Medicine and Health Sciences Commons^™

Cd19 Signaling Is Impaired In Murine Peritoneal And Splenic B-1 B Lymphocytes, Trivikram Dasu, Vishal Sindhava, Stephen H. Clarke, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells reside predominantly within the coelomic cavities, tonsils, Peyer's patches, spleen (a minor fraction – ∼5%) and are absent in the lymph nodes. They are the primary sources of natural IgM in the body. B-1 cells express polyreactive B cell receptors (BCRs) that cross react with self-antigens and are thus implicated in auto-immune disorders. Previously, we reported that peritoneal B-1 cells are deficient in CD19-mediated intracellular signals leading to Ca²⁺ mobilization. Here, we find that splenic B-1 cells, like peritoneal B-1 cells, are defective in Ca²⁺ release upon B cell activation by co-cross-linking BCR and CD19. In …

Solid Waste Driver Dies After Single Vehicle Rollover, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

On the morning of a fall day in 2008, a 59 year-old male solid waste worker (Driver 1) entered the cab of a company solid waste truck parked in his driveway and drove to a restaurant a few miles away. After leaving the restaurant, the driver was observed weaving by another solid waste driver (Driver 2) at least two times in the northbound lane of a two-lane state highway. After he had driven 1.8 miles in a little over 2 minutes away from the restaurant, the driver entered a right-hand curve in the highway. While in the curve, the driver …

Lipid Nanoparticles With Accessible Nickel As A Vaccine Delivery System For Single And Multiple His-Tagged Hiv Antigens, Weili Yan, Anekant Jain, Ronan O'Carra, Jerold Woodward, Wenxue Li, Guanhan Li, Avindra Nath, Russell J. Mumper

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel (Ni-NPs) were developed to easily formulate the HIV his-tagged Tat protein, as well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one particle. Female BALB/c mice were immunized by s.c. injection with his-Tat/Ni-NP formulation (1.5 μg Tat-his/mouse) and control formulations on day 0 and 14. The day 28 anti-Tat specific IgG titer with his-Tat/Ni-NP was significantly greater than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP immunized mice secreted significantly higher IFN-γ than those from mice immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant activity …

Programmable Multi-Dose Intranasal Drug Delivery Device, Daniel Wermeling, Ryan Vallance, Aravind Balasubramanian, Bruce L. Walcott, John A. Main, James E. Lumpp

Pharmacy Practice and Science Faculty Patents

An apparatus and method for the self-administration of a plurality of doses of an intranasal liquid pharmaceutical composition, including opioid analgesics, that includes a drug delivery device containing a plurality of sealed vials, each vial containing a predetermined volume of the pharmaceutical composition, a pump assembly for conveying the liquid pharmaceutical composition from the interior of the vial and discharging it as a nasal spray in response to manual activation by the patient, and programmable means for sequentially advancing a vial to the ready position after passage of a prescribed time interval following the last activation of the delivery device.

Dna-Binding By Haemophilus Influenzae And Escherichia Coli Ybab, Members Of A Widely-Distributed Bacterial Protein Family, Anne E. Cooley, Sean P. Riley, Keith Kral, M. Clarke Miller, Edward Demoll, Michael G. Fried, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Genes orthologous to the ybaB loci of Escherichia coli and Haemophilus influenzae are widely distributed among eubacteria. Several years ago, the three-dimensional structures of the YbaB orthologs of both E. coli and H. influenzae were determined, revealing a novel "tweezer"-like structure. However, a function for YbaB had remained elusive, with an early study of the H. influenzae ortholog failing to detect DNA-binding activity. Our group recently determined that the Borrelia burgdorferi YbaB ortholog, EbfC, is a DNA-binding protein. To reconcile those results, we assessed the abilities of both the H. influenzae and E. coli YbaB proteins to bind DNA …

Method And System For In Situ Spectroscopic Evaulation Of An Object, Robert A. Lodder

Pharmaceutical Sciences Faculty Patents

A method and system for spectroscopically determining surface and product characteristics is employed for rapid detection of product characteristics and/or the presence or absence of suspected analytes, and the concentration of the analyte. The method and system uses a signal wide band detector that does not require focusing optics in many environments. It can be used for cleaning validation of pharmaceutical products and process equipment.

