diethylstilbestrol (DES) are more likely than unexposed women to receive recommended or additional breast cancer screening examinations.

Methods: 1994 Diethylstilbestrol-Adenosis (DESAD) cohort data are used to assess the degree of recommended compliance of breast cancer screenings found in 3140 DES-exposed and 826 unexposed women. Participants were enrolled at four sites: Houston, Boston, Rochester, and Los Angeles. Logistic regression modeling was used to analyze mailed questionnaire data that included reported frequency over the preceding 5 years (1990–1994) of breast-self examinations (BSEs), clinical breast examinations (CBEs), and mammograms.

Results: DES-exposed women exceeded annual …

Ethnic Disparities In Cervical Cancer Survival Among Medicare Eligible Women In A Multiethnic Population, Ann L. Coker, Katherine S. Eggleston, Xianglin L. Du, Lois Ramondetta

CRVAW Faculty Journal Articles

To determine predictors of cervical cancer survival by socioeconomic status (SES), urbanization, race/ethnicity, comorbid conditions, and treatment among elderly Medicare-eligible women whose conditions were diagnosed with cervical cancer in a multiethnic population.

Methods: A total of 538 women with cervical cancer aged 65 years or older were identified from 1999 to 2001 from the Texas Cancer Registry and were linked with the state Medicare data and Texas Vital Records to determine survival times. All women had similar access to care through Medicare fee-for-services insurance. A composite measure of SES was created using census tract-level data as was urbanization. Treatment and …

Obesity And Contraception, Donald E. Greydanus, Hatim A. Omar, Artemis Tsitsika

Pediatrics Faculty Publications

All sexually active youth, whether obese or normal weight, should be offered counseling regarding contraception and appropriate contraceptive methods. However, obese youth who are sexually active may be less likely than their normal weight peers to use contraceptives correctly. Methods of contraception for obese adolescents are reviewed in this discussion. Combined oral contraceptives (COCs) and the contraceptive patch have higher failure rates in obese versus normal weight females, though failure rates are lower than noted with barrier contraceptives. The risk for venous thrombosis is higher in obese youth on COCs. Progestin-only pills and the levonorgestrel intrauterine system appear to be …

Rafinesque, Transylvania’S Famous Naturalist, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Pyrilamine In The Horse: Detection And Pharmacokinetics Of Pyrilamine And Its Major Urinary Metabolite O-Desmethylpyrilamine, L. Dirikolu, A. F. Lehner, J Daniel Harkins, W. E. Woods, W. Karpiesiuk, R. S. Gates, M. Fisher, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Pyrilamine is an antihistamine used in human and veterinary medicine. As antihistamines produce central nervous system effects in horses, pyrilamine has the potential to affect the performance of racehorses. In the present study, O-desmethylpyrilamine (O-DMP) was observed to be the predominant equine urinary metabolite of pyrilamine. After intravenous (i.v.) administration of pyrilamine (300 mg/horse), serum pyrilamine concentrations declined from about 280 ng/mL at 5 min postdose to about 2.5 ng/mL at 8 h postdose. After oral administration of pyrilamine (300 mg/horse), serum concentrations peaked at about 33 ng/mL at 30 min, falling to <2 ng/mL at 8 h postdose. Pyrilamine was not detected in serum samples at 24 h postdosing by either route. After i.v. injection of pyrilamine (300 mg/horse) O-DMP was recovered at a level of about 20 ̄g/mL at 2 h postdose thereafter declining to about 2 ng/mL at 168 h postdose. After oral administration, the O-DMP recovery peaked at about 12 ̄g/mL at 8 h postdose and declined to <2 ng/mL at 168 h postdose. These results show that pyrilamine is poorly bioavailable orally (18%), and can be detected by sensitive enzyme-linked immunosorbent assay tests in urine for up to 1 week after a single administration. Care should be taken as the data suggest that the withdrawal time for pyrilamine after repeated oral administrations is likely to be at least 1 week or longer.

Retrofitting Tractors With Rollover Protective Structures: Perspective Of Equipment Dealers, Shalome M. Tonelli, Kelley J. Donham, Kerry Leedom-Larson, Wayne Sanderson, Mark A. Purschwitz

Biosystems and Agricultural Engineering Faculty Publications

This study was one of a cluster of studies that originated via requests for proposals from the NIOSH National Agricultural Tractor Safety Initiative. The present study design consisted of several steps: (1) formation of an advisory group, (2) development and testing of a standard paper self-responding survey instrument, (3) sample selection of farm equipment dealers, (4) administration of the survey, (5) assessment and analysis of the survey, and (6) in-person response panel of dealers (n = 80) to review results of the questionnaire for further definition and sharpening of the recommendations from the survey. A key finding is that most …

Preparation And Characterization Of Blackberry Extracts And Their Anticancer And Anti-Inflammatory Properties, Jin Dai

University of Kentucky Doctoral Dissertations

Blackberries are rich in polyphenols including anthocyanins. Polyphenols are hypothesized to have biological activities that impact positively on human health. The purpose of these studies was to develop phenolic extracts from selected cultivars of blackberries currently grown in Kentucky as potential Botanical Drug Products for the treatment and prevention of cancer and inflammatory diseases.

An ultrasound-assisted ethanol extraction method was employed to obtain anthocyanin-containing extracts (ACEs) from puree or powder (lyophilized puree) of blackberries. ACEs were analyzed for total anthocyanin and phenolics content, polymeric color, and total antioxidant capacity (TAC). The influence of water content in the extraction system was …