Carolus Linnaeus (Carl Von Linné), 1707-78: The Swede Who Named Almost Everything, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Georges-Louis Leclerc, Compte De Buffon (1701-1788): The French Rival Of Linnaeus, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Vegf-A As An Inhibitor Of Angiogenesis And Methods Of Using Same, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

The invention relates to methods and compositions for the treatment or prevention of ocular angiogenesis and neovascularization associated with neovascular disease. Administration of vascular endothelial growth factor (VEGF)-A into the eye when macrophage infiltration is reduced inhibits ocular angiogenesis.

T10b9 Monoclonal Antibody: A Short-Acting Nonstimulating Monoclonal Antibody That Spares Γδ T-Cells And Treats And Prevents Cellular Rejection, Thomas H. Waid, John S. Thompson, Maria Siemionow, Stephen A. Brown

Internal Medicine Faculty Publications

T10B9.1A-31/MEDI-500 is a nonmitogenic immunoglobulin M kappa murine monoclonal antibody (mAb) directed against the alpha-beta (αβ) heterodimer of the T-lymphocyte receptor complex. The hybridoma was first produced by fusing spleen cells from BALB/C mice immunized with human peripheral blood T-lymphocytes with SP2/O-Ag14 mutant myeloma cells. The mAb is produced and purified using multistep ion exchange and molecular sieve chromatography protocols. T10B9 has been used successfully to treat acute cellular rejection in renal transplantation and as an immunosuppression induction agent in heart and simultaneous kidney-pancreas transplantation. Because T10B9 is nonmitogenic and causes minimal cytokine release, both treatment of rejection and induction …

Hibernation-Like State Induced By An Opioid Peptide Protects Against Experimental Stroke, Cesar V. Borlongan, Teruo Hayashi, Peter R. Oeltgen, Tsung-Ping Su, Yun Wang

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Delta opioid peptide [D-ala2,D-leU5]enkephalin (DADLE) induces hibernation in summer ground squirrels, and enhances preservation and survival of isolated or transplanted lungs and hearts. In the present study, we investigated the protective effect of DADLE in the central nervous system.

RESULTS: Adult Sprague-Dawley rats were pretreated with DADLE (4 mg/kg every 2 h x 4 injections, i.p.) or saline prior to unilateral occlusion of the middle cerebral artery (MCA). Daily behavioral tests revealed that ischemic animals treated with DADLE did not show any significant behavioral dysfunctions compared with saline-treated ischemic animals. Opioid antagonists only transiently inhibited the protective effect of …

Opportunities For Comparative Research In Public Health Pbrns : A Baseline Analysis Of Local Practice Settings, Glen P. Mays, Sharla A. Smith, Elaine B. Wootten, Sylvia J. Porchia

Health Management and Policy Presentations

This analysis describes the organizational and operational characteristics of local public health agencies participating in an initial cohort of five (5) public health PBRNs in the U.S. We examine variation in practice settings within and between PBRNs; compare practice settings to state and national norms; and identify opportunities for comparative research that can be conducted through PBRNs.

A Retrospective Claims Analysis Of Combination Therapy In The Treatment Of Adult Attention-Deficit/Hyperactivity Disorder (Adhd), Gerhardt M. Pohl, David L. Van Brunt, Wenyu Ye, William W. Stoops, Joseph A. Johnston

Behavioral Science Faculty Publications

BACKGROUND: Combination therapy in managing psychiatric disorders is not uncommon. While combination therapy has been documented for depression and schizophrenia, little is known about combination therapy practices in managing attention-deficit/hyperactivity disorder (ADHD). This study seeks to quantify the combination use of ADHD medications and to understand predictors of combination therapy.

METHODS: Prescription dispensing events were drawn from a U.S. national claims database including over 80 managed-care plans. Patients studied were age 18 or over with at least 1 medical claim with a diagnosis of ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 314.0), a pharmacy claim for …

Cancer Information-Seeking Experiences: The Implications Of Hispanic Ethnicity And Spanish Language, Robin C. Vanderpool, Julie Kornfeld, Lila Finney Rutten, Linda Squiers

Health, Behavior & Society Faculty Publications

BACKGROUND: Strategies to support cancer information-seeking among Hispanics are needed.

METHODS: We analyzed data from the 2005 Health Information National Trends Survey (HINTS) to explore cancer information-seeking experiences among respondents according to ethnicity and language of interview.

RESULTS: Over 80% of Spanish-speaking Hispanics had never looked for cancer information. Compared to English-speaking respondents, Spanish-speaking Hispanics who sought cancer information indicated their search took a lot of effort (67%), was hard to understand (54%), and frustrating (42%). Spanish-speaking Hispanics noted minimal confidence in obtaining cancer information.

CONCLUSIONS: Language and cultural differences must be considered in the design, implementation, and dissemination of …

Bridging The Gaps: Biomedicine, Complementary And Alternative Medicine In A Holistic Approach, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

The 4^th international conference on holistic health and medicine was held during September 24-26, 2008 in Lexington, Kentucky in the United States of America. This conference brought many participants from 23 countries, both mainstream health care providers as well as holistic health practitioners to address the latest in knowledge and research, and in turn to find ways to collaborate and work together to provide the best possible care for their patients and clients. These conferences are held to build bridges between the various fractions of medicine and health care providers. The scientific program included plenary sessions, keynotes, workshops and …

Weight Gain Associated With Hormonal Contraception Use In Adolescents Is Not Different From Control, Abdel Salous, Valerie Jones, Maria Melguizo Castro, Linah Al-Alem, Hatim A. Omar

Pediatrics Faculty Publications

The use of hormonal contraception is commonly associated with weight gain. The purpose of this retrospective study was to explore the association between the use of hormonal contraception and weight change in an outpatient adolescent patient population in Lexington, Kentucky. Data were gathered from the charts of 259 adolescent female patients seen in an outpatient adolescent clinic for up to 72 months. At the initial visit, all patients were evaluated for risk-taking behavior and received preventive counseling. Patients were categorized as either contraception users or non-users (control group). Contraception users were subdivided into Depot Medroxyprogesterone Acetate (DMPA) user group or …

It Is More Than Just A Reproductive Healthcare Visit: Experiences From An Adolescent Medicine Clinic, Marlene B. Huff, Kimberly K. Mcclanahan, Heather A. Brown, Hatim A. Omar

Pediatrics Faculty Publications

The gynecologist may be the only physician that an adolescent depends on for primary and reproductive healthcare services. Because adolescent females often make personal healthcare decisions without the benefit of supportive parents/caregivers, it is imperative that the gynecologist understands the developmental issues encountered during this phase of life. The objective of this study is to identify cited complaints of adolescent females seeking reproductive care and, thus, provide gynecologists with needed information about the medical/mental health issues that may be encountered during routine reproductive care exams. The study group was adolescent females between the ages of 12 and 20 years old. …

Holistic Approach To Health, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

No abstract provided.

Driver Of A Semi-Tractor Pulling Twin Trailers Fatally Injured In Single Vehicle Crash, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

In the spring of 2008, a 40-year-old tractor-trailer driver died after his vehicle left the interstate highway, crashed, and was engulfed in flames. The tractor drifted over the fog line and rumble strip onto the right shoulder, began to skid and left the highway. The tractor slid through the grass beside the roadway, struck a concrete culvert, sideswiped a small tree and then hit a large tree head-on. The tractor and trailers then skidded back down the embankment toward the highway where the entire unit came to rest. The tractor and lead trailer overturned onto the driver’s side. The second …

Genes Encoding Several Poly (Adp-Ribose) Glycohydrolase (Parg) Enzymes, The Proteins And Fragments Thereof, And Antibodies Immunoreactive Therewith, Myron Jacobson, Elaine L. Jacobson, Jean-Christoph Amé, Winston Lin

Pharmaceutical Sciences Faculty Patents

The isolation and characterization of cDNAs encoding poly(ADP-ribose) glycohydrolase (PARG) enzymes and the amino acid sequences of PARGs from several species are described. PARG is involved in the cellular response to DNA damage and its proper function is associated with the body's response to neoplastic disorder inducing agents and oxidative stress. Expression vectors containing the cDNAs and cells transformed with the vectors are described. Probes and primers that hybridize with the cDNAs are described. Expression of the cDNA in E. coli results in an enzymatically active protein of about 111 kDa and an active fragment of about 59 kDa. Methods …

A Gene Expression Predictor Of Response To Egfr-Targeted Therapy Stratifies Progression-Free Survival To Cetuximab In Kras Wild-Type Metastatic Colorectal Cancer, Justin M. Balko, Esther P. Black

Pharmaceutical Sciences Faculty Publications

BACKGROUND: The anti-EGFR monoclonal antibody cetuximab is used in metastatic colorectal cancer (CRC), and predicting responsive patients garners great interest, due to the high cost of therapy. Mutations in the KRAS gene occur in ~40% of CRC and are a negative predictor of response to cetuximab. However, many KRAS-wildtype patients do not benefit from cetuximab. We previously published a gene expression predictor of sensitivity to erlotinib, an EGFR inhibitor. The purpose of this study was to determine if this predictor could identify KRAS-wildtype CRC patients who will benefit from cetuximab therapy.

METHODS: Microarray data from 80 metastatic CRC patients subsequently …

Coal Truck Driver Dies In Rollover After Tire On Trailer Fails, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Motor Vehicle

In the fall of 2006, a twenty-three year old male tractor-trailer driver who was hauling coal, died when a rear outer tire on the trailer failed. After the tire failed, the trailer slipped off the right side of the road, overturned, and went over an embankment. The trailer remained attached to the tractor as both went over the embankment, flipping the entire unit upside down. A witness called emergency medical services who arrived and called the county coroner. The coroner arrived and declared the driver dead at the scene. It was determined by Kentucky State Police that the driver was …

Striatal Neuroinflammation Promotes Parkinsonism In Rats, Dong-Young Choi, Mei Liu, Randy L. Hunter, Wayne A. Cass, Jignesh D. Pandya, Patrick G. Sullivan, Eun-Joo Shin, Hyoung-Chun Kim, Don M. Gash, Guoying Bing

Neuroscience Faculty Publications

BACKGROUND: Sporadic Parkinson's disease (PD) is a progressive neurodegenerative disorder with unknown cause, but it has been suggested that neuroinflammation may play a role in pathogenesis of the disease. Neuroinflammatory component in process of PD neurodegeneration was proposed by postmortem, epidemiological and animal model studies. However, it remains unclear how neuroinflammatory factors contribute to dopaminergic neuronal death in PD.

FINDINGS: In this study, we analyzed the relationship among inducible nitric oxide synthase (iNOS)-derived NO, mitochondrial dysfunction and dopaminergic neurodegeneration to examine the possibility that microglial neuroinflammation may induce dopaminergic neuronal loss in the substantia nigra. Unilateral injection of lipopolysaccharide (LPS) …

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

Public Health Systems And Services Research: Dataset Development, Dissemination, And Use, F. Douglas Scutchfield, Nikki Lawhorn, Rick Ingram, Debra Joy Pérez, Rick Brewer, Michelyn Bhandari

Preventive Medicine and Environmental Health Faculty Publications

Public health systems and services research (PHSSR) is defined as "a field of study that examines the organization, financing, and delivery of public health services within communities and the impact of those services." PHSSR is a relatively young field and suffers from a paucity of research resources. In this article, we describe the development and utility of a data resource, housed on the Health Services and Sciences Research Resources website maintained by the National Library of Medicine, which provides easy access to instruments, indices, and datasets that are relevant to PHSSR researchers. We also investigate efforts to promote the use …

Addressing Cervical Cancer In Central Appalachia, Baretta R. Casey, Richard A. Crosby, Wallace Bates, Tonya D. Godsey, Mark B. Dignan

Center of Excellence in Rural Health Presentations

Rural women, particularly those residing in Appalachia, have some of the nation’s highest cervical cancer mortality rates. With support from federal and private grants, the University of Kentucky Center for Excellence in Rural Health-Hazard is attempting to address this issue. Eastern Kentucky-based researchers are surveying 18- to 26-year-old female community health center patients and college students about their risk factors for the disease, and then offering them free Gardasil, a vaccine against the virus that causes most cervical cancer cases.

Nucleic Acids Encoding Sarcocystis Neurona Antigen And Uses Thereof, Daniel K. Howe

Veterinary Science Faculty Patents

The present invention provides novel isolated nucleic acids encoding antigenic proteins derived fromSarcocystis neurona, or unique fragments thereof. In particular, the invention provides novel isolated nucleic acids encoding membrane-associated polypeptides SnSAG2, SnSAG3, and SnSAG 4. Also provided are purified antigenic polypeptide fragments encoded by the novel nucleic acid sequences set forth herein that encode for SnSAG2, SnSAG3, and SnSAG 4. Also provided are isolated nucleic acids capable of selectively hybridizing with the nucleic acid from Sarcocystis neurona. The invention also provides vectors comprising the nucleic acids of the invention encoding an antigenic protein derived from Sarcocystis neurona or a …

Compositions And Methods For Detecting And Treating Atherosclerosis, Nancy R. Webb, Frederick C. De Beer

Internal Medicine Faculty Patents

Methods for detecting atherosclerotic plaque and quantifying the amount of Group V sPLA₂ in plasma are disclosed. These methods can be used to assess the risk of cardiovascular pathology in a patient.

Metallic Nickel Nano- And Fine Particles Induce Jb6 Cell Apoptosis Through A Caspase-8/Aif Mediated Cytochrome C-Independent Pathway, Jinshun Zhao, Linda Bowman, Xingdong Zhang, Xianglin Shi, Binghua Jiang, Vincent Castranova, Min Ding

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: Carcinogenicity of nickel compounds has been well documented. However, the carcinogenic effect of metallic nickel is still unclear. The present study investigates metallic nickel nano- and fine particle-induced apoptosis and the signal pathways involved in this process in JB6 cells. The data obtained from this study will be of benefit for elucidating the pathological and carcinogenic potential of metallic nickel particles.

RESULTS: Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we found that metallic nickel nanoparticles exhibited higher cytotoxicity than fine particles. Both metallic nickel nano- and fine particles induced JB6 cell apoptosis. Metallic nickel nanoparticles produced higher apoptotic induction than fine …

Monoclonal Antibody 1a7 And Use For The Treatment Of Melanoma And Small Cell Carcinoma, Malaya Chatterjee, Kenneth A. Foon, Sunil K. Chatterjee

Microbiology, Immunology and Molecular Genetics Faculty Patents

The present invention relates to monoclonal antibody 1A7. This is an anti-idiotype produced by immunizing with an antibody specific for ganglioside GD2, and identifying a hybridoma secreting antibody with immunogenic potential in a multi-step screening process. Also disclosed are polynucleotide and polypeptide derivatives based on 1A7, including single chain variable region molecules and fusion proteins, and various pharmaceutical compositions. When administered to an individual, the 1A7 antibody overcomes immune tolerance and induces an immune response against GD2, which comprises a combination of anti-GD2 antibody and GD2-specific T cells. The invention further provides methods for treating a disease associated with altered